Background In Uganda, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) showed excellent treatment efficacy for uncomplicated malaria in prior trials. Because the frequency of resistance to artemisinins and piperaquine is increasing in Southeast Asia and the prevalence of Plasmodium falciparum polymorphisms associated with resistance has changed, we reassessed treatment efficacies at 3 sites in Uganda. Methods For this randomized, single-blinded clinical trial, children aged 6–59 months with uncomplicated falciparum malaria were assigned treatment with AL or DHA-PQ and followed for 42 days. Primary end points were risks of recurrent parasitemia, either unadjusted or adjusted to distinguish recrudescence from new infection. We assessed selection by study regimens of relevant P. falciparum genetic polymorphisms associated with drug resistance. Results Of 599 patients enrolled, 578 completed follow-up. There were no early treatment failures. The risk of recurrent parasitemia was lower with DHA-PQ as compared to AL at all 3 sites at 42 days (26.0% vs 47.0%; P < .001). Recrudescent infections were uncommon in both the DHA-PQ and AL arms (1.1% and 2.2%, respectively; P = .25). Neither regimen selected for pfcrt or pfmdr1 polymorphisms associated with drug resistance. Conclusions AL and DHA-PQ remain effective for the treatment of malaria in Uganda. Neither regimen selected for genetic polymorphisms associated with drug resistance. Clinical Trials Registration ISRCTN15793046.

IntroductionUganda is conducting a second mass LLIN distribution campaign and Katakwi district recently received LLINs as part of this activity. This study was conducted to measure the success of the campaign in this setting, an area of high transmission, with the objectives to estimate LLIN ownership, access and use pre and post campaign implementation.MethodsTwo identical cross sectional surveys, based on the Malaria Indicator Survey methodology, were conducted in three sub-counties in this district (Kapujan, Magoro and Toroma), six months apart, one before and another after the mass distribution campaign. Data on three main LLIN indicators including; household LLIN ownership, population with access to an LLIN and use were collected using a household and a women’s questionnaire identical to the Malaria Indicator Survey.ResultsA total of 601 and 607 households were randomly selected in survey one and two respectively. At baseline, 60.57% (56.53–64.50) of households owned at least one net for every two persons who stayed in the household the night before the survey which significantly increased to 70.35% (66.54–73.96) after the campaign (p = 0.001). Similarly, the percentage of the household population with access to an LLIN significantly increased from 84.76% (82.99–86.52) to 91.57% (90.33–92.81), p = 0.001 and the percentage of household population that slept under an LLIN the night before the survey also significantly increased from 56.85% (55.06–58.82) to 81.72% (76.75–83.21), p = 0.001.ConclusionThe LLIN mass campaign successfully achieved the national target of over eighty-five percent of the population with access to an LLIN in this setting, however, universal household coverage and use were fourteen and three percent points less than the national target respectively. This is useful for malaria programs to consider during the planning of future campaigns by tailoring efforts around deficient areas like mechanisms to increase universal coverage and behavior change communication.

BackgroundThere is growing interest to add mass drug administration (MDA) to the already existing malaria prevention strategies, such as indoor residual spraying (IRS). However, successful MDA and IRS requires high population-wide coverage, emphasizing the importance of community acceptance. This study’s objectives were to identify community-level facilitators and barriers during the implementation of both MDA and IRS in communities with high malaria transmission intensity.MethodsThis was a qualitative study conducted in two sub-counties in Katakwi district. Kapujan sub-county residents received two rounds of IRS and MDA while Toroma sub-county residents received two rounds of IRS only. Key informant interviews and focus group discussions were conducted with key influential district and sub-county personnel and community members. Data were analysed using thematic analysis. Transcripts and interview notes from the in-depth interviews were analysed using a coding scheme developed from pre-defined topics together with themes emerging from the data. The Nvivo software program was used to aggregate the data by codes and to present study findings.ResultsOverall, 14 key informants were interviewed: 4 from Katakwi district and 5 each from Kapujan and Toroma sub-counties. Five focus group discussions were conducted: 4 with community members (men and women), 2 in each sub-county and one with medical staff of Toroma health centre IV. Important themes for consideration raised by the respondents include community sensitization, conducting implementation during the low activity dry season, involvement of government and local leadership, use of the competent locally composed team, community knowledge of malaria effects and consequences, combining interventions and evidence of malaria reduction from interventions. Potential barriers such as spreading of misinformation regarding interventions, the strong unpleasant smell from Actellic and inadequate duration of engagement with the community should be taken into consideration.ConclusionThis study documents important community engagement strategies that need to be considered when implementing malaria MDA in combination with IRS, for malaria prevention in such settings. This information is useful for malaria programmes, especially during the design and implementation of such community level interventions.

Background Mass drug administration (MDA) is a suggested mean to accelerate efforts towards elimination and attainment of malaria-free status. There is limited evidence of suitable methods of implementing MDA programme to achieve a high coverage and compliance in low-income countries. The objective of this paper is to assess the impact of this MDA delivery strategy while using coverage measured as effective population in the community and population available. Methods Population-based MDA was implemented as a part of a larger program in a high transmission setting in Uganda. Four rounds of interventions were implemented over a period of 2 years at an interval of 6 to 8 months. A housing and population census was conducted to establish the eligible population. A team of 19 personnel conducted MDA at established village meeting points as distribution sites at every village. The first dose of dihydroartemisinin–piperaquine (DHA-PQ) was administered via a fixed site distribution strategy by directly observed treatment on site, the remaining doses were taken at home and a door-to-door follow up strategy was implemented by community health workers to monitor adherence to the second and third doses. Results Based on number of individuals who turned up at the distribution site, for each round of MDA, effective coverage was 80.1%, 81.2%, 80.0% and 80% for the 1st, 2nd, 3rd and 4th rounds respectively. However, coverage based on available population at the time of implementing MDA was 80.1%, 83.2%, 82.4% and 82.9% for rounds 1, 2, 3 and 4, respectively. Intense community mobilization using community structures and mass media facilitated community participation and adherence to MDA. Conclusion A hybrid of fixed site distribution and door-to-door follow up strategy of MDA delivery achieved a high coverage and compliance and seemed feasible. This model can be considered in resource-limited settings.

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 quasi-experimental controlled before-and-after trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) of Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty at study start: MDA+IRS, IRS, SOC. 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 = 0.0001) 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 < 0.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of study arms, the single large cluster per arm, and the lack of an MDA-only arm, considered to violate equipoise. Conclusions Despite being assessed at long time points 5–7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Randomized trials of MDA in large areas undergoing IRS recommended as well as cohort studies of impact on incidence. Trial registration: This trial was retrospectively registered 11/07/2018 with the Pan African Clinical Trials Registry (PACTR201807166695568).