oxyuris equi: lack of efficacy in treatment with macrocyclic lactones
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Veterinary Parasitology 201 (2014) 163–168
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Veterinary Parasitology
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hort Communication
xyuris equi: Lack of efficacy in treatment with macrocyclicactones
enis Wolf ∗, Carlos Hermosilla, Anja Taubertnstitute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany
a r t i c l e i n f o
rticle history:eceived 10 October 2013eceived in revised form 2 December 2013ccepted 11 December 2013
eywords:orsexyuris equireatment failurenthelmintic resistance
a b s t r a c t
Whilst anthelminthic resistance of small strongyles is well documented, anthelmintic fail-ures against infections with Oxyuris equi have scarcely been published so far. We describetwo cases of equine oxyurosis and the anthelminthic failure of macrocyclic lactones (mox-idectin, ivermectin) resulting in persistent O. equi infections with continuous egg shedding.The horses were kept in two different herds in the federal state of Hessia, Germany. HerdA kept two geldings: an 8-year-old Welsh-Cob-Mix and a 7-year-old Haflinger. Herd Bwas composed of four animals: 2 Connemara-mares, 31 and 19 years old, one 18-year-old Connemara-gelding and a 27-year-old Norwegian Fjord mare. All animals had a casehistory of various anthelmintic treatments with macrocyclic lactones (moxidectin and iver-mectin alternating irregulary) in 2010 and 2011, nonetheless, they continued to shed O.equi nematodes and eggs. Animals were treated anew with moxidectin by members ofthe institute and were continuously monitored on a daily base by adhesive tape samples.Follow-up examinations for the reappearance of eggs were performed for 30 days in HerdA and 57 days in Herd B. In total, recurrence of O. equi egg shedding was detected in threeout of six horses within 1–4 weeks after treatment. In both herds accompanying horsessharing the same stable and paddock remained negative for detection of O. equi-eggs or
worms throughout the whole observation period. This is the first report in Europe showinginefficacy of commercial ivermectin compounds and furthermore the first report at all doc-umenting ineffectiveness of moxidectin compounds in the treatment of O. equi-infections inhorses indicating a possible development of resistance or confirming an existing incompleteoxyuricidal efficacy.. Introduction
The equine pinworm Oxyuris equi is a common horsearasite with a worldwide distribution. In the past,
esearch on equine nematodes has mainly been focusedn members of the superfamily Strongyloidea, especiallyyathostomes, since resistance of these parasites against∗ Corresponding author at: Institute of Parasitology, Justus Liebig Uni-ersity Giessen, Rudolf-Buchheim-Straße 2, 35392 Giessen, Germany.el.: +49 641 99 38461; fax: +49 641 99 38469.
E-mail addresses: [email protected],enis [email protected] (D. Wolf), [email protected]. Hermosilla), [email protected] (A. Taubert).
304-4017/$ – see front matter © 2014 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.vetpar.2013.12.009
© 2014 Elsevier B.V. All rights reserved.
anthelmintics represents a global problem (Coles et al.,2006). O. equi follows a direct life cycle with adults inhabit-ing mainly the right dorsal colon and in case of heavy infec-tions also the adjoining parts of the colon of equines (Enigk,1949). Females measure up to 15 cm and, after mating,they migrate to the anus to deposit eggs in sticky clumps(8000–60,000 eggs/female) seen grossly as yellowish whitegelatinous streaks on the skin of the perianal region (Enigk,1949). O. equi infections generally are recognized by horseowners owing to the pruritus caused by these semi-liquid
substances when desiccating, which can result in scratch-ing and damage to the tail. Exogenous development ofO. equi is rapid, and within 4–5 days the egg containsan infective L3. Eggs are rubbed off and contaminate the
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164 D. Wolf et al. / Veterinaryenvironment. Horses become infected by ingestion of eggscarrying an L3 on fodder, grass and bedding. Hatched lar-vae will invade the crypts of Lieberkühn in the ventralcolon and caecum, and within 3–11 days p.i. developmentinto 4th stage larvae takes place. The L4 will move slowlytowards the dorsal colon and from day 50 p.i. moulting into5th stage larvae begins and it will take another hundreddays to reach sexual maturity (Enigk, 1949). Nevertheless,the whole prepatent period may also take place within only4½–5 months (Hasslinger, 1990). Most of the pathogeniceffects of O. equi in the intestine are due to the feedinghabits of the larval stages, mainly of L4 within the mucosalcrypts, which result in small erosions of the mucosa and, inheavy infections, these may be widespread and accompa-nied by an inflammatory response (Enigk, 1949).
O. equi has been reported as sensitive for a broad numberof anthelmintics including benzimidazoles, hydropyrim-idines and macrocyclic lactones (Klei and Torbert, 1980;Lyons et al., 1980; Egerton et al., 1981; Yazwinski et al.,1982; Lyons et al., 1992; Bello and Lanningham, 1994;Xiao et al., 1994; Eysker et al., 1997; Bauer et al., 1998;Cleale et al., 2006). Anecdotal reports of treatment failuresusing ivermectin have recently been published (Durhamand Coles, 2010; Reinemeyer et al., 2010), as well astwo documented records from the USA and New Zealand(Reinemeyer, 2012; Rock et al., 2013).
In the past years our Institute was consulted severaltimes by veterinarians reporting on failures of macrocycliclactone treatments against O. equi. In this report we doc-ument two cases of equine oxyurosis with continuousshedding of O. equi-eggs despite repeated treatments witheither ivermectin or/and moxidectin compounds. The dataprovide first evidence beyond anecdotal reports for lack ofefficacy of ivermectin in the treatment of equine oxyurosisin Europe. Furthermore this is the first demonstration atall for treatment failure of moxidectin compounds. Theseresults call for more detailed studies on this topic, clarify-ing the actual incidence and molecular background of thisphenomenon.
2. Materials and methods
2.1. Study animals
Two veterinary surgeons medicating recreation-horsesfrom two different farms situated in the federal state ofHessia, Germany, independently contacted the Instituteof Parasitology, Justus Liebig University Giessen, in Marchand April 2012. They requested advice concerning effec-tive treatment alternatives for equine oxyurosis owing tothe fact that despite repeated anthelmintic treatments withmacrocyclic lactones horses continued to excrete adultnematodes in faeces and showed sticky tenacious eggmasses in the perianal region, accompanied by severe pru-ritus as the main clinical finding.
In farm A (Weilmünster, county of Limburg-Weilburg)
two geldings were kept: an 8-year-old Welsh-Cob-Mix(A1) and a 7-year-old Haflinger (A2). Both animals sharedthe same pen and a twin stable with two separate boxes.Both horses had received several anthelmintic treatmentslogy 201 (2014) 163–168
in 2010 and in 2011 (Table 1). After deworming the ani-mals in May 2011 the owner continuously found adultO. equi nematodes in horse dung of A1 within weeklyintervals. The same held true for the second treatmentin December 2011, in addition egg masses were foundin the perianal region. Consequently, moxidectin was re-administered in March 2012 but O. equi-worms and eggmasses reappeared within 5 days. In horse A2 neithernematodes nor egg masses were found during this observa-tion period. According to the owner the general conditionof A1 had been deteriorating when parasites appeared,the horse showing fatigue, decreased performance, alteredhoof growth and quality as well as incomplete shedding ofthe coat.
In farm B (Ehringshausen, county of Lahn-Dill) four ani-mals were kept: 2 Connemara-mares of 31 and 19 years ofage (B1 and B2), an 18-year-old Connemara-gelding (B3)and a 27-year-old Norwegian Fjord mare (B4). All animalswere kept in individual boxes but shared the same sta-ble and paddock. Animals received several anthelmintictreatments in 2010, 2011 and 2012 (Table 1). The horseowner first noticed O. equi-infections in winter 2010. Alsoin November 2011 infections were observed in form ofworms and egg masses and were accompanied by incom-plete shedding of the coat and damages of the tail. Clinicalfindings and parasitic stages were only observed in two (B1and B2) out of the four horses.
2.2. Surveyed treatments and sample collection by theInstitute of Parasitology
Whilst Horse A2 was left untreated, Horse A1 was med-icated anew by oral application of moxidectin [0.4 mg/kgbwt p.o. Equest®, Fort Dodge] according to the instruc-tions of the manufacturer. Thereafter, the animals werekept separately for ten days and the total horse faeces werecollected for further investigation. Both horses were mon-itored daily by adhesive tape samples for a period of 54days. Owners on both facilities were advised to clean theperianal areas of the horses after each sampling thoroughlywith wet cleaning tissues to prevent false positive resultsand to relieve the animals from itchiness. Additionally, thefaeces were analyzed by both, a combined sedimentation-flotation-technique for the detection of nematode eggs(Bauer, 1990) and sieving assays for the detection of adultnematodes (samples were rinsed through sieves of 4 mmand 0.5 mm aperture). Furthermore, horse A1 was med-icated with mebendazole [10 mg/kg bwt p.o. Telmin®,Janssen-Cilag] one month after moxidectin treatment.Thereafter, adhesive tape samples were continuously takenon a daily basis.
Horses B1–B4 had all just received an ivermectin-treatment (Table 1) when contacting the Institute ofParasitology. From two days later onwards animals weremonitored daily by adhesive tape samples for a period of115 days. To parallel the anthelmintic treatment sched-
ule of farm A, all animals were treated with moxidectin[[0.4 mg/kg bwt p.o. Equest®, Fort Dodge] after 5 weeks andwith mebendazole [10 mg/kg bwt p.o. Telmin®, Janssen-Cilag] after 13 weeks.
D. Wolf et al. / Veterinary Parasitology 201 (2014) 163–168 165
Table 1History of anthelmintic treatments of horses in two farms in the federal state of Hessia, Germany before the surveyed treatments and sample collection bythe Institute of Parasitology.
Date Farm A Farm B
Chemical class Dosage (mg/kg bwt p.o.);brand name
Chemical class Dosage (mg/kg bwt p.o.);brand name
2010January Ivermectin 0.2/Furexele
May Moxidectin 0.4/Equesta
August Ivermectin 0.2/Eraquellb
October Ivermectin 0.2/Vectinf
December Moxidectin + praziquantel 0.4 + 2.5/Pramoxc
2011January Ivermectin + praziquantel 0.2 + 1.5/Equimaxb
February Moxidectin (only B2) 0.4/Equesta
April Moxidectin 0.4/Equesta
May Pyrantel 19/Hippoparexd
June Moxidectin 0.4/Equesta
November Ivermectin (only B1) 0.2/Eqvalang
December Ivermectin + praziquantel 0.2 + 1.5/Equimaxb Ivermectin (only B1) 0.2/Paramectinh
2012January Ivermectin (only B1) 0.2/Vectinf
February Ivermectin (B1 and twice B2) 0.2/Vectinf
March Moxidectin 0.4/Equesta Ivermectin (only B1) 0.2/Eqvalang
April Ivermectin 0.2/Ivomec-Pg
Ivermectin 0.2/Furexele
Manufacturers’ details:a Fort Dodge Veterinär GmbH, Adenauerstr. 20, 52146 Würselen, Germany.b Virbac Tierarzneimittel GmbH, Rögen 20, 23843 Bad Oldesloe, Germany.c Zoetis Deutschland GmbH, Schellingstr. 1, 10785 Berlin, Germany.d Serumwerk Bernburg, Hallesche Landstr. 105b, 06406 Bernburg, Germany.e Janssen-Cilag GmbH, Johnson & Johnson-Platz 1, D-41470 Neuss, Germany.
heim, G
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f MSD Animal Health Innovation GmbH, Zur Propstei, 55270 Schwabeng Merial GmbH, Am Söldnermoos 6, D-85399 Hallbergmoos, Germany.h IDT Biologika, Am Pharmapark, D-06861 Dessau-Rosslau, Germany.
. Results
All faecal samples of horses A1 and A2 were diagnosedegative for nematode eggs by sedimentation-flotation-echnique and no (pre)adult O. equi were recovered byhe sieving assays. However, three days after moxidectinreatment nine dead adult worms were shed in the faecesf horse A1. No shedding of O. equi-eggs after applicationf moxidectin was observed in horse A2 (Fig. 1). How-ver, in horse A1 O. equi-egg excretion ceased within twoays after moxidectin treatment, but reoccurred within oneeek and continued for more than three weeks (Fig. 1a).orse A1 was then medicated with mebendazole 23 daysfter moxidectin treatment. Thereafter, shedding of O. equi-ggs diminished continuously. From day 9 post treatmentnwards O. equi-eggs were no longer detected and did noteoccur within the testing period of 14 days (Fig. 1b).
Within farm B, two animals (horse B1 and B2) showedrregular egg excretion from the 3rd (beginning of samp-ing) to the 11th day post ivermectin treatment (Fig. 2a).rom day 12 until day 17 no eggs were found on adhe-ive tapes. However, shedding of O. equi-eggs reoccurredrom day 18 onwards (Fig. 2a). After moxidectin applica-ion, O. equi egg excretion was detected for another five
ays (Fig. 2b). Thereafter, no more eggs were detected forhree consecutive weeks (Fig. 2b). However, 26 days afteroxidectin treatment, egg shedding reoccurred in horse B2nd four days later in horse B1 and continued irregularly
ermany.
onwards (Fig. 2b). Simultaneously the owner reported ontail rubbing of horse B1 due to severe pruritus. After meben-dazole treatment eggs were detected for five more days inhorse B2 but not in B1 (Fig. 2c). Thereafter, no more O. equi-eggs were detected in adhesive films until the end of thesampling period.
4. Discussion
Anthelminthic treatments with macrocyclic lactonesproved ineffective in eliminating O. equi infections in threerecreation horses from two different farms in the federalstate of Hessia, Germany. The effect of macrocyclic lactoneswas tested in a considerable number of controlled testsor critical controlled tests (Klei and Torbert, 1980; Lyonset al., 1980; Egerton et al., 1981; Yazwinski et al., 1982;Bello and Lanningham, 1994; Xiao et al., 1994; Eysker et al.,1997; Bauer et al., 1998; Cleale et al., 2006). It seems note-worthy though, that testing the effect of these compoundson O. equi was rather a side-effect than the main goal ofthese studies. As a result pinworms are not discussed verymuch in detail and only some authors report about thepre-treatment status of O. equi-infection (Klei and Torbert,1980; Lyons et al., 1980; Yazwinski et al., 1982; Bauer et al.,
1998). In many of the trials prevalence and efficacy wereonly based on the mere findings in the untreated control-group (Egerton et al., 1981; Bello and Lanningham, 1994;Xiao et al., 1994; Eysker et al., 1997; Cleale et al., 2006) and
166 D. Wolf et al. / Veterinary Parasitology 201 (2014) 163–168
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Fig. 1. O. equi egg excretion after anthelmintic treatment with moxidectin (a) and mebendazole (b) in horses A1 (grey column) and A2 (black column). Theintensity of eggs found on adhesive tapes is displayed in a semiquantitative scale: 1, sporadic; 2, moderately; 3, numerous; 4, massive.
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Fig. 2. O. equi egg excretion after anthelmintic treatment with ivermection (a), moxidectin (b) and mebendazole (c) in horses B1 (grey column) and B2(black column). The intensity of eggs found on adhesive tapes is displayed in a semiquantitative scale: 1, sporadic; 2, moderately; 3, numerous; 4, massive.
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ome studies do not represent an appropriate assessmentf efficacy against adult O. equi as stated by the authorshemselves (Eysker et al., 1997; Cleale et al., 2006). Nev-rtheless, most reports attest macrocyclic lactones to beotent agents against pinworms; Yazwinski et al. (1982)ound 100% removal of adult worms in ten horses with nat-ral infection after treatment with ivermectin and 95.7% to9.9 of L4 depending on the dosage used. Bauer et al. (1998)eported reduction of 99.9% of O. equi after treatment of 8aturally infected animals with moxidectin but does notiscriminate between adult and larval stages. Lyons et al.1980) reported an efficacy of ivermectin of 100% againstdults in 5 horses and more than 99% against immaturetages except for one animal in the group treated with theowest dosage [0.05 mg/kg bwt]. Another study states mox-dectin to be 100% efficient against L4 as well as adults at
dosage of 0.4 mg/kg bwt but only 88.2% at 0.3 mg/kg bwtXiao et al., 1994).
A rather poor performance compared to the studiesentioned above was found in another critical test by
yons et al. (2009) where small numbers of remaining pin-orms (n = 4–14) were found in three out of four horses
fter ivermectin treatment and removal of L4 was only 37%.Other reports of treatment failures in the United States,
ew Zealand and on anecdotal basis in the United Kingdomave recently been published (Durham and Coles, 2010;einemeyer et al., 2010; Reinemeyer, 2012; Rock et al.,013). Reinemeyer (2012) reported on survival of O. equifter ivermectin medication in three horses in Tennessee.hese horses were treated with ivermectin followed byyrantel pamoate two weeks later. This resulted in adultorm findings in the faeces, indicating survival of the first
reatment. Similar cases are reported from two horses fromifferent locations in New Zealand. One animal was treatedith ivermectin and the other with abamectin and both
eceived a consecutive treatment with oxfendazol after days leading likewise to the expulsion of several adultorms (Rock et al., 2013).
In the current report treatments with ivermectin andoxidectin led to reappearance of considerable numbers
f O. equi-eggs within one to three weeks after treatmentn two different groups of horses. Considering the longrepatent period of O. equi of at least 4½ months, the egghedding cannot result from a reinfection post-treatment.onsequently neither ivermectin nor moxidectin treat-ent have been fully effective. This does not comprise
nequivocal evidence of anthelmintic resistance as nonef the currently marketed anthelmintic compounds is rec-gnized by their respective regulatory agencies as beingonsistently 100% effective against adult O. equi. It couldlso confirm an existing but unnoticed incomplete oxyuri-idal efficacy of these compounds. Our results have to beeen in the context with similar findings (Reinemeyer et al.,010; Reinemeyer, 2012; Rock et al., 2013), indicating thathis could be a worldwide phenomenon which should be
ore thoroughly investigated.The uses of macrocyclic lactones in the involved herds
t least partly constitutes an excessively frequent use of single chemical class as to be seen in the history ofnthelmintic treatments, especially in farm B in 2011 and012 (Table 1). If a pinworm infection persists after a
logy 201 (2014) 163–168 167
repeated treatment with macrocyclic lactones a compoundfrom a different chemical class like benzimidazoles oracetylcholine receptor agonists (like levamisole or pyran-tel) should be used as an alternative. In this context itshould also be noted that anal pruritus or tail rubbing isnot a definitive evidence of O. equi infection. Owners mayconsider continued tail-rubbing after anthelmintic treat-ment to be definitive evidence of treatment failure. Thus,veterinarians should insist to apply more rigorous andevidence-based criteria for diagnosis.
A remarkable finding was the fact that in both farmssome horses seemed completely unaffected and freefrom pinworm infection though sharing the same stableand paddock as the infected animals and therefore thesame egg-contaminated environment. So far, there is noplausible explanation for this phenomenon, though theindividual immune status may most probably play a rolein this context.
O. equi inhabits the colon of domestic and wild equidsworldwide and is often described as a parasite of lowpathogenicity and thus of minor importance (Reinemeyerand Nielsen, 2009; Hasslinger, 1990). Nevertheless, ownerswill not be content with this statement and will not toleratepersisting pinworm infections but expect complete para-site elimination. Also, whilst the adult worms themselves,which seem to feed on ciliates (Bauer, 1986), apparentlycause no significant damage in the colon, the 4th stagelarvae will attach to the mucous membrane by sucking aproportion of the stratum glandulare into their cup-shapedoral cavity (Wetzel, 1930). As these larvae often changetheir place of attachment and require considerable nutri-tion their activity may cause a certain destruction of thesuperficial layers of the mucous membrane and lead tointestinal inflammation as shown by experimental infec-tions (Enigk, 1949). In the present case, three horses (A1, B1,B2) showed decreased general condition for a prolongedperiod. Horse A1, without apparently being ill, showedsigns of fatigue, reduced performance, altered hoof growth,and a poor quality of the coat, attributes, which accord-ing to the owner’s statement, improved significantly afterthe last treatment with mebendazole. The results of adhe-sive film testing indicated successful treatment of O. equiby mebendazole. Horses B1 and B2 showed less distinctbut still clearly perceivable deterioration of the generalcondition mainly concerning poor quality as well as incom-plete shedding of the coat. Overall, faecal examinationsvia sedimentation-flotation assays indicated no evidenceof other gastrointestinal parasites, such as cyathostomesor ascarids; an unsurprising fact, taking into account thepatient’s history of intense anthelmintic treatments. Thus,it remains possible that the poor general condition of theanimals could be attributed to the existing oxyurosis. Butit is also feasible that being in poor condition made theseindividuals more susceptible to the parasite.
5. Conclusion
O. equi specimens were no longer sensitive for bothcompounds ivermectin and moxidectin, indicating a possi-ble development of resistance in these horses or confirmingan existing incomplete oxyuricidal efficacy of these
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idectin and ivermectin against hypobiotic and encysted cyathostomes
168 D. Wolf et al. / Veterinary
compounds. Thus, veterinarians should be aware of thisdevelopment and consider other compounds than macro-cyclic lactones in treatment schedules for horses.
Conflicts of interest
The authors declare no conflicts of interest.
Acknowledgements
We thank the horse owners for their kind cooperationand their patience for the daily sampling of the animals.
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