Therapeutic trial of ivermectin against Notoedres cati var. cuniculi

Article available at http://www.parasite-journal.org or http://dx.doi.org/10.1051/parasite/1996031087
THERAPEUTIC TRIAL OF IVERMECTIN AGAINST NOTOEDRES CATI
VAR. CUNICULI INFECTION I N RABBITS
SINGLA L.D.*, JUYAL P.D.* & GUPTA P.P.**
Résumé : ÉTUDE THÉRAPEUTIQUE DE L'IVERMECTINE CONTRE
Summary:
L'INFECTION À NOTOEDRES CATI VAR. CUNICULI CHEZ LE LAPIN
Effect of 400 µg/kg of ivermectin against natural infection of
Notoedres cati var. cuniculi mange in rabbits was evaluated in L'effet de 400 pg/kg d'ivermectine contre l'infection naturelle du
lapin par Notoedres cati var. cuniculi a été évalué chez 20 lapins
twenty rabbits which showed typical symptoms of notoedric
montrant des signes typiques de gale notoédrique et divisés en
mange and were randomly divided into two groups. Group I
deux groupes randomisés. Le groupe I comportait 15 lapins traités
consisted of 15 rabbits treated with single s/c injection of
par une injection sous-cutanée unique d'ivermectine. Le groupe II a
ivermectin (Ivomec®, Dynamic Pharmacals, Bombay). In group II,
été formé de cinq lapins témoins infectés et non traités.
five infected untreated rabbits were kept as control. Daily
L'observation quotidienne de l'amélioration clinique, basée sur
observations of clinical improvement and on the basis of
l'examen des lésions de grattage, a été effectuée aux jours 0, 3,
examination of skin scrapings on days 0, 3, 6, 9, 16, 23 and
6, 9, 16, 23 et 30 après traitement. Une disparition complète
30 post treatment were done. Complete visual shedding of lesions
des lésions cliniques a été observée au 6 jour après traitement, et
was seen on day 6 after treatment and skin scrapping were found
l'examen cutané s'est négative à partir du 7 jour. Sur le plan
negative for mites after 7th day of treatment till the end of
histopathologique, les agents infectieux était présents dans la
experiment. Histopathologically mites were present in stratum
couche cornée et nombreux dans les galeries creusées dans
corneum and many were noticed in the burrows in epidermis.
l'épiderme. Une hyperkératose, une hyperplasie et une acantholyse
Marked hyperkeratosis, hyperplasia and acantholysis along with
marquées ainsi qu'une dégénérescence ballonniforme des cellules
ballooning degeneration of epithelial cells of epidermis were seen.
e
e
épithéliales de l'épiderme ont été observées.
KEY WORDS : Notoedres cati, ivermectin, rabbit.
MOTS CLES : Notoedres cati, ivermectine, lapin.
INTRODUCTION
I
vermectin has b e e n extensively used in domestic
animals against e c t o and endoparasitic infestations
(Campbell & B e n z , 1984). In rabbits it has b e e n
tried against ectoparasites but for this, as p e r the literature it does not have a product licence ( M c Kellar
et al, 1992). However, ivermectin w a s s h o w n to have
activity against ectoparasites o f rabbits for the first time
by Wilkins et al. ( 1 9 8 0 ) . Subsequently, it w a s effectively used 4 0 0 ug/kg by subcutaneous ( s / c ) injections
against e a r mite Psoroptes
cuniculi
(Wright & Riner,
1985; Singh & Gill, 1 9 8 9 ; and Pandey, 1 9 8 9 ) and also
against Notoedres cati (Singh & Gill, 1989). Ivermectin
is easy to administer and as the drug reaches to the
skin it c a n affect the mites which otherwise would not
b e affected by the topical application o f any other drug
(McKeller et al, 1992). Therefore, in the present study
* Department of Veterinary Parasitology and
** Department of Veterinary Pathology, College of Veterinary Science,
Punjab Agricultural University, Ludhiana, 141004, India.
Parasite, 1996, 3, 87-89
it w a s decided to use ivermectin ( I v o m e c ® Injection,
Dynamic Pharmacals, B o m b a y ) for the treatment o f clinical cases o f m a n g e in rabbits.
MATERIAL AND METHODS
T
wenty New Zealand white rabbits o f either
s e x e s weighing 2.0 to 3-5 kg (average 2.7 k g )
were kept in the department for the experimental studies. All rabbits were kept in iron cages (two
rabbits p e r c a g e ) a n d maintained o n nutritionally
b a l a n c e d diet. Almost all were found infected with
mange at different degree o f infestation. T h e symptoms
and lesions o f the clinical cases were recorded. Skin
scrapings o f the affected rabbits were collected for examination and identification o f the mange mites after
routine treatment with 1 0 % K O H (Soulsby, 1 9 8 2 ) .
Microscopic examination o f skin revealed abundant
mites at various developmental stages. T h e mites were
identified as Notoedres
cati var. cuniculi
o n the basis
of description given in Muller et al. ( 1 9 8 3 ) . All the rabbits showing clinical symptoms and lesions o f the
disease were randomly divided into two groups. T h e
group I consisted o f 15 rabbits and group II o f five rab­
bits. T h e rabbits o f group I w e r e treated subcutaneously (behind the shoulder) with undiluted Ivomec®
Injection (ivermectin 1 % w / v ) 4 0 u l / k g b o d y weight
with 2 4 gauge n e e d l e . Group II rabbits served as
untreated control. This form o f ivermectin was selected
o n the basis o f prior successful use in rabbits, availa­
bility and ease o f administration. T h e treated rabbits
were physically e x a m i n e d daily for clinical improve­
ment and their skin scrapings w e r e e x a m i n e d o n day
0, 3, 6, 9, 16, 23 and 30 post treatment for the pre­
s e n c e o f m a n g e mites.
For histopathology skin biopsies w e r e taken randomly
from infected untreated rabbits to detect mites and their
pathological effects. T h e s e w e r e preserved in 10 %
neutral buffered formalin and 5 u thick paraffin sec­
tions w e r e cut and stained with haematoxylin and
eosin (H & E ) .
greyish white exudate was c o m i n g out from both the
eyes.
T h e group I o f rabbits were infected with an average
of 120 m i t e s / c m
2
before treatment w h i c h
included
various stages o f life cycle viz. eggs, larvae, nymph and
adults. T w o days after treatment with ivermectin, rab­
bits stopped scratching and biting. Marked progressive
improvement
in t h e a p p e a r a n c e
of lesions
was
observed. T h e sheding o f lesions i.e. crusts and scars
started on 3rd day and c o m p l e t e visual sheding o f
lesions was recorded o n 6th day o f treatment r e s p e c ­
tively. T h e r e was n o visible c h a n g e in the lesions and
symptoms o f infected, untreated control rabbits e x c e p t
that two o f the rabbits developed generalised infection
(group II). T w e l v e rabbits o f treated group had
no
mites b y the 7th day o f treatment and all the rabbits
w e r e negative b y 9th day. T h e rabbits remained free
o f mites until the e n d o f trial. T h e
corresponding
2
figures for untreated controls w e r e 115 m i t e s / c m . B y
the 25th day all the treated animals w e r e r e c o v e r e d
RESULTS
completely with the n e w growth o f hairs ( T a b l e I).
I
n the infected rabbits lesions w e r e noticed in the
form o f whitish crusts and scabs which were found
chiefly in the areas w h e r e hairs w e r e spars and
short i.e. on the nose, head, eyelids and ears. In s o m e
cases lesions w e r e found on the feet specially in toe
region. T h e r e was formation o f remarkable wart-like
or horn-like e x c r e s c e n c e s o f considerable size on the
nose. Heavy crusts around the eyes interfered with
vision, in s o m e rabbits there was conjunctivitis and
Days
after
treatment
sections o f the mites in the stratum c o r n e u m and most
o f t h e m h a d dug
burrows
2
Mites/cm
(means ± SEM)
120 ± 4.34
3
70.53 ± 5.17
6
9
id
14.06 ± 2.55
(four rabbits negative)
2.6 ± 1.43
(three rabbits positive)
All were negative
Negative
23
25
Negative
Negative
30
Negative
—
epider­
were marked hyperkeratosis, hyperplasia and acantholysis o f the epidermis and at places ballooning
degeneration o f epithelial cells in the epidermis. T h e r e
was infiltration o f eosinophils, lymphocytes, fibroblasts
and few neutrophils.
Infected and untreated
Clinical
observations
Mites/cm
(means ± SEM)
Clinical
observations
115 ± 5.93
No v i s i b l e c h a n g e in
l e s i o n s and s y m p t o m s
e x c e p t two r a b b i t s in
which there was progres­
sive development of gene­
ralized infection.
Pruritis and crust forma­
tion was there and rabbits
kept on scratching.
2
—
Stopped scratching and
biting
Shedding o f crusts and
scars started
Crusts and scars disap­
peared
Wrinkling and keratinization decreased
Healing of lesions started
Normal texture visible with
new growth of hairs
118.2 ± 5.27
114.8 ± 4.17
—
126.8 ± 2 . 1 5
124.8 ± 2.87
—
Complete
growth of
Complete
growth of
d e e p into the
mis (Fig. 1). Pathological c h a n g e s apparent in the skin
Infected and treated
0
2
7
T h e sections o f skin o f infected rabbits s h o w e d cut
120.8 ± 2.35
cure with new
hair
cure with new
hair
127.4 ± 2.82
2
Table I. — Clinical observations and parasitic burden (mites/cm ) in Notoedric rabbit mange.
88
Parasite, 1996, 3, 87-89
IVERMECTIN AGAINST NOTOEDRES CATI VARCUMCULIINFECTION
remove n e w generation o f mites as the egg hatch
(Pandey, 1989 and McKellar ETAL., 1992). T h e s e results
suggest that the prolonged availability o f ivermectin in
the rabbits has a residual effect against mites (Pandey,
1989). T h e efficacy o f ivermectin against the mange
mite NOTOEDRES CATI var. CUNICULI which w e r e present
in the keratin layer m a y b e b e c a u s e o f high c o n c e n ­
tration which is achieved in the skin (McKellar ET AL.,
1992). It is c o n c l u d e d that a single subcutaneous injec­
tion o f ivermectin o f 4 0 0 Ltg/kg b o d y weight could b e
used for successful elimination o f m a n g e in rabbits.
ACKNOWLEDGEMENT
A
uthors are thankful
to Professor-cum-Head,
Department o f Veterinary Parasitology, PAU,
Ludhiana, for facilities provided.
REFERENCES
CAMPBELL W . C & BENZ G.W. Ivermectin: a review of efficacy
and safety. Journal of Veterinary Pharmacology and The­
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GORDON R.M., UNSWORTH K. & SEATON D.R. The development
and transmission of scabies as studies in rodent infections.
Annals of Tropical Medicine and Parasitology, 1943, 37,
174-184.
MCKELLAR Q.A., MIDGLEY D.M., GALBRAITH E.A., SCOTT E.W. &
BRADLEY A. Clinical and Pharmacological properties of
ivermectin in rabbits and guinea pigs. Veterinary Record,
1992, 130, 71-73.
Fig. 1. — Section of skin showing Notoedres cati var. cuniculi mite
(arrow) in a burrow in the epidermis along with marked hyperke­
ratosis (H), hyperplasia (hyp) in the epidermis and infiltration of
inflammatory cells (IC) in the dermis below the parasite. H & E x 70.
MULLER G.H., KIRK R.W. & SCOTT D.W. Small animal Der­
matology. 3rd ed. W.B. Saunders Company, Philadelphia,
1983, 351-363.
DISCUSSION
RENUKAPRASAD C, RAMASWAMY M., KUMAR M.M., GOPAL T. &
KESHAVAMURTHY B.S. Therapeutic effect of ivermectin on
rabbit mange. Indian Veterinary Journal, 1989, 66, 10551057.
T
he present study demonstrates that 4 0 0 ug/kg
bociy weight single injection o f ivermectin is
successful in clinical and parasitological cure
o f NOTOEDRES CATI var. CUNICULI associated m a n g e infec­
tion in rabbits. T h e s e findings are in a c c o r d a n c e with
Renukaprasad ET AL. (1989)- However, Wright & Riner
( 1 9 8 5 ) reported that a single injection o f ivermectin o f
4 0 0 Ug/kg b . w . could not eliminate PSOROPTIC m a n g e
infestation in rabbits. Ivermectin has n o ovicidal effect
(Pandey, 1989). Normally the eggs o f NOTOEDRES spe­
cies hatch in four to five days ( G o r d o n ET AL., 1943).
T h e a b s e n c e o f mites from 7th day to the e n d o f e x p e ­
riment after ivermectin treatment indicates that suffi­
cient concentration o f drug is available to kill a n y
PANDEY V.S. Effect of ivermectin on the ear mange mite,
Psoroptes cuniculi, of rabbits. British Veterinary Journal,
1989, 145, 54-56.
SINGH J. & GILL B.S. Treatment of mange of rabbits with
ivermectin. Indian Journal of Parasitology, 1989, 13, 115-118.
SOULSBY E.J.L. Helminths, Arthropods and Protozoa of
Domesticated Animals. 7th Edn. ELBS and Bailliere
Tindall, London, 1982, 764.
WILKINS C.A., CONROYJ-A., H O P., O'SHANNY W.J., MALATESTA
P.F. & EGERTON J.R. Treatment of Psoroptic mange with
avermectins. American Journal of Veterinary Research,
1980, 41, 2112-2113.
WRIGHT F.C. & RINER J.C. Comparative efficacy of injection
routes and doses of ivermectin against Psoroptes in rabbits.
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larvae hatching from the eggs. It has b e e n suggested
that drug persists in rabbit tissues sufficiently long to
Parasite, 1996, 3, 87-89
Note d e recherche
Reçu le 4 mars 1995
Accepté le 25 septembre 1995
89