Ivermectin for causal malaria prophylaxis: a randomised controlled human infection trial

Abstract

Objective 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 WHO. 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 A total of 4 volunteers were randomised to placebo, and 8 volunteers were randomised to receive ivermectin 0.4 mg/kg, orally, once 2 h 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 volunteer became thick blood smear positive between day 11 and day 12 after infection, and there was no significant effect of ivermectin on parasitaemia. Conclusion Ivermectin – at the dose used – has no clinically relevant activity against the pre‐erythrocytic stages of P. falciparum.

Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults

“…This substantially contributed to lower VE calculations in both arms of the study. Although 100% of nonimmune control subjects in the United States and Europe (73/73) 13,26,27,29,40,41 and Tanzania (34/34) 15,18 have been infected with this dose, in other settings in Africa, including Gabon (20/25), 27,42 Gambia (17/ 19), 28 and unpublished data from Mali (8/15) and Kenya (137/ 170) (submitted), this has not been the case.…”

Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus Macaques

“…Neither in vitro nor in vivo P. cynomolgi models indicate a radical cure efficacy potential for ivermectin. A recent human challenge trial ( n = 8) with intravenous injection of cryopreserved Plasmodium falciparum sporozoites ( n = 3,200) and a single oral dose ivermectin (400 μg/kg) failed to show liver-stage inhibition in terms of time to blood-stage patency ( 22 ).…”

Recombinase Polymerase Amplification and Lateral Flow Assay for Ultrasensitive Detection of Low-Density Plasmodium falciparum Infection from Controlled Human Malaria Infection Studies and Naturally Acquired Infections

“…Samples for evaluation of the RT-RPA were collected from volunteers enrolled in CHMI trials conducted in Tübingen, Germany (n ϭ 39), and Lambaréné, Gabon (n ϭ 36). Details of the three studies in Tübingen are published elsewhere (5,6,13). CHMI samples from Lambaréné included volunteers recruited for a malaria vaccine trial (PACTR201503001038304) published recently (12).…”

“…The approach utilized abundant asexual stage-expressed rRNA and the coding genes (GenBank AL844504 and AL844506) as the template for amplification and the lateral flow strip for the readout. The diagnostic performance was evaluated in healthy volunteers with low-density parasitemia induced by standardized controlled human malaria infection (CHMI) with cryopreserved P. falciparum sporozoites (Sanaria PfSPZ challenge) (5,6,12,13). A further simplified direct blood amplification approach was tested in Lambaréné, Gabon, to evaluate the assay in asymptomatic individuals from a setting where malaria is endemic.…”