{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:09:15Z","timestamp":1767179355473,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012971","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022083","name":"VLIRUOS","doi-asserted-by":"publisher","award":["671055"],"award-info":[{"award-number":["671055"]}],"id":[{"id":"10.13039\/501100022083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0A0522N"],"award-info":[{"award-number":["G0A0522N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nodding syndrome (NS) is a disabling childhood-onset epilepsy occurring in onchocerciasis-endemic regions. High\n                      <jats:italic>Onchocerca volvulus<\/jats:italic>\n                      microfilarial loads in childhood are a key risk factor, but not all heavily infected individuals develop NS, suggesting a possible role for host genetic susceptibility. Human leukocyte antigen (HLA) haplotypes have been implicated in susceptibility to various infectious and autoimmune diseases, including onchocerciasis. We investigated potential associations between HLA haplotypes and onchocerciasis-associated epilepsy (OAE), including NS, in Tanzania.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A case-control study was conducted in an onchocerciasis-endemic area in the Mahenge area, Tanzania, including 98 persons with epilepsy and 112 controls. DNA was extracted from dry blood spots and HLA sequence-based typing was performed by Histogenetics (Ossining, USA). A total of 11 HLA loci (HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1) were exon sequenced. The HLA-typed dataset was analysed using pyHLA, including Bonferroni as multi-test adjustment, to test for associations with\n                      <jats:italic>O. volvulus<\/jats:italic>\n                      anti-Ov16 seropositivity, epilepsy, OAE and NS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Anti-Ov16 seropositivity was significantly higher in cases than controls (76.5% vs 58.9%; p\u2009=\u20090.01). No HLA alleles were significantly associated with epilepsy, OAE, NS, or anti-Ov16 seropositivity after correction. Before adjustment, HLA-C07:01 appeared to be a risk factor for epilepsy, HLA-DQB106:02 was associated with OAE, HLA-B35:01 with NS, and HLA-C08:02 and DRB1*03:01 with anti-Ov16 seropositivity. Post-hoc power analysis indicated that substantially larger sample sizes would be required to confirm these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study did not identify statistically significant HLA associations with epilepsy, OAE, NS, or\n                      <jats:italic>O. volvulus<\/jats:italic>\n                      exposure. However, several alleles\u2014particularly HLA-B*35:01, also reported in a previous South Sudanese study\u2014emerged as potential candidates for further investigation. Larger, multi-country studies with sufficient power are needed to clarify whether host genetic factors contribute to susceptibility to OAE and NS. Strengthening onchocerciasis elimination programmes remains essential, as NS is a preventable disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0012971","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:42:19Z","timestamp":1764182539000},"page":"e0012971","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating HLA haplotypes as a potential risk factor for nodding syndrome: A case-control study in the Mahenge area, 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