Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda

Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda Dorothy C. Echodu, Adoke Yeka, Thomas Eganyu, Wycliff Odude, Fred Bukenya, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1510812/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Declines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC). Methods : The 32-month prospective controlled community trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) in Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty: MDA+IRS, IRS, and SOC (insecticide treated bednets and case management). IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round. Results : Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months, post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z=9.6, p= 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5's (95% CI: [10.5%, 16.8%], Z=4.02, p= 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z=4.7, p= 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%,83.0%, p<.0001] in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p<.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of MDA+IRS, which may have understated the impact of MDA, and lack of MDA-only arm, considered to violate equipoise. Conclusions : Despite being assessed at long timepoints 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Future cohort studies of impact on incidence recommended. Trial registration: This trial was retrospectively registered July 7th, 2018 with the Pan African Clinical Trials Registry (PACTR 201807166695568). MDA malaria IRS high burden Uganda controlled trial pirimiphos dihydroartemisinin Full Text Additional Declarations No competing interests reported. Supplementary Files MDAandIRSmain.tex SIMalariaPrev.Tables033122.xlsx SupplementaryInformation.pdf malariaRefs.bib supplement.tex Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1510812","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":95366647,"identity":"d68c3708-7a22-458c-a1af-bc5c9d59804d","order_by":0,"name":"Dorothy C. 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PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"MDA, malaria, IRS, high burden, Uganda, controlled trial, pirimiphos, dihydroartemisinin","lastPublishedDoi":"10.21203/rs.3.rs-1510812/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1510812/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:\u003c/p\u003e\u003cp\u003eDeclines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\u003cp\u003eThe 32-month prospective controlled community trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) in Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty: MDA+IRS, IRS, and SOC (insecticide treated bednets and case management). IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003c/p\u003e\u003cp\u003eComparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months, post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z=9.6, p= 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5's (95% CI: [10.5%, 16.8%], Z=4.02, p= 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z=4.7, p= 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%,83.0%, p\u0026lt;.0001] in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p\u0026lt;.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of MDA+IRS, which may have understated the impact of MDA, and lack of MDA-only arm, considered to violate equipoise.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e:\u003c/p\u003e\u003cp\u003eDespite being assessed at long timepoints 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Future cohort studies of impact on incidence recommended. Trial registration: This trial was retrospectively registered July 7th, 2018 with the Pan African Clinical Trials Registry (PACTR 201807166695568).\u003c/p\u003e","manuscriptTitle":"Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-05 14:08:26","doi":"10.21203/rs.3.rs-1510812/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7c74192f-5d02-4e7a-a614-5ba2873b437d","owner":[],"postedDate":"April 5th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-08T18:59:15+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-05 14:08:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1510812","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1510812","identity":"rs-1510812","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}