Periodic Reporting for period 1 - SEMA ReACT (SEvere MAlaria treatment with Rectal artesunate and Artemisinin-based Combination Therapy [in remote settings])
Période du rapport: 2023-04-01 au 2024-09-30
Severe malaria in remote areas: Closing the evidence gap (SEMA ReACT) is a project that focuses on reducing the gap on timely access to treatment of severe malaria in children under-fives. SEMA ReACT project is a consortium of the University of Antwerp, Belgium, Medicines for Malaria Venture (MMV), Switzerland, The University of Kinshasa (DRC), The Tropical Diseases Research Centre (TDRC), Zambia and the National Institute for Medical Research (NIMR), Tanzania.
Annually, almost 500,000 children under 5 years die from malaria in Africa. Timely access to effective antimalarial therapies is lifesaving as treatment with pre-referral rectal artesunate capsules (RAS), followed by injectable artesunate and 3-day treatment with artemisinin-based Combination therapies (ACTs) leads to an observed 96% reduction in mortality. Though this full treatment algorithm is not always feasible when access to care is limited due to lack of transport, non-availability of services, and cost. For untreated severe malaria, the mortality approaches 100% while prompt treatment with effective antimalarial and supportive care reduces this rate to 10–20%. While referral to a higher care facility remains the gold standard in severe malaria management, alternative, evidence-driven, recommendations are needed that acknowledge this is not always feasible. The iCCM program offers a good avenue to attain the goal of prompt treatment and hence save lives. Thus, this study will evaluate feasibility of provision of rapid treatment of severe malaria with RAS in children 6 months to 5 years by a community health worker or in Health Facility (HF) where there is no injectable artesunate available. In two districts (one from DRC-Kapolowe and other from Zambia-Nchelenge), all HFs will implement iCCM as per national guidelines that will be upgraded in a step wedged fashion as dictated by the pace of provision of the required commodities, RAS, RDTs and amoxicillin. Sentinel sites (as the whole district is not feasible to carry out close follow-up assessments) in Kapolowe and in Nchelenge will be selected at random in both study sites to act as for close monitoring of the clinical outcomes and for evaluation of the implementation. CHWs will identify/diagnose, treat and follow-up patients with severe disease including (severe) malaria as part of iCCM with supervision from the study research team in collaboration with MoH staff. The execution of the proposed study brings together vital experience in the rollout and deployment of RAS, study design and execution, social science, data collection and management, stakeholder engagement and translation of research results into clinical practice/policy.
Annually, almost 500,000 children under 5 years die from malaria in Africa. Timely access to effective antimalarial therapies is lifesaving as treatment with pre-referral rectal artesunate capsules (RAS), followed by injectable artesunate and 3-day treatment with artemisinin-based Combination therapies (ACTs) leads to an observed 96% reduction in mortality. Though this full treatment algorithm is not always feasible when access to care is limited due to lack of transport, non-availability of services, and cost. For untreated severe malaria, the mortality approaches 100% while prompt treatment with effective antimalarial and supportive care reduces this rate to 10–20%. While referral to a higher care facility remains the gold standard in severe malaria management, alternative, evidence-driven, recommendations are needed that acknowledge this is not always feasible. The iCCM program offers a good avenue to attain the goal of prompt treatment and hence save lives. Thus, this study will evaluate feasibility of provision of rapid treatment of severe malaria with RAS in children 6 months to 5 years by a community health worker or in Health Facility (HF) where there is no injectable artesunate available. In two districts (one from DRC-Kapolowe and other from Zambia-Nchelenge), all HFs will implement iCCM as per national guidelines that will be upgraded in a step wedged fashion as dictated by the pace of provision of the required commodities, RAS, RDTs and amoxicillin. Sentinel sites (as the whole district is not feasible to carry out close follow-up assessments) in Kapolowe and in Nchelenge will be selected at random in both study sites to act as for close monitoring of the clinical outcomes and for evaluation of the implementation. CHWs will identify/diagnose, treat and follow-up patients with severe disease including (severe) malaria as part of iCCM with supervision from the study research team in collaboration with MoH staff. The execution of the proposed study brings together vital experience in the rollout and deployment of RAS, study design and execution, social science, data collection and management, stakeholder engagement and translation of research results into clinical practice/policy.
In this reporting period we cover the project inception through a kickoff meeting (Deliverable 39) conducted in June 2023. Now, from study commencement all the way to current study status, the following activities have been achieved in relation to the deliverables(D) reported so far as per this periodic reporting time:
1) Kick off meeting was held in June 2023 (D39), from this meeting different documents were discussed and finalized these include the steering committee and advisory bodies charter(D2, 40), Project oversight structure(D1), Procedure for immediate reporting to EDCTP(D3), Standard Operating procedures (SOPs) (D4-7) were finalized.
2) The study protocol was finalized and obtained ethical approvals from both sites, first in Kapolowe, DRC and then in Nchelenge, Zambia. (D8, 9).
3) The study team training covering implementation with the MoH staff as well as research staff in the sentinel area (D61,63) was conducted and finalised allowing for study participants recruitment in both longitudinal follow up phase 1 as well as cluster randomised cross section surveys for community assessments as per protocol (D20,21).
4) The consortium also formulated the independent advisory committee (IAC) (D2) to provide advice on various aspect of study implementation, the charter has been agreed upon and signed by IAC members and two formal meetings have been conducted one for protocol build up and the other providing preliminary findings following completion of phase 1 in DRC plus plans for the second phase for improvement following the process evaluation meeting in DRC.
5) Following the study protocol approvals Data management and statistical analysis plan (D26-27) and also Database build, Trainings, data quality were all finalized and submitted (D28, 61, 62, 63).
6) The study officially started recruitment in Kapolowe first on 11 March 2024 and then in Nchelenge in on 5th Aug 2024. The delay in recruitment for Nchelenge was ere due to delays in ethical and regulatory procedures, however the finalized protocol as approved by the Zambian authorities was also submitted to DRC as an amendment and was approved to ensure both sites implement the same protocol version as submitted (D8,9).
7) Kapolowe site was the first to implement cross section survey (in Mar 2024) and also completed phase 1 of the study (in June 2024), thus reports in the periodic report will mostly cover the Kapolowe site as described in deliverables D20-21. Kapolowe site (DRC) completed phase 1 of the study implementation by end of June 2024 and entered the second phase in which RAS was introduced in half of the health areas as per protocol. This happened after having completed a process evaluation meeting conducted in the last week of June 2024.
8) In addition, as part of WP5, the Project webpage (D29), Communication and dissemination plan (D30), Communication toolkit (D31), Two Newsletters (D64-65) and two Presentations at conferences (D73,74) have been accomplished and submitted as deliverables to EDCTP portal.
1) Kick off meeting was held in June 2023 (D39), from this meeting different documents were discussed and finalized these include the steering committee and advisory bodies charter(D2, 40), Project oversight structure(D1), Procedure for immediate reporting to EDCTP(D3), Standard Operating procedures (SOPs) (D4-7) were finalized.
2) The study protocol was finalized and obtained ethical approvals from both sites, first in Kapolowe, DRC and then in Nchelenge, Zambia. (D8, 9).
3) The study team training covering implementation with the MoH staff as well as research staff in the sentinel area (D61,63) was conducted and finalised allowing for study participants recruitment in both longitudinal follow up phase 1 as well as cluster randomised cross section surveys for community assessments as per protocol (D20,21).
4) The consortium also formulated the independent advisory committee (IAC) (D2) to provide advice on various aspect of study implementation, the charter has been agreed upon and signed by IAC members and two formal meetings have been conducted one for protocol build up and the other providing preliminary findings following completion of phase 1 in DRC plus plans for the second phase for improvement following the process evaluation meeting in DRC.
5) Following the study protocol approvals Data management and statistical analysis plan (D26-27) and also Database build, Trainings, data quality were all finalized and submitted (D28, 61, 62, 63).
6) The study officially started recruitment in Kapolowe first on 11 March 2024 and then in Nchelenge in on 5th Aug 2024. The delay in recruitment for Nchelenge was ere due to delays in ethical and regulatory procedures, however the finalized protocol as approved by the Zambian authorities was also submitted to DRC as an amendment and was approved to ensure both sites implement the same protocol version as submitted (D8,9).
7) Kapolowe site was the first to implement cross section survey (in Mar 2024) and also completed phase 1 of the study (in June 2024), thus reports in the periodic report will mostly cover the Kapolowe site as described in deliverables D20-21. Kapolowe site (DRC) completed phase 1 of the study implementation by end of June 2024 and entered the second phase in which RAS was introduced in half of the health areas as per protocol. This happened after having completed a process evaluation meeting conducted in the last week of June 2024.
8) In addition, as part of WP5, the Project webpage (D29), Communication and dissemination plan (D30), Communication toolkit (D31), Two Newsletters (D64-65) and two Presentations at conferences (D73,74) have been accomplished and submitted as deliverables to EDCTP portal.
The study is ongoing. The SEMA ReACT work will contribute towards increased local capacity in severe malaria management. This will have enduring impact, potentially, this operational framework could be used as a template by other malaria control programmes, creating valuable local reservoirs of knowledge, which can be disseminated throughout communities. Reducing the burden of severe malaria may also help to address gender disparities, as women are often the primary caregivers for sick children. This has the potential to contribute towards significant and longer-term positive economic impact. Early access to care ensures limited severity of the disease and hence early cure and so getting back to work earlier. There are six PhD candidates who have been enrolled as part of the study, they will add more capacity to the local institutions within the consortium and mainly study sites countries.