Addressing Both Naturally Occurring and ACT-induced Plasmodium Reservoirs Using Artemisia Infusions to Accelerate Malaria Elimination and Eradication in Rwanda: A Proof of Concept Randomized Controlled Trial

According to the World Health Organization (WHO) world malaria 2021 report, there were 241 million cases of malaria in 2020, with 627 000 estimated deaths during the same year - an increase of 69 000 deaths over the previous year. The African continent continues to carry a disproportionately high share of the global malaria burden. In 2020 the Region was home to 95% of all malaria cases and 96% of deaths. Children under 5 years of age accounted for about 80% of all malaria deaths in the Region. Despite admirable progress in the first 15 years of this century, there has been setbacks with regard to achieving malaria elimination.

Malaria is a parasitic vector-transmitted infection caused by Plasmodium species. Four main human species are: P. falciparum, the most virulent and predominant specie in Sub-Saharan Africa, P. Ovale, P. vivax and P. malariae, and one zoonotic specie P. knowlesi. It is a disease responsible for catastrophic health and socio-economic impact mainly due to Plasmodium falciparum, which is responsible for substantial morbidity and mortality especially in children under five years and pregnant women.

When a Plasmodium-carrying Anopheles mosquito takes a blood meal on an individual, saliva is injected together with the sporozoites, which migrate to the liver, thereby beginning a cycle. Once humans become infected, the hepatic cycle lasts 10 to 14 days (in the case of P. falciparum), after which thousands of asexually reproducing merozoites are released into the peripheral blood where they invade and develop inside mature erythrocytes. The blood stage parasites are those that cause the symptoms of malaria. In a continuous pattern, during asexual replication in the blood stream, a small proportion of the parasites undergo sexual development that lasts approximately 10 days in the case of P. falciparum, resulting in the production of transmissible gametocyte forms. These gametocytes responsible for parasite transmission from humans to the mosquito vector, are insensitive to most conventional antimalarial drugs and are often long-lived (population lifespan of up to 55 days following successful antimalarial therapy), thereby ensuring malaria transmission over several weeks. Disrupting malaria transmission therefore requires the development of new anti-gametocyte drugs with safety profiles that allow for population-wide treatment campaigns.

Rwanda has made great strides during the last two decades by investing strategically in health system strengthening, increasing access to care by establishing community based health insurance, resulting in substantial declines in disease burden. However, since 2012, the country has been experiencing a persistent upsurge of malaria. From 2012 to 2018, malaria incidence increased significantly from 48 per 1000 to 403 per 1000, an almost 10x increase. By 2019-2020, the number of cases was reduced by more than half, to 198 per 1000. Although transmission is heterogeneous in Rwanda, the entire population is considered at risk of malaria. The primary Plasmodium (P.) species found in Rwanda, the agent responsible for this disease, is P. falciparum, but P. malariae and P. ovale have also been identified and this is mostly in the cosmopolitan main city of Kigali that receives frequent travelers and tourists.

Despite the gains made, recent upsurges and concerns about growing drug resistance calls for more dynamic, accessible, cost effective and adaptive mechanisms to combat, and potentially eliminate malaria all together. Over the past decade, several public health measures attempting to eradicate malaria were instituted, but this goal remains elusive to date and the country, and like most of sub-Saharan Africa, Rwanda continues to face a high burden of malaria mortality and morbidity.