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SLD-PQ may be beneficial in mass drug administration (MDA) campaigns to prevent malaria transmission but uptake is limited by concerns of hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The aim of this study was to improve the evidence on the safety of MDA with SLD-PQ in a sub-Saharan African setting.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A nonlinear mixed-effects model describing the pharmacokinetics and treatment-induced hemolysis of primaquine was developed using data from an adult (<jats:italic>n<\/jats:italic>\u2009=\u200916, G6PD deficient) and pediatric study (<jats:italic>n<\/jats:italic>\u2009=\u200938, G6PD normal). The relationship between primaquine pharmacokinetics and hemolysis was modeled using an established erythrocyte lifespan model. The safety of MDA with SLD-PQ was explored through Monte Carlo simulations for SLD-PQ at 0.25 or 0.4\u00a0mg\/kg using baseline data from a Tanzanian setting with detailed information on hemoglobin concentrations and G6PD status.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The predicted reduction in hemoglobin levels following SLD-PQ was small and returned to pre-treatment levels after 25\u00a0days. G6PD deficiency (African A- variant) was associated with a 2.5-fold (95% CI 1.2\u20138.2) larger reduction in hemoglobin levels. In the Tanzanian setting where 43% of the population had at least mild anemia (hemoglobin\u2009&lt;\u200911\u201313\u00a0g\/dl depending on age and sex) and 2.73% had severe anemia (hemoglobin\u2009&lt;\u20097\u20138\u00a0g\/dl depending on age and sex), an additional 3.7% and 6.0% of the population were predicted to develop at least mild anemia and 0.25% and 0.41% to develop severe anemia after 0.25 and 0.4\u00a0mg\/kg SLD-PQ, respectively. Children &lt; 5\u00a0years of age and women \u2265 15\u00a0years of age were found to have a higher chance to have low pre-treatment hemoglobin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study supports the feasibility of MDA with SLD-PQ in a sub-Saharan African setting by predicting small and transient reductions in hemoglobin levels. In a setting where a substantial proportion of the population had low hemoglobin concentrations, our simulations suggest treatment with SLD-PQ would result in small increases in the prevalence of anemia which would most likely be transient.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-021-05034-4","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T20:16:05Z","timestamp":1633896965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8020-1934","authenticated-orcid":false,"given":"Stijn W.","family":"van Beek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elin M.","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred B.","family":"Tiono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Okebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"D\u2019Alessandro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bronner P.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Drakeley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"5034_CR1","unstructured":"World Health Organisation. 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