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GLOBVAC-Global helse- og vaksin.forskn

Malaria Chemoprevention for the post-discharge management of severe anaemia in children in Malawi, Uganda and Kenya: Moving towards policy

Alternative title: Forebygging av malaria hos barn som har hatt alvorleg anemi etter utskriving frå sjukehus i Malawi, Uganda og Kenya

Awarded: NOK 32.8 mill.

Severe anaemia is a leading cause of hospital admissions in Africa and contributes substantially to paediatric morbidity and mortality. Children are at high risk of dying both during the acute phase, while they are at the hospital, but also for several months after they leave hospital. While management of malaria and severe anaemia follow well-established protocols when patients are in the hospital, systematic follow-up management has not been established for the post-discharge period. The main objectives of this project was to evaluate whether it is safe and efficacious to routinely prevent malaria by giving children antimalarial drugs during the first three months after discharge from hospital (PMC). To test this, studies were carried out in Kenya and Uganda, where children will be randomized to receive either three courses of the combination drug dihydroartemisinin-piperaquine (DHP), or three courses of a placebo. The project also explored how to best deliver these prevention strategies in the real world. In Malawi, the effectiveness, acceptability and feasibility of five different delivery strategies were assessed, and also their cost-effectiveness. Additionally using modelling techniques we determine the epidemiological and geographical settings where this prevention strategy will have the most impact in order to build up evidence for WHO policy development. The multidisciplinary team, led by Prof. Phiri (University of Malawi), has an exceptional publication record in this field, and includes senior researchers from Makerere University (Uganda), Kenya Medical Research Institute, Liverpool School of Tropical Medicine, London School of Hygiene and Tropical Medicine, Imperial College London, University of Amsterdam, Indiana University, and Chr. Michelsen Institute (Norway). The project is hosted by the Centre for International Health and the Section for Ethics and Health Economics (University of Bergen), with Prof. Bjarne Robberstad as project manager. By July 2020, all data collection and most analyses are completed, with 1049 patients in Kenya and Uganda and 375 patients in Malawi. The results show that the intervention reduces death or re-admission by 35%, and will likely support a general recommendation of PMC with DHP in the WHO East Africa Region, and is already being prepared for implementation in Uganda and Malawi. The results from the implementation trial in Malawi indicate that adherence of parents is higher if drugs are distributed to the parents through community-based methods. Facility-based distribution was found to result in comparably lower adherence. These results, too, are expected to inform the discussion on a Regional recommendation for PMC. Research on the communities' acceptability of these different delivery methods was published in 2018. The cost-effectiveness analysis as well as the impact modelling of PMC in other malaria-endemic areas is still ongoing and we expect the results to be published within 2020 and early 2021, respectively. This project is funded by GLOBVAC and is part of the EDCTP2-Program supported by the European Union.

The trial produced results that increase effectiveness of management of severely ill children and reduce the associated health care costs, thereby reducing costs to poor households. Women will be relieved and consequently welfare for households is expected to improve. Ultimate beneficiaries are children whose quality of life, health, welfare and creative output will be enhanced. The project likely contributes to WHO policy change. Other beneficiaries are international organisations and funders of large scale, malaria control initiatives that support malaria control policies in SSA. National policy makers and stakeholders are informed about the study outcomes and receive country specific data on safety, efficacy and cost effectiveness, but also information on effective delivery. MOHs in the countries were involved from the outset. The study contributed to the training and mentoring of PhD and postdoctoral candidates, that increased the research capacity of the three African partners.

BACKGROUND: Children hospitalised with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No strategy specifically addresses this post-discharge period. We recently showed that 3 months malaria chemoprevention with monthly Intermittent Preventive Therapy post-discharge (IPTpd) in Malawian children with severe anaemia prevented 31% of deaths and readmissions. The effect was in addition to the effect by bednets. These promising findings now need to be confirmed in other settings and the delivery mechanisms evaluated. OBJECTIVES: To generate the evidence needed by WHO to consider IPTpd as a strategy to reduce post-discharge morbidity and mortality in malaria endemic areas in Africa. MAJOR ACTIVITIES: This 5-year project comprises of: 1) Confirmatory Efficacy Trial in Kenya and Uganda: multi-centre, 2-arm, placebo-controlled, superiority trial of 3 courses of monthly IPTpd with dihydroartemisinin-piperaquine among 2212 children with severe anaemia. Composite primary endpoint: death and all-cause re-admission by 3 months; 2) Delivery mechanism trial in Malawi: Single-centre, cluster randomized, 4-arm factorial design trial in 380 children comparing the uptake, feasibility and acceptability of IPTpd delivered through outpatient departments or community based village health workers, with or without support from a phone text messaging reminder; 3) Impact analysis to define the target population and map the epidemiological and geographical settings in which IPTpd would be an appropriate intervention and estimate the potential public health impact through systematic reviews and modeling; 4) economical evaluation of the cost-effectiveness of IPTpd; and 5) IPTpd policy taskforce to liaise with WHO. PARTNERS: Univ of Bergen; Chr. Michelsens Institute; Univ of Malawi; Makerere Univ; KEMRI-CDC, Kenya; Univ of Indiana; Liverpool Sch of Trop Med; London Sch of Hyg &Trop Med; Imperial College London; Univ of Amsterdam.

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GLOBVAC-Global helse- og vaksin.forskn