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 quasi-experimental controlled before-and-after trial in northeastern Uganda.

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).

Implementing population-based mass drug administration for malaria: experience from a high transmission setting in North Eastern Uganda.

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.

Long lasting insecticidal bed nets ownership, access and use in a high malaria transmission setting before and after a mass distribution campaign in Uganda.

INTRODUCTION: Uganda 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. METHODS: Two 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. RESULTS: A 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. CONCLUSION: The 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.