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Background Global gains toward malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. Methods Twenty clusters were randomly assigned to 3 rounds of MTaT per year for 2 years or control (standard of care for testing and treatment at public health facilities along with government-sponsored mass long-lasting insecticidal net [LLIN] distributions). During rounds, community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after 3 rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year, adjusted for age, reported LLIN use, enhanced vegetative index, and socioeconomic status. Results Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage across the 3 annual rounds ranged between 75.0% and 77.5% in year 1, and between 81.9% and 94.3% in year 2. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (95% confidence interval [CI],.79–1.08) and 0.92 (95% CI,.76–1.10) after year 1 and year 2, respectively. Conclusions MTaT performed 3 times per year over 2 years did not reduce malaria parasite prevalence in this high-transmission area. Clinical Trials Registration NCT02987270. [ABSTRACT FROM AUTHOR]

In large experimental trials throughout Africa, insecticide-treated bednets and curtains have reduced child mortality in malaria-endemic communities by 15%-30%. While few questions remain about the efficacy of this intervention, operational issues around how to implement and sustain insecticide-treated materials (ITM) projects need attention. We revisited the site of a small-scale ITM intervention trial, 3 years after the project ended, to assess how local attitudes and practices had changed. Qualitative and quantitative methods, including 16 focus group discussions and a household survey (n = 60), were employed to assess use, maintenance, retreatment and perceptions of ITM and the insecticide in former study communities. Families that had been issued bednets were more likely to have kept and maintained them and valued bednets more highly than those who had been issued curtains. While most households retained their original bednets, none had treated them with insecticide since the intervention trial was completed 3 years earlier. Most of those who had been issued bednets repaired them, but none acquired new or replacement nets. In contrast, households that had been issued insecticide-treated curtains often removed them. Three (15%) of the households issued curtains had purchased one or more bednets since the study ended. In households where bednets had been issued, children 10 years of age and younger were a third as likely to sleep under a net as were adults (relative risk (RR) = 0. 32; 95% confidence interval (95%CI) = 0.19, 0.53). Understanding how and why optimal ITM use declined following this small-scale intervention trial can suggest measures that may improve the sustainability of current and future ITM efforts. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions. Objective: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya. Methods: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention. Results: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data. Conclusions: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT. [ABSTRACT FROM AUTHOR]

Background: The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited., Methods: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay., Results: Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. No related grade 3 AEs, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P < .001)., Conclusions: PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic., Clinical Trials Registration: NCT02687373., (Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Prior to implementation of a randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) in western Kenya, ethnographic studies were conducted to understand local perceptions of disease, sleeping patterns, and other factors that might affect use of ITNs. Educational activities took place prior to distribution, but immediately after distribution in Asembo only approximately half of the ITNs were in use. A qualitative study was then conducted to identify the community's perceptions about ITNs and the ITN project. While participants ranked malaria as important and recognized that malaria prevention could be beneficial, they believed ITNs would be only partly effective due to the perception that malaria has multiple causes. Concerns expressed included fear of the insecticide, thought by some to be a toxic family planning aid, the taking of blood during clinical studies, and the mixing up of family ITNs during net re-treatment, which would violate cultural taboos. Attempts were made to allay fears by improved communication on these subjects and modification of the study design.

A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.

Randomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it.

This paper describes the study design and methods used in a large community-based, group-randomized, controlled trial of permethrin-treated bed nets (ITNs) in an area with intense, perennial malaria transmission in western Kenya conducted between 1996 and 1999. A multi-disciplinary framework was used to explore the efficacy of ITNs in the reduction of all-cause mortality in children less than five years old, the clinical, entomologic, immunologic, and economic impact of ITNs, the social and behavioral determinants of ITN use, and the use of a geographic information system to allow for spatial analyses of these outcomes. Methodologic difficulties encountered in such large-scale field trials are discussed.