Emerging treatments
Triple artemisinin-based combination therapies
Triple artemisinin-based combination therapies (e.g., artemether/lumefantrine/amodiaquine, artesunate/mefloquine/piperaquine) are in development, and may be useful to delay the emergence and spread of artemisinin resistance and treatment failure.[158]
Ivermectin
Ivermectin is an antiparasitic agent that works in malaria by killing mosquitoes that are exposed to the drug while feeding on the blood of people who have ingested the drug. A Cochrane review concluded that it is uncertain whether community administration of ivermectin has an effect on malaria transmission. There was no notable difference in the presence of malaria between the treatment and control groups (very low‐certainty evidence). However, this was based on the only trial published to date which included eight villages in Burkina Faso. Several research studies are in progress.[159]
Acetaminophen
Regular doses of acetaminophen have been found to be renoprotective in patients with severe malaria. Acute kidney injury is often a fatal complication of severe malaria. Hemolysis is thought to be a major contributor to acute kidney injury, and acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation. A small phase 2, open-label, randomized controlled trial found that acetaminophen had renoprotective effects in adults with severe falciparum malaria, particularly in participants with prominent intravascular hemolysis.[160] It has also been found to improve renal function in patients with severe knowlesi malaria, particularly in participants with acute kidney injury and hemolysis.[161] Further research is ongoing.
Monoclonal antibodies
Monoclonal antibodies are in development for the prevention of malaria. Monoclonal antibodies can potentially act at the following points in the life cycle: the pre-erythrocytic stage; the asexual erythrocytic stage; and the sexual erythrocytic stage. One small phase 1 trial of L9LS, which targets the circumsporozoite protein 1 (CSP-1) at the pre-erythrocytic stage, found that it protected recipients against malaria after controlled infection.[162] One small phase 2 trial of L9LS in children found that it protected children against P falciparum infection and clinical malaria over a period of 6 months.[163]
Cabamiquine
A novel investigational antimalarial that inhibits P falciparum translation elongation factor 2. Cabamiquine has a long half-life and has the potential to be developed as a single-dose monthly injection. A phase 1b, randomized, double-blind, placebo-controlled trial found a dose-dependent causal chemoprophylactic effect with cabamiquine when administered to healthy, malaria-naive adults (18-45 years of age). However, further research is required.[164]
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