Anthelmintic resistance in South Africa: surveys indicate an extremely serious situation in sheep and goat farming

Surveys to determine the prevalence and degree of resistance of Haemonchus spp. of sheep and goats to the available anthelmintics in South Africa indicate that small ruminant production is entering a crisis situation. Three surveys employing the faecal egg count reduction (FECR) test to determine resistance were conducted in some of the main sheep-producing areas in the summer rainfall region of South Africa, where H. contortus is the principal worm species in sheep. After analyzing the data recorded in the surveys by six different methods, including the RESO test at two different levels of confidence, the results obtained in the least stringent one (geometric mean reduction of the worm egg counts of drenched, vs untreated group of sheep) are reported in this paper, so that if any bias was obtained it would be in the favour of the anthelmintic. In Mpumalanga and KwaZulu-Natal there was anthelmintic resistance in Haemonchus spp. on all the 52 farms surveyed. Sixteen percent of the strains of H. contortus were < 60% susceptible to three of the four anthelmintics tested, and 8% of the strains were < 40% susceptible to all four of the anthelmintics. FECR tests of sheep in six localities in the Lebowa district of Northern Province indicated that even in previously disadvantaged communities where anthelmintic treatment is less intensive, anthelmintic resistance is developing, and is possibly at the level at which the situation on commercial sheep and goat farms in South Africa was 25 years ago. From the data it appears that the level of anthelmintic resistance of H. contortus in South Africa is possibly the highest that has so far been recorded in the world and that strains of it are emerging that may soon not be controllable by treatment with any of the existing anthelmintics. Farmers in the summer rainfall region, if not the whole country, must be alerted to the immediate need for testing the parasite burdens of their sheep for susceptibility to preparations in all four groups of anthelmintic compounds currently available. Alternative methods of integrated worm control, including biological, must be sought and implemented with urgency, to reduce further selection for resistance and to induce reversion of the resistance that has already developed.     

The problem of escalating resistance of Haemonchus contortus to the modern anthelmintics in South Africa

During the past decade in South Africa there has been a continual increase in sheep of strains of gastrointestinal helminths resistant to the modern anthelmintics. Five strains of Haemonchus contortus are described in this paper. Despite the fact that 2 of the 5 strains were tested for susceptibility only to ivermectin, a total of 10 instances of resistance were found. Four of the 5 strains were resistant to ivermectin, 2 to closantel, 2 to rafoxanide and 2 to the benzimidazoles. One of these strains was concurrently resistant to 3 different anthelmintic groups, namely, the ivermectins, the benzimidazoles and the salicylanilides. Resistance to ivermectin developed in 2 strains of H. contortus after a history of only 3 treatments with this compound in one instance and 11 treatments in the other. In the latter case drenching with ivermectin was well interspersed with that of other anthelmintics. This rapid development of resistance suggests that there may be cross-resistance between ivermectin and another anthelmintic group. Two of the ivermectin resistant strains were recovered from separate properties in the south-western Cape Province, where Ostertagia circumcincta, which is usually the dominant parasite in this region, was virtually eliminated by the anthelmintic treatment. On each of these properties it was apparently replaced by a resistant strain of H. contortus. A serious threat to control is the dissemination of worm strains with multiple resistance to anthelmintics. The strain of H. contortus resistant to 3 anthelmintic groups has already been widely dispersed, as the farmer concerned suddenly decided to give up farming with sheep and to sell his flock.     

Multiple Anthelmintic Resistance in Haemonchus Contortus on a Sheep Farm in Kenya

Multiple resistance to albendazole, thiophanate, levamisole and orally administered ivermectin was detected in an isolate of Haemonchus contortus in sheep on a farm where benzimidazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the benzimidazole-resistant isolate were treated with the recommended doses of various anthelmintics. Compared to the control group, the percentage reductions in the faecal egg counts of sheep treated with albendazole, thiophanate, levamisole and ivermectin varied between 38.2% and 79.1% and the residual worm counts between 27.3% and 57.5%. The results indicate the presence of multiple anthelmintic resistance in this isolate of H. contortus. Sheep treated with closantel showed 100% reductions in faecal egg and worm counts, indicating that this drug was very effective against the population of H. contortus on the farm.     

Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus

The development of moxidectin resistance (MOX-R) in sheep parasitic gastrointestinal nematodes already carrying multiple resistances to other anthelmintic groups has made control of these strains very difficult. The anthelmintic resistance patterns of MOX-R strains of Trichostrongylus colubriformis and Haemonchus contortus were characterized to provide an insight into the remaining role of anthelmintics in the control of such strains. Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72% reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%. Consequently, in H. contortus, the degree of dominance differs markedly between the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H. contortus but only 85 and 7%, respectively against the MOX-R homozygous T. colubriformis.     

Two field strains of Haemonchus contortus resistant to rafoxanide

Two field strains of Haemonchus contortus, one from Pretoria on the Highveld and the other from White River in the Lowveld of the Transvaal, showed pronounced resistance to rafoxanide at a dosage rate of 7.5 mg/kg live mass per os. Both of these strains originated from kikuyu pastures under irrigation. Resistance in South Africa to rafoxanide and other anthelmintics, namely, closantel, ivermectin and the benzimidazoles is reviewed. It is concluded that apart from avoiding farming practices where integrated worm control is not possible, there is at present no solution to the problem of worm resistance in the country.     

Efficacy of 3 anthelmintics in communally grazed sheep as reflected by faecal egg count reduction tests in a semi-arid area of South Africa

A survey was conducted on the occurrence of anthelmintic resistance of nematodes in communally grazed sheep in a semi-arid area near Mafikeng, South Africa, from January to March 2006. In the herds belonging to twelve smallholder sheep farmers, the efficacies of albendazole, levamisole and closantel were tested by faecal egg count reduction tests where 80 % efficacy was considered the cut off for anthelmintic resistance. The results of the faecal egg count reduction tests showed more than 80% efficacy with all the drugs used in most cases, but there were notable exceptions. In 1 case, closantel had an efficacy of 72%, albendazole had an efficacy of 68% and levamisole showed efficacies of 58%, 60% and 75% respectively on 4 farms. The occurrence of anthelmintic resistance in this farming sector is of concern and steps should be taken to prevent its further spread and development to avoid a situation developing as on numerous commercial sheep farms in South Africa where resistance is common.     

Anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area of South Africa

A survey was conducted on the occurrence of anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area in South Africa. In herds belonging to 10 small-holder goat farmers, the efficacies of fenbendazole, levamisole and rafoxanide were tested by faecal egg count reduction (FECR) tests. Efficacies of 80% were considered a threshold for anthelmintic resistance. The FECR tests showed that all drugs tested more than 80% effective in most instances, but there were notable exceptions. In 1 case, rafoxanide was only 31% effective and in another case fenbendazole was only 47% effective. The occurrence of anthelmintic resistance in this farming sector is of concern. Steps should be taken to prevent its further spread and to avoid the development of a situation as on numerous commercial sheep farms in South Africa where resistance is very common.     

Use of FAMACHA Scoring System as a diagnostic aid for the registration of distinguishing marks in the breeding program for lambs exposed to an experimental Haemonchus contortus infection

The control of gastro-intestinal nematodes in sheep has almost entirely been based on the use of anthelmintics and pasture management. Therefore anthelmintic resistance escalated in the past. One way of reducing this problem may be the limitation of anthelmintic treatment to those animals with clinical symptoms only. The FAMACHA Eye-colour-chart is based on the principle knowledge that the colour of mucous membranes are correlated with the anaemiae situation of an animal. To monitor anaemic animals they are identified and classified in a 1 to 5-color scale based on the colour of the conjunctiva, and anaemic animals can be selectively treated. It helps to reduce treatments and therefore the development of drug resistance. The objective of this study was to estimate the correlation between FAMACHA-scores, haematocrit values, faecal egg counts, plasma albumin level and worm burden following an experimental infection with Haemonchus contortus in lambs. The estimated correlations have been low. This proofs the limits of the FAMACHA system under a situation of low parasite pressure.     

The epidemiology and control of gastrointestinal nematode infestation of sheep and cattle in South Africa. I. The historic role of Onderstepoort and a short discussion of present research priorities

The research activities of the Veterinary Research Institute, Onderstepoort, from its inception in 1908 until recent times are reviewed in this first article of a series on nematode epidemiology of sheep and cattle. While the taxonomic and certain biological aspects of the subject and the testing of anthelmintic compounds have been well covered on the whole in various parts of the country, the testing of control methods under field conditions has largely been neglected. It is suggested that all known methods of integrated worm control should be scrutinized and the most promising methods be tested under practical farming conditions in the country to reduce our dependence on anthelmintic compounds for worm control. Furthermore, unless we are able to employ the available anthelmintics to better advantage and thus reduce the tempo of selection for resistance, the situation may well develop where highly effective remedies are no longer available for worm control.     

The FAMACHA system for managing haemonchosis in sheep and goats by clinically identifying individual animals for treatment

Escalating anthelmintic resistance has made it essential to develop alternative ways of worm management for reducing selection for worm resistance, and one of the most promising approaches is to treat only those animals unable to cope with worm challenge, thus favouring unselected worms originating from untreated animals. Only clinical evaluation of anaemia (FAMACHA system) and the body condition score are regarded as being of practical value or having potential, respectively, for repeatedly examining flocks or herds and identifying individuals for treatment. Only the FAMACHA system has been tested well enough for use under practical farming conditions. However, further investigation is needed on its effect on animal production, and methods to reduce labour. Trials over several seasons showed that most sheep under severe Haemonchus contortus challenge required no, or only one treatment over a full summer season. A small minority (usually < 5%) needed more than two treatments. Most sheep could cope without regular treatment. With sufficient training, clinical evaluation of anaemia was found reliable for practical use. The overwhelming majority of trainees (some poorly literate) were able to implement the FAMACHA system successfully. The dynamics of haemonchosis in a flock can easily be monitored. Farmers, farm workers and veterinarians all rated the system very highly (> 80%) and treatment costs dropped by approximately 58%. The heritability of FAMACHA values obtained by clinical evaluation was high at 0.55 +/- 0.17% in a Merino stud with +/- 550 young rams and ewes which were the progeny of 21 sires. The FAMACHA system may not be as applicable to goats as to sheep, but further work is necessary. The main benefits of the system are the reduction in treatments, its use for discriminating between animals of varying ability to cope with infection (thus allowing genetic selection), and its lowering of selection pressure on H. contortus for anthelmintic resistance.     

Efficacy of a combined oral formulation of derquantel-abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains

Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(?)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal and respiratory nematode parasites of sheep, as follows: ≥ 98.9% efficacy against Haemonchus contortus (adult and L4); Teladorsagia circumcincta (adult, L4 and hypobiotic L4); Teladorsagia trifurcata (L4); Trichostrongylus axei (adult and L4); Trichostrongylus colubriformis (adult and L4); Trichostrongylus falculatus (adult); Trichostrongylus rugatus (adult); Trichostrongylus vitrinus (adult and L4); Cooperia curticei (adult and L4); Cooperia oncophora (adult and L4); Nematodirus spathiger (adult); Nematodirus battus (adult); Nematodirus spp. (hypobiotic L4); Strongyloides papillosus (adult); Strongyloides spp. (L4); Chabertia ovina (adult); Oesophagostomum venulosum (adult); Dictyocaulus filaria (adult); and Protostrongylus rufescens (adult); ≥ 97.0% efficacy against Trichuris ovis (adult); and ≥ 95.9% efficacy against T. trifurcata (adult). Derquantel-abamectin is a highly effective combination anthelmintic, which will provide an important new tool for controlling helminths of sheep when used in conjunction with sustainable drenching practices.     

Refugia--overlooked as perhaps the most potent factor concerning the development of anthelmintic resistance

Anthelmintic resistance involving particularly the gastrointestinal nematodes of small ruminants is escalating globally, to the extent that in certain countries, such as South Africa, it has already reached alarming proportions, and is affecting practically all the anthelmintics. In this paper it is argued that the high levels of resistance in nematodes of veterinary importance indicate that the drugs have been used incorrectly. It is suggested that the phenomenon of refugia plays a much more important role in the selection of anthelmintic resistance than other phenomena that are more frequently investigated and recommended for counteracting it, such as reduced drenching frequency and avoiding under-dosing. While refugia is commonly mentioned in passing in most papers on anthelmintic resistance, it is, almost without exception, not incorporated in the final control/ management proposals. On the strength of the conclusions arrived at in the present paper strategies such as the drench-and-move system in which all the animals in a flock are drenched before they are moved to pastures containing few or no worms in refugia, and the system of strategic drenching on safe pastures should be condemned and never recommended. If such strategies are indeed unavoidable, the farmer should be warned that the farming system would probably not be sustainable even in the short term, in view of the generally high levels of resistance already present in most of the important sheep-producing regions. Farmers should be educated to consider refugia above all else when designing worm management programmes. Finally there seems to be too much complacency concerning the possibility that anthelmintic resistance may also escalate in cattle, eventually to reach the proportions that it has in sheep.     

High perinatal mortality associated with triple anthelmintic resistance in a German sheep flock

High perinatal mortality, low milk yields and occasional ewe deaths were investigated in a Dorper sheep flock in Southern Germany. Parasitic gastroenteritis due to Trichostrongylus spp. associated with severe weight loss despite regular anthelmintic treatments of the flock was identified as the underlying cause. A faecal egg count reduction (FECR) test revealed zero reduction after treatment with ivermectin or albendazole, respectively, and a FECR of 57.9% following treatment with levamisole. These results indicate a lack of, or considerably reduced efficacy of substances from all three classical groups of anthelmintics and demonstrate that triple anthelmintic resistance is also present in Germany. The introduction of resistant worm populations with imported livestock, excessive use of anthelmintic drugs and under-dosing of goats have possibly led to the problem in the flock described. Veterinary advice on anthelmintic treatments and responsible parasite control programmes are therefore crucial in small ruminant flocks.     

Drug resistance in ostertagiasis

Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance. Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue.     

A preliminary undifferentiated faecal egg count reduction test survey in the Caledon area

During October 1998 a study was performed in the Caledon area to determine the presence of anthelmintic resistance in the southern Western Cape, which falls within the winter rainfall region of South Africa. The study took the form of an undifferentiated faecal egg count reduction test (FECRt) survey. The predominant worm genera of the region are Teladorsagia and Trichostrongylus, but Haemonchus causes occasional outbreaks in sheep. No resistance data for any area in the Western Cape Province are available at present. Resistance (< 90% FECR) was recorded on 73% of the farms included in the study, with 46% of these involving resistance to 1 drench, 36% to 2 drenches and 18% to 3 drenches. No moxidectin resistance was detected when it was administered at the therapeutic dosage of 0.2 mg/kg. The results of this study show clearly that resistance of nematodes to other anthelmintics occurs in the Caledon area.     

Haemonchus contortus with low inhibited development in sheep from the highveld of Zimbabwe

The abomasa of sheep grazing on natural pastures in the highveld of Zimbabwe were examined for Haemonchus contortus. Of 304 abomasa, 213 (70%) harboured H. contortus. The worm burden increased during the rains to reach the peak in February-March. This was followed by a decline with low worm loads throughout the dry season. The fourth stage larvae (L4) accounted for 1-7% of the total H. contortus population, except during July and August when they comprised 22 and 54% of the worm burden, respectively. It appears that the inhibition of H. contortus is not common in the commercial farming sector where sheep are treated very frequently.     

Possible application of a nematophagous fungus as a biological control agent of parasitic nematodes on commercial sheep farms in South Africa

Biological control of parasitic nematodes of livestock is currently under development and represents another tool that may be integrated into helminth parasite control strategies. This paper presents a brief introduction to commercial sheep farming in South Africa and currently available nematode parasite control methods. These include the FAMACHA clinical assay, strategies of pasture management, dilution of resistant worm species by introduction of susceptible worms, breed resistant sheep and nutritional supplementation. The purpose of this paper is to outline the principles of biological control using nematophagous fungi and how it may be applied on sheep farms in South Africa.     

South African field strains of Haemonchus contortus resistant to the levamisole/morantel group of anthelmintics

A strain of Haemonchus contortus from the Pietermaritzburg district of Natal was found to be resistant to levamisole (geometric mean efficacy 76.5%), morantel (41.9%), the benzimidazoles (oxfendazole: 33.7%) and rafoxanide (82.0%), but apparently fully susceptible to closantel and disophenol. In the case of ivermectin, a mean of 5.2% of the H. contortus was not removed at a dosage of 200 micrograms kg-1 live mass. A second strain of H. contortus, from Amsterdam in the south-eastern Transvaal, showed reduced susceptibility to levamisole (80.8%) and morantel (46.2%), the only 2 drugs tested. This is apparently the first report of resistance to the levamisole/morantel group of anthelmintics in sheep in South Africa.