Treatment seeking and case management for suspected severe malaria in the context of implementing rectal artesunate

Despite major reductions since the year 2000, malaria is still a leading cause of morbidity and mortality in children under 5 years of age, especially in sub-Saharan Africa. The World Health Organization (WHO) recommends that children with severe malaria receive immediate treatment with parenteral antimalarial medication, followed by a three-day treatment course with an artemisinin-based combination therapy (ACT). However, many cases of severe malaria happen in areas where injections are not available. To reduce the mortality of these children, the WHO recommends rectal artesunate (RAS) as a pre-referral treatment for children under six years with fever and danger signs indicative of severe malaria. So far, this recommendation came with limited operational guidance. The “Community Access to Rectal Artesunate for Malaria” (CARAMAL) project aimed to generate evidence on the operational aspects of implementing and scaling up RAS. Within this context, understanding treatment-seeking and case management practices contributes to identifying inefficiencies within the continuum of care for severe malaria, eventually showing the need for supportive interventions accompanying the implementation of RAS.
The aim of this thesis was to investigate treatment-seeking and case management practices for suspected severe malaria in children under five years in three diverse settings in sub-Saharan Africa, and to evaluate the implications of these practices for the implementation of RAS. Children attending a community health worker (CHW) or primary health centre (PHC) in three health zones in the Democratic Republic of the Congo (DRC), three Local Government Areas in Adamawa State in Nigeria, and three districts in Uganda were enrolled if they presented to a community-based provider with fever and danger signs. Eligible children were followed up 28 days post-enrolment to assess their final health outcome, treatment-seeking and case management history.
Referral completion to a designated referral facility ranged from 48% in Nigeria to 67% in DRC. There was evidence that the administration of RAS may have negatively affected referral completion to designated referral facilities in DRC and among children attending a PHC in Nigeria. In Uganda, children who completed referral were more likely to receive appropriate post-referral treatment for malaria (treatment completion with an ACT) than children pursuing alternative treatment-seeking pathways or children who were not brought to any post-referral provider. Yet, alternative post-referral treatment-seeking pathways often also led to appropriate treatment. Inappropriate post-referral treatment was particularly a problem in Nigeria where none of the children completing referral to a designated referral facility were administered an ACT at the facility. Even though the situation presented better in DRC and Uganda, there was evidence that a considerable number of children did not complete malaria treatment with an ACT. This finding is concerning considering that the emergence and spread of artemisinin resistance in sub-Saharan Africa is now factual.
The case fatality rate (CFR) of children with suspected severe malaria initially seeing a community-based provider ranged from 0.5% in Uganda to 12% in Nigeria. The administration of RAS was not associated with a higher chance of survival, but reduced death or illness 28 days after enrolment in Uganda. Meanwhile, the administration of injectable antimalarials and ACTs had a positive effect on health outcomes in all project countries. Referral completion was associated with better health outcomes only in Nigeria. The CFR was particularly high among children attending a PHC in Nigeria (19%).
RAS did not prove to be effective in reducing deaths in any project country due to underlying shortfalls in the health systems. Because RAS has already been scaled up in many sub-Saharan African countries, future guidance on RAS needs to focus on mitigating the risks of the potentially negative effect of RAS administration on referral completion, with consequences for the quality of post-referral treatment and health outcomes. More generally, there is a need to strengthen appropriate post-referral treatment seeking; yet, with respect to local treatment-seeking practices leading to appropriate malaria case management, which may include providers outside of the public health system. However, disease-specific interventions often lack sustainability and only benefit the target population of the intervention. In contrast, strengthening the health system could lead to more equitable access to healthcare in the long-term, improving treatment seeking and case management of children with severe malaria and other severe febrile illnesses often mistaken for severe malaria. However, funding for health system strengthening is often allocated to interventions supporting single functions of the health system, which is less sustainable and has less broad impact. In addition, the active role of the population as a co-producer of health is often ignored in research and policymaking, subjecting people to passive recipients of health services. To effectively improve access to healthcare, equal attention has to be given to demand-side and supply-side determinants of access.
The historical and present efforts against malaria show that major progress in the future is only realistic if built on the solid ground of strong health systems and through strategies beyond technical solutions. Even though this conclusion is not new, the problem of weak health systems in malaria-endemic countries has not been adequately addressed in the past. Unless health budgets are increased, the aim of preventing malaria cases and deaths in the short-term contradicts the long-term goal of building stronger health systems.