Albendazole, a new anthelmintic drug was evaluated in Malaysia in 91 patients, with single or mixed infections of Ascaris, Trichuris, and hookworm. Albendazole was administered as a single dose of 400 mg, 600 mg, or 800 mg. The cure rate for Ascaris at all three doses was 100% at days 14 and 21 post-treatment; for hookworm it was 98.8%, 100% and 98%, respectively, at day 14 and 68.8%, 100% and 84%, respectively, at day 21; for Trichuris it was 31.2%, 57.1% and 42.3%, respectively, at day 14 and 27.3%, 60.9% and 48.0%, respectively, at day 21. The egg reduction rate at day 21 was 100% at all three doses for Ascaris, 94.5%, 100% and 96.1%, respectively, for hookworm; and 39.2%, 85.1% and 72.8%, respectively, for Trichuris. There were no side effects, and biochemical examination of blood and urine did not indicate any unfavourable changes. Based on this trial, the recommended dosage for Ascaris and hookworm is a 400 mg single dose, and for Trichuris is a 600 mg single dose. Albendazole appears to be more effective than other available anthelmintic drugs.
Once-yearly, mass deworming with broad spectrum anthelmintics over a period of five years among four types of communities in Malaysia resulted in an overall education in the prevalence of soil-transmitted helminthiases by one-third to two-thirds. The reduction in prevalence of infection was highest among inhabitants in semi-urban settlements (65.5%), followed by those in the rural estates (53.0%) and high-rise flats (43.9%). Soil-transmitted helminthiases were only reduced by 35.5% in the urban slums. Reduction in infection with Trichuris trichiura was better than that with Ascaris lumbricoides whereas hook-infection was completely eliminated in some of the communities surveyed. The reduction in prevalence ofsoil-transmitted helminthiases by long-term, once-yearly deworming alone, without other supplementary interventions, reinforces the potential and feasibility of regular mass-deworming as an immediate and effective measure for the control ofsoil-transmitted helminthiases. This is of great public health significance especially in highly endemic communities where some form of intervention is urgently needed and facilities for other control measures such as the improvement of environmental sanitation and nutritional status and health education are neither feasible nor possible nor immediately available.
Serum IgG levels and complement C3 levels were assayed on Day 0, 1, 3-4, 7 and 56-70 post-treatment with diethylcarbamizine citrate (DEC) in a series to 26 patients with Brugia malayi infection and 6 volunteers without infection. On treatment, the microfilariae were cleared from the blood within 24 hours. The eosinophils decreased dramatically on Day 1 post-treatment but increased rapidly by Day 4 to 7 and then dropped to normal levels in 45 days. The serum IgG mean levels decreased briefly following treatment with DEC but then returned to original levels. However, the complement C3 levels gradually increased over the 2 months period of study reaching statistical significance levels (p less than 0.01) in patients with initial high blood microfilariae. The observation suggests that Brugia malayi infection probably induces a high rate of synthesis of complement C3 and this process continued in the post-treatment phase. Since, DEC treatment did not cause a decrease in complement C3 with the elimination of blood microfilariae, it would appear that the complement C3 is consumed following antibody attachment to the microfilariae as they enter the blood circulation.
CGP 20376, a 5-methoxyl-6-dithiocarbamic-S- (2-carboxy-ethyl) ester derivative of benzothiazole was evaluated for its antifilarial properties and shown to be extremely effective against subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata at oral doses of 20-100 mg/kg. The compound and/or its metabolites had complete micro- and microfilaricidal activities even when given at a single dose of 20 mg/kg. Lower doses had incomplete filaricidal action.
Efficacy of eight recently developed and used anthelmintics of the benzimidazole carbamates; mebendazole, flubendazole, oxfendazole, albendazole, oxibendazole, 790163 proflubendazole, 780118 "cyanide" benzimidazole and 780120 "selenium" benzimidazole was tested orally against the enteral immature larval and adult stages of Trichinella spiralis in mice. Six of these derivatives of methyl benzimidazole-2-carbamates have an aryl and two have an alkyl substituent at the 5'-position of the parent benzimidazole ring. The nature of these substituents was found to be related to the antitrichinellous activity of the compounds. Compounds with the 5'-substituent linked to the parent benzimidazole ring by either a carbon, sulfur or an oxygen atom are more potent than those bridged by selenium or by the carbon with an attached-CN group. The result clearly indicates that the benzimidazoles are invariably more potent against immature enteral phase than the adult worms. This finding would be of importance in a targeted synthesis of new, effective derivatives of benzimidazole, e.g., in the screening for more important tissue-dwelling nematodes like filarial worms.
Albendazole, oxfendazole, fenbendazole, levamisole, closantel, ivermectin and febantel were administered to sheep on four farms and their efficacy assessed by faecal egg count reduction test. High level of resistance of Haemonchus contortus was found to benzimidazoles (albendazole, oxfendazole, fenbendazole) on all farms and to febantel on the one farm where it was tested. No resistance to closantel and levamisole was observed. Resistance to ivermectin was absent on the three farms examined under this study, but has been reported on the fourth farm in earlier work. It is concluded that anthelmintic resistance to benzimidazoles and the probenzimidazole, febantel, is a serious and widespread problem in H. contortus in sheep in Malaysia.
The therapeutic and prophylactic effects of closantel on natural infections with Haemonchus contortus were studied in goats in Peninsular Malaysia. Closantel was highly effective against H. contortus, either at a subcutaneous (s.c.) injection of 5.0 mg kg-1 body weight (100%), or in an oral drench mixture with mebendazole at a dose of 10.0 mg kg-1 (99.2%), as indicated by faecal egg counts. H. contortus larvae were absent from faecal cultures for 5, 6 and 7 weeks following treatment with s.c. injections of closantel at doses of 2.5 mg kg-1, 5.0 mg kg-1 and 10.0 mg kg-1 respectively, and for 6 weeks after treatment with closantel at 10.0 mg kg-1, given orally. Through its sustained activity, closantel not only prevented reinfection with H. contortus but also caused a dramatic reduction in pasture contamination. The potential utility of closantel in the strategic control of haemonchosis in goats, and as an alternative treatment for benzimidazoles and levamisole resistant H. contortus strains, is discussed.
Matched MeSH terms: Anthelmintics/administration & dosage; Anthelmintics/therapeutic use
The anthelmintic efficacy of benzimidazoles, levamisole, closantel, ivermectin and moxidectin was evaluated on an institutional farm in Malaysia using faecal egg count reduction tests, controlled slaughter trials and an in vitro egg hatch assay. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles and ivermectin and of Trichostrongylus colubriformis against benzimidazoles and levaminsole on the same farm. Moxidectin was effective against the ivermectin resistant H. contortus.
A previous study had suggested that local strains of goat trichostrongyles, comprising largely Haemonchus contortus, might have developed resistance to benzimidazole anthelmintics. A trial involving 18 goats was conducted to confirm this. There was a significant (P < 0.01) reduction in worm burdens in goats given levamisole, but this was not so for those animals given albendazole, fenbendazole, oxfendazole and mebendazole (P > 0.05).
The prevalence of drug-resistant parasites in goats in West Malaysia has rarely been reported. Ten commercial goat farms were surveyed for resistance to anthelminthics by measuring the reduction in faecal egg counts (FECs) after treatment with levamisole, pyrantel pamoate and fenbendazole. Resistance to fenbendazole was seen in most farms; there was no evidence of resistance to levamisole but some resistance to pyrantel pamoate was detected on one farm. The significance of the findings are discussed.
Ninety-six randomly selected farms, located throughout peninsular Malaysia, were surveyed for goat nematodes resistant to benzimidazoles (BZ). On 33 farms BZ resistance was demonstrated by means of an egg hatch assay. Haemonchus contortus was found to be the main species involved in anthelmintic resistance. There was a positive association between the frequency of anthelmintic treatments on a farm and the presence of benzimidazole resistance. To assess the value of the egg hatch assay, faecal egg count reduction (FECR) tests were also performed on 20 farms. On six farms the LD50 of thiabendazole (TBZ) was less than 0.10 micrograms ml-1 and the FECR higher than 95% and on ten farms with an LD50 TBZ of over 0.10 micrograms ml-1 a FECR of less than 95% was measured. On four farms the FECR was less than 95%, although the egg hatch assay showed LD50 TBZ values of less than 0.10 micrograms ml-1 and on two of these three farms a controlled efficacy test confirmed the presence of BZ resistant H. contortus. From these results it can be concluded that the egg hatch assay underestimated the true incidence of benzimidazole resistance. Levamisole resistance was detected with a FECR test on two of ten farms investigated.