Cat Scratch Disease and Other Bartonella Importance

Transcription

Cat Scratch
Disease and Other
Zoonotic Bartonella
Infections
Bartonellosis,
Cat Scratch Fever, Benign
Inoculation Lymphoreticulosis,
Benign Inoculation Reticulosis,
Regional Granulomatous
Lymphadenitis, Parinaud
Oculoglandular Syndrome,
Bacillary Angiomatosis
Last Updated: July 2012
Importance
Members of the genus Bartonella are maintained in many domesticated and wild
animal hosts. Bartonella henselae, the best understood species, infects housecats and
other members of the Felidae. Additional species of Bartonella are found in cats,
dogs, cattle, rodents, rabbits, bats or other wild and domesticated animals. While the
vast majority of these infections are asymptomatic, Bartonella spp. have been
implicated occasionally in illnesses in animals. However, proving a causative role is
difficult, and at present, their significance as pathogens for animals is unclear.
B. henselae is, however, a zoonotic pathogen. In immunocompetent people, this
organism usually causes cat scratch disease, a benign, self-limiting illness
characterized by fever and regional lymphadenopathy. Occasionally, cat scratch
disease may progress to complications such as neuroretinitis, neurological signs,
osteomyelitis and other conditions. The complications usually resolve without
sequelae in healthy people, although they can be life-threatening in rare cases.
Endocarditis is usually the most serious concern. In contrast, B. henselae infections
are often severe in immunocompromised individuals, and can be fatal without
antibiotic treatment. Other species of Bartonella have also been linked occasionally to
human illnesses, with varying levels of evidence for a causative role.
Etiology
Bartonella spp. are fastidious, pleomorphic, Gram negative rods (bacilli) in the
family Bartonellaceae. Some of these organisms were previously classified in the
genera Rochalimaea and Grahamella. The Bartonellaceae formerly belonged to the
order Rickettsiales, but are now in the α-2 subgroup of the Proteobacteria. More than
20 species of Bartonella have been described in animals, and a number of these
organisms are thought to be zoonotic or potentially zoonotic. Among them, only B.
henselae is well understood. Two species, B. quintana and B. bacilliformis, are
maintained in human populations, and cause illness in people. All Bartonella species
are closely related and may cross-react in some serologic assays. Some species, such
as B. clarridgeiae and B. rochalimae, are particularly close. Co-infection with more
than one species of Bartonella is possible.
B. henselae, B. quintana and B. bacilliformis have been established as the causative
agents for well-defined syndromes in people. Other species have also been implicated
rarely in clinical cases in people or animals. However, proving that a Bartonella
infection is the cause of an illness, rather than an incidental finding, can be difficult. In
animals, criteria proposed for possible Bartonella involvement include detection of the
organism by culture, PCR assay or serology, together with the exclusion of other causes,
and response to treatment with a drug that has activity against this organism. If the
syndrome is associated with Bartonella infection in other species, this is also
suggestive. However, diagnosis can still be challenging, and findings should be
interpreted with caution. Bartonella spp. infect erythrocytes and vascular endothelial
cells, and asymptomatic bacteremia can be very common, especially in the reservoir
hosts. PCR does not prove that viable organisms are present, and contamination with
Bartonella spp. in blood or flea dirt may result in false positive results. Serology is
particularly problematic, as IgG antibodies to Bartonella can persist for some time after
infection, and many healthy animals and humans are seropositive. Conversely,
Bartonella spp. are fastidious and can be difficult to culture, antibodies are not always
present in infected individuals, and the organism is not always detected by PCR.
Bartonella henselae: Cat scratch disease, bacillary angiomatosis and
peliosis hepatis
Bartonella henselae (formerly Rochalimaea henselae) is thought to cause most
cases of cat scratch disease in humans. This organism also causes bacillary
angiomatosis and peliosis hepatis, mainly in immunocompromised individuals. It has
been implicated in other conditions such as fever of unknown origin. There are two
major genotypes of B. henselae: type I (Houston-1) and type II (BA-TF/Marseille).
Strain variations exist within these genotypes. There is some evidence that genotypes
or strains might vary in their zoonotic potential.
© 2012
page 1 of 20
Cat Scratch Disease
Cats and other felids are the reservoir hosts, and
usually carry the organism asymptomatically. Most human
infections are thought to be acquired from housecats. B.
henselae can also infect other animal species, and rare cases
of human illness have been reported after bites or scratches
from dogs. Illnesses in cats and other animals have
occasionally been attributed to B. henselae, but proof of a
causative role can be elusive.
Other Bartonella species maintained in animals
Cats are thought to be the reservoir hosts for B.
clarridgeiae. This organism has been implicated in rare
cases of cat scratch disease in people. It was also detected
in a dog with endocarditis, and another dog with
hepatopathy. Cats may also be the reservoir hosts for B.
koehlerae. This organism appears to be very difficult to
isolate. It has been implicated in a few cases of endocarditis
in humans and dogs, as well as in rare cases of cat scratch
disease.
B. vinsonii subsp. berkhoffii is common in dogs and
wild canids including coyotes and foxes. Both dogs and
coyotes have been suggested as possible reservoir hosts.
Most canids appear to be infected asymptomatically, but
various illnesses have been attributed to this organism in
case reports. In addition, B. vinsonii subsp. berkhoffii has
been implicated in a few clinical cases in other animal
species and people. B. rochalimae has also been found in
dogs and wild canids, including foxes and coyotes, as well
as in raccoons and various rodents. This organism has been
implicated in rare cases of febrile illness in humans and
endocarditis in dogs.
Cattle are the reservoir hosts for B. bovis (formerly B.
weisii). Although this organism is common in apparently
healthy cattle, some authors suggest that it might have a
causative role in bovine endocarditis. It has been detected
occasionally in other animals. B. chomelii has also been
found in cattle.
The candidate species B. melophagi infects sheep. It
was co-isolated with B. henselae from the blood of one
person with a febrile illness. It was also isolated from
another individual with symptoms of fatigue and muscle
weakness.
Numerous Bartonella species have been detected in
mice, rats, shrews, ground squirrels, chipmunks, gerbils,
jerboas and other rodents. Species that appear to be
maintained in rodents include B. vinsonii subsp. arupensis,
B. vinsonii subsp vinsonii, B. birtlesii, B. doshiae, B.
peromysci, B. phoceensis, B. rattimassiliensis, B. talpae, B.
taylorii, B. tribocorum, B. grahamii, B. elizabethae, B.
queenslandensis and B. washoensis, among others. Many
rodent-associated Bartonella species were formerly
classified in the genus Grahamella. Some organisms,
including B. vinsonii subsp. arupensis, B. vinsonii subsp
vinsonii, B. elizabethae, B. washoensis, B. grahamii, B.
rattimassiliensis and B. tribocorum, have been detected in
rare cases of endocarditis, ocular disease or other illnesses
© 2012
in people. B. washoensis was implicated in endocarditis in a
dog.
The candidate species B. tamiae was cultured from the
blood of three patients enrolled in a prospective study to
determine the etiology of febrile illnesses in Thailand. The
organisms isolated from these patients caused illness in
experimentally infected mice. The reservoir host for B.
tamiae is not known, although rats have been proposed.
B. alsatica infects rabbits. Evidence of infection with
this organism was found in two people with endocarditis, as
well as an elderly woman with regional lymphadenopathy.
All three had close contact with domesticated or wild
rabbits.
B. capreoli and B. schoenbuchensis have been found in
deer. B. capreoli has also been isolated from elk (Cervus
elephas), and B. schoenbuchensis was found in a cow.
Bartonella DNA from an apparently novel species was
detected by PCR in North American river otters (Lontra
canadensis). Bartonella species, which appear to be distinct
from the organisms found in small mammals, have been
detected in a number of bat species.
Non-zoonotic organisms: Bartonella quintana
and Bartonella bacilliformis
Two species of Bartonella are maintained in human
populations.
B. bacilliformis, which is endemic in areas of South
America, causes Oroya fever (Carrión disease) in people.
This syndrome is characterized by fever and hemolytic
anemia, and is often followed by the development of
cutaneous angioproliferative lesions (verruga peruana/
Peruvian wart). B. bacilliformis is not known to affect
animals.
B. quintana (formerly Rochalimaea quintana) is
maintained in human populations, but it has been detected
in animals on rare occasions. Notably, DNA from this
organism was found in two feral cats and in an
asymptomatic woman who had been bitten by one of the
cats. In people, B. quintana causes trench fever, a louseborne, self-limited, febrile illness characterized by relapsing
fever, malaise, arthralgia and other systemic signs, and
often by erythematous macules or papules. B. quintana has
also been linked to cases of endocarditis, and it can cause
bacillary angiomatosis and peliosis hepatis in
immunocompromised individuals. It is not known to cause
illness in animals.
Geographic Distribution
B. henselae occurs worldwide in cats. The prevalence
of different genotypes varies with the geographic region. B.
henselae type I (Houston-1) is more common than type II in
Japan and the Philippines. This genotype is also more
prevalent in the eastern U.S., where it represents
approximately half of all isolates, than in the western states.
B. henselae type II (Marseille) is more common than type I
in the western U.S., western Europe (France, Germany,
page 2 of 20
Cat Scratch Disease
Italy, the Netherlands and the U.K.) and Australia. Within a
geographic area, the predominant genotypes in human
clinical cases may or may not match the dominant
genotypes in cats.
Based on serological surveys, Bartonella vinsonii
subsp. berkhoffii also appears to be present worldwide.
Transmission
Bartonella spp. are transmitted between animals by
arthropods. Fleas appear to be the vectors for a number of
species, but some organisms are spread by other arthropods
including sandflies, lice, keds and possibly ticks.
Bartonella henselae
B. henselae is transmitted between cats by cat fleas
(Ctenocephalides felis), probably via flea feces rather than
saliva. This organism is reported to survive for 3 days in
flea feces, which might result in contamination of the
environment. Cats can also be infected experimentally by
intravenous or intramuscular injection of feline blood,
suggesting that iatrogenic spread (including transmission
through blood transfusions) might be possible.
Transmission was not reported when cats were in contact,
but fleas were absent, indicating that casual contact and the
sharing of food or water dishes are not significant sources
of exposure. In one experiment, B. henselae was not spread
by sexual contact (bacteremic females and uninfected
males) or vertically to kittens.
B. henselae occasionally infects other animals, and
DNA from this organism has been detected in oral swabs
from dogs, as well as in dog fleas (Ctenocephalides canis)
removed from dogs.
Other species of Bartonella
Fleas are thought to be important vectors for a number
of Bartonella species, including many that are associated
with rodents. Although vector competence has not been
determined in most cases, the rodent flea Ctenophthalmus
nobilis was shown to transmit B. grahamii and B. taylorii
between voles in the laboratory. Organisms that have been
detected in the cat flea, in addition to B. henselae, include
B. clarridgeiae, B. koehlerae and B. quintana. Evidence for
Bartonella spp. was also found in other fleas including
Pulex irritans found on a pet monkey, Pulex sp. from
humans (the latter contained organisms most closely related
to B. rochalimae and B. vinsonii subsp. berkhoffii), and P.
irritans from the carcasses of red foxes.
Other arthropods are also proven or potential vectors
for some Bartonella species. B. bacilliformis is transmitted
between people by the sandfly Lutzomyia verrucarum.
Other Lutzomyia sandflies or other arthropods might also be
capable of transmitting this organism, as outbreaks have
been reported in areas where Lu. verrucarum is not
endemic. The human body louse (Pediculus humanus
humanus) is the main vector for B. quintana, but species
such as head lice (Pediculus humanus capitis) might also be
© 2012
able to transmit this organism. DNA from rodent-associated
Bartonella spp. has been detected in several species of lice
that parasitize these animals.
B. henselae and B. schoenbuchensis were found in deer
keds (Lipoptena mazamae and Lipoptena cervi), and these
organisms are thought to be vectors for B. schoenbuchensis.
Sheep keds (Melophagus ovinus) might be important in
transmitting B. melophagi. B. bovis DNA was reported in
horn flies (Haematobia sp.), and B. henselae DNA in a
stable fly (Stomoxys sp.). Bartonella DNA has also been
found in the fly Hippobosca equina, bat flies (Trichobius
major), bat bugs (Cimex adjunctus) and various mites on
rodents and bats, as well as in some arthropods that clearly
have no relevance as vectors, such as honeybees (Apis
mellifera). It should be noted that evidence of infection
does not, by itself, prove that an arthropod is a vector for an
organism.
The relevance of ticks as vectors for Bartonella is
controversial. The possibility of tick-borne transmission
was suggested by circumstantial or anecdotal evidence,
such as rare case reports of Bartonella infections diagnosed
soon after a tick bite. Bartonella spp. including B. henselae,
B. vinsonii subsp. berkhoffii, B. quintana, B. washoensis
and B. capreoli have been detected in various tick species,
mainly by PCR. A few studies found that antibodies to
Bartonella were more common in animals or people
frequently exposed to ticks, although concurrent exposure
to fleas and other vectors could not be ruled out. Three
laboratory studies also suggest that ticks might serve as
vectors for Bartonella, although they do not prove they are
epidemiologically important. In one study, Dermacentor
andersoni was shown to transmit B. bacilliformis between
monkeys in the laboratory, probably by mechanical
transmission. Transstadial transmission of B. henselae was
demonstrated in Ixodes ricinus, using an artificial feeding
system, and cats inoculated with dissected salivary gland
from these ticks became bacteremic. Recently, I. ricinus
was shown to act as a biological vector, when it transmitted
B. birtlesii (a species found in rodents) between mice in the
laboratory.
Transmission of zoonotic Bartonella to humans
People mainly seem to acquire B. henselae in scratches
and bites from cats, although some details of transmission
are not completely understood. More than 90% of clinical
cases occur in people who have been in contact with cats,
most often kittens, and the majority of these patients report
having been scratched, bitten or licked. In most cases, B.
henselae probably enters the body through a scratch
contaminated by flea feces. Organisms in feline saliva may
be transmitted to people in bites, or abrasions that are licked
by the cat. It is still unproven whether the bacteria in feline
saliva come from the cat’s blood, or from flea feces
ingested while grooming. However, one recent study found
that bacteremic cats were more likely to have Bartonella
DNA in oral swabs, compared to nonbacteremic cats.
page 3 of 20
Cat Scratch Disease
Entry of B. henselae through the eyelid or conjunctiva
is thought to account for Parinaud oculoglandular
syndrome, a form of cat scratch fever that affects the eye.
This could occur when patients rub their eyes after contact
with a cat. The authors of one article speculated that cases
of hepatosplenic involvement without lymphadenopathy
might be caused by ingestion. The possibility of
transmission directly from fleas to humans (e.g., through
flea bites) has also been proposed, but there is no evidence
that this is possible.
A few cases of cat scratch disease have occurred after
exposure to inanimate objects such as crab claws, thorns,
splinters and barbed wire, or after bites or scratches from
animals other than cats. In some cases, the bacteria may
have come from a cat that licked the wound. Scratches or
bites from dogs have been implicated in a small number of
B. henselae infections, and DNA from this organism (as
well as B. vinsonii subsp. berkhoffii, B. quintana and B.
bovis) has been detected occasionally in oral swabs from
dogs. There are also a few reports of cat scratch disease
associated with monkey bites. In a few cases, there is no
history of animal contact, and the source of the organism
is uncertain.
Human infections with Bartonella species other than
B. henselae are poorly understood, although bites or
scratches have been implicated in some cases. One
infection with B. vinsonii subsp. berkhoffii was diagnosed
after a bite from a dog, and another after a bite from a
coyote. A veterinarian became infected with B. vinsonii
subsp. berkhoffii after a needlestick injury acquired while
aspirating a neoplastic mass from a dog. Illness associated
with B. alsatica was reported in a woman who had been
scratched while butchering a wild rabbit. B. quintana
DNA was found by PCR in an asymptomatic woman and
in two feral cats, one of which had bitten the woman. In a
number of these cases, only circumstantial evidence was
available to support the route of transmission. Some
animals could not be tested for Bartonella, while the feral
cats with B. quintana were exposed to the same
environment as the infected woman, and were unavailable
for testing until 3 months after the bite.
Disinfection
Disinfectant susceptibility does not seem to have been
published for Bartonella species including B. henselae, B.
quintana or B. bacilliformis; however, there is no indication
that these organisms are unusually resistant to inactivation.
In many cases, bacteria can be disinfected with 70%
ethanol, 1% sodium hypochlorite and 2% formaldehyde, as
well as phenolic disinfectants, 2% aqueous glutaraldehyde
and peracetic acid (0.001% to 0.2%). Physical methods of
inactivation are moist heat of 121°C, held for 15 to 30
minutes, and dry heat of 160-170°C for 1-2 hours.
© 2012
Infection in Humans
Incubation Period
Cutaneous lesions usually develop at the inoculation
site within 7 to 15 days after exposure, and
lymphadenopathy is typically seen after 1-3 weeks.
However, clinical signs have been reported as soon as 3
days and up to 50 days after exposure.
Clinical Signs
B. henselae appears to infect some immunocompetent
people without causing clinical signs. Most others develop
a self-limiting condition called cat scratch disease.
Immunocompromised individuals infected with B. henselae
may develop a more severe form of cat scratch disease, as
well as bacillary angiomatosis and peliosis hepatis.
Cat scratch disease
In many cases, the first sign of cat scratch disease is the
development of one or more small, reddish-brown,
erythematous papules, pustules, macules, vesicles or ulcers
at the inoculation site. These lesions disappear in 1-3
weeks, and may be mistaken for insect bites; however, they
are not usually pruritic. The characteristic solitary
lymphadenopathy
or
(less
frequent)
regional
lymphadenopathy usually develops within a few weeks of
exposure. Affected lymph nodes are often painful or tender,
and the skin over the nodes can be warm, reddened and
indurated. Cellulitis is, however, rare. Occasionally, the
nodes may suppurate, especially when they are large.
Lymphadenopathy usually lasts for a few weeks to a few
months, and occasionally up to a year. Rarely, enlarged
lymph nodes may persist longer. Cat scratch disease
without lymphadenopathy is possible, but appears to be
unusual in young, healthy patients. It is reported to be more
common in elderly individuals and transplant patients.
Other common symptoms are a low grade fever, malaise
and fatigue. The fever usually disappears within 1-2 weeks
but fatigue may persist for weeks or months. Less often,
there may be other nonspecific signs such as headache,
anorexia, vomiting, nausea, weight loss, generalized pain or
a sore throat.
Complications,
systemic
signs
and
atypical
presentations are reported to occur in at least 5% and
possibly up to 25% of patients, with an increased incidence
in the elderly and people who are immunocompromised.

Parinaud oculoglandular syndrome is the most
common atypical presentation. It is thought to
result from inoculation of the organism into the
eye. This syndrome is characterized by
nonpurulent unilateral conjunctivitis and/or
conjunctival
granuloma,
together
with
preauricular,
submandibular,
or
cervical
lymphadenopathy. It usually resolves in several
weeks without permanent damage.
page 4 of 20
Cat Scratch Disease


Neurological complications are uncommon.
Encephalitis, the most common syndrome, has
been reported in as many as 4-5% of patients in
some series. It typically occurs 1-6 weeks after the
classic symptoms, but cases without lymph node
involvement, as well as cases preceding
lymphadenopathy, have been reported. This
condition may progress rapidly to seizures, coma
with respiratory depression and other severe signs,
but patients usually recover completely without
permanent damage. Cranial or peripheral nerve
involvement is less common than encephalitis. A
wide variety of syndromes, such as transverse
myelitis, transient facial nerve paresis, sensory
loss, alterations in reflexes and motor deficits may
be seen. Some neurological syndromes appear to
be rare, and have been documented in only a few
case reports in the literature.
Ocular complications: Neuroretinitis is an
uncommon but well-recognized condition in cat
scratch disease. It is characterized by the sudden
onset of painless visual loss, usually unilateral.
Although the condition is temporary and resolves
in months, some patients may have residual
defects such as mildly decreased visual acuity, or
abnormal color vision or contrast sensitivity.
Various other ocular conditions such as anterior
uveitis have also been attributed to B. henselae.
Subretinal masses have been reported in HIVpositive patients.

B. henselae bacteremia can result in endocarditis,
most often in people with existing heart valve
abnormalities.

Disseminated disease with granulomatous hepatitis
and/or splenitis has been reported in some patients.
The usual signs are a persistent spiking fever and
abdominal pain. Chills, weight loss, headache and
myalgia may be seen. Lymphadenopathy may or
may not be present. In most cases, the lesions and
symptoms resolve within 6 months.

Arthropathy has been reported in patients infected
with Bartonella. The knee, wrist, ankle and elbow
joints are most often involved. Arthropathy can
persist for weeks after the lymphadenopathy has
resolved.

Osteomyelitis has been reported rarely. The
osteolytic lesions are usually localized to one area,
although cases of multifocal disease have been
reported. The vertebrae and pelvic girdle are
involved most often. The main symptoms are fever
with pain and tenderness over the affected bone.
Patients with bone involvement have usually
recovered completely, although antibiotics were
given in most cases.
© 2012

Various nonspecific rashes are reported
infrequently. They are usually nonpruritic and
resolve in days to weeks.

Pulmonary involvement is rare. In most cases, it
was characterized by pneumonia or pleural
thickening and/or effusion. Patients have usually
recovered completely, with a mean recovery time
of 2 months.

Other complications or syndromes have also been
attributed to B. henselae, based on diagnosis by
serology and/or PCR. They include fever of
unknown origin, thrombocytopenic purpura
(usually transient), hemolytic anemia, vasculitis,
monoclonal gammopathy, biclonal gammopathy
and glomerulonephritis, as well as soft tissue
masses in the mammary gland, the liver or the
spleen that may mimic neoplasia. Septic shock was
reported in a transplant patient. Some of these
complications seem to be rare, and have been
documented in only a few case reports.
Immunocompetent individuals with cat scratch disease
usually recover without antibiotic treatment, and even
complications generally resolve without sequelae. Although
residual deficits have been reported, this is uncommon.
Deaths are very rare. Endocarditis is usually the most
serious concern; however, fatal encephalitis was reported in
one child. In immunocompromised individuals, the clinical
signs may be more severe; complications, bacteremia and
atypical presentations are more common; and most cases
are treated with antibiotics.
Recurrent illness has been described in a few people
with severe signs, including a transplant patient. The
clinical signs recurred at 4-20 month intervals, and
consisted of lymphadenopathy in one patient,
lymphadenopathy and fever in another patient, and fever,
headache, malaise and weight loss in two others.
Bacillary angiomatosis and bacillary peliosis
B. henselae can also cause bacillary angiomatosis
(epithelioid angiomatosis) and peliosis hepatis. Although
rare cases have been reported in immunocompetent
individuals, these conditions occur mainly in those who are
immunocompromised.
Bacillary angiomatosis is a vascular proliferative
disease of the skin and/or internal organs. It is most often an
AIDS-related disease in people with a very low CD4 count.
The most apparent symptoms are one to hundreds of
cutaneous papules and nodules, which may resemble
granulomas, Kaposi’s sarcoma (violaceous nodules), or
lichenoid violaceous plaques. They vary in size from
pinhead-sized to 10 cm in diameter. Subcutaneous nodules
resembling a common abscess may also be seen. In
addition, bacillary angiomatosis can involve the internal
organs including the heart, brain, liver, spleen, bone, larynx,
page 5 of 20
Cat Scratch Disease
lymph nodes and gastrointestinal tract. The symptoms vary
with the organ(s) affected, and may include neurological
signs, bone pain, weight loss or symptoms related to
massive visceral lymphadenopathy.
Peliosis hepatis is a rare condition, caused by B.
henselae as well as other pathogens, drugs and toxins. It is
characterized by vascular proliferation in the liver, which
can result in multiple blood-filled cysts and sinusoidal
dilatation. The symptoms of peliosis hepatis may include
fever, weight loss, abdominal pain, nausea, vomiting,
diarrhea and hepatosplenomegaly. In some cases, this
condition may be an incidental finding at necropsy. Peliosis
hepatis can be seen in some patients with bacillary
angiomatosis.
based on serology alone. The signs consisted of
papules at the inoculation site, fever and regional
lymphadenopathy. The organism was not cultured
or detected by PCR.

Regional lymphadenopathy was associated with B.
alsatica infection in an elderly woman who had
been scratched while butchering a wild rabbit.
Bacteria consistent with Bartonella were identified
by Warthin-Starry silver staining in the enlarged
lymph node, and these bacteria stained for B.
alsatica by immunohistochemistry. PCR on the
lymph node was also positive for this organism.
Her condition responded to doxycycline.

B. rochalimae was isolated from the blood of a
person who developed an acute febrile illness with
a diffuse macular rash, mild anemia and
splenomegaly, soon after returning to the U.S.
from a trip to South America. The infection
responded to a short course of levofloxacin. A
macaque that was inoculated with this organism
had bacteremia and a decreased hematocrit.

B. washoensis was isolated from the blood of a
woman with fever, chills, headache, nausea, joint
pain, an episode of vomiting, epigastric and lower
left sided abdominal pain, and signs of meningitis.
The symptoms improved after treatment with
moxifloxacin, but persistent body aches and bone
pain were still reported after 2 months.

Both B. melophagi and B. henselae were isolated
from the blood of a person who developed a
relatively large (“hand-sized”), nonpruritic, red,
cutaneous plaque, followed by a febrile illness
with neutropenia, myalgia, neurological signs and
joint pain. The illness waxed and waned at 3-4
week intervals. A heart murmur with mild aortic
insufficiency and mild mitral regurgitation were
also identified. Babesia microti, Anaplasma
phagocytophilum and Borrelia burgdorferi were
ruled out. Some improvement was seen with drugs
effective
for
Bartonella
(rifampin
and
azithromycin), but the symptoms did not resolve
until cefuroxime was also added. In another case
reported in the same paper, B. melophagi was
isolated from the blood of a woman who had
residual fatigue and muscle weakness, 6 months
after an episode of pericarditis of uncertain
etiology. No further information was given for the
second case.

B. tamiae was cultured from the blood of three
patients enrolled in a prospective study to
determine the etiology of febrile illnesses in
Thailand. The clinical signs consisted of fever and
nonspecific signs such as fatigue and headache, as
well as anemia and mild liver function
abnormalities. One patient had a maculopapular
Other zoonotic Bartonella
Additional zoonotic Bartonella spp. have been reported
in people with various illnesses. A number of these case
reports are described below. The type of evidence presented
for the involvement of Bartonella in the condition, as well
as the strength of the evidence, varies between cases.



Endocarditis has been attributed to several species
of Bartonella, and might also be caused by others.
This condition occurs most often in people with
pre-existing abnormalities of the heart valves.
Most cases have been caused by B. henselae or the
human pathogen B. quintana, but culture or PCR
evidence has linked B. elizabethae, B. koehlerae,
B. vinsonii subsp. berkhoffii, B. vinsonii subsp.
arupensis, B. washoensis and B. alsatica to a few
cases. Additional cases have been diagnosed based
on serology alone.
A B. vinsonii subsp. berkhoffii infection was
reported in a veterinarian who sustained a
needlestick injury while aspirating a neoplastic
mass from a dog. There was no evidence of
infection 5 days after exposure, but DNA from the
organism was detected in the veterinarian’s blood
at 34 days, after he reported frequent headaches,
fatigue and intermittent paresthesia. B. vinsonii
subsp. berkhoffii was also isolated from his blood,
and seroconversion occurred. The symptoms
resolved after treatment with doxycycline and
rifampin. While the evidence suggests that the dog
was the source of the infection, this could not be
proved. Only one tissue sample was available for
testing from the dog, and although B. vinsonii
subsp. berkhoffii DNA was detected, it was of a
different genotype. Antibodies to B. vinsonii
(subspecies not identified) were also found in a
child with fever and regional lymphadenopathy,
who had been bitten by a dog (of unknown
Bartonella status) 3 weeks earlier.
B. clarridgeiae was suggested as the cause of cat
scratch disease symptoms in at least three people,
© 2012
page 6 of 20
Cat Scratch Disease
rash that had lasted 22 days, while another had a
transient petechial rash. The report did not indicate
whether the patients responded to antibiotics, or
what other agents were ruled out. However, the
organisms isolated from all three patients caused
illness when inoculated into mice, and DNA was
detected in the lesions in these animals. PCR
assays detected DNA from B. vinsonii subsp.
arupensis, B. elizabethae, B. rattimassiliensis and
B. tribocorum in other febrile patients in this
study. Further investigations of the latter cases
have not been published.

B. vinsonii subsp. arupensi was isolated from the
blood of a U.S. cattle rancher who had high fever,
headache, myalgia and neurological signs. The
condition responded to treatment with ceftriaxone
and prednisone. The rancher had a history of a
relapsing rheumatologic syndrome with vasculitis
and neurological signs, which was responsive to
corticosteroids. The authors of this study
concluded that his symptoms were consistent with
his previously diagnosed condition, and the
contribution of the Bartonella to the symptoms
was uncertain.
Communicability
There is no evidence that B. henselae infections can be
transmitted from person to person by casual contact.
B. henselae was cultured from human RBC units that
had been inoculated with this organism and stored at 4ºC
for 35 days. The authors of this study suggest that blood
transfusions might be able to transmit this organism.
Diagnostic Tests
Cat scratch disease is often diagnosed by the history
and physical examination, with supporting evidence from
laboratory tests. Providing definitive evidence for the
involvement of Bartonella spp. in a medical condition may
be difficult. Diagnostic tests for this organism have
limitations, and many healthy people are seropositive.
Bartonella spp. can sometimes be cultured from blood
or tissues; however, these organisms are fastidious and
isolation can be difficult. Conventional blood cultures from
immunocompetent patients without systemic disease are
often negative for B. henselae. Bartonella are usually
cultured on specialized media such as fresh chocolate agar
or brain–heart infusion agar enriched with blood. Some new
media introduced in research laboratories or reported in the
literature may increase the probability of detecting these
organisms. B. henselae can take from 9 days to 6-8 weeks
to form visible colonies. Multilocus sequence typing
(MLST) and multiple locus variable number tandem repeat
analysis (MLVA) have been used to identify genotypes of
B. henselae.
© 2012
PCR assays are also available, and can differentiate
species of Bartonella. PCR is sometimes negative in
infected individuals.
Serological tests for B. henselae include various
indirect immunofluorescence assays and enzyme-linked
immunosorbent assays (ELISAs). A fourfold rise in titer or
the presence of IgM suggests a recent infection. IgM
antibodies to B. henselae have been reported to persist for
less than three months, while IgG may be detected for more
than two years. Cross-reactions can occur between species
of Bartonella. Cross-reactions have also been reported with
other organisms such as Chlamydia spp. and Coxiella
burnetii.
Biopsies are not used routinely for cat scratch disease,
but they may be employed in some instances (e.g., when
neoplasia must be ruled out). Histopathology is suggestive
but not diagnostic. The lesions of cat scratch fever and
bacillary angiomatosis differ; cat scratch fever is
characterized by stellate abscesses, granulomas and
lymphocytic infiltrates, while vascular proliferation is seen
with bacillary angiomatosis. Organisms may be detected in
tissues with Warthin-Starry silver stain and Brown-Hopps
Gram stains. Bartonella spp. are Gram negative, small,
curved, pleomorphic rods. Immunostaining has been used
to identify the bacteria, especially in research.
Imaging studies can aid the diagnosis of hepatosplenic
involvement and other complications.
Skin testing, using crude lymph node antigens, was
employed in the past, but is no longer recommended. This
technique was abandoned due to fears of transmitting other
infectious agents such as hepatitis viruses. It was also
poorly standardized, and less specific and sensitive than
serology.
Treatment
Immunocompetent patients
Most cases of cat scratch disease in immunocompetent
individuals are self-limiting. Treatment is usually
supportive and symptomatic. Suppurating nodes may be
aspirated to remove pus and reduce the pain. Severely
affected lymph nodes or persistent ocular granulomas are
occasionally excised. Although B. henselae is sensitive to a
number of antimicrobials in vitro, antibiotics are not
consistently effective for cat scratch disease in
immunocompetent individuals. Antibiotics (azithromycin)
were demonstrated to reduce lymph node size in some
patients in one randomized, double blind study, although
this drug did not decrease the duration of the illness or have
any other effect on clinical signs. Other evidence for
antibiotic use in uncomplicated cases is limited or
anecdotal, and some studies have demonstrated no benefit.
Serious, potentially life-threatening complications,
such as Bartonella endocarditis, are treated with antibiotics.
Surgical excision and replacement of the involved valve
may also be necessary. Patients with non-life-threatening
page 7 of 20
Cat Scratch Disease
complications are sometimes treated with antibiotics, even
when there is no evidence of immunosuppression. This is
usually
based
on
the
good
responses
of
immunocompromised individuals to these drugs (see
below). However, some physicians may recommend only
conservative treatment for complications that usually
resolve on their own.
Morbidity and Mortality
Although antibodies to B. henselae are expected to be
more common in people exposed to cats, the seroprevalence
rates reported in high risk groups vary widely. A study from
Poland detected antibodies to B. henselae in 45% of
veterinarians, 53% of cat owners and 48% of homeless
alcoholics. The seroprevalence rate in veterinarians was
15% in Japan, while a U.S. study found that 7% of
veterinarians had antibodies to either B. henselae or B.
quintana. In contrast, antibodies to B. henselae were
detected in only 2% of people associated with the
veterinary profession in Taiwan, although 24% of cats were
seropositive. A study from Austria reported that the
seroprevalence was 23% in the general population, with no
statistically significant correlation between seroprevalence
and pet ownership or residence in a rural environment.
Similarly, there was no statistically significant difference
between people with or without exposure to cats in Greece,
where the seroprevalence was 20% in healthy populations.
Relatively few surveys have studied exposure to other
Bartonella species. Antibodies to B. elizabethae are
common in some areas. In Sweden, 14% of healthy blood
donors had antibodies to this organism, while
approximately 3% had antibodies to B. grahamii and 3% to
B. henselae, and no donors were seropositive for B. vinsonii
subsp. vinsonii. Antibodies to B. elizabethae were detected
in approximately 10% of patients presenting to rural
hospitals in Thailand, although only 4% had antibodies to
B. henselae and 4% to B. vinsonii subsp vinsonii. Among
intravenous drug users in the inner city area of Baltimore,
Maryland, 33% had antibodies to B. elizabethae and 11% to
B. henselae. One U.S. study reported that 57% of a
population with more than 10 years of occupational animal
exposure had antibodies to B. henselae, B. quintana or B.
vinsonii subsp. berkhoffii. In this study, B. henselae or B.
vinsonii subsp. berkhoffii was also detected by PCR (or
isolated, in a few cases) in all study participants. The source
of the participants was not specified; however, all reported
intermittent or nonspecific chronic symptoms such as
headache, fatigue, arthralgia, myalgia and ataxia.
Exposure to Bartonella spp.
Antibodies to B. henselae seem to be relatively
common in human populations, and in some studies, most
seropositive individuals report no apparent history of cat
scratch disease. A number of studies, conducted in several
countries, found seroprevalence rates varying from less than
1% to 25% or more in the general population. One study
from Italy reported an unusually high rate of reactors:
antibodies to B. henselae were detected in approximately
62% of children and adolescents who presented as
outpatients to a clinic for health check-ups or minor
illnesses, and who had no symptoms that might indicate
bartonellosis. In this study, 8.5% of the participants had
high titers, suggesting recent or ongoing infections. A study
from Chile found antibodies in 13% of children, and 10%
of technical and professional workers who cared for cats.
Illness
Cat scratch disease is not reportable in any country,
and the incidence of illness is uncertain. The high
seroprevalence in healthy people may indicate that
asymptomatic or mild infections with B. henselae are
common. One 1993 study, however, estimated that 22,00024,000 cases of cat scratch disease may occur each year in
the U.S. Most clinical cases are thought to involve children,
although an increasing number have been identified in
adults. In the U.S., cat scratch disease is most frequently
seen between July and January, with the greatest number of
hospitalizations between July and October. In France, one
study found that the highest incidence was from September
to April, with a peak in April. Seasonality in temperate
regions in thought to be caused by the seasonal
concentration of births, the acquisition of kittens as pets,
Immunocompromised patients
B. henselae infections in immunocompromised
patients, including bacillary angiomatosis, usually respond
well to various antibiotics. Uncomplicated cat scratch
disease is treated in most cases, due to the elevated
susceptibility to severe illness and complications.
Prolonged treatment (4-6 months) has been used in patients
who relapse.
Prevention
Bites and scratches from cats, particularly kittens,
should be avoided. Rough play with kittens is inadvisable,
and any bites or scratches should immediately be washed
with soap and water. Declawing does not appear to affect
transmission, but keeping the nails clipped has been
suggested by some sources. Cats should be discouraged
from licking a person’s skin, particularly the eyes, face and
areas with abrasions or other open wounds. Hand washing
after contact with a cat might be helpful.
The ability of cats to transmit B. henselae is transient,
and authorities do not recommend removing them from the
household. The efficacy of antibiotics in eliminating B.
henselae bacteremia in cats is uncertain (see Treatment in
Animals, below). The 2009 Guidelines for Preventing
Opportunistic Infections Among HIV-infected Adults and
Adolescents note that there is no evidence that routine
culture or serological testing of healthy cats for Bartonella
provides any benefit for owners. Flea control decreases the
risk that household cats will acquire B. henselae or transmit
it to other cats.
© 2012
page 8 of 20
Cat Scratch Disease
and peaks in the flea population. Cat scratch disease is not
thought to be seasonal in tropical regions.
In immunocompetent individuals, cat scratch disease is
usually self-limiting and benign, although the symptoms
may last for 1-5 months and occasionally longer.
Significant illness is reported to occur in 5-10% of cases,
usually from neurological signs or multisystem
disseminated disease. Nearly all individuals, including
those with neurological involvement, recover fully, and
deaths are very rare. Endocarditis is usually the most
serious complication. It has a reported prevalence of 0-3%
in northern and central Europe (studies in France, Germany,
Sweden and the U.K.), and 10% or greater in northern
Africa. Reinfection seems to be infrequent.
Complications, systemic illnesses and bacillary
angiomatosis are more likely to develop in people who are
immunocompromised. Bacillary angiomatosis and other
conditions can be fatal in this population if left untreated.
However, most immunocompromised individuals recover
fully, provided the disease is treated appropriately. In one
review, 28% of solid organ transplant recipients developed
localized cat scratch disease, and 72% had disseminated
infections. In this study, all patients with cat scratch disease
and 19 of 21 patients with disseminated bartonellosis were
cured with antibiotics. Two cases of endocarditis were fatal.
Infections in Animals
Species Affected
Bartonella henselae
Cats and other felids are the reservoir hosts for B.
henselae. Organisms have been detected, by culture or
PCR, in domesticated cats, cheetahs (Acinonyx jubatus),
African lions (Panthera leo), cougars (Felis concolor; also
known as pumas or mountain lions), bobcats (Lynx rufus)
and wildcats (Felis silvestris). B. henselae has also been
reported occasionally, by PCR or culture, in dogs, horses,
cattle, feral pigs, seals, whales and porpoises Armadillos
are susceptible to experimental infection. Mice can be
infected under some laboratory conditions.
Bartonella clarridgeiae and Bartonella koehlerae
Cats are thought to be the reservoir hosts for B.
clarridgeiae and possibly B. koehlerae. Both organisms
have been detected rarely in dogs. DNA from B. koehlerae
was found in feral pigs.
Bartonella vinsonii subsp. berkhoffii
B. vinsonii subsp. berkhoffii infects dogs and wild
canids including coyotes (Canis latrans), gray foxes
(Urocyon cinereoargenteus) and island foxes (Urocyon
litorralis). This organism is thought to maintained in
canids, and both dogs and coyotes have been suggested as
reservoir hosts. DNA from B. vinsonii subsp. berkhoffii was
detected in a horse and in feral pigs.
© 2012
Bartonella rochalimae
B. rochalimae has been found in dogs and wild canids,
including red foxes (Vulpes vulpes), gray foxes, island
foxes, coyotes and a wolf (Canis lupus), as well as in
raccoons (Procyon lotor) and various rodents including rats,
shrews and gerbils.
Bartonella bovis and Bartonella chomelii
Cattle are the reservoir hosts for B. bovis (formerly B.
weisii). This organism has been isolated or detected by PCR
in a few cats and dogs, and some asymptomatic horses were
seropositive. B. chomelii has been found in cattle.
Bartonella melophagi
B. melophagi has been reported in sheep.
Bartonella alsatica
B. alsatica has been found in rabbits.
Bartonella capreoli and Bartonella
schoenbuchensis
B. capreoli and B. schoenbuchensis have been detected
in deer. B. capreoli has also been isolated from elk (Cervus
elephas), and B. schoenbuchensis from a cow.
Bartonella species found in rodents
Numerous Bartonella species have been detected in
mice, rats, voles, shrews, ground squirrels, chipmunks,
gerbils, jerboas, jirds and other rodents. Bartonella spp.
reported to have rodent reservoir hosts include B. vinsonii
subsp. arupensis, B. vinsonii subsp vinsonii, B. birtlesii, B.
doshiae, B. peromysci, B. phoceensis, B. rattimassiliensis,
B. talpae, B. taylorii, B. tribocorum, B. grahamii, B.
elizabethae, B. queenslandensis and B. washoensis, as well
as newly proposed species such as B. japonica sp. nov. and
B. silvatica sp. nov. B. vinsonii subsp. arupensis, B.
elizabethae, B. grahamii, B. taylorii and B. washoensis
have also been detected in a few dogs. Many cats in
Sweden are seropositive for B. elizabethae.
Bartonella tamiae
The reservoir host for B. tamiae is not known, although
rats have been proposed. Isolates from humans caused
illness in experimentally infected laboratory mice.
Bartonella quintana
B. quintana, a pathogen maintained in human
populations, has been reported from a few cats and dogs.
Bartonella in other animals
Bartonella species or their DNA have also been
detected in other mammals including North American river
otters, kangaroos, wild badgers (Meles meles) and bats.
Incubation Period
In experimentally infected cats, cutaneous lesions may
appear at the inoculation site within 2 days. Fever was first
seen 2 to 16 days after inoculation.
page 9 of 20
Cat Scratch Disease
Clinical Signs

B. henselae infections were reported in two cats
with fatal pyogranulomatous myocarditis and
diaphragmatic myositis at an animal shelter. Ten
cats at this shelter developed fever, lethargy and
diarrhea after a litter of flea-infested cats entered
the facility. Feline leukemia virus (FeLV), feline
panleukopenia virus, and feline immunodeficiency
virus (FIV) were ruled out. One kitten died after
developing acute respiratory distress, and an 8month-old cat, which had been in contact with the
litter, died acutely 2 weeks later. Bacteria were
found in inflammatory foci in the heart of both
cats, as well as the diaphragm of one cat. These
bacteria were identified as B. henselae by
immunohistochemistry. PCR detected B. henselae
DNA in the heart of one cat, and in multiple
tissues including heart and diaphragm of the other
cat.

B. vinsonii subsp. berkhoffii was detected in
lesions from a cat with recurrent osteomyelitis.
Salmonella enterica subsp. enterica was also
isolated from a bone marrow aspirate. The
condition
responded
to
treatment
with
azithromycin and amoxicillin-clavulanate.

A number of studies have investigated whether B.
henselae might be associated with stomatitis or
gingivitis. In a study from Japan, the incidence of
lymphadenopathy and gingivitis was significantly
increased in cats seropositive for both FIV and B.
henselae, compared to cats with antibodies only to
FIV. A Swiss study reported a correlation between
seropositivity to B. henselae and stomatitis. In a
recent study that examined sick cats presented to a
U.S. referral hospital, Bartonella was cultured
more often from the blood of cats with
gingivostomatitis than cats without this condition,
although there was no correlation with
seropositivity for B. henselae or B. clarridgeiae.
However, one study reported no statistically
significant relationship between gingivostomatitis
and the prevalence of Bartonella DNA in blood
samples, while another found no correlation with
DNA in oral swabs. Similarly, a study of healthy
shelter cats found no significant correlation
between stomatitis and the prevalence of either
antibodies to Bartonella spp. or DNA, when pairmatched samples were analyzed.

One study reported that the presence of antibodies
to B. henselae was correlated with an increased
incidence of various unspecified urinary tract
diseases. A newer study found a weak association
between seropositivity, but not bacteremia, and
idiopathic lower urinary tract disease. In this
study, there was no correlation with urolithiasis or
chronic kidney disease.
The importance of Bartonella spp. as pathogens in
animals is still unclear. Most infections appear to be
asymptomatic. Some experimental infections, case reports
and studies have suggested possible links to disease, but
other studies have been unable to substantiate a role for
Bartonella. Investigations are complicated by the high
prevalence of infections in healthy animals, the
uncertainties in diagnostic testing for these organisms, and
the possibility of co-infection with other microorganisms.
Cats
Naturally-infected bacteremic cats are usually
asymptomatic. Some studies have suggested that B.
henselae might be pathogenic under some circumstances,
but at present, definitive evidence is lacking.
In experimental studies, most cats inoculated with B.
henselae remained asymptomatic or had only mild clinical
signs. In one experiment, cats developed inflammatory
swellings or pustules at the inoculation site. Other clinical
signs reported in experimentally infected cats were
lymphadenopathy, myalgia and transient fever with
lethargy and anorexia during febrile periods. Transient mild
behavioral or neurological dysfunction, consisting of
disorientation, nystagmus, hypersensitivity to stimuli,
decreased responsiveness to environmental stimuli, or
increased aggressiveness, as well as mild transient anemia,
eosinophilia, and reproductive disorders have also been
reported. In a recent study, no cats inoculated intravenously
with B. henselae became ill, although bacteremia was
detected in all cats. However, 3 of 6 cats exposed to B.
henselae-infected fleas developed fever and inappetence.
One of these cats was euthanized, as it became severely ill,
and myocarditis was found at necropsy. There was some
evidence that this cat may have failed to mount an adequate
immune response: it had the lowest IgM titer to Bartonella,
and was the only cat that did not have detectable IgG to this
organism.
No clinical signs have been reported in cats inoculated
with B koehlerae or B. rochalimae. Two cats inoculated
with B. quintana seroconverted with no evidence of
bacteremia.
A limited number of case reports and case series in
naturally infected cats suggest that B. henselae or other
Bartonella species might cause disease. Other studies have
found no link to illness.

A few case reports have attributed cardiac
conditions, especially endocarditis, to Bartonella.
B. henselae DNA was detected by PCR in the
diseased heart valves of two cats that died of
endocarditis. B. henselae was also isolated from
the blood of a young cat with aortic valve
endocarditis, and antibiotic treatment resulted in
total resolution of the heart murmur and valvular
lesion.
© 2012
page 10 of 20
Cat Scratch Disease



A possible association between B. henselae and
uveitis was proposed, after antibodies to this
organism were found in the serum and aqueous
humor of an immunocompetent cat with uveitis,
which responded clinically to doxycycline. In a
follow-up study, anti-Bartonella IgG was found in
the aqueous humor of 7 of 49 client-owned cats
with uveitis, and 0 of 49 healthy shelter cats. Four
of 9 experimentally infected cats also had IgG
antibodies in the aqueous humor. Uveitis was not
correlated with antibodies in the serum. Two
newer studies were unable to substantiate a link
between uveitis and either seroprevalence or
bacteremia. Unexplained cataracts were reported
in SPF cats from a commercial vendor within a
year after the cats became naturally infected with
Bartonella. The relationship between the cataracts
and the infection (if any) is not known, and this
association may be coincidental.
One study found no correlation between
neurological signs and B. henselae or B.
clarridgeiae bacteremia. There was also no
correlation with antibodies to these organisms.
Another study detected no difference in
seroprevalence or the magnitude of antibody titers
to B. henselae, in a comparison of cats with
neurological disease, cats with non-neurological
illnesses and healthy cats, when age and flea
exposure were controlled. However, one
retrospective study reported evidence of local antiBartonella antibody production in the central
nervous system (CNS). These antibodies were
detected in 31% of cats that had neurological signs
together with serological or DNA evidence of
Bartonella infection. A small number of cats had
both B. henselae DNA in the CSF and Bartonellaspecific IgG in the cerebrospinal fluid. The
findings are not conclusive, as Bartonella DNA
can also be found in the brain of healthy cats;
however, the authors suggest that further studies
might be warranted.
Studies reported no evidence for B. henselae in the
lesions from 26 cats with peliosis hepatis, or 14
cats with plasmacytic pododermatitis. One study
reported no evidence for Bartonella as a cause of
chronic rhinosinusitis in cats.
Dogs
No clinical signs other than transient fever were
reported in dogs inoculated with B. vinsonii subsp.
berkhoffii. Two dogs inoculated with B. rochalimae also
remained asymptomatic, with the exception of
inflammation at the inoculation site. However, Bartonella
spp. have been suggested as possible etiologic agents in
some case reports. As with cats, it is difficult to establish a
© 2012
causative role, especially for organisms maintained in dogs,
such as B. vinsonii subsp. berkhoffii.

Bartonella spp. have been detected, by PCR or
culture, in a few cases of endocarditis in dogs.
Reported organisms include B. vinsonii subsp.
berkhoffii, B. henselae, B. clarridgeiae, B.
washoensis, B. quintana and B. rochalimae. B.
koehlerae DNA was found in the aortic valve of
another dog that died of endocarditis; however, E.
coli was also cultured from aortic valve tissue.
Additional
cases
of
Bartonella-associated
endocarditis have been suggested based on
serology alone. B. vinsonii subsp. berkhoffii was
implicated in a case of myocarditis.

One dog infected with B. vinsonii subsp. berkhoffii
developed clinical signs resembling human
bacillary angiomatosis, after treatment with
immunosuppressive drugs for pancytopenia. The
condition was characterized by widespread, round
to oval, erythematous, angioproliferative skin
nodules. B. vinsonii subsp. berkhoffii DNA was
found in the skin lesions, as well as in the blood.
Bacteria consistent with Bartonella were also
detected in the lesions, although some bacteria
were either close to or within the endothelial cells.
Azithromycin treatment was effective, with
clinical resolution beginning within 2 days of
starting the antibiotic.

Bartonella spp. DNA was detected in the enlarged
submandibular lymph node from a dog that
developed fever, facial and cervical edema, and
granulomatous lymphadenitis of the left regional
lymph nodes, soon after a tick bite to the ear.
Bacteria consistent with Bartonella were also
detected in the node by Warthin–Starry silver
staining. The dog did not have antibodies to
Ehrlichia canis, Babesia canis, Rickettsia rickettsii
or various fungi, but it was seropositive for B.
vinsonii subsp. berkhoffii. Treatment with
enrofloxacin for three weeks resulted in resolution
of the fever and edema, and decreased lymph node
size.

Bartonella spp. were detected in a few case reports
of liver disease. B. henselae DNA was found in the
liver of one dog with peliosis hepatis (blood-filled
cysts and cavities in the liver). DNA from this
organism was also identified in two dogs with
granulomatous hepatitis. Both dogs were treated
with antibiotics for bartonellosis. One dog
progressed to hepatic cirrhosis in spite of
treatment. The other dog improved clinically,
although the clinical signs appeared to recur when
it was taken off azithromycin. It was apparently
stable on this drug for approximately a year, then
deteriorated and was euthanized. Other drugs and
page 11 of 20
Cat Scratch Disease
vitamins had also been administered by the owner.
Limited necropsy results suggested death might
have been caused by a toxic insult to the liver. B.
clarridgeiae DNA was found in the liver of a dog
with lymphocytic hepatopathy. This dog
responded to treatment with azithromycin (for
bartonellosis), prednisone and other drugs, and
remained well for a year, but then developed signs
consistent with liver failure before being lost to
follow-up.


In a dog with pyogranulomatous lymphadenitis,
arthritis consistent with immune-mediated
polyarthropathy, protein-losing nephropathy and
conjunctivitis, B. henselae DNA was found in
blood samples and in an affected lymph node. The
dog had no antibodies to Bartonella or to several
other organisms (Anaplasma phagocytophilum,
Borrelia
burgdorferi,
Dirofilaria
immitis,
Ehrlichia canis and Rickettsia rickettsii), and
culture of the joints was negative. The
conjunctivitis in one eye initially worsened despite
treatment with carprofen, doxycycline, enalapril
and an ophthalmic solution containing neomycin,
polymyxin, and dexamethasone. However, all
clinical signs later resolved after a 6-week course
of doxycycline. Another case of pyogranulomatous
lymphadenitis attributed to Bartonella was based
on positive serology and the detection of B.
henselae DNA in blood and lymph nodes, together
with negative bacterial and fungal cultures and the
exclusion of seroreactivity to various fungi and
Anaplasma
phagocytophilum,
Borrelia
burgdorferi, E. canis, and R rickettsii. The dog
was treated with a number of antibiotics over the
course of the illness. Initial treatment with
enrofloxacin, metronidazole and carprofen was
unsuccessful; however, the clinical signs later
resolved with a 7-day course of enrofloxacin and
carprofen. When signs recurred 4 months later, the
dog was treated for Bartonella with azithromycin
and doxycycline. This resulted in limited
improvement, but the clinical signs resolved with
the addition of an immunosuppressive dose of
prednisone.
B. henselae and B. vinsonii subsp. berkhoffii were
both isolated from the blood of a 4-year-old dog
with a 2-year history of joint pain progressing to
pelvic limb ataxia and refusal to walk. B. vinsonii
subsp. berkhoffii was isolated from joint fluid. The
condition was partially responsive to non-steroidal
anti-inflammatory medications, and became
progressively worse despite treatment with
antibiotics for bartonellosis, including two 7-week
courses of azithromycin. Bartonella spp. were still
isolated from the blood and synovial fluid after
treatment.
© 2012

Other case reports in the literature describe the
isolation of B. vinsonii subsp. berkhoffii, or its
detection by PCR, in syndromes as diverse as
neoplasia, seroma after a traumatic injury, and
panniculitis.

One retrospective survey reported the diagnostic
findings in sick dogs that also had antibodies to B.
vinsonii subsp. berkhoffii. The diagnoses
encompassed a diverse group of conditions, with
most syndromes reported in only one to a few
dogs. They included endocarditis, myocarditis,
lymphadenitis, polyarthritis, cutaneous vasculitis,
meningoencephalitis and other neurological
syndromes,
immune-mediated
hemolytic
anemia/immune thrombocytopenia, and ocular
signs (anterior uveitis, chorioretinitis, ocular
hemorrhage, and retinal detachment associated
with hypertension). Thrombocytopenia was
detected in approximately half of the dogs, and
anemia in a third. A wide variety of antibiotics
were used, and most but not all cases responded to
treatment. After treatment, titers to Bartonella
were no longer detected in the subset of cases
where titers were measured. Whether Bartonella
had a role in any of the cases was not established.

In one case report, B. vinsonii subsp. berkhoffii
DNA was found in a granulomatous nasal mass
from an afebrile dog with rhinitis and proteinlosing nephropathy. No bacteria could be
identified in the lesion by any technique, including
Warthin–Starry silver staining. The dog had
antibodies to both B. vinsonii subsp. berkhoffii and
Ehrlichia canis, and E. canis DNA was detected in
the blood 9 months after the mass was removed.
The clinical signs resolved after removal of the
mass and treatment with doxycycline for 30 days.
In a recent case control study of dogs with
idiopathic rhinitis, no dogs had antibodies to B.
henselae or B. vinsonii subsp berkhoffii, and there
was no evidence for these organisms by PCR. This
study does not rule out the possibility that some
cases of rhinitis are caused by Bartonella, but
suggests that it is not a common etiology.
Cattle
The effect of Bartonella infections in cattle, if any, is
unknown. Because B. bovis is very common in some herds,
it is difficult to attribute clinical signs to this organism. B.
bovis was suggested as the cause of endocarditis in two
older cows. These animals had high antibody titers to this
organism, and DNA was detected in the lesions. One study
of a dairy herd suggested that adverse effects on health and
reproductive success are uncommon. In this herd, there was
no correlation between bacteremia and milk yield, milk cell
count or various parameters of reproductive success. Fewer
page 12 of 20
Cat Scratch Disease
bacteremic cows retained the placenta, and the interval
from calving to first artificial insemination was shorter.
Horses
Four horses inoculated intradermally with an equine
isolate of B. henselae developed injection site reactions
(mild edema, sensitivity and pruritus, sometimes
accompanied by purulent drainage), and had mild,
nonpainful, unilateral enlargement of the regional lymph
node, without fever. Three of the horses also had mild to
moderate limb edema. One of these horses had evidence of
concurrent infection with B. vinsonii subsp. berkhoffii,
apparently acquired during the experiment. In the same
experiment, four horses inoculated intradermally with a
bovine isolate of B. bovis had milder injection site reactions
consisting of sensitivity and mild edema. Two horses
developed mild, unilateral, nonpainful regional enlargement
of the regional lymph node, two horses had nonpruritic
urticaria, and one horse had mild colic and mild hind limb
edema. However, only one horse had evidence of infection
with B. bovis (transient low titers to this organism).
Possible involvement of B. henselae was suggested in a
few case reports:

B. henselae DNA was detected in the tissues of an
aborted equine fetus that had necrosis and
vasculitis in multiple tissues. Gram-negative
bacteria, which stained with Warthin-Starry silver
stain and labeled with a monoclonal antibody to B.
henselae, were found in many of the inflammatory
lesions. No known agents of equine abortion could
be detected in this fetus. The mare had no history
of clinical signs or prior abortions. Other mares on
the same farm successfully carried foals to term.

In one report, B. henselae was detected in blood
samples from a horse with chronic arthropathy and
another horse with vasculitis. Whether Bartonella
had any role in these conditions is unclear. The
horse with vasculitis had a high antibody titer to
Streptococcus equi, and was diagnosed as having
purpura hemorrhagica. In the horse with chronic
arthropathy, the clinical signs did not resolve after
treatment with antibiotics effective against
Bartonella.
Rodents
Experimentally infected rodents have remained
asymptomatic in some studies. Granulomatous hepatitis
was the only necropsy lesion in rodents inoculated with
large numbers of bacteria. However, the incidence of fetal
death and placental vasculitis was increased in mice
infected with B. birtlesii. Inoculation of mice with two B.
tamiae isolates from humans resulted in axillary and
inguinal lymphadenopathy, ulcerative skin lesions and
subcutaneous masses on the thorax. Myocarditis,
lymphadenitis with vascular necrosis, and granulomatous
hepatitis and nephritis were reported at necropsy. Mice
© 2012
inoculated with another human isolate of B. tamiae (from a
patient with less severe symptoms) developed dermatitis
and granulomas in the kidneys, but did not have
lymphadenitis.
Non-human primates
In one experiment, simian immunodeficiency virus
(SIV)-infected macaques inoculated with B. henselae
remained asymptomatic. These monkeys did not become
bacteremic or seroconvert. In another experiment, two
macaques became febrile and developed subcutaneous
purple-red spots at the inoculation site. The significance of
this finding is unclear, as B. henselae was not recovered
from the regional lymph nodes and the animals did not
seroconvert.
Communicability
B. henselae does not seem to be transmitted between
cats by casual contact, in the absence of fleas. Infected cats
can infect humans with B. henselae, via scratches and bites.
Other animal species also seem to be able to transmit
Bartonella to humans.
Diagnostic Tests
A number of tests can be used to detect infection with
Bartonella spp. Culture of blood or other tissues is the most
definitive method; however, organisms cannot always be
isolated from infected animals. Bartonella spp. may be
easier to culture from some hosts (e.g., B. henselae in cats)
than others. Even in cats, several attempts may be necessary
to detect bacteria in the blood, as bacteremia can be
intermittent. Bartonella spp. are fastidious, and isolation
requires specialized media such as fresh chocolate agar or
brain–heart infusion agar enriched with blood. Visible
colonies of B. henselae usually develop in 9 days to 6-8
weeks. Some new media introduced in research laboratories
or reported in the literature may improve isolation of
Bartonella spp., especially in species other than the
reservoir hosts. In specialized laboratories, genotypes of B.
henselae can be identified by multilocus sequence typing
and multiple locus variable number tandem repeat analysis.
PCR assays are commonly used to detect Bartonella
spp. in research, and may be available in some laboratories.
One sensitive technique employs isolation in a Bartonella
α-Proteobacteria growth medium (BAPGM) based
enrichment culture, followed by multiplex real-time PCR.
Contamination with flea feces on the skin, or other sources
of Bartonella organisms or DNA, can cause false positive
results in PCR tests and culture. PCR inhibitors may be
present in some biological samples.
Immunocytochemical
and
immunohistochemical
methods can detect Bartonella spp. in lesions. These tests
may not be available outside research laboratories.
Serological
tests
for
B.
henselae
include
immunofluorescent antibody, ELISA and immunoblotting
(Western blotting); however, there is only limited
page 13 of 20
Cat Scratch Disease
experience with immunoblotting. In cats with uveitis, tests
should include the demonstration of intraocular Bartonellaspecific antibody production. False-positive test results
appear to be common in all serological assays, and authors
recommend the use of serology in conjunction with blood
culture or PCR testing. Some infected cats and dogs do not
have antibodies to Bartonella, although the organism can be
identified in blood and/or tissues by culture or PCR.
Conversely, IgG antibodies to Bartonella can persist in
infected animals even after the infection has been cleared.
Treatment
Treatment is usually recommended only for animals
that are ill. Antibiotic resistant isolates of Bartonella spp.
have occasionally been reported.
Routine treatment of asymptomatic, bacteremic cats is
not recommended as a method of zoonosis prevention. No
treatment regimen is proven to be consistently effective in
eliminating B. henselae bacteremia in cats, although some
antibiotics have apparently been successful in individual
animals. Documenting clearance of the organism is
difficult, because bacteremia fluctuates. Routine treatment
might also promote the generation of antibiotic-resistant
strains. Animals that have eliminated the organism,
including cats, may be reinfected with other Bartonella
species, and sometimes by different genotypes or strains.
Prevention
Flea control decreases the risk of B. henselae
transmission between cats. One experiment specifically
examined a once-a-month flea control product (topical
imidacloprid and moxidectin). In this experiment, six
treated cats did not become infected with B. henselae after
exposure to infected fleas, but six untreated cats became
bacteremic. When using cats as blood donors, the
possibility of transmission from infected animals should be
considered.
Infection with many Bartonella species is not well
understood; however, arthropods are thought to be involved
in all cases, and vector control should decrease
transmission.
Morbidity and Mortality
Clinical cases do not seem to occur frequently in
animals, but asymptomatic infections with Bartonella spp.
are common, especially in reservoir hosts.
Cats and other Felidae
Asymptomatic infections with B. henselae are very
common in cats. In studies from the U.S., Brazil, Ireland,
the U.K., eastern Australia and other locations, the
prevalence of bacteremia in cats varied from 3% to greater
than 40%, and was as high as 70-72% in some populations
by PCR. Bartonella DNA was detected in the saliva of a
few percent of cats in some studies, but up to 60% in others.
Young cats are more likely to be bacteremic than older
animals. Feral cats are also more likely to be infected with
© 2012
B. henselae than pet cats. Bacteremia can last for weeks to
months, and the number of bacteria in the blood can
fluctuate greatly during this time. Intermittent B henselae or
B clarridgeiae bacteremia was reported to persist for almost
15 months in some experimentally infected cats, with
relapses occurring irregularly at one to 4.5 month intervals.
Intermittent bacteremia has been reported for as long as 3
years in naturally infected cats, although it is possible that
these cats were reinfected. Seasonality has been reported in
temperate climates. In a study from the U.S., more than
twice as many cats were reported to be bacteremic in
September compared to June.
While bacteremia is more common in young cats, older
cats are more likely to be seropositive. Seroprevalence
tends to be higher in warm, humid regions, where fleas are
more common. In one 1995 survey, the overall
seroprevalence in U.S. cats was 28%, with rates varying
from a low of 4-7% in the Midwest, Rocky Mountain-Great
Plains region and Alaska, to 34% in the Pacific Northwest,
37% in the south-central plains, 40% in coastal California,
47% in Hawaii and 55% in the Southeast. Internationally,
studies using a variety of tests reported seroprevalence rates
of 27% to 68% in the Philippines, eastern Australia, Brazil,
Ireland, Italy and Turkey, and 1% or less in Sweden and
Norway. More than 80% of the cats in some animal shelters
may have antibodies to B. henselae.
Antibodies to B. henselae are also common in other
captive and wild members of the Felidae. In California
zoos, antibodies to this organism were reported in 17% of
cats of the genus Panthera (lions, tigers, leopards and
jaguars), 18% of cheetahs and 47% of small wild cats of the
genus Felis. Approximately 53% of wild bobcats and 35%
of wild cougars tested in California, 18% of wild Florida
panthers, and 28% of wild cougars from Texas were also
seropositive. Overall, antibodies to B. henselae were found
in 19% of cougars and 23% of bobcats in North, Central
and South America. Among lions and cheetahs captured in
Africa between 1982 and 2002, 5.2% of the lions and 5.9%
of the cheetahs were bacteremic with B. henselae or an
unidentified Bartonella, and antibodies to B. henselae were
found in 17% of the lions and 31% of the cheetahs. In
South Africa, another study reported antibodies to B.
henselae in 29% of lions tested.
B. clarridgeiae is thought to be less common in cats
than B. henselae. This organism accounted for
approximately 10% of the isolates from bacteremic cats in
the U.S., and 30% in France and the Philippines. Another
study reported that 21% of cats in the U.S. had B.
clarridgeiae DNA in the blood, and 35% had DNA from B.
henselae. In one study of shelter cats, however, antibodies
to B. henselae were found in 8% of Michigan cats and
antibodies to B. clarridgeiae in 18%, while 39% of
California cats were seropositive for B. henselae and 52%
for B. clarridgeiae. A survey of cats in Sweden reported
that 25% were seropositive for B. elizabethae. B koehlerae
is thought to be rare.
page 14 of 20
Cat Scratch Disease
Canidae
Similarly to B. henselae in cats, seroconversion to B.
vinsonii subsp. berkhoffii is reported to be lower in temperate
than tropical regions. In various surveys, the seroprevalence
in dogs was 1% in North Carolina, 12% in rural north-coastal
California, 10% in Israel, 5% in Greece, 9% on Reunion
Island, and as high as 65% in some areas of sub-Saharan
Africa. Within some individual kennels, the seroprevalence
can be as high as 93%. One study reported that, on average,
approximately 9% of U.S. military working dogs had
antibodies to B. vinsonii subsp. berkhoffii, with the highest
seroprevalence in dogs from the southern and northeastern
states, and low rates in dogs from the Midwest and mountain
states. In a study from Turkey, antibodies to this organism
were found in 3% of urban stray dogs, and 12% of shepherd
and farm guard dogs in rural areas. In Morocco, the
seroprevalence was 4% in pet dogs, and 36-47% in stray
dogs, varying by region. Some surveys examined serum
samples submitted from sick animals. In several studies from
the U.S., the prevalence of antibodies to B. vinsonii subsp.
berkhoffii in sick dogs ranged from less than 0.5% to as high
as 11%. In Thailand, 38% of the sick dogs examined were
seropositive, but DNA was not detected in any dog by PCR.
One survey did not find antibodies to B. vinsonii subsp.
berkhoffii in any serum samples submitted for diagnostic
testing in southern Ontario and Quebec, Canada.
Other species of Bartonella can also infect dogs. Overall
Bartonella spp. seroprevalence was reported to be 10% in
dogs from Colombia, 8% in Brazil, 5% in Sri Lanka and 0%
in Vietnam. In various surveys worldwide, antibodies to B.
henselae were found in 3–35% of dogs. One study from the
US reported that 10% of the healthy dogs examined, and
27% of the sick dogs, were seropositive for this organism.
Another U.S. study found antibodies to Bartonella spp. in
approximately 3% of samples from sick dogs, with the vast
majority of these dogs reacting to B. henselae, B.
clarridgeiae or multiple species, and fewer than 0.5%
reacting to B. vinsonii subsp. berkhoffii alone.
Among wild canids, antibodies to B. vinsonii subsp.
berkhoffii were detected in approximately 12% of gray
foxes in West/ Central Texas; 10% of island foxes on Santa
Rosa Island, California; and 35% or 76% of coyotes in
California. Approximately 28% of the coyotes in the latter
study had evidence of bacteremia, by PCR. Antibodies to B.
rochalimae were found in 33% of gray foxes in
West/Central Texas, 43% of gray foxes in northern
California and 31% of island foxes on Santa Rosa Island.
Cattle
Infection with B. bovis seems to be common in cattle,
especially beef breeds. One survey from North Carolina
reported that 95% of the cattle tested were seropositive for
B. bovis. Another study from the same state detected
Bartonella DNA in 82% of beef cattle. In California,
Bartonella bacteremia was found in 81–96% of beef cattle
and 17% of dairy cattle. B. bovis was detected in 0.2% of
© 2012
dairy cows and 42.5% of beef cattle in Taiwan. In France,
this organism was found in the blood of 59% of the animals
in one dairy herd, with the highest prevalence (93%) in
heifers. Despite the high prevalence, there were no adverse
effects on reproductive function or health in this herd.
Rodents and other small mammals
Bartonella spp. may be common among wild rodents in
urban locations. In urban Los Angeles, California, Bartonella
DNA was found in 68% of blood samples from wild rats, and
44% of the PCR-positive blood samples were also culture
positive. B. rochalimae was detected in 19% of these rats,
and B. tribocorum in 58%. Several other rodent-associated
species were also identified by PCR. Bartonella spp. can also
be common in other wild animals, such as rabbits.
One study detected Bartonella spp. in blood samples
from 26% of exotic small mammals imported into Japan as
pets. The prevalence was much higher in animals that had
been captured from the wild (37%), compared to animals
from breeders (approximately 3%). In animals bred for the
pet trade, Bartonella was found only in Siberian chipmunks
(Tamias sibiricus) from China. Among pet rodents captured
from the wild, bacteremia was detected in approximately
39% of animals in the family Muridae, and 44% in the
family Sciuridae, while no organisms were found in
animals from the families Octodontidae and Erinaceidae.
High prevalence was reported in the bushy-tailed jird,
Sekeetamys calurus; (100%); large Egyptian gerbil,
Gerbillus pyramidum (90%), greater Egyptian jerboa,
Jaculus orientalis (81%), and lesser Egyptian jerboa, J.
jaculus (75%). In contrast, the prevalence was only 10% in
the Cairo spiny mouse (Acomys cahirinus).
Post Mortem Lesions
Lymphadenomegaly, inoculation site lesions and
myocarditis were reported in some cats experimentally
infected with B. henselae or B. clarridgeiae.
Histopathologic lesions included lymph node hyperplasia,
splenic follicular hyperplasia, lymphocytic cholangitis, and
foci of lymphocytic, pyogranulomatous or neutrophilic
inflammation in the liver, spleen, lungs, kidneys and heart.
Some cats had small foci of hepatic or splenic necrosis.
Granulomatous hepatitis has been reported in
experimentally infected rodents. Mice inoculated with two
human isolates of B. tamiae had myocarditis, lymphadenitis
with vascular necrosis, and granulomatous hepatitis and
nephritis at necropys. Mice inoculated with another human
isolate of B. tamiae had dermatitis and granulomas in the
kidneys, without lymphadenitis.
Various lesions including endocarditis, granulomatous
lesions, and bacillary angiomatosis, as well as areas of
vasculitis and necrosis in an aborted fetus, have been
reported in naturally infected animals with syndromes
attributed to Bartonella. However, as this organism was not
proven to be the cause of these syndromes, it remains
possible that the lesions were not caused by Bartonella.
page 15 of 20
Cat Scratch Disease
Internet Resources
Centers for Disease Control and Prevention (CDC)
http://www.cdc.gov/healthypets/diseases/catscratch.ht
m
eMedicine.com - Cat scratch disease
http://www.emedicinehealth.com/cat_scratch_disease/a
rticle_em.htm
http://emedicine.medscape.com/article/214100overview
eMedicine.com - Bacillary angiomatosis
http://emedicine.medscape.com/article/1051846overview
Public Health Agency of Canada. Pathogen Safety
Data Sheets
http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/indexeng.php
The Merck Manual
http://www.merck.com/pubs/mmanual/
The Merck Veterinary Manual
http://www.merckvetmanual.com/mvm/index.jsp
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*Link defunct as of July 2012
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Cat Scratch Disease and Other Bartonella Importance

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