Management of severe malaria: challenges and lessons learned with the introduction of pre-referral Rectal Artesunate in the Democratic Republic of the Congo

Malaria causes over 240 million cases and over 600,000 deaths annually, mostly among children under the age of five years. The Democratic Republic of the Congo (DRC) has the second highest malaria mortality in the world, accounting for 12% of the global burden of malaria. Despite substantial improvements in prevention and treatment during the past 10 years, malaria remains the principal cause of morbidity and mortality, accounting for 44% of all deaths among outpatient visits in children, and 22% of all in-patient deaths. One of the major challenges in severe malaria case management remains the limited access to higher-level health facilities where a full treatment can be provided. This is especially an issue for populations living in remote areas, resulting in treatment delays of several hours or even days. In such situations, the World Health Organization (WHO) recommends pre-referral treatment, either with a single dose of a parenteral anti-malarial, or with a single dose of rectal artesunate (RAS). The Congolese National Malaria Control Programme (NMCP) is committed to reducing the high number of malaria-related deaths through proven interventions such as pre-referral RAS. The aim of this thesis was to identify challenges and draw lessons learned from the implementation of pre-referral RAS in DRC, in view of supporting its responsible introduction into the national health system. The present work was entirely conducted in the frame of the multi-country Community Access to Rectal Artesunate for Malaria (CARAMAL) project.
In DRC, we setup a patient surveillance system (PSS) in three Health Zones to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death. To contextualize the data gathered through the PSS, we also conducted cross-sectional household surveys in the same locations to assess treatment seeking predictors and the prevalence of malaria.
Findings showed a high prevalence of malaria (45.1%, 95% CI 39.8–50.4) and anaemia (79.5%, 95% CI 77.1–81.7) in these communities. The presence of danger signs was not optimal but still increased the likelihood of seeking treatment (aOR=2.12, 95% CI 1.03–4.38). Unfortunately, still many children with danger signs were not brought to health facilities, or were brought late. Importantly, danger signs were well recognized by health provider at the primary care level, and RAS is acceptable and can be given without problem by low-level health care workers.
Referral Health Facilities (RHF) are the subsequent point of contact for severely ill children, after they successfully complete their referral.
According to the current treatment recommendations, the post-referral treatment of severe malaria comprises the provision of parenteral artesunate for at least 24 hours, followed by a full course of an Artemisinin Combination Therapy (ACT) once the patient can tolerate oral medication. In the RHFs, our aim was to assess the compliance of health care workers with the recommended treatment in children under 5 years. While only half of children were given parenteral antimalarial treatment (50.3%, 2,117/4,208), inpatient ACT administration was more common (78.7%, 1,314/1,669). The overall poor quality of severe malaria case management at higher-level facilities is an important health system issue and it is probably the reasons why the introduction of RAS did not have an impact on the Case Facility Rate of the pediatric patients. In addition, parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favor the selection of resistant parasites. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality.
Finally, we assessed the health system costs and constraints to the successful implementation of pre-referral RAS at community level. We did so to inform operational guidance and financial planning for the scale-up of RAS as pre-referral treatment for severe malaria. The equivalent annual costs of preparing the health system for managing severe malaria with RAS was $4.19 per child at risk, and $464 per child treated. Strengthening essential routine health system components accounted for the majority of these costs (76.4%).
In conclusion, introducing pre-referral RAS as a single intervention seemed not to add value in terms of reducing child mortality. Deploying successful pre-referral RAS at large scale requires preceding investments to strengthen the health system along the entire cascade of care. Only then can the potential of RAS as a pre-referral treatment be realized.