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Public Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sex differences in\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb) exposure likely contribute to sex differences in tuberculosis (TB) burden. However, population-level age- and sex-specific patterns of Mtb exposure among adolescents and adults have not been recently characterised in Malawi. We therefore conducted a cross-sectional survey to estimate age- and sex-specific Mtb immunoreactivity prevalence in Blantyre City, Malawi, and to assess whether prevalence diverges by sex with increasing age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used an open-access dataset of building footprints, known as Open Buildings, to obtain a random sample of households from 33 peri-urban neighbourhoods in Blantyre City. Adolescents and adults aged 10\u201340 years were recruited, participant characteristics recorded, and venous blood samples collected to determine Mtb immunoreactivity using the QuantiFERON-TB Gold Plus (QFT-Plus) assay. We fitted Bayesian multilevel logistic regression models to estimate the association between age, sex, and other risk factors with Mtb immunoreactivity, and compared predicted immunoreactivity prevalence across age-sex strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 2833 participants, 40.0% (1133\/2833) were male, the median age was 21 years (interquartile range: 16\u201328 years), and 8.7% (179\/2047) self-reported living with HIV. Overall, 17.8% (503\/2833) of participants were Mtb positive, Mtb immunoreactivity prevalence was 17.8% (95% credible interval [CrI]: 16.4\u201319.2%), corresponding to an annual risk of TB infection of 0.88% (95% CrI: 0.80%-0.95%). Prevalence was similar by sex among 10-19- and 30-40-year-olds. However, among 20-29-year-olds, prevalence was higher among males compared to females: 26.3% (95% CrI: 22.0%-30.8%) and 17.7% (95% CrI: 14.8%-20.8%), respectively. The annual risk of Mtb immunoreactivity conversion increased, on average, at a faster rate among males compared to females from age 10 years, peaking at 21 years, where it was 1.58 (95% CrI: 0.82\u20132.80) times higher among males compared to females. Tobacco smoking and alcohol drinking, more prevalent among males compared to females, were associated with increased immunoreactivity probability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adolescence appears to be a period of vulnerability for Mtb exposure, during which sex-specific vulnerabilities begin to emerge. Identifying the biological and social drivers of these vulnerabilities could inform targeted strategies to reduce sex disparities in TB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s44263-026-00302-w","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:18:10Z","timestamp":1784783890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drivers of sex differences in Mycobacterium tuberculosis immunoreactivity among adolescents and adults in Blantyre, Malawi"],"prefix":"10.1186","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4072-9715","authenticated-orcid":false,"given":"Mphatso D","family":"Phiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M","family":"Rickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Mbale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena RA","family":"Feasey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marriott","family":"Nliwasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Schwalb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tisungane E","family":"Mwenyenkulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuzani N","family":"Mbendera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C","family":"Mwandumba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L","family":"Corbett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Bertel","family":"Squire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc YR","family":"Henrion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C","family":"Horton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"MacPherson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"302_CR1","volume-title":"Global tuberculosis report 2025","author":"World Health Organization","year":"2025","unstructured":"World Health Organization. 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For minors\u2009<\u200918 years old, we obtained written assent in addition to guardian consent. Illiterate participants provided a thumbprint in the presence of an impartial witness. Kamuzu University of Health Sciences (COMREC, Ref P.04\/22\/3611) and London School of Hygiene & Tropical Medicine Research Ethics Committee (Ref 2774) provided ethics review and approval, with additional approval from the Malawi National Tuberculosis and Leprosy Elimination Programme and Blantyre District Health Office [\n                      \n                      ]. All study processes followed principles of the Helsinki Declaration for the protection of human research participants. Trained field research assistants and nurse obtained informed consent from enrolled participants and administered study procedures. 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