Impact of Intermittent Mass Testing and Treatment on Incidence of Malaria Infection in a High Transmission Area of Western Kenya.

Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: development of study site infrastructure and lessons learned.

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.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial.

Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial.

BACKGROUND: Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. METHODS: We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0·5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (<10, 10-14, 15-19, and ≥20). Data were obtained in an observer-blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459. FINDINGS: Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41·4%, 95% CI 31·6-51·8) of 99 RTS,S/AS01 recipients and 37 (36·6%, 27·3-46·8) of 101 rabies-vaccine recipients (relative risk 1·1, 95% CI 0·8-1·6). 20 (20·2%, 95% CI 12·8-29·5) of 99 RTS,S/AS01 recipients and 12 (11·9%, 6·3-19·8) of 101 rabies-vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5·1%, 95% CI 1·7-11·4) of 99 RTS,S/AS01 recipients and four (4·0%, 1·1-9·8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients). INTERPRETATION: RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes. FUNDING: GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative.

Deaths ascribed to non-communicable diseases among rural Kenyan adults are proportionately increasing: evidence from a health and demographic surveillance system, 2003-2010.

BACKGROUND: Non-communicable diseases (NCDs) result in more deaths globally than other causes. Monitoring systems require strengthening to attribute the NCD burden and deaths in low and middle-income countries (LMICs). Data from health and demographic surveillance systems (HDSS) can contribute towards this goal. METHODS AND FINDINGS: Between 2003 and 2010, 15,228 deaths in adults aged 15 years (y) and older were identified retrospectively using the HDSS census and verbal autopsy in rural western Kenya, attributed into broad categories using InterVA-4 computer algorithms; 37% were ascribed to NCDs, 60% to communicable diseases (CDs), 3% to injuries, and <1% maternal causes. Median age at death for NCDs was 66y and 71y for females and males, respectively, with 43% (39% male, 48% female) of NCD deaths occurring prematurely among adults aged below 65y. NCD deaths were mainly attributed to cancers (35%) and cardio-vascular diseases (CVDs; 29%). The proportionate mortality from NCDs rose from 35% in 2003 to 45% in 2010 (χ2 linear trend 93.4; p<0.001). While overall annual mortality rates (MRs) for NCDs fell, cancer-specific MRs rose from 200 to 262 per 100,000 population, mainly due to increasing deaths in adults aged 65y and older, and to respiratory neoplasms in all age groups. The substantial fall in CD MRs resulted in similar MRs for CDs and NCDs among all adult females by 2010. NCD MRs for adults aged 15y to <65y fell from 409 to 183 per 100,000 among females and from 517 to 283 per 100,000 population among males. NCD MRs were higher among males than females aged both below, and at or above, 65y. CONCLUSIONS: NCDs constitute a significant proportion of deaths in rural western Kenya. Evidence of the increasing contribution of NCDs to overall mortality supports international recommendations to introduce or enhance prevention, screening, diagnosis and treatment programmes in LMICs.

Assessment of the consistency of national-level policies and guidelines for malaria in pregnancy in five African countries.

BACKGROUND: At least 39 sub-Saharan African countries have policies on preventing malaria in pregnancy (MIP), including use of long-lasting insecticidal nets (LLINs), intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) and case management. However, coverage of LLINs and IPTp-SP remains below international targets in most countries. One factor contributing to low coverage may be that MIP policies typically are developed by national malaria control programmes (NMCPs), but are implemented through national reproductive health (RH) programmes. METHODS: National-level MIP policies, guidelines, and training documents from NMCPs and RH programmes in Kenya, Mali, Mozambique, mainland Tanzania and Uganda were reviewed to assess whether they reflected WHO guidelines for prevention and treatment of MIP, and how consistent MIP content was across documents from the same country. Documents were compared for adherence to WHO guidance concerning IPTp-SP timing and dose, directly observed therapy, promotion and distribution of LLINs, linkages to HIV programmes and MIP case management. RESULTS: The five countries reviewed had national documents promoting IPTp-SP, LLINs and MIP case management. WHO guidance from 2004 frequently was not reflected: four countries recommended the first dose of IPTp-SP at 20 weeks or later (instead of 16 weeks), and three countries restricted the first and second IPTp-SP doses to specific gestational weeks. Documents from four countries provided conflicting guidance on MIP prevention for HIV-positive women, and none provided complete guidance on management of uncomplicated and severe malaria during pregnancy. In all countries, inconsistencies between NMCPs and RH programmes on the timing or dose of IPTp-SP were documented, as was the mechanism for providing LLINs. Inconsistencies also were found in training documents from NMCPs and RH programmes in a given country. Outdated, inconsistent guidelines have the potential to cause confusion and lead to incorrect practices among health workers who implement MIP programmes, contributing to low coverage of IPTp-SP and LLINs. CONCLUSIONS: MIP policies, guidelines and training materials are outdated and/or inconsistent in the countries assessed. Updating and ensuring consistency among national MIP documents is needed, along with re-orientation and supervision of health workers to accelerate implementation of the 2012 WHO Global Malaria Programme policy recommendations for IPTp-SP.

Community response to intermittent preventive treatment of malaria in infants (IPTi) delivered through the expanded programme of immunization in five African settings.

BACKGROUND: IPTi delivered through EPI has been shown to reduce the incidence of clinical malaria by 20-59%. However, new health interventions can only be effective if they are also socially and culturally acceptable. It is also crucial to ensure that attitudes to IPTi do not negatively influence attitudes to and uptake of immunization, or that people do not misunderstand IPTi as immunization against malaria and neglect other preventive measures or delay treatment seeking. METHODS: These issues were studied in five African countries in the context of clinical trials and implementation studies of IPTi. Mixed methods were used, including structured questionnaires (1,296), semi-structured interviews (168), in-depth interviews (748) and focus group discussions (95) with mothers, fathers, health workers, community members, opinion leaders, and traditional healers. Participant observation was also carried out in the clinics. RESULTS: IPTi was widely acceptable because it resonated with existing traditional preventive practices and a general concern about infant health and good motherhood. It also fit neatly within already widely accepted routine vaccination. Acceptance and adherence were further facilitated by the hierarchical relationship between health staff and mothers and by the fact that clinic attendance had a social function for women beyond acquiring health care. Type of drug and regimen were important, with newer drugs being seen as more effective, but potentially also more dangerous. Single dose infant formulations delivered in the clinic seem to be the most likely to be both acceptable and adhered to. There was little evidence that IPTi per se had a negative impact on attitudes to EPI or that it had any affect on EPI adherence. There was also little evidence of IPTi having a negative impact on health seeking for infants with febrile illness or existing preventive practices. CONCLUSION: IPTi is generally acceptable across a wide range of settings in Africa and involving different drugs and regimens, though there is a strong preference for a single dose infant formulation. IPTi does not appear to have any negative effect on attitudes to EPI, and it is not interpreted as immunization against malaria.