rhabdoviridae - Department of Library Services

Transcription

RHABDOVIRIDAE
There are currently more than 100 viruses that are classified
as being members of this family, which has a remarkable
host-range encompassing vertebrates (including reptiles
and fish), invertebrates and plants. They all have a bulletshaped (sometimes conical) or, in the case of plant viruses,
bacilliform morphology as well as other biophysical and
biochemical features in common.1
Subdivision of the family into genera and serogroups has
so far been based entirely on serological cross-reactivities
which are extensive but often asymmetric.2 An abridged
classification for the viruses associated with vertebrates and
haematophagous arthropods is shown in Table 1.
Table 1 An abridged classification of
rhabdoviruses of vertebrates and
haematophagous arthropods. (Adapted
from Calisher et al.2)
Most members of the family Rhabdoviridae have no
known association with disease, but among them are the
causative agents of three very different and important diseases — rabies, bovine ephemeral fever, and vesicular stomatitis. Rabies in particular is an increasingly troublesome
health problem in humans and animals. This and its complex epidemiology portends the necessity for increasingly
complex control strategies, despite the availability of excellent vaccines. Rabies control, therefore, will be more and
more dependent upon the existence of efficient veterinary
infrastructures. Rabies-related viruses, although so far unimportant as causes of either human or animal disease, add
RHABDOVIRIDAE
ORIGINALLY
COUNTRY
YEAR
France
1882
ISOLATED FROM
Lyssavirus
Rabies
Cow
Lagos bat
Bat
Nigeria
1956
Mokola
Shrew
Nigeria
1968
Duvenhage
Human
South Africa
1970
Kolongo
Bird
Central African Republic
1970
Sandjimba
Bird
1970
Nasoule
Bird
1970
Kotonkan
Ceratopogonid midges
Nigeria
1967
Obodhiang
Mosquitoes
Sudan
1963
Rochambeau
Mosquitoes
French Guiana
1973
Charleville
Phlebotomine flies
Australia
1969
Cow
South Africa
1967
Ephemerovirus
Bovine ephemeral fever
Adelaide River
Cow
Australia
1981
Kimberley
Cow
Australia
1980
Berrimah
Cow
Australia
1981
Coastal Plains
Cow
Australia
1981
Humpty Doo
Phlebotomine flies
Australia
1975
Tibrogargan
Australia
1976
Ngaingan
Australia
1970
Bivens Arm
USA
1982
Sweetwater Branch
USA
1982
Oak-Vale
Mosquitoes
USA
1981
Malakal
Mosquitoes
Sudan
1963
Muchong
Mosquitoes
Malaysia
1965
Parry Creek
Mosquitoes
Australia
1977
Vesiculovirus (26 viruses)
1121
1122
SECTION FOUR:
Viral diseases: Rhabdoviridae
to the complexity of the problem. The antigenic relationship
between the rabies and bovine ephemeral fever serogroups
is interesting and has been used as a basis for speculation on
the phylogeny and intercontinental spread of lyssaviruses.2
Vesicular stomatitis, important in its own right but also
because it is difficult to distinguish clinically from footand-mouth disease, is fortunately confined to the western
hemisphere, although other vesiculoviruses which could
potentially cause animal disease are not.2
It is thought that ‘an enormous number of rhabdoviruses
are yet to be discovered’.2 This, and the fact that there is serological evidence of infection of mammals with some
members of the family Rhabdoviridae which have so far only
been isolated from haematophagous arthropods, indicate
that not all the diseases caused by viruses within this family
are recognized at present.
References
1
brown, f., bishop, d.h.l., crick, j., francki, r.i.b., holland, j.j., hull, r.,
johnson, k., martelli, g., murphy, f.a., obijeski, j.f., peters, d.,
pringle, c.r., reichmann, m.e., schneider, l.g., shope, r.e., simpson,
d.i.h., summers, d.f. & wagner, r.r., 1979. Rhabdoviridae. Intervirology,
12, 1–7.
2
calisher, c.h., karabatsos, n., zeller, h., digoutte, j-p., tesh, r.b.,
shope, r.e., travassos da rosa, a.p.a. & st. george, t.d., 1989. Antigenic
relationships among rhabdoviruses from vertebrates and
hematophagous arthropods. Intervirology, 30, 241–257.
99
Rabies
Synonyms: Hondsdolheid (Afrik.)
r swanepoel
Introduction
Rabies (rabidus, L. = mad) is a highly fatal disease of humans
and all other warm-blooded vertebrates, caused by a virus
which is present in saliva late in infection and which is generally transmitted by the bite of diseased animals, most
commonly dogs and other carnivores. Virus introduced into
the bite wound enters peripheral nerves and, during an incubation period of weeks to months, spreads to the spinal
cord and brain to produce severe nervous disease that lasts
from a few days to weeks. The disease is usually marked by
excitability, furious behaviour, inability to swallow, salivation, convulsions, paralysis, coma and death. Human patients often exhibit fear of water and this has given rise to the
alternative name of hydrophobia for the disease in humans.
The disease appears to have occurred widely in Europe,
Asia and Africa throughout recorded history, but it never
had the significant impact on human and livestock populations classically associated with diseases such as bubonic
plague, smallpox, bovine pleuropneumonia or rinderpest.
Nevertheless, the dramatic nature of the signs and symptoms and the invariably fatal outcome of infection has long
caught the imagination, and recognizable descriptions of
the disease can be traced back further in early Chinese,
Egyptian, Greek and Roman records than descriptions of
any other infectious disease.765 Controversy raged for centuries as to whether the disease arose spontaneously, or was
caused by an agent transmitted by bite, and it was not until
1804 that Zinke784 published a description of the experimental transmission of the disease to dogs and cats by
brushing saliva from a rabid dog into wounds. In 1879,
Galtier276 described the transmission of the disease to a
laboratory host, the rabbit, and thereby paved the way for
the historic work of Pasteur and his associates.
Pasteur soon established the essential association of the
causative agent of rabies with nerve tissue, and demonstrated by serial intracerebral passage of infected nerve tissue in laboratory animals that wild or ‘street virus’ could be
transformed into ‘fixed virus’ with a shortened and repro-
ducible incubation period.520 The concept of specific immunization against infectious diseases had recently been
developed by Pasteur and his associates for fowl cholera and
anthrax, and in logical extension of their work they reasoned
that vaccine could be administered to humans after exposure to rabies virus in order to induce immunity before the
infection became established in the victim. They ‘attenuated’ rabies virus by desiccating strips of infected rabbit
spinal cord over potassium hydroxide, and administered
suspensions of increasing ‘virulence’ to patients, starting
with material dried for 14 days and ending with material
dried for two days. The technique was first applied in 1885
on a nine-year-old boy, who survived, and within a short
period the technique found widespread application and had
a lasting impact on rabies immunization practices.519 It can
be deduced that Pasteur’s method of preparing vaccine did
not constitute attenuation of virus in the modern sense of
the term, but resulted in the initial administration of inactivated virus followed by increasing doses of live virus.
Despite the development of a vaccine, the true nature of the
infectious agent remained obscure and it was not until 1903
that Remlinger554 demonstrated that it passed through filters
which retained bacteria, and thus conformed to the newly defined group of agents known as viruses. In the same year, Negri492 described the occurrence of cytoplasmic inclusions in
infected nerve cells, and while the discovery of these ‘Negri
bodies’ facilitated the specific diagnosis of rabies, the author
himself considered the inclusions to be protozoan parasites,
thereby fuelling controversy about the aetiology of the disease
which was to continue for many years.
Pasteur’s vaccine had the disadvantage that fresh
batches had to be prepared constantly, and hence Fermi introduced a method in 1907 of preserving vaccine, while at
the same time achieving partial inactivation of virus,
through treating infected nerve tissue with phenol.251 The
method was modified by Semple in 1911 to achieve more
complete inactivation of virus.601 Semple-type vaccines prepared from infected nerve tissue from a variety of animals
(particularly mouse brain) and inactivated with a variety of
1123
1124
SECTION FOUR:
chemicals, especially formalin, remained in general use for
humans and domestic animals for many decades, in some
countries up to the present day, until superseded by inactivated or attenuated vaccines prepared from virus grown in
chick embryos, duck embryos and cell cultures.
In parallel with the development of an understanding of
the mode of transmission of rabies infection, the early literature reflects growing opinion that the disease could be controlled by restriction and muzzling, or quarantine, of dogs,
plus the destruction of strays.765 Elimination of rabies
through the application of such measures was achieved in
very few instances only, when the control of the disease was
uniquely favoured by the insularity of the country concerned
and by the lack of wild reservoirs of infection. Control was
first achieved in the Scandinavian countries of Norway, Denmark and Sweden in 1826345 and in Britain in 1902 after the
promulgation of Anti-rabies Regulations in 1897, and again in
1922 following re-introduction of the disease in 1918.648
Japan was the first country to attempt mass vaccination of
dogs, in 1920,611, 648 and it finally achieved eradication of the
disease in 1956.649 Taiwan and Portugal are among the few
other countries to have eradicated rabies.649, 681 Several other
countries were historically free of rabies, and apart from rare
instances of importation of human cases, or animals in quarantine, have remained free of the disease. In many parts of
the world, however, rabies is rampant to this day.
Since many epidemics have been observed to develop
and spread in recent times, such as those involving wild vertebrates (sylvatic rabies) in Europe and North America, the
current high prevalence of rabies in the world cannot simply
be ascribed to increased recognition of the disease through
the application of improved surveillance and diagnostic
procedures. Ironically, the highly developed nations of
western Europe and North America, which had virtually
eliminated dog and human rabies, recorded the highest annual numbers of cases of the disease in wild vertebrates during the second half of the twentieth century, although the
position in Europe has been reversed dramatically since the
introduction of oral vaccination of foxes (see below). In the
developing nations of Central and South America, Africa
and Asia, dog rabies (urban rabies) is predominant and
there may be as many as 50 000 human cases each year, over
90 per cent of which result from transmission by dogs and
many of which involve young children.125, 126, 252, 338, 606
Significant losses also occur in livestock, a particular example being the heavy losses of cattle associated with rabies
transmitted by vampire bats in Central and South
America.252 Control of rabies in the developing nations is
hampered by poverty, the inexorable trend toward uncontrolled urbanization, sociopolitical turmoil and wars, and
the lack of the national infrastructure and financial resources required for dealing with the problem.125, 252, 408, 606
Southern Africa, and South Africa in particular, has a
high prevalence of the disease with a unique blend of urban
and sylvatic rabies.376, 634, 667
Aetiology
The family Rhabdoviridae (rhabdos, Gr. = rod) includes the
genus Lyssavirus (lyssa, Gr. = rage or fury; also the fibrous
structure in the tip of a dog’s tongue, the removal of which
prevented the development of madness according to superstitious belief as related by Pliny the Elder), the genus
Ephemerovirus (named for bovine ephemeral fever virus),
and the genus Vesiculovirus (named for vesicular stomatitis
virus), plus a genus of fish viruses, two genera of plant viruses and a number of unassigned viruses. The genus Lyssavirus in turn includes rabies virus (designated lyssavirus
genotype 1) and the so-called rabies-related viruses, Lagos
bat, Mokola and Duvenhage (lyssavirus genotypes 2, 3 and
4), which are associated with bats, shrews and rodents in Africa, plus European bat lyssaviruses 1 and 2 (lyssavirus
genotypes 5 and 6), which are associated with serotine and
myotine bats respectively in Europe, and the Australian bat
lyssavirus (lyssavirus genotype 7).123, 146, 284, 375, 376, 411, 488,
624, 694, 732
Within the lyssaviruses, the genetic relatedness is
closest between488 (genotype 1) and Duvenhage, European
bat lyssaviruses 1 and 2, plus the Australian bat lyssavirus
(genotypes 4, 5, 6 and 7), which are consequently placed together in a phylogroup I, and between Lagos bat and Mokola
viruses (genotypes 2 and 3), which constitute phylogroup II
lyssaviruses.58, 624 The genetic relationships are reflected in
antigenic relationships, and have implications for immunization: rabies vaccines can be used to immunize against
Duvenhage, the Euopean bat and the Australian bat lyssaviruses, but are less effective against Lagos bat and Mokola
viruses.58, 59 Mokola virus, which is capable of sustained
subculture in mosquito cells and live mosquitoes,9, 136 provides a biological and antigenic link between the lyssaviruses and the ephemeroviruses.146 A Nigerian equine
encephalitis virus, described in the literature as an unclassified virus,353, 544 has been identified as rabies virus,
lyssavirus 1.373
From phylogenetic analysis of 36 carnivoran and 17 bat
lyssavirus isolates, representing all major genotypes and
variants, it was concluded that lyssaviruses probably developed in bats, and that host switching to carnivores occurred
approximately 1 000 years ago.59
The results of monoclonal antibody and phylogenetic
studies led to the recognition that strains of rabies virus
proper, lyssavirus 1, which circulate in particular host species
within given geographic regions tend to undergo genetic adaptation, resulting in the development of so-called biotypes,
with subtle changes in antigenicity and pathogenicity which
are of great epidemiological significance.163, 215, 375, 569, 577,
589, 591, 623, 624, 625, 626–631, 662, 663, 694, 744, 758, 760, 761
Despite the
relative ease with which mutations can be induced experimentally, the antigenic structure of rabies virus biotypes appears to have remained remarkably stable over many years in
nature and is not ordinarily affected by passage in laboratory
hosts or cell cultures.215 Nevertheless, the results of
Rabies
phylogenetic analysis of 87 canine lyssavirus 1 isolates from
Asia, Africa, Europe and the Americas indicates that there has
been nucleotide sequence divergence which can be estimated to date back to the times of European colonization of
each region, so that the introduction of dog rabies may have
been a legacy of colonization.215, 628
Rhabdoviruses are rod- or bullet-shaped, rounded at one
end and plano-concave at the other, and tend to have a constant diameter of 75 nm with a length that varies from 130 to
300 nm, but some are conical, with the sides tapering to a
point.14, 168, 200, 250, 456, 465, 485 The genome consists of a
single segment of single-stranded, negative-sense RNA
(complementary to mRNA), and there are five structural
proteins.230, 283, 445, 642
Rabies virus particles are bullet-shaped, measure 180 ×
75 nm and consist of a nucleocapsid, 160 × 50 nm, which is
surrounded by a bilayer lipid envelope, derived from host
cell membranes, and through which flattened spikes or peplomers, each composed of three molecules of glycoprotein
(G protein), project over the entire surface of the virion, except at the blunt end.214, 485 Underlying the lipid membrane
is a layer of membrane or matrix protein (M protein, also
designated M2 protein), which binds to the nucleocapsid
(N) protein of the viral core, and holds the envelope in
place.229 The ribonucleoprotein core of the nucleocapsid
consists of the RNA genome, MW 4,5 × 106 with 11 932
nucleotides643, 695, 696 intimately bound to the phosphorylated N protein, which covers the RNA molecule along its
entire length, and this complex forms a tightly wound helix
of 30 to 35 coils. Minor quantities of two more proteins are
associated with the ribonucleoprotein complex: a phosphorylated protein, misleadingly named non-structural (NS)
protein (earlier termed M1 protein since at one time it was
believed to be associated with the membrane), plus a large
(L) protein which constitutes the viral transcriptase, an
RNA-dependent RNA polymerase.
The G protein is responsible for the recognition of receptor sites for the attachment of virus on the surfaces of susceptible cells, and for inducing production of and binding
with protective, virus-neutralizing antibodies. It also stimulates and is a target for T cell-mediated immune response.151, 152, 187, 191, 192, 440, 709, 759, 763, 775 Although there
is greater than 94 per cent sequence homology between the
amino acids of the G proteins of strains of rabies virus that
have been studied, the substitution of even a single amino
acid at a critical site may result in marked changes in pathogenicity, glycosylation or antigenicity.183, 184, 185, 215, 220, 547,
597, 772, 773, 776, 777, 779
Antigens associated with the N protein and possibly with
the other proteins of the ribonucleoprotein complex can
also induce a degree of protective immunity.216, 217, 273, 427,
657
Consequently, the efficacy of a vaccine against a particular street virus cannot be predicted solely on the basis of the
compatibility of their G protein antigens, but should be
based on potency tests in animals, preferably involving the
1125
intended target species.215 The protective mechanism is believed to involve stimulation of T cell-mediated immunity.150, 216, 230 There is 98 to 99 per cent homology in the
deduced amino acid sequences of the N proteins of strains
of rabies virus that have been studied,697, 698, 777 and this is
reflected in the highly conserved antigenic structure of the N
protein generally observed in tests with polyclonal antisera,
although differences are readily discernible with monoclonal antibodies.163, 216, 402, 569, 589, 594, 629, 631, 663, 744, 761
Attachment of rabies virus to susceptible cells is as yet imperfectly understood. Infection can occur in the absence of
the virus envelope, but with greatly reduced efficiency.229
There is evidence that infection of the nervous system can
occur through the attachment of virus to the acetylcholine receptors at neuromuscular junctions,140, 413, 740 but cultured
cells which lack or have few acetylcholine receptors, nevertheless have receptors which are broadly specific for rhabdoviruses, and which appear to be associated with particular
carbohydrate moieties of the phospholipids and glycolipids
of cell membranes.339, 551, 552, 703, 705, 778 Recently, a neural
cell adhesion factor has been identified as a rabies virus receptor.684 It can be concluded that the virus probably uses
different receptors on different cells.195, 339, 704
Following their attachment to the cell surface, virus particles are internalized by endocytosis (viropexis) and the
virus in cytoplasmic vesicles is uncoated by fusion with lysosomes.474, 534 The ribonucleoprotein complexes which are
released, constitute active templates for transcription of the
genome. As with all negative-strand RNA viruses, the nucleic
acid is non-infectious in the absence of viral transcriptase.
Replication occurs in the cytoplasm of the infected cell, and
virus matures and is released by budding through the cell
surface membrane,180, 229, 314, 396, 526, 697, 698, 774, 777 but in
nerve cells the virus matures predominantly on internal
membranes.458
Accumulations of viral proteins in the cytoplasm constitute the inclusions seen histologically in infected cells, and
accretions of virus particles apparently account for the ‘inner
structure’ described for Negri bodies.282, 324, 430, 456, 457, 492
The replication of rabies virus is slower, less abundant and
less inhibitory of host cell macromolecular synthesis than
that of vesiculoviruses, and the virus is therefore less inclined
to produce readily discernible cytopathic effects.195, 696
During replication, rabies virus readily gives rise to mutants with part of the genome deleted, resulting in shorter
nucleocapsids and hence truncated mature virions. These
so-called defective interfering (DI) particles are able to replicate only in the presence of standard virus, but at the same
time they interfere with replication of the standard virus.
Production of DI particles is enhanced by subculture of undiluted virus, and the presence of the particles can lead to
loss of infectivity or help to induce and maintain a state of
persistent viral infection with low output of virus and minimal deleterious effect on the cells.193, 195, 229, 362, 753, 754 Induction of interferon production also plays a role in the
1126
SECTION FOUR:
generation of persistent infection.315 It is not known
whether DI particles influence the course of infection in intact animals, but interferon induced within the central nervous system during infection appears to be inconsequential
to the outcome of infection.428
Rabies virus is sensitive to sunlight and ultraviolet irradiation, heat, detergents, halogens and lipid solvents. Infectivity is destroyed in minutes by 0,2 per cent quaternary
ammonium compounds, 1 per cent soap solution, 5 to 7 per
cent iodine solution or 45 to 70 per cent alcohol. The virus is
also inactivated by heating to 56 °C for 30 minutes, or by exposure to 50 per cent ether or low concentrations of sodium
desoxycholate, formalin or beta-propriolactone for a few
hours. Infectivity is labile in suspensions of less than 0,1 per
cent tissue extract without the addition of protective protein, but is stable for weeks in nerve tissue held in glycerolsaline at room temperature (22 °C) or for months at 4 °C.
Virus can be preserved for years at temperatures below
−60 °C, or by freeze drying and storing at 4 °C.345, 356, 379
Rabies virus has been cultured in a variety of laboratory
hosts for diagnostic and research purposes, and for production of vaccine, from the time of Pasteur onwards, but mice
have been the most commonly used animals since 1935.742
Culture of the virus in embryonated eggs was introduced in
1938.380 Various tissue suspension, explant and cell cultures
were used from 1913 onwards,195, 415, 509, 753 but successful
serial subculture of rabies virus in cell cultures was first reported in 1958,378 and shortly after that it was shown that
cell cultures could be used for the production of vaccine.379
Currently, a wide range of primary cell cultures as well as
diploid and transformed cell lines are used for different purposes. Rabies virus generally has to be adapted to cell cultures by passage to obtain efficient replication, and uptake
of virus can be enhanced by treating cells with the polycation DEAE-dextran prior to initial infection.195, 358, 751
Cell lines commonly used in research and the diagnosis
of rabies include BHK21, CER and Nil2, all of hamster origin,
Vero cells derived from vervet monkey kidney, and neuroblastoma cell lines of murine and human origin.124, 147, 171,
195, 336, 566, 567, 585, 620, 621, 632, 633, 761
Cells used for the largescale production of virus for vaccines include a variety of
primary cultures, such as chick embryo fibroblasts, foetal
bovine kidney and dog kidney cells, as well as line cells such
as Vero, Nil2 and NL-ST-1 (swine testicle cells), and the
human diploid cell lines WI38 and MRC5.89, 90, 431, 479, 548,
565, 602, 716, 757
The rabies-related viruses can also be cul196, 687
tured in cells,
including Mokola virus in invertebrate
cells.136
Epidemiology
Rabies-free countries
Countries reported to be free of rabies in recent years are
mainly islands and peninsulas. They include Great Britain,
Ireland, Iceland, Sweden, Norway (apart from the Svalbard
Islands to the north of the mainland), Denmark, Portugal,
Spain, Gibraltar, Malta, Albania, Cyprus, Bahrain, Oman,
Qatar, United Arab Emirates, Hong Kong, the Malaysian
peninsula, Singapore, certain Indonesian and Philippine islands, Republic of Korea, Japan, New Zealand, Fiji, Hawaii
and certain other western Pacific and Caribbean islands,
Libya, Cape Verde, Sao Tome, Comores, Mauritius and Antarctica, but several of the countries mentioned in the Persian Gulf and South East Asia occasionally experience reintroductions of the disease.34, 37, 111 Several countries in
western Europe are on the point of eradicating rabies of terrestrial vertebrates (lyssavirus 1) as a result of conducting
successful oral vaccination campaigns on fox populations,52, 53, 782 but have nevertheless reported the presence
of bat-associated lyssaviruses (see below). In 1996, European bat lyssavirus 2 was also found in a bat in Britain, hitherto considered to be free of lyssaviruses.747 Apart from rare
imported cases of the disease,286 Australia has always been
free of rabies proper, lyssavirus 1, but recently the presence
of a lyssavirus genotype 7 has been recognized in fruit bats
(flying foxes) as well as in insectivorous bats, and there have
been two human infections with fatal disease resembling rabies.253, 270, 301, 317, 579, 617, 645 The degree of genetic divergence between fruit and insectivorous bat isolates in
Australia suggests that bat lyssavirus was probably present
before European colonization.739 The remaining countries
of the world have endemic rabies with marked variations in
prevalence and species affected, but the disease is poorly
monitored and under-reported in many instances.111
Europe
In western Europe, outbreaks of rabies involving dogs, foxes
and wolves were described in the eleventh and thirteenth
centuries, but urban rabies only became widespread after
the industrialization of the eighteenth century.133, 345, 648
From the time of the Second World War, rabies in the red fox
(Vulpes vulpes) spread steadily westwards from an original
focus in eastern Poland in 1935, to reach France by 1968,
with simultaneous eastward extension of the epidemic into
the former USSR, and many countries in Europe each reported one to several thousand cases of the disease in foxes
per annum in the 1970s and 1980s.34, 37, 63, 111, 692 Field trials
on oral vaccination of foxes were conducted in Switzerland
in 1978.647 A sustained oral vaccination campaign was
started in Switzerland in 1985, in France in 1986, and in 13
other European countries shortly thereafter.52, 53 After
minor setbacks, fox rabies was virtually eliminated from
western Europe by the end of the century, and it became necessary to extend the campaign into eastern Europe to prevent
re-introduction of the virus to the west.51, 52, 53, 652, 782
Dog rabies was still highly prevalent in western Europe in
the 1940s and 1950s, but the use of increasingly effective
vaccines and the rigorous application of control methods
over four decades reduced the annual incidence of the
Rabies
disease from thousands of cases to the point where the few
residual cases in dogs, cats, domestic ruminants and occasional deer, badgers and martens represented spill-over of
infection from foxes.34, 37, 111, 353 Fortunately cats and dogs
are partially resistant to fox virus.114 Human rabies virtually
disappeared from western Europe with the decline in dog
rabies; people seldom acquire infection from foxes and most
of the occasional cases of the disease seen recently have occurred in persons exposed to infection elsewhere.
Dog rabies remains a problem in Yugoslavia and in enclaves in the southernmost areas of the former USSR.111
Elsewhere in the western and southern portions of the
former USSR, the red fox is the major host of rabies, but the
raccoon dog (Nyctereutes procyonoides), a fur-bearing animal translocated from eastern to western USSR in the 1930s
and 1940s, is an increasingly important vector that has migrated westwards through the Baltic republics to become established in Poland and Finland.111, 166
Arctic rabies, regarded as an ancient and epidemiologically distinct entity, extends across the northern part of the
former USSR, Finland, the Svalbard Islands of Norway,
Greenland, the Northwest Territories of Canada, and
Alaska.111, 188, 353 The Arctic fox (Alopex lagopus) is the principal vector throughout but there is spill-over of infection to
wolves, bears, seals, sled dogs and reindeer. Wolves (Lupus
lupus) are extinct in much of Europe but are still important
vectors in parts of Iran, Afghanistan, Iraq and the former
USSR.111
Asia
Rapid population growth and urbanization in much of Asia
have created conditions which are highly conducive to the
occurrence of urban rabies. Several thousand cases of rabies
in dogs are recorded each year in India, Pakistan, Indonesia,
Thailand and Vietnam, while countries such as Bangladesh,
Burma, Iran, Iraq and the Philippines, which report comparatively few cases of animal rabies, nevertheless report
thousands of human cases or post-exposure treatments of
humans.111, 733 India has the highest number of human
deaths from rabies in the world, with estimates ranging from
15 000 to 25 000 cases per annum, but it has been argued
that the true figure may be as low as 4 000 cases per annum.8,
111
Monitoring of rabies in livestock and wild vertebrates is
even more deficient than in dogs and humans, but mongoose and jackal rabies occur in India and possibly elsewhere in Asia.8
North America
In North America, rabies was first described in dogs and
foxes in New England in the mid-eighteenth century and it
has been suggested that the disease was brought in with
dogs by European colonists.133, 612, 768 On the other hand,
there is a long history of the disease in Inuit folklore, and
Arctic rabies may have been introduced into North America
from northern Asia during the migration of humans and
1127
other animals across the Bering land bridge 30 000 to 75 000
years ago.188, 768 Dog rabies became widely distributed in
the USA in the second half of the nineteenth century following the civil war, and by 1944 dogs accounted for 86 per cent
(9 067/10 540) of cases of rabies recorded in that year, with
only 3 per cent of cases being recorded in wild vertebrates.133, 646 Following the institution of increasingly effective control measures in the 1940s and 1950s, the incidence
of dog rabies declined steadily to 128 cases in 1988, with no
cases being recorded in humans in that year.37, 646 At the
same time, however, there was a steady increase in sylvatic
rabies and by 1988 wild vertebrates (mainly skunks, raccoons, bats and foxes) accounted for 88 per cent (4 173/
4 723) of cases of rabies in the USA, with the remaining 422
(9 per cent) cases occurring in domestic cats and herbivores,
and in dogs particularly in the Texas–Mexico border area37
Moreover, it was found that ordinary passive surveillance
detects only 1 to 10 per cent of the number of cases of rabies
which are diagnosed when wild animals are deliberately
trapped for examination.95, 516, 724
Dog rabies extended across the USA border into central
and eastern Canada early in the twentieth century and, as in
the USA and western Europe, was brought under control following the introduction of effective vaccines in the 1940s
and 1950s, but here too there was an increase in sylvatic rabies as the disease in dogs declined, and by 1988 wild vertebrates accounted for 80 per cent of confirmed cases of the
disease in Canada.37, 95
Despite early reports to the contrary,451, 507, 513, 635 infection of bats with rabies virus proper, lyssavirus 1, has been
confirmed as occurring only in the Americas.95, 623, 625 The
first isolations of rabies virus from non-haematophagous
bats were made in the course of investigations into vampire
bat-associated rabies in Trinidad in the 1930s, but these
aroused little interest until 1953, when recovery of the virus
from an insectivorous bat which attacked a child in Florida,
USA, prompted investigations which culminated in isolations being made from 30/39 indigenous species of insectivorous bats of the USA and temperate Canada, and from
virtually all of the countries of Central and South America.60,
62, 177, 524, 581, 623, 723
In the late 1950s, when sylvatic rabies was only beginning
to assume its subsequent proportions in Europe and North
America, the hypothesis was developed that rabies virus is
maintained in vertebrates which only sporadically manifest
disease and that epidemics occur when infection spreads to
aberrant hosts such as wild or domestic canids which regularly develop encephalitis.344, 345 Mustelids, vivverids and
bats were implicated as the cryptic maintenance hosts in
various parts of the world and it was postulated that a climax
state of host–parasite relationship had evolved through long
association between the virus and these vertebrates.154, 333,
344, 345
A corollary to the theory was that effective control or
eradication of the disease could only be achieved by
identifying such cryptic maintenance hosts and directing
1128
SECTION FOUR:
appropriate control measures towards them. This view of
rabies has persisted in many countries, and the existence of
a sylvatic reservoir of infection is still widely cited as a reason
for failure to control dog rabies.
In practice, it was observed that the escalation of sylvatic
rabies in Europe and North America after the 1940s arose as
a series of outbreaks that involved the spread of infection in
specific hosts within separate geographic regions.167, 623–625
In a given area, the disease is manifested predominantly by
a single host species, or rarely by more than one, and this
same host appears to be responsible for the maintenance
and spread of the virus; disease in other animals represents
spill-over of infection resulting from sporadic contact with
the major host species.389, 391, 572, 573, 623, 625 The major host
is not determined simply by the relative prevalence of the
species since skunks, for instance, may be as numerous in
an area where fox rabies predominates as they are in an area
where skunk rabies predominates, and the converse is true
for foxes.515, 517 Nor can the phenomenon be ascribed simply to the isolation of vertebrate species from each other in
ecological niches since spill-over of infection causes sporadic disease, but only rarely initiates independent spread of
the virus in a second species. This suggests that strains of
rabies virus become uniquely adapted to circulate in
specific hosts, and indeed it was found, for instance, that
skunks are relatively resistant to virus of fox origin, but that
foxes are highly susceptible to skunk virus and succumb
rapidly without excreting the virus in saliva, i.e. without
being able to transmit infection.516, 518, 609 However, it is
implicit in these and similar findings with other species
that vertebrates vary inherently in their susceptibility to
infection and ability to excrete virus, so that the mechanisms responsible for the compartmentalization of circulation of rabies in species include both host and viral
factors.110, 156, 516, 518, 609
Proof that the circulation of rabies virus strains is compartmentalized in vertebrate species came from monoclonal antibody and phylogenetic studies, which in effect
resulted in the recognition of virus biotypes.110, 163, 215, 569,
573, 577, 589, 591, 623–626, 629–631, 663, 744, 758, 760, 761
It was found,
for instance, that a single biotype of virus occurs in red foxes
in western Europe;623 that rabies virus which affects the
North American red fox (Vulpes fulva) in hyperendemic
areas in south-eastern Canada and northern New York
State, USA, corresponds to the Arctic fox virus biotype from
which it was ostensibly derived by southwards spread of infection in the 1950s;345, 542, 623, 625, 768 that virus in the
striped skunk (Mephitis mephitis), which engulfed the
north-central states of the USA and south-central Canada, is
of a different biotype from that which occurs in skunks in the
south-central states and there is an area of overlap in the
distribution of the two biotypes where they converged, with
yet another biotype occurring in northern California;95, 165,
516, 623, 625
that virus associated with rabies in the raccoon
(Procyon lotor) in the Atlantic states corresponds to the en-
demic raccoon biotype of south-eastern USA, from which it
was apparently derived through translocation of raccoons
by hunters in 1977;342, 462, 501, 623, 625 and that separate
biotypes occur in grey foxes (Urocyon cinereoargenteus) in
Arizona and Texas.389
There appears to be surprisingly few biotypes of rabies
virus in relation to the range of vertebrates which become
infected, and those which are known to be in existence appear to have remained unchanged for at least a period of
several decades, indicating that the evolution of new biotypes is infrequent and thus most likely to occur where
there is large-scale transmission of virus to a second host: it
can be said that, in effect, a variant virus is selected only to
take advantage of changed circumstances.690 Lyssavirus 1,
which affects dogs all over the world, appears to have
transferred with facility between canine species, a recent
example being the spread of dog virus in coyotes (Canis latrans) in southern Texas.389, 561 More surprisingly, it appears that a bat variant of lyssavirus 1 had become
established in skunks in northern Arizona in 2001, when
the diagnosis was confirmed in 19 skunks. A control programme of trapping, vaccinating and releasing skunks was
instituted, and it remains to be seen whether transmission
has been successfully interrupted.414
The occurrence of rabies in bats does not exhibit the
same marked geographic bias as that which occurs in terrestrial vertebrates in North America, but there does appear to be an analogous compartmentalization of
circulation of virus in some species with spill-over of infection to others.623 Thus, monoclonal antibody and phylogenetic studies revealed that more than 30 distinct lineages of
virus circulate in insectivorous and vampire bats in the
Americas, with a tendency for migratory species of bats,
either colonial or solitary, to yield the same biotype in different locations, while sedentary species may yield a variety of biotypes.623–625 Interestingly, the sporadic cases of
rabies in humans and livestock which occur in parts of
North America where the disease is not known to be
present in terrestrial vertebrates, are most frequently
found to be associated with bat biotypes of virus.390, 623, 624,
625
Indeed, the isolated cases of rabies which occur in humans in the USA each year are almost all caused by virus
associated either with the silver-haired bat (Lasionycteris
noctivagans) or the eastern pipistrelle (Pipistrellus subfavus), and enigmatically it is usually difficult to obtain a history of exposure to bats, while a limited number of cases of
rabies occurs in immigrants exposed to infection with dog
virus abroad.390, 624
At the end of the twentieth century, the USA was still
experiencing more than 8 000 cases of animal rabies per
annum, with over 80 per cent occurring in wildlife.43, 389, 391
By then, raccoon rabies extended from Florida to Maine,
and had spread northwards into Ontario, Canada, and westwards to Ohio, overlapping fox rabies in the north, and
skunk rabies in the west.43, 132, 608 Control of wildlife rabies
Rabies
has proved to be more difficult in North America than in
Europe, largely because the problem is more complex, with
vast areas and multiple vector species being involved, as discussed in relation to oral vaccination below.
Central and South America
At the USA–Mexico border there is an abrupt transition
from the predominantly wildlife rabies of North America to
the dual problem of urban rabies in dogs and sylvatic
rabies in vampire bats in Central and South America.
Vampire bat-associated rabies was apparently first encountered by Spanish colonists early in the sixteenth century, and the problem was exacerbated by the growth of the
ranching industry in the late nineteenth and early twentieth centuries, which provided highly suitable hosts for the
bats, and roosting sites in otherwise inhospitable grasslands through the digging of wells.45, 46, 60, 62, 149, 306, 416,
442, 524
There are three species of vampire bat, each belonging to a separate genus, but Desmodus rotundus is the most
common and the most important transmitter of rabies.45
Vampire bats occur only in Central and South America and
Trinidad, from 28 °N in Mexico to 33 °S in Argentina, and
throughout this region they are associated with a paralytic
form of rabies which affects mainly cattle, but also to a
lesser extent humans and other animals.46 The disease of
cattle, known colloquially as derriengue (limping illness) or
mal de caderas (hip illness), is most prevalent in Brazil,
Mexico, Venezuela and Argentina, and total losses have
been estimated variously at 100 000 to more than 500 000
cattle per annum, but the true figure may be much greater
since more than 260 000 cattle are believed to have succumbed in part of Bolivia alone in one year.2, 46, 60, 416 Although there are no records of humans acquiring infection
from butchering the carcasses of rabid cattle in South
America, it is known that virus occurs in saliva and salivary
glands of a low proportion of such cattle.207
The results of experimental infections in the 1930s suggested that vampire bats were uniquely capable of acting
as true carriers of rabies virus, being able to survive frank
disease or to excrete the virus in saliva for extended periods
without developing overt disease, but the validity of the experimental methods has been questioned, and it is currently believed that the bats undergo variable incubation
periods and disease similar to other animals, excreting
virus in saliva for up to eight days before manifesting disease.60, 481 Although a proportion of vampire bats appears
to survive infection, as evidenced by the occurrence of antibody in free-living populations, it is thought that salivary
gland infection does not occur in the absence of brain infection.60, 481 It has also been suggested that insectivorous
bats and hibernating rodents could serve as reservoirs of
rabies virus through the persistence of infection in brown
fat during hibernation. Virus replication is suppressed by
the lowering of the body temperature and metabolic activity in hibernating animals, and the disease runs its normal
1129
course on the emergence of the host from hibernation.119,
120, 655
However, the relevance of the persistence of
infection in brown fat to the pathogenesis of the nervous
disease has been questioned and, as with vampire bats, it is
now believed that salivary gland infection does not occur
in the absence of brain infection.62, 119, 120
Urban rabies constituted a serious problem in Latin
American cities such as Mexico City, Lima, Bogota, Sao
Paulo and Buenos Aires, which are among the most populous cities in the world, but concerted urban vaccination
campaigns have improved the situation markedly since
1980.2, 167 A peculiar feature of the disease in Latin America
is the tendency for greater numbers of domestic cats to be
involved than elsewhere in the world.2
Caribbean countries
During the 1860s and 1870s, the grey mongoose (Herpestes
auropunctatus) of India was deliberately introduced into certain Pacific and Caribbean islands and a few mainland countries in South America with the intention that it would control
rats and snakes in sugar cane plantations. However, it filled a
vacant carnivore niche and in less than two decades had multiplied to the extent that it had itself become a pest.2, 233, 625
Rabies was first recognized in the mongoose in Puerto Rico in
1950, and since then the disease has been diagnosed in Cuba,
Dominica, Haiti, Grenada and the Virgin Islands, with the
mongoose being the dominant host of the virus in most instances, although dogs are also important hosts on some of
the islands.2, 95, 233, 625 A disturbing feature is that antibody
prevalence rates in excess of 50 per cent have been recorded
on occasion, indicating that a high proportion of the mongooses survives rabies, and it appears that such high immune
rates suppress circulation of virus, so that there are cyclical
epidemics as the proportion of susceptible individuals in the
population waxes and wanes.232, 233 Many Caribbean countries which are currently free of rabies have large mongoose
populations, and thus have the potential for the spread of the
disease. The results of feasibility studies suggest that oral vaccination could be used on mongooses.189, 419
Africa
Rabies is least well monitored in Africa. For instance, the
2 081 confirmed cases of the disease in domestic and wild
animals reported for the continent as a whole in 1988 constituted less than 5 per cent of the total for the world.37 Virtually all African countries have the requisite veterinary and
medical infrastructures, but many have been unable to devote adequate resources to monitoring and controlling rabies in the face of poverty, prolonged droughts, other
priorities, or armed conflict.4, 54, 211, 265, 329, 359, 370, 408, 429,
433, 441, 453, 483, 510, 616, 693, 707, 790
North Africa
Rabies has been present in North Africa since antiquity. It
occurs principally as an urban disease in the countries of the
1130
SECTION FOUR:
Mediterranean littoral such as Morocco, Algeria and Egypt
with each recording up to several hundred cases in dogs
annually, with lesser numbers of domestic cats, herbivores
and humans being affected, but it is under control in Tunisia
and Libya.74, 111, 153 The belt of countries lying immediately
to the south, including the northern part of Senegal, Mauritania, Mali, Niger, Chad, Sudan, Ethiopia, Djibouti and Somalia, span the Sahara Desert and are largely arid and
sparsely populated. Here rabies occurs in scattered urban
foci, but is translocated with the dogs of nomads or refugees
fleeing drought or war. Camels are sometimes victims of the
disease following outbreaks in dogs, and occasionally infection is recognized in jackals and hyenas.111 The occurrence
of rabies in the Ethiopian wolf (Canis simensis),613, 749 is a
matter for concern since this species, plus Blanford’s fox of
Asia (Vulpes cana), and the African wild dog (Lycaon pictus)
are considered to be the only carnivores which are sufficiently rare so as to be threatened with extinction by
rabies.437
Sub-Saharan Africa
In sub-Saharan Africa, where humans and other animals are
more widely distributed than in northern Africa, there has
been a greater tendency for epidemics of dog rabies to
spread over large areas and for the disease to be observed in
domestic herbivores and wild vertebrates.111 This trend is
most noticeable in the more developed countries of southernmost Africa, where the high proportions of cases recorded in wild animals must to some extent reflect more
intensive monitoring of the disease, but where specific
problems with sylvatic rabies are nevertheless encountered.667
West Africa
In West Africa, rabies was first diagnosed in Nigeria, Senegal and Niger in 1912, and the general pattern in the region
has been for the disease to affect mainly dogs and to a
lesser extent cattle, other livestock and humans.4, 10, 80, 121,
228, 510, 512, 693
It is notable that the region yielded the first
isolates of Lagos bat and Mokola viruses, plus five other
rhabdoviruses, and that strains of rabies virus with reduced virulence for dogs have been isolated at intervals
over many years in the area extending from West Africa
across to Ethiopia, suggesting that lyssaviruses have undergone a long period of evolution and dissemination in
the region, and fuelling speculation that Africa may be the
cradle of rabies.146
A non-fatal form of rabies in dogs, known colloquially
as oulou fato (mad dog disease), was first recognized in
Senegal and Niger in 1912, and its distribution apparently
extended across Zaire, Cameroon, Ivory Coast, Ghana, Nigeria and the Sudan.121, 558, 639, 682 There have been no recent reports of a disease by the name of oulou fato, a term
which appears to have fallen into disuse, but strains of
virus capable of producing non-fatal and chronic infection
of dogs were isolated in Ethiopia in the 1950s and 1970s,
and similar findings were reported in India.18, 240, 241, 721
Naturally affected dogs were capable of transmitting fatal
disease to humans, in some instances over a period of
years. The site of chronic infection may be the tonsil.245 In
a recent investigation of the phenomenon, four isolations
of rabies virus were made from the saliva of healthy dogs
presented for vaccination over a period of five years in Nigeria, and only one of these isolates produced fatal disease
in puppies.6 At about the same time, 1989, six cases of
symptomatic rabies in dogs were linked to the use of the
Flury strain of attenuated virus vaccine in Nigeria,511 a
phenomenon more commonly seen in cats. It was demonstrated in Russia that a proportion of dogs can survive intracerebral inoculation with rabies strains associated with both
the convulsive and paralytic forms of the disease.290
East Africa
In East Africa, the presence of endemic rabies of dogs and
jackals was recognized in Kenya from 1900 onwards and
the diagnosis was first confirmed in a dog bitten by a jackal
in the Nairobi district in 1912, but the disease had been
known to the indigenous inhabitants of the country before
the arrival of European colonists.321, 359 Endemic rabies of
dogs was recognized in north-western Tanzania on the
Kenya border in 1932 and was first confirmed in 1936.562,
575
In 1956, an outbreak of more serious proportions
occurred in Mbeya district in the south-west of the
country, adjacent to the borders with Zambia and Malawi,
spread north-eastwards across the country during the
1960s, and swung north-westwards in the 1970s to produce
a severe epidemic in the extreme north-west of Tanzania at
the end of the decade.447, 575 Spread of the epidemic
continued into Kenya and by the mid-1980s had engulfed
most of that country.359, 616 Dog rabies remains a problem
in Kenya and Tanzania. During the 1990s, rabies devastated populations of the wild dog (Lycaon pictus) on the
Serengeti plains of Tanzania and Kenya, with infection
apparently spreading from the domestic dogs of nomadic
herdsman.11, 12, 141, 142, 224, 277, 360, 361, 436, 480 Contentions
that the wild dog had been predisposed to rabies through
stress induced by handling in ongoing ecological studies,
could not be supported on the basis of experiences
elsewhere in Africa.204 The wild dog in the Selous Game
Reserve in the south of Tanzania appeared to have
been spared, but rabies was also recorded in bateared foxes (Otocyon megalotis) (Figure 99.1) in the
north.190, 435
In Uganda, sporadic outbreaks of dog rabies were recognized from 1935 onwards, but from 1971 monitoring and
control of the disease deteriorated as a result of political
instability, and it is believed that the mere 12 cases confirmed in the decade from 1981 to 1990 do not reflect the
seriousness of the problem which has developed in that
country.330, 562
Rabies
1131
Figure 99.1 Bat-eared foxes
(Otocyon megalotis). (By
courtesy of the National Parks
Board, P O Box 787, Pretoria
0001, South Africa)
Malawi, Zambia and Angola
Namibia
Rabies is endemic throughout Malawi, where the occurrence of the disease was suspected in 1916 and confirmed in
1926.639 At least 1 656 cases of rabies were confirmed from
1977 to 1987, with the vast majority occurring in dogs, although the disease also occurs in jackals and hyenas.483
In Zambia, rabies was apparently present in the nineteenth century, and in 1901 Chief Lewanika of the Barotse in
the west of the country ordered the destruction of all dogs in
the area in an attempt to control a serious outbreak of the
disease.226, 605, 639 The diagnosis of the disease was first confirmed in 1913 and it has continued to occur throughout the
country.615, 707, 790 The disease mainly affects dogs, but appreciable numbers of cattle fall victim to the disease in the
south-central part of the country, particularly in locations
where jackal rabies is diagnosed close to nature reserves.790
There appears to be a much higher ratio of dogs to people in
rural communities in Zambia than in urban centres, and the
rural dogs are less accessible to vaccination.202 Recently
virus which cross-reacts with anti-rabies fluorescein conjugate was isolated from the brain of an unidentified bat found
dead in Zambia, but no definitive characterization of the bat
or isolate was performed.7 Lyssavirus 1 has only been identified in bats from the Americas, so the Zambian isolate is
likely to have been a rabies-related virus, possibly Lagos bat
or Duvenhage virus.
Rabies was first confirmed in Angola in 1929 and since
then the disease has been diagnosed mainly in dogs, with
very few cases being recorded in other domestic or wild animals,223 but the protracted civil war in the country has hampered monitoring and control of the disease over several
decades.
An outbreak of disease fitting the description of rabies and
involving dogs, cattle and small livestock was apparently observed in Namibia in 1887,328, 583 and from 1925 onwards
there were sporadic reports of outbreaks of disease involving dogs, humans and, on one occasion a hyena, in the
Ovambo, Kavango and Caprivi Strip districts in the north,
bordering Angola and Zambia, with an isolated case being
recorded further south in a child bitten by a dog in Swakopmund in 1928 and another in a woman bitten by a wild cat in
Grootfontein in 1937.727 A diagnosis of rabies was finally
confirmed in a dog from Rundu in Kavango in 1938, but a
suspected outbreak of the disease which occurred on farms
in the Gibeon and Mariental districts in the south in 1945
could not be confirmed.727 The position changed sharply
with the occurrence of the second confirmed case of rabies
in 1947, also in a dog in Rundu, which was followed in 1948
by the appearance of the disease south of the Etosha National Park in cattle in Outjou district, whence spread of disease involving black-backed jackals (Canis mesomelas)
(Figure 99.2) and cattle continued southwards to reach Otjiwarongo in 1949 and the central districts of Gobabis and
Windhoek by 1951.13, 40, 583, 727 Since then, rabies has remained a problem in Namibia, with dog and human cases
being recorded mainly in the north where the density of the
rural population is greatest, jackal and cattle rabies dominating in the central ranching area, and sporadic disease
being associated with felids (the African wild cat, Felis lybica, and caracal, Felis caracal) and vivverids (genets and
mongooses) in the sheep-rearing areas of the south.40, 208,
583
Outbreaks of rabies in black-backed jackals have a threeto four-year periodicity in central Namibia, and these
1132
SECTION FOUR:
Figure 99.2 Black-backed jackal
(Canis mesomelas)
outbreaks are significant predictors of disease activity in
domestic ruminants and dogs.186
There were two unusual developments in Namibia: epidemic spread of rabies in kudu antelope (Tragelaphus strepsiceros) from 1977 to 1985 in the central ranching area, and
the subsequent occurrence of the disease in carnivores
ranging from bat-eared foxes and jackals to lions in the Etosha National Park. A localized outbreak of rabies in kudus
occurred in Windhoek district in 1975, but the epidemic
which followed began in Okahandja district in 1977 and over
the next few years spread to Karibib, Omaruru, Windhoek,
Otavi, Otjiwarongo, Outjou, Gobabis, Grootfontein and
Tsumeb districts, causing an estimated loss of 30 000 to
50 000 antelope, or 20 per cent of the population, by the time
the outbreak subsided in 1985.84, 85, 303, 328, 583, 603 It is believed that the kudu population had attained an unprecedented density during the 15 years preceding the epidemic,
and this was ascribed to the conservation of kudu and control of predators because of the increasing value of trophy
hunting and export of venison; overgrazing of pastures by
cattle resulting in encroachment by bushes and trees which
favour browsing animals; increased installation of watering
points on ranches; and the occurrence of a succession of
seasons of above average rainfall. An increase in jackal rabies was noted prior to the epidemic and it was surmised
that rabid jackals initiated the infection in the kudus, but
thereafter the number of cases recorded in the antelope was
disproportionately high in comparison to that in jackals,
suggesting that the disease was also transmitted directly between kudus. This possibility was strengthened by the fact
that eastward extension of the outbreak was initially
checked for two years by a game control fence, which hindered the passage of antelope but not small carnivores.
Rabies virus is not ordinarily resistant enough for indirect transmission to occur through contamination of the environment with infected saliva, and it is believed that
transmission between kudus was favoured by their propensity to indulge in self and mutual grooming, and by the fact
that oral transmission would have been facilitated by the
mouth injuries which kudus sustain when browsing on the
Acacia thorn trees which predominate in the affected area.
However, individuals sometimes browse in close proximity
to each other, so that transmission of infection through contamination of vegetation was possible. It was shown that
kudus are highly susceptible to infection by the oral route,
and that infected individuals excrete high concentrations of
rabies virus in saliva.85 The social behaviour of kudus further
facilitated the spread of infection through the dispersal of
individuals in winter and re-grouping into matriarchal units
in summer, with solitary breeding bulls showing the greatest
tendency to range over long distances and to make contact
with members of different groups.
The infection was apparently communicated to other herbivores, since the epidemic in kudus was followed by a surge of
rabies in cattle and to a lesser extent in eland antelope (Taurotragus oryx), which are grazers by preference. Cattle and
game animals generally congregate separately at places, such
as watering points, but rabid kudus do not avoid contact with
other species. It is notable that Von Maltitz727 had earlier postulated that oral transmission occurred in cattle, in order to account for the high incidence of the disease which occurred on
some ranches when rabies spread southwards in Namibia at
the end of the 1940s. He had observed on one ranch that where
cattle were being fed bone meal that contained coarse chips
capable of causing mouth injuries, a rabid individual had
salivated into the feeding trough.
Rabies
Etosha National Park lies in the pathway of the southwards spread of rabies in 1948, and so the outbreak observed
in the park in the early 1980s could have originated from endemic disease, but it is believed that the infection was probably re-introduced from Tsumeb district in the 1980s by
jackals which are able to penetrate the game-proof fence of
the park.91 The outbreak in the park was unusual because
rabies has never become established in major game reserves, such as Hwange National Park in Zimbabwe and the
Kruger National Park in South Africa, despite the marginal
intrusion of jackal rabies into the former on one occasion in
the early 1980s,264 and the known periodic incursion of
rabid dogs into the latter.40 Foggin264 postulated that the diversity of carnivores which occurs in large undisturbed
areas such as the Hwange and Kruger national parks dictates
that no single species becomes so numerous that it exceeds
threshold density for spread of the disease, and that there is
insufficient interspecific contact for the maintenance of infection. In contrast, the Etosha National Park supports a
lesser species diversity and its arid nature is probably more
conducive to the occurrence of intra- and interspecific confrontation. The same is probably true of the Kgalagadi
Transfrontier Park in the South African part of the park
where rabies has been recorded in the spotted hyena (Crocuta crocuta).40 Antibody to rabies virus was found in 30 per
cent of domestic dogs in Tsumkwe district, north-eastern
Namibia, but not in the wild dog.406, 407
Botswana
In Botswana, there were unconfirmed focal outbreaks of
rabies in Lobatse in the south-east in 1919 and 1922, and in
1133
Ngamiland district in the north-west in 1936, where the diagnosis was first confirmed in a dog in 1938.40, 173, 309, 449,
639
According to veterinary correspondence cited by Foggin,264 an outbreak of dog rabies of more serious proportions was noted in Ngamiland, adjacent to the Caprivi Strip
and Kavango districts of Namibia, at some stage before
March 1950, and by September the disease had crossed to
Serowe in the east and swept down the eastern border to
the south of the country, i.e. infection spread to all areas
where the human, and therefore dog population was most
dense. Along the way, the infection spread into southwestern Zimbabwe and the northernmost Limpopo Province of South Africa. The disease has remained active in all
of the areas of Botswana initially affected, but in addition
to the original problem of dog rabies with occasional
human cases, there has been a tendency for increasing
numbers of jackals, cattle and other livestock to be
involved.446, 455, 482
From about 1980 onwards a separate outbreak of rabies involving domestic herbivores and wild animals developed in
the Ghanzi district on the western border of Botswana, apparently as an extension of the kudu epidemic in Namibia, and
within a few years had spread 1 000 km south-eastwards across
the country to Kgatleng district on the North West Province
border of South Africa.482 Southward extension occurred into
the Kgalagadi district482 and Kgalagadi Transfrontier Park, and
in 1986 rabies was diagnosed in spotted hyena in the South African part of the park.40 Sporadic cases of rabies are diagnosed
in the yellow mongoose (Cynictis penicillata) (Figure 99.3)
and in the small-spotted genet (Genetta genetta) in southern
Botswana.446, 455, 482
Figure 99.3 Yellow
mongoose
(Cynictis penicillata)
1134
SECTION FOUR:
Zimbabwe
Zimbabwe was apparently free of rabies in 1890 when European colonists arrived in the country, but some of the older
inhabitants could recall that the disease had been present
when they were young.226 In 1902, dog rabies appeared in
the Bulawayo area in south-western Zimbabwe, and there
appears to be little doubt that the disease was introduced
from western Zambia which had considerable traffic with
Zimbabwe at the time, and where the disease was known to
be rampant in the Barotseland area in 1901 (see above).226,
605
Within two years 60 000 dogs were destroyed in an attempt to control the disease in Zimbabwe, and, although
this must have represented a considerable proportion of the
population at the time, the disease continued to spread
throughout most of the country. Control of the disease was
finally achieved in 1913, this being ascribed largely to the
imposition of a dog tax, which provoked drastic voluntary
reduction of the population on the part of dog owners.226,
605
The infection apparently did not become established in
wild hosts, and failure of the outbreak to extend into South
Africa was ascribed to preventive action in the form of a
radical reduction of the dog population within an 80-kmwide strip along the Limpopo River where it forms the
northern borders of the country with Zimbabwe and
Botswana.449
After 1913, Zimbabwe remained free of rabies until 1938,
when two cases were diagnosed in dogs at Victoria Falls,
and, as before, the evidence indicated that the infection had
been introduced from Zambia.605 Except for bridges at certain points, the Zambezi River forms an effective natural
barrier to the spread of rabies from Zambia, and after 1938
Zimbabwe again remained free of the disease until dog rabies crossed the south-western and southern borders of the
country from Botswana and the Limpopo Province of South
Africa in 1950 — it is believed that the virus was introduced
by dogs which accompanied people who crossed the borders illegally to purchase grain.3, 605 The disease spread rapidly through Zimbabwe, following routes along the more
densely populated communal farming areas, and by 1954
had reached the north of the country.3, 605 The growth in the
human population since 1913 made it difficult to enforce
control measures, such as dog ‘tie-up’ orders and the destruction of strays, and from 1951 onwards mass immunization campaigns were conducted with Flury LEP (low egg
passage) vaccine, which had then only recently become
available.3, 605, 766
By the early 1960s control of the disease had been
achieved over most of Zimbabwe, apart from resistant foci
on the eastern and western borders with Mozambique and
Botswana, and vaccination campaigns were scaled
down.264, 444, 766 From 1965 onwards, however, political unrest culminating in civil war rendered it increasingly difficult
to immunize dogs in the communal farming areas, and the
prevalence of rabies progressively rose to a record level of
861 confirmed cases in 1981, after the cessation of the war in
1980.264, 266, 408, 665 Following the formal ending of the war,
the control of dog rabies was complicated by continued
strife in Matabeleland in the south-west, and by an influx of
refugees from the civil war in Mozambique in the east, while
elsewhere in the country jackal rabies assumed serious proportions.264 Dogs, jackals and cattle comprise 89,9 per cent
(6 726/7 483) of all animals in which rabies has been confirmed in Zimbabwe from 1950 to 1991, and no other country has recorded as many cases of jackal rabies.
A minor portion of the land in Zimbabwe is devoted to national parks and urban development, while the bulk of the
country is divided approximately equally between commercial
and communal farming. Commercial farms are generally well
wooded, and apart from large wild carnivores and herbivores
which have been eliminated, wildlife, including jackals, is generally preserved or tolerated, and few dogs are kept.264 In contrast, communal farming areas are generally overgrazed and
deforested, wildlife is scarce, and dogs are kept for hunting.
Consequently, dog rabies has occurred mainly in or close to
communal farming areas, and jackal rabies has occurred almost exclusively on commercial farms.264
Jackal rabies was first diagnosed in Zimbabwe in 1952,
some 15 months after the disease had entered the country in
1950, and the first outbreaks occurred along the eastern border in Chipinge district from 1952 to 1953 and Odzi district
from 1952 to 1955.197, 263, 264 Thereafter, outbreaks of jackal
rabies occurred in widely separated districts at irregular intervals of many years, including Chipinge again on two occasions, Harare, Marondera and the Midlands twice each,
and Plumtree, Bulawayo and Lomagundi districts once
each.197, 264, 368 Since the outbreaks always occurred in
proximity to outbreaks of dog rabies and did not recur in the
same areas for periods of seven years or more, it was argued
that the virus was not adapted for maintenance in jackals
but had to be re-introduced by dogs.197 However, several of
the outbreaks which have occurred since 1965, and sporadic
isolations of rabies virus from jackals, have taken place well
away from known centres of infection in other species.264
An alternative explanation given for the failure of rabies
to persist in areas where epidemics occurred in jackals was
that the disease reduced the density of jackals to below the
threshold required for spread of infection.264 Both the
black-backed jackal and the side-striped jackal (Canis adustus) occur in Zimbabwe, with partially overlapping distributions, and both are involved in outbreaks of rabies. Although
outbreaks of the disease in jackals are invariably accompanied by disease in cattle, the degree of involvement of cattle
varies. In one outbreak it was established that 1 200 cattle
had died, of which 140 were confirmed to have been rabid.264 It can be concluded that rabies is transmitted by jackals in Zimbabwe, and that infection is freely communicable
between dogs and jackals, as appears to be the case in other
parts of southern Africa, but that jackal populations are
probably too sparse to perpetuate virus in the absence of reintroduction of infection from dogs.98, 100, 559 The results of
Rabies
laboratory investigations suggest that oral vaccination of
jackals is possible, but field trials would be necessary.67, 101,
103, 104
The occurrence of rabies in most other species in
Zimbabwe appears to represent spill-over of infection from
dogs or jackals, but there have been clusters of cases of the
disease in the slender mongoose (Galerella sanguinea) in
the south-west of the country on occasion, with some indication of progressive spread of the centres of infection.264
Control of dog rabies remains a problem particularly in
communal farming areas, and dog population studies
are important for planning and assessing vaccination
coverage.99, 131, 537
South Africa, Mozambique and Swaziland
Historical writings have been cited to the effect that suspected rabies involving dogs and/or humans was observed
in the Western Cape Province of South Africa in 1772, 1825,
1826 and 1883, in KwaZulu-Natal Province in 1823 and 1857,
and in the Free State Province in 1861, although at least two
early travellers remarked on the complete absence of the
disease in the country.173, 309, 493, 639 In 1893, an outbreak of
the disease in dogs in the Eastern Cape Province was diagnosed by inoculation of rabbits, and this was the first occasion on which a diagnosis of rabies was confirmed on the
continent of Africa.327 The outbreak was initially recognized
in Port Elizabeth in April, 1893, but the results of inquiries
suggested that the first case had occurred in September 1892
in a dog imported from England, which had become rabid a
few weeks after its arrival. The outbreak was believed to have
affected about 90 dogs, seven cats and a few cattle, but no
wild animals, and had spread to the Uitenhage, Jansenville,
Willowmore and Albany districts by the time it was brought
under control in August 1894 through the muzzling and restriction of dogs and the destruction of strays.225, 309, 327
After 1894, rabies was not confirmed again in South Africa for 34 years, but there was mounting anecdotal evidence to indicate that an endemic form of the disease
associated with viverrids was present. In particular, there
was a general belief in the Eastern and Northern Cape provinces that bites from genets (Genetta genetta) caused fatal,
rabies-like illness in humans, and specific reports of such incidents dated back to 1885.173, 259, 639 Cluver173 documented
11 unconfirmed cases of human rabies which occurred in
what is today southern Gauteng, Free State and Northern
Cape from 1916 to 1927, following bites by yellow mongooses, dogs and a genet. The disease was finally confirmed
in 1928 in two children bitten by a yellow mongoose in Wolmaransstad district in the North West Province,310 and since
that time rabies has been diagnosed regularly in South Africa.
Within a short period after the diagnosis of the disease
was confirmed in 1928, rabies was recognized in numerous
locations in South Africa in dogs, domestic cats, yellow
mongooses, suricates (Suricata suricatta), genets and wild
felids, and in humans and farm animals which had been bit-
1135
ten by these carnivores.221, 493–495, 638 The veterinary investigators were well aware that the disease, which occurred
principally in the yellow mongoose, differed fundamentally
from what they termed classical European-type dog rabies
in that there were sporadic cases in dogs, but no real tendency for the infection to spread among them; in essence
pre-empting the concept of biotypes by several decades.493
Initial conjecture that the endemic disease might have
arisen by extension from the epidemics of dog rabies which
had occurred in the Eastern Cape Province from 1892 to
1894 and in Zimbabwe from 1902 to 1913 gave way to the
conviction that viverrid rabies had long been present in
South Africa, possibly for centuries, but had simply not been
recognized.221, 222, 493–495, 638, 639 Subsequently, brief reference was made to the fact that experimentally infected mongooses were unable to transmit infection to dogs by bite, but
the strain of virus, species of mongoose and numbers of animals on experiment, were not specified.13 It was subsequently shown that the yellow mongoose is more
susceptible to lethal infection with mongoose virus than
with dog virus, and excretes mongoose virus more readily in
saliva than dog virus.13, 155
As the area known to be affected by rabies expanded,
there was speculation that this was due to both recent
spread and the fact that the true distribution of the disease
was still being elucidated,639 but later the results of deliberate investigations revealed that the occurrence of endemic
rabies was confluent over the greater part of the interior plateau of South Africa west of the Drakensberg mountains.466,
467
The only areas to be excluded were those which fell outside the distribution of the yellow mongoose — Limpopo
Province in the north, KwaZulu-Natal apart from the northwestern margin of the province adjoining the Free State, the
easternmost Transkei portion of the Eastern Cape Province
and a narrow coastal strip extending from Port Elizabeth towards Cape Town.466, 467 The mongoose occurs less abundantly in Botswana, where it is absent in the east, and it is
present in Namibia apart from the coastal Namib Desert.
The yellow mongoose is diurnal and its role as a maintenance host for rabies virus is facilitated by the fact that it
lives in colonies of ten or more individuals. It is most abundant in the north-western Free State Province and in the adjacent North West Province,639 where figures recorded in a
study of population density suggest that there were about
78 078 individuals in an area of 122 551 hectares.785, 788 The
mongoose prefers open country, devoid of dense bush
cover, and lives in proximity to water courses or vleis where
soft soil facilitates burrowing. Over much of its distribution,
the mongoose utilizes and adapts warrens pioneered by
ground squirrels (Xerus inauris) (Figure 99.4) with which it
shares the warrens in apparent harmony. Warrens vary from
relatively simple, branched burrows, to complex networks
of interconnecting tunnels 0,3 to 1 m below the surface, covering an area 50 m or greater in diameter, and with 90 or
more openings.639, 788 Peak mating activity occurs in August
1136
SECTION FOUR:
and September, at which time the progeny of the previous
year disperse, and after a gestation period of 42 days unisexual litters of up to four pups are born, of which only one
or two are successfully weaned.785, 787, 788 Recent evidence
suggests that immature individuals do not disperse, but assist in the rearing of the young of the succeeding litter.550, 745
The lifespan of the mongoose is estimated to be between
one and four years under natural conditions, but longevity
of 13 years has been recorded in captivity.788 The yellow
mongoose is mainly insectivorous, but also preys on small
vertebrates and feeds on carrion.639, 786 Individuals forage
from 600 to 3 000 m from the warren, and range furthest during the dry winter months and in drought years.639, 785, 788
Comparatively few cases of rabies have been recorded in
ground squirrels and suricates, the distributions of which
largely coincide with that of the yellow mongoose, but there
appear to have been no specific attempts to determine the
relative population densities of the three species. It is possible that rabid ground squirrels and suricates have been
misidentified as yellow mongooses on occasion, or categorized as unidentified mongooses. In the north of its distribution range, the ground squirrel, and by implication the
yellow mongoose, occurs focally on lime outcrops where
burrows are easier to keep open than in the intervening
Kalahari sands,639 and this may account for the more sporadic occurrence of viverrid rabies in northernmost Northern Cape Province, Botswana and Namibia, than further to
the south. On the other hand, there is marked genetic variation in populations of the mongoose and this could theoretically be associated with differences in susceptibility to
rabies.677, 678 Ground squirrels, which are rodents, occur in
Figure 99.4 Ground squirrel
(Xerus inauris). (By courtesy of
the National Parks Board,
PO Box 787, Pretoria 0001,
South Africa)
colonies of 8 to 30 individuals and are largely vegetarian,
feeding on plant bulbs, roots, stems and seeds, but also take
insects.637, 639, 786 Suricates, which are viverrids, occur in
migratory groups of up to 30 individuals, and are insectivorous but also feed on plant material. Itinerant groups of suricates677 periodically evict yellow mongooses and ground
squirrels from warrens, which they then occupy temporarily, usually for a matter of days.639, 785
As early as 1930 efforts were made to control viverrid rabies through the eradication of the yellow mongoose by
trapping, poisoning, gassing, or destroying warrens with explosives.639 Carbon monoxide, sulphurous gases, cyanide
gas and phosphine were tested, and from 1939 onwards the
standard method used to eradicate colonies of the mongoose was to pump cyanogas (later phosphine) into warrens, and to follow this with the setting of gin traps to catch
individuals that escaped gassing.639, 789 The method was applied on farms or town commonages where mongoose rabies was diagnosed, and about 50 000 to 160 000 hectares
were treated annually until exceptionally heavy rains in 1974
to 1976 restricted the access of control teams to affected locations.40, 639 From that time onwards mongoose control,
which had become prohibitively expensive, has been applied more selectively to about 5 000 hectares each year in
strategic locations where mongoose rabies occurs in proximity to urban centres, and in addition, chemicals for gassing have been made available to farmers. Furthermore, in
the past dogs were immunized within a radius varying from
15 to 25 km from outbreaks of mongoose rabies, while at
present dogs are immunized only as deemed necessary by
state veterinary officials.
Rabies
It was realized from an early stage that focal eradication
of the mongoose provided only temporary control of rabies,
that re-colonization of gassed warrens began almost immediately and that there was a compensatory increase in litter
sizes, with populations being restored to initial levels within
three years.639, 785 It was noted that rabies recurred from
1932 to 1936 on several of the farms where mongooses had
been eradicated in the initial experiments of 1930 and
1931.639 The prevalence of mongoose rabies rose progressively in each decade from 1950 onwards to reach epidemic
proportions by the early 1970s, despite the application of the
control measures, and continued to fluctuate at high levels
in the 1970s and 1980s following the abandonment of systematic mongoose control. In retrospect, it is difficult to discern whether or not mongoose control had any significant
suppressive effect on the occurrence of rabies, or whether it
merely created disturbances in population dynamics which
ultimately favoured epidemic spread of infection,785 but at
least it is clear that control of the disease was not attained.
Veterinary officials in South Africa were conscious of the
threat posed by the invasive canid form of rabies which had
appeared in Namibia and Botswana at the end of the 1940s,
and spread of the disease from Botswana into the Limpopo
Province was duly recognized in June 1950, and thence into
southern Zimbabwe by August, but enquiries revealed that
the virus had probably entered both countries some months
earlier.3, 13, 203, 449, 640 The disease did not extend southwards in the relatively dry and sparsely inhabited western
part of Limpopo Province and adjoining North West Province, but spread to the more densely populated areas to the
east and entered Mozambique in 1952 via the extreme
north-eastern corner of South Africa, which at that time had
not been incorporated into the Kruger National Park.13, 449,
712
Some 22 000 dogs were destroyed within two years in an
attempt to control the disease in the Limpopo Province, and
from 1952 onwards Flury LEP vaccine was used to immunize
dogs in the area.3, 13, 449, 640 The outbreak had subsided to a
few sporadic cases by 1954, and although 181 414 dogs had
been vaccinated in north-eastern Limpopo Province by
1962, dog rabies has remained present in the area.40, 449, 450
Cases of rabies in black-backed jackals and cattle were
recorded on bushveld ranches during the initial outbreak of
the disease in the Limpopo Province in 1950, and attempts
were made to control jackals by trapping or poisoning them
with meat baits laced with strychnine.449 The jackal is
mainly nocturnal and solitary, but females attract a following of several males during the mating season from May to
July, at which time dispersal of the previous year’s progeny
occurs, and litters of one to five pups are born from August
to October. Individuals forage over distances of up to 40 km
a night, preferring to travel along roads or open pathways.134, 449 There is evidence that individual jackals are
loosely associated in cryptic packs, with the implication that
disruption of the hierarchy through persecution may increase agonistic encounters and hence the prevalence of ra-
1137
bies.461 Nevertheless, the system which apparently proved
to be most effective for the control of jackals consisted of
laying a scent trail by dragging fresh or decomposed carcasses, meat or entrails of domestic or wild ungulates along
roads or paths, and placing poisoned baits at set intervals
along the trail. Comparisons of relative population densities
could be made from the numbers of jackal tracks observed
on roadways, and the numbers killed could be estimated
from the number of baits taken and the fact that dead jackals
were found to have consumed an average of two baits.449 Attempts to control jackals were also made in Namibia,
Botswana and Zimbabwe, and in the 1960s the explosive
coyote-getter device was brought into use.264, 715
An estimated 3 900 jackals were poisoned from 1951 to
1956 in Limpopo Province,449 and although the campaigns
provided only temporary and localized control of rabies, the
impression had been gained by the mid-1960s that the disease had not become permanently established in wild animals in the region.451 Jackal and cattle rabies became a
serious problem again in the mid-1970s, and it was thought
that a further introduction of jackal rabies had occurred in
the vicinity of Messina (now known as Mussina) in 1974,
from Zimbabwe across the Limpopo river.134 Immunization
of cattle with Flury HEP (high egg passage) vaccine was introduced in 1976,134 but the disease in jackals and cattle remains a problem in the Limpopo Province. Barnard82 drew
attention to the fact that where jackal rabies occurs in Limpopo Province and Namibia, the number of cases of the disease recorded in domestic herbivores, particularly cattle,
exceeds that in all vector species by up to three-fold or more,
and that this ratio is reversed in areas where viverrid rabies
predominates. It is a common finding in all areas where
jackal rabies occurs in Botswana, Zimbabwe and Zambia
that laboratory confirmation of the diagnosis is sought only
in a minor proportion of the cases of the disease actually observed in cattle.134, 263, 264, 446, 482, 727, 790 Over the years, sporadic cases of rabies have also been recorded in civets
(Civettictis civetta), honey badgers (Mellivora capensis), and
antelope in Limpopo Province, and isolated cases have been
confirmed in genets, bat-eared foxes, hyraxes (Procavia capensis), the brown hyena (Hyaena brunnea) and Selous’ mongoose (Paracynictis selousi), which is nocturnal and
solitary.40, 134, 449 In the 1990s, the canid biotype of rabies
virus extended to North West Province, and affected wild
dogs in the Madikwe Game Reserve.313
Rabies was thought to be endemic in central Mozambique from at least 1908 onwards, and was first confirmed in
Tete district in 1950.712 In 1952, the epidemic of dog rabies
which was raging in the north-eastern Limpopo Province of
South Africa extended into Mozambique and spread rapidly
throughout the central and southern districts of the country,
where the disease has remained prevalent since that
time.712 Rabies has been diagnosed predominantly in dogs
in Mozambique, and it is hyperendemic in the southernmost Maputo district where the population is densest, but
1138
SECTION FOUR:
monitoring and control of the disease was hampered by prolonged civil war.210, 211, 429, 712 In 1954, dog rabies spread
from Maputo district into Swaziland, where the occurrence
of the disease was confirmed for the first time, and since
then there have been periodic incursions of rabies from
Mozambique into Swaziland and the adjoining portion of
the Mpumalanga Province of South Africa which lies between Swaziland and the southern boundary of the Kruger
National Park.40, 312
In mid-1961, dog rabies spread from Maputo district in
southern Mozambique into northern KwaZulu-Natal in
South Africa.40, 450, 452, 672 Apart from the fact that there had
been unconfirmed reports of the disease in the nineteenth
century,309 KwaZulu-Natal had hitherto been free of rabies,
and the epidemic which followed the introduction of the
virus in 1961 was of an intensity unprecedented in South Africa. The density of the rural population in the coastal and
many of the midlands districts of KwaZulu-Natal favoured
the spread of the disease in dogs, and the epidemic extended
progressively down the length of the province. Vigorous efforts were made to control the disease through the vaccination of dogs and the prohibition of translocation of
unvaccinated individuals,450 and these led to the outbreak
in KwaZulu-Natal being finally brought to an end late in
1968.40 The numbers of dogs immunized annually from
1961 to 1968 never exceeded 41 per cent of the estimated
total population, but higher degrees of vaccination coverage
were attained in the most severely affected areas, which received the most attention.
Rabies reappeared in the northern districts of KwaZuluNatal, adjacent to the Maputo district of Mozambique, in
mid-1976,40 at a time when there was an influx of refugees
fleeing the unsettled conditions which followed the assumption of independence by Mozambique from Portugal.
During the eight years since rabies had last been diagnosed
the population of KwaZulu-Natal had continued to burgeon, and since many rural inhabitants sought livelihoods
in urban centres, informal settlements flourished, where
uncontrolled dog populations provided fertile ground for
epidemic spread of the disease. Moreover, the increased
mobility of the human population is thought to account for
the fact that the disease spread rapidly, appearing per saltum in widely separated locations, and also extending inland towards the borders of Lesotho and the Free State. Dog
rabies spread from KwaZulu-Natal to the Transkei area of
the Eastern Cape Province in 1987, and by the early 1990s
had reached the Ciskei area.40, 42 Like KwaZulu-Natal, the
Transkei and Ciskei areas in the Eastern Cape have dense
rural and peri-urban populations.
After its re-introduction into KwaZulu-Natal in 1976, dog
rabies proved to be intractable. Peak numbers of cases were
recorded at three- to four-year intervals, each time constituting a new record,363 but resurgence of the disease did not
invariably occur in the same locations on each occasion.
Peak vaccination coverage of 59 per cent of the estimated
total dog population of KwaZulu-Natal was attained in 1980
to 1981, but the immunization of unrestricted dogs in informal settlements constitutes a formidable task which was
rendered increasingly difficult by the political unrest which
prevailed in the province up to the mid-1990s. Consequently, inadequate vaccination coverage was attained in
the strategically important locations where the problem was
most severe. The position has improved since then.
Most cases of human rabies in South Africa result from
dog bites in KwaZulu-Natal (see below) but there has been
remarkably little spill-over of infection to domestic cats and
herbivores or wild animals in the province, which suggests
that the disease could again be eradicated, as in 1968, by
obtaining effective vaccination coverage of dogs.
Elsewhere in South Africa rabies transmitted by jackals
and dogs remains endemic in Limpopo Province, while rabies which is transmitted by the yellow mongoose is hyperendemic in North West Province, across southern Gauteng
Province to the Ermelo and Carolina districts of Mpumalanga Province, and extends northwards in a narrow central
strip that passes through the Soutpansberg district of Limpopo Province. There is spill-over of infection to cattle, dogs,
cats and less frequently other domestic animals, and sporadic cases of the disease occur in the striped polecat
(Ictonyx striatus) and the slender and water (Atilax paludinosus) mongooses in the south, and also sporadic cases in
suricates, genets, bat-eared foxes and wild felids, particularly the African wild cat, in the south-west.40
In the Free State, yellow mongoose rabies is hyperendemic in the north-west, but occurs throughout the province and the mongoose constitutes about 60 per cent of all
animals in which rabies is confirmed.40 Rabies in all other
species appears to represent spill-over of infection from the
yellow mongoose, and involves mainly cattle, less frequently
dogs, cats and other domestic animals, sporadically suricates, ground squirrels and striped polecats, and on rare
occasions black-backed jackals, and slender and water
mongooses. Sporadic cases of rabies are also recorded in
wild felids and genets, mainly in the west, and on isolated
occasions in small antelope, bat-eared foxes and the aardwolf (Proteles cristatus).40 The striped polecat is a mustelid
which is predominantly insectivorous, and it is considered
possible that at least some of the cases of rabies recorded in
this species are the result of misidentification of its carnivorous relative, the striped weasel (Poecilogale albinucha).
The distribution of yellow mongoose does not extend into
the easternmost part of the Eastern Cape Province, but in the
1980s dog rabies extended from KwaZulu-Natal to the Transkei
and Ciskei areas in the east, where it remains a serious problem. Elsewhere in the Eastern and Western Cape provinces the
occurrence of the disease in dogs remains sporadic. Yellow
mongooses constitute less than 30 per cent of rabid animals,
and positive diagnoses are made in significant numbers of
several other species of carnivore, with definite indications
that at least some of these have been involved in independent
Rabies
transmission of the virus. Suricates, striped polecats and
ground squirrels appear to acquire the infection only where
the disease occurs in the yellow mongoose. In contrast, there
have been comparatively few confirmed cases of rabies in the
banded and water mongooses, and the small grey mongoose
(Galerella purverulenta) which occurs mainly south of the Gariep (formerly Orange) River, but there have been clusters of
cases in the water and small grey mongooses in circumscribed
foci, suggesting that there has been localized spread of infection in these two species.40
It is clear that there is independent spread of rabies in
the bat-eared fox, a small canid which occurs in the drier
parts of the country, including Limpopo, North West,
western Free State, Northern and Western Cape provinces,
as well as in Botswana and Namibia.496, 683 The fox is diurnal where it is not disturbed, otherwise nocturnal, occurs
singly or in pairs, and is mainly insectivorous, preferring
termites, but it also takes small rodents, reptiles and birds.
A few cases of rabies in the bat-eared fox, less than ten,
were recorded regularly each year in Namibia from 1967
onwards, and sporadic cases have been recorded in
Botswana.40 In South Africa, sporadic cases of rabies were
recorded in the bat-eared fox from 1955 onwards, but an
increase in the prevalence of the disease was noted in the
Northern and Western Cape provinces during the 1970s,
and from 1980 onwards there have been up to 24 confirmed cases each year, with progressive spread of the disease to the west coast.40 The bat-eared fox is clearly the
dominant host of rabies in the Western Cape Province at
present, but during the evolution and spread of the outbreak lesser numbers of cases of the disease were recorded
in the black-backed jackal and in the aardwolf, which is a
solitary and nocturnal hyenid that subsists almost entirely
on termites. Isolated cases of rabies have also been recorded in the Cape fox (Vulpes chama). It is not clear
whether the sporadic cases of rabies recorded in bat-eared
foxes in the North West and western Free State provinces
represents spread of infection from the Northern Cape
Province, or are the result of spill-over of infection from
other hosts. Rabies has been diagnosed more frequently in
antelope in the Western and Eastern Cape provinces than
elsewhere in the country, particularly in small species such
as the duiker (Sylvicapra grimmia) and this trend has been
more marked since the increase in the incidence of the disease occurred in bat-eared foxes, jackals and aardwolves.
Over the years, rabies of genets and wild felids has been
diagnosed most commonly in the Northern Cape Province,
where the disease was anecdotally associated with genets
as far back as the nineteenth century. Among the felids, the
disease has been confirmed most frequently in the African
wild cat and the caracal and on isolated occasions in the
small-spotted cat (Felis nigripes). It is believed that the majority of the unspecified felids in which the disease has
been confirmed (Table 99.1), are African wild cat,40 animals which are somewhat larger than the domestic cat, but
1139
which have interbred to a large extent with domestic cats
which have become feral. The African wild cat and the
small-spotted cat prey on birds, reptiles and small mammals, but the larger caracal preys on animals up to the size
of lambs or small antelope. Although the genet is a viverrid,
its behaviour is more like that of a cat than a mongoose. It
is solitary, nocturnal, largely arboreal and preys on rodents, reptiles and birds, but also takes insects and fruits.
The area where felid-genet rabies is most prevalent extends from the Northern Cape Province into southern
Namibia, but sporadic cases also occur in North West and
Free State provinces, and in southern Botswana. It is not
clear whether the circulation of virus in felids and genets is
independent of other hosts, or whether these animals acquire infection from mongooses, possibly in their role as
predators. However, Barnard drew attention to the fact
that there is a much higher prevalence of rabies in the domestic cat in the area where felid-genet rabies occurs than
elsewhere.82 This could indicate that there is spread of infection among felids, with the African wild cat serving as a
link to domestic cats.
The final example of possible compartmentalized circulation of rabies virus in South Africa concerns the occurrence during the mid-1980s of the disease in spotted hyenas
in the Kgalagadi Transfrontier Park which straddles the
boundary between the north-western part of the Northern
Cape Province of South Africa and the south-western part of
Botswana, where the infection may have resulted from the
spread of the kudu virus from Namibia through carnivores
in western Botswana (see above). Attention has been drawn
to the fact that rabies is much more likely to spread rapidly
through wild dog packs than through the more loosely associated hyena clans.476
There are approximately three times as many sheep as
cattle in South Africa, and the disparity is even greater in the
sheep-rearing areas of the southern Gauteng, Free State and
Eastern and Western Cape provinces where mongoose rabies predominates, yet the ratio of cattle to sheep in which
the disease has been diagnosed since 1928, exceeds 18:1. It is
known that both species on occasion predispose themselves
to facial bites by displaying curiosity towards rabid mongooses,13, 40, 221, 451, 452 and it must be concluded either that
sheep are fairly resistant to infection,20 or that the disease in
sheep is frequently not recognized.644
Prior to 1950, approximately half the cases of human rabies in South Africa resulted from mongoose bites in the
southern Gauteng, North West, Free State and Northern,
Eastern and Western Cape provinces, but following the incursion of the canid virus into the Limpopo Province, and
later KwaZulu-Natal, dogs became the most important
source of human infection.41, 666 Currently, 10 to 20 cases of
human disease are recorded each year in South Africa,
mainly in association with dog bites in KwaZulu-Natal and
to a lesser extent Eastern Cape Province. Most victims are
under 15 years of age and many are less than ten years old.
1140
SECTION FOUR:
Table 99.1 Total numbers of
confirmed cases of infection with
rabies and rabies-related viruses
recorded in South Africa, 1928–
2000. The information was obtained
from references 40, 41, 42 and 496
DOMESTIC ANIMALS
NUMBER
Dogs
5 755
Cats
583
Cattle
3 029
Sheep
158
Goats
134
Horses and donkeys
81
Pigs
36
Guinea pigs
1
Total domestic animals
9 777
WILD ANIMALS
COMMON NAME
NUMBER
Cynictis penicillata
Yellow mongoose
2 587
1 314a
Unspecified mongooses
Galerella sanguinea
Slender mongoose
62
G. purverulenta
Small grey mongoose
51
Herpestes ichneumon
Large grey mongoose
1
Mungos mungo
Banded mongoose
5
Atilax paludinosus
Water mongoose
28
Paracynictis selousi
Selous’ mongoose
1
Helogale parvula
Dwarf mongoose
1
Ichneumia albicauda
White-tailed mongoose
2
Suricata suricatta
Suricate
Civettictis civetta
Civet
Genetta genetta
Small-spotted genet
Mellivora capensis
Honey badger
27
Ictonyx striatus
Striped polecat
71b
Poecilogale albinucha
Striped weasel
2
Unspecified otter species
198
6
192
1
Panthera leo
Lion
Felis lybica
African wildcat
37
F. caracal
Caracal
17
F. serval
Serval
3
F. nigripes
Small-spotted cat
5
Unspecified felids
Canis mesomelas
1
185
Black-backed jackal
Unidentified jackal
386c
5
Rabies
Table 99.1 (continued )
WILD ANIMALS
COMMON NAME
Otocyon megalotis
Bat-eared fox
Lycaon pictus
Wild dog
7
Vulpes chama
Cape fox
18
Proteles cristatus
Aardwolf
53
Hyaena brunnea
Brown hyaena
1
Crocuta crocuta
Spotted hyaena
1
Xerus inauris
Ground squirrel
43
Paraxerus cepapi
Tree squirrel
2
Thryonomys swinderianus
Greater canerat
2
Procavia capensis
Cape hyrax
Papio ursinus
Chacma baboon
1
Phacochoerus aethiopicus
Warthog
1
Sylvicapra grimmia
Duiker
Raphicerus campestris
Steenbok
4
Tragelaphus strepsiceros
Kudu
7
Tragelaphus scriptus
Bushbuck
1
Taurotragus oryx
Eland
3
Aepyceros melampus
Impala
1
Damaliscus dorcas phillipsi
Blesbuck
1
Redunca arundinum
Reedbuck
1
Antidorcus marsupialis
Springbok
3
Equus burchelli
Burchell’s zebra
2
Unspecified herbivores
NUMBER
423
11
20
6
14d
Epomophorus wahlbergi
Epauletted fruit bat
Nycteris thebaica
Slit-faced bat
1
Miniopterus schreibersii
Long-fingered bat
1e
L. saxatilis
Scrub hare
1
Unspecified/unidentified
TOTAL WILD ANIMALS
TOTAL ANIMALS
(WILD & DOMESTIC)
HUMANS
a
b
c
d
e
36
5 853
15 630
441
Believed to be mainly C. penicillata
Probably includes some P. albinucha
Possibly includes a few C. adustus in north-eastern Transvaal (now Limpopo Province)
Only two bats positively identified as E. wahlbergi
Identification of species based on circumstantial evidence
1141
1142
SECTION FOUR:
In a unique incident in the 1930s, a person became infected after being bitten by an ox, but the widely publicized
death of a patient in the 1970s after exposure to the regurgitated ingesta of a rabid cow is believed to have resulted from
an encephalitic reaction to mouse brain vaccine, rather than
from rabies.40, 468 Despite reports that many people on
farms in southern Africa and South America have butchered
and consumed rabid cattle, and that rabies has been diagnosed in cattle at abattoirs in Mexico and South Africa, it has
never been recorded that humans have acquired the infection by ingesting the tissues of infected livestock.40, 41, 60, 288
It was reported that a butcher in India developed rabies after
skinning a calf which had ostensibly died of the disease, and
that two people in China acquired infection from preparing
dog meat for human consumption.395, 671
In another noteworthy incident, a person developed
rabies after being bitten by a baboon (Papio ursinus) in the
Pietersburg (now called Polokwane) district in Limpopo
Province in 1961, but the virus has only once been isolated
from a baboon, from the Middelburg district in the Eastern
Cape Province in 1964, and there has been no further
evidence of infection of non-human primates in South
Africa.40, 41, 500
At an early stage in the investigation of rabies in South
Africa, the impression was gained that the occurrence of the
disease increased in times of drought and during the dry
months of late winter. It was concluded that the scant vegetation cover at such times increased confrontation by forcing mongooses to range further afield or to migrate in search
of food, and rendered rabid individuals more readily visible
to susceptible livestock and to humans,452, 495, 638 and later
also that stress activated latent rabies in the mongoose
population.785, 788 It is now well known that there is seasonal
variation in the occurrence of rabies, and although changes
in vegetation and foraging activity are contributory factors,
it is believed that the major determinant is increased intraspecific confrontation in the dominant host brought
about by mating activities and the probing for unoccupied
territories by progeny at the time of dispersal.438, 690 Analysis of the cases of rabies recorded in South Africa on the
basis of species, province involved, and month of occurrence, confirms that there is a strong seasonal bias to the
disease, with the incidence being highest in the late winter
and early spring months of July to September.666 This tendency is most readily apparent in dog rabies in KwaZuluNatal, where a large segment of the dog population in
informal settlements and densely inhabited rural areas is
unrestricted and breeding is uncontrolled. Seasonal bias is
less apparent for the disease in individual species in the
other provinces, largely because the exact timing of peak
rabies activity varies each year with the effects of the vagaries of climate on animals which are directly dependent on
natural resources and food chains. Data for individual years
clearly indicate that there is a peak in the incidence of rabies
in most species in later winter, but in some instances, such
as in bat-eared foxes, it appears that the seasonal increase in
incidence may be bimodal. A greater understanding of the
mechanisms responsible for seasonal exacerbation of rabies
in South Africa would be beneficial in the planning of control measures.
The total range of species and numbers of cases in which
rabies has been confirmed since regular monitoring was instituted in South Africa in 1928, up until 2000, are shown in
Table 99.1.36, 40–42, 493, 667 The results of monoclonal antibody and phylogenetic studies confirm the presence of
canid and mongoose rabies virus lineages in southern Africa, and indicate that spill-over of infection between hosts
occurs on occasion.376, 377, 499, 591, 729
Lesotho
Dog rabies spread from KwaZulu-Natal Province of South Africa into the north-eastern corner of Lesotho in 1982, when the
disease was recorded there for the first time, and within two
years it had spread throughout the country.370, 371 Rabies has
been recorded in dogs, cats, cattle, sheep, goats, horses and
donkeys in Lesotho, but monitoring of the disease has proved
to be difficult in the mountainous terrain of the country and
human disease has been recorded with disproportionate frequency. There are few feral carnivores in the country and the
disease has not been recorded in wild animals. Dog rabies
reached the western border of Lesotho in the mid-1980s, but
did not penetrate deeply into the Free State Province of South
Africa where preventive vaccination had been undertaken, and
where the dog population is less dense.373
Transmission and susceptibility
Factors that determine the successful transmission of rabies
include the dose, route of administration and biotype of the
virus, and the susceptibility of the recipient. Rabies is ordinarily transmitted by bite, and the occurrence and concentration of virus in saliva varies with virus biotype and host
species.110, 156 Salivary gland infection rates in excess of 80 per
cent have been recorded in naturally infected cattle, kudus and
black-backed jackals; infection rates of 20 to 74 per cent have
been recorded in the salivary glands of naturally and experimentally infected dogs, and 70 to 80 per cent in cats.85, 110, 156,
227, 264, 718, 719
Virus is usually present in saliva from the time of
onset of discernible illness and its presence may be intermittent and may terminate one or two days before death, but it has
been demonstrated in salivary glands or saliva up to 13 days
before the onset of illness in dogs and three days in cats.244, 719
Titres of virus detected in the salivary glands of experimentally
infected dogs ranged from 101 to 107,3 mouse intracerebral 50
per cent lethal doses (MICLD50) per gram of tissue, and titres
were slightly higher in cats than in dogs.244, 718, 719 The actual
amount of virus transferred by bite presumably varies markedly and would be difficult to determine, but it has been suggested that a dose of 5 000 MICLD50 is involved in fox-to-fox
transmission, although the LD50 dose for foxes is much
lower.108, 109, 148, 156
Rabies
For comparative purposes, the susceptibility of vertebrate species to rabies should be determined by a standard
method that involves the inoculation of salivary gland virus
from a naturally infected host into the masseter muscle, but
in the absence of experimental data for many species, estimates have been based on cumulative epidemiological
data.20 Foxes, coyotes and jackals have been rated as extremely susceptible; skunks, raccoons, cats, cattle, mongooses and most rodents as highly susceptible; dogs, sheep,
goats, horses and primates including humans as moderately
susceptible, while opossums are considered to have a low
susceptibility to infection with rabies virus.20, 264 In extension of this classification it can be noted, for example, that
the LD50 dose of virus was 100,5MICLD50 for foxes, 103,5 for
cattle and 106,0 for dogs when a fox biotype of virus was used
to produce experimental infections.110 Generalizations are
misleading, however, and susceptibility to a particular biotype of rabies virus is not invariably predictable on the basis
of either the size of an animal or its phylogenetic relationships.110 It has been suggested that one factor determining
differences in susceptibility between species could be differences in density of acetylcholine receptors in muscle, although some investigators doubt the importance of these
receptors in uptake of infection by nerve cells.69, 157
The severity, location and multiplicity of bites inflicted
on the victim also influence the outcome of potential exposure to infection, and bites on the head and neck are generally associated with the shortest incubation periods and the
highest mortality rates. The severity and location of bites are
in turn influenced by the relative sizes of the vector and the
victim, and it was found in South America that 25,6 per cent
of dog bites in children under 15 years of age occurred on the
head and neck, as compared to 11,7 per cent in adults.2 In an
early treatise on rabies55 it was recorded that death rates in
non-immunized persons bitten by presumed rabid animals
ranged from 80 to 100 per cent for severe multiple bites on
the face by wolves, through 15 per cent for severe bites on
the hands and fingers by dogs to 0,5 per cent for bleeding,
superficial bites through clothing by wolves, cats or dogs.
The death rate was 0,1 per cent in instances where the saliva
of wolves, cats or dogs came into contact with fresh, pre-existing wounds, and no deaths occurred if the wounds were
older than 24 hours. More recent estimates of human death
rates following bites by proven rabid animals include 4,7 per
cent for bites by various species, 32 per cent for severe bites
by dogs and jackals, and approximately 60 per cent for bites
by wolves.289, 506, 596, 720 Similar data do not exist for lower
animals, but it can be concluded that rates of transmission
by bite are generally below 50 per cent, and may be as low as
15 per cent on average for humans bitten by dogs.64
Most reports of non-bite transmission of rabies have
dealt with sporadic incidents, but the phenomenon may assume greater significance in particular circumstances. Oral
infection through the ingestion of infected milk from the
mother has been recorded in a lamb and a human baby, and
1143
may occur in bats since virus has been found in their milk.5,
62, 584
The occurrence of infection through scavenging, cannibalism or predation is potentially of epidemiological importance and may be a factor in the transmission of Arctic
rabies, and in the occasional cases of infection ostensibly recorded in birds of prey in Europe.156, 333 Although birds are
susceptible to experimental infection, virus is restricted to
the central nervous system and cannot be transmitted to
other animals. Early reports of disease have not been confirmed, and there are no recent records of disease in
birds.505 Oral transmission of rabies virus between herbivores is believed to have been an important factor in the epidemic which occurred in kudus in Namibia, and was earlier
suspected to have occurred in an outbreak of rabies in deer
in Britain during the nineteenth century.85, 333
Aerosol transmission may have occurred in two humans
who were exposed to the breath of a rabid wolf without being
bitten or scratched, according to an early report from Europe,55 but no similar events have subsequently been recorded.
In 1957 and 1960, rabies was diagnosed in two humans who
had separately visited a bat cave in Texas, USA, and it was
shown that animals placed in insect-proof cages in the cave acquired aerosol infection, and subsequently virus was isolated
from the atmosphere of the cave.175, 176, 325, 332, 767 It was
stressed that conditions were unique in the cave, with rabies
being highly endemic in the more than 20 million bats which
roosted there.767 The findings suggested that aerosol transmission was a likely mode of spread of infection in colonial bats,
but higher infection rates have been found in solitary bat species, probably because solitary bats are most readily encountered when rabid.62, 767 Non-contact transmission was
subsequently observed in a poorly ventilated laboratory animal colony where experiments were being conducted with bat
isolates.770 In 1972 and 1977, infection occurred in two persons
who worked with rabies virus in laboratory equipment which
generated aerosols.19, 22, 23
Transplacental transmission of infection has been demonstrated in the foetus of a pregnant cow which had died of
the disease,454 and it has been recorded in dogs, and once in
a human patient.5, 738
Although there are anecdotal reports of human-to-human
transmission dating back many years,738 the only documented
recent instances concern the transmission by breastmilk and
the transplacental transmission referred to above, an incident
in Pakistan where saliva was applied to circumcision wounds
of several young boys by a surgeon-barber who was in the early
stages of rabies, and a 41-year-old woman and a five-year-old
child who ostensibly became infected in separate incidents
from contact with relatives suffering from rabies in Ethiopia.242, 502 In addition, there have been eight cases in which
infection was transmitted by the transplantation of corneas
from cadavers in the USA, France, Thailand, and Iran, while a
further potential case in France is believed to have been
averted by intensive post-exposure prophylaxis and treatment
with interferon.24, 25, 26, 279, 318, 341, 661
1144
SECTION FOUR:
Sylvatic rabies
Much of our present understanding of the epidemiology of
rabies derives from the study of fox rabies in Europe and
North America.110, 438, 690 The front wave of the epidemic of
fox rabies which swept over much of Europe during the second half of the twentieth century advanced at 20 to 60 km
per annum, generally at a steady rate, but with occasional
leaps of greater magnitude. Since the average home range of
foxes in Europe has a diameter of 1,6 km, and the average
interval between successful serial transmissions of infection
(incubation plus morbid periods) is one month, it was surmised that the disease was generally propagated from one
resident social group to the next, with the occasional leap of
infection ahead of the wave front being associated with the
long-range dispersal of sub-adults seeking new territories.
In Ontario, Canada, fox home ranges or territories are larger
than in Europe, and accordingly epidemic wave fronts travel
at rates of over 100 km per year, which also appears to be the
case with jackal rabies in southern Africa. Interestingly, radio-tracked foxes in Europe and Canada which developed
rabies did not necessarily travel beyond their normal home
ranges.17, 438
As in most vectors in southern Africa, seasonal peaks in
the incidence of fox rabies occur in late winter, one month
after the dispersal of young foxes and mating, and the velocity of the front wave of the epidemic increases at this time.
Apart from the increased encounters between individuals
which mating and dispersal activities entail, it is believed
that dispersing sub-adults are predisposed to rabies by
stress, and that females are similarly predisposed by pregnancy. Male cubs disperse over longer distances than females, and there is seasonal disparity in the sex and age of
foxes which develop rabies, a feature noted in jackal rabies
in Zimbabwe.264
Epidemic wave fronts of fox rabies falter temporarily, or
are deflected into new directions at major physiographic
barriers such as mountain ranges or large rivers, with the result that the barriers delimit epidemiological units within
which the occurrence of rabies is out of synchronization
with neighbouring units. However, barriers do not necessarily act by debarring the passage of animals, but may simply
lack suitable habitats to support populations of threshold
density for spread of the disease. Thus, areas with loose,
sandy soils may not suit burrowing animals in parts of
southern Africa. Epidemiological units have also been
termed geographical cells.443
In epidemiological units, which meet threshold requirements for endemicity, epidemic peaks are followed by silent
phases of two to four years during which rabies activity is
minimal or undetectable, and during which the population
is restored. Restoration periods are followed by secondary
epidemic peaks of rabies, which recur regularly at four- to
five-year intervals. Endemicity is not determined simply by
the size of an epidemiological unit or the density of the host
population, since high morbidity may reduce the popula-
tion to below threshold density for transmission in an area
which is uniformly favourable for the host. Carrying capacity is more important than size, and the disease is more
likely to become endemic in areas which contain an admixture of less favourable habitats where transmission is retarded and infection can smoulder.
In epidemiological units which do not meet requirements for endemicity, transmission stops after the initial
epidemic peak has reduced the population to below threshold density. In such areas, the virus spreads again only if it is
re-introduced after the host population has been restored,
and so epidemic peaks tend to recur at irregular intervals of
many years.
The occurrence of periodic epidemic cycles in individual
epidemiological units is likely to be masked in instances
where data on the incidence of rabies are pooled for large
regions or countries. Nevertheless, it can be discerned that
endemic rabies with periodic epidemic cycles appears to
occur in at least some of the areas where rabies affects unrestricted dog populations in KwaZulu-Natal in South Africa,
and that blocks of commercial farmland in which epidemics
of jackal rabies occur at irregular intervals in Zimbabwe do
not meet requirements for endemicity.
The recovery of fox populations after the devastation of
rabies epidemics is brought about partly by increased reproductive efficiency resulting from decreased competition for
food resources, and partly by re-colonization of vacated territories by neighbouring foxes. Apart from the fact that dispersing sub-adults seek territories, foxes and many other
wild animals generally carry out spacing activity at the periphery of their territories and hence are drawn into vacant
niches by the so-called vacuum effect. Competition for and
re-establishment of territories may initially increase confrontation and thereby exacerbate outbreaks. Generally,
populations recover rapidly, which is why the culling of vectors has succeeded as a means of controlling rabies in exceptional circumstances only, usually where it has been applied
ahead of advancing outbreaks and the additional protective
effects of natural barriers have been utilized. Even then, the
benefits of culling are temporary and, in an epidemiological
model devised for coyotes, it was projected that with the killing of 75 per cent of individuals annually, it would have
taken more than 50 years to exterminate coyotes and that
the population would recover rapidly if culling were discontinued at any stage.174
Urban rabies
Urban rabies occurs particularly where there are large
populations of unrestricted dogs. Although appreciable
numbers of dogs may be abandoned under certain circumstances, as occurred during the civil war in Zimbabwe,264,
408
there are only a few places in the world, such as India,
where there are truly feral packs of dogs. However, in much
of the world the concept of dog ownership varies with socioeconomic class and ethnicity of people. Ownership may be
Rabies
vested in individuals or families, or loosely in neighbourhood, village or tribal groupings. The dogs are kept as pets,
guard dogs, hunting dogs or even as food animals, and the
extent to which they are supervised, sheltered and fed varies.734, 736 Consequently, not all dogs which are left unrestricted to fend for themselves are genuine strays, and there
may be repercussions when, for instance, decisions are
made to eliminate dogs which are found to be inaccessible
for rabies vaccination.96
The epidemiology of urban rabies has been studied most
intensively in Latin American cities where there has been
rapid growth of large informal settlements in which lack of
sanitation and proper refuse disposal has created conditions that favour marked increases in populations of rats,
cats and dogs.170,404 It was found in Guayaquil, Ecuador,
that no dogs were regarded by community residents as
being unowned, but that the dog population was made up of
three segments.96 Dogs of upper-income households were
relatively restricted at all times and were commonly vaccinated at their owner’s initiative. In middle-income households where both spouses were in employment, dogs were
frequently confined during working hours, but were allowed
to roam at other times of the day. In low-income households, dogs were commonly confined to guard homes at
night, but were free to roam and scavenge during the day.
Unrestricted dogs formed territories within which there was
an order of dominance. The mobility of males and the confrontations between them were increased when females
were in oestrus.
Elimination of more than 25 per cent of the estimated dog
population of Guayaquil in each of 9 out of 18 years during
which campaigns were conducted did not lead to an appreciable long-term reduction in the number of dogs. Instead,
control campaigns alienated community residents and increased confrontation between dogs competing for vacated
territories and re-establishing orders of dominance. Where the
area of dog elimination was large, the relative increase in the
supply of food available to the remaining scavengers led to increased fecundity of bitches and improved survival of pups.
Dogs that had been eliminated, including vaccinated individuals, were thus replaced with younger, susceptible dogs. The inference is that inadequate or inappropriate dog control
measures actually increase the risk of transmission of rabies.96
It can be concluded that, although there are fundamental differences between urban and sylvatic rabies, there are also
some striking parallels between the two.
Many of the complex interactions of the spatial and/or
temporal processes which determine the occurrence of the
disease can be simulated in computerized models, such as
those devised for sylvatic rabies in the northern hemisphere.56, 57, 75, 76, 477, 478, 580, 619, 726 The models can be used
to assess the potential impact of intervention strategies, but
are not necessarily applicable to problems in southern Africa without adaptation to take account, for instance, of the
social behaviour and ecology of jackals or mongooses.
1145
Rabies-related viruses
The large number of isolations of rabies virus made from
non-haematophagous bats in the Americas during the 1950s
prompted investigations elsewhere in the world, and, as a
consequence, Lagos bat virus was isolated from strawcoloured fruit bats (Eidolon helvum) in Nigeria in 1956,122
but it was not until 1970 that the virus was identified as a
rhabdovirus antigenically related to, but distinct from, rabies virus.607 In 1968, a virus was isolated from three Crocidura sp. shrews trapped in Mokola Forest near Ibadan,
Nigeria, in a survey of arthropod-borne viruses, and from a
fourth shrew found dead in Ibadan.365, 366 Identification of
the Mokola virus as a rhabdovirus related to rabies virus was
reported in the same publication as the identification of
Lagos bat virus, and hence the concept of a rabies-related
subgroup of rhabdoviruses was established.607 In 1970, an
adult man living in the Bela-Bela (formerly Warmbaths)
district about 100 km north of Pretoria, South Africa, died of
rabies-like disease five weeks after being bitten by an insectivorous bat, possibly Miniopterus schreibersii.714 A virus
isolated from his brain was found to be yet another rabiesrelated virus; named Duvenhage after the victim.470, 687
These three rabies-related viruses have been encountered in only a few countries of western and southern Africa.666 In general, isolates obtained from ostensibly healthy
bats, shrews or rodents in surveys were deliberately subjected to tests appropriate for the identification of rabies-related viruses, whereas isolates obtained from specimens
submitted from humans and lower animals for the investigation of suspected rabies, were only recognized as rabiesrelated viruses because the investigators concerned were
alert to non-specific features which distinguished the infections from rabies: routine diagnostic procedures do not
allow rabies and rabies-related viruses to be differentiated
with certainty. Thus, Lagos bat virus was isolated in surveys
from a fruit bat in the Central African Republic in 1974, and
from a fruit and an insectivorous bat in Senegal in 1985.28,
660, 664
Immunofluorescence was detected with anti-rabies
conjugate in the brains of 13 Epomophorus wahlbergi fruit
bats which had behaved abnormally in KwaZulu-Natal,
South Africa, in 1980 to 1981, but only three isolations of
virus were made and identified as Lagos bat virus, with a further isolation being made in 1990, although two of the isolates were at one stage mistakenly reported to be Mokola
virus.105, 196, 374, 471, 591 Lagos bat virus was isolated from
two cats, one in South Africa in 1982 and one in Zimbabwe
in 1986, which had been vaccinated against rabies and exhibited atypical signs of the disease, plus a dog which behaved abnormally in Ethiopia in 1990.264, 374, 463, 464 The
virus has also reportedly been imported into France in an
infected Roussettus aegyptiacus fruit bat.340
Mokola virus was isolated in 1969 from the cerebrospinal
fluid of a young girl with fever and seizures in Ibadan, Nigeria, who had no specific history of exposure to infection and
who recovered without sequelae, but the validity of this
1146
SECTION FOUR:
isolation has been questioned.234, 623 Subsequently, the
virus was isolated from the brain of a girl who died of paralytic disease in Ibadan in 1971, and again no source of infection could be identified.235 Mokola virus was isolated from a
shrew in a survey in Cameroon in 1974, and a rodent in the
Central African Republic in 1983.410, 578 The possibility that
the rabies-related viruses were capable of spread among domestic carnivores was raised when Mokola virus was isolated from the brains of six cats and a vaccinated dog from
Bulawayo, Zimbabwe, in 1981 and 1982, which had been
submitted for the investigation of suspected rabies, but the
outbreak possibly resulted from spill-over of infection from
rodents or shrews.260–262, 264, 761 The findings in Zimbabwe
prompted retrospective investigation of a virus which had
been isolated in 1970 from a cat with atypical rabies in KwaZulu-Natal, South Africa, and the isolate was identified as
Mokola virus,373, 468, 591 but has also been reported as Lagos
bat virus.623 In 1995 and 1996 three isolations of Mokola
virus was made from cats with suspected rabies in the Eastern Cape Province of South Africa, and in 1997 and 1998
from a further three cats in KwaZulu-Natal Province; four of
the cats had been vaccinated against rabies.469, 728 The virus
has also been isolated from a cat which behaved abnormally
in Ethiopia in 1990.463, 464
Mokola virus has never been isolated from bats, and it is
thought that it may be harboured in shrews or myomorph
rodents. Antibody to the virus was found in rodents in Zimbabwe, particularly bushveld gerbils (Tatera leucogaster),264
and it is notable that virus isolation and characterization
was not attempted on the brains of two greater cane rats
(Thryonomys swinderianus) from Limpopo Province, South
Africa, which fluoresced in diagnostic tests with anti-rabies
conjugate in 1985 and 1987.668
Following its initial isolation from a human patient,
Duvenhage virus was isolated in 1981 from a bat, thought to
be M. schreibersii,714 caught in daylight by a cat in Louis
Trichardt (now called Makhado) in Limpopo Province,
South Africa,591 and in 1986 from a common slit-faced bat
(Nycteris thebaica) caught in a survey in south-eastern Zimbabwe.264 In 1963, prior to the recognition of the rabies-related viruses, virus was isolated from a N. thebaica bat
collected in a survey from a cave in Mpumalanga Province,
South Africa, but the isolate was simply described as rabies
virus, presumably on the basis of histopathological lesions
observed in mice.451
Numerous viruses isolated in southern Africa from the
brains of humans and lower animals which fluoresced in diagnostic tests with anti-rabies conjugate, have been
screened with monoclonal antibodies and in phylogenetic
studies, and, apart from the cases mentioned above, no evidence of infection with rabies-related viruses has been
found.376, 377, 497, 499, 591, 729 The implication is that the rabies-related viruses have not adapted to spread in carnivores, but that sporadic infections may be encountered in
humans and domestic animals, particularly cats, which are
predators of small mammals such as shrews, myomorph
rodents and bats.
Only insectivorous bats occur in Europe, and prior to
1985 there were 12 isolations of lyssaviruses from bats in
Yugoslavia, Turkey, Germany and Poland, and one from a
human who died in the former USSR in 1977 after having
been bitten by a bat.374 Many of these isolates were obtained
prior to the recognition of the rabies-related viruses, and
most were thought to be rabies virus at the time of isolation
and have not remained available for definitive characterization.374 However, three of the viruses obtained from unidentified, apparently sick bats in Germany in 1968, 1970 and
1982 were preserved and later found to be antigenically
close to Duvenhage virus from Africa, and at that stage it was
speculated that the virus may have been introduced into
Europe from Africa, possibly in bats carried by boat.591
In 1985, a lyssavirus was isolated from an Eptesicus serotinus bat which attacked a person in Denmark, another
from a bat zoologist who died in Finland, and one from a
person who died after being bitten by a bat in the former
USSR. In the ensuing investigations more than 450 isolations of virus were made from bats in Denmark, USSR,
Poland, Netherlands, Germany, Spain, France and
Czechoslovakia.29, 32, 35, 287, 373, 374, 432, 592 The isolates
were obtained mainly from E. serotinus bats, but also from
Myotis dasycneme and a few other species. Many of the bats
had behaved abnormally or were found dead, and it appears that an epidemic situation existed among bats in
Europe from about 1985 onwards. Isolations from bats in
Europe subsequently declined to about 40 per annum.373
Various terms were applied to the isolates, such as Duvenhage, Duvenhage-like and Denmark bat virus, but it is now
clear that European bat lyssaviruses differ from the Duvenhage virus of Africa, and that distinct subtypes are associated with serotine and myotine bats: European bat
lyssavirus 1 (= lyssavirus genotype 5) is associated almost
exclusively with E. serotinus, while European bat lyssavirus
2 (= lyssavirus genotype 6) is associated mainly with M.
dasycneme and Myotis daubentonii.106, 123, 375, 376, 488, 592,
624, 694, 732
As in Africa, the monoclonal antibody and molecular studies failed to reveal evidence that rabies-related
viruses have adapted to spread in carnivores. Recently,
European bat lyssavirus 2 was isolated for the first time
from a M. dasycneme bat in Britain, presumed to be a migrant from mainland Europe.747
Reference has been made above to the recent discovery
of an Australian bat lyssavirus (= lyssavirus genotype 7),
which occurs in both fruit and insectivorous bats, and which
has been associated with fatal infection in two humans.253,
270, 301, 317, 579, 617, 645
Genetic divergence between fruit and
insectivorous bat isolates suggests that bat lyssaviruses have
long been present in Australia.739
Since rabies virus, genotype 1, has been isolated from
bats only in the Americas, it seems likely that incompletely
characterized lyssaviruses isolated from bats in Thailand,
Rabies
India and Zambia may have been rabies-related viruses,7,
513, 635
with the implication that these viruses may be more
widely distributed than realized at present.
Pathogenesis
The most superficial portals for entry of rabies virus into the
nervous system are sensory nerve endings of the epithelial
and subepithelial tissues of the skin and mucous membranes, and this route is involved when transmission results
from superficial bites, licking of mucous membranes or
shallow skin wounds and abrasions, and ingestion or inhalation of infected material. It has been shown that rodents,
other laboratory animals, foxes, skunks and kudus are susceptible to oral infection, that infection occurs with greater
efficiency when there are mouth lesions, and that virus replication, as indicated by immunofluorescence, occurs first
in epithelial cells or tonsils and sensory organs, such as taste
buds, and later in nerve bundles of the submucosa of the
oral cavity and tongue.85, 92, 107, 115, 179, 256, 258, 487, 549, 555, 641
Rabies virus is inactivated in vitro by the digestive enzymes
and low pH of stomach contents, but laboratory animals can
be infected by stomach tube, as well as by rectal instillation
of virus.5, 258, 553
Nerve tissue is particularly exposed in the nasal cavity.
Experimental infection with rabies virus by the intranasal
route has been demonstrated in laboratory rodents, rabbits,
bats and skunks.49, 66, 159, 161, 257, 319, 320, 343, 487, 557, 576 Infection appears to involve both the olfactory end organ in
the nares, neuroepithelial cells which are in contact with the
surface of the body and extend directly into the olfactory
bulb of the brain via the olfactory nerve, and terminations of
trigeminal nerve fibres which ramify in the nasal mucosa.156, 256, 320, 486 Aerosol transmission of rabies virus has
been recorded in nature only in exceptional circumstances
(see above), but intranasal infection may also occur when
infected material is eaten.156
The eye is also an extension of the central nervous system, but following inoculation of rabies virus into the anterior chamber of the eye of rats it was found that the virus is
taken up by parasympathetic oculomotor nerve fibres, retinopetal fibres of pretectal origin and fibres of the ophthalmic branch of the trigeminal nerve; not by the optic
nerve, although ultimately infection extends back from the
brain to the optic nerve and retina.393 The cornea has only
sensory innervation and ocular infection has been recorded
after transplantation of infected corneas in humans (see
above).
Following deep introduction by bite, rabies virus enters
the nervous system either through neuromuscular spindles
(stretch proprioceptors consisting of modified muscle cells
wrapped in unmyelinated nerve endings) or through motor
end plates (motor nerve endings in muscle cells).486, 740
There is no evidence that virus is taken up directly by severed nerve endings.156
1147
After a variable period of hours following inoculation,
rabies virus enters a so-called eclipse, during which infectivity can no longer be demonstrated at the site of inoculation
or elsewhere, but during which the virus may nevertheless
have initiated infection of cells at the site of inoculation, or
have been transported in non-demonstrable low concentration in nerves towards the central nervous system.61 The
virus is capable of entering nerve endings immediately and
leaving the site of inoculation rapidly: virus particles may
accumulate at motor nerve endings within one hour of inoculation, nerve resection or amputation of limbs within
four hours may fail to save the lives of a proportion of mice
inoculated with a fixed (laboratory passaged) strain of virus
in the foot-pad, and virus inoculated into a front paw in
mice can initiate replication in neurons of the dorsal root
ganglia and spinal cord within 18 hours.181, 205, 740 On the
other hand, mice inoculated with a strain of virus producing
incubation periods of one to three months, similar in duration to those occurring commonly in humans, can be saved
by limb amputation up to 18 days after inoculation, i.e. the
virus can remain at the site of inoculation for a prolonged
period, implying that there is replication of virus in nonneural tissue at the site of inoculation.68 Such replication
has been demonstrated in myocytes within 36 hours of inoculation of virus, and it appears that the virus can remain
in muscle at the site of inoculation for up to 28 and possibly
35 days, but ultimately the muscle infection is abortive.119,
160, 162, 487
Theoretically, infection of muscle can proceed in
parallel with the infection of nerves, but there is the clear
implication that in some instances replication of virus in
muscle occurs as a preliminary to the infection of nerves,
and this may account for the delay in pathogenesis which
occurs in incubation periods of intermediate length.68, 156,
160, 162, 487, 704
However, it is not universally accepted that infection of myocytes is a link in the pathogenesis of the disease.157 The site of sequestration of virus during long to
extreme incubation periods remains undetermined, but on the
basis of the low intensity of replication seen in cultures of sensory neurons of dorsal root ganglia infected in vitro, it has been
suggested that these cells are poorly permissive for the virus
and could harbour infection for prolonged periods.434
Once virus has entered nerves, there is passive centripetal transport of subviral genome-containing particles,
presumably ribonucleocapsids, by retrograde axoplasmic
flow to the central nervous system.486 Proof that virus is
transported within axons includes the facts that neurectomy
or the administration of drugs that impair nerve function
can spare life in experimental infections; localized early paralysis and lesions in the central nervous system are associated with the entrance of nerves from the inoculation site;
the paraesthesias which occur in humans and the self mutilation sometimes seen in rabid animals are frequently referable to the infection site, and furthermore, it is notable that
the lymphatic drainage system of the epineural spaces does
not constitute a direct pathway to the central nervous
1148
SECTION FOUR:
system.68, 70, 156, 205, 355, 700 More specifically, virus antigen
and infectivity are first demonstrable ipsilateral to the site of
infection in segments of the spinal cord which have nerve
connections to the inoculation site, and axonal transport of
rabies virus has been demonstrated in in vitro cultures of
neurons.71, 181, 434, 586 The presence of viral matrix and virions in axons has been demonstrated in vivo, but this could
have represented centrifugal spread following virus replication in neurons.181, 343, 487, 489 Estimates of the rate of passage of virus along nerves, ranging from 0,5 to 3 mm/hour,
are too fast to allow for cycles of replication and cell-to-cell
transfer of virus en route, and in any event there is little evidence of infection of Schwann cells or endoneural fibrocytes
even late in infection.156, 181, 205, 393, 434, 701
The axoplasm lacks free ribosomes and granular endoplasmic reticulum, so the first possible location for replication of virus which has gained direct entry into peripheral
nerves would be the perikaryon of either sensory neurons in
dorsal root or cranial ganglia, or motor neurons of the ventral horn of the spinal cord or autonomic ganglia.156 Neurons of the dorsal root ganglia are unipolar, with the single
axon bifurcating a short distance from the cell body into a
peripheral and a central process, so it has been speculated
that virus ascending the axon following peripheral infection
could by-pass the perikaryon of the neuron and proceed directly to the spinal cord.156
Evidence that infection can occur via either sensory or
motor nerves includes the results of experiments in which
either sensory or motor nerve roots were severed, demonstration of sensory spread following ocular infection, the accumulation of inoculated virus at motor end plates, and the
demonstration of early virus replication in both sensory
neurons of the dorsal root ganglia and ventral motor neurons of the spinal cord.156, 181, 205, 393
Although peripheral nerves are considered to constitute
the main pathway for infection, it has been known since the
time of Pasteur that the disease can be produced by intravenous administration of rabies virus, and it has since been
shown that neurectomy may fail to protect immature laboratory animals or those given large doses of virus peripherally.205 On this basis it was postulated that haematogenous
spread of inoculated virus to the nervous system can occur
in very young animals, animals of exceptionally susceptible
species and those in which resistance has been lowered as,
for instance, by trauma or shock.205 It is believed that the
immunosuppressive effects of pregnancy can also facilitate
the occurrence of viraemia and thus account for the transplacental transmission of infection which has been demonstrated experimentally in a variety of animals,5, 178, 258, 383,
384, 556, 582, 584, 595, 614
but which has only been recorded in
nature on rare occasions (see above).
Spread of virus in the spinal cord proceeds via axons and
dendrites, and the process is thought to involve either prior
maturation of virions by budding on intracytoplasmic
membranes or direct transfer of genome-containing moiety
through membrane fusion at synaptic junctions.335, 486, 659
Hence, spread of infection occurs between neurons that
have nerve connections and it is notable that there does not
appear to be direct spread of infection from cell body to cell
body between contiguous neurons in the spinal cord.181 The
initial cycle of virus replication in the spinal cord is followed
by further cycles at intervals of several hours with exponential increase in the number of infected neurons.181 Spread
does not proceed in a strictly progressive fashion: virus can
leap-frog via nerve connections from an infected neuron to
another in a distant segment of the spinal cord, and infection can reach the brain stem in a matter of days.181 Occasionally, infection may be limited to the spinal cord.473
Spread of infection is rapid within the brain, with some
tendency to occur in a spatially integrated manner whereby
adjacent structures are involved in turn,156, 588 i.e. infection
tends to spread from the medulla and pons to the cerebellum, thalamus and hypothalamus, the limbic system
(palaeocortex) and ultimately to the neocortex. It has been
suggested that the cerebrospinal fluid may act as a vehicle
for the rapid dissemination of rabies virus in the brain, but
the virus can seldom be isolated from cerebrospinal
fluid.227, 335, 588 Moreover, there appears to be selective involvement of neurons with little evidence of infection of
pial, ependymal or endothelial cells, and relative sparing of
glial cells.156, 349, 489, 588
Although infection is usually widespread in the brain in
the agonal stages of the disease, there is a tendency for lesions to be most advanced and for highest concentrations of
virus antigen to occur in particular locations, and these localizations may account for characteristic signs of the disease.156, 347, 348, 700 Thus, early selectivity for the limbic
system which controls the emotions, with relative sparing of
the neocortex, could explain the initial retention of alertness
with manifestation of aggressiveness, sexual arousement
and loss of fear which often characterizes the disease.348, 486
Indeed, most of the signs of the disease can be ascribed to
neural dysfunction, but there is some uncertainty as to the
extent to which this represents dysfunction of neurons, or
interference with neurotransmission, possibly resulting
from blockage of post-synaptic receptors by virus particles.702, 738 Electroencephalograph studies indicate that
there is progressive extinction and final cessation of electrical activity of the brain before cardiac arrest.285
From the time that the infection reaches the central nervous system, passive centrifugal spread of virus by anterograde axoplasmal flow proceeds simultaneously with
centripetal spread. Within hours of virus reaching a point in
the spinal cord ipsilateral to the inoculation site, for instance, infection may become demonstrable in contralateral dorsal root ganglia and nerves.181 Centrifugal spread
proceeds throughout the body, resulting in a variable degree
of infection of non-neural cells, and virus or antigen has
been demonstrated in terminal illness in a range of tissues
and organs, including the cornea, nerve fibres surrounding
Rabies
hair follicles, the interscapular brown fat in bats, myocardium, lungs, pancreas, adrenal medulla, kidneys and bladder, as well as in milk, tears and urine.156 Spread to the
salivary glands coincides with widespread dissemination of
infection in the brain, and the virus, which matures predominantly on internal membranes of neurons up to this
stage, exhibits a remarkable adaptation during replication
in the acinar epithelial cells of the salivary glands by budding from the apical surfaces of the cell plasma membranes
directly into intercellular caniculi and acinar lumens, apparently in a highly infective form, i.e. uniform virions free of
debris and DI particles.212, 213
It is well documented that rabid animals may exhibit
wasting, emaciation or cachexia and dehydration, or failure
to thrive in the young, and in the past these phenomena
have tended to be regarded merely as the consequences of
impaired uptake of food and water resulting from paralysis.
However, the onset of wasting precedes changes in consumption of food and water and is not initially accompanied
by the marked changes in plasma glucose levels which are to
be expected in fasting.699 It was established in mice, rats,
cattle and cats that there is regular infection of the hypothalamus and/or adenohypophysis in rabies, with dysfunction of growth hormone production.699 Suppression of cellmediated immunity is also well documented in rabies,752,
755, 756, 762
and it is postulated that this, together with the
wasting syndrome, results from the effects of the virus on
the hypothalamic-pituitary-adrenergic axis, with impaired
production of growth hormone and excess corticosteroids
leading inter alia to atrophy of the thymus and suppression
of T lymphocyte cell-mediated immunity.699 Terminally, the
virus-induced wasting is augmented by the secondary wasting resulting from food and water deprivation. Contradictory evidence indicates that adrenalectomy does not modify
immunosuppression in rabies infection, and it is proposed
that in rabies encephalitis there is direct neural delivery of
catecholamine neurotransmitters to peripheral immune organs, stimulating immune cells to secrete cytokines such as
IL-6, TNF-α or IL-10 that impair peripheral immune
response.401, 654
The role of the immune response is complex in rabies.
There is no doubt that pre-exposure vaccination is protective in humans and animals and that post-exposure immunization is effective in humans.73, 79, 708 The response to the
administration of inactivated virus or attenuated live virus is
three-fold: there is production of interferon and circulating
antibody, and induction of cell-mediated immunity, with
antibody becoming demonstrable and interferon and cellmediated responses being maximal six to ten days after inoculation of virus.752, 755, 756 Attenuated strains of virus used
as veterinary vaccines produce abortive infection of the central nervous system, and all three components of the response to infection contribute to the clearance of virus;
immunosuppression renders infection of adult mice with
the attenuated viruses fatal.257, 622, 627
1149
Proof that humoral immunity plays a protective role in
rabies stems from the fact that neutralizing antibody titres
induced by pre-exposure immunization correlate well with
resistance to infection with virulent virus, although no such
correlation can be made for post-exposure immunization.194, 752 Furthermore, passively acquired antibody can
be protective if adequate amounts are administered prior to
infection, but antibody administered at the time of, or soon
after, infection may only prolong survival.145, 610 Deficiency
of B lymphocytes responsible for the humoral response, induced by the administration of anti-µ chain antiserum, increases susceptibility to fatal intracerebral infection with
attenuated virus.475
Peripheral immunization does not necessarily protect
against intracerebral challenge since antibody does not
penetrate the blood–brain barrier, and the demonstration of
antibody in cerebrospinal fluid implies that virus has
reached immunocompetent cells within the central nervous
system.93, 156, 335, 392 The blood–brain barrier is only
breached late in symptomatic or fatal infection.439 The intracellular location of rabies virus in nerve tissue and its direct manner of spread from cell to cell renders it inaccessible
to antibody, as evidenced by the inability of an antibody
overlay to prevent spread of infection in in vitro cell cultures.218 Apart from the possible direct action of antibody
on extracellular virus in the infective inoculum, therefore, it
is postulated that humoral immunity protects through antibody- and complement-mediated lysis of infected cells,
such as myocytes, which express viral antigen on their surfaces, neutralization of released virus and sequestration of
the immune complexes formed by virus and antibody in phagocytic cells.439
Mice that have been rendered T cell-deficient are more
susceptible to infection with attenuated or virulent virus
than are B cell-deficient mice, confirming that both humoral and cell-mediated immunity are required for optimum clearance of infection, and survival correlates better
with cytotoxic T cell response than with interferon or antibody responses.357, 474, 475, 622, 752, 755, 756 Cell-mediated immunity acts through cytotoxic lysis of infected cells, but it
also appears that the induction of antibody response is dependent on T-helper cells since athymic nude mice succumb to infection without producing antibody.357, 752, 755,
756
Furthermore, T cells, including helper, suppressor and
cytotoxic cells, are responsible for the release of interferon.439 It has been shown that timely administration of exogenous interferon or interferon inducers is beneficial in
rabies infection.302, 752 Interferon counteracts spread of the
virus by conferring resistance to infection on susceptible
cells, and also promotes expression of histocompatibility
antigens which are recognized as a complex with rabies antigen on infected cells by T-effector cells.439
In contrast to killed or attenuated virus, infection with
street virus does not induce cell-mediated immune response,
although antibody response becomes demonstrable in seven
1150
SECTION FOUR:
to ten days if a high dose of virus is inoculated.164, 752, 755, 756
Following inoculation of low doses of street virus or occurrence of natural infection, however, antibody response
only becomes demonstrable after the onset of illness, irrespective of the duration of the incubation period; in humans antibody is detectable five to ten days or more after
the onset of signs of the disease.16, 164, 304, 752, 755, 756 It appears that little or inadequate antigen is presented to immunocompetent cells in the inoculum in natural
transmission and once nervous infection occurs, virus is
ensconced intracellularly and is further protected from
host immune surveillance by myelin sheaths and the
blood–brain barrier, and by the paucity of lymphatic drainage and lymphocyte trafficking in nerve tissue.439, 486, 706
Moreover, virus replication produces little cytopathology
which would facilitate the presentation of antigen to immune surveillance. Following its long trajectory in the
nervous system, virus antigen ‘surfaces’ from its immunologically priviliged position when the blood barrier is
breached during spread of infection in the brain, and when
non-neural tissues, such as salivary glands, become
infected as a result of centrifugal spread of virus.439
The relative lack of inflammatory response in the central
nervous system of non-immunized animals which develop rabies,486, 489, 528 as opposed to other viral infections of the nervous system, has been attributed in the past partly to the
relative lack of antigenic stimulus early in the infection and
partly to the suppression of cell-mediated immunity which occurs in rabies, as discussed above. It has been found in mice,
for instance, that there is atrophy and loss of cellularity of lymphoid organs, including the thymus and spleen, and abolition
of the ability to mount cytotoxic T cell response not only to rabies virus, but also to other antigens such as influenza virus or
skin grafts.439, 755, 756 More specifically, it was shown in monoclonal antibody studies in lethally infected mice that there is
virtual disappearance of the T lymphocyte subpopulation responsible for cytotoxic response.762 However, it is now known
that the nervous system, including eyes, brain and nerves, is an
immunoprivileged site for a number of reasons: tight endothelial cell junctions and lack of lymph ducts constituting the socalled blood–brain barrier not only restrict lymphocyte
migration, but also passage of antibodies and complement.400,
401
Moreover, there is a lack of antigen presenting cells in the
nervous system; the MHC I and II molecules are down-regulated in healthy neurons, which are consequently unable to
present antigen to inactivate T cells. In injury, infection or
stress, such as late in rabies infection, glial cells can act as antigen presenting cells, but they cannot migrate from the central
nervous system to secondary lymphoid organs to trigger a primary immune response. Dendrocytes in meninges, the choroid plexus and cerebrospinal fluid can migrate to regional
lymph nodes to initiate a response, but when activated lymphocytes bearing Fas molecules on their surface subsequently
enter the nervous system they die on encountering resident
cells bearing Fas ligand molecules. Furthermore, glial cells
secrete a range of immunosuppressive factors,762 including
tumour growth factor-beta and alpha-melanocyte stimulating
hormone.401
From the foregoing it is clear that the immune response
can either prevent infection from taking place, or act to clear
virus in non-lethal infections, such as those associated with
attenuated viruses. As in many other infectious diseases,
however, the immune response is double-edged in rabies. It
was observed that peripherally inoculated virus reaches the
brain in mice a week or more before illness is discernible,
suggesting that the presence of virus alone is not the crucial
factor which precipitates signs and symptoms of rabies, and
that there is an immunopathological basis to the disease.63,
71, 156, 439
Immunosuppression of mice increases the mortality produced by attenuated and street viruses to 100 per
cent, but profoundly lengthens the incubation period by
one or two weeks, despite the fact that virus is present in the
brain during this time.622, 627 Administration of antibody to
the immunocompromised mice with brain infection results
in death some 48 hours later, the so-called early death phenomenon, while administration of immune spleen cells results in death about six days later, indicating that there can
be both humoral and cell-mediated immunopathological
effect.546, 622, 627 In infected mice in which immunosuppression is discontinued, deaths tend to coincide with the return
to immunoresponsiveness as marked by the appearance of
antibody in serum.627 The early death phenomenon is observed when infection occurs in partially immune or inadequately immunized animals.112, 113, 610, 722 In such
instances, the immune response is capable of not only accelerating the course of the disease but also limiting centrifugal spread of infection to non-neural tissues, such as
salivary glands, and the same effect is seen when the inoculation of large doses of street virus in susceptible animals
stimulates the occurrence of an early antibody response.156,
164, 609
Antibody limits extracellular spread of infection in
non-neural tissue and neutralizes virus present in saliva.156
It is implicit in the above discussion that there are many
variations to the pattern of rabies pathogenesis, and that
these can be ascribed to differences in virus strain and dose,
route of infection and host factors, including inherent susceptibility of the species and immune status. The structure
of the G protein is at least one of the factors which determines the pathogenicity of strains of rabies virus.184, 185, 547
Although the exact mechanism of attenuation is poorly understood, it has been shown that virulent virus in which a
single substitution is made at amino acid position 333 in the
G protein, can reach the spinal cord following peripheral inoculation in mice, but has a reduced capacity for spread in
the cord after an initial cycle of replication.181, 183 This site of
mutation appears to be involved in certain well-known veterinary vaccine strains of rabies virus.219
From the results of studies in inbred mice, it can be concluded that there is genetic control of resistance to rabies,
and that in mice this is controlled by one or two dominant
Rabies
genes not linked to the H-2 locus or to the neutralizing antibody response gene, although it is expressed in collaboration with immune response since immunosuppression
of a resistant animal can convert asymptomatic into lethal
infection.422, 679
Johnson348 and Murphy486 have drawn attention to the
fact that the sequence of events in the pathogenesis of rabies
is diabolically well suited to the perpetuation and spread of
the disease: virus is hidden from immune surveillance until
it is too late to matter; early selectivity for the limbic system
and relative sparing of the neocortex result in behavioural
changes which promote confrontation between rabid and
susceptible animals; the occurrence of the brain infection
and onset of altered behaviour coincide with virus being
available for transmission in saliva; the high mortality serves
to ensure that there is minimal accumulation of immune
animals in the population, and the occasional occurrence of
long incubation periods ensures that the virus survives until
susceptible individuals are recruited to the population. In
other virus infections of the central nervous system, the occurrence of encephalitis does not play a similar essential
role in promoting transmission of infection.
The sequence of events observed following peripheral
inoculation of Mokola and Lagos bat viruses in hamsters is
essentially similar to that seen in the pathogenesis of rabies:
replication of virus in muscle cells at the site of inoculation,
centripetal spread of infection along nerves and dissemination of virus in the central nervous system.487, 489 However,
the rabies-related viruses tend to replicate to a greater extent in non-neural tissues and organs and may produce demonstrable viraemia.264, 367, 527, 595, 687, 689
Clinical signs
Humans
More detailed observations have been made on the clinical
course of rabies in human patients than in other species.
The incubation period in humans may be as short as nine
days after infection has occurred through the infliction of
severe bites on the head but, at the other extreme, an incubation period of 19 years was apparently suspected to have
occurred in one patient.305 It was demonstrated recently by
means of molecular studies that three immigrants who developed rabies in the USA had been infected with virus associated with their native lands up to seven years prior to
developing the disease.626 However, only about 14 per cent
of incubation periods in humans are longer than 90 days,
and in South Africa most fall between 20 and 60 days, with a
mode of 34 days.41, 304
At the end of the incubation period there may be a prodromal phase of one to four days during which patients develop non-specific signs and symptoms of illness including
fever, headache, malaise, sore throat, nausea, anorexia, diarrhoea and fatigue. One- to two-thirds of patients experience paraesthesia or pain at the site of the infecting bite or in
1151
the affected extremity, and in some there is intense itching
leading to frenzied scratching of the wound site.304, 738 Some
display characteristic anxiety, irritability, depression and insomnia at this stage.
Patients next enter an acute neurologic or agitated phase
corresponding to the furious form of rabies seen in dogs.
They display hyperactive episodes of running or thrashing
about, or undergo convulsive seizures, which may arise
spontaneously or be precipitated by tactile, auditory, visual
or olfactory stimuli. In between such episodes they may be
anxious, but lucid and co-operative. They lose the ability to
swallow, hypersalivate and manifest hydrophobia, which is
variously ascribed to painful spasms of the pharynx and larynx or clonic reflex contractions of the diaphragm and accessory inspiratory muscles, triggered by being offered
water to drink.304, 738 Aerophobia is an analagous reaction
which occurs when patients are exposed to a draught of
air.354 Rabid humans hyperventilate and develop muscular
fasciculations, and occasionally priapism. Their mental
state passes through stages of disorientation, hallucinations, confusion, stupor and coma. Death may supervene
abruptly after one to ten days or paralysis may set in gradually as patients enter the final comatose phase of the illness
and develop cluster breathing marked by apnoeic periods.
The patients may be kept alive for weeks on life support systems, but in southern Africa they are generally brought to
medical attention at a late stage and most succumb within
hours to two days of admission to hospital.
Five to 20 per cent of human patients do not manifest
agitated behaviour, and paralytic signs predominate
throughout the course of an illness which corresponds to
the so-called dumb form of rabies in dogs. Onset of paralysis
may be diffuse and symmetrical, or maximal in the extremity where the infection occurred, or be of the ascending Landry type, but progresses and spreads until ultimately there is
respiratory paralysis.304
Only four instances of human survival of rabies have been
well documented.206, 338 One case involved a boy bitten by a
bat in the USA in 1970 and another a woman bitten by a dog in
Argentina in 1972, both of whom received post-exposure vaccination and recovered without sequelae, and the third involved a pre-immunized laboratory worker who gained
aerosol infection with an ostensibly attenuated strain of virus
in the USA in 1977 (see above) and recovered with severe neurological sequelae.22, 23, 305, 543 The fourth survivor was a Mexican boy who received vaccine after being bitten by a dog in
1992 and developed neurologic disease and coma, from which
he recovered with severe sequelae, including quadriparesis
and visual impairment, only to die four years later.15 These reported recoveries have inspired intense efforts to treat patients, but at most prolongation of the morbid period has been
achieved.338 It is also claimed that a prominent research scientist became infected while working on vampire bat-associated
rabies of cattle in Mexico and made a protracted recovery from
paralytic disease.649
1152
SECTION FOUR:
Domestic animals
Incubation periods in dogs commonly range from two to
eight weeks, and, although Henning309 cites an instance in
India where an incubation period of three years was recorded, the longest incubation period observed in a dog imported into Britain was just under eight months.95, 505, 686
Nevertheless, by analogy with humans it may be expected
that lower animals occasionally undergo protracted incubation periods. In South Africa and Zimbabwe, most incubation periods recorded in dogs fall between two and four
weeks.81, 264 A prodromal phase of illness analogous to that
which occurs in humans is likely to be noticed only in closely
observed pet animals, but it is notable that non-specific febrile illness of four to five days’ duration was commonly encountered as a prelude to paralytic illness in dogs when
rabies first entered KwaZulu-Natal Province in South Africa
in 1961.672 There may be a subtle change in temperament at
this stage, with, for instance, highly strung dogs becoming
affectionate or devoted pets becoming shy and irritable. Pupils may become dilated and pupillary reflexes slowed. Dogs
may manifest photophobia, preferring to shun people and
hide in dark places.95, 686
Within two to three days of the onset of illness, dogs pass
into the acute neurologic or furious phase of the disease,
showing restlessness, nervousness and exaggerated responses to visual or auditory stimulation. They may snap at
imaginary flies and inflict self injury at the site of the infecting wound, sometimes tearing away flesh down to the bone.
As they become increasingly irritable and aggressive they
may attack and bite anything they encounter, including restraining chains or cages, and damage their teeth and injure
their mouths in the process. Rabid dogs may develop a depraved appetite, swallowing a variety of objects, including
wood, stones and soil. At this stage they may become disoriented and wander aimlessly, attacking people and other animals, and sometimes return home in an advanced stage of
illness. They develop a fixed stare, described as a far-away
look, lose the ability to swallow, drool saliva and develop a
hoarse howl as spasm and paralysis of the laryngeal muscles
set in. They may develop bouts of convulsive seizures which
leave them exhausted, or die suddenly during a seizure. After
one to seven days they become uncoordinated, develop progressive paralysis, become comatose and die.95, 686
Dogs that develop so-called dumb rabies may show transient signs of furious rabies or progress directly to the paralytic disease, and may be difficult to recognize as being
rabid. The most characteristic sign is drooping of the jaw.
The muscles of mastication and deglutition are paralysed
and owners are often convinced that the dog has a bone
stuck in its throat. The dogs drool saliva and may emit a
choking sound or hoarse cough. After two to four days the
paralysis spreads to the rest of the body and they become
comatose and die.95, 686
It appears that in excess of 70 per cent of rabid dogs in
South Africa and Zimbabwe develop the furious form of the
disease, many of the remainder develop dumb rabies, but in
some instances little or no information on the nature of the
illness is received with specimens submitted for laboratory
investigation.81, 264 Classification of a case of rabies as either
dumb or furious may also vary with the stage of illness at
which the animal is examined. Foggin noted that 11,7 per
cent of rabid dogs in Zimbabwe conformed to neither the
furious nor the dumb rabies categories, and that many of
these exhibited signs suggestive of cerebellar ataxia: aimless
wandering and circling with the head held at a tilt, and emesis.264 He also noted that a significantly greater proportion
of dogs that developed non-furious forms of rabies had been
vaccinated than of those which developed furious disease.
Apart from the few instances of dogs surviving rabies or
developing chronic infection in West Africa, Ethiopia and
India (see Epidemiology), there have been isolated reports,
mostly unconfirmed, of similar incidents occurring elsewhere in the world, but until further evidence is produced it
can be assumed that the carrier state in dogs is extremely
rare.95
Less is known of incubation periods following natural infection in cats than in dogs, presumably because they are
often exposed to infection during their nocturnal wanderings, but it is generally agreed that they have somewhat
shorter incubation periods than dogs.95 Incubation periods
of two to six weeks have been recorded in southern Africa.40,
264
Cats are also considered more likely to acquire infection
from wild vertebrates than dogs because of their propensity
to prowl and hunt at night, and it is notable that the disease
may be more common in cats than in dogs in parts of North
America and Europe where dog rabies has been controlled
and sylvatic rabies is present.95, 717 Similarly, cats are more
likely than dogs to acquire infection with rabies-related viruses in southern Africa. Cats are also more likely than dogs
to develop the furious form of the disease, and are generally
more aggressive than rabid dogs.81, 95, 264, 717 Foggin264
noted that 89 per cent of unvaccinated cats which developed
rabies in Zimbabwe manifested the furious form of the disease. There may be a brief prodromal phase of less than a
day during which there is a change in temperament, followed by the furious or excitatory phase which commonly
lasts one to five days. Cats may froth at the mouth, show
muscular tremors, dilated pupils and cast flashing stares at
animate beings in their presence. They may assume a
threatening posture, with back arched and claws extended.
They are less likely than rabid dogs to recognize or to respond to familiar persons and make unprovoked attacks,
sometimes from behind, and often seek out the face of their
victim. They may bite without releasing their grip and have
to be prised off the victim. As the disease progresses they
may develop convulsions, an uncoordinated gait with ascending paralysis, become comatose and die. In the paralytic form of the disease cats may become affectionate and
purr, or hide as paralysis sets in, and death usually supervenes in one to two days.81, 95, 264, 717
Rabies
Incubation periods of 2 to 12 weeks have been recorded in
cattle in South Africa and Zimbabwe, but longer periods have
been recorded elsewhere, including 87 weeks in experimental
infection.81, 95, 264 About half of the rabid cattle for which information is available in South Africa, and a higher proportion in Zimbabwe, manifested aggressive behaviour.81, 264
Often several animals in a herd develop the disease within a
short space of time in areas where jackal or mongoose rabies
is prevalent. Early signs of illness observed in southern Africa
include separation from the rest of the herd, anorexia and docility or irritability. Milk production drops and there may be
increased sexual excitability, particularly in bulls. Pupils become dilated and cattle assume a fixed stare, grind their teeth,
and sometimes develop pica. There is frequently paralysis of
the tongue and jaw with copious salivation (Figure 99.5), and
1153
cattle often develop a characteristic hoarse bellow (Figure
99.6) which is recognized by stockmen. Aggression varies
from a tendency to butt other cattle, to mania with vicious attacks being made on humans, other animals or even inanimate objects such as fence posts. As the disease progresses
there is locomotory disturbance, sometimes with posterior
paresis, a swaying gait, tail paralysis, dragging of the hooves
and tenesmus with diarrhoea and frequent urination. There
is usually a rapid loss of condition. After a morbid period of
one to five days animals may assume ventral or lateral recumbency and die in convulsion, or become progressively paralysed, comatose and die. Sometimes there is subcutaneous
emphysema originating from pulmonary emphysema as a result of bellowing. In the paralytic form of the disease the excitatory phase is short or absent.81, 95, 264, 322
Figure 99.5 Note profuse
salivation in a rabid bovine.
(By courtesy of Dr H. van de
Pypekamp, Department of Animal
Health, Private Bag X138,
Pretoria 0001,
South Africa)
Figure 99.6 Rabid Afrikander
ox showing salivation, bellowing
and loss of condition. (By courtesy
of Dr H. van de Pypekamp,
Department of Animal Health,
Private Bag X138, Pretoria 0001,
South Africa)
1154
SECTION FOUR:
Incubation periods of two to four weeks have been recorded in sheep and goats in South Africa, but periods of up
to 17 weeks have been recorded elsewhere.81, 95 The disease
in these animals generally resembles that in cattle, but
sexual excitability is more common in sheep, while goats
have a tendency to bleat incessantly and are more frequently aggressive than cattle.81, 322, 644
Incubation periods of up to six weeks have been recorded in horses, and prodromal signs may include low
grade fever, altered behaviour and rubbing or biting the site
of the infecting wound.95 Rabid horses frequently develop
the furious form of the disease and may be extremely dangerous, and the same is true of the few donkeys in which the
disease has been observed in South Africa.81, 95 Horses become restless, excitable and show signs of colic such as abdominal straining, and whinny as if in great pain. They may
display marked sexual excitability, and attack furiously by
biting and kicking at humans and any inanimate objects
which they perceive as a threat or a restraint. The disease
runs a course of five to eight days and as paralysis sets in the
animals may fall repeatedly and finally remain down and
thrash their legs about until they become comatose and die.
Some horses develop the paralytic form of the disease and
wander or stagger about aimlessly, pressing their heads
against solid objects and ultimately enter a rapidly progressive terminal paralysis.95, 323
Rabies is seldom diagnosed in pigs in southern Africa
(Table 99.1). Rabid pigs may attempt to hide in corners of
their pen, but often display aggressive behaviour and attempt to bite humans if approached, and sows may kill their
offspring.95
Wild animals
Rabid yellow mongooses in South Africa tend to lose their
fear of humans and other animals and are often found in or
close to farm homesteads, outbuildings or stables. Only
about 38 per cent of rabid mongooses are overtly aggressive and humans are usually bitten when they attempt to
handle what are perceived to be tame animals.82 Dogs frequently attack and kill rabid mongooses, while cattle and
sheep are bitten when they display curiosity towards the
mongooses. The other species of mongoose which develop
rabies in southern Africa behave in a similar manner to
yellow mongooses, except that nocturnal species may become active in daylight.82, 264
Aggressive and non-aggressive patterns of behaviour appear to have been observed with almost equal frequency in
rabid jackals in Zimbabwe, South Africa and Namibia.82, 263,
264
Aggressive rabid jackals have been reported to attack the
wheels of moving vehicles, enter human dwellings and attack sleeping residents, or to attack cattle gathered at watering points. Non-aggressive rabid jackals lose their fear of
humans and dogs and approach farm buildings in daylight,
but do not initiate attacks.
Rabid wild cats and genets behave in a similar manner to
rabid domestic cats in that they make unprovoked and vicious attacks on humans and other animals, including humans who are asleep at night indoors or outdoors, and they
may also bite without releasing their hold on the victim. Like
mongooses, they frequently approach farm buildings when
rabid and can be particularly vicious if cornered.82
Honey badgers are ordinarily vicious and fierce fighters,
and although they seldom approach human dwellings they
can be formidable opponents for humans or dogs when
rabid.82 In one instance a rabid badger was apparently
responsible for the deaths of 47 sheep in a flock in Zimbabwe.198
The most frequently observed signs of disease in rabid
kudus in the 1977 to 1985 epidemic in Namibia were salivation, docility and paresis or paralysis.84, 85, 303, 328, 583, 603
The antelope approached and even attempted to enter farm
buildings (Figure 99.7), and could not be scared away easily.
They sometimes displayed a playful attitude towards humans and farm animals and readily entered pens with cattle.
In contrast, rabid small antelope in South Africa, such as
duikers, were sometimes found to be very aggressive towards humans and livestock and capable of inflicting severe
wounds with their sharp horns.40
As in all wild animals, the features of rabies in major reservoir hosts, such as foxes, raccoons, skunks, coyotes and
bats, have been described as difficult to discern.167, 505 All
are said to have very short morbid periods, less than a week.
It is more important to be aware of abnormal behaviour
than to look for classical signs of aggressive rabies: nocturnal animals become active in daylight, animals lose their
fear of humans and may enter buildings and public spaces,
either ignoring or attacking road traffic. Those that appear
abnormally tame and approachable constitute a particular
threat.
Pathology
There are no consistent macroscopic lesions in animals that
die of rabies; often the only visible abnormality is congestion of
the blood vessels of the leptomeninges. Animals may be emaciated and there may be self-inflicted injury, particularly at the
site of infection in carnivores, or injuries sustained in fights.
Foreign bodies may be found in the stomach, particularly in
monogastric animals, and dogs that have strayed may harbour
numerous ectoparasites, such as ticks.
The most significant microscopic lesions occur in the
central nervous system, and cranial and spinal ganglia, and
were first described in the 1870s.529 They consist of perivascular cuffing, focal and diffuse gliosis, neuronal degeneration, and intracytoplasmic inclusions, or Negri bodies
(Figure 99.8), in neurons.156, 331, 403, 337, 529, 656 Negri bodies
are sharply defined, rounded, acidophilic inclusions, which
measure 2 to 8 nm in diameter, but they assume an elongated shape in axons and dendrites. They may contain a basophilic internal structure, or one or more vacuoles, and are
Rabies
1155
Figure 99.7 Rabid kudu that
entered a farm building. (By
courtesy of Dr B.J.H. Barnard,
Section of Virology, OVI,
Onderstepoort 0110, South Africa)
Figure 99.8 Negri bodies in a
neuron. Acid fuchsin-methylene
blue staining method
sometimes surrounded by a clear halo. Negri bodies tend to
vary in size depending on the host, being large in dogs and
cattle, and are found most commonly in neurons of the hippocampus, or in Purkinje cells of the cerebellum in cattle.
They are found less frequently in glial cells, in ganglion cells
of the salivary glands and adrenal medulla, and in the
retina.331, 656, 710 Negri bodies must be distinguished from
lyssa bodies, which are small, homogeneous, eosinophilic
neuronal inclusions found in normal cats, and to a lesser extent in dogs and other animals.331, 669 Small, angulated,
dust-like, non-specific inclusions may be found in the neurons of healthy, aged sheep and cattle.656
The degree and distribution of neuronal degeneration,
satellitosis, neuronophagia and inflammatory infiltration
are extremely variable in rabies, and are generally most pronounced in dogs, and may be slight in ruminants.156, 656 It
has been suggested, but not demonstrated conclusively,
that the intensity and distribution of the lesions in the central nervous system are related to the anatomic location of
the infecting wound site.529 The perivascular infiltrate consists primarily of lymphocytes, with fewer macrophages and
plasma cells, and with the number of plasma cells generally
increasing with the duration of the illness. Neuronophagic
nodules, also termed Babes’ nodes, consist mainly of activated microglial cells. The nodules are not invariably associated with degenerative neurons and occur in both white
1156
SECTION FOUR:
and grey matter, as does diffuse gliosis, and there is a variable degree of meningitis.529 Vacuolar lesions similar to
those of the subacute spongiform encephalopathies of humans and lower animals have been described in naturally or
experimentally infected cats, dogs, cattle, sheep, horses,
foxes and skunks.156 Electron microscopic examination reveals that viral infection is usually widespread in the brain at
the time that death supervenes, despite the fact that demonstrable viral antigen and the lesions seen by light microscopy, may have a limited distribution.487 However, the use
of immunofluorescence or immunohistochemistry reveals
that rabies virus antigen is far more widely distributed in
nerve tissue than are the Negri bodies visible by ordinary
microscopy.489
Ganglioneuritis occurs particularly in the Gasserian ganglion, and it has been recommended that this site should be
examined when traumatic destruction or putrefaction renders it impossible to examine brain tissue for Negri bodies.
In the absence of Negri bodies, however, lesions in ganglia
are not specific for rabies, but lack of lesions in the Gasserian
ganglion is considered to be an indication that a diagnosis of
rabies is unlikely.331, 403, 529, 656 Lesions in salivary glands
consist of degeneration and necrosis of acinar epithelial
cells, with infiltration of lymphocytes, neutrophils and
plasma cells.264, 656
Diagnosis
It is more important to be aware that rabies induces abnormal behaviour than to suspect the disease only when animals exhibit the furious behaviour classically associated
with it. Suspicion of rabies is heightened when the affected
animal comes from an area where the disease is known to be
active, or when there is a history that suggests possible exposure to infection. A history of immunization renders a diagnosis of rabies less likely, but there are numerous instances
on record of the disease occurring even in animals which
have received multiple vaccinations.
In instances where a domestic animal has been provoked
to furious behaviour or to attack humans or other animals,
yet appears to exhibit its normal pattern of behaviour on examination, authorized persons (in most countries these are
state veterinary officials) may make the decision to confine
the animal and keep it under observation for a period of ten
days, and to kill it for laboratory examination only if it develops overt signs of the disease. This applies particularly to
vaccinated animals in situations where exposure of the animal to infection appears to have been unlikely. Feral animals, animals showing signs of illness considered to be
suggestive of rabies, or animals whose owner and history
cannot be traced should be killed for examination at the
time that the suspicion of rabies arises; the severity of the
lesions theoretically increases as the disease progresses, but
it has not invariably been found that the chances of establishing a laboratory diagnosis are better in animals that die
naturally than in those that are killed for examination.710
Animals should be killed in such a manner as to avoid
damaging the cranium. Protective clothing to be worn while
collecting specimens should include gloves, an impermeable apron and a face mask or visor, and personnel should
be immunized. The hippocampus is commonly used for the
diagnosis of rabies, but the distribution of lesions, or virus
antigen and infectivity, varies and it should be routine to
take tissue samples from a variety of sites in the brain.743
Brain specimens to be submitted for laboratory examination include 10 to 20 mm3 blocks of cerebrum, cerebellum,
hippocampus, medulla, thalamus and brain stem preserved
in duplicate in 50 per cent glycerol-saline solution for virological examination and in 10 per cent buffered formalin for
histopathological examination. Where small animals are involved, half of the brain (sectioned sagittaly) may simply be
placed in the glycerol-saline preservative and the other half
in the formalin. Adequate samples for making an accurate
diagnosis may also be collected in wide-bore, plastic drinking straws by a method which obviates the need to skin the
head and saw the cranium open: the occipital foramen is exposed with a knife and the sample is collected by inserting
the straw through the foramen and pushing it with a slight
twisting motion towards one of the eyes.87, 88, 311 The end of
the straw containing the plug of brain tissue is cut off into
the container with preservative. In large animals, straw
samples may be taken through a hole made by driving a
metal punch or large nail through an orbit or the forehead
into the cranium. Occasionally, virus antigen or infectivity
may be demonstrated in salivary glands and not brain, and it
is recommended that samples of submaxillary salivary gland
should also be submitted in glycerol-saline and formalin
preservatives. Examination of salivary glands also provides
valuable epidemiological information on the excretion of
virus by different vertebrates. Specimen containers are
sealed tightly and packed in sufficient absorbent material to
soak up the entire liquid contents of the containers should
they leak or break during transmission to the laboratory.
Formalin-fixed tissue is used for making a diagnosis by
examining histological sections stained with acid fuchsin
and methylene blue713 or similar stains, for the presence of
Negri bodies (Figure 99.8). Preparing and examining the
sections may take two days or more and the method lacks
sensitivity: in southern Africa, positive histological diagnoses were made in 66 to 87,7 per cent of cases in which
virus was isolated in mice or antigen demonstrated by immunofluorescence.264, 710 It was found in Zimbabwe that
histopathological diagnoses were made significantly less
frequently in dogs with the paralytic form of the disease than
in those with furious rabies,264 and it should be borne in
mind that occasionally the presence of virus and lesions
may be limited to the spinal cord.473 Nevertheless, histopathological examination of specimens has the merit that it
sometimes allows an alternative diagnosis to be established
in cases of nervous disease which are not due to rabies, such
Rabies
as distemper in dogs, or cerebral theileriosis and babesiosis
in cattle.264, 618
Negri bodies can also be demonstrated in impression
smears prepared from fresh (glycerol-saline preserved)
brain tissue and stained by the method of Sellers.600 The
technique is of similar sensitivity to histopathological examination of brain sections, and takes only one hour, but is
less useful for establishing alternative diagnoses and is
rarely used.
The standard method of making a diagnosis is to demonstrate rabies virus antigen in impression smears of fresh
brain by immunofluorescence.281 The test takes only one to
three hours to perform, and is of comparable sensitivity to
mouse inoculation, with a concordance of 95 to 99 per cent
between the two methods when the immunofluorescence
test is performed by experienced investigators.124, 731, 743
Immunofluorescence may demonstrate antigen in a small
proportion of instances in which specimens are too decomposed to yield virus isolates and, conversely, virus which is
present in low concentration can occasionally be isolated in
mice in instances where immunofluorescence is negative.
Inclusion bodies frequently lose their intracellular position
in impression smears, and the structures demonstrated by
immunofluorescence range from characteristic Negri bodies with inner structure, to fine particles, sometimes termed
rabies dust. Microwave fixation has been used successfully
as an alternative to acetone fixation of tissues for examination by immunofluorescence.201
Most laboratories use immunofluorescence as the sole
diagnostic test and resort to mouse inoculation as a confirmatory test only in instances where a negative result is recorded in an animal which has potentially been involved in
the exposure of a human to infection. However, it has been
argued that the chances of virus being present in infective
concentrations in saliva are negligible when the immunofluorescence test on brain is negative, and that mouse
inoculation is therefore not strictly necessary.27 It is nevertheless recommended that the immunofluorescence test
should be repeated in such instances.
Formalin-fixed brain tissue has been used successfully in
immunofluorescence tests.750 However, formalin fixation
may mask virus antigen, and when only fixed tissue is available for examination, the tissue can be treated with trypsin
to unmask antigen prior to performing the immunofluorescence test.86, 346, 711
Virus antigen may also be demonstrated by enzymelinked immunoassay,50 and kits for performing the test in
microplates are available commercially.535, 536 The test can
be performed in the course of a working day and there is 95
per cent concordance with results obtained by immunofluorescence.124 The results can be read accurately by the
naked eye, without need for a colorimeter, so that the test is
suitable for use in laboratories which lack facilities for performing immunofluorescence tests.124, 535, 536 Modified antigen detection kits are available to increase sensitivity for
1157
the detection of rabies-related viruses in addition to rabies
virus.530
The isolation of virus by intracerebral inoculation of
brain suspension into weaned mice was the standard diagnostic method prior to the widespread adoption of the immunofluorescence test. Isolation of virus is confirmed by
histopathological examination of the mouse brain, or preferably by performing an immunofluorescence test on it. The
method is sensitive, yielding isolates from virtually all
infected specimens received at the laboratory in a wellpreserved state, but it may take up to four weeks or longer
to obtain a result. Quicker results may be obtained by using
suckling mice and sacrificing individuals for examination by
immunofluorescence from the third or fourth day postinoculation onwards.280, 508, 731
Virus may be isolated in a variety of line cell cultures in
place of mice, and greatest sensitivity is claimed for neuroblastoma cells of murine and human origin.124, 171, 336, 566,
567, 568, 620, 621, 783
Brain or other tissue suspensions may be
toxic to cells, and it is usually necessary to subculture cells in
order to isolate virus. Since rabies virus is poorly cytopathic,
its isolation has to be demonstrated by performing immunofluorescence tests on the cultures. Under optimum conditions, isolation of virus can be achieved in two to four days
with a sensitivity similar to the detection of virus by enzymelinked immunoassay.124
The demonstration of virus antigen by immunofluorescence in corneal impression smears, or in nerve fibres surrounding hair follicles in frozen sections of nuchal skin
biopsies, were developed as tests for making a diagnosis in
live animals or in instances where the brain has been destroyed, and have also been applied to intra vitam diagnosis
of the disease in human patients, but the results obtained
have been inconsistent.102, 117, 118, 135, 405, 587, 636, 781 Isolation of virus from saliva can also be used to make a diagnosis
in live human patients or lower animals.743
Monoclonal antibodies can be used in indirect immunofluorescence tests to identify rabies-related viruses directly in field specimens,731 but in view of the apparently
rare occurrence of infection with these viruses it is doubtful whether the extra labour and expense involved in
routine use of monoclonal antibodies in diagnostic
laboratories is justified. It is probably better to perform
tests for the identification of the rabies-related viruses only
when there are indications that they may be involved (see
above). Otherwise, monoclonal antibodies can be used to
identify rabies virus biotypes or rabies-related viruses in
specific surveys.
Reverse transcription polymerase chain reaction can be
used to detect viral nucleic acid in brain tissue, saliva, and
cerebrospinal fluid.292, 334, 577, 626, 730, 748 The technique has
been used successfully on decomposed and formalin-fixed
brain tissue,199, 394, 749 and can be combined with nucleotide sequencing, or the use of selective primers to identify
the genotype of lyssavirus involved.307, 490, 498, 626
1158
SECTION FOUR:
Antibody to rabies virus may be demonstrated by a variety of methods including indirect immunofluorescence,
complement fixation, haemagglutination-inhibition, radioimmunoassay, enzyme-linked immunoassay and neutralization tests.147, 172, 238 The tests can be used to establish a
diagnosis of rabies in live human patients, who develop an
antibody response five days or more after the onset of the
illness, but this approach is less applicable in animals since
antibody only becomes demonstrable in terminal illness or
not at all.147 Serological tests are also performed to assess
response to vaccine, or to identify virus isolates.
Differential diagnosis
Diseases which may be, or have been, confused with rabies
in southern Africa include distemper, infectious canine
hepatitis, ehrlichiosis, cerebral babesiosis, toxoplasmosis,
cerebral cysticercosis (caused by Taenia solium), tetanus,
diminazine toxicity, pesticide (such as metaldehyde) and
strychnine poisonings in dogs; cerebral theileriosis and babesiosis, thrombotic meningoencephalitis (caused by Haemophilus somnus), sporadic bovine encephalomyelitis
(caused by Chlamydophila pecorum), botulism, lead, urea,
chlorinated hydrocarbon and organophosphate poisonings,
and cerebrocortical necrosis (caused by thiamine deficiency) in cattle; coenurus cerebralis (Taenia multiceps
coenurosis) in sheep; heartwater and a variety of plant
poisonings (such as those caused by Homeria and Morea
spp., Matricaria nigellifolia, Cestrum spp., Cynanchum spp.,
and Dipcadi glauca) and the mycotoxicosis, diplodiosis,
caused by the fungus Diplodia maydis in domestic ruminants; encephalomyelitis caused by equid herpesvirus 1
infection, tetanus, leukoencephalomalacia (caused by
fumonisin B1 produced by the fungus Fusarium moniliforme) and poisoning by Senecio spp. in horses; and pesticide poisonings in all animals.264, 364, 727 Some of these
conditions can be diagnosed on histological examination of
sections of the brain, but most have to be diagnosed by undertaking appropriate epidemiological, microbiological or
toxicological investigations. Many of these same conditions
occur elsewhere in the world,505 and as a generalization it
can be added that local viral encephalitides and plant poisons should be borne in mind.
Control
Control programmes
The existence of appropriate enabling legislation is a prerequisite to the control of rabies.30, 734 In addition, there is a
need for surveillance and the compilation of information on
the distribution and occurrence of the disease, which implies the existence of an adequate veterinary field service
infrastructure with diagnostic laboratory support. For the
control of urban rabies, information is needed on the number of dogs in the area where the disease is to be controlled,
and this can be assessed by establishing the dog to human
ratio in a random survey of households, or by a variety of
methods for estimating populations of free roaming dogs.30,
44, 131
It is also desirable to determine the age and sex structure of the dog population, and to derive estimates for longevity and the reproduction rate, since this will influence
decisions on the frequency with which vaccination campaigns need to be conducted. It should be determined
whether or not there are wild reservoirs of infection or
whether, as in Europe and North America, dog rabies can be
controlled independently of sylvatic rabies.
The assembled information is used to plan and budget
for control campaigns, and this could include cost-benefit
analysis in which the expense of controlling rabies is
weighed against the cost of vaccinating and treating humans, and the other losses incurred in continuing to cope
with the disease. Cumulative experience suggests that it
takes six to ten years to eradicate dog rabies from a large
country and currently dog vaccination campaigns cost in
the order of US $100 000 per million human residents, assuming a ratio of one dog to ten humans.472
The first step in controlling the disease is generally to declare the area where it occurs to be an affected area in terms
of the legislation, thus permitting the enforcement of control measures. Vaccination of dogs in the affected area then
becomes compulsory, and dogs may not be removed from
the area without a movement permit and proof of vaccination at least one month prior to movement. The importance
of educating members of the public and obtaining their support for rabies control campaigns cannot be overemphasized.30, 734 In affluent countries, control campaigns consist
of three elements: restriction of the movement of dogs, removal of unrestricted dogs and vaccination of restricted
dogs. Members of the public in such countries generally accept and fulfil their obligations, and neither the state nor the
public lack the resources for complying with the requirements for control of the disease.96 Even in developing nations, it is relatively easy to obtain restriction of the
movement of dogs of the higher-income segment of the
population, and to a variable extent the vaccination of such
dogs may be catered for by private veterinary practitioners,
but it is necessary for the state to conduct specific vaccination campaigns for the dogs of the lower-income segments
of the population, preferably at no cost to dog owners. Depending on local circumstances, it may be preferable to arrange for dogs to be vaccinated at pre-selected sites and
dates, or to conduct house to house vaccinations. It is preferable to use one of the current generation of inactivated cell
culture vaccines incorporating an adjuvant, which provides
protection for up to three years, and it is important to obtain
maximum coverage of the dogs within a given epidemiological unit (geographic cell) in as short a time as possible: the
high turnover rate in populations of unrestricted dogs
renders it ineffective to perform piecemeal or protracted
campaigns.404
Rabies
It is generally impractical or inconvenient to issue vaccination certificates during campaigns, but dogs may be given
neckbands with tags, or tattooed on the inner surface of the
ear.766 An alternative is to issue certificates only on request
or payment of a fee. At the least, a count should be kept of
the numbers of dogs vaccinated, and dogs should be marked
at some of the locations where vaccination is performed,
even temporarily by daubing them with paint, to allow subsequent assessment of vaccination coverage. The degree of
vaccination coverage attained is assessed by comparing estimates of dog populations with numbers vaccinated, or by
determining the ratio of marked (vaccinated) to unvaccinated dogs after campaigns, or by conducting antibody surveys. The success of campaigns is judged by continuing to
monitor for the occurrence of the disease, and it cannot be
assumed that complete control has been achieved until the
affected area has remained free of rabies for at least two
years. It is generally claimed that 70 to 80 per cent vaccination coverage is required in order to achieve control of the
disease in dogs, but this depends on the transmission rate in
the area concerned, and, for instance, Foggin264 calculated
from figures recorded in Zimbabwe that control could be
achieved by sustained 50 per cent vaccination coverage of
dogs in the communal farming areas of that country. Excellent control of urban rabies has been attained recently in
certain South American cities with 64,8 to 99,6 per cent vaccination coverage of dogs.30, 404, 734
The frequency with which campaigns need to be conducted depends on the prevalence of the disease, the age
structure of the dog population, and the rate of recruitment
of susceptible individuals to the population. Current immunization regulations in force in some African countries are
still based on the immunity induced by modified live vaccines, in particular Flury LEP or HEP vaccines, and require
the vaccination of dogs to be performed at three months of
age, again at one year of age, and every three years thereafter, but for practical purposes vaccination campaigns are
generally conducted at yearly intervals and all dogs over the
minimum age are vaccinated or re-vaccinated on these occasions unless proof of immunization status can be produced by the owner. Once control of dog rabies has been
achieved, it may be necessary to maintain a cordon sanitaire
by continuing to conduct vaccination campaigns along borders where the disease could be reintroduced.
Cats generally play a lesser role in the propagation of
urban rabies and their vaccination is usually recommended,
but left to the discretion of the owner. They can be included
in vaccination campaigns where cat rabies is a particular
problem, but they are more prone to lead a semi-feral existence than dogs, and it is neither necessary nor feasible to
obtain the same degree of vaccination coverage as in dogs. It
is recommended that fully susceptible domestic pets which
are exposed to infection by a proven rabid animal should be
destroyed, but dogs which are immunized in conformity
with legal requirements may be given a booster and kept
1159
under observation for a period of three months.27 Immunization of feral animals in captivity is generally discouraged
and in many countries may be performed only with the express approval of the state veterinary service when, for instance, valuable breeding animals of endangered species
are involved. Uncertainty or a false sense of security may
arise when feral animals which are kept as pets are immunized since the efficacy of the vaccine in the species concerned may be unknown, as may be the history of possible
exposure of the animal to infection. Vaccination of farm herbivores is generally made optional, to be performed at the
discretion and expense of the owner when problems with
rabies are encountered.
The removal or destruction of unvaccinated dogs has
been found to be counter-productive as a means of controlling rabies where dogs are unrestricted (see Epidemiology).
Owing to the recuperative reproductive capacity of populations of unrestricted dogs, it is estimated that 50 to 80 per
cent of individuals must be removed each year if the campaign is to have a sustained effect on the population, and it is
much more effective to reduce the carrying capacity of the
neighbourhood through proper refuse disposal.734 Alternatives include offering and promoting a service to sterilize
dogs. The same principles apply to populations of feral animals, and rather than applying ineffective or indiscriminate
methods for removing individuals it is better to use methods
which leave existing social structures and hierarchies intact,
such as the use of drugs to control breeding,255 or to develop
a method for oral immunization analagous to that which has
recently been applied with great success to foxes in Europe
(see below).
Import and quarantine regulations constitute another
important facet of rabies control. Some countries which are
free of rabies in terrestrial species, such as Britain, require
imported dogs to be vaccinated and subjected to six months
quarantine, and have nevertheless recorded a few cases of
the disease after expiry of the quarantine period.143 Other
countries which are free of the terrestrial disease, such as
Australia, allow importation only from rabies-free countries,
so that Britain is sometimes used as a ‘stepping-stone’ in the
movement of animals. South Africa requires that cats and
dogs from countries with rabies should be immunized one
month prior to importation and be held in quarantine for a
month after arrival. Conditions for the importation of other
animals, including zoo animals, are determined by the state
veterinary services as the occasion arises. In all instances of
intended international movement of animals it is necessary
to establish the latest requirements of the recipient country
prior to the translocation of the animals.
Vaccines and immunization of domestic animals
The immunogenicity of the inactivated nerve tissue vaccines originally used in humans and lower animals was generally poor,460, 741 but improved after potency assays were
introduced in 1940.293, 598 However, the vaccines caused
1160
SECTION FOUR:
paralytic neuritis and encephalomyelitis in a proportion of
recipients due to an auto-allergic demyelinating reaction induced by the lipoprotein myelin, present in the nerve tissue
from which the vaccines were prepared (the myelins of different species share antigens).291, 326, 352, 398, 560 Consequently, a change was made in the 1950s to the use of
immature animals, particularly suckling mice,274 for the
preparation of vaccine at a stage before brain tissue is fully
myelinated, while vaccine prepared from virus cultured in
embryonated duck eggs was introduced for use in humans.545 Neither of these two types of vaccine was entirely
free of allergens21, 308 and there were still doubts about their
immunogenicity.78, 192 In particular, nerve tissue and duck
embryo vaccines were found to have a much higher content
of rabies virus N protein than G protein antigen. Nevertheless, inactivated nerve tissue vaccines remain in use for
humans and lower animals in many countries,37 while
production of duck embryo vaccine was discontinued in
1981.397, 398
From the 1950s onwards there was a trend in the developed nations towards replacing nerve tissue vaccines with
attenuated or so-called modified live virus vaccines for veterinary use. These included the LEP derivative385, 387 of the
Flury strain of virus412 for use in dogs, the HEP derivative of
the Flury strain for use in cats and cattle,386 the ERA vaccine
strain1 derived from the SAD (Street Alabama Dufferin)
strain of virus249 for use in dogs and other animals, the
Vnukovo-32 vaccine strain derived from the SAD strain in
the former USSR,599 the SAD-B19 clone of virus used for oral
immunization of foxes in Europe,593 and the Kelev vaccine
strain developed from a strain of rabies virus isolated from a
dog in Israel.382
The modified live vaccines were used successfully to
control dog rabies in many western nations, but carried the
potential danger of reversion to virulence and were associated with a small proportion of vaccination failures,94, 137,
138, 144, 525, 746
problems which were also encountered in
southern Africa.40, 83, 264, 449, 605
Currently, a range of highly effective, safe and thermostable, inactivated veterinary vaccines, prepared from virus
grown in a variety of primary and line cell cultures, is available,90, 548, 602, 716 and vaccines of this type have been
brought into use in most southern African countries. Some
of the vaccines may be used in all domestic carnivores and
herbivores, while others are designed for use in specific species and may be multivalent, incorporating antigens of other
infectious disease agents, which affect the species. Some are
recommended specifically for either intramuscular or subcutaneous use, but others may be administered by either
route. The duration of the protective immunity to challenge
with rabies virus induced in the target species varies from
one to three years with the antigen content of the vaccines.
The more potent vaccines may be used in pups and the
progeny of other carnivores as young as four to six weeks of
age, or 11 weeks if the dam has been immunized, and
booster doses are administered at three yearly intervals.
Young herbivores may be vaccinated initially at the age of
four months, or nine months if the dam has been immunized, with boosters being administered every one, two or
three years depending on the antigen content of the vaccine
and the prevailing challenge rate.
Recombinant vaccines are becoming commercially
available and, for instance, several manufacturers in the
USA market canary pox virus expressing the rabies virus glycoprotein gene for use in cats and horses.271, 491, 675, 676 A
vaccine strain of the poxvirus causing lumpy skin disease in
cattle in Africa, has been used to prepare a recombinant expressing rabies glycoprotein, which has proved to be highly
immunogenic in cattle.48 DNA-based vaccines are also
being explored for use in immunizing against rabies virus,
and have the advantage over recombinant antigens that
they can be used to induce cell-mediated immunity as well
as humoral immunity.127, 531, 680, 780 Moreover, the DNA
vaccines can also be made multivalent to protect against
rabies-related viruses.72, 532, 533, 423, 425, 426 However, one
problem which is still receiving attention is the relatively
slow immune response induced by DNA vaccines.424
Oral vaccination
The basic requirements for oral immunization of animals
are that the viruses or recombinants used in oral vaccines
should be easy to produce in high concentraion, stable at
high ambient temperatures, and immunogenic for the target species without being pathogenic for non-target species.
Baits should be able to be mass produced, attractive to the
target species and readily chewed so that the immunizing
agent is exposed when the bait is taken.65, 116, 593
The concept of oral vaccination arose from the demonstration of susceptibilty to oral infection in laboratory animals,179, 641 and the feasibility of immunizing foxes by this
route was demonstrated in the USA, using the ERA derivative of SAD virus since the other available attenuated strains
of rabies virus were known to be pathogenic for foxes.65 It
was subsequently shown that foxes could be immunized by
enclosing a plastic straw filled with vaccine in a sausage
bait.760 Following successful field trials in Switzerland in
1978, in which foxes were immunized with SAD-Berne virus
in capsules inserted into chicken head baits,647 immunization of foxes was extended with good effect to Germany,
Italy, Austria, Luxembourg, Belgium and France, using the
SAD-B19 clone of virus enclosed in artificial baits produced
industrially from fat and fishmeal.93, 523, 590, 737
The possibility was raised that SAD virus derivatives
could produce disease and become established in nontarget species which took baits, particularly rodents and
mustelids,65, 503, 771 but the problem did not materialize in
the field.116, 735, 737 Nevertheless, the SAG-1 (SAD-Avirulent-Gif) and SAG-2 strains were developed as further derivatives of the SAD strain in order to improve safety.116
The SAG-1 virus was a monoclonal antibody escape
Rabies
mutant of SAD virus that had a substitution of serine for
arginine at amino acid position 333 in the glycoprotein,
brought about by a single nucleotide mutation in codon
333, while SAG-2 had a double mutation in the codon, rendering reversion less likely, and substituting116 glutamine
for the arginine.182, 183, 399, 409
Subsequently a vaccinia-rabies glycoprotein recombinant (VRG) vaccine was produced to overcome concerns
about safety in non-target species,372, 571, 763 and this was
found safe and effective for use in racoons in the USA and
foxes in Europe.128, 129, 130, 209, 574, 522 Other poxviruses used
successfully to produce recombinants expressing rabies
virus antigens included racoonpox, fowlpox and canarypox
viruses.48, 231, 673, 674 Recombinants were used to demonstrate the protective immunogenicity of rabies nucleoprotein.248, 275, 316 Adenoviruses-vectored recombinants
expressing rabies glycoprotein were also developed successfully,158 and there is even the prospect that food plants can
be used for the production and delivery of rabies vaccines
through the expression of virus-vectored genes, as demonstrated with tomatoes and spinach.459
Baits can be distributed economically by helicopter or
fixed-wing aircraft, but are generally attractive to a wide
range of vertebrates, and greater selectivity for the intended
target species can be attained by placing baits by hand in appropriate niches.351, 593, 737, 484 The taking of baits by target
and non-target species is assessed by the incorporation of
biological markers, such as tetracycline which is deposited
in bone and can be demonstrated in cross-sections of
teeth,737 or by the use of automatic cameras. Other markers
include Du Pont Oil Blue A, Rhodamine B, and sulphadimethoxine which is a serum marker.298, 300, 350, 419
During the 1990s, the vaccination of foxes in Europe was
extended to 15 countries and proved to be extremely successful, with minor setbacks where vaccination was discontinued too soon, allowing infection to be reintroduced from
areas where the disease was still present to areas where
eradication had already been achieved. Nevertheless, before
the turn of the century control had been achieved in western
Europe, and it became necessary to extend the campaign to
eastern Europe.51–53, 521, 652, 782 It was suggested that in
order to ensure eradication of fox rabies in Europe, 70 per
cent vaccination coverage should be maintained for at least
six years, and that the immunization campaigns should be
combined with strategic reduction of populations in certain
locations.51, 691
Control of rabies in wildlife is considerably more complex in North America than it is in Europe, with more vector
species, sometimes overlapping in distribution, and much
vaster areas being involved. Immunizing agents tested in
target and non-target species include SAG-1 and -2 attenuated rabies viruses, vaccinia-rabies glycoprotein recombinant, racoon pox-rabies glycoprotein recombinant,
baculovirus-expressed rabies glycoprotein, and canine adenovirus 2-rabies glycoprotein recombinant, in racoons,
1161
skunks, arctic foxes, red foxes, grey foxes, and coyotes.47, 247,
267, 268, 272, 297, 570, 763
A variety of specific baits were developed and tested for coyotes, grey foxes, and racoons.236, 237,
296, 300, 418, 421, 539, 563, 650, 651
In general, the immunizing
agents all performed well, but canine adenovirus 2 recombinant virus proved to be potentially pathogenic for
racoons.297 Only VRG has been registered for use in rabies
control programmes in wildlife in the USA, and its use is
restricted to state authorities.491 The first trial release of
recombinant oral vaccine, VRG, in the USA was directed at
racoons in Virginia, in 1990, and proved to be successful.299
Although no universal approach to the control of rabies
in wildlife in North America is possible, a number of programmes have been instituted to address specific problems.
In Ontario, Canada, where there is a complicated situation,
with rabies in racoons, skunks and foxes all being involved
as vectors, a programme of capture, vaccination and release
of animals plus oral immunization of racoons with the ERA
derivative of SAD virus has proved to be effective in controlling the threat of infection to humans.563, 564 Oral vaccination of racoons with VRG has met with initial successes in a
number of locations from Florida to Massachusetts, chosen
as strategic sites to limit further spread of infection.350 Oral
vaccination of grey foxes and coyotes is proving to be effective in different locations in Texas.237, 239, 254 Capture, vaccination and release is being used to combat spread of rabies
virus of bat origin in skunks in northern Arizona.414
The efficacy of oral vaccination, and/or the suitability of
baits, has also been explored for use in foxes in Israel, jackals
in Zimbabwe, African wild dogs in South Africa, and mongooses in Antigua.101, 103, 104, 189, 381, 420 It has been mooted
that oral immunization could be extended to populations of
unrestricted dogs which are inaccessible to vaccination by
ordinary means.65, 67, 243, 538, 417, 540
Human immunization and post-exposure treatment
It was not until the use of rabies antiserum in conjunction
with vaccine was standardized that convincing evidence of
post-exposure protection of humans was obtained.77, 294, 295
Antiserum is used to provide immediate protection until
vaccine-induced immunity becomes effective, but the timing and dosage of passively administered antibody must be
controlled or else there is interference with the response to
vaccine.
An inactivated and purified vaccine prepared from virus
grown in human diploid cell cultures was developed during
the 1960s and became increasingly available for use in humans during the 1970s and 1980s.397, 398, 757, 764 The vaccine
is prepared in France from virus grown in WI38 diploid cells
and in Germany from virus grown in MRC5 diploid cells,448,
504
and is highly effective and safe. Only two disputed instances of transient peripheral neuritis resembling the Guillain-Barré syndrome were recorded among the first 533 000
patients to be treated, although minor local and systemic reactions such as itchiness, urticaria, arthralgia and fever were
1162
SECTION FOUR:
observed in a small proportion of patients.397, 398 There
were about 20 instances of vaccine failure, but most cases
involved patients in whom treatment was delayed, or who
failed to receive immunoglobulin or the full course of treatment, or who had underlying disease.31, 397, 398, 685 Moreover, it is noticeable that several of the patients in whom
vaccine failure occurred had short incubation periods, including a South African patient,31, 604 so that it is possible
that nerve infection occurred too rapidly in these instances
for treatment to be effective.
Poor virus yields are obtained from diploid cells so that
the human vaccine is expensive to produce and this has limited its use in many countries. Consequently, cheaper inactivated vaccines for use in humans have been developed
from virus grown on primary chick embryo cells,89 or Vero
line cells,479 or from virus grown in duck embryos and subjected to a high degree of purification and concentration.278
Several other vaccines of a similar nature have been developed, but have not found wide usage, or are used mainly in
eastern Europe, the former USSR and China. An effective
aluminium phosphate adsorbed, inactivated vaccine was
also developed from virus grown in diploid foetal rhesus
monkey kidney cells.139 All of these vaccines are purified,
safe and of similar potency to the human diploid cell culture
vaccine.
In terms of control legislation, rabies is generally a notifiable disease and it is the duty of state veterinary officials,
including veterinarians and animal health inspectors, to investigate incidents of potential exposure of humans to infection and to report diagnostic findings on the animal
concerned to the medical personnel responsible for treating
the exposed humans. All veterinarians should, moreover, be
familiar with current recommendations on pre- and postexposure treatment of humans in order to ensure that they
and their assistants are adequately protected. Recommendations on pre- and post-exposure treatment of humans are
published periodically in Reports of the World Health Organization Expert Committee on Rabies and the following information is based on the recommendations included in the
Eighth Report published in 1992, and a subsidiary report on
intradermal immunization published in 1997.33, 38, 39, 685
Reference below to vaccine implies human diploid cell culture vaccine or one of the equivalent purified and inactivated products with an antigenic potency of >2,5 IU/ml. Full
doses of modern cell culture vaccines vary from 0,5 to 1,0 ml
in volume, depending on the manufacturer, but all contain
the same amount of antigen.
It is recommended that persons with an occupational
risk of exposure to infection, such as veterinary staff, should
be subjected to pre-exposure prophylaxis through the administration of an initial three full doses of vaccine into the
deltoid muscle on days 0, 7 and 28; a few days’ variation in
the timing of the repeat doses is acceptable. The inactivated
vaccines stipulated above may all be used effectively and
there is generally no need to monitor antibody response.
Single booster doses are administered every two to three
years depending on risk, i.e. the frequency with which rabid
animals or infected materials are handled. For people at
constant risk, such as veterinary and laboratory staff, it is
recommended that rabies neutralizing antibody titres are
checked, and a booster administered when titres fall below
0,5 IU/ml, although recent findings suggest that immunity
may last five to ten years.39, 653 Pre-exposure immunization
was also achieved with 0,1 ml intradermal doses in place of
the full intramuscular doses, but poor response was observed in persons who were taking chloroquine as an antimalarial prophylaxis.97, 514, 678 Persons who are preimmunized receive a single intramuscular dose of vaccine
after exposure to infection, followed by a second dose on
day 3 or later; the exact timing is not critical. Such persons
should not, however, receive rabies antiserum or immunoglobulin if their last immunization occurred during the previous five years since this interferes with their rapid
anamnestic response to vaccine. Preventive pre-exposure
immunization is generally performed at the expense of the
vaccinee or the employer, but in many countries, including
South Africa, post-exposure treatment is performed at state
expense.
All bite wounds inflicted by potentially rabid animals
should be cleansed thoroughly with soap and water or a
quaternary ammonium compound detergent (never both
together since their effects are antagonistic), or water alone,
and an antiseptic should be applied, preferably consisting of
either tincture of iodine, aqueous iodine or 70 per cent alcohol. Bleeding should be encouraged and suturing of the
wound should be avoided if possible, but anti-tetanus treatment and antibiotic therapy should be applied as deemed
necessary. If anti-rabies serum or immunoglobulin is to be
used (see below), as much as possible of the calculated dose
should be infiltrated into the tissues around the wound and
instilled into the depth of the wound, and the rest administered at a single site into the gluteal muscle. The dosage is
20 IU/kg body weight for human anti-rabies immunoglobulin, or 40 IU/kg for antiserum or immunoglobulin
prepared in horses.
The indications for specific anti-rabies therapy vary with
the degree of risk attached to the exposure to infection, and
three categories are defined.
Category I In this category risk of exposure to infection
occurs where persons have touched or fed, or have been
licked on unbroken skin by, confirmed or suspected rabid
domestic or wild animals, or animals which have not remained available for observation, or animals from which
specimens suitable for laboratory examination have not
been obtained, and no specific treatment is indicated in
such instances if a reliable history has been obtained.
Category II In category II risk of exposure to rabies arises
where the animals stipulated above have nibbled uncovered
Rabies
skin, or have inflicted minor bites and scratches without
drawing blood, or have licked broken skin. In these instances a course of vaccination is started immediately but
may be discontinued if the animal remains healthy throughout an observation period of ten days, or has been killed for
laboratory examination and found to be negative for rabies.
The start of vaccination may be delayed in instances where
apparently healthy dogs or cats from a low-risk area are
placed under observation. The use of anti-rabies immunoglobulin is not essential in risk Category II exposures. The
standard treatment (Essen schedule) to be applied where
Category II risk of exposure arises consists of a course of five
full doses of vaccine (0,5 or 1,0 ml according to the manufacturer’s product) delivered into the deltoid muscle, or anterolateral thigh muscle in small infants, on days 0, 3, 7, 14 and
30; day 0 being the day on which the patient first presents for
treatment. Administration of vaccine into the buttock is
contra-indicated since fat deposits may impair uptake of
vaccine. Alternative abbreviated courses of vaccination may
be applied in risk Category II exposures, and these are of
particular advantage in underdeveloped nations since there
is a saving in the amount of vaccine used and in the number
of visits to clinics which patients have to make for treatment.
In the so-called 2-1-1 schedule (Zagreb schedule) two full
doses of vaccine are administered bilaterally into the deltoid
muscles on day 0, and single doses are administered on days
7 and 21.725 The 2-1-1 schedule should only be used in Category II exposures and should not be combined with the use
of immunoglobulin or antiserum. In the Thai Red Cross intradermal schedule, two 0,1-ml intradermal doses are administered bilaterally on the fore or upper arms on days 0, 3
and 7, followed by single 0,1-ml intradermal doses on days
28 and 90, resulting in a total usage of only 0,8 ml of vaccine.
The Oxford intradermal schedule involves the use of eight
0,1-ml doses of vaccine at multiple sites on day 0 chosen for
proximity to lymph nodes (bilateral deltoids, anterior
thighs, lower abdominal quadrants, and suprascapular regions), followed by four 0,1-ml doses on day 7 (bilateral deltoids and thighs), and single 0,1-ml intradermal doses on
days 28 and 90.39 The intradermal schedules should only be
used where good technique can be guaranteed, and once an
ampoule of vaccine has been opened, it should be kept refrigerated and used only on the same day.
Category III This category risk of exposure to infection
arises where the animals stipulated above inflict single or
multiple transdermal bites or scratches, and the correct
treatment is to administer anti-rabies immunoglobulin (or
antiserum) and vaccine on the day that the patient presents
for treatment, irrespective of the time elapsed since the exposure to infection occurred (this represents a modification
of previous recommendations in which the use of immunoglobulin was only advocated if patients presented for treatment within a week of exposure to infection). Moreover, it
was formerly advocated that immunoglobulin should only
1163
be given at the time that the first dose of vaccine is administered so as not to depress response to vaccine, but it is often
difficult to obtain immunoglobulin immediately, and it is
now considered acceptable to administer immunoglobulin
up to seven days after the first post-exposure immunization
since it is reasoned that there is still a need for passive immunity until antibody response occurs.369 Vaccination
schedules to be used in Category III exposures include the
standard intramuscular regime, or the intradermal schedules as described above. Use of immunoglobulin with abbreviated schedules of immunization is controversial, and
conflicting results have been obtained,169, 658 but the eightsite Oxford schedule of immunization is intended to be
effective without immunoglobulin. As with Category II
exposures, treatment may be stopped if animals under observation remain normal for ten days or are found to be
negative for rabies on laboratory investigation.
The first dose of vaccine to be administered should be
doubled or trebled where:
• treatment is delayed for 48 hours or more post-exposure,
particularly if immunoglobulin or antiserum is used;
• patients incorrectly receive immunoglobulin or antiserum 24 hours or more before vaccine;
• there is chronic underlying disease such as cirrhosis;
• patients have a congenital or acquired immunodeficiency state;
• patients are under treatment with immunosuppressive
drugs, including antimalarials; or
• patients are aged or malnourished.
It should be stressed that the guidelines for use of abbreviated schedules of immunization produced by WHO are only
recommendations, and that the decision to implement such
schedules resides with the government agencies which select policies for their own countries. In South Africa, for instance, there is as yet little experience of intradermal
technique in rural clinics, and it is recommended that the
abbreviated schedules be applied only after discussion with
state authorities in certain situations requiring immunization of large numbers of people with low risk exposure. A low
risk of infection occurs in instances where persons have had
contact with rabid human patients or have butchered and
consumed rabid farm animals (see Epidemiology). It is generally suggested that by careful questioning such persons
are classified as either definitely being at risk and in need of
treatment, or unlikely to be at risk, and that persons in the
latter category be given the option of receiving treatment if
they are concerned for their own safety. As with other schedules of immunization, there have been vaccine failures with
intradermal vaccination, particularly in immunocompromised patients, but the results of one study suggest that
good immune responses can be obtained even where intradermal technique is deficient.541, 670
Among the rabies-related viruses, Duvenhage is antigenically closest to rabies virus, and rabies vaccine affords
1164
SECTION FOUR:
the greatest protection against this virus, and least protection against Mokola virus.246, 388, 688 In the absence of specific vaccines, however, rabies vaccine should be used in all
instances where it is deemed that persons have been poten-
tially exposed to infection with a rabies-related virus. Persons who have been accidentally inoculated with SAD or
Flury vaccine strains of rabies virus should not be considered at risk, and no specific treatment is indicated.21, 269
References
1
abelseth, m.k., 1964. An attenuated rabies vaccine for domestic animals
produced in tissue culture. Canadian Veterinary Journal, 5, 279–286.
2
acha, p.n. & arambulo, p.v.i., 1985. Rabies in the Tropics — history and
current status. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
(eds). Rabies in the Tropics. Berlin: Springer-Verlag.
21
anonymous, 1976. Recommendations of the Public Health Service
Advisory Committee on Immunization Practices. Rabies. Morbidity and
Mortality Weekly Report, 25, 403–406.
22
anonymous, 1977. Follow-up on rabies — New York. Morbidity and
Mortality Weekly Report, 26, 249–250.
3
adamson, j.s., 1954. Ecology of rabies in Southern Rhodesia. Bulletin of
the World Health Organization, 10, 753–759.
23
anonymous, 1977. Rabies in a laboratory worker — New York. Morbidity
and Mortality Weekly Report, 26, 183–184.
4
addy, p.a.k., 1985. Epidemiology of rabies in Ghana. In: kuwert, e.,
mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in the Tropics.
Berlin: Springer-Verlag.
24
anonymous, 1979. Human-to-human transmission of rabies by a
corneal transplant — Idaho. Morbidity and Mortality Weekly Report, 28,
109–111.
5
afshar, a., 1979. A review of non-bite transmission of rabies virus
infection. British Veterinary Journal, 135, 142–148.
25
6
aghomo, h.o. & rupprecht, c.e., 1989. Further studies on rabies virus
isolated from healthy dogs in Nigeria. Veterinary Microbiology, 22,
17–22.
anonymous, 1980. Human-to-human transmission of rabies via a
corneal transplant — France. Morbidity and Mortality Weekly Report,
29, 25–26.
7
ahmadu, b. & zulu, l.n., 1998. Rabies in a Zambian bat. The Veterinary
Record, 143, 148.
8
ahuja, s., tripathi, k.k., saha, s.m., & saxena, s.n., 1985. Epidemiology of
rabies in India. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
9
aitken, t.h.g., kowalski, r.w., beaty, b.j., buckley, s.m., wright, j.d.,
shope, r.w. and others, 1984. Arthropod studies with rabies-related
Mokola virus. American Journal of Experimental Medicine and Hygiene,
33, 945–952.
10
akakpo, a.j., 1985. Le chien dans la Société) Noire Africaine: Un téservoir
de rage. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
Rabies in the Tropics. Berlin: Springer-Verlag.
11
alexander, k.a., kat, p.w., wayne, r.k. & fuller, t.k., 1994. Serologic
survey of selected canine pathogens among free-ranging jackals in
Kenya. Journal of Wildlife Diseases, 30, 486–491.
12
13
alexander, k.a., smith, j.s., macharia, m.j. & king, a.a., 1993. Rabies in
the Masai Mara, Kenya: preliminary report. Onderstepoort Journal of
Veterinary Research, 60, 411–414.
alexander, r.a., 1952. Rabies in South Africa: a review of the present
position. Journal of the South African Veterinary Medical Association, 23,
135–139.
14
almeida, j.d., howatson, a.f., pinteric, l. & fenje, p., 1962. Electron
microscope observations on rabies virus by negative staining. Virology,
18, 147–152.
15
alvarez, l., fajardo, r., lopez, e., pedroza, r., hemachudha, t., cortes,
g. and others, 1994. Partial recovery from rabies in a nine-year-old boy.
Paediatric Infectious Diseases, 13, 1154–1155.
16
anderson, l.j., nicholson, k.g., tauxe, r.v. & winkler, w.g., 1984.
Human rabies in the United States, 1960 to 1979: Epidemiology,
diagnosis, and prevention. Annals of Internal Medicine, 100, 728–735.
17
andral, l., artois, m., aubert, m.f. & blancou, j., 1982. [Radio-tracking
of rabid foxes]. Comparative Immunology, Microbiology and Infectious
Diseases, 5, 285–291.
18
andral, l. & serie, c., 1957. Etudes experimentales sur la rage en
Ethiopie. Annales de l’Institut Pasteur, 93, 475–488.
19
anonymous, 1972. Human rabies — Texas. Morbidity and Mortality
Weekly Report, 21, 113–114.
20 anonymous, 1973. World Health Organization Expert Committee on
Rabies, Sixth Report. Technical Report Series, 523. Geneva: World Health
Organization.
26 anonymous, 1981. Human-to-human transmission of rabies via corneal
transplant — Thailand. Morbidity and Mortality Weekly Report, 30,
473–474.
27
anonymous, 1984. World Health Organization Expert Committee on
Rabies, Seventh Report. Technical Report Series, 709. Geneva: World
Health Organization.
28 anonymous, 1985. Isolations of Lagos bat virus in West Africa. Internal
Reports of Centre Collabrateur OMS de Référence et Recherche Pour les
Arbovirus. Institut Pasteur, Dakar, Senegal.
29 anonymous, 1986. Bat rabies — Europe. Morbidity and Mortality Weekly
Report, 35, 430–432.
30 anonymous, 1987. Guidelines for dog rabies control. Geneva: World
31
anonymous, 1988. Rabies vaccines failures. Lancet, 1, 917–918.
32
anonymous, 1989. [Bat rabies in Europe]. Rabies Bulletin Europe, 13,
3–11.
33
anonymous, 1989. Rabies treatment. Weekly Epidemiological Record, 64,
112–114.
34
anonymous, 1989. World survey of rabies 23 (for the years 1986/87).
Geneva: World Health Organization.
35
anonymous, 1990. Rabies — bat rabies. Weekly Epidemiological Record,
65, 24–25.
36 anonymous, 1991. Directorate of Animal Health, Department of
Agriculture, Private Bag X138, Pretoria 0001. Unpublished records.
37
anonymous, 1991. World Survey of Rabies 24 (for the year 1988). Geneva:
World Health Organization.
38 anonymous, 1992. WHO expert committee on rabies, Eighth Report.
Technical Report Series, 824. Geneva: World Health Organization.
39 anonymous, 1997. WHO recommendations on rabies post-exposure
treatment and the correct technique of intradermal immunization
against rabies. WHO/EMC/ZOO.96.6. Geneva: World Health
Organization.
40 anonymous, 2000. ARC Onderstepoort Veterinary Institute,
Onderstepoort, 0110 South Africa. Unpublished laboratory records
1932–2000.
41
anonymous, 2000. National Institute for Communicable Diseases,
Sandringham 2131, South Africa. Unpublished laboratory records,
1953–2000.
42
anonymous, 2000. Regional Veterinary Laboratory, Allerton,
Pietermaritzburg 3200, South Africa. Unpublished laboratory records
1987–2000.
Rabies
1165
43
anonymous, 2000. Update: Raccoon rabies epizootic — United States
and Canada, 1999. Morbidity and Mortality Weekly Report, 49, 31–35.
66 baer, g.m. & bales, g.l., 1967. Experimental rabies infection in the
Mexican freetail bat. Journal of Infectious Diseases, 117, 82–90.
44
arbuckle, d.d., 1990. Survey on dogs in Natal and KwaZulu. Report to
the Regional Director of Veterinary Services, Pietermaritzburg. 3200.
3 August 1990.
67
45
arellano-sota, c., 1988. Biology, ecology and control of the vampire
bat. Reviews of Infectious Diseases, 10, 615–619.
68 baer, g.m. & cleary, w.f., 1972. A model in mice for the pathogenesis and
treatment of rabies. Journal of Infectious Diseases, 125, 520–527.
baer, g.m., brooks, r.c. & foggin, c.m., 1989. Oral vaccination of dogs fed
canine adenovirus in baits. American Journal of Veterinary Research, 50,
836–837.
46 arellano-sota, c., 1988. Vampire bat-transmitted rabies in cattle.
Reviews of Infectious Diseases, 10, 707–709.
69 baer, g.m., shaddock, j.h., quirion, r., dam, t.v. & lentz, t.l., 1990.
Rabies susceptibility and acetylcholine receptor. Lancet, 335, 664–665.
47
70 baer, g.m., shanthaveerappa, t.r. & bourne, g.h., 1965. Studies on the
pathogenesis of fixed rabies virus in rats. Bulletin of the World Health
Organization, 33, 783–794.
artois, m., charlton, k.m., tolson, n.d., casey, g.a., knowles, m.k., &
campbell, j.b., 1990. Vaccinia recombinant virus expressing the rabies
virus glycoprotein: Safety and efficacy trials in Canadian wildlife.
Canadian Journal of Veterinary Research, 54, 504–507.
48 aspden, k., dijk, a.a., bingham, j., cox, d., passmore, j.a. & williamson,
a.l., 2002. Immunogenicity of a recombinant lumpy skin disease virus
(Neethling vaccine strain) expressing the rabies virus glycoprotein in
cattle. Vaccine, 20, 2693–2701.
49 atanasiu, p., 1965. Transmission de la rage par la voie respiratoir aux
animaux de laboratoire. Comptes Rendus des Séances de l’Académie des
Sciences, 261, 277–279.
50 atanasiu, p., perrin, p. & delagneau, j.f., 1980. Use of an enzyme
immunoassay with protein A for rabies antigen and antibody
determination. Developments in Biological Standardization, 46, 207–
215.
71
baer, g.m., shanthaveerappa, t.r. & bourne, g.h., 1968. The
pathogenesis of street rabies virus in rats. Bulletin of the World Health
72
bahloul, c., jacob, y., tordo, n. & perrin, p., 1998. DNA-based
immunization for exploring the enlargement of immunological
cross-reactivity against the lyssaviruses. Vaccine, 16, 417–425.
73
bahmanyar, m., fayaz, a., nur-salehi, s., kopamdei, m. & koprowski, h.,
1976. Successful protection of humans exposed to rabies infection by
post-exposure treatment with the new human diploid cell rabies
vaccine and antirabies serum. Journal of the American Medical
Association, 236, 2751–2754.
74
bakkali, m.m., 1985. Epidémiologie et prophylaxie de la rage au Maroc.
In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in
the Tropics. Berlin: Springer-Verlag.
51
aubert, m., 1994. Control of rabies in foxes: What are the appropriate
measures? The Veterinary Record, 134, 55–59.
52
aubert, m., 1995. [Epidemiology and campaign against rabies in France
and in Europe]. Bulletin de l’Académie Nationale de Medecine, 179,
1033–1054.
75
ball, f.g., 1985. Front-wave velocity and fox habitat heterogeneity. In:
bacon, p.j., (ed.) Population Dynamics of Rabies in Wildlife. London:
Academic Press.
53
aubert, m.f.a., masson, e., artois, m. & barrat, j., 1994. Oral wildlife
rabies vaccination field trials in Europe, with recent emphasis on
France. In: rupprecht, c.e., dietzschold, b. & koprowski, h., (eds).
Current Topics in Microbiology and Immunology, 187: Lyssaviruses.
76
ball, f.g., 1985. Spatial models for the spread and control of rabies
incorporating group size. In: bacon, p.j., (ed.) Population Dynamics of
Rabies in Wildlife. London: Academic Press.
77
baltazard, m., bahmanjar, m., ghodssi, m., sabeti, a., gajdusek, c. &
rouzbehi, e., 1955. Essai pratique du sérum antirabique chez les mordus
par loups enragés. Bulletin of the World Health Organization, 13,
747–772.
54
ayalew, y., 1985. Analysis of 159 human rabies cases in Ethiopia. In:
kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in the
Tropics. Berlin: Springer-Verlag.
55
babes, v., 1912. Traité de la rage. Paris: Baillière et Fils.
56 bacon, p.j., 1985. A systems analysis of wildlife rabies epizootics. In:
bacon, p.j., (ed.). Population Dynamics of Rabies in Wildlife. London:
Academic Press.
57 bacon, p.j., 1985. Discrete time temporal models of rabies. In: bacon, p.j.,
(ed.). Population Dynamics of Rabies in Wildlife. London: Academic
Press.
58 badrane, h., bahloul, c., perrin, p. & tordo, n., 2001. Evidence of two
Lyssavirus phylogroups with distinct pathogenicity and
immunogenicity. Journal of Virology, 75, 3268–3276.
78 baltazard, m. & ghodssi, m., 1953. Prévention de la rage humaine.
Traitment des mordus par loups enragés en Iran. Revue d’Immunologie
et de Thérapie Antimicrobienne, 17, 366–371.
79
baltazard, m. & ghodssi, m., 1954. Prevention of human rabies.
Treatment of persons bitten by rabid wolves in Iran. Bulletin of the
World Health Organization, 10, 797–803.
80 banerjee, a.k. & elegbe, s.o., 1970. The incidence and diagnosis of rabies
in Nigeria. Bulletin of Epizootic Diseases of Africa, 18, 53–56.
81
barnard, b.j.h., 1979. Simptome van hondsdolheid by huis- en
plaasdiere in Suid-Afrika en Suidwes-Afrika. Journal of the South African
Veterinary Association, 50, 109–111.
59 badrane, h. & tordo, n., 2001. Host switching in Lyssavirus history from
the Chiroptera to the Carnivora orders. Journal of Virology, 75, 8096–
8104.
82 barnard, b.j.h., 1979. The role played by wildlife in the epizootiology of
rabies in South Africa and South West Africa. Onderstepoort Journal of
60 baer, g.m., 1975. Bovine paralytic rabies and rabies in the vampire bat.
In: baer, g.m., (ed.). The Natural History of Rabies, Vol. 2. New York:
Academic Press.
83 barnard, b.j.h., geyer, h.j. & de koker, w.c., 1977. Neurological
symptoms in a cat following vaccination with high egg passage vaccine
of chicken embryo origin. Onderstepoort Journal of Veterinary Research,
44, 195–196.
61
baer, g.m., 1975. Pathogenesis to the central nervous system. In: baer,
g.m., (ed.). The Natural History of Rabies, Vol. 2. New York: Academic
Press.
62 baer, g.m., 1975. Rabies in nonhematophagous bats. In: baer, g.m., (ed.).
The Natural History of Rabies, Vol. 2. New York: Academic Press.
63 baer, g.m., 1985. Rabies virus. In: fields, b.n., (ed.) Virology. New York:
Raven Press.
64 baer, g.m., 1988. Animal models in the pathogenesis and treatment of
rabies. Reviews of Infectious Diseases, 10, 739–750.
65 baer, g.m., 1988. Oral rabies vaccination: an overview. Reviews of
Infectious Diseases, 10, 644–648.
84 barnard, b.j.h. & hassel, r.h., 1981. Rabies in kudus (Tragelaphus
strepsiceros) in South West Africa/Namibia. Journal of the South African
Veterinary Association, 52, 309–314.
85 barnard, b.j.h., hassel, r.h., geyer, h.j., & de koker, w.c., 1982. Non-bite
transmission of rabies in kudu (Tragelaphus strepsiceros). Onderstepoort
Journal of Veterinary Research, 49, 191–192.
86 barnard, b.j.h. & voges, s.f., 1982. A simple technique for the rapid
diagnosis of rabies in formalin-preserved brain. Onderstepoort Journal
of Veterinary Research, 49, 193–194.
87 barrat, j. & halek, h., 1988. Simplified and adequate sampling and
1166
SECTION FOUR:
preservation techniques for rabies diagnosis in Mediterranean
countries. Document WHO/Rab. Res./88.27. Geneva: World Health
Organization.
88 barrat, j., 1996. Simplified technique for the collection, storage and
shipment of brain specimens for rabies diagnosis. In: meslin, f.x.,
kaplan, m.m. & koprowski, h., (eds). Laboratory Techniques in Rabies,
4th edn. Geneva: World Health Organization.
89 barth, r., bijok, u., gruschkau, h., jaeger, o. & weinmann, e., 1985.
Purified chick embryo cell (PCEC) rabies vaccine for human use —
laboratory data. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
90 barth, r., gruschkau, h., & jaeger, o., 1985. Chick-embryo-cell
inactivated rabies vaccine for veterinary use. Laboratory and field
experience. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
91
basson, p.a., 1992. P.O. Box 81, Grootfontein, Namibia 9000. Personal
communication.
92 bell, j.f. & moore, g.j., 1971. Susceptibility of carnivores to rabies virus
administered orally. American Journal of Epidemiology, 93, 176–182.
93 bell, j.f. & moore, g.j., 1979. Allergic encephalitis, rabies antibodies and
the blood–brain barrier. Journal of Laboratory and Clinical Medicine,
94, 5–11.
94 bellinger, d.a., chang, j., bunn, t.o., pick, j.r., murphy, m. & rahija, r.,
1983. Rabies induced in a cat by high-egg passage Flury strain vaccine.
Journal of the American Veterinary Medical Association, 183, 997–998.
95 beran, g.w., 1981. Rabies and infections by rabies-related viruses. In:
beran, g.w., (ed.). CRC Handbook Series in Zoonoses, Section B: Viral
Zoonoses, Vol. II. Boca Raton, Florida: CRC Press, Inc.
96 beran, g.w. & frith, m., 1988. Domestic animal rabies control: An
overview. Reviews of Infectious Diseases, 10, 672–677.
97
bernard, k.w., fishbein, d.b., miller, k.d., parker, r.a., waterman, s.,
sumner, j.w. and others, 1985. Pre-exposure rabies immunization with
human diploid cell vaccine: Decreased antibody responses in persons
immunized in developing countries. American Journal of Experimental
Medicine and Hygiene, 34, 633–647.
107 black, j.g. & lawson, k.f., 1973. Further studies of sylvatic rabies in the
fox (Vulpes vulpes). Vaccination by the oral route. Canadian Veterinary
Journal, 14, 206–211.
108 black, j.g. & lawson, k.f., 1980. The safety and efficacy of immunizing
foxes (Vulpes vulpes) using bait containing attenuated rabies virus
vaccine. Canadian Journal of Comparative Medicine,
109 blancou, j., 1985. La rage animale de Pasteur à nos jours. Évolution de
son épidémiologie et de sa prophylaxie. Bulletin de l’Académie
Vétérinaire de France, 58, 455–461.
110 blancou, j., 1988. Ecology and epidemiology of fox rabies. Reviews of
111 blancou, j., 1988. Epizootiology of rabies: Eurasia and Africa. In: campbell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
112 blancou, j. & andral, b., 1979. Cinétique des réactions à l’infection
expérimentale de la souris vaccinée ou non contre la rage: étude
étio-pathogénique. Annals of Microbiology, 130B, 485–492.
113 blancou, j. & andral, b., 1980. A model in mice for the study of the early
death phenomenon after vaccination and challenge with rabies virus.
Journal of General Virology, 50, 433–435.
114 blancou, j. & aubert, m.f., 1997. [Transmission of rabies virus:
importance of the species barrier]. Bulletin de l’Academie Nationale de
Medecine, 181, 301–311.
115 blancou, j., aubert, m.f.a. & artois, m., 1979. Rage expérimentale du
renard roux (Vulpes vulpes). I. Sensibilité selon la voie d’infection et la
dose infectante. Revista de Medicina Veterinaria, 130, 1001–1015.
116 blancou, j., pastoret, p.p., brochier, b., thomas, i. & agel, k., 1988.
Vaccinating wild animals against rabies. Revue Scientifique et
Technique, 7, 1005–1013.
117 blenden, d.c., bell, j.f., tsao, a.t. & umoh, j.u., 1983. Immunofluorescent examination of the skin of rabies-infected animals as a
means of early detection of rabies virus antigen. Journal of Clinical
Microbiology, 18, 631–636.
98 bingham, j. & foggin, c.m., 1993. Jackal rabies in Zimbabwe.
Onderstepoort Journal of Veterinary Research, 60, 365–366.
118 blenden, d.c., creech, w. & torres-anjel, m.j., 1986. Use of
immunofluorescence examination to detect rabies virus antigen in skin
of humans with clinical encephalitis. Journal of Infectious Diseases, 154,
698–701.
99 bingham, j., foggin, c.m., wandeler, a.i. & hill, f.w., 1999. The
epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis
familiaris). Onderstepoort Journal of Veterinary Research, 66, 1–10.
119 botvinkin, a.d. & nikiforova, t.a., 1986. Dlitel ‘noe sokhranenie virusa
beshenstva v mestakh vvedeniia v eksperimente na zimospiashchikh
gryzunakh. Voprosy Virusologii, 4, 504–506.
100 bingham, j., foggin, c.m., wandeler, a.i. & hill, f.w., 1999. The
epidemiology of rabies in Zimbabwe. 2. Rabies in jackals (Canis adustus
and Canis mesomelas). Onderstepoort Journal of Veterinary Research, 66,
11–23.
120 botvinkin, a.d., nikiforova, t.a. & sidorov, g.n., 1985. Experimental
rabies in hibernator rodents. Acta Virologica, 29, 44–50.
101 bingham, j., kappeler, a., hill, f.w., king, a.a., perry, b.d. & foggin,
c.m., 1995. Efficacy of SAD (Berne) rabies vaccine given by the oral route
in two species of jackal (Canis mesomelas and Canis adustus). Journal of
Wildlife Diseases, 31, 416–419.
122 boulger, l.r. & porterfield, j.s., 1958. Isolation of a virus from Nigerian
fruit bats. Transactions of the Royal Society of Tropical Medicine and
Hygiene, 52, 421–424.
102 bingham, j. & mlambo, p., 1995. Ante-mortem diagnosis of human rabies
by the skin biopsy technique: Three case reports from Zimbabwe.
Central African Journal of Medicine, 41, 258–260.
103 bingham, j., schumacher, c.l., aubert, m.f., hill, f.w. & aubert, a., 1997.
Innocuity studies of SAG-2 oral rabies vaccine in various Zimbabwean
wild non-target species. Vaccine, 15, 937–943.
104 bingham, j., schumacher, c.l., hill, f.w. & aubert, a., 1999. Efficacy of
SAG-2 oral rabies vaccine in two species of jackal (Canis adustus and
Canis mesomelas). Vaccine, 17, 551–558.
105 bishop, g. & swanepoel, r., 1990. Regional Veterinary Laboratory,
Allerton, Pietermaritzburg 3200 and National Institute for
Communicable Diseases, Sandringham, 2131 South Africa.
Unpublished observations.
106 black, e.m., mcelhinney, l.m., lowings, j.p., smith, j., johnstone, p. &
heaton, p.r., 2000. Molecular methods to distinguish between classical
rabies and the rabies-related European bat lyssaviruses. Journal of
Virological Methods, 87, 123–131.
121 bouffard, g., 1912. Sur l’existence de la rage canine dans le
Haut-Senégal et le Niger. Annales de l’Institut Pasteur, 26, 727–731.
123 bourhy, h., kissi, b., & tordo, n., 1993. Molecular diversity of the
Lyssavirus genus. Virology, January, 1–12.
124 bourhy, h., rollin, p.e., vincent, j. & sureau, p., 1989. Comparative field
evaluation of the fluorescent-antibody test, virus isolation from tissue
culture, and enzyme immunodiagnosis for rapid laboratory diagnosis of
rabies. Journal of Clinical Microbiology, 27, 519–523.
125 bögel, k., 2002. Control of dog rabies. In: jackson, a.c. & wunner, w.h.,
(eds). Rabies. Amsterdam: Academic Press.
126 bögel, k. & motschwiller, e., 1986 . Incidence of rabies and
post-exposure treatment in developing countries. Bulletin of the World
Health Organization, 64, 883–887.
127 briggs, d.j., dreesen, d.w. & wunner, w.h., 2002. Vaccines. In: jackson,
a.c. & wunner, w.h., (eds). Rabies. Amsterdam: Academic Press.
128 brochier, b., boulanger, d., costy, f., & pastoret, p.p., 1994. Towards
rabies elimination in Belgium by fox vaccination using a vaccinia-rabies
glycoprotein recombinant virus. Vaccine, 12, 1368–1371.
129 brochier, b., kieny, m.p., costy, f., coppens, p., bauduin, b., lecocq, j.p.
Rabies
and others, 1991. Large-scale eradication of rabies using recombinant
vaccinia-rabies vaccine. Nature, 354, 520–522.
130 brochier, b., thomas, i., bauduin, b., leveau, t., pastoret, p.p.,
languet, b. and others, 1990. Use of a vaccinia-rabies recombinant
virus for the oral vaccination of foxes against rabies. Vaccine, 8, 101–104.
131 brooks, r., 1990. Survey of dog population in Zimbabwe and its level of
rabies vaccination coverage. The Veterinary Record, 127, 592–596.
132 brown, c.i. & szakacs, j.g., 1997. Rabies in New Hampshire and Vermont:
an update. Annals of Clinical and Laboratory Science, 27, 216–223.
133 brown, f. & crick, j., 1979. Natural history of the rhabdoviruses of
vertebrates and invertebrates. In: bishop, d.h.l., (ed.). Rhabdoviruses.
Boca Raton, Florida: CRC Press, Inc.
134 brückner, g.k. & hurter, l.r.b.j.n., 1978. Field observations on the
occurrence of rabies in cattle in the magisterial districts of
Soutpansberg and Messina. Journal of the South African Veterinary
Association, 49, 33–36.
1167
152 celis, e., ou, d., dietzschold, b., otvos, l., jr. & koprowski, h., 1989.
Rabies virus-specific T cell hybridomas: Identification of class II
MHC-restricted T-cell epitopes using synthetic peptides. Hybridoma, 8,
263–275.
153 chadli, a. & benlasfar, z., 1985. Epidémiologie de la rage en Tunisie.
Analyse des résultats des 30 dernières années. In: kuwert, e., mérieux, c.,
koprowski, h. & bögel, k., (eds). Rabies in the Tropics. Berlin:
Springer-Verlag.
154 chalmers, a.w. & scott, g.r., 1969. Ecology of rabies. Tropical Animal
Health and Production, 1, 33–55.
155 chaparro, f. & esterhuysen, j.j., 1993. The role of the yellow mongoose
(Cynictis penicillata) in the epidemiology of rabies in South Africa —
preliminary results. Onderstepoort Journal of Veterinary Research, 60,
373–377.
156 charlton, k.m., 1988. The pathogenesis of rabies. In: campbell, j.b. &
charlton, k.m., (eds). Rabies. Boston: Kluwer Academic Publishers.
135 bryceson, a.d.m., greenwood, b.m., warrel, d.a., davidson, n.m., pope,
h.m., lawrie, j.h. and others, 1975. Demonstration during life of rabies
antigen in humans. Journal of Infectious Diseases, 131, 71–74.
157 charlton, k.m., 1994. The pathogenesis of rabies and other lyssaviral
infections: recent studies. In: rupprecht, c.e., dietzschold, b. &
koprowski, h., (eds). Current Topics in Microbiology and Immunology,
187: Lyssaviruses. Berlin: Springer-Verlag.
136 buckley, s.m., 1975. Arbovirus infection of vertebrate and insect cell
cultures, with special emphasis on Mokola, Obodhiang and kotonkan
viruses of the rabies serogroup. Annals of the New York Academy of
Sciences, 266, 241–250.
158 charlton, k.m., artois, m., prevec, l., campbell, j.b., casey, g.a.,
wandeler, a.i. and others, 1992. Oral rabies vaccination of skunks and
foxes with a recombinant human adenovirus vaccine. Archives of
Virology, 123, 169–179.
137 bunn, t.o., 1985. Rabies vaccine for use in dogs. In: kuwert, e., mérieux,
c., koprowski, h. & bögel, k., (eds). Rabies in the Tropics. Berlin:
Springer-Verlag.
159 charlton, k.m. & casey, g.a., 1979. Experimental oral and nasal
transmission of rabies virus in mice. Canadian Journal of Comparative
Medicine, 43, 10–15.
138 bunn, t.o., 1988. Vaccines and vaccination of domestic animals. In: campbell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
160 charlton, k.m. & casey, g.a., 1979. Experimental rabies in skunks.
Immunofluorescence, light and electron microscopic studies.
Laboratory Investigation, 41, 36–44.
139 burgoyne, g.h., kajiya, k.d., brown, d.w. & mitchell, j.r., 1985. Rhesus
diploid rabies vaccine (adsorbed): A new rabies vaccine using FRhL-2
cells. Journal of Infectious Diseases, 152, 204–210.
161 charlton, k.m. & casey, g.a., 1979. Experimental rabies in skunks: Oral,
nasal, tracheal and intestinal exposure. Canadian Journal of
Comparative Medicine, 43, 168–172.
140 burrage, t.g., tignor, g.h. & smith, a.l., 1985. Rabies virus binding at
neuromuscular junctions. Virus Research, 2, 273–289.
162 charlton, k.m. & casey, g.a., 1981. Experimental rabies in skunks:
Persistence of virus in denervated muscle at the inoculation site.
Canadian Journal of Comparative Medicine, 45, 357–362.
141 burrows, r., 1992. Rabies in wild dogs. Nature, 359, 277.
142 burrows, r., 1994. Rabies in African wild dogs of Tanzania. Journal of
143 buxton, a. & fraser, g., 1977. Rhabdoviruses. In: buxton, a. & fraser, g.,
(eds). Animal Microbiology, Vol. 2. Oxford: Blackwell Scientific
Publications.
144 cabasso, v.j., 1962. Achievements of rabies vaccines (Flury) in animals
and problems associated with their use. Cyanamid Internal Veterinary
Bulletin, 1, 21–28.
145 cabasso, v.j., 1975. Passive immunization. In: baer, g.m., (ed.). The
Natural History of Rabies, Vol. 2. New York: Academic Press.
146 calisher, c.h., karabatsos, n., zeller, h., digoutte, j.p., tesh, r.b.,
shope, r.e. and others, 1989. Antigenic relationships among
rhabdoviruses from vertebrates and hematophagous arthropods.
Intervirology, 30, 241–257.
147 campbell, j.b. & barton, l.d., 1988. Serodiagnosis of rabies: Antibody
tests. In: campbell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer
Academic Publishers.
148 carey, a.b., 1985. Multispecies rabies in the eastern United States. In:
Academic Press.
149 carini, a., 1911. Sur un grande épizootie de rage. Annales de l’Institut
Pasteur, 25, 843–846.
150 celis, e., miller, r.w., wiktor, t.j., dietzschold, b. & koprowski, h.,
1986. Isolation and characterization of human T cell lines and clones
reactive to rabies virus: antigen specificity and production of interferon.
Journal of Immunology, 136, 551–564.
151 celis, e., ou, d., dietzschold, b. & koprowski, h., 1988. Recognition of
rabies and rabies-related viruses by T cells derived from human vaccine
recipients. Journal of Virology, 62, 3128–3134.
163 charlton, k.m., casey, g.a., boucher, d.w. & wiktor, t.j., 1982. Antigenic
variants of rabies virus. Comparative Immunology, Microbiology and
164 charlton, k.m., casey, g.a. & campbell, j.b., 1987. Experimental rabies in
skunks: Immune response and salivary gland infection. Comparative
Immunology, Microbiology and Infectious Diseases, 10, 227–235.
165 charlton, k.m., webster, w.a., casey, g.a. & rupprecht, c.e., 1988. Skunk
rabies. Reviews of Infectious Diseases, 10 Suppl 4:S626–8, S626–S628.
166 cherkasskiy, b.l., 1988. Roles of the wolf and the raccoon dog in the
ecology and epidemiology of rabies in the USSR. Reviews of Infectious
Diseases, 10 Suppl 4:S634–6, S634–S636.
167 childs, j.e., 2002. Epidemiology. In: jackson, a.c. & wunner, w.h., (eds).
Rabies. Amsterdam: Academic Press.
168 chow, t.l., chow, f.h. & hanson, r.p., 1954. Morphology of vesicular
stomatitis virus. Journal of Bacteriology, 68, 724–726.
169 chutivongse, s., wilde, h., fishbein, d.b., baer, g.m. & hemachudha, t.,
1991. One-year study of the 2-1-1 intramuscular postexposure rabies
vaccine regimen in 100 severely exposed Thai patients using rabies
immune globulin and Vero cell rabies vaccine. Vaccine, 9, 573–576.
170 cifuentes, e.e., 1988. Program for the elimination of urban rabies in
Latin America. Reviews of Infectious Diseases, 10, 689–692.
171 clark, h.f., 1980. Rabies serogroup viruses in neuroblastoma cells:
propagation, ‘autointerference,’ and apparently random back-mutation
of attenuated viruses to the virulent state. Infection and Immunity, 27,
1012–1022.
172 cliquet, f., aubert, m. & sagne, l., 1998. Development of a fluorescent
antibody virus neutralisation test (FAVN test) for the quantitation of
rabies-neutralising antibody. Journal of Immunological Methods, 212,
79–87.
1168
SECTION FOUR:
173 cluver, e., 1927. Rabies in South Africa. Journal of the Medical
Association of South Africa, 1, 247–253.
174 connolly, g.e. & longhurst, w.m., 1975. The effects of control of coyote
populations. A simulation model. Division of Agriculture Science
Bulletin 1872, University of California, Davis.
175 constantine, d.g., 1962. Rabies transmission by the nonbite route.
Public Health Report, 77, 287–289.
176 constantine, d.g., 1967. Rabies transmission by air in bat caves. US
Department of Health, Education and Welfare, Public Health Service
Publication No. 1617. Washington: US Government Printing Office.
177 constantine, d.g., 1979. An updated list of rabies-infected bats in North
America. Journal of Wildlife Diseases, 15, 347–349.
178 constantine, d.g., solomon, g.c. & woodall, d.f., 1968. Transmission
experiments with bat rabies isolates: Responses of certain carnivores
and rodents to rabies viruses from four species of bats. American
179 correa-giron, e.p., allen, r. & sulkin, s.e., 1970. The infectivity and
pathogenesis of rabies virus administered orally. American Journal of
Epidemiology, 91, 203–215.
180 coslett, g.d., holloway, b.p. & obijeski, j.f., 1980. The structural
proteins of rabies virus and evidence for their synthesis from separate
monocistronic RNA species. Journal of General Virology, 49, 161–180.
181 coulon, p., derbin, c., kucera, p., lafay, f., prehaud, c. & flamand, a.,
1989. Invasion of the peripheral nervous systems of adult mice by the
CVS strain of rabies virus and its avirulent derivative AvO1. Journal of
Virology, 63, 3550–3554.
182 coulon, p., lafay, f., leblois, h., tuffereau, c., artois, m., blancou, j.
and others, 1992. The SAG: a new attenuated oral rabies vaccine. In:
bögel, k., meslin, f.x. & kaplan, m., (eds). Wildlife Rabies Control. Kent:
Wells Medical.
183 coulon, p., lafay, f., tuffereau, c. & flamand, a., 1994. The molecular
basis for altered pathogenicity of lyssavirus variants. In: rupprecht, c.e.,
dietzschold, b. & koprowski, h., (eds). Current Topics in Microbiology
and Immunology, 187: Lyssaviruses. Berlin: Springer-Verlag.
184 coulon, p., rollin, p., aubert, m. & flamand, a., 1982. Molecular basis of
rabies virus virulence. I. Selection of avirulent mutants of the CVS strain
with anti-G monoclonal antibodies. Journal of General Virology, 61,
97–100.
185 coulon, p., rollin, p.e. & flamand, a., 1983. Molecular basis of rabies
virus virulence. II. Identification of a site on the CVS glycoprotein
associated with virulence. Journal of General Virology, 64, 693–696.
186 courtin, f., carpenter, t.e., paskin, r.d. & chomel, b.b., 2000. Temporal
patterns of domestic and wildlife rabies in central Namibia
stock-ranching area, 1986–1996. Preventive Veterinary Medicine, 43,
13–28.
187 cox, j.h., dietzschold, b. & schneider, l.g., 1977. Rabies virus
glycoprotein. II. Biological and serological characterization. Infection
and Immunity, 16, 754–759.
188 crandell, r.a., 1975. Arctic fox rabies. In: baer, g.m., (ed.). The Natural
History of Rabies, Vol. 2. New York: Academic Press.
189 creekmore, t.e., linhart, s.b., corn, j.l., whitney, m.d., snyder, b.d. &
nettles, v.f., 1994. Field evaluation of baits and baiting strategies for
delivering oral vaccine to mongooses in Antigua, West Indies. Journal of
190 creel, s., creel, n.m., munson, l., sanderlin, d. & appel, m.j., 1997.
Serosurvey for selected viral diseases and demography of African wild
dogs in Tanzania. Journal of Wildlife Diseases, 33, 823–832.
191 crick, j. & brown, f., 1969. Viral subunits for rabies vaccination. Nature,
221, 92–94.
192 crick, j. & brown, f., 1970. Efficacy of rabies vaccine prepared from virus
grown in duck embryo. Lancet, 1, 1106–1107.
vaccine. Developments in Biological Standardization, 40:179–182.
195 crick, j. & king, a., 1988. Culture of rabies virus in vitro. In: campbell, j.b.
& charlton, k.m., (eds). Rabies. Boston: Kluwer Academic Publishers.
196 crick, j., tignor, g.h., & moreno, k., 1982. A new isolate of lagos bat virus
from the Republic of South Africa. Transactions of the Royal Society of
Tropical Medicine and Hygiene, 76, 211–213.
197 cumming, d.h.m., 1982. A case history of the spread of rabies in an
African country. South African Journal of Science, 78, 443–447.
198 darbyshire, j.h., 1953. Some observations on rabies in sheep. The
Veterinary Record, 65, 261–262.
199 david, d., yakobson, b., rotenberg, d., dveres, n., davidson, i. & stram,
y., 2002. Rabies virus detection by RT-PCR in decomposed naturally
infected brains. Veterinary Microbiology, 87, 111–118.
200 davies, m.c., englert, m.e., sharpless, g.r. & cabasso, v.j., 1963. The
electron microscopy of rabies virus in cultures of chicken embryo
tissue. Virology, 21, 642–651.
201 davis, c., neill, s. & raj, p., 1997. Microwave fixation of rabies specimens
for fluorescent antibody testing. Journal of Virological Methods, 68,
177–182.
202 de balogh, k.k., wandeler, a.i. & meslin, f.x., 1993. A dog ecology study
in an urban and a semi-rural area of Zambia. Onderstepoort Journal of
203 de kock, g., 1949. In the service of the livestock farming industry:
Divisional Report for Veterinary Services. Annual Report of the
Secretary for Agriculture. Farming in South Africa, 25, 521–523.
204 de villiers, m.s., meltzer, d.g., van heerden, j., mills, m.g.,
richardson, p.r. & van jaarsveld, a.s., 1995. Handling-induced stress
and mortalities in African wild dogs (Lycaon pictus). Proceedings of the
Royal Society of London. B: Biological Sciences, 262, 215–220.
205 dean, d.j., evans, w.m. & mcclure, r.c., 1963. Pathogenesis of rabies.
Bulletin of the World Health Organization, 29, 803–811.
206 debbie, j.g., 1988. Rabies: An old enemy that can be defeated. World
Health Forum, 9, 536–541.
207 delpietro, h.a., larghi, o.p. & russo, r.g., 2001. Virus isolation from
saliva and salivary glands of cattle naturally infected with paralytic
rabies. Preventive Veterinary Medicine, 48, 223–228.
208 depner, k., 1992. National report on rabies in Namibia. Proceedings of a
Joint CVRI, WHO, FAO and OIE Seminar on Rabies in Southern Africa,
Lusaka, Zambia, 2–5 June, 1992. Geneva: World Health Organization.
209 desmettre, p., languet, b., chappuis, g., brochier, b., thomas, i.,
lecocq, j.p. and others, 1990. Use of vaccinia rabies recombinant for
oral vaccination of wildlife. Veterinary Microbiology, 23, 227–236.
210 dias, m.p.r.t., 1992. National report on rabies in Mozambique.
Proceedings of a Joint CVRI, WHO, FAO and OIE Seminar on Rabies in
Southern Africa, Lusaka, Zambia, 2–5 June, 1992. Geneva: World Health
Organization.
211 dias, p.t., novoa, a.m. & cliff, j.l., 1985. Rabies in Mozambique. In:
212 dierks, r.e., 1975. Electron microscopy of extraneural rabies infection.
In: baer, g.m.. (ed.). The Natural History of Rabies, Vol. 1. New York:
Academic Press.
213 dierks, r.e., murphy, f.a. & harrison, a.k., 1969. Extraneural rabies virus
infection. Virus development in fox salivary gland. American Journal of
Pathology, 54, 251–273.
214 dietzschold, b., cox, j.h., schneider, l.g., wiktor, t.j. & koprowski, h.,
1978. Isolation and purification of a polymeric form of the glycoprotein
of rabies virus. Journal of General Virology, 40, 131–139.
193 crick, j. & brown, f., 1974. An RNA-containing interfering component of
rabies virus. In: mahy, b.w.j. & barry, r.d., (eds). Negative Strand
Viruses. London: Academic Press.
215 dietzschold, b., rupprecht, c.e., tollis, m., lafon, m., mattei, j.,
wiktor, t.j. and others, 1988. Antigenic diversity of the glycoprotein
and nucleocapsid proteins of rabies and rabies-related viruses:
implications for epidemiology and control of rabies. Reviews of
Infectious Diseases, 10 Suppl 4:S785–S798.
194 crick, j. & brown, f., 1978. Questions concerning the potency of rabies
216 dietzschold, b., tollis, m., rupprecht, c. e., celis, e. & oprowski, h.,
Rabies
1987. Antigenic variation in rabies and rabies-related viruses:
Cross-protection independent of glycoprotein-mediated
virus-neutralizing antibody. Journal of Infectious Diseases, 156, 815–822.
217 dietzschold, b., wang, h.h., rupprecht, c.e., celis, e., tollis, m., ertl,
h. and others, 1987. Induction of protective immunity against rabies by
immunization with rabies virus ribonucleoprotein. Proceedings of the
National Academy of Sciences of the United States of America, 84,
9165–9169.
218 dietzschold, b., wiktor, t.j., trojanowski, j.q., macfarlan, r.i.,
wunner, w.h., torres-anjel, m.j. and others, 1985. Differences in
cell-to-cell spread of pathogenic and apathogenic rabies virus in vivo
and in vitro. Journal of Virology, 56, 12–18.
219 dietzschold, b., wunner, w.h., macfarlan, r.i., wiktor, t.j., kiel, m.,
houghtenn, r. and others, 1985. The antigenic structure of the rabies
virus glycoprotein. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
220 dietzschold, b., wunner, w.h., wiktor, t.j., lopes, a.d., lafon, m.,
smith, c.l. and others, 1983. Characterization of an antigenic
determinant of the glycoprotein that correlates with pathogenicity of
rabies virus. Proceedings of the National Academy of Sciences of the
United States of America, 80, 70–74.
221 du toit, p.j., 1929. Proceedings of the Pan African Agricultural and
Veterinary Congress. Proceedings of the Pan African Agricultural and
Veterinary Congress, Pretoria, August 1992, 272–284.
222 du toit, p.j., 1936. Wild carnivora as carriers of rabies. Quarterly Bulletin
of the Health Organization of the League of Nations, 5, 162–165.
223 duarte, v.m.s., rosliacov, a.a., nsalambi, d. & gomes, a.f., 1985.
Epidémiologie et diagnostic de la rage en Angola. In: kuwert, e.,
224 east, m.l. & hofer, h., 1996. Wild dogs in the Serengeti. Science, 271,
275–276.
225 eddington, a., 1895. Report of the Director of the Colonial Bacteriology
Institute, Cape, for the year 1894. Department of Agriculture, Cape of
Good Hope.
226 edmonds, c.r., 1922. Diseases of Animals in South Africa. London:
Ballière, Tindall & Cox.
1169
vaccine baits. Journal of Wildlife Diseases, 34, 13–22.
237 farry, s.c., henke, s.e., beasom, s.l. & fearneyhough, m.g., 1998. Efficacy
of bait distributional strategies to deliver canine rabies vaccines to
coyotes in southern Texas. Journal of Wildlife Diseases, 34, 23–32.
238 favoretto, s.r., carrieri, m.l., tino, m.s., zanetti, c.r. & pereira, o.a.,
1993. Simplified fluorescent inhibition microtest for the titration of
rabies neutralizing antibodies. Revista do Instituto de Medicina Tropical
de Sao Paulo, 35, 171–175.
239 fearneyhough, m.g., wilson, p.j., clark, k.a., smith, d.r., johnston,
d.h., hicks, b.n. and others, 1998. Results of an oral rabies vaccination
program for coyotes. Journal of the American Veterinary Medical
240 fekadu, m., 1972. Atypical rabies in dogs in Ethiopia. Ethiopian Medical
Journal, 10, 79–86.
241 fekadu, m., 1988. Pathogenesis of rabies virus infection in dogs. Reviews
of Infectious Diseases, 10 Suppl 4, S678–683.
242 fekadu, m., endeshaw, t., alemu, w., bogale, y., teshager, t. & olson,
j.g., 1996. Possible human-to-human transmission of rabies in Ethiopia.
Ethiopian Medical Journal, 34, 123–127.
243 fekadu, m., nesby, s.l., shaddock, j.h., schumacher, c.l., linhart, s.b. &
sanderlin, d.w., 1996. Immunogenicity, efficacy and safety of an oral
rabies vaccine (SAG-2) in dogs. Vaccine, 14, 465–468.
244 fekadu, m., shaddock, j.h., & baer, g.m., 1982. Excretion of rabies virus
in the saliva of dogs. Journal of Infectious Diseases, 145, 715–719.
245 fekadu, m., shaddock, j.h., chandler, f.w. & baer, g.m., 1983. Rabies
virus in the tonsils of a carrier dog. Archives of Virology, 78, 37–47.
246 fekadu, m., shaddock, j.h., sanderlin, d.w. & smith, j.s., 1988. Efficacy
of rabies vaccines against Duvenhage virus isolated from European
house bats (Eptesicus serotinus), classic rabies and rabies-related
viruses. Vaccine, 6, 533–539.
247 fekadu, m., shaddock, j.h., sumner, j.w., sanderlin, d.w., knight, j.c.,
esposito, j.j. and others, 1991. Oral vaccination of skunks with raccoon
poxvirus recombinants expressing the rabies glycoprotein or the
nucleoprotein. Journal of Wildlife Diseases, 27, 681–684.
227 eichwald, c. & pitzschke, h., 1967. Die Tolwut bei Mensch und Tier.
Jena: Gustav Fischer.
248 fekadu, m., sumner, j.w., shaddock, j.h., sanderlin, d.w. & baer, g.m.,
1992. Sickness and recovery of dogs challenged with a street rabies virus
after vaccination with a vaccinia virus recombinant expressing rabies
virus N protein. Journal of Virology, 66, 2601–2604.
228 elegbe, s.o. & banerjee, a.k., 1970. A case report of rabies in the bovine
in the north-western state of Nigeria. Bulletin of Epizootic Diseases of
Africa, 18, 57–62.
249 fenje, p., 1960. A rabies vaccine from hamster kidney tissue cultures:
preparation and evaluation in animals. Canadian Journal of
Microbiology, 6, 605–609.
229 emerson, s.u., 1985. Rhabdoviruses. In: fields, b.n., (ed.). Virology. New
York: Raven Press.
250 fenner, f., perreir, h.g., porterfield, j.s., joklik, w.k. & downie, a.w.,
1974. Family and generic names for viruses approved by the
International Committee on Taxonomy of Viruses. Intervirology, 3,
193–198.
230 ertl, h.c., dietzschold, b., gore, m., otvos, l., jr., larson, j.k., wunner,
w.h. and others, 1989. Induction of rabies virus-specific T-helper cells
by synthetic peptides that carry dominant T-helper cell epitopes of the
viral ribonucleoprotein. Journal of Virology, 63, 2885–2892.
231 esposito, j.j., knight, j.c., shaddock, j.h., novembre, f.j. & baer, g.m.,
1988. Successful oral rabies vaccination of raccoons with raccoon
poxvirus recombinants expressing rabies virus glycoprotein. Virology,
165, 313–316.
232 everard, c.o.r. & everard, j.d., 1985. Mongoose rabies in Grenada. In:
Academic Press.
233 everard, j.d. & everard, c.o.r., 1988. Mongoose rabies. Reviews of
Infectious Diseases , 10, 610–614.
234 familusi, j.b. & moore, d.l., 1972. Isolation of a rabies related virus from
the cerebrospinal fluid of a child with ‘aseptic meningitis’. African
Journal of Medical Sciences, 3, 93–96.
235 familusi, j.b., osunkoya, b.o., moore, d.l., kemp, g.e., & fabiyi, a., 1972. A
fatal human infection with Mokola virus. American Journal of
Experimental Medicine and Hygiene, 21, 959–963.
236 farry, s.c., henke, s.e., anderson, a.m. & fearneyhough, m.g., 1998.
Responses of captive and free-ranging coyotes to simulated oral rabies
251 fermi, c., 1908. Über die immunisierung gegen wutkrankheit. Zeitskrift
für Hygiene und Infektionskrankheiten, 58, 233–276.
252 fernandes, m.v. & arambulo, p.v.i., 1985. Rabies as an international
problem. In: koprowski, h. & plotkin, s.a., (eds). World’s Debt to
Pasteur. New York: Alan R. Liss, Inc.
253 field, h., mccall, b. & barrett, j., 1999. Australian bat lyssavirus
infection in a captive juvenile black flying fox. Emerging Infectious
Diseases, 5, 438–440.
254 finley, d., 1998. Mad dogs: new rabies plague. College Station, Texas:
Texas A & M University Press.
255 fischman, h.r., 1985. Rabies in wildlife and tropical canines — a
population problem. In: kuwert, e., mérieux, c., koprowski, h. & bögel,
k., (eds). Rabies in the Tropics. Berlin: Springer-Verlag.
256 fischman, h.r. & schaeffer, m., 1971. Pathogeneis of experimental rabies
as revealed by immunofluorescence. Annals of the New York Academy of
Sciences, 177, 78–97, 78–97.
257 fischman, h.r. & strandberg, j.d., 1973. Inapparent rabies virus
infection of the central nervous system. Journal of the American
Veterinary Medical Association, 163, 1050–1055.
1170
SECTION FOUR:
258 fischman, h.r. & ward, f.e., iii, 1968. Oral transmission of rabies virus in
experimental animals. American Journal of Epidemiology, 88, 132–138.
280 goldschmidt, m.h., 1972. The use of suckling mice for the diagnosis of
rabies. Rhodesian Veterinary Journal, 3, 4–5.
259 fitzsimmons, f.w., 1919. Natural History of South Africa, Vol. 2. London:
Longmans, Green & Co.
281 goldwasser, r.a. & kissling, r.e., 1958. Fluorescent antibody staining of
street and fixed rabies virus antigens. Proceedings of the Society for
Experimental Biology and Medicine, 98, 219–223.
260 foggin, c.m., 1982. Atypical rabies virus in cats and a dog in Zimbabwe.
The Veterinary Record, 110, 338.
261 foggin, c.m., 1983. Mokola virus infection in cats and a dog in
Zimbabwe. The Veterinary Record, 113, 115.
262 foggin, c.m., 1985. Mokola virus infection in domestic cats in
Zimbabwe. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
263 foggin, c.m., 1985. The epidemiological significance of jackal rabies in
Zimbabwe. In: kuwert, e., mérieux, c., koprowski, h. & bömgel, k.,
264 foggin, c.m., 1988. Rabies and rabies-related viruses in Zimbabwe:
Historical, virological and ecological aspects. D.Phil. Thesis: University
of Zimbabwe.
282 goldwasser, r.a., kissling, r.e., carski, t.r. & hosty, t.s., 1959.
Fluroescent antibody staining of rabies virus antigens in the salivary
glands of rabid animals. Bulletin of the World Health Organization, 20,
579–588.
283 gosztonyi, g., 1994. Reproduction of lyssaviruses: ultrastructural
composition of lyssavirus and functional aspects of pathogenesis. In:
rupprecht, c.e., dietzschold, b. & koprowski, h., (eds). Current Topics
in Microbiology and Immunology, 187: Lyssaviruses. Berlin:
Springer-Verlag.
284 gould, a.r., hyatt, a.d., lunt, r., kattenbelt, j.a., hengstberger, s. &
blacksell, s.d., 1998. Characterisation of a novel lyssavirus isolated
from Pteropid bats in Australia. Virus Research, 54, 165–187.
265 foggin, c.m. & swanepoel, r., 1979. Rabies in Rhodesia: The current
situation. Central African Journal of Medicine, 25, 98–103.
285 gourmelon, p., briet, d., court, l. & tsiang, h., 1986.
Electrophysiological and sleep alterations in experimental mouse
rabies. Brain Research, 398, 128–140.
266 foggin, c.m. & swanepoel, r., 1985. Rabies in Africa with emphasis on
rabies-related viruses. In: koprowski, h. & plotkin, s.a., (eds). World’s
Debt to Pasteur. New York: Alan R. Liss, Inc.
286 grattan-smith, p.j., o’regan, w.j., ellis, p.s., o’flaherty, s.j., mcintyre,
p.b. & barnes, c.j., 1992. Rabies. A second Australian case, with a long
incubation period. Medical Journal of Australia, 156, 651–654.
267 follmann, e.h., ritter, d.g. & baer, g.m., 1992. Oral rabies vaccination of
arctic foxes (Alopex lagopus) with an attenuated vaccine. Vaccine, 10,
305–308.
287 grauballe, p.c., baagoe, h.j., fekadu, m., westergaard, j.m. &
zoffmann, h., 1987. Bat rabies in Denmark. Lancet, 1, 379–380.
268 follmann, e.h., ritter, d.g. & baer, g.m., 1996. Evaluation of the safety
of two attenuated oral rabies vaccines, SAG1 and SAG2, in six Arctic
mammals. Vaccine, 14, 270–273.
269 fox, j.p., conwell, d.p. & gerhardt, p., 1957. Antirabies vaccination of
man with HEP Flury virus. Veterinary Medicine, 52, 81–85.
270 fraser, g.c., hooper, p.t., lunt, r.a., gould, a.r., gleeson, l.j., hyatt,
a.d. and others, 1996. Encephalitis caused by a Lyssavirus in fruit bats
in Australia. Emerging Infectious Diseases, 2, 327–331.
271 fries, l.f., tartaglia, j., taylor, j., kauffman, e.k., meignier, b.,
paoletti, e. and others, 1996. Human safety and immunogenicity of a
canarypox-rabies glycoprotein recombinant vaccine: An alternative
poxvirus vector system. Vaccine, 14, 428–434.
272 fu, z.f., rupprecht, c.e., dietzschold, b., saikumar, p., niu, h.s., babka,
i. and others, 1993. Oral vaccination of racoons (Procyon lotor) with
baculovirus-expressed rabies virus glycoprotein. Vaccine, 11, 925–928.
273 fu, z.f., wunner, w.h. & dietzschold, b., 1994. Immunoprotection by
rabies virus nucleoprotein. In: rupprecht, c.e., dietzschold, b. & koprowski, h., (eds). Current Topics in Microbiology and Immunology,
274 fuenzalida, e. & palacios, r., 1955. Rabies vaccine prepared from brains
of infected suckling mice. Boletin del Instituto Bacteriologico de Chile, 8,
3–10.
275 fujii, h., takita-sonoda, y., mifune, k., hirai, k., nishizono, a. &
mannen, k., 1994. Protective efficacy in mice of post-exposure
vaccination with vaccinia virus recombinant expressing either rabies
virus glycoprotein or nucleoprotein. Journal of General Virology, 75,
1339–1344.
276 galtier, v., 1879. Études sur la rage. Recueil de Médecine Vétérinaire, 6,
857–867.
277 gascoyne, s.c., laurenson, m.k., lelo, s. & borner, m., 1993. Rabies in
African wild dogs (Lycaon pictus) in the Serengeti region, Tanzania.
Journal of Wildlife Diseases , 29, 396–402.
278 glück, r., keller, h., mischler, r., wegmann, a. & germanier, r., 1985.
New aspects concerning the immunogenicity of rabies vaccine
produced in animal brains (duck embryo). In: kuwert, e., mérieux, c.,
Springer-Verlag.
279 gode, g.r. & bhide, n.k., 1988. Two rabies deaths after corneal grafts
from one donor. Lancet, 2, 791.
288 greathead, m.m. & ehret, w.j., 1963. Rabies in slaughter cattle at the
Johannesburg Municipal Abattoir. Journal of the South African
289 gremliza, l., 1953. Kasuistik zum Lyssa-Problem. Zeitschrift für
Tropenmedizin und Parasitologie, 4, 382–389.
290 gribencha, s.v., gribanova, l.i., mal’kov, g.b. & barinskii, i.f., 1989.
[Abortive and recurrent rabies in dogs intracerebrally infected with the
rabies street virus]. Voprosy Virusologii, 34, 217–221.
291 griffin, d.e. & hemachudha, t., 1988. Encephalomyelitis after rabies
vaccine. Clinical Immunology Newsletter, 9, 193–194.
292 gupta, p.k., singh, r.k., sharma, r.n., rao, y.u. & butchaiah, g., 2001.
Preliminary report on a single-tube, non-interrupted reverse
transcription-polymerase chain reaction for the detection of rabies
virus in brain tissue. Veterinary Research Communications, 25, 239–247.
293 habel, k., 1940. Evaluation of a mouse test for the standardization of the
immunizing power of anti-rabies vaccines. Public Health Report, 55,
1473–1487.
294 habel, k., 1945. Seroprophylaxis in experimental rabies. Public Health
Report, 60, 455–460.
295 habel, k. & koprowski, h., 1955. Laboratory data supporting the clinical
trial of antirabies serum in persons bitten by a rabid wolf. Bulletin of the
296 hable, c.p., hamir, a.n., snyder, d.e., joyner, r., french, j., nettles, v.
and others, 1992. Prerequisites for oral immunization of free-ranging
raccoons (Procyon lotor) with a recombinant rabies virus vaccine: Study
site ecology and bait system development. Journal of Wildlife Diseases,
28, 64–79.
297 hamir, a.n., raju, n. & rupprecht, c.e., 1992. Experimental oral
administration of canine adenovirus (type 2) to raccoons (Procyon
lotor). Veterinary Pathology, 29, 509–513.
298 hanlon, c.a., buchanan, j.r., nelson, e., niu, h.s., diehl, d. &
rupprecht, c.e., 1993. A vaccinia-vectored rabies vaccine field trial:
Ante- and post-mortem biomarkers. Revue Scientifique et Technique, 12,
99–107.
299 hanlon, c.a., niezgoda, m., hamir, a.n., schumacher, c., koprowski, h.
& rupprecht, c.e., 1998. First North American field release of a
vaccinia-rabies glycoprotein recombinant virus. Journal of Wildlife
Diseases, 34, 228–239.
300 hanlon, c.l., hayes, d.e., hamir, a.n., snyder, d.e., jenkins, s., hable,
c.p. and others, 1989. Proposed field evaluation of a rabies
Rabies
recombinant vaccine for raccoons (Procyon lotor): Site selection, target
species characteristics, and placebo baiting trials. Journal of Wildlife
Diseases, 25, 555–567.
301 hanna, j.n., carney, i.k., smith, g.a., tannenberg, a.e., deverill, j.e.,
botha, j.a. and others, 2000. Australian bat lyssavirus infection: A
second human case, with a long incubation period. Medical Journal of
Australia, 172, 597–599.
302 harmon, m.w. & janis, b., 1975. Therapy of murine rabies after exposure:
efficacy of polyriboinosinic-polyribocytidylic acid alone and in
combination with three rabies vaccines. Journal of Infectious Diseases,
132, 241–249.
303 hassel, r.h., 1982. Incidence of rabies in kudu in South West Africa/
Namibia. South African Journal of Science, 78, 421.
304 hattwick, m.a.w. & gregg, m.b., 1975. The disease (rabies) in man. In:
baer, g.m., (ed.). The Natural History of Rabies, Vol. 2. New York:
Academic Press.
305 hattwick, m.a.w., weis, t.t., stechschulte, c.j., baer, g.m. & gregg,
m.b., 1972. Recovery from rabies. Annals of Internal Medicine, 76,
931–942.
306 haupt, h. & rehaag, h., 1921. Durch Vledermause verbreitete
Seuchenhafte Tollwut unter Viehbeständen in Santa Catharina
(Süd-Brasielien). Zentralblatt für Infektionskrankheit,
Parasitärekrankheiten und Hygiene der Haustiere, 22, 104–127.
307 heaton, p.r., mcelhinney, l.m. & lowings, j.p., 1999. Detection and
identification of rabies and rabies-related viruses using rapid-cycle
PCR. Journal of Virological Methods, 81, 63–69.
308 held, j.r. & adaros, h.l., 1972. Neurological disease in man following
administration of suckling mouse brain antirabies vaccine. Bulletin of
309 henning, m.w., 1956. Rabies. In: Animal Diseases in South Africa, 2nd
edn. Pretoria: Central News Agency Ltd.
310 herzenberg, l., 1928. Two cases of hydrophobia. Journal of the Medical
Association of South Africa, 2, 659–661.
311 hirose, j.a., bourhy, h. & sureau, p., 1991. Retro-orbital route for brain
specimen collection for rabies diagnosis. The Veterinary Record, 129,
291–292.
312 hlatshwako, p., 1992. National report on rabies in Swaziland.
Southern Africa, Lusaka, Zambia, 2–5 June, 1992. Geneva: World Health
Organization.
1171
322 hudson, l.c., weinstock, d., jordan, t. & bold-fletcher, n.o., 1996.
Clinical features of experimentally induced rabies in cattle and sheep.
Zentralblatt für Veterinärmedizin [B], 43, 85–95.
323 hudson, l.c., weinstock, d., jordan, t. & bold-fletcher, n.o., 1996.
Clinical presentation of experimentally induced rabies in horses.
Zentralblatt für Veterinärmedizin [B], 43, 277–285.
324 hummeler, k., koprowski, h. & wiktor, t.j., 1967. Structure and
development of rabies virus in tissue culture. Journal of Virology, 1,
152–170.
325 humphrey, g.l., kemp, g.e. & wood, e.g., 1960. Fatal case of rabies in a
woman bitten by insectivorous bat. Public Health Report, 75, 317–326.
326 hurst, e.w., 1932. The effects of the injection of normal brain emulsion
into rabbits, with special reference to the aetiology of the paralytic
accidents of antirabic treatment. Journal of Hygiene, 32, 33–44.
327 hutcheon, d., 1894. Reports of the Colonial Veterinary Surgeon and
Assistant Veterinary Surgeons for the year 1893. Department of
Agriculture, Cape of Good Hope.
328 hübschle, o.j.b., 1988. Rabies in the kudu antelope (Tragelaphus
strepsiceros). Reviews of Infectious Diseases, 10 Suppl 4, S629–633.
329 ibrahim, a.e., eltigani, a. & ali, a.a., 1985. Epidemiology of rabies in the
Sudan. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
330 illango, j., 1992. National report on rabies in Uganda. Proceedings of a
Lusaka, Zambia, 2–5 June, 1992. Geneva: World Health Organization.
331 innes, j.r.m. & saunders, l.z., 1962. Rabies. In: Comparative
Neuropathology. New York: Academic Press.
332 irons, j.w., eads, r.b., grimes, j.e. & conklin, a., 1957. The public health
importance of bats. Texas Reports on Biology and Medicine, 15, 292–298.
333 irvin, a.d., 1970. The epidemiology of wildlife rabies. The Veterinary
Record, 87, 338–348.
334 ito, m., itou, t., sakai, t., santos, m.f., arai, y.t., takasaki, t. and
others, 2001. Detection of rabies virus RNA isolated from several
species of animals in Brazil by RT-PCR. Journal of Veterinary Medical
Science, 63, 1309–1313.
335 iwasaki, y. & clark, h.f., 1975. Cell to cell transmission of virus in the
central nervous system. II. Experimental rabies in mouse. Laboratory
Investigation, 33, 391–399.
336 iwasaki, y. & clark, h.f., 1977. Rabies virus infection in mouse
neuroblastoma cells. Laboratory Investigation, 36, 578–4.
313 hofmeyer, m., bingham, j., lane, e.p., ide, a. & nel, l., 2000. Rabies in
African wild dogs (Lycaon pictus) in the Madikwe Game Reserve, South
Africa. The Veterinary Record, 146, 50–52.
337 iwasaki, y. & tobita, m., 2002. Pathology. In: jackson, a.c. & wunner, w.h.,
314 holloway, b.p. & obijeski, j.f., 1980. Rabies virus-induced RNA synthesis
in BHK21 cells. Journal of General Virology, 49, 181–195.
338 jackson, a.c., 2002. Human disease. In: jackson, a.c. & wunner, w.h.,
315 honda, y., kawai, a. & matsumoto, s., 1985. Persistent infection of rabies
virus (HEP-Flury strain) in human neuroblastoma cells capable of
producing interferon. Journal of General Virology, 66, 957–967.
339 jackson, a.c., 2002. Pathogenesis. In: jackson, a.c. & wunner, w.h.,
316 hooper, d.c., pierard, i., modelska, a., otvos, l., jr., fu, z.f.,
koprowski, h. and others, 1994. Rabies ribonucleocapsid as an oral
immunogen and immunological enhancer. Proceedings of the National
Academy of Sciences of the United States of America, 91, 10908–10912.
317 hooper, p.t., fraser, g.c., foster, r.a. & storie, g.j., 1999.
Histopathology and immunohistochemistry of bats infected by
Australian bat lyssavirus. Australian Veterinary Journal, 77, 595–599.
318 houff, s.a., burton, r.c., wilson, r.w., henson, t.e., london, w.t., baer,
g.m. and others, 1979. Human-to-human transmission of rabies virus
by corneal transplant. New England Journal of Medicine, 300, 603–604.
319 hronovsky, v. & benda, r., 1969. Development of inhalation rabies
infection in suckling guinea pigs. Acta Virologica, 13, 198–202.
320 hronovsky, v. & benda, r., 1969. Experimental inhalation infection of
laboratory rodents with rabies virus. Acta Virologica, 13, 193–197.
321 hudson, j.r., 1944. A short note on the history of rabies in Kenya. East
African Medical Journal, 21, 322–327.
340 jaussaud, r., strady, c., lienard, m. & strady, a., 2000. [Rabies in
France: an update]. Revue de Medecine Interne, 21, 679–683.
341 javadi, m.a., fayaz, a., mirdehghan, s.a. & ainollahi, b., 1996.
Transmission of rabies by corneal graft. Cornea, 15, 431–433.
342 jenkins, s.r., perry, b.d. & winkler, w.g., 1988. Ecology and
epidemiology of raccoon rabies. Reviews of Infectious Diseases, 10,
Suppl. 4, S620–625.
343 jenson, a.b., rabin, e.r., bentinck, d.c. & melnick, j.l., 1969. Rabiesvirus
neuronitis. Journal of Virology, 3, 265–269.
344 johnson, h.n., 1959. Rabies. In: rivers, t.m. & horsfall, f.l., (eds). Virus
and Rickettsial Infections of Man. 3rd edn. Philadelphia: Lippincott.
345 johnson, h.n., 1965. Rabies virus. In: horsfall, f.l. & tamm, i., (eds).
Viral and Rickettsial Infections of Man. 4th edn. Philadelphia:
Lippincott.
346 johnson, k.p., swoveland, p.t. & emmons, r.w., 1980. Diagnosis of rabies
by immunofluorescence in trypsin-treated histologic sections. Journal
of the American Medical Association, 244, 41–43.
1172
SECTION FOUR:
347 johnson, r.t., 1965. Experimental rabies studies of cellular vulnerability
and pathogenesis using fluorescent antibody staining. Journal of
Neuropathology and Experimental Neurology, 24, 662–674.
348 johnson, r.t., 1971. The pathogenesis of experimental rabies. In: nagano,
y. & davenport, f.m., (eds). Rabies. Tokyo; University of Tokyo Press.
349 johnson, r.t. & mercer, e.h., 1964. The development of fixed rabies virus
in mouse brain. Australian Journal of Experimental Biology and Medical
Science, 42, 449–456.
350 johnston, d.h. & tinline, r.r., 2002. Rabies control in wildlife. In: jackson, a.c. & wunner, w.h., (eds). Rabies. Amsterdam: Academic Press.
351 johnston, d.h., voigt, d.r., macinnes, c.d., bachmann, p., lawson, k.f. &
rupprecht, c.e., 1988. An aerial baiting system for the distribution of
attenuated or recombinant rabies vaccines for foxes, raccoons, and
skunks. Reviews of Infectious Diseases, 10, Suppl. 4, S660–664.
352 kabat, e.a., wolf, a. & bezer, a.e., 1947. The rapid production of acute
disseminated encephalomyelitis in rhesus monkeys by injection of
heterologous and homologous brain tissue with adjuvants. Journal of
Experimental Medicine, 85, 117–130.
353 kaplan, c., 1985. Rabies: A worldwide disease. Proceedings of the
International Conference on Epidemiology,Control and Prevention of
Rabies and Brucellosis in Eastern and Southern African Countries,
Gaberone, Botswana, 23–25 November 1988.
354 kaplan, c., turner, g.s. & warrel, d.a., 1986. Rabies — the Facts. Oxford:
Oxford University Press.
355 kaplan, m.m., cohen, d., koprowski, h., dean, d. & ferrigan, l., 1962.
Studies on the local treatment of wounds for the prevention of rabies.
Bulletin of the World Health Organization, 26, 765–775.
356 kaplan, m.m., wiktor, t. & koprowski, h., 1966. An intracerebral assay
procedure in mice for chemical inactivation of rabies virus. Bulletin of
357 kaplan, m.m., wiktor, t.j. & koprowski, h., 1975. Pathogenesis of rabies
in immunodeficient mice. Journal of Immunology, 114, 1761–1765.
358 kaplan, m.m., wiktor, t.j., maes, r.f., campbell, j.b. & koprowski, h.,
1967. Effect of polyions on the infectivity of rabies virus in tissue culture:
construction of a single-cycle growth curve. Journal of Virology, 1, 145–151.
359 kariuki, d.p. & ngulo, w.k., 1985. Epidemiology of animal rabies in
Kenya (1900–1983). In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
360 kat, p.w., alexander, k.a., smith, j.s. & munson, l., 1995. Rabies and
African wild dogs in Kenya. Proceedings of the Royal Society of London.
B: Biological Sciences, 262, 229–233.
361 kat, p.w., alexander, k.a., smith, j.s., richardson, j.d. & munson, l.,
1996. Rabies among African wild dogs (Lycaon pictus) in the Masai Mara,
Kenya. Journal of Veterinary Diagnostic Investigation, 8, 420–426.
362 kawai, a. & matsumoto, s., 1977. Interfering and noninterfering defective
particles generated by a rabies small plaque variant virus. Virology, 76,
60–71.
363 keightley, a.i., struthers, j.k., johnson, s. & barnard, b.j.h., 1987.
Rabies in South Africa, 1980–84. South African Journal of Science, 83,
466–472.
364 kellerman, t.s., coetzer, j.a.w. & naudé, t.w., 1988. Plant Poisonings
and Mycotoxicoses of Livestock in Southern Africa. Cape Town: Oxford
University Press.
365 kemp, g.e., causey, o.r., moore, d.l., odelola, a. & fabiyi, a., 1972.
Mokola virus. Further studies on IbAn 27377, a new rabies-related
etiologic agent of zoonosis in Nigeria. American Journal of Tropical
Medicine and Hygiene, 21, 356–359.
369 khawplod, p., wilde, h., chomchey, p., benjavongkulchai, m.,
yenmuang, w., chaiyabutr, n. and others, 1996. What is an acceptable
delay in rabies immune globulin administration when vaccine alone
had been given previously? Vaccine, 14, 389–391.
370 khomari, l., 1988. Rabies in Lesotho. Proceedings of the International
Conference on Epidemiology,Control and Prevention of Rabies and
Brucellosis in Eastern and Southern African Countries, Gaberone,
Botswana, 23–25 November 1988.
371 khomari, l., 1992. National report on rabies in Lesotho. Proceedings of a
Lusaka, Zambia, 2–5 June 1992. Geneva: World Health Organization.
372 kieny, m.p., lathe, r., drillien, r., spehner, d., skory, s., schmitt, d.
and others, 1984. Expression of rabies virus glycoprotein from a
recombinant vaccinia virus. Nature, 312, 163–166.
373 king, a., 1991. Central Veterinary Laboratory, New Haw, Weybridge,
Surrey KT15 3NB, UK. Personal communication.
374 king, a. & crick, j., 1988. Rabies-related viruses. In: campbell, j.b. &
375 king, a.a., 1993. Monoclonal antibody studies on rabies-related viruses.
376 king, a.a., meredith, c.d. & thomson, g.r., 1993. Canid and viverrid
rabies viruses in South Africa. Onderstepoort Journal of Veterinary
Research, 60, 295–299.
377 king, a.a., meredith, c.d. & thomson, g.r., 1994. The biology of southern
African lyssavirus variants. 267–295. In: rupprecht, c.e., dietzschold, b.
& koprowski, h., (eds). Current Topics in Microbiology and Immunology,
378 kissling, r.e., 1958. Growth of rabies virus in non-nervous tissue culture.
Proceedings of the Society for Experimental Biology and Medicine, 98,
223–225.
379 kissling, r.e. & reese, d.r., 1963. Anti-rabies vaccine of tissue culture
origin. Journal of Immunology, 91, 362–368.
380 kligler, i.j. & bernkopf, h., 1938. Cultivation of rabies virus in the
allantois of the developing chick embryo. Proceedings of the Society for
Experimental Biology and Medicine, 39, 212.
381 knobel, d.l., du toit, j.t. & bingham, j., 2002. Development of a bait and
baiting system for delivery of oral rabies vaccine to free-ranging African
wild dogs (Lycaon pictus). Journal of Wildlife Diseases, 38, 352–362.
382 komarov, a. & hornstein, k., 1953. Studies on the pathogenicity of an
avianized street rabies. Cornell Veterinarian, 43, 344–361.
383 konradi, d., 1908. Ist die wut vererbbar? Ist das blut lyssakranker
infektionfahig? Zentralblatt für Bakteriologie, Parasitenkunde,
Infektionskrankheiten und Hygiene, 47, 203–212.
384 konradi, d., 1916. Hérédité de la rage. Annales de l’Institut Pasteur, 30,
33–48.
385 koprowski, h. & black, j., 1950. Studies on chick-embryo adapted rabies
virus. II. Pathogenicity for dogs and use of egg-adapted strains for
vaccination purposes. Journal of Immunology, 64, 185–196.
386 koprowski, h., black, j. & nelson, d.j., 1954. Studies on
chick-embryo-adapted-rabies virus. VI. Further changes in pathogenic
properties following prolonged cultivation in the developing chick
embryo. Journal of Immunology, 72, 94–106.
387 koprowski, h. & cox, h.r., 1948. Studies on chick embryo adapted rabies
virus. I. Culture characteristics and pathogenicity. Journal of
Immunology, 60, 533–554.
366 kemp, g.e., causey, o.r., setzer, h.w. & moore, d.l., 1974. Isolation of
viruses from wild mammals in West Africa, 1966–1970. Journal of
388 koprowski, h. & wiktor, t.j., 1985. Cross-reactivity and cross-protection:
rabies variants and rabies-related viruses. In: kuwert, e., mérieux, c.,
Springer-Verlag.
367 kemp, g.e., moore, d.l., isoun, t.t. & fabiyi, a., 1973. Mokola virus:
Experimental infection and transmission studies with the shrew, a
natural host. Archiv für Die Gesamte Virusforschung, 43, 242–250.
389 krebs, j.w., smith, j.s., rupprecht, c.e. & childs, j.e., 1999. Rabies
surveillance in the United States during 1998. Journal of the American
368 kennedy, d.j., 1988. An outbreak of rabies in north-western Zimbabwe
1980 to 1983. The Veterinary Record, 122, 129–133.
390 krebs, j.w., smith, j.s., rupprecht, c.e. & childs, j.e., 2000. Mammalian
reservoirs and epidemiology of rabies diagnosed in human beings in the
Rabies
United States, 1981–1998. Annals of the New York Academy of Sciences,
916:345–353.
391 krebs, j.w., strine, t.w., smith, j.s., noah, d.l., rupprecht, c.e. & childs,
j.e., 1996. Rabies surveillance in the United States during 1995. Journal
of the American Veterinary Medical Association, 209, 2031–2044.
392 kubes, v. & gallia, f., 1944. Brain-tissue neutralization. A new biological
reaction for rabies virus. Its relation to the protection and serum
neutralization tests. Canadian Journal of Comparative Medicine, 8,
48–60.
393 kucera, p., dolivo, m., coulon, p. & flamand, a., 1985. Pathways of the
early propagation of virulent and avirulent rabies strains from the eye to
the brain. Journal of Virology, 55, 158–162.
394 kulonen, k., fekadu, m., whitfield, s. & warner, c.k., 1999. An
evaluation of immunofluorescence and PCR methods for detection of
rabies in archival Carnoy-fixed, paraffin-embedded brain tissue.
Zentralblatt für Veterinarmedizin [B], 46, 151–155.
395 kureishi, a., xu, l.z., wu, h. & stiver, h.g., 1992. Rabies in China:
recommendations for control. Bulletin of the World Health
396 kurilla, m.g., cabradilla, c.d., holloway, b.p. & keene, j.d., 1984.
Nucleotide sequence and host La protein interactions of rabies virus
leader RNA. Journal of Virology, 50, 773–778.
397 kuwert, e. & schleiermann, n., 1985. Rabies: Post-exposure prophylaxis
in man. Annales de l’Institut Pasteur Microbiologie, 136E, 425–445.
398 kuwert, e., triau, r. & thraenhart, o., 1985. Innocuity and side effects
of human diploid cell rabies vaccine: rationale and facts after
vaccination of >500,000 persons. In: kuwert, e., mérieux, c., koprowski,
h. & bögel, k., (eds). Rabies in the Tropics. Berlin: Springer-Verlag.
399 lafay, f., benejean, j., tuffereau, c., flamand, a. & coulon, p., 1994.
Vaccination against rabies: Construction and characterization of SAG2,
a double avirulent derivative of SADBern. Vaccine, 12, 317–320.
400 lafon, m., 1994. Immunobiology of lyssaviruses: The basis for
immunoprotection. In: rupprecht, c.e., dietzschold, b. & koprowski,
h., (eds). Current Topics in Microbiology and Immunology, 187:
Lyssaviruses. Berlin: Springer-Verlag.
401 lafon, m., 2002. Immunology. In: jackson, a.c. & wunner, w.h., (eds).
402 lafon, m. & wiktor, t.j., 1985. Antigenic sites on the ERA rabies virus
nucleoprotein and non-structural protein. Journal of General Virology,
66, 2125–2133.
403 lapi, a., davis, c.l. & anderson, w.a., 1952. The gasserian ganglion in
animals dead of rabies. Journal of the American Veterinary Medical
404 larghi, o.p., arrosi, j.c., nakajata, a. & villa-nova, a., 1988. Control of
urban rabies. In: campbell, j.b. & charlton, k.m., (eds). Rabies. Boston:
Kluwer Academic Publishers.
1173
411 le mercier, p., jacob, y. & tordo, n., 1997. The complete Mokola virus
genome sequence: structure of the RNA-dependent RNA polymerase.
412 leach, c.n. & johnson, h.n., 1940. Canine rabies vaccination. An
experimental study of the efficacy of the single subcutaneous method
with phenol treated vaccine. American Journal of Hygiene, 32, 46.
413 lentz, t.l., burrage, t.g., smith, a.l., crick, j. & tignor, g.h., 1982. Is the
acetylcholine receptor a rabies virus receptor? Science, 215, 182–184.
414 leslie, m.j., hanlon, c., smith, j., rohde, r., cheshier, r. & rupprecht,
c., 2002. Emerging zoonoses: A novel epizootic of skunks infected with a
bat variant of rabies virus. Proceedings of an International Conference on
Emerging Infectious Diseases, Atlanta, 24–27 March 2002.
415 levaditi, c., 1913. Virus rabique et culture des cellules in vitro. Comptes
Rendus des Séances de la Société de Biologie et des Ses Filiales, 75,
505–509.
416 linhart, s.b., 1975. The biology and control of vampire bats. In: baer,
g.m., (ed.). The Natural History of Rabies, Vol. 2. New York: Academic
Press.
417 linhart, s.b., 1993. Bait formulation and distribution for oral rabies
vaccination of domestic dogs: an overview. Onderstepoort Journal of
418 linhart, s.b., blom, f.s., dasch, g.j., roberts, j.d., engeman, r.m.,
esposito, j.j. and others, 1991. Formulation and evaluation of baits for
oral rabies vaccination of raccoons (Procyon lotor). Journal of Wildlife
Diseases, 27, 21–33.
419 linhart, s.b., creekmore, t.e., corn, j.l., whitney, m.d., snyder, b.d. &
nettles, v.f., 1993. Evaluation of baits for oral rabies vaccination of
mongooses: Pilot field trials in Antigua, West Indies. Journal of Wildlife
Diseases, 29, 290–294.
420 linhart, s.b., king, r., zamir, s., naveh, u., davidson, m. & perl, s., 1997.
Oral rabies vaccination of red foxes and golden jackals in Israel:
Preliminary bait evaluation. Revue Scientifique et Technique, 16,
874–880.
421 linhart, s.b., wlodkowski, j.c., kavanaugh, d.m., motes-kreimeyer, l.,
montoney, a.j., chipman, r.b. and others, 2002. A new flavor-coated
sachet bait for delivering oral rabies vaccine to raccoons and coyotes.
Journal of Wildlife Diseases, 38, 363–377.
422 lodmell, d.l., 1988. Genetic control of resistance to rabies. In: campbell,
j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
423 lodmell, d.l., parnell, m.j., bailey, j.r., ewalt, l.c. & hanlon, c.a., 2001.
One-time gene gun or intramuscular rabies DNA vaccination of
non-human primates: comparison of neutralizing antibody responses
and protection against rabies virus 1 year after vaccination. Vaccine, 20,
838–844.
405 larghi, o.p., gonzalez, e. & held, j.r., 1973. Evaluation of the corneal
test as a laboratory method for rabies diagnosis. Applied Microbiology,
25, 187–189.
424 lodmell, d.l., parnell, m.j., bailey, j.r., ewalt, l.c. & hanlon, c.a., 2002.
Rabies DNA vaccination of non-human primates: Post-exposure studies
using gene gun methodology that accelerates induction of neutralizing
antibody and enhances neutralizing antibody titers. Vaccine, 20,
2221–2228.
406 laurenson, k., esterhuysen, j., stander, p. & van heerden, j., 1997.
Aspects of rabies epidemiology in Tsumkwe District, Namibia.
425 lodmell, d.l., ray, n.b. & ewalt, l.c., 1998. Gene gun particle-mediated
vaccination with plasmid DNA confers protective immunity against
rabies virus infection. Vaccine, 16, 115–118.
407 laurenson, k., van heerden, j., stander, p. & van vuuren, m.j., 1997.
Seroepidemiological survey of sympatric domestic and wild dogs
(Lycaon pictus) in Tsumkwe District, north-eastern Namibia.
426 lodmell, d.l., ray, n.b., parnell, m.j., ewalt, l.c., hanlon, c.a.,
shaddock, j.h. and others, 1998. DNA immunization protects
nonhuman primates against rabies virus. Nature Medicine, 4, 949–952.
408 lawrence, j.a., foggin, c.m. & norval, r.a., 1980. The effects of war on
the control of diseases of livestock in Rhodesia (Zimbabwe). The
Veterinary Record, 107, 82–85.
409 le blois, h., tuffereau, c., blancou, j., artois, m., aubert, a. &
flamand, a., 1990. Oral immunization of foxes with avirulent rabies
virus mutants. Veterinary Microbiology, 23, 259–266.
410 le gonidec, g., rickenbach, a., robin, y. & heme, g., 1978. Isolement
d’une souche de virus Mokola au Cameroun. Annals of Microbiology
(Paris), 129A, 245–249.
427 lodmell, d.l., sumner, j.w., esposito, j.j., bellini, w.j. & ewalt, l.c.,
1991. Raccoon poxvirus recombinants expressing the rabies virus
nucleoprotein protect mice against lethal rabies virus infection. Journal
of Virology, 65, 3400–3405.
428 lodmell, d.l., wiedbrauk, d.l. & ewalt, l.c., 1989. Interferon induced
within the central nervous system during infection is inconsequential as
a mechanism responsible for murine resistance to street rabies virus.
429 lopes perreira, c.m., pinto, f.g. & baule, c., 1988. Rabies in
Mozambique: update. Proceedings of the International Conference on
1174
SECTION FOUR:
Epidemiology, Control and Prevention of Rabies and Brucellosis in
Eastern and Southern African Countries, Gaborone, Botswana, 23–25
November, 1988.
430 loretu, k., blenden, d.c., torres-anjel, m.j. & satalowich, f.t., 1988.
Morphologic appearance of inclusion bodies and their association with
the antigenic composition of naturally occurring rabies viruses. Journal
of Clinical Microbiology, 26, 283–286.
431 loucq, c., albert, j.p., michel, p., harry, t.o., rollin, p. & sureau, p.,
1985. Essais cliniques du vaccin rabique préparé sur cerveau de
souriceau nouveau-né. In: kuwert, e., mérieux, c., koprowski, h. &
bögel, k., (eds). Rabies in the Tropics. Berlin: Springer-Verlag.
432 lumio, j., hillbom, m., roine, r., ketonen, l., haltia, m., valle, m. and
others, 1986. Human rabies of bat origin in Europe. Lancet, 1, 378.
433 luusah, c.d., 1988. Rabies control in the Republic of Kenya. Proceedings
of the International Conference on Epidemiology, Control and
Prevention of Rabies and Brucellosis in Eastern and Southern African
Countries, Gaborone, Botswana, 23–25 November 1988.
434 lycke, e. & tsiang, h., 1987. Rabies virus infection of cultured rat sensory
neurons. Journal of Virology, 61, 2733–2741.
435 maas, b., 1993. Bat-eared fox behavioural ecology and the incidence of
rabies in the Serengeti National Park. Onderstepoort Journal of
436 macdonald, d.w., 1992. Cause of wild dog death. Nature, 360, 633–634.
437 macdonald, d.w., 1993. Rabies and wildlife: a conservation problem?
438 macdonald, d.w. & voigt, d.r., 1985. The biological basis of rabies
models. Proceedings of the International Conference on Epidemiology,
Control and Prevention of Rabies and Brucellosis in Eastern and
Southern African Countries, Gaborone, Botswana, 23–25 November,
1988.
439 macfarlan, r.i., 1988. Immune responses to rabies virus: vaccines and
natural infection. In: campbell, j.b. & charlton, k.m., (eds). Rabies.
Boston: Kluwer Academic Publishers.
440 macfarlan, r.i., dietzschold, b., wiktor, t.j., kiel, m., houghten, r.,
lerner, r.a. and others, 1984. T cell responses to cleaved rabies virus
glycoprotein and to synthetic peptides. Journal of Immunology, 133,
2748–2752.
441 machuva, p., 1988. Rabies in Tanzania. Proceedings of the International
Conference on Epidemiology, Control and Prevention of Rabies and
Brucellosis in Eastern and Southern African Countries, Gaborone,
Botswana, 23–25 November 1988.
442 macinnes, c.d., 1988. Control of wildlife rabies: The Americas. In: campbell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
443 macinnes, c.d., tinline, r.r., voigt, d.r., broekhoven, l.h. & rosatte,
r.r., 1988. Planning for rabies control in Ontario. Reviews of Infectious
Diseases, 10, Suppl. 4, S665–669.
444 mackinnon, j., 1963. Rabies in Southern Rhodesia 1950–1962. Bulletin de
l’Office International des Epizooties, 60, 87–95.
445 madore, h.p. & england, j.m., 1977. Rabies virus protein synthesis in
infected BHK-21 cells. Journal of Virology, 22, 102–112.
446 maganu, e.t. & staugard, f., 1985. Epidemiology of rabies in Botswana.
447 magembe, s.r., 1985. Epidemiology of rabies in the United Republic of
Tanzania. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
448 majer, m., hilfenhaus, j., gruschkau, h., mauler, r. & hennessen, w.,
1978. A purified human diploid cell rabies vaccine. Developments in
Biological Standardization, 40:25–8, 25–28.
449 mansvelt, p.r., 1956. Rabies in the northern Transvaal (1950) outbreak.
Journal of the South African Veterinary Medical Association, 27, 167–178.
450 mansvelt, p.r., 1962. Rabies in South Africa. Field control of the disease.
451 mansvelt, p.r., 1965. The role of wild life in the epizootiology of some
infectious and parasitic animal diseases in South Africa. Bulletin de
l’Office International des Épizooties, 64, 825–835.
452 maré, c.j., 1962. Rabies in South Africa. The epizootiology and diagnosis
of the disease. Journal of the South African Veterinary Medical
453 mariam, s.h., 1985. Epidemiology of rabies in Ethiopia. In: kuwert, e.,
454 martell, m.a., montes, f.c. & alcocer, r., 1973. Transplacental
transmission of bovine rabies after natural infection. Journal of
455 masupu, k.v., 1992. National report on rabies in Botswana. Proceedings
of a Joint CVRI, WHO, FAO and OIE Seminar on Rabies in Southern
Africa, Lusaka, Zambia, 2–5 June 1992. Geneva: World Health
Organization.
456 matsumoto, s., 1962. Electron microscopy of nerve cells infected with
street rabies virus. Virology, 17, 198–201.
457 matsumoto, s., 1963. Electron microscope studies of rabies virus in
mouse brain. Journal of Cell Biology, 19, 565–591.
458 matsumoto, s., schneider, l.g., kawai, a. & yonezawa, t., 1974. Further
studies on the replication of rabies and rabies-like viruses in organized
cultures of mammalian neural tissues. Journal of Virology, 14, 981–996.
459 mcgarvey, p.b., hammond, j., dienelt, m.m., hooper, d.c., fu, z.f.,
dietzschold, b. and others, 1995. Expression of the rabies virus
glycoprotein in transgenic tomatoes. Biotechnology (N.Y. ), 13, 1484–
1487.
460 mckendrick, a.g., 1940. A ninth analytical review of reports from Pasteur
Institutes on the results of anti-rabies treatment. Bulletin of the Health
Organization of the League of Nations, 9, 31–78.
461 mckenzie, a.a., 1993. Biology of the black-backed jackal Canis mesomelas
with reference to rabies. Onderstepoort Journal of Veterinary Research,
60, 367–371.
462 mclean, r.g., 1975. Raccoon rabies. In: baer, g.m., (ed.). The Natural
463 mebatsion, t., cox, j.h. & conzelmann, k.k., 1993. Molecular analysis of
rabies-related viruses from Ethiopia. Onderstepoort Journal of
464 mebatsion, t., cox, j.h. & frost, j.w., 1992. Isolation and
characterization of 115 street rabies virus isolates from Ethiopia by
using monoclonal antibodies: identification of 2 isolates as Mokola and
Lagos bat viruses. Journal of Infectious Diseases, 166, 972–977.
465 melnick, j.l. & mccombs, r.m., 1966. Classification and nomenclature of
animal viruses. Progress in Medical Virology, 8, 400–408.
466 meredith, c.d., 1977. Recent studies on rabies in southern Africa. In: gear,
j.h.s., (ed.). Medicine in a Tropical Environment. Cape Town:
A.A.Balkema.
467 meredith, c.d., 1982. Wildlife rabies: past and present in South Africa.
South African Journal of Science, 78, 411–415.
468 meredith, c.d., 1991. ARC Onderstepoort Veterinary Institute,
Onderstepoort 0110. Personal communication.
469 meredith, c.d., nel, l.h. & von teichman, b.f., 1996. A further isolation
of Mokola virus in South Africa. Onderstepoort Journal of Veterinary
Research, 138, 119–120.
470 meredith, c.d., rossouw, a.p. & koch, h.p., 1971. An unusual case of
human rabies thought to be of chiropteran origin. South African
Medical Journal, 45, 767–769.
471 meredith, c.d. & standing, e., 1981. Lagos bat virus in South Africa.
Lancet, 1, 832–833.
472 meslin, f.x., 1992. Feasibility of canine rabies control. Proceedings of a
473 meyer, e.e., morris, p.g., elcock, l.h. & weil, j., 1986. Hindlimb
hyperesthesia associated with rabies in two horses. Journal of the
American Veterinary Medical Association, 188, 629–632.
Rabies
474 mifune, k., ohuchi, m. & mannen, k., 1982. Hemolysis and cell fusion by
rhabdoviruses. FEBS Letters, 137, 293–297.
475 miller, a., morse, h.c., iii, winkelstein, j. & nathanson, n., 1978. The
role of antibody in recovery from experimental rabies. I. Effect of
depletion of B and T cells. Journal of Immunology, 121, 321–326.
476 mills, m.g., 1993. Social systems and behaviour of the African wild dog
(Lycaon pictus) and the spotted hyaena (Crocuta crocuta) with special
reference to rabies. Onderstepoort Journal of Veterinary Research, 60,
405–409.
1175
495 neitz, w.o. & thomas, a.d., 1934. Rabies in South Africa. Occurrence and
distribution of cases during 1933. Onderstepoort Journal of Veterinary
Science and Animal Industry, 3, 335–342.
496 nel, j.a., 1993. The bat-eared fox: a prime candidate for rabies vector?
497 nel, l., jacobs, j., jaftha, j., von teichman, b., bingham, j. & olivier, m.,
2000. New cases of Mokola virus infection in South Africa: A genotypic
comparison of Southern African virus isolates. Virus Genes, 20, 103–106.
477 mollison, d., 1985. Sensitivity analysis of simple endemic models. In:
Academic Press.
498 nel, l.h., bingham, j., jacobs, j.a. & jaftha, j.b., 1998. A
nucleotide-specific polymerase chain reaction assay to differentiate
rabies virus biotypes in South Africa. Onderstepoort Journal of
478 mollison, d. & kuulasmaa, k., 1985. Spacial epidemic models: theory
and simulations. In: bacon, p.j., (ed.). Population Dynamics of Rabies in
Wildlife. London: Academic Press.
499 nel, l.h., thomson, g.r. & von teichman, b.f., 1993. Molecular
epidemiology of rabies virus in South Africa. Onderstepoort Journal of
479 montagnon, b.j., fournier, p., vincent-falquet, j.c. & agel, k., 1985. Un
nouveau vaccin antirabique à usage humain: rapport préliminaire. In:
500 nelson, h., 1962. Rabies in South Africa. Rabies from the point of view of
the medical officer of health or medical practitioner. Journal of the
South African Veterinary Medical Association, 33, 327–340.
480 morell, v., 1995. Dogfight erupts over animal studies in the Serengeti.
Science, 270, 1302–1303.
481 moreno, j.a. & baer, g.m., 1980. Experimental rabies in the vampire bat.
American Journal of Tropical Medicine and Hygiene, 29, 254–259.
482 mosienyane, m.g., 1988. Rabies situation in Botswana. Proceedings of the
International Conference on Epidemiology, Control and Prevention of
Rabies and Brucellosis in Eastern and Southern African Countries,
Gaborone, Botswana, 23–25 November 1988.
483 msiska, j.g.m., 1988. The epidemiology and control of rabies and
brucellosis in Malawi. Proceedings of the International Conference on
Epidemiology, Control and Prevention of Rabies and Brucellosis in
Eastern and Southern African Countries, Gaborone, Botswana, 23–25
November 1988.
484 muller, t., stohr, k., teuffert, j. & stohr, p., 1993. [Experiences with the
aerial distribution of baits for the oral immunization of foxes against rabies
in eastern Germany]. Deutsche Tierärztliche Wochenschrift, 100, 203–207.
485 murphy, f.a., 1975. Morphology and morphogenesis. In: baer, g.m.,
(ed.). The Natural History of Rabies. Vol. 2. New York: Academic Press.
486 murphy, f.a., 1985. The pathogenesis and pathology of rabies virus
infection. Annales de l’Institut Pasteur Virologie, 136, 373–386.
487 murphy, f.a., bauer, s.p., harrison, a.k. & winn, w.c., jr., 1973.
Comparative pathogenesis of rabies and rabies-like viruses. Viral
infection and transit from inoculation site to the central nervous
system. Laboratory Investigation, 28, 361–376.
488 murphy, f.a., fauquet, c.m., bishop, d.h.l., ghabrial, s.a., jarvis, a.w.,
martelli, g.p. and others, 1995. Sixth Report of the International
Committee on Taxonomy of Viruses. Archives of Virology, Supplement
10, 1–586.
489 murphy, f.a., harrison, a.k., winn, w.c. & bauer, s.p., 1973. Comparative
pathogenesis of rabies and rabies-like viruses. Infection of the central
nervous system and centrifugal spread of virus to peripheral tissues.
Laboratory Investigation, 29, 1–16.
490 nadin-davis, s.a., 1998. Polymerase chain reaction protocols for rabies
virus discrimination. Journal of Virological Methods, 75, 1–8.
491 national association of state public health veterinarians, 2001.
Compendium of animal rabies prevention and control, 2001. Morbidity
and Mortality Weekly Report, 50 RR-8, 1–10.
492 negri, a., 1903. Zur Aetiologie der Tollwith. Die Diagnose der Tollwuth
auf Grund der neueren Befunde. Zeitschrift für Hygiene und
Infektionskrankheiten, 44, 519–540.
493 neitz, w.o. & marais, i.p., 1932. Rabies as it occurs in the Union of South
Africa. In: Eighteenth Report of the Director of Veterinary Services and
Animal Industry, Union of South Africa.
494 neitz, w.o. & thomas, a.d., 1933. Rabies in South Africa. Occurrence and
distribution of cases during 1932. Onderstepoort Journal of Veterinary
Science and Animal Industry, 1, 51–56.
501 nettles, v.f., shaddock, j.h., sikes, r.k. & reyes, c.r., 1979. Rabies in
translocated raccoons. American Journal of Public Health, 69, 601–602.
502 nicholson, k.g., 1990. Rabies. In: zuckerman, a.j., banatvala, j.e. & pattison, j.r., (eds). Principles and Practice of Clinical Virology. 2nd edn.
Chichester: John Wiley & Sons Ltd.
503 nicholson, k.g. & bauer, s.p., 1981. Enteric inoculation with ERA rabies
virus: evaluation of a candidate wildlife vaccine in laboratory rodents.
Archives of Virology, 67, 51–56.
504 nicolas, a.j., patet, j., falquet, j.c., branche, r., delaiti, p.,
montagnon, b. and others, 1978. Production of inactivated rabies
vaccine for human use on WI38 diploid cells. Results of potency tests.
Stability of the vaccine in liquid and freeze-dried forms. Developments
in Biological Standardization, 40:17–24., 17–24.
505 niezgoda ,m., hanlon, c.a. & rupprecht, c.e., 2002. Animal rabies. In:
jackson, a.c. & wunner, w.h., (eds). Rabies. Amsterdam: Academic
Press.
506 nikolic, m., 1952. Tollwuttodesfälle bei Menschen ohne Verletzungen
oder Kontrakt nit einem Tollwutigen oder an Tollwut verdächtigen
Tiere. Archiv für Hygiene und Bakteriologie, 136, 80–84.
507 nikolic, m. & jelesic, z., 1956. Isolation of rabiesvirus from insectivorous
bats in Yugoslavia. A preliminary report. Bulletin of the World Health
508 nilsson, m.r. & sugay, w.o., 1966. Uso de camundongos lactantes no
diagnostico da raiva. Arquivodo Instituto Biologica de Sao Paulo, 33,
47–48.
509 noguchi, h., 1913. Contribution to the cultivation of the parasite of
rabies. Journal of Experimental Medicine, 18, 314–316.
510 oduye, o.o. & aghomo, h.o., 1985. Epidemiology of rabies in Nigeria. In:
511 okolo, m.i., 1989. Vaccine-induced rabies infection in rural dogs in
Anambra State, Nigeria. Microbios, 57, 105–112.
512 owolodun, b.y., 1968. Rabies in cattle in Northern States-Nigeria.
Bulletin of Epizootic Diseases of Africa, 16, 425–427.
513 pal, s.r., arora, b., chhuttani, p.n., broor, s., choudhury, s., joshi,
r.m. and others, 1980. Rabies virus infection of a flying fox bat, Pteropus
poliocephalus, in Chandigarh, northern India. Tropical and
Geographical Medicine, 32, 265–267.
514 pappaianou, m., fishbein, d.b., dreesen, d.w., schwartz, i.k., campbell,
g.h., sumner, j.w. and others, 1986. Antibody response to pre-exposure
human diploid-cell rabies vaccine given concurrently with chloroquine.
New England Journal of Medicine , 314, 280–284.
515 parker, r.l., 1961. Rabies in skunks in the north-central States.
Proceedings of the 65th Annual Meeting of the US Livestock Sanitary
Association, 273–280.
516 parker, r.l., 1975. Rabies in skunks. In: baer, g.m., (ed.). The Natural
History of Rabies. Vol. 2. New York: Academic Press.
1176
SECTION FOUR:
517 parker, r.l., kelly, j.w., cheatum, e.l. & dean, d.j., 1957. Fox population
densities in relation to rabies. New York Fish and Game Journal, 4,
219–228.
f.w., 1988. A baiting system suitable for the delivery of oral rabies
vaccine to dog populations in Zimbabwe. The Veterinary Record, 123,
76–79.
518 parker, r.l. & wilsnack, r.e., 1966. Pathogenesis of skunk rabies virus:
quantitation in skunks and foxes. American Journal of Veterinary
Research, 27, 33–38.
539 perry, b.d., garner, n., jenkins, s.r., mccloskey, k. & johnston, d.h.,
1989. A study of techniques for the distribution of oral rabies vaccine to
wild raccoon populations. Journal of Wildlife Diseases, 25, 206–217.
519 pasteur, l., 1885. Méthode pour prévenir la rage, après morsure.
Comptes Rendus de l’Académie des Sciences, 101, 765–774.
540 perry, b.d. & wandeler, a.i., 1993. The delivery of oral rabies vaccines to
dogs: An African perspective. Onderstepoort Journal of Veterinary
Research, 60, 451–457.
520 pasteur, l., chamberland, m.m. & roux, e., 1884. Sur la rage. Bulletin de
l’Académie de Médecine, 13, 661–664.
521 pastoret, p.p. & brochier, b., 1998. Epidemiology and elimination of
rabies in western Europe. Veterinary Journal, 156, 83–90.
522 pastoret, p.p., brochier, b. & coppens, p., 1993. Deliberate release of a
recombinant vaccinia-rabies virus for vaccination of wild animals
against rabies. Microbial Releases, 1, 191–195.
523 pastoret, p.p., frisch, r., blancou, j., wolff, f., brochier, b. &
schneider, l.g., 1987. Campagne internationale de vaccination
antirabique du renard par voie orale menée au grand-duché de
Luxembourg, en Belgique et en France. Annales de Médecine
Vétérinaire, 131, 441–447.
524 pawan, j.l., 1936. Rabies in the vampire bat of Trinidad with special
reference to the clinical cause and latency of infection. Annals of
Tropical Medicine and Parasitology, 30, 401–422.
525 pedersen, n.c., emmons, r.w., selcer, r., woodie, j.d., holliday, t.a. &
weiss, m., 1978. Rabies vaccine virus infection in three dogs. Journal of
the American Veterinary Medical Association, 172, 1092–1096.
526 pennica, d., holloway, b.p., heyward, j.t. & obijeski, j.f., 1980. In vitro
translation of rabies virus messenger RNAs. Virology, 103, 517–521.
527 percy, d.h., bhatt, p.n., tignor, g.h. & shope, r.e., 1973. Experimental
infection of dogs and monkeys with two rabies serogroup viruses, Lagos
bat and Mokola (IbAn 27377). Gross pathologic and histopathologic
changes. Veterinary Pathology, 10, 534–549.
528 perl, d.p., 1975. The pathology of rabies in the central nervous system.
In: baer, g.m., (ed.). The Natural History of Rabies. Vol. 1. New York:
Academic Press.
529 perl, d.p. & good, p.f., 1991. The pathology of rabies in the central
nervous system. In: baer, g.m., (ed.). The Natural History of Rabies. 2nd
edn. Boca Raton, Florida: CRC Press Inc.
530 perrin, p., gontier, c., lecocq, e. & bourhy, h., 1992. A modified rapid
enzyme immunoassay for the detection of rabies and rabies-related
viruses: RREID-lyssa. Biologicals, 20, 51–58.
531 perrin, p., jacob, y., aguilar-setien, a., loza-rubio, e., jallet, c.,
desmezieres, e. and others, 1999. Immunization of dogs with a DNA
vaccine induces protection against rabies virus. Vaccine, 18, 479–486.
532 perrin, p., jacob, y., desmezieres, e. & tordo, n., 2000. DNA-based
immunisation against rabies and rabies-related viruses: towards
multivalent vaccines. Developmental Biology (Basel), 104:151–7,
151–157.
533 perrin, p., jacob, y. & tordo, n., 2000. DNA-based immunization
against Lyssaviruses. Intervirology, 43, 302–311.
534 perrin, p., portnoi, d. & sureau, p., 1982. Etude de l’absorption et de la
penetration du virus rabique: Interactions avec les cellules BHK 21 et
des membranes artificelles. Annales de l’Institut Pasteur Virologie, 133,
403–422.
535 perrin, p., rollin, p.e. & sureau, p., 1986. A rapid rabies enzyme
immuno-diagnosis (RREID): A useful and simple technique for the
routine diagnosis of rabies. Journal of Biological Standardization, 14,
217–222.
536 perrin, p. & sureau, p., 1987. A collaborative study of an experimental kit
for rapid rabies enzyme immunodiagnosis (RREID). Bulletin of the
537 perry, b.d., 1993. Dog ecology in eastern and southern Africa:
Implications for rabies control. Onderstepoort Journal of Veterinary
Research, 60, 429–436.
538 perry, b.d., brooks, r., foggin, c.m., bleakley, j., johnston, d.h. & hill,
541 phanuphak, p., khaoplod, p., benjavongkulchai, m., chutivongse, s. &
wilde, h., 1990. What happens if intradermal injections of rabies
vaccine are partially or entirely injected subcutaneously? Bulletin of the
542 plummer, p.j.g., 1947. Preliminary note on arctic dog disease and its
relationship to rabies. Canadian Journal of Comparative Medicine, 11,
154–160.
543 porras, c., barboza, j.j., fuenzalida, e., adaros, h.l., oviedo, a.m. &
furst, j., 1976. Recovery from rabies in man. Annals of Internal
Medicine, 85, 44–48.
544 porterfield, j.s., hill, d.h. & morris, a.d., 1958. Isolation of a virus from
the brain of a horse with ‘staggers’ in Nigeria. British Veterinary Journal,
114, 25–33.
545 powell, h.m. & culbertson, c.g., 1954. Recent advances in preparation
of antirabies vaccines containing inactivated virus. Bulletin of the World
Health Organization, 10, 815–822.
546 prabhakar, b.s. & nathanson, n., 1981. Acute rabies death mediated by
antibody. Nature, 290, 590–591.
547 prehaud, c., coulon, p., diallo, a., martinet-edelist, c. & flamand, a.,
1989. Characterization of a new temperature-sensitive and avirulent
mutant of the rabies virus. Journal of General Virology, 70, 133–143.
548 précausta, p., soulebot, j.p., chappuis, g., brun, a., bugand, m. &
petermann, h.g., 1985. NIL2 cell inactivated tissue culture vaccine
against rabies — immunization of carnivores. In: kuwert, e., mérieux, c.,
Springer-Verlag.
549 ramsden, r.o. & johnston, d.h., 1975. Studies on the oral infectivity of
rabies virus in carnivora. Journal of Wildlife Diseases, 11, 318–324.
550 raza, o.a.e., wenhold, b.a., howard, p., marais, a. & pallett, j., 1992.
Reproduction in the yellow mongoose revisited. South African Journal
of Zoology, 27, 192–195.
551 reagan, k.j. & wunner, w.h., 1985. On the nature of rabies virus-cellular
receptor interactions. In: kuwert, e., mérieux, c., koprowski, h. & bögel,
k., (eds). Rabies in the Tropics. Berlin: Springer-Verlag.
552 reagan, k.j. & wunner, w.h., 1985. Rabies virus interaction with various
cell lines is independent of the acetylcholine receptor. Archives of
Virology, 84, 277–282.
553 reagan, r.l., day, w.c., moore, s., kehne, e.f. & brueckner, a.l., 1953.
Response of the Syrian hamster to two strains of rabies street virus by
rectal installation. American Journal of Experimental Medicine and
Hygiene, 2, 70–73.
554 remlinger, p., 1903. Le passage du virus rabique à travers les filtres.
Annales de l’Institut Pasteur, 17, 834–849.
555 remlinger, p., 1908. Transmission de la rage à la souris par ingestion.
Comptes Rendus des Séances de la Société de Biologie et des Ses Filiales,
70, 385–386.
556 remlinger, p., 1919. Contribution à l’étude de l’hérédité de la rage.
Annales de l’Institut Pasteur, 33, 375–388.
557 remlinger, p. & bailly, j., 1938. Sur un mode exceptionnel de
contamination rabique. Bulletin de l’Académie Nationale de Médecine,
119, 720–724.
558 remlinger, p. & curasson, m., 1924. Identité de l’oulou fato (maladie du
chien fou de l’ouest Africain) et de la rage.Bulletin de l’Académie
Nationale de Médecine, 92, 1112–1117.
559 rhodes, c.j., atkinson, r.p., anderson, r.m. & macdonald, d.w., 1998.
Rabies in Zimbabwe: Reservoir dogs and the implications for disease
Rabies
control. Philosophical Transactions of the Royal Society of London. B:
Biological Sciences, 353, 999–1010.
560 rivers, t.m. & schwentker, f.f., 1935. Encephalomyelitis accompanied
by myelin destruction experimentally produced in monkeys. Journal of
Experimental Medicine, 61, 689.
561 rohde, r.e., neill, s.u., clark, k.a. & smith, j.s., 1997. Molecular
epidemiology of rabies epizootics in Texas. Clinical and Diagnostic
Virology, 8, 209–217.
562 rollinson, d.h.l., 1956. Problems of rabies control in Africa. Bulletin of
Epizootic Diseases of Africa, 4, 7–16.
563 rosatte, r.c., lawson, k.f. & macinnes, c.d., 1998. Development of baits
to deliver oral rabies vaccine to raccoons in Ontario. Journal of Wildlife
Diseases, 34, 647–652.
564 rosatte, r.c., macinnes, c.d., power, m.j., johnston, d.h., bachmann, p.,
nunan, c.p. and others, 1993. Tactics for the control of wildlife rabies in
Ontario (Canada). Revue Scientifique et Technique, 12, 95–98.
565 roumiantzeff, m., montagnon, b., vincent-falquet, j.c., bussy, l. &
charbonnier, c., 1985. Rapport sur l’utilisation du vaccine rabique
préparé sur culture de cellules diploides humaines pour l’immunisation
avant et après exposition. In: kuwert, e., mérieux, c., koprowski, h. &
bögel, k., (eds). Rabies in the Tropics. Berlin: Springer-Verlag.
566 rudd, r.j. & trimarchi, c.v., 1987. Comparison of sensitivity of BHK-21
and murine neuroblastoma cells in the isolation of a street strain rabies
virus. Journal of Clinical Microbiology, 25, 1456–1458.
567 rudd, r.j. & trimarchi, c.v., 1989. Development and evaluation of an in
vitro virus isolation procedure as a replacement for the mouse
inoculation test in rabies diagnosis. Journal of Clinical Microbiology, 27,
2522–2528.
568 rudd, r.j., trimarchi, c.v. & abelseth, m.k., 1980. Tissue culture
technique for routine isolation of street strain rabies virus. Journal of
Clinical Microbiology, 12, 590–593.
569 rupprecht, c.e., glickman, l.t., spencer, p.a. & wiktor, t.j., 1987.
Epidemiology of rabies virus variants. American Journal of
570 rupprecht, c.e., hanlon, c.a., cummins, l.b. & koprowski, h., 1992.
Primate responses to a vaccinia-rabies glycoprotein recombinant virus
vaccine. Vaccine, 10, 368–374.
571 rupprecht, c.e. & kieny, m.p., 1988. Development of a vaccinia-rabies
glycoprotein recombinant virus vaccine. In: campbell, j.b. & charlton,
k.m., (eds). Rabies. Boston: Kluwer Academic Publishers.
572 rupprecht, c.e., smith, j.s., krebs, j., niezgoda, m. & childs, j.e., 1996.
Current issues in rabies prevention in the United States health
dilemmas. Public coffers, private interests. Public Health Reports, 111,
400–407.
573 rupprecht, c.e., smith, j.s., krebs, j.w. & childs, j.e., 1997. Molecular
epidemiology of rabies in the United States: Re-emergence of a classical
neurotropic agent. Journal of Neurovirology, 3, Suppl. 1, S52–3, S52–S53.
574 rupprecht, c.e., wiktor, t.j., johnston, d.h., hamir, a.n., dietzschold,
b., wunner, w.h. and others, 1986. Oral immunization and protection
of raccoons (Procyon lotor) with a vaccinia-rabies glycoprotein
recombinant virus vaccine. Proceedings of the National Academy of
Sciences of the United States of America, 83, 7947–7950.
575 rweyemamu, m.m., loretu, k., jakob, h. & gorton, e., 1973. Observations
on rabies in Tanzania. Bulletin of Epizootic Diseases of Africa, 21, 19–27.
576 sabin, a.b., casals, j. & webster, l.t., 1940. Localization of virus and
lesions after nasal instillation of rabies in mice. Journal of Bacteriology,
39, 67–68.
577 sacramento, d., bourhy, h. & tordo, n., 1991. PCR technique as an
alternative method of diagnosis and molecular epidemiology of rabies
virus. Molecular and Cellular Probes, 5, 229–240.
578 saluzzo, j.f., rollin, p.e., daugard, c., digoutte, j.p., georges, a.j. &
sureau, p., 1984. Premier isolement du virus Mokola a partir d’un
rongeur (Lophuromys sikapusi). Annales de l’Institut Pasteur Virologie,
135E, 57–66.
579 samaratunga, h., searle, j.w. & hudson, n., 1998. Non-rabies Lyssavirus
1177
human encephalitis from fruit bats: Australian bat Lyssavirus (pteropid
Lyssavirus) infection. Neuropathology and Applied Neurobiology, 24,
331–335.
580 sayers, b.m., saengcharoenrat, p., ross, a. j., & mansourian, b. g., 1985.
Pattern analysis of the case occurrences of fox rabies in Europe. In:
Academic Press.
581 scatterday, j.e., 1954. Bat rabies in Florida. Journal of the American
Veterinary Medical Association, 124, 125.
582 scheidegger, s., 1953. Experimental viral infections in embryo and fetus;
preliminary notes on pathologic findings with viruses of psittacosis,
ectromelia and rabies. American Journal of Pathology, 29, 185–197.
583 schneider, h.p., 1985. Rabies in South West Africa/Namibia. In: kuwert,
e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in the Tropics.
584 schneider, j.e. & mcgroarty, b.j., 1933. Transmission of experimental
rabies from mother to young. Journal of the American Veterinary
Medical Association, 82, 627–627.
585 schneider, l.g., 1973. Cell monolayer plaque tests. In: kaplan, m.m. &
koprowski, h., (eds). Laboratory Techniques in Rabies. Geneva: World
586 schneider, l.g., 1969. Die Pathogenese der Tollwut bei der Maus. I. Die
Virusausbreitung vom Infektionsortzum Zentralnervensystem.
Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten
und Hygiene, 211, 281–308.
587 schneider, l.g., 1969. The cornea test: A new method for the intra-vitam
diagnosis of rabies. Zentralblatt für Veterinärmedizin, 16, 24–31.
588 schneider, l.g., 1975. Spread of virus within the central nervous system.
In: baer, g.m., (ed.). The Natural History of Rabies, Vol. 1. New York:
Academic Press.
589 schneider, l.g., 1982. Antigenic variants of rabies virus. Comparative
Immunology, Microbiology and Infectious Diseases, 5, 101–107.
590 schneider, l.g., 1985. Oral immunization of wildlife against rabies.
Annales de l’Institut Pasteur Virologie, 136, 469–473.
591 schneider, l.g., barnard, b.j.h. & schneider, h.p., 1985. Application of
monoclonal antibodies for epidemiological investigations and oral
vaccination studies: I. African virus. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in the Tropics. Berlin:
Springer-Verlag.
592 schneider, l.g. & cox, j.h., 1994. Bat lyssaviruses in Europe. In: rupprecht, c.e., dietzschold, b. & koprowski, h., (eds). Current Topics in
Microbiology and Immunology, 187: Lyssaviruses. Berlin:
Springer-Verlag.
593 schneider, l.g., cox, j.h., aller, w.w. & hohnsbeen, k.p., 1988. Current
oral rabies vaccination in Europe: An interim balance. Reviews of
594 schneider, l.g., dietzschold, b., dierks, r.e., matthaeus, w., enzmann,
p.j. & strohmaier, k., 1973. Rabies group-specific ribonucleoprotein
antigen and a test system for grouping and typing of rhabdoviruses.
Journal of Virology, 11, 748–755.
595 schneider, l.g. & schoop, u., 1972. Pathogenesis of rabies and
rabies-like viruses. Annales de l’Institut Pasteur, 123, 469–476.
596 schoop, g., 1970. Zentralblatt für Bakteriologie, Abt. 1, Parasitenkunde,
Infektionskrankheiten und Hygiene, Supplement 3, 57–75.
597 seif, i., coulon, p., rollin, p.e. & flamand, a., 1985. Rabies virulence:
effect on pathogenicity and sequence characterization of rabies virus
mutations affecting antigenic site III of the glycoprotein. Journal of
Virology, 53, 926–934.
598 seligmann, e.b.j., 1973. The NIH potency test. In: kaplan, m.m. &
koprowski, h., (eds). Laboratory Techniques in Rabies. Geneva: World
599 selimov, m., aksenova, t., gribenca, l., kljueva, e., guliev, m.,
mirozoeva, s. and others, 1974. Live and inactivated tissue-culture
rabies virus vaccine made from strain Vnukova-32. Symposia Series in
Immunobiological Standardization, 21, 179.
1178
SECTION FOUR:
600 sellers, t.f., 1954. Rabies. In: harrison, t.r., (ed). Principles of Internal
Medicine. New York: McGraw-Hill.
623 smith, j.s., 1989. Rabies virus epitopic variation: Use in ecologic studies.
Advances in Virus Research, 36, 215–253.
601 semple, d., 1911. The preparation of a safe and efficient antirabic vaccine.
Science Memorandum No. 44,Medical Sanitation Department, Calcutta,
India.
624 smith, j.s., 2002. Molecular epidemiology. In: jackson, a.c. & wunner,
w.h., (eds). Rabies. Amsterdam: Academic Press.
602 sharpee, r.l., nelson, l.d. & beckenhauer, w.h., 1985. Inactivated tissue
culture rabies vaccine with three years immunogenicity in dogs and
cats. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies
in the Tropics. Berlin: Springer-Verlag.
603 shaw, j.j.h., 1980. Hondsdolheid by koedoes. Journal of the South
African Veterinary Association, 51, 209–209.
604 shill, m., baynes, r d. & miller, s.d., 1986. Fatal rabies encephalitis
despite appropriate post-exposure prophylaxis. New England Journal of
Medicine, 316, 1257–1258.
605 shone, d.k., 1962. Rabies in Southern Rhodesia 1900–1961. Journal of the
606 shope, r.e., 1984. Rabies enigma: Human and animal disease control. In:
kurstak, e., (ed.). Applied Virology. Orlando, Florida: Academic Press,
Inc.
607 shope, r.e., murphy, f.a., harrison, a.k., causey, o.r., kemp, g.e.,
simpson, d.i.h. and others, 1970. Two African viruses serologically
related to rabies virus. Journal of Virology, 6, 690–692.
608 sibbald, b., 2001. Raccoon rabies secures 2 bridgeheads in Canada.
Canadian Medical Association Journal, 165, 327.
609 sikes, r.k., 1962. Pathogenesis of rabies in wildlife. I. Comparative effect
of varying doses of rabies inoculated into foxes and skunks. American
610 sikes, r.k., cleary, w.f., koprowski, h., wiktor, t.j. & kaplan, m.m., 1971.
Effective protection of monkeys against death by street virus by
post-exposure administration of tissue culture rabies vaccine. Bulletin
of the World Health Organization, 45, 1–11.
611 sikes, r.k. sr, 1975. Canine and feline vaccines — past and present. In:
baer, g.m., (ed.). The Natural History of Rabies, Vol. 2. New York:
Academic Press.
612 sikes, r.k. sr, 1975. Rabies. In: hubbert, w.t., mcculloch, w.f. & schnurrenberger, p.r., (eds). Diseases Transmitted from Animals to Man.
Illinois: Charles C. Thomas.
613 sillero-zubiri, c., king, a.a. & macdonald, d.w., 1996. Rabies and
mortality in Ethiopian wolves (Canis simensis). Journal of Wildlife
Diseases, 32, 80–86.
614 sims, r.a., allen, r., & sulkin, s. e., 1963. Studies on the pathogenesis of
rabies in insectivorous bats. III. Influence of the gravid state. Journal of
615 sinyangwe, p.g., 1992. National report on rabies in Zambia. Proceedings of
a Joint CVRI, WHO, FAO and OIE Seminar on Rabies in Southern Africa,
616 siongok, t.k.a. & karama, m., 1985. Epidemiology of human rabies in
Kenya. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds).
625 smith, j.s. & baer, g.m., 1988. Epizootiology of rabies: The Americas. In:
campbell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
626 smith, j.s., fishbein, d.b., rupprecht, c.e. & clark, k., 1991. Unexplained
rabies in three immigrants in the United States. New England Journal of
Medicine, 324, 205–211.
627 smith, j.s., mcclelland, c.l., reid, f.l. & baer, g.m., 1982. Dual role of the
immune response in street rabies virus infection of mice. Infection and
Immunity, 35, 213–221.
628 smith, j.s., orciari, l.a., yager, p.a., seidel, h.d. & warner, c.k., 1992.
Epidemiologic and historical relationships among 87 rabies virus
isolates as determined by limited sequence analysis. Journal of
629 smith, j.s., reid-sanden, f.l., roumillat, l.f., trimarchi, c., clark, k.,
baer, g.m. and others, 1986. Demonstration of antigenic variation
among rabies irus isolates by using monoclonal antibodies to
nucleocapsid proteins. Journal of Clinical Microbiology, 24, 573–580.
630 smith, j.s., sumner, j., roumillat, f., baer, g.m. & winkler, w.g., 1985.
Epidemiological analysis of street rabies viruses from enzootic areas of
the United States. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
631 smith, j.s., sumner, j.w., roumillat, l.f., baer, g.m. & winkler, w.g.,
1984. Antigenic characteristics of isolates associated with a new
epizootic of raccoon rabies in the United States. Journal of Infectious
Diseases, 149, 769–774.
632 smith, j.s., yaeger, p.a. & baer, g.m., 1973. A rapid reproducible test for
determining rabies neutralizing antibody. Bulletin of the World Health
633 smith, j.s., yaeger, p.a. & baer, g.m., 1973. A rapid tissue culture test for
determining rabies neutralizing antibody. In: kaplan, m.m. & koprowski,
h., (eds). Laboratory Techniques in Rabies. Geneva: World Health
Organization.
634 smith, j.s., yager, p.a. & orciari, l.a., 1993. Rabies in wild and domestic
carnivores of Africa: Epidemiological and historical associations
determined by limited sequence analysis. Onderstepoort Journal of
635 smith, p.c., lawhaswasdi, k., vick, w.e. & stanton, j.s., 1967. Isolation of
rabies virus from fruit bats in Thailand. Nature, 216, 384–384.
636 smith, w.b., blenden, d.c. & tsu-luei-fuh, h.l., 1972. Diagnosis of rabies
by immunofluorescence of frozen sections of skin. Journal of the
American Veterinary Medical Association, 161, 1495–1501.
637 smithers, r.h.n., 1983. Mammals of the Southern African Subregion.
Pretoria: University of Pretoria.
638 snyman, p.s., 1937. Rabies in South Africa. Journal of the South African
617 skerratt, l.f., speare, r., berger, l. & winsor, h., 1998. Lyssaviral
infection and lead poisoning in black flying foxes from Queensland.
Journal of Wildlife Diseases, 34, 355–361.
639 snyman, p.s., 1940. The study and control of the vectors of rabies in
South Africa. Onderstepoort Journal of Veterinary Science and Animal
Industry, 15, 9–140.
618 smit, j.d., 1961. The lesions found at autopsy in dogs and cats which
manifest clinical signs referrable to the central nervous system. Journal
of the South African Veterinary Medical Association, 32, 47–55.
640 snyman, p.s., 1953. Rabies in the Union of South Africa. Bulletin of
Epizootic Diseases of Africa, 1, 94–105.
619 smith, a.d.m., 1985. A continuous time deterministic model of temporal
rabies. In: bacon, p.j., (ed.) Population Dynamics of Rabies in Wildlife.
London: Academic Press.
620 smith, a.l., tignor, g.h., emmons, r.w. & woodie, j.d., 1978. Isolation of
field rabies virus strains in CER and murine neuroblastoma cell
cultures. Intervirology, 9, 359–361.
621 smith, a.l., tignor, g.h., mifune, k. & motohashi, t., 1977. Isolation and
assay of rabies serogroup viruses in CER cells. Intervirology, 8, 92–99.
622 smith, j.s., 1981. Mouse model for abortive rabies infection of the central
nervous system. Infection and Immunity, 31, 297–308.
641 soave, o.a., 1966. Transmission of rabies to mice by ingestion of infected
tissues. American Journal of Veterinary Research, 27, 44–46.
642 sokol, f., 1975. Chemical composition and structure of rabies virus. In:
baer, g.m., (ed.). The Natural History of Rabies. Vol. 1. New York:
Academic Press.
643 sokol, f., schlumberger, h.d., wiktor, t.j., koprowski, h. & hummeler,
k., 1969. Biochemical and biophysical studies on the nucleocapsid and
the RNA of rabies virus. Virology, 38, 651–665.
644 soria, b.r., artois, m. & blancou, j., 1992. [Experimental infection of
sheep with a rabies virus of canine origin: study of the pathogenicity for
that species]. Revue Scientifique et Technique, 11, 829–836.
Rabies
1179
645 speare, r., skerratt, l., foster, r., berger, l., hooper, p., lunt, r. and
others, 1997. Australian bat lyssavirus infection in three fruit bats from
north Queensland. Communicable Diseases Intelligence, 21, 117–120.
667 swanepoel, r., barnard, b.j., meredith, c.d., bishop, g.c., bruckner,
g.k., foggin, c.m. and others, 1993. Rabies in southern Africa.
646 starr, l.e., 1963. Rabies. In: gibbons, w.j., (ed.). Diseases of Cattle.
Wheaton, Illinois: American Veterinary Publications, Inc.
668 swart, h., 1989. Hondsdolheid in Suid-Afrika. South African Veterinary
Medicine, 2, 163–166.
647 steck, f., wandeler, a., biochel, p., capt. s., hafliger, v. & schneider,
l., 1982. Oral immunisation of foxes against rabies: Laboratory and field
studies. Comparative Immunology, Microbiology and Infectious
Diseases, 5, 165–171.
669 szlachta, h.l. & habel, r.e., 1953. Inclusions resembling Negri bodies in
the brains of nonrabid cats. Cornell Veterinarian, 43, 207–212.
648 steele, j.h., 1975. History of rabies. In: baer, g.m., (ed.). The Natural
670 tantawichien, t., jaijaroensup, w., khawplod, p. & sitprija, v., 2001.
Failure of multiple-site intradermal postexposure rabies vaccination in
patients with human immunodeficiency virus with low CD4+ T
lymphocyte counts. Clinical Infectious Diseases, 33, 122–124.
649 steele, j.h., 1988. Rabies in the Americas and remarks on global aspects.
671 tariq, w.u., shafi, m.s., jamal, s. & ahmad, m., 1991. Rabies in man
handling infected calf. Lancet, 337, 1224.
650 steelman, h.g., henke, s.e., & moore, g.m., 1998. Gray fox response to
baits and attractants for oral rabies vaccination. Journal of Wildlife
Diseases, 34, 764–770.
672 tarr, a.f., o’grady, j.m. & jenkins, w.l., 1962. Rabies in South Africa.
Rabies and the private practitioner. Journal of the South African
651 steelman, h.g., henke, s.e., & moore, g.m., 2000. Bait delivery for oral
rabies vaccine to gray foxes. Journal of Wildlife Diseases, 36, 744–751.
652 stohr, k. & meslin, f.m., 1996. Progress and setbacks in the oral
immunisation of foxes against rabies in Europe. The Veterinary Record,
139, 32–35.
653 strady, a., lang, j., lienard, m., blondeau, c., jaussaud, r. & plotkin,
s.a., 1998. Antibody persistence following pre-exposure regimens of
cell-culture rabies vaccines: 10-year follow-up and proposal for a new
booster policy. Journal of Infectious Diseases, 177, 1290–1295.
654 straub, r.h., westermann, j., schölmerich, j. & falk, w., 1998. Dialogue
beween the CNS and the immune system in lymphoid organs.
Immunology Today, 19, 409–413.
655 sulkin, s.e. & allen, r., 1975. Experimental rabies virus infection in bats.
In: baer, g.m., (ed.). The Natural History of Rabies. Vol. 2. New York:
Academic Press.
656 sullivan, n.d., 1985. The Nervous System. In: jubb, k.v.f., kennedy, p.c. &
palmer, n., (eds). The Pathology of Domestic Animals. 3rd edn. Orlando,
Florida: Academic Press.
657 sumner, j.w., fekadu, m., shaddock, j.h., esposito, j.j. & bellini, w.j.,
1991. Protection of mice with vaccinia virus recombinants that express
the rabies nucleoprotein. Virology, 183, 703–710.
658 suntharasamai, p., chaiprasithikul, p., wasi, c., supanaranond, w.,
auewarakul, p., chanthavanich, p. and others, 1994. A simplified and
economical intradermal regimen of purified chick embryo cell rabies
vaccine for postexposure prophylaxis. Vaccine, 12, 508–512.
659 superti, f., derer, m. & tsiang, h., 1984. Mechanism of rabies virus entry
into CER cells. Journal of General Virology, 65, 781–789.
660 sureau, p., germain, m., herve, j.p., geoffroy, b., cornet, j.p., heme, g.
and others, 1977. [Isolation of the Lagos-bat virus in the Central African
Republic]. Bulletin de la Société de Pathologie. Exotique et de Ses.
Filiales, 70, 467–470.
661 sureau, p., portnoi, d., rollin, p., lapresle, c. & chaouni-berbich, a.,
1981. Prevention de la transmission inter-humaine d la rage aprés greffe
de cornée. Comptes Rendus Hebdomadaires des Seances de l’Academie
des Sciences, 293, 689–692.
662 sureau, p., rollin, p. & lafon, m., 1984. Characterization of rabies virus
strains used for vaccine production by means of monoclonal
antibodies. Developments in Biological Standardization, 57, 227–231.
663 sureau, p., rollin, p. & wiktor, t. j., 1983. Epidemiologic analysis of
antigenic variations of street rabies virus: Detection by monoclonal
antibodies. American Journal of Epidemiology, 117, 605–609.
664 sureau, p., tignor, g.h. & smith, a.l., 1980. Antigenic characterization of
the Bangui strain (ANCB-672d) of Lagos bat virus. Annals of Virology,
131, 25–32.
673 taylor, j., meignier, b., tartaglia, j., languet, b., vanderhoeven, j.,
franchini, g. and others, 1995. Biological and immunogenic properties
of a canarypox-rabies recombinant, ALVAC-RG (vCP65) in non-avian
species. Vaccine, 13, 539–549.
674 taylor, j. & paoletti, e., 1988. Fowlpox virus as a vector in non-avian
species. Vaccine, 6, 466–468.
675 taylor, j., tartaglia, j., riviere, m., duret, c., languet, b., chappuis, g.
and others, 1994. Applications of canarypox (ALVAC) vectors in human
and veterinary vaccination. Developments in Biological
Standardization, 82:131–135.
676 taylor, j., trimarchi, c., weinberg, r., languet, b., guillemin, f.,
desmettre, p. and others, 1991. Efficacy studies on a canarypox-rabies
recombinant virus. Vaccine, 9, 190–193.
677 taylor, p.j., 1993. A systematic and population genetic approach to the
rabies problem in the yellow mongoose (Cynictis penicillata).
678 taylor, p.j., campbell, g.k., van dyk, d., watson, j.p., pallett, j. &
erasmus, b.h., 1990. Genic variation in the yellow mongoose (Cynictis
penicillata) in Southern Africa. South African Journal of Science, 86,
256–262.
679 templeton, j.w., holmberg, c., garber, t., & sharp, r. m., 1986. Genetic
control of seum neutralizing-antibody response to rabies vaccination
and survival after a rabies challenge infection in mice. Journal of
Virology, 59, 98–102.
680 terre, j., chappuis, g., lombard, m. & desmettre, p., 1996. Eradication of
rabies, using a rec-DNA vaccine. Journal of Biotechnology, 46, 156–157.
681 texeira, m.j., 1985. Rabies-epidemiology in Portugal. In: kuwert, e.,
682 thiery, g., 1959. Particularities de la rage dans l’ouest Africaine. Bulletin
of Epizootic Diseases of Africa, 7, 265–265.
683 thomson, g.r. & meredith, c.d., 1993. Rabies in bat-eared foxes in South
Africa. Onderstepoort Journal of Veterinary Research, 60, 399–403.
684 thoulouze, m.i., lafage, m., schachner, m., hartmann, u., cremer, h. &
lafon, m., 1998. The neural cell adhesion molecule is a receptor for
rabies virus. Journal of Virology, 72, 7181–7190.
685 thraenhart, o., 1992. Human post-exposure treatment. Proceedings of a
686 tierkel, e.s., 1975. Canine rabies. In: baer, g.m., (ed.). The Natural
665 swanepoel, r., 1978. The occurrence, diagnosis, treatment and control
of rabies in Rhodesia. Central African Journal of Medicine, 24, 107–113.
687 tignor, g.h., murphy, f.a., clark, h.f., shore, r.e., madore, p., bauer,
s.p. and others, 1977. Duvenhage virus: Morphological, biochemical,
histopathological and antigenic relationships to the rabies serogroup.
666 swanepoel, r., 1994. Rabies. In: coetzer, j.a.w., thomson, g.r. & tustin,
r.c., (eds). Infectious Diseases of Livestock with Special Reference to
Southern Africa. Cape Town: Oxford University Press, Southern Africa.
688 tignor, g.h. & shope, r.e., 1972. Vaccination and challenge of mice with
viruses of the rabies serogroup. Journal of Infectious Diseases, 125,
322–324.
1180
SECTION FOUR:
689 tignor, g.h., shope, r.e., bhatt, p.n. & percy, d.h., 1973. Experimental
infection of dogs and monkeys with two rabies serogroup viruses, Lagos
bat and Mokola (Iban 27377): Clinical, serologic, virologic, and
fluorescent-antibody studies. Journal of Infectious Diseases, 128,
471–478.
690 tinline, r.r., 1988. Persistence of rabies in wildlife. In: campbell, j.b. &
691 tischendorf, l., thulke, h.h., staubach, c., muller, m.s., jeltsch, f.,
goretzki, j. and others, 1998. Chance and risk of controlling rabies in
large-scale and long-term immunized fox populations. Proceedings of
the Royal Society of London. B: Biological Sciences, 265, 839–846.
692 toma, b. & andral, l., 1977. Epidemiology of fox rabies. Advances in
Virus Research, 21, 1–36.
693 tomori, o. & david-west, k.b., 1985. Epidemiology of rabies in Nigeria.
694 tordo, n., badrane, h., bourhy, h. & sacramento, d., 1993. Molecular
epidemiology of lyssaviruses: focus on the glycoprotein and
pseudogenes. Onderstepoort Journal of Veterinary Research, 60, 315–
323.
695 tordo, n. & kouknetzoff, a., 1993. The rabies virus genome: an
overview. Onderstepoort Journal of Veterinary Research, 60, 263–269.
696 tordo, n. & poch, o., 1988. Structure of rabies virus. In: campbell, j.b. &
697 tordo, n., poch, o., ermine, a. & keith, g., 1986. Primary structure of
leader RNA and nucleoprotein genes of the rabies genome: segmented
homology with VSV. Nucleic Acids Research, 14, 2671–2683.
698 tordo, n., poch, o., ermine, a., keith, g. & fougeon, f., 1986. Walking
along the rabies genome: is the large G-L intergenic region a remnant
gene? Proceedings of the National Academy of Sciences, 83, 3914–3918.
699 torres-anjel, m.j., volz, d., torres, m.j.r., turk, m. & tshikuka, j.g.,
1988. Failure to thrive, wasting syndrome, and immunodeficiency in
rabies: A hypophyseal/hypothalamic thymic axis effect of rabies virus.
700 trimarchi, c.v., rudd, r.j. & abelseth, m.k., 1986. Experimentally
induced rabies in four cats innoculated with a rabies virus, isolated
from a bat. American Journal of Veterinary Research, 47, 777–780.
711 umoh, j.u., ezeokoli, c.d. & okoh, a.e.j., 1985. Immunofluorescent
staining of trypsinized formalin-fixed brain smears for rabies antigen:
Results compared with those obtained by standard methods for 221
suspect animal cases in Nigeria. Journal of Hygiene, 94, 129–134.
712 valadao, f.g., 1968. The most important aspects of the rabies problem
in Mozambique. Veterinaria. Moçambicana, 2, 13–20.
713 van der merwe, j.l.d.b., 1962. A routine stain for rabies. Journal of the
714 van der merwe, m., 1982. Bats as vectors of rabies. South African Journal
of Science, 78, 421–422.
715 van rensburg, r.d.j., 1965. Preliminary report on the ‘humane
coyote-getter’ for the control of black-backed jackal Thos mesomelas in
the Transvaal. Zoologica Africana, 1, 193–198.
716 van steenis, g., van wezel, a.l., hannik, c.a., van der marel, p.,
osterhaus, a.d.m.e., de groot, i.g.m. and others, 1985.
Immunogenicity of dog kidney cell rabies vaccine (DKCV). In: kuwert, e.,
717 vaughn, j.b., 1975. Cat rabies. In: baer, g.m., (ed.). The Natural History of
Rabies, Vol. 2. New York: Academic Press.
718 vaughn, j.b., gerhardt, p. & newell, k.w., 1965. Excretion of street
rabies virus in the saliva of dogs. Journal of the American Medical
719 vaughn, j.b., gerhardt, p. & paterson, j.c.s., 1963. Excretion of street
rabies in saliva of cats. Journal of the American Medical Association, 184,
705–708.
720 veeraraghavan, n., 1954. Phenolized vaccine treatment of people
exposed to rabies in southern India. Bulletin of the World Health
721 veeraraghavan, n., 1970. Annual Report of the Director 1968 and
Scientific Report 1969, Pasteur Institute of Southern India. Coonor,
Madras: Diocesan Press.
722 veeraraghavan, n., 1973. Annual Report of the Director 1971 and
Scientific Report 1972, Pasteur Institute of Southern India. Coonor,
Tamilnaidu, India.
723 venters, h.d., hoffert, d.r., scatterday, j.e. & hardy, a.v., 1954. Rabies
in bats in Florida. American Journal of Public Health, 44, 182–185.
701 tsiang, h., 1979. Evidence for an intra-axonal transport of fixed and
street rabies virus. Journal of Neuropathology and Experimental
Neurology, 38, 286–296.
724 verts, b.j. & storm, g.l., 1966. A local study of prevalence of rabies
among foxes and striped skunks. Journal of Wildlife Management, 30,
419–421.
702 tsiang, h., 1982. Neuronal function impairment in rabies infected rat
brain. Journal of General Virology, 61, 277–281.
725 vodopija, i., sureau, p., lafon, m., baklaic, z., ljubicic, m., svjetlicic, m.
and others, 1986. An evaluation of second generation tissue culture
rabies vaccines for use in man: A four-vaccine comparative
immunogenicity study using a pre-exposure vaccination schedule and
an abbreviated 2-1-1 postexposure schedule. Vaccine, 4, 245–248.
703 tsiang, h., 1985. An in vitro study of rabies pathogenesis. Bulletin de
l’Institut Pasteur, 83, 41–45.
704 tsiang, h., 1988. Interactions of rabies virus and host cells. In: campbell,
j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
705 tsiang, h., 1988. Rabies virus infection of myotubes and neurons as
elements of the neuromuscular junction. Reviews of Infectious Diseases,
10, 733–738.
706 tsiang, h. & guillon, j.c., 1981. Presence of specific antigens in neuronal
cells infected with fixed and street rabies virus strains. Acta
Neuropathologica, 55, 263–267.
707 tuchili, l.m., 1988. Epidemiology and prevention of rabies in Zambia.
Southern Africa, Lusaka, Zambia, 2–5 June 1992. Geneva: World Health
Organization.
708 turner, g.s., 1978. Immunoglobulin (IgG) and (IgM) antibody responses
to rabies vaccine. Journal of General Virology, 40, 595–604.
709 turner, g.s., 1985. Immune response after rabies vaccination: Basic
aspects. Annales de l’Institut Pasteur Virologie, 136, 453–460.
710 tustin, r.c. & smit, j.d., 1962. Rabies in South Africa: An analysis of
histological examination. Journal of the South African Veterinary
Medical Association, 33, 295–310.
726 voigt, d.r., tinline, r.r. & broekhoven, l.h., 1985. A spatial simulation
model for rabies control. In: bacon, p.j., (ed.) Population Dynamics of
Rabies in Wildlife. London: Academic Press.
727 von maltitz, l., 1950. Rabies in the northern districts of South West
Africa. Journal of the South African Veterinary Medical Association, 21,
4–12.
728 von teichman, b.f., de koker, w.c., bosch, s.j., bishop, g.c., meredith,
c.d. & bingham, j., 1998. Mokola virus infection: Description of recent
South African cases and a review of the virus epidemiology. Journal of
the South African Veterinary Association, 69, 169–171.
729 von teichman, b.f., thomson, g.r., meredith, c.d. & nel, l.h., 1995.
Molecular epidemiology of rabies virus in South Africa: evidence for two
distinct virus groups. Journal of General Virology, 76, 73–82.
730 wacharapluesadee, s. & hemachudha, t., 2001. Nucleic-acid sequence
based amplification in the rapid diagnosis of rabies. Lancet, 358,
892–893.
731 wachendörfer, g., frost, j.w. & fröhlich, t., 1985. Current diagnostic
procedures of rabies and related viruses. In: kuwert, e., mérieux, c.,
Springer-Verlag.
Rabies
732 walker, p.j., benmansour, a., dietzen, r.g., fang, r.-x. and others, 2002.
Rhabdoviridae. In: büchen-osmond,c., (ed.). ICTVdB — The Universal
Virus Database, http://www.ncbi.nlm.nih.gov/ICTVdB, version 3. Oracle,
Arizona: ICTVdB Management, Columbia University, The Earth
Institute, Biosphere 2 Center.
733 wallerstein, c., 1992. Rabies cases increase in the Philippines. British
Medical Journal, 318, 1306.
734 wandeler, a.i., 1985. Ecological and epidemiological data requirements
for the planning of dog rabies control. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k., (eds). Rabies in the Tropics. Berlin:
Springer-Verlag.
735 wandeler, a.i., bauder, w., prochaska, s. & steck, f., 1982. Small
mammal studies in a SAD baiting area. Comparative Immunology,
Microbiology and Infectious Diseases, 5, 173–176.
736 wandeler, a.i., budde, a., capt, s., kappeler, a. & matter, h., 1988. Dog
ecology and dog rabies control. Reviews of Infectious Diseases, 10, Suppl.
4, S684–S688.
737 wandeler, a.i., capt, s., kappeler, a. & hauser, r., 1988. Oral
immunization of wildlife against rabies: Concept and first field
experiments. Reviews of Infectious Diseases, 10, Suppl. 4, S649–S653.
738 warrell, d.a. & warrell, m.j., 1988. Human rabies and its prevention:
An overview. Reviews of Infectious Diseases, 10, Suppl. 4. S726–S731.
1181
from rabies by inactivated vaccines of tissue culture origin.
Developments in Biological Standardization, 40:255–64, 255–264.
753 wiktor, t.j. & clark, h.f., 1975. Growth of rabies virus in cell culture. In:
baer, g.m., (ed.). The Natural History of Rabies. Vol. 1. New York:
Academic Press.
754 wiktor, t.j., dietzschold, b., leamnson, r.n. & koprowski, h., 1977.
Induction and biological properties of defective interfering particles of
rabies virus. Journal of Virology, 21, 626–635.
755 wiktor, t.j., doherty, p.c. & koprowski, h., 1977. In vitro evidence of
cell-mediated immunity after exposure of mice to both live and
inactivated rabies virus. Proceedings of the National Academy of Sciences
of the United States of America, 74, 334–338.
756 wiktor, t.j., doherty, p.c. & koprowski, h., 1977. Suppression of
cell-mediated immunity by street rabies virus. Journal of Experimental
Medicine, 145, 1617–1622.
757 wiktor, t.j., fernandes, m.v. & koprowski, h., 1964. Cultivation of rabies
virus in human diploid cell strain WI-38. Immunology, 93, 353–366.
758 wiktor, t.j., flamand, a. & koprowski, h., 1980. Use of monoclonal
antibodies in diagnosis of rabies virus infection and differentiation of
rabies and rabies-related viruses. Journal of Virological Methods, 1,
33–46.
739 warrilow, d., smith, i.l., harrower, b. & smith, g.a., 2002. Sequence
analysis of an isolate from a fatal human infection of Australian bat
lyssavirus. Virology, 297, 109–119.
759 wiktor, t.j., gyorgy, e., schlumberger, d., sokol, f. & koprowski, h.,
740 watson, h.d., tignor, g.h. & smith, a.l., 1981. Entry of rabies virus into
the peripheral nerves of mice. Journal of General Virology, 56, 372–382.
760 wiktor, t.j. & koprowski, h., 1978. Monoclonal antibodies against rabies
virus produced by somatic cell hybridization: Detection of antigenic
variants. Proceedings of the National Academy of Sciences of the United
States of America, 75, 3938–3942.
741 webster, l.t., 1942. Rabies. New York: MacMillan & Co.
742 webster, l.t. & dawson, j.r., 1935. Early diagnosis of rabies by mouse
inoculation. Measurement of humoral immunity to rabies by mouse
protection test. Proceedings of the Society for Experimental Biology and
Medicine, 32, 570–573.
743 webster, w.a. & casey, g.a., 1988. Diagnosis of rabies infection. In: cambell, j.b. & charlton, k.m., (eds). Rabies. Boston: Kluwer Academic
Publishers.
744 webster, w.a., casey, g.a. & charlton, k.m., 1986. Major antigenic
groups of rabies virus in Canada determined by anti-nucleocapsid
monoclonal antibodies. Comparative Immunology, Microbiology and
745 wenhold, b.a., 1990. The ethology and social structure of the yellow
mongoose (Cynictis penicillata). M.Sc. thesis: University of Pretoria.
746 whetstone, c.a., bunn, t.o., emmons, r.w. & wiktor, t.j., 1984. Use of
monoclonal antibodies to confirm vaccine-induced rabies in ten dogs,
two cats, and one fox. Journal of the American Veterinary Medical
747 whitby, j.e., heaton, p.r., black, e.m., wooldridge, m., mcelhinney,
l.m. & johnstone, p., 2000. First isolation of a rabies-related virus from a
Daubenton’s bat in the United Kingdom. The Veterinary Record, 147,
385–388.
748 whitby, j.e., heaton, p.r., whitby, h.e., o’sullivan, e. & johnstone, p.,
1997. Rapid detection of rabies and rabies-related viruses by RT-PCR
and enzyme-linked immunosorbent assay. Journal of Virological
Methods, 69, 63–72.
749 whitby, j.e., johnstone, p. & sillero-zubiri, c., 1997. Rabies virus in the
decomposed brain of an Ethiopian wolf detected by nested reverse
transcription-polymerase chain reaction. Journal of Wildlife Diseases,
33, 912–915.
750 whitfield, s.g., fekadu, m., shaddock, j.h., niezgoda, m., warner, c.k. &
messenger, s.l., 2001. A comparative study of the fluorescent antibody
test for rabies diagnosis in fresh and formalin-fixed brain tissue
specimens. Journal of Virological Methods, 95, 145–151.
751 wiktor, t.j., 1973. Tissue culture methods. In: kaplan, m.m. & koprowski,
h., (eds). Laboratory Techniques in Rabies. Geneva: World Health
Organization.
752 wiktor, t.j., 1978. Cell-mediated immunity and postexposure protection
1973. Antigenic properties of rabies virus components. Journal of
Immunology, 110, 269–276.
761 wiktor, t.j., macfarlan, r.i., foggin, c.m. & koprowski, h., 1984.
Antigenic analysis of rabies and Mokola virus from Zimbabwe using
monoclonal antibodies. Developments in Biological Standardization,
57:199–211.
762 wiktor, t.j., macfarlan, r.i. & koprowski, h., 1985. Rabies virus
pathogenicity. In: kuwert, e., mérieux, c., koprowski, h. & bögel, k.,
763 wiktor, t.j., macfarlan, r.i., reagan, k.j., dietzschold, b., curtis, p.j.,
wunner, w.h. and others, 1984. Protection from rabies by a vaccinia
virus recombinant containing the rabies virus glycoprotein gene.
Proceedings of the National Academy of Sciences, 81, 7194–7198.
764 wiktor, t.j., plotkin, s.a. & koprowski, h., 1978. Development and
clinical trials of the new human rabies vaccine of tissue culture (human
diploid cell) origin. Developments in Biological Standardization, 40:3–9.
765 wilkinson, l., 1988. Understanding the nature of rabies. In: campbell, j.b.
& charlton, k.m., (eds). Rabies. Boston: Kluwer Academic Publishers.
766 williamson, j.m., 1976. The history of rabies in Rhodesia and control
measures. Rhodesia Science News, 10, 221–222.
767 winkler, w.g., 1975. Airborne rabies. In: baer, g.m., (ed.). The Natural
768 winkler, w.g., 1975. Fox Rabies. In: baer, g.m., (ed.). The Natural History
of Rabies. Vol. 1. New York: Academic Press.
769 winkler, w.g. & baer, g.m., 1976. Rabies immunization of red foxes
(Vulpes fulva) with vaccine in sausage baits. American Journal of
770 winkler, w.g., baker, e.f., jr. & hopkins, c.c., 1972. An outbreak of
non-bite transmitted rabies in a laboratory animal colony. American
Journal of Epidemiology, 95, 267–277.
771 winkler, w.g., shaddock, j.h. & williams, l.w., 1976. Oral rabies vaccine:
evaluation of its infectivity in three species of rodents. American Journal
of Epidemiology, 104, 294–298.
772 wunner, w.h., 1985. Structure of rabies virus. In: koprowski, h. & plotkin,
s.a., (eds). World’s Debt to Pasteur. New York: Alan R. Liss, Inc.
773 wunner, w.h., 2002. Rabies virus. In: jackson, a.c. & wunner, w.h. (eds).
1182
SECTION FOUR:
774 wunner, w.h., curtis, p.j. & wiktor, t.j., 1980. Rabies mRNA translation
in Xenopus laevis oocytes. Journal of Virology, 36, 133–142.
775 wunner, w.h., dietzschold, b., curtis, p.j. & wiktor, t.j., 1983. Rabies
subunit vaccines. Journal of General Virology, 64, 1649–1656.
776 wunner, w.h., dietzschold, b., smith, c.l., lafon, m. & golub, e., 1985.
Antigenic variants of CVS rabies virus with altered glycosylation sites.
Virology, 140, 1–12.
777 wunner, w.h., larson, j.k., dietzschold, b. & smith, c.l., 1988. The
molecular biology of rabies viruses. Reviews of Infectious Diseases, 10,
Suppl. 4, S771–S784.
778 wunner, w.h., reagan, k.j. & koprowski, h., 1984. Characterization of
saturable binding sites for rabies virus. Journal of Virology, 50, 691–697.
779 wunner, w.h., smith, c.l., lafon, m., ideler, j. & wiktor, t.j., 1984.
Comparative nucleotide sequence analysis of the glycoprotein gene of
antigenically altered rabies virus. In: bishop, d.h.l. & compans, r.w.,
(eds). Nonsegmented negative strand viruses. San Diego: Academic
Press.
780 xiang, z.q., spitalnik, s.l., cheng, j., erikson, j., wojczyk, b. & ertl, h.c.,
1995. Immune responses to nucleic acid vaccines to rabies virus.
Virology, 209, 569–579.
781 zaidman, g.w. & billingsley, a., 1998. Corneal impression test for the
diagnosis of acute rabies encephalitis. Ophthalmology, 105, 249–251.
782 zanoni, r.g., kappeler, a., muller, u.m., muller, c., wandeler, a.i. &
breitenmoser, u., 2000. [Rabies-free status of Switzerland following 30
years of rabies in foxes]. Schweizer Archiv für Tierheilkunde, 142,
423–429.
783 zimmer, k., wiegand, d., manz, d., frost, j.w., reinacher, m. & frese, k.,
1990. Evaluation of five different methods for routine diagnosis of
rabies. Zentralblatt für Veterinärmedizin [B], 37, 392–400.
784 zinke, g.g., 1804. Neue Ansichten der Hundswuth, ihrer Ursachen und
Folgen, nebst einer sichern Behandlungsart der von tollen Tieren
gebissenen Menschen. Jena: C.E. Gabler.
785 zumpt, i., 1982. The yellow mongoose as a rabies vector on the central
plateau of South Africa. South African Journal of Science, 78, 417–418.
786 zumpt, i.f., 1968. The feeding habits of the yellow mongoose, Cynictis
penicillata, the suricate, Suricata suricatta and the Cape ground
squirrel, Xerus inauris. I. Analysis of stomach contents. II. Observations
on free-living and captive animals. Journal of the South African
787 zumpt, i.f., 1969. Factors influencing rabies outbreaks: The age and
breeding cycle of the yellow mongoose, Cynictis penicillata (G. Cuvier).
788 zumpt, i.f., 1976. The yellow mongoose (Cynictis penicillata) as a latent
focus of rabies in South Africa. Journal of the South African Veterinary
789 zumpt, i.f. & debruyn, h.w., 1967. The merits of ‘Phostoxin’ in the
eradication of small Viverridae. Journal of the South African Veterinary
790 zyambo, g.c.n., sinyangwe, p.g. & bussein, n.a., 1985. Rabies in Zambia.

rhabdoviridae - Department of Library Services

Transcription

Similar documents

north star news - North Star Havanese Club

presentation5.7 Mb pdf

Upcoming Events! - Oromocto and Area SPCA

Development of a rabies vaccine in cell culture for veterinary use in

The Hammerling Experiment The Hammerling Experiment

Fruity Loops.indd

December 8, 2015 - Rock Island Rotary

zoonotic diseases of public health importance

Five Steps To a Healthier PC A guide to simple preventive

Inglês