Early Exposure of Infants to GI Nematodes Induces Th2 Dominant Immune Responses Which Are Unaffected by Periodic Anthelminthic Treatment

Abstract

We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections in this age group, this was unexpected, and it was proposed that immune responses to the worms rather than their direct effects may play a significant role in morbidity in infants and that anthelminthic treatment may alleviate such effects. Therefore, the primary aims of this study were to characterise the immune response to initial/early GI nematode infections in infants and the effects of anthelminthic treatment on such immune responses. The frequency and levels of Th1/Th2 cytokines (IL-5, IL-13, IFN-γ and IL-10) induced by the worms were evaluated in 666 infants aged 6–24 months using the Whole Blood Assay. Ascaris and hookworm antigens induced predominantly Th2 cytokine responses, and levels of IL-5 and IL-13 were significantly correlated. The frequencies and levels of responses were higher for both Ascaris positive and hookworm positive infants compared with worm negative individuals, but very few infants made Trichuris-specific cytokine responses. Infants treated every 3 months with mebendazole showed a significantly lower prevalence of infection compared with placebo-treated controls at one year following baseline. At follow-up, cytokine responses to Ascaris and hookworm antigens, which remained Th2 biased, were increased compared with baseline but were not significantly affected by treatment. However, blood eosinophil levels, which were elevated in worm-infected children, were significantly lower in treated children. Thus the effect of deworming in this age group on anaemia and wasting malnutrition, which were replicated in this study, could not be explained by modification of cytokine responses but may be related to eosinophil function.

Author Summary

Infants and very young children commonly become infected with intestinal nematode infections. However, the worm burdens are generally very light, so a beneficial effect of deworming on wasting malnutrition and anaemia in this age group which we have demonstrated was unexpected and the mechanism unclear. To investigate this, we have, for the first time, determined whether such worm infections in infants induce significant immune reactions which might be detrimental to nutrition and growth e.g. by inducing inflammation in the gut or by cytokine effects on erythropoiesis. We also determined if such responses are modulated by regular deworming over a 9 month period. Peripheral blood cells from infants infected with Ascaris and hookworms in particular responded to stimulation with worm antigens, producing predominantly Th2 cytokines. Although the Th2 cytokine responses in the periphery were not significantly altered by deworming, the levels of eosinophils, which are regulated by the Th2 cytokine, IL-5, were lower after treatment. It is possible that eosinophils play a role in gut pathology leading to wasting malnutrition and anaemia in the very young and that this effect is reduced by deworming.