Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood: A Randomised Controlled Trial

Abstract

BackgroundHelminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.Methods and FindingsA randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome.ConclusionsRoutine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.Trial registrationCurrent Controlled Trials ISRCTN32849447

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

“…Previous studies examining the effect of anthelmintic treatment on clinical outcomes (8,26) as well as on Mycobacterium bovis BCG vaccination (27,28) have yielded conflicting results. However, examination of T cell responses in helminth-infected individuals clearly showed diminished T cell proliferation and IFN-␥ production in response to purified protein derivative (PPD) and partial reversal of the diminished levels following albendazole therapy, although the LTB status of the population was not ascertained (29).…”

Helminth infection during pregnancy: insights from evolutionary ecology

“…For example, W. bancrofti infection during pregnancy is associated with changes in cytokine production in response to helminth antigens, as well as reductions in interferon (IFN)-γ production in response to tuberculosis antigen 73,79,80. There is also evidence that infants with helminth-infected mothers are less likely to develop eczema, suggesting reductions in certain allergic responses 81,82. In many cases, these alterations resemble the effects of infection on adult immunity 77,78.…”

“…Several have found that treatment is associated with an increased incidence of eczema, suggesting that treatment may affect the development of mechanisms regulating infant immune responses 81,82,112. Others have examined whether treatment affects infant immune responses to helminth antigens.…”

Allergie und Würmer: Sollen wir uns gute alte Freunde zurückholen?

“…Thus, the inverse association between allergic disease and helminth infections in a high-prevalence population has been interpreted to require an active suppression by present/active worms [22]. Interestingly, a study conducted in Uganda found that treatment against helminths during pregnancy was associated with increased risk of infantile eczema [74] and eczema in childhood [76]. These data suggest that allergic disease may be programmed in utero or very early in the postnatal life and perinatal exposure to helminths may be beneficial and protect against allergy in infancy.…”