{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:26:29Z","timestamp":1787567189627,"version":"build-2736575974"},"reference-count":28,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome","award":["10.35802\/105882"],"award-info":[{"award-number":["10.35802\/105882"],"id":[{"id":"10.35802\/105882","id-type":"DOI","asserted-by":"publisher"}]}]},{"award":["10.35802\/105882"],"award-info":[{"award-number":["10.35802\/105882"],"id":[{"id":"10.35802\/105882","id-type":"DOI","asserted-by":"publisher"}]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Chronic malaria exposure has been proposed to modulate immune function, but its long-term effects on antibody-mediated responses to unrelated pathogens remain poorly defined. Whether these effects persist beyond periods of active infection and how early-life exposure shapes humoral immunity over time is not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We leveraged a natural experiment in coastal Kenya \u2013 where two regions (Junju and Ngerenya) diverged sharply in malaria transmission from around 2004 \u2013 to evaluate the long-term immunological consequences of malaria exposure in childhood. Using a protein microarray platform, we measured IgG responses to vaccine and pathogen antigens in 123 children sampled longitudinally over a 15-year period. Active weekly malaria surveillance enabled precise reconstruction of individual exposure histories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      IgG responses to\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      apical membrane antigen 1 (AMA1) tracked closely with clinical malaria episodes, confirming the ability of the microarray platform to detect biologically meaningful variation in antigen-specific immunity. Despite comparable vaccination histories, children from the high malaria transmission setting (Junju) exhibited persistently lower measles-specific IgG levels than children from the low-transmission setting (Ngerenya), a pattern validated by ELISA. In longitudinal analyses, children from Junju exhibited lower antibody responses to a range of unrelated antigens, including\n                      <jats:italic>Bordetella pertussis<\/jats:italic>\n                      , CMV, rubella, and measles, with similar differences evident in cross-sectional analyses at 10 years of age. Within the Ngerenya cohort, children with documented early-life malaria had broadly lower IgG responses at age 10 compared to malaria-naive peers, despite identical geography, vaccines, and follow-up duration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These findings suggest that malaria exposure during early childhood is linked with durable suppression of antibody responses to unrelated pathogens and vaccines. This effect persists long after infection and may partially explain the overall diminished long-term vaccine effectiveness in malaria-endemic settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>This study was supported by fellowship funding to C.J.S. from the Wellcome Trust (WT105882MA). The funder played no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. M.S.S was funded in whole by Science for Africa Foundation to the Developing Excellence in Leadership, Training, and Science in Africa (DELTAS Africa) program [DEL-22\u2013012] with support from Wellcome Trust and the UK Foreign, Commonwealth &amp; Development Office and is part of the EDCPT2 programme supported by the European Union. For purposes of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.107820","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T14:30:44Z","timestamp":1761229844000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.107820","source":"Crossref","is-referenced-by-count":0,"title":["A natural experiment in Kenya reveals durable immunosuppressive effects of early childhood malaria: a longitudinal cohort study"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7610-8252","authenticated-orcid":true,"given":"Mercy S","family":"Safari","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03my81p15","id-type":"ROR","asserted-by":"publisher"}],"name":"Bioscience Department, KEMRI-Wellcome Trust Research Programme","place":["Kilifi, 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