Safety and Tolerability of Mosquito-Bite Induced Controlled Human Infection with P. vivax in Malaria-Naïve Study Participants - Clinical Profile and Utility of Molecular Diagnostic Methods.

Background Plasmodium vivax controlled-human-malaria-infection (PvCHMI) is an important tool for the evaluation of drugs, vaccines and pathologies associated with this parasite. However, there is little data on its safety due to the limited number of PvCHMIs performed to-date. Methods We report clinical and laboratory data collected, to include hematological and biochemical profiles and adverse-events, following mosquito-bite induced PvCHMI in malaria-naive study-participants (ClinicalTrials.gov_NCT01157897). Malaria diagnosis and treatment initiation was based on microscopic analysis of Giemsa-stained slides. Exploratory molecular assays were used to detect parasites using real-time PCR. Results Adverse-events (AEs) were mild to moderate and no study-related severe AEs were observed in any of the study participants. Majority of the symptoms were transient, resolving within 48hours. Molecular-diagnostic methods detected parasitemia in 100% of study-participants before malaria diagnosis using microscopy. Of the reported AEs, microscopy detected 67-100%, qPCR 79-100% and qRT-PCR detected 96-100% of the study-participants prior to appearance of symptoms. Almost all the symptoms appeared after the initiation of treatment, likely as a known consequence of drug treatment. Conclusions PvCHMI is safe with majority of the infections being detected prior to the appearance of clinical symptoms, which can be further alleviated by using sensitive molecular methods for clinical diagnosis.