Ivermectin for Causal Malaria Prophylaxis: A Randomized Controlled Human Infection Trial

Abstract

Background: Ivermectin is safe and widely used for treating helminth infections. It also kills arthropods feeding on treated subjects, including malaria vectors. Thus, ivermectin mass drug administration as an additional tool for malaria control is being evaluated by the World Health Organization: As in vitro data, animal experiments and epidemiological observations suggest that ivermectin has a direct effect on the liver stages of the malaria parasite, this study was designed to assess the prophylactic effect of ivermectin on Plasmodium falciparum controlled human malaria infection. Methods: 4 volunteers were randomized to placebo, and 8 volunteers were randomized to receive ivermectin 0,4 mg/kg, orally, once 2 hours before being experimentally infected intravenously with 3200 P. falciparum sporozoites. The primary endpoint was time to parasitaemia detected by positive thick blood smear; RT-qPCR was performed in parallel. Results: All but one volunteers became thick blood smear positive between day 11 and day 12 after infection and there was no significant effect of ivermectin on parasitaemia. Conclusions: Ivermectin - at the dose used - has no clinically relevant activity against the preerythrocytic stages of P. falciparum. Clinical Trial Registration Number: The study was registered with the European Clinical Trials Register (EudraCT-Nr. 2017-002723-16). Funding Statement: This study was carried out at the clinical trial platform at the Institute of Tropical Medicine at the University of Tubingen, Germany, and was partly funded by the Else Kroner-Fresenius-Stiftung/Bad Homburg, Germany. Declaration of Interests: Dr. Metzger has nothing to disclose. All other authors have nothing to disclose. Ethics Approval Statement: The study complied with the International Council for Harmonisation Good Clinical Practice guidelines and the German Medicines Law and was approved by the ethics committee of the Eberhard Karls Universitat and the Universitatsklinikum Tubingen and the competent regulatory authority Bundesinstitut fur Arzneimittel und Medizinprodukte and the Regierungsprasidium Tubingen. A Safety Monitoring Committee reviewed the study to evaluate the safety of individual volunteers.