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1051/parasite/2000073221

EFFICACY OF OXFENDAZOLE FOR THE TREATMENT OF GIARDIOSIS IN DOGS.


EXPERIMENTS I N DOG BREEDING KENNELS
VILLENEUVE V.*, BEUGNET F.** & BOURDOISEAU G.*

Summary : Résumé : EFFICACITÉ DE L'OXFENDAZOLE DANS LE TRAITEMENT DE


L'INFECTION DES CHIENS PAR GIARDIA DUODENALIS. ESSAIS EN ÉLEVAGES
Giardiosis is one of the most frequent parasites of dogs and cats.
DE CHIENS
Since several years, the treatment is based on the use of
metronidazole. A coproscopic study in four dog kennels was La giardiose est l'une des parasitoses digestives les plus fréquentes
conducted to demonstrate, at a significant level, the efficacy of chez le chien ou le chat. Le traitement a longtemps reposé sur
oxfendazole (Dolthène®, Merial). At the posology of 11.3 mg/kg l'emploi du métronidazole. Un essai conduit dans quatre élevages
each day during three days (D1, D2 and D3), no dogs eliminated de chiens démontre significativement l'efficacité de l'oxfendazole,
Giardia cysts and all dogs are clinically cured. The importance of Dolthène . Employé à la posologie de 11,3 mg/kg pendant trois
®

hygienic measures is underlined. In kennels 1 and 2 where jours de suite (J1, J2 et J3), l'oxfendazole négative l'excrétion des
hygienic conditions were poor, dogs reexcreted cysts again after kystes de Giardia duodenalis et entraîne une guérison clinique.
treatment. In kennels where the boxes were disinfected, no dogs, L'importance des mesures sanitaires de désinfection des box,
treated with 2 2 . 6 or 1 1 .3 mg/kg, reexcreted Giardia cysts. empêchant les réinfections, est soulignée. Dans les deux élevages
où les conditions hygiéniques sont médiocres, les chiens traités
KEY WORDS : Giardia duodenalis, dog, oxfendazole. réexcrètent des kystes de protozoaires. Dans les élevages où des
mesures de désinfection ont été mises en œuvre avant les
traitements, aucun chien, traité à 22,6 ou 11,3 mg/kg, n'a
réexcrété de kystes de Giardia.

MOTS CLÉS : Giardia duodenalis, chien, oxfendazole.

1994; Bourdeau, 1993; Leib & Zajac, 1999; T h o m p s o n


INTRODUCTION
& Reynoldson, 1997; Zajac, 1 9 9 2 ) . Giardiosis is also o f

G
great importance in livestock and is frequently asso-
iardiosis is an infectious disease o f the small
ciated with diarrhea in dairy cattle (O'Handley, 2 0 0 0 ) .
intestine due to Giardia duodenalis (= Giardia
It is considered b y several authors to b e a zoonosis,
intestinalis = G. lamblia) clinically showing the
even though various adjusted strains host species are
development o f an enteritis with chronic diarrhoea with
genetically singled out (Capon, 1989; Gasser, 1990;
steatorrhea (Barr & B o w m a n , 1994; Bourdeau, 1993;
Hopkins, 1997; T h o m p s o n et al., 2 0 0 0 ) . S o m e strains
Leib & Zajac, 1999; T h o m p s o n & Reynoldson, 1997;
s e e m to be able to infect human from livestock or dogs
T h o m p s o n et al., 2000; Zajac, 1 9 9 2 ) . Infections are
and vice versa, and, in the opposite, other strains s e e m
associated with a decrease o f microvillus surface area,
to b e very specific. Further genetic studies are n e e d e d
reduced intestinal e n z y m e activity and increased intes-
to understand these variations (Gasser, 1990; Hopkins,
tinal transit (Deselliers et al, 1 9 9 7 ) . T h e s e pathological
1997; Meloni et al., 1995; T h o m p s o n et al., 2 0 0 0 ) . Giar-
c h a n g e s result in a malabsorptive diarrhea, w h i c h is
diosis is the most c o m m o n l y non viral reported intes-
the major clinical sign o f giardiosis. This protozoan is
tinal infection in humans. Domestic carnivores could
the most commonly identified pathogen of humans and
represent a significant parasite source for their owners.
animals (livestock and pets) throughout the world
This digestive parasite is underestimated b y veterina-
( T h o m p s o n et al., 2 0 0 0 ) . Giardiosis is frequent in car-
rian practice b e c a u s e o f the difficult diagnosis w h i c h
nivorous c o m p a n i o n animals, showing living s o u n d
is based on faeces coproscopy (Barr & coll., 1994; Beu-
carriers that form the parasite tank (Barr & B o w m a n ,
gnet, 1998; Beugnet, 1 9 9 6 ) . It is considered as a major
cause o f diarrhoea in dogs, in k e n n e l s or at h o m e .
A study on urban domestic carnivores intestinal para-
sitism ( B e u g n e t et al., 2 0 0 0 ) w a s led in Paris suburbs
* Service de Parasitologic, ENVL, 1, avenue Bourgelat, F-69280 Marcy in 1998/1999. It s h o w e d that 14.7 % of cats w e r e
l'Étoile. Giardia duodenalis infected. 30.4 % of dogs under six
** Merial, 29, avenue Tony Gamier, F- 69348 Lyon Cedex 07.
months-old w e r e infected versus 7.1 % of adults. This
Correspondence: F. Beugnet.

Parasite, 2000, 7, 221-226 221


Mémoire
VILLENEUVE V., B E U G N E T F. & B O U R D O I S E A U G.

flagellate s e e m s to b e o n e o f the most frequent intes- Out o f 199 dogs, 34 ( 1 8 males and 16 females) proved
tinal parasites in dogs and cats, as helminths (Franc et to b e Giardia duodenalis infected. T h e s e w e r e added
al., 1 9 9 7 ) . A first study led b y the Parasitology labo- to the treatment trials. 19 dogs w e r e under o n e year
ratory o f the Lyon Vet School s h o w e d Giardia cysts old, and five a b o v e . S e x and age are m e n t i o n e d in
in 10 % of the faeces by coproscopic studies conducted Table I for e a c h dog.
on carnivores suffering from diarrhoea and having O x f e n d a z o l e (Dolthène®, Merial Laboratories) is a
g o n e to consulting ( B e u g n e t , 1 9 9 8 ) . liquid orally given at a posology of 11.3 or 22.6 mg/kg,
Evolution is favourable after the implementation of a three days running. A coproscopic follow-up shows the
symptomatic and specific treatment. This latter has long possible decrease o f protozoan cysts in faeces. Treat-
b e e n b a s e d on metronidazole ( F l a g y l ) oral use, at a
®
ment is carried out at D 1 , D2 and D 3 . Semi-quantita-
p o s o l o g y of 20 mg/kg, twice a day during 10 days tive c o p r o s c o p i c studies w e r e m a d e b y MacMaster's
(Barr & B o w m a n , 1994; Zajac, 1 9 9 2 ) . S o m e experi- technique at DO, D5, D7, D9 and D 1 2 . After experi-
ments stated a p o o r efficacy and existing intolerance mental infection with Giardia cysts, the dogs e x c r e t e d
signs such as nausea, vomiting or ataxy ( T h o m p s o n & cysts in 4 8 to 72 hours (Leib & Zajac, 1999); s o a survey
Reynoldson, 1992). Metronidazole chemoresistant para- during 10 days will s h o w if dogs are cured or not.
sitic strains s e e m recrudescent in the field and could There is n o description in dogs of long periods without
explain human medecine therapeutic failures (Johnson, excretion, and three c o p r o s c o p i e s at 4 8 hours interval
1993; Upcroft & Upcroft, 1 9 9 7 ) .
Benzimidazoles activity was demonstrated more recently
with an efficacy a b o v e 90 % (Barr et al., 1993; Barr et Oxfendazole use at a posology of 11.3 mg/kg each day during
al., 1994; Barr et al., 1998; Morgan et al., 1993). T h e use three days
of these molecules could b e favourable due to their tole- Age
rance, even at a high posology. Albendazole seems the- Kennel 1 Sex (M/F) (month) DO 1» D12
Mean 6 dogs: 4.67 5 0* 1.67*
refore effective w h e n administrated to dogs at a poso-
3M, 3F
logy o f 25 mg/kg twice a day during two days (Barr et Sem 2.58 0 0 0.52
al., 1993) while fenbendazole (Panacur 250®, Intervet) U Rank test: significant difference beteween DO and D12 with risk
is also effective at 50 mg/kg during three days (Barr et error of 10 -4

al., 1994). Oxfendazole (Dolthène®, Merial) is an anthel- Oxfendazole use at a posology of 22.6 mg/kg, three days run-
minthic used in several countries like France, Italy, ning
Spain, or Germany for dogs deworming. Its potency on Kennels 1 Age
Giardia duodenalis may prove very interesting joint to and 2 Sex (month) DO D5 D7 D9
the standard anthelminthic spectrum. Oxfendazole is o n e Mean 11 dogs: 3.81 3.64 2 0.82* 1.73*
7M, 4F
o f the anthelmintic most often used in Europe to
Sem 2.08 1.57 2.05 0.87 1.19
deworm the dogs. Febantel, fenbendazole, and oxfen- U Rank test: significant difference beteween DO and D9 with risk
dazole are three benzimidazoles which are based on the error of 2 %
same nuclear and which have the same metabolites after Oxfendazole use at a posology of 22.6 mg/kg, three days run-
administration (Fig. 1) (Towsend & Wise, 1990). As fen- ning. Treatment in disinfected boxes.
bendazole is active against Giardia, it was of great
Age
interest to demonstrate the efficacy o f oxfendazole (the Kennel 3 Sex (month) DO D5 D7 D9
active sulfoxyde metabolite of fenbendazole). Mean 10 dogs: 5 5 0* 0* 0*
In this study, the trials w e r e d o n e b y veterinary prac- 5M, 5F
Sem 0 0 0 0 0
titioners in dog k e n n e l s . A c o p r o s c o p i c s c r e e n i n g
U Rank test: significant difference at D5, D7 and D9 with DO at les:
helped to identify Giardia infected dogs and later to than 10"6

treat them. Both Giardia cysts excretion and these ani-


Oxfendazole use at a posology of 11.3 mg/kg, three days run-
mals clinical state w e r e followed up.
ning. Treatment in disinfected boxes.
Age
Kennel 4 Sex (month) DO D5 D7 1)')
MATERIALS A N D M E T H O D S Mean 9 dogs: 24.11 4.33 0* 0* 0*

I
4M 5F
nfected dogs c o m e from five pup kennels dedicated Sem 21.47 1 0 u (1
to sale. A c o p r o s c o p i c study h e l p e d to identify U Rank test: significant difference at D5, D7 and D9 with DO at less
than 10 -6

Giardia duodenalis infected dogs. 199 dogs (73 males


and 126 f e m a l e s ) w e r e added to the previous study. Sem: standard error of the mean.
T h e s e dogs b e l o n g to various breeds: Scottish, Westie, * Significant difference between the number of Giardia cysts at D0
Lhassa Apso, Poodle, American Cocker, Setter, Alsatian, compare to D5, D7 or D9.
Leonberg, and St Bernard. Table I. - Results of the four successive experiments.

222 Parasite, 2000. 7, 221-226


EFFICACY OF OXFENDAZOLE FOR THE TREATMENT OF GIARDIOSIS IN DOGS

Fig. 1. - Chemical structures of some benzimidazoles anthelmintics (Towsend & Wise, 1990).

c a n diagnose giardiosis with a sensibility superior to Four successive experiments w e r e conducted. T h e first
9 5 % (Barr et al., 1992; Leib & Zajac, 1 9 9 9 ) . t w o in two k e n n e l s w h e r e hygienic conditions were
T h e floating technique, using a high density liquid, p o o r and with n o disinfection measures before treat-
especially suits protozoan cysts research, since these ment. T h e following two trials w e r e carried out in t w o
latter are not very dense (Barr et al., 1992). Magnesium other kennels w h e r e dogs are in b o x e s with disinfec-
sulfate with 1.28 density up to 25° C (35 g o f m a g n e - tion measures before treatment. T h e disinfection was
sium sulfate per 100 ml o f water) w a s held. Cysts p r e c e d e d b y a cleaning with high pressure water
n u m b e r quantification is given with an order of size. (using Karcher). T h e n the disinfection w a s made using
Quantification notions: both sodium hypochlorite solution and an a m m o n i u m
( 5 ) : m o r e than 1,000 Giardia cysts /5 g faeces, IV solution for farms ( T H 4 , Sogeval Laboratory).
+ ®

( 4 ) : b e t w e e n 200 and 1,000,


( 3 ) : b e t w e e n 100 and 200,
( 2 ) : b e t w e e n 10 and 100, RESULTS
( 1 ) : p r e s e n c e : less than 10,
( 0 ) : n o cysts.
PRELIMINARY SURVEY
Statistical comparisons have b e e n m a d e b e t w e e n the

O
n u m b e r o f cysts excreted before and after the anthel- ut o f the 199 dogs added to the survey, 136
mintic treatment using non parametric test (Mann & (68.3 % ) are at least infected b y o n e parasite.
Whitney U test). Giardia duodenalis was found in 34 dogs

Parasite, 2000, 7, 221-226


223
VILLENEUVE V., BEUGNET F. & BOURDOISEAU G.

(17.1 % ) . This p r e v a l e n c e w a s increased to 4 4 . 4 5 % in It appears to b e necessary to carry out a supervised


dogs u n d e r six m o n t h s (24/54). trial in w h i c h reinfections are restricted to a minimum
b y strict hygiene measures.
O X F E N D A Z O L E AT A P O S O L O G Y O F 1 1 . 3 MG/KG,
W I T H N O DISINFECTION MEASURES OXFENDAZOLE AT A POSOLOGY OF 22.6 MG/KG,
WITH BOXES DISINFECTION
At first, o x f e n d a z o l e was orally given three days run-
ning (D1 to D 3 ) at a p o s o l o g y o f 11.3 mg/kg to all B o x e s disinfection is d o n e on the first day o f treatment.
animals proved positive at screening. B o x e s washing followed by a disinfection with a m m o -
In k e n n e l 1, Giardia cysts w e r e detected in six dogs nium IV and/or sodium hypochlorite w e r e m a d e in
including four pups under three months-old and two k e n n e l s 3 and 4.
y o u n g a g e d eight months. All these pups had a diar- In kennel 3 with very g o o d hygiene conditions (regular
rhoeic enteritis. Results are s h o w n in T a b l e I. worming, daily b o x e s cleaning, animals b r e a k d o w n by
A d e c r e a s e in the Giardia cysts n u m b e r is underlined, a g e groups, maternity placing for pregnant and nur-
alongside with negativation for all puppies at D 9 . In sing females) and after b o x e s disinfection o n the first
spite o f a reexcretion o f cysts on D a y 12, the diffe- day o f treatment, there is a 100 % efficacy o n 10 pups
r e n c e is significant at 1 0 . All pups showing digestive
- 4 with n o excretion c o m i n g b a c k . T h e s e 10 pups u n d e r
troubles s t o p p e d at D 5 , without later r e a p p e a r a n c e . five months-old (five males and five f e m a l e s ) all suf-
H o w e v e r , k e n n e l condition, with p o o r hygiene (ani- fered from a clinical giardiosis. All signs disappeared
mals in p a d d o c k s with grassy path from w h i c h floor since D7, and never r e a p p e a r e d .
disinfection is unfeasible), surely results in a fast n e w
infection o f pups. Since D12, a cysts reexcretion is OXFENDAZOLE AT A POSOLOGY OF 1 1 . 3 MG/KG,
n o t i c e d in lesser ratio. WITH BOXES DISINFECTION

T h e following trials w e r e led according to t w o a x e s This e x p e r i m e n t was carried out in k e n n e l 4. Eight


so as to cure it all: 22.6 mg/kg posology trial and health adults infected and a six months-old pup were
measures implementation to restrict reinfections by detected. B o x e s w e r e w a s h e d and disinfected o n the
cysts. first day o f treatment. As in the previous experiment,
dogs did not g o out o f their b o x e s during the w h o l e
OXFENDAZOLE AT A POSOLOGY OF 22.6 MG/KG, e x p e r i m e n t (from D1 until D 9 ) in order to avoid all
WITH NO JOINT DISINFECTION MEASURES reinfection risk. T h e r e is a stop o f cysts excretion in
100 % o f cases.
Animals from k e n n e l 1 that proved positive at the e n d
o f the first trial t o o k part again in the trial with d o u b l e
p o s o l o g y , e x c e p t dogs o n e up to four that w e r e sold
DISCUSSION
m e a n w h i l e . Other pups, suffering from diarrhoea and

I
emaciation, and excreting Giardia cysts w e r e included
n the first e x p e r i m e n t ( k e n n e l 1), dogs have b e e n
in this s e c o n d trial. In k e n n e l 2, five d o g s were
treated with o x f e n d a z o l e at the p o s o l o g y u s e d for
detected a m o n g w h i c h four pups under six months-
anthelmintic treatment. Results s h o w e d a significant
old and o n e y o u n g adult aged eight months.
decrease in the n u m b e r o f cysts ( > 95 % ) but n o disap-
All these animals orally t o o k o x f e n d a z o l e ( D o l t h è n e )
®

p e a r a n c e o f their excretion. T h e r e are two possible


at a p o s o l o g y o f 22.6 mg/kg, three days running.
explanations: either the o x f e n d a z o l e p o s o l o g y was not
At d o u b l e p o s o l o g y there is a significant d e c r e a s e o f high enough to o v e r t h r o w Giardia, or dogs got
the cysts number, from thousands per gram o f f a e c e s infected again b e t w e e n the e n d o f the treatment and
to n o n e , since D 5 for k e n n e l 2. That is to say a 100 % c o p r o s c o p i c studies. Reinfection assumption is plau-
efficacy at D 5 . This k e n n e l had higher hygiene condi- sible due to cysts resistance in the outside s p a c e ( t w o
tions than k e n n e l 1. A clinical recovery is noticed o n m o n t h s at 8 ° C ; o n e m o n t h at 21° C; partial resistance
all pups. at - 13° C during t w o w e e k s ) , and the fact that floor
In k e n n e l 1, the cysts n u m b e r d e c r e a s e is less impor- disinfection w a s not d o n e b e c a u s e o f k e n n e l condi-
tant, going from thousands to f e w hundreds. Reinfec- tions ( B a r r & B o w m a n , 1994; Thompson & Rey-
tions or Giardia multiplication retakings o c c u r from D7 noldson, 1993; Zajac, 1 9 9 2 ) . O n the other hand, only
and D 9 according to experiments, that is to say t w o o n e c o p r o s c o p i c study was carried out during s c r e e -
up to three days after the e n d o f the treatment. In spite ning, with the result that s o m e carriers animals may
o f the r e e x c r e t i o n o f cysts, the difference b e t w e e n DO not have b e e n detected and therefore remained sources
and D7 counts is significant at less than 1 1 0 - 3
and bet- o f cysts for dogs o n test (Barr & B o w m a n , 1994; Barr
w e e n DO and D 9 is significant at 2 %. et al., 1992).

224 Parasite, 2000, 7, 221-226


Mémoire
EFFICACY OF OXFENDAZOLE FOR THE TREATMENT OF GIARD.OSIS IN DOGS

T o m e e t these t w o assumptions a double dose c o m - Giardiosis is nowadays considered b y many investi-


pared to the previous o n e ( 2 2 . 6 mg/kg) was tested, set- gators as o n e o f the main digestive parasitosis in dogs
ting u p o r not hygiene conditions ( k e n n e l premises and cats, in kennels but also at t h e owner's place.
disinfection). S o m e strains o f this protozoan have a zoonotic aspect:
In kennels 1 and 2, the d o u b l e d o s e w a s used without s o m e animal strains being able to infect human. There
floor disinfection ( p a d d o c k , m u d floor and grass ken- are populations adjusted to each kind o f host, but
nels) a n d the efficacy o f treatment remained partial interspecific transmissions are still possible (Capon,
(decrease o f the emitted cysts n u m b e r ) . 1989; Gasser, 1990; Hopkins, 1997; Meloni et al., 1995).
In k e n n e l 3, t h e d o u b l e d o s e o f oxfendazole joint to Screening and struggle measures against this enteritic
floor disinfection h e l p e d achieve a total disappearance parasite are b o u n d to expand. They will join health and
of cysts excretion a n d pups clinical recovery. This medical measures. T h e treatment o f infected dogs is
e x p e r i m e n t underlines t h e importance o f the dogs o n e point, t h e v a c c i n e d e v e l o p m e n t a n o t h e r o n e
reinfection risk b y cysts existing in their environment. (Olson et al., 1997; Olson et al., 2 0 0 0 ) . Since a few
F e n b e n d a z o l e is effective in the canine giardiasis treat- months, a vaccine h a s b e e n commercialised for dogs
ment at the usual anthelminthic posologies and admi- in kennels (Giardia Vax®, Fort D o d g e Laboratories)
nistration rates for dogs (Barr et al., 1994; Zajac et al., (Olson et al., 2 0 0 0 ) . T h e dogs s h o w n o diarrhea but
1998; Zajac et al., 1992). Oxfendazole should have the excretion o f kysts is still present. Like for other
b e e n tested at anthelmintic posology ( 1 1 . 3 mg/kg) res- parasitosis, the control measures will b e integrated and
tricting reinfections. T h e experiment in kennel 4 proves b a s e d o n both vaccination in collectivities, treatments,
and disinfection in k e n n e l s . As t h e cats are often
this effect, since n o n e o f the nine treated dogs reex-
infected b y Giardia intestinalis, the possibility o f treat-
creted cysts during the three running controls. Canine
ment with benzimidazoles should n o w be investigated
giardiosis treatment c a n b e b a s e d o n oxfendazole use
in this species.
at a posology o f 11.3 mg/kg per os three days running.
Out o f 3 4 treated dogs, at simple or double posology,
n o n e s h o w e d troubles or signs o f toxicity o f the mole-
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Mémoire 225
VILLENEUVE V., BEUGNET F. & BOURDOISEAU G.

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Reçu le 1 1 mai 2 0 0 0
Accepté le 2 7 juin 2 0 0 0

226 Parasite, 2000, 7, 221-226


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