title: Community deworming alleviates geohelminth-induced immune hyporesponsiveness.
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. Helminth-specific 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 lymphocyte-associated antigen 4 (CTLA-4) on CD4+T cells of albendazole-treated 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.
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Linda J
authors: LJ
authors: Wammes
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.|Department of Microbiology, Faculty of Medicine, Hasanuddin University, 90245 Makassar, Indonesia.
authors: Firdaus
authors: F
authors: Hamid
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.|Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Aprilianto Eddy
authors: 0000-0002-6482-424X
authors: AE
authors: Wiria
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Linda
authors: L
authors: May
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.|Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Maria M M
authors: MM
authors: Kaisar
authors: Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Margaretta A
authors: MA
authors: Prasetyani-Gieseler
authors: Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Yenny
authors: Y
authors: Djuardi
authors: Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Heri
authors: H
authors: Wibowo
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Yvonne C M
authors: YC
authors: Kruize
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.|Laboratory for Medical Microbiology and Immunology, St. Elisabeth Ziekenhuis, 5022 GC Tilburg, The Netherlands.
authors: Jaco J
authors: JJ
authors: Verweij
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Sanne E
authors: 0000-0002-6696-7359
authors: SE
authors: de Jong
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Roula
authors: R
authors: Tsonaka
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.|Department of Statistics, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors: Jeanine J
authors: JJ
authors: Houwing-Duistermaat
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors: Erliyani
authors: E
authors: Sartono
authors: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors: Adrian J F
authors: AJ
authors: Luty
authors: Department of Parasitology, Faculty of Medicine, University of Indonesia, 10430 Jakarta, Indonesia.
authors: Taniawati
authors: T
authors: Supali
authors: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; M.Yazdanbakhsh@lumc.nl.
authors: Maria
authors: M
authors: Yazdanbakhsh
mesh_terms: D000293:Adolescent; D000328:Adult; D015766:Albendazole / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D002648:Child; D017714:Community-Acquired Infections / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006373:Helminthiasis / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D006376:Helminths / Q000187:drug effects* / Q000276:immunology; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology; D015995:Prevalence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D060908:CTLA-4 Antigen; D016207:Cytokines; D015766:Albendazole
keywords: Indonesia; albendazole; cytokine responses; deworming; helminths