G. C. Coles

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance

Methods have been described to assist in the detection of anthelmintic resistance in strongylid nematodes of ruminants, horses and pigs. Two tests are recommended, an in vivo test, the faecal egg count reduction test for use in infected animals, and an in vitro test, the egg hatch test for detection of benzimidazole resistance in nematodes that hatch shortly after embryonation. Anaerobic storage for submission of faecal samples from the field for use in the in vitro test is of value and the procedure is described. The tests should enable comparable data to be obtained in surveys in all parts of the world.

Resistance of Schistosoma mansoni to praziquantel: is there a problem?

Evidence for resistance to praziquantel (PZQ) in Schistosoma mansoni has been sought in parasites taken from treated, but uncured human patients, and in a laboratory isolate of S. mansoni subjected to successive passages under drug pressure. Patients from villages in Egypt and Senegal have yielded isolates that can tolerate higher dosages of PZQ than other ostensible control isolates when passaged and subjected to drug treatment in mice. In vitro tests on these and the laboratory-selected isolate support the conclusion that a degree of resistance to PZQ can occur in S. mansoni, but the levels of drug resistance found so far are low. Preliminary studies have begun on these isolates to identify genetic, physiological and morphological characteristics associated with PZQ resistance and some of these may find use as markers for monitoring whether or not resistance is developing in endemic areas where the drug is used. More intensive application of PZQ can be expected in future, particularly in other parts of Africa, and vigilance will be needed to ensure that it continues to be useful as a drug for treatment of schistosomiasis. Further work is needed to elucidate the mode of action of PZQ and there is already a need for alternative drugs to treat PZQ-resistant schistosomiasis, such as already exists in northern Senegal.

The role of targeted selective treatments in the development of refugia-based approaches to the control of gastrointestinal nematodes of small ruminants

Anthelmintic resistance is recognised as a major problem affecting small ruminant production worldwide and now threatens the sustainability of many of these systems. One method that has been proposed to prolong the efficacy of our current anthelmintics is the maintenance of a parasite population in refugia (unexposed to a drug) which will maintain the genes for susceptibility within the parasite population. Management strategies that employ refugia-based methods include targeted or strategically timed whole flock treatments, targeted selective treatments (TST), whereby only a proportion of the flock is treated at any one time, and the dilution of resistant with susceptible parasites. The ability to effectively target anthelmintic use relies on the identification of those animals that will most benefit from treatment. This review explains the concept of refugia, describes the role of refugia-based approaches to the management of anthelmintic resistance and reviews the markers that have been studied as indicators for TSTs as well as the implementation of refugia-based strategies. Recent results suggest that targeting anthelmintic treatment on the basis of anaemia, milk production and liveweight gain may offer a means of reducing anthelmintic usage whilst still maintaining animal performance.

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possible.

Haemonchus contortus Glycoproteins Contain N-Linked Oligosaccharides with Novel Highly Fucosylated Core Structures

Structural studies on the N-linked oligosaccharides of Haemonchus contortus, an economically important nematode that parasitizes domestic ruminants, have revealed core fucosylation of a type not previously observed in any eukaryotic glycoprotein. Mass spectrometric analyses were performed on detergent extracts of homogenized adult H. contortus and on purified H11, a glycoprotein isolated from intestinal brush borders which has been previously shown to be an effective vaccine antigen. The major N-linked glycans identified in the present study have up to three fucose residues attached to their chitobiose cores. The fucoses are found at the 3- and/or 6-positions of the proximal GlcNAc and at the 3-position of the distal GlcNAc. The latter substitution is unique in N-glycans. Most anti-H11 monoclonal antibodies are known to recognize carbohydrate epitopes, and it is possible that the newly discovered multifucosylated core structures are highly immunogenic in this glycoprotein.

Anthelmintic resistant nematodes in Brazilian horses

ANTHELMINTIC resistance in nematodes in horses is an increasing problem. In the south-eastern usa, all thoroughbred yards investigated in one study had benzimidazole-resistant nematodes and nearly half had pyrantel-resistant worms, but there was no evidence of resistance to the macrocyclic lactones

Head Lice: Prevalence in Schoolchildren and Insecticide Resistance

Several small case studies have shown a therapeutic response for oral cotrimoxazole22xShashindran, C.H. et al. Br. J. Dermatol. 1978; 98: 699Crossref | PubMedSee all References22, oral and topical ivermectin23xGlaziou, P. et al. Trop. Med. Parasitol. 1994; 45: 253–254PubMedSee all References, 24xYoussef, M.Y. et al. Am. J. Trop. Med. Hyg. 1995; 53: 652–653PubMedSee all References, topical crotamiton25xKaracic, I. and Yawalkar, S.J. Int. J. Dermatol. 1982; 21: 611–613Crossref | PubMedSee all References25, and topical 1% copper oleate shampoo26xIannantuono, R.F. et al. Adv. Ther. 1997; 14: 134–139See all References26. We have also assessed the novel flea adulticides, fipronil and imidicloprid, and found them to be 97 and 100% effective in vitro against head and body lice (unpublished). Alternative carbamates such as propoxur or alternative organophosphates such as temephos27xMazzarri, M.B. and Georghiou, G.P. J. Am. Mosq. Control Assoc. 1995; 11: 315–322PubMedSee all References27 may be unaffected by the resistance mechanism against malathion. All these agents may have a place in the control of head lice. If a new agent is introduced into the human market, it is likely that head lice will eventually develop resistance. To reduce chronic use, and so slow the development of resistance, an option would be to have all insecticides available by prescription only. Strategies should be used to keep head lice levels to a socially acceptable minimum level. Strategies such as educational campaigns by community nurses, doctors and school teachers should promote head lice eradication. Although it is doubtful whether regular combing will cure a head lice infestation, it is likely to reduce the numbers of lice carried and should be promoted as the first line of treatment before insecticides. Children who fail to clear their infestations should be targeted by school nurses for treatment. All family members and classmates should be assessed for asymptomatic carriage. Ideally, all schoolchildren should be at separate desks during lessons to reduce transmission of head lice. Given the national rise in the prevalence of head lice and in insecticide sales, it is likely that the resistance phenomenon we have observed in Bristol and Bath is nationwide, and will require national changes in attitudes towards the treatment and surveillance of this ectoparasite.

Activity of oxyclozzanide, nitroxynil, clorsulon and albendazole against adult triclabendazole resistant Fasciola hepatica

mouths are being examined for the presenc( tion. However, where there is a high perce lesions, some consideration should be ma length, herbage contamination by poachir feeding blocks, and stress factors. With no such factors may be inducing the OMAGOD le dence for any possibility of FMD infection sho up. Such factors are speculative, but, because upon time and the inability to submit blood FMD-induced restrictions, it was not possible 1 other epidemiological investigations, or any other than histopathology.

Drought and flock isolation may enhance the development of anthelmintic resistance in nematodes

A survey of anthelmintic resistant nematodes was conducted in sheep and goat flocks in Greece using in vivo and in vitro tests. Faecal egg count reduction tests in Macedonia were all greater than 99% indicating very high sensitivity of the nematodes to anthelmintics. In vitro tests showed benzimidazole resistant Teladorsagia circumcincta in 17 out of 106 flocks on small islands. On the mainland there were only three cases of benzimidazole resistance out of 310 flocks and animals had recently been introduced to the flocks. Flocks on the islands are isolated and there are higher temperatures than on the more mountainous mainland, where flocks tend to intermingle. It is concluded that drought and isolation are likely to be the major factors accounting for the development of anthelmintic resistance in nematodes in the island flocks.

In vitro responses of praziquantel-resistant and -susceptible Schistosoma mansoni to praziquantel

The resistance status of five praziquantel-susceptible and five praziquantel-resistant isolates was confirmed by chemotherapy in CD(1) mice with 3 x 200mg/kg micronised praziquantel. Micronised praziquantel had higher efficacy than two other praziquantel formulations (prepared without milling). The five resistant isolates were less responsive to praziquantel than the five susceptible isolates (59-74% reduction in worm burden in resistant isolates compared with 92-100% in susceptible isolates). Observations were made on the in vitro responses of different stages of 10 isolates to praziquantel. There were different in vitro responses to praziquantel at the egg, miracidial, cercarial and adult stages of Schistosoma mansoni between praziquantel-resistant and praziquantel-susceptible isolates. There were differences in the response of resistant and susceptible isolates following exposure of freshly hatched miracidia to 10(-6)M praziquantel for 1 min and observing the percent change in shape. Using this test it should be possible to determine whether failed therapy in patients infected with S. mansoni is due to the presence of praziquantel-resistant worms. Similarly, by exposing freshly shed cercariae to 4 x 10(-7)M praziquantel and observing the percent of tail shedding over 80 min it should be possible to monitor for the presence of praziquantel-resistant worms in snails collected in the field.