Community deworming alleviates geohelminth-induced immune hyporesponsiveness

Linda J. Wammes, Firdaus Hamid, Aprilianto Eddy Wiria, Linda May, Maria M.M. Kaisar, Margaretta A. Prasetyani-Gieseler, Yenny Djuardi, Heri Wibowo, Yvonne C.M. Kruize, Jaco J. Verweij, Sanne E. De Jon, Roula Tsonaka, Jeanine J. Houwing-Duistermaat, Erliyani Sartono, Adrian J.F. Luty, Taniawati Supali, Maria Yazdanbakhsh

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Abstract

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.

Original languageEnglish
Pages (from-to)12526-12531
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number44
DOIs
Publication statusPublished - 1 Nov 2016

Keywords

  • Albendazole
  • Cytokine responses
  • Deworming
  • Helminths
  • Indonesia

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    Wammes, L. J., Hamid, F., Wiria, A. E., May, L., Kaisar, M. M. M., Prasetyani-Gieseler, M. A., Djuardi, Y., Wibowo, H., Kruize, Y. C. M., Verweij, J. J., De Jon, S. E., Tsonaka, R., Houwing-Duistermaat, J. J., Sartono, E., Luty, A. J. F., Supali, T., & Yazdanbakhsh, M. (2016). Community deworming alleviates geohelminth-induced immune hyporesponsiveness. Proceedings of the National Academy of Sciences of the United States of America, 113(44), 12526-12531. https://doi.org/10.1073/pnas.1604570113