These datasets are from the prospective controlled community trial described in "Impact of population based indoor residual spraying with and without the mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda." Abstract BackgroundDeclines 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). MethodsThe 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 participantswere 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 4co-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. ResultsComparing malaria prevalence by qPCR in MDA+IRS and IRS only arms over all 6surveys (intention-to-treat analysis), roughly every 6 months,post-interventions, a geostatistical model found a significantadditional 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 under5’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 ConclusionsDespite 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 registrationThis trial was retrospectively registered July 7th, 2018 with the Pan African Clinical Trials Registry (PACTR 201807166695568). Datasets shared here include: (a) CompleteEnumerationR1toR4: De-identified enumeration dataset of all subjects enrolled in the open cohort of this prospective controlled community trial from Q4 2016 to Q2 2019; (b) MDACoverageR1toR4: 4 rounds of MDA coverage data; and (c) Surveys1to6_Mar2022: malaria prevalence and LLIN data for all 6 cross-sectional population surveys from November 2016 to April 2019.