Low efficacy of mebendazole against hookworm in Vietnam: Two randomized controlled trials

Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone (R)) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-con trolled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI-9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30-81%) for triple mebendazole, 75% (47-88%) for single albendazole, and 88% (58-97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs

Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study

BACKGROUND: Geohelminth infection and poor hygiene may be protective against allergic sensitization. OBJECTIVE: To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection. METHODS: A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected. RESULTS: A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75). CONCLUSION: Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection. CLINICAL IMPLICATIONS: If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease

Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam.

BACKGROUND: Observational evidence suggests that infection with helminths protects against allergic disease and allergen skin sensitization. It is postulated that such effects are mediated by helminth-induced cytokine responses, in particular IL-10. OBJECTIVE: We tested this hypothesis in a rural area of central Vietnam where hookworm infection is endemic. METHODS: One thousand five hundred and sixty-six schoolchildren aged 6-17 were randomly allocated to receive either anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. We compared changes in the prevalence of exercise-induced bronchoconstriction, allergen skin sensitization, flexural eczema on skin examination, questionnaire-reported allergic disease (wheeze and rhinitis symptoms), and immunological parameters (hookworm-induced IFN-gamma, IL-5, IL-10) between 0 and 12 months. RESULTS: One thousand four hundred and eighty-seven children (95% of these randomized) completed the study. The most common helminth infections were hookworm (65%) and Ascaris lumbricoides (7%). There was no effect of the therapy on the primary outcome, exercise-induced bronchoconstriction (within-participant mean percent fall in peak flow from baseline after anti-helminthic treatment 2.25 (SD 7.3) vs. placebo 2.19 (SD 7.8, P=0.9), or on the prevalence of questionnaire-reported wheeze [adjusted odds ratio (OR)=1.16, 95% confidence interval (CI) 0.35-3.82, P=0.8] and rhinitis (adjusted OR=1.39, 0.89-2.15, P=0.1), or flexural dermatitis on skin examination (adjusted OR=1.15, 0.39-3.45, P=0.8). However, anti-helminthic therapy was associated with a significantly higher allergen skin sensitization risk (adjusted OR=1.31, 1.02-1.67, P=0.03). This effect was particularly strong for children infected with A. lumbricoides at baseline (adjusted OR=4.90, 1.48-16.19, P=0.009). Allergen skin sensitization was inversely related to hookworm-specific IL-10 at baseline (adjusted OR=0.76, 0.59-0.99, P=0.04). No cytokine tested, including IL-10, changed significantly after the anti-helminthic therapy compared with the placebo. CONCLUSION: A significant reduction in worm burden over a 12-month period in helminth-infected children increases the risk of allergen skin sensitization but not of clinical allergic disease. The effect on skin sensitization could not be fully explained by any of the immunological parameters tested

Large scale screening for haemoglobin disorders in southern Vietnam: implications for avoidance and management.

In order to obtain an approximate assessment of the public health burden that will be posed by the inherited disorders of haemoglobin in southern Vietnam, several thousand individuals were screened for these conditions. A smaller sample was screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The important haemoglobin disorders identified were beta thalassaemia, haemoglobin E and a variety of different forms of alpha thalassaemia. There were sufficient G6PD-deficient individuals to materially affect malaria control programme design. The most remarkable finding was wide variation in the gene frequencies of these conditions among the ethnic groups sampled. The approximate number of babies expected to be born with clinically significant haemoglobin disorders in Vietnam was estimated from the gene-frequency data. This study emphasizes the importance of wide-scale population screening, including ethnic subgroups, to establish the requirements for inherited haemoglobin disorder programmes in resource-limited settings