Abstract
BackgroundThe prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity.MethodsIn an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly.ResultsThe outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms.ConclusionsDespite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions.Clinical Trials RegistrationISRCTN47196031.
Highlights
The prevalence of allergy-related diseases (ARD) such as eczema, rhinitis and asthma increased rapidly in high-income countries in the twentieth century [1] and is increasing in tropical, lowincome countries (LICs) [2]
Intensive mass drug administration (MDA) had no effect on wheeze, skin prick test positivity (SPT) or allergen-specific immunoglobulin E (asIgE) (risk ratios (95% confidence intervals): 1.11 (0.64,1.93), 1.10 (0.85,1.42) and 0.96 (0.82,1.12), respectively)
Intensive MDA reduced S. mansoni infection intensity: prevalence from Kato-Katz examination of one stool sample was 23% versus 39% (RR 0.70 (0.55,0.88)), but the more-sensitive urine circulating cathodic antigen test remained positive in 85% participants in both trial arms
Summary
The prevalence of allergy-related diseases (ARD) such as eczema, rhinitis and asthma increased rapidly in high-income countries in the twentieth century [1] and is increasing in tropical, lowincome countries (LICs) [2]. Populations in LICs, in rural settings, remain relatively protected [3]. Understanding this phenomenon is crucial to elucidating causes, and improving prevention, of ARD. LICs carry the largest burden of parasitic helminth infections: these are associated with some severe and much subtle morbidity [4, 5]. Some studies show increased atopy after anthelminthic intervention, but two large, school-based, individually-randomised intervention trials focussing on soil-transmitted helminths (STH) reported no effect on atopy or ARD [11, 12]. We hypothesised that intensive community-wide anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity
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