Impact of scaling up the use of rectal artesunate pre-referral treatment on selection of artemisinin drug resistance in hard-to-reach communities in Africa
PhD summary
Malaria remains a major public health challenge in tropical and sub-tropical countries. Globally, it was estimated that 249 million cases of malaria occurred in malaria-endemic countries of which approximately 94% were in Africa. An estimated 608,000 deaths occurred were attributed to malaria (WMR, 2023). Children under the age of 5 and the population living in hard-to-reach settings are at higher risk of malaria deaths. Improved malaria case management remains a high priority for malaria control program in endemic areas.
A multi-country research project on the treatment of severe malaria with rectal artesunate (RAS) plus artemisinin-based combination therapy (ACT) for children aged 6 months to 5 years with symptoms of malaria in remote areas where referral to a health facility for treatment with injectable artesunate is not possible, is currently being implemented in remote settings in Democratic Republic of Congo and Zambia by SEMAReACT consortium partners (https://www.severemalaria.org/sema-react).
The SEMAReACT project is an effectiveness-implementation hybrid type III, to evaluate the implementation of RAS+ ACT policy by community health workers (CHWs) and in health facilities (HF) where there is not injectable artesunate for children aged 6 months to 5 years in remote settings of Nchelenge district in Zambia and Kapolowe district in DR Congo. Health facilities in these two districts will be randomized in two groups to implement either Integrated Community Case Management (iCCM) with RAS+ACT and amoxicillin or iCCM alone at different time points. RAS would be implementable through CHWs participating in iCCM. The implementation of the intervention will be introduced in a step wedged fashion meaning that, at the end of the project period all HFs will have implemented the intervention. A systematic cluster sampling method will be used and samples will be collected during the implementation of the SEMAReACT project for the longitudinal observation study at days 0, 14, 28 or at the unscheduled visit of 1100 children 6 months to 5 years of age presenting with symptoms of malaria and confirm the diagnosis by rapid diagnosis test for malaria by CHWs. Also the samples will be collected during community survey for the cross-sectional study before and after implementation in a selected households in the randomized villages.
The PhD project will focus on assessing the impact of scaling up the use of RAS pre-referral treatment on the selection of mutations related to artemisinin drug resistance in hard-to-reach communities in Africa.
This project will leverage the advances in genomic surveillance of antimalarial drug resistance to assesses the clinical effectiveness rectal artesunate as pre-referral treatment for severe malaria cases. Furthermore, the PhD project will assess different malaria genotyping to generate parasite data on parasite microsatellite, multiplicity of infection, and treatment outcomes based on new approaches to determine parasite recrudescence and new infections. The results will inform the SEMAReACT project, drug resistance surveillance and therapeutic malaria trials in the region.