In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminthspecific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 mo - estimate [95% confidence interval], 0.37 [0.21-0.53], P value over time (Ptime) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) on CD4+ T cells of albendazoletreated individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21 mo, respectively; Ptime = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low- compared with high-income countries.

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Proceedings of the National Academy of Sciences of the United States of America
Department of Medical Microbiology and Infectious Diseases

Wammes, L.J. (Linda J.), Hamid, F. (Firdaus), Wiria, A.E. (Aprilianto Eddy), May, L. (Linda), Kaisar, M.M.M. (Maria M.M.), Prasetyani-Gieseler, M.A. (Margaretta A.), … Yazdanbakhsh, M. (2016). Community deworming alleviates geohelminth-induced immune hyporesponsiveness. In Proceedings of the National Academy of Sciences of the United States of America (Vol. 113, pp. 12526–12531). doi:10.1073/pnas.1604570113