J.A. Van Wyk

How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics

This paper describes an exceptional spectrum of multiple anthelmintic resistance in two strains of Haemonchus contortus in South Africa, one from Howick in KwaZulu-Natal, and the other from Badplaas, in Mpumalanga. Apparently for the first time, a helminth strain is described with resistance to compounds from all five of the modern anthelmintic groups used for nematode control in sheep; also, two strains of H. contortus show resistance to the two substituted phenols, dinitrophenol and nitroxynil. Only closantel at 5 mg kg-1 of nine compounds tested appears to have undiminished efficacy against the Howick strain, but even in the case of closantel, the residual activity and minimal effective level need to be tested before it can be concluded that its efficiency is unaffected. The exceptional resistance of the Howick strain is demonstrated by the fact that sequential daily drenching of sheep infected with the strain, with levamisole at 18 mg kg-1, oxfendazole at 20 mg kg-1, levamisole at 20 mg kg-1 and a mixture of fenbendazole at 10 mg kg-1 plus trichlorfon at 132 mg kg-1 on the fourth day, failed to clear sheep of the infection. There are strong indications that side-resistance occurs between dinitrophenol and nitroxynil, on the one hand, and the salicylanilides, on the other, and it is suggested that, before long, strains of H. contortus will be found with high levels of resistance to all the currently available anthelmintics.

Genetic parameters for FAMACHA© score and related traits for host resistance/resilience and production at differing severities of worm challenge in a Merino flock in South Africa.

The objectives of this study were to estimate genetic parameters for FAMACHA score and related traits at different levels of worm challenge in sheep and to assess the effect of different methods for modelling records from treated lambs on estimates of genetic parameters. Data were collected over five consecutive Haemonchus seasons from a total of l671 Merino lambs using the FAMACHA clinical evaluation system, and anaemic individuals were treated as needed, until flock health necessitated mass treatment at the peak of the worm season. Records of each sampling occasion were classified into low, moderate, or peak levels of worm challenge. Animal models were run separately for traits within each data set. Alternative analyses were conducted in which records of treated lambs were (1) included without adjustment, (2) included along with a fixed effect representing treatment status of the lamb for each record, and (3) included after application of a penalty to offset any phenotypic improvement or advantage due to that treatment. Estimates of heritability for individual FAMACHA data sets ranged from 0.06+/-0.04 to 0.24+/-0.05, the highest estimates being obtained for peak worm challenge data. Estimates of genetic correlation for FAMACHA with other traits varied, but were always near negative unity for FAMACHA score with haematocrit value. When data of treated lambs were penalised, higher estimates of heritability were obtained than when not penalised, hence this may be an effective method for allowing for early treatment of overly susceptible animals before the level of worm challenge is at an optimum level for BLUP (Best Linear Unbiased Prediction) evaluation. The estimate of genetic correlation for FAMACHA score in moderate worm challenge with that in peak worm challenge was almost unity. This suggests that estimation of breeding values for this trait using data from moderate worm challenge may be as effective as that from peak challenge.

Preliminary observations on the potential of gut membrane proteins of Haemonchus contortus as candidate vaccine antigens in sheep on naturally infected pasture.

In a trial lasting 11 months in South Africa, faecal egg counts and haematocrits of sheep vaccinated with gut membrane proteins of adult Haemonchus contortus were compared with unvaccinated controls grazing pasture contaminated with the parasite. Vaccination reduced egg output by >82% on average during one 4 month period of the trial and simultaneously significantly reduced the degree of anaemia and deaths due to haemonchosis. Although vaccine immunity was not sufficiently long lasting to prevent a surge in egg output which occurred after the onset of a period of irrigation, re-vaccinating the sheep at this point cleared their newly acquired infection and rapidly restored protection to approximately the level observed beforehand. It was clear that a vaccine based on parasite gut membrane proteins could offer substantial benefits in the control of natural haemonchosis.

Validation of the FAMACHA© eye colour chart using sensitivity/specificity analysis on two South African sheep farms

A validation study of the FAMACHA(©) system for clinical evaluation of anaemia due to Haemonchus contortus was conducted on two commercial sheep farms in the summer rainfall region of South Africa. In this region, the Haemonchus season lasts from October to April. On Farm 1 the system was tested over a period of five successive years in consecutive sets of young stud Merino replacement rams and ewes examined at intervals of 3-5 weeks over each Haemonchus season, under routine farming conditions. When FAMACHA(©) scores of 3, 4, and 5 and haematocrit values of ≤ 22%, ≤ 19%, and ≤ 15% were separately considered to be anaemic, sensitivity on Farm 1 ranged from a maximum of 83% for a haematocrit cut-off of ≤ 15%, to 40% for a haematocrit cut-off of ≤ 22%. Sensitivity increased to 93% when FAMACHA(©) scores of 2, 3, 4, and 5 were considered anaemic at a cut-off value of ≤ 19%, but the positive predictive value decreased to 0.43, indicating that many non-anaemic animals would be treated. The analysis indicated a high level of classification bias on Farm 1, with the animals consistently being classified one FAMACHA(©) category lower (i.e. less anaemic) than reality. On Farm 2 the test was conducted over two successive years in yearling rams evaluated at weekly to fortnightly intervals during each worm season. Every ram judged to be in FAMACHA(©) category 4 or 5 was bled for haematocrit determination, and it was only dewormed with effective anthelmintics if the haematocrit was 15% or lower. When FAMACHA(©) scores of 3, 4, and 5 and haematocrit values of ≤ 22% and ≤ 19% were separately considered to be anaemic on Farm 2, sensitivity ranged from 64% for a haematocrit cut-off of ≤ 22%, to 80% for a cut-off of ≤ 19%. For identical haematocrit cut-off values and proportions of the sampled flock considered to be diseased as for Farm 1, sensitivity was always higher for Farm 2. On the other hand, further analysis of the data indicated that the magnitude of the error on Farm 1 was very consistent on average over the entire trial period. The results of this study indicate that (i) persons introduced to the system should not only be trained, but also be evaluated for accuracy of application; (ii) the sensitivity of the FAMACHA(©) diagnostic system should ideally be evaluated at shorter intervals to avoid production losses due to failure to detect anaemic animals which may be at risk of death; (iii) that calibration of the FAMACHA(©) scoring is essential per individual evaluator, and (iv) that animals should be examined at weekly intervals during periods of the highest worm challenge.

A novel approach to the control of anthelmintic-resistant Haemonchus contortus in sheep.

Abstract This paper reports attempts to control a resistant strain of Haemonchus contortus on pasture by replacing it with a susceptible strain. By making use of artificially infected donor sheep, six camps (paddocks) were seeded with a resistant field strain of H. contortus until it was confirmed by means of worm-free tracer lambs that the grazing had become infective. Thereafter, using donor sheep infected with a susceptible laboratory strain of H. contortus for seeding the pasture, attempts were made at various times of the year to replace the resistant strain on the pasture with the susceptible strain in five of the camps. The sixth remained as a control camp, in which no attempt was made to replace the resistant strain. In two of the five test camps, the susceptible strain was introduced in the autumn after 8–10 weeks of nil grazing; in the remaining three camps the introduction was made in spring (two camps) or summer without having a period of nil grazing. The susceptibility of the worm strains introduced initially, as well as of those that developed in the various camps, was gauged both by controlled non-parametric anthelmintic slaughter trials at the beginning and at the conclusion of the trial, and by an in vitro egg hatch test. A reversion to susceptibility occurred in three of the five camps. These included both of the camps infested with the susceptible strain in the spring and one of the two infested in the autumn. Possible reasons for the failure to replace the resistant strain in the remaining two test camps are discussed.

Quality control in generic anthelmintics: Is it adequate?

We became increasingly concerned about indications of possible substandard efficacy of some generic anthelmintics, particularly after P.C. van Schalkwyk (personal communication, 1990) had found some batches of imported generic products obtained from international brokers to be poorly active, despite apparently normal physical characteristics. Therefore, considering the serious consequences this would have for sheep farming, it was decided to test the efficacy of some of the generic rafoxanide products available on the South African market. One of the three commercial formulations (of highly reputable companies) tested against a known susceptible strain of Haemonchus contortus in sheep was markedly substandard, with an arithmetic mean efficacy of 66.2% (Class B, Reinecke, 1973), compared to Class A efficacy of the other two, which also differed significantly from one another (Mann-Whitney; P = 0.01). Larger differences were found between the three products against a natural infection with a partially resistant strain of H. contortus than against the susceptible strain, with corresponding arithmetic mean efficacies of 28.7% (Class X, or ineffective), 71.3% (Class B) and 87.7% (also Class B). It is concluded that the most likely reason for the observed differences is that international brokers do not disclose the sources of supply of different batches of active ingredient (with the result that the companies buying anthelmintics from them have no way of telling when a source of supply is changed); that the efficacy of such batches differs; and that efficacy testing of individual batches in some cases is inadequate. It is suggested that registering authorities should consider simplified efficacy testing of each new batch of active ingredient before it may be marketed.

Blueprint for an automated specific decision support system for countering anthelmintic resistance in Haemonchus spp. at farm level.

This article is the first of a series aimed at developing specific decision support software for on-farm optimisation of sustainable integrated management of haemonchosis. It contains a concept framework for such a system for use by farmers and/or their advisors but, as reported in the series, only the first steps have been taken on the road to achieve this goal. Anthelmintic resistance has reached such levels of prevalence and intensity that recently it evoked the comment that for small ruminants the final phase of resistance was being entered, without effective chemotherapeutic agents on some farms with which to control worms at a level commensurate with profitable animal production. In addition, in the case of cattle, a recent survey in New Zealand showed 92% of worm populations to be resistant to at least one anthelmintic group. Ironically, new technology, such as the FAMACHA(©) system which was devised for sustainable management of haemonchosis, is at present being adopted relatively slowly by the majority of farmers and it is suggested that an important reason for this is the complexity of integration of new methods with epidemiological factors. The alternatives to the simple drenching programmes of the past are not only more difficult to manage, but are also more labour-intensive. The problem is further complicated by a progressive global shortage of persons with the necessary experience to train farmers in the new methods. The opinion is advanced that only computerised, automated decision support software can optimise the integration of the range of factors (such as rainfall, temperature, host age and reproductive status, pasture type, history of host and pasture infection, and anthelmintic formulation) for more sustainable worm management than is obtainable with present methods. Other than the conventional method (in which prospective analysis of laboratory and other data is mainly used to suggest when strategic prophylactic drenching of all animals for preventing excessive helminthosis should be conducted during the relevant worm season), the computer model being proposed is to be based on targeted selective treatment, supported by progressive periodic retrospective analysis of clinical data of a given worm season. It is emphasised that, in order not to repeat the mistakes of the past, such an automated support system should ideally be developed urgently in a attempt to engineer greater sustainability of any unrelated new anthelmintics which may reach the market.

Wildlife parasites: Lessons for parasite control in livestock

For sustainable livestock production it is suggested that the parasitologist take a leaf out of Natures book in the search for solutions to the mounting problems concerning parasite control. While the farmer has come to regard all parasites affecting livestock as entirely without benefit, indigenous parasites and diseases are normal and play an essential role as interacting components of a natural environment in an ecosystem such as the 19,000 km2-sized Kruger National Park, Republic of South Africa. The parasites help to select their hosts for fitness and are assisted by predators and intra-species territorial aggression which continually eliminate the weak individuals from the system. It is essential to guard against the introduction of foreign parasites or infectious agents which have no real ecological niche or role in an established ecosystem, however, as they cause untoward interactions, sometimes of a violent nature. The policy must be to block off or, failing that, to control or eliminate these foreign parasites and diseases as far as possible. Often, when Man intervenes in an ecosystem, it leads to stress, overcrowding and stagnation and predisposes to disease and death. Intensification of the system, as in farming units, denies Nature the chance to manage on its own, because of clashing interests with Man. Frank parasitism and disease should almost invariably be seen as indicators of an imbalance in the ecosystem and should be rectified. Chemicals and vaccines should be used to produce sufficient food for all, but without exploiting Nature, or else Nature will be unable to continue catering for Mans needs.

Effects of time of day, season and stratum on Haemonchus contortus and Haemonchus placei third-stage larvae on irrigated pasture.

The effect of time of day, season and stratum of herbage and soil on the availability of Haemonchus contortus and Haemonchus placei third-stage larvae (L3) on pasture was assessed. Feces from infected calves and lambs were placed on pasture plots and samples of upper herbage, lower herbage, mat and soil were collected at five intervals per day throughout the daylight hours on 18 sample days over 12 months. Using recovery rate factors derived from a preliminary investigation on the efficacy of larval recovery from each stratum, the data on larval recoveries were analyzed for the effect of season, time and stratum, and their interactions. Significant (P less than 0.05) differences were found for season, stratum and the season-with-stratum interaction for both parasites. No significant differences were detected for larval counts at different times of the day. Larval recoveries of H. contortus were larger throughout the study than those of H. placei. Most H. contortus L3 were recovered in the summer and autumn, and H. placei in the spring and summer. For both parasites, the recoveries of larvae from the upper and lower herbage were larger than those from the mat and soil. The implications of these findings are discussed in terms of control strategies.

Moisture requirements for the migration of Haemonchus contortus third stage larvae out of faeces

The abomasal nematode Haemonchus contortus causes severe disease and production loss in small ruminants in warmer regions and is also an emerging threat in many temperate climates. Specific knowledge of the effects of climate on the epidemiology of H. contortus is needed to effectively apply sustainable control strategies, which rely on prediction of infection risk. Although the effects of temperature and rainfall on larval development in this species have been characterised, much less is known about migration out of faeces and onto herbage. This is an important deficit in our understanding of the epidemiology of haemonchosis in regions with relatively low and particularly erratic rainfall. Methods were developed to assess the migration of third stage larvae (L3) out of faeces under simulated rainfall in the laboratory. These were applied in a series of experiments, which showed that rainfall is required for migration. However, a single rainfall event was not sufficient for migration from faeces of which the crust has hardened after having been kept in dry conditions. Light and regular rainfall resulted in rapid emergence from moist faeces kept in humid conditions, but much slower emergence from dry faeces in dry conditions. Ambient relative humidity therefore appears to act through faecal moisture content to modify the effect of rainfall on larval migration. Larvae survived well in dry faeces for a number of days, but did not migrate in the absence of rainfall, so sheep faeces could potentially act as a larval reservoir in dry conditions, with peaks of infection following rainfall. Rates of faecal desiccation and rehydration on pasture could therefore be highly relevant to temporal patterns of larval availability.