Echodu, Dorothy C.Yeka, AdokeEganyu, ThomasOdude, WycliffBukenya, FredNankabirwa, Joaniter2022-11-202022-11-202022Echodu, DC, Yeka, A., Eganyu, T., Odude, W., Bukenya, F., Amoah, B., ... & Opigo, J. (2022). 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. https://doi.org/10.21203/rs.3.rs-1510812/v1https://doi.org/10.21203/rs.3.rs-1510812/v1https://nru.uncst.go.ug/handle/123456789/5346Declines 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.enMDAMalariaIRSHigh burdenUgandaControlled trialPirimiphosDihydroartemisininArticle