BACKGROUND: Plasmodium vivax controlled human malaria infection (PvCHMI) is an important tool for evaluation of drugs, vaccines, and pathologies associated with this parasite. However, there are few data on safety due to limited numbers of PvCHMIs performed. METHODS: We report clinical and laboratory data, including hematological and biochemical profiles and adverse events (AEs), following mosquito bite-induced PvCHMI in malaria-naive study participants. 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 polymerase chain reaction (PCR). RESULTS: AEs were mild to moderate and no study-related severe AEs were observed in any study participants. The majority of symptoms were transient, resolving within 48 hours. Molecular diagnostic methods detected parasitemia in 100% of study participants before malaria diagnosis using microscopy. Of reported AEs, microscopy detected 67%-100%, quantitative PCR 79%-100%, and quantitative real-time reverse-transcription PCR 96%-100% of study participants prior to appearance of symptoms. Almost all symptoms appeared after initiation of treatment, likely as known consequence of drug treatment. CONCLUSIONS: PvCHMI is safe with the majority of infections being detected prior to appearance of clinical symptoms, which can be further alleviated by using sensitive molecular methods for clinical diagnosis. Clinical Trials Registration. NCT01157897. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
BACKGROUND: Plasmodium vivax controlled human malaria infection (PvCHMI) is an important tool for evaluation of drugs, vaccines, and pathologies associated with this parasite. However, there are few data on safety due to limited numbers of PvCHMIs performed. METHODS: We report clinical and laboratory data, including hematological and biochemical profiles and adverse events (AEs), following mosquito bite-induced PvCHMI in malaria-naive study participants. 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 polymerase chain reaction (PCR). RESULTS: AEs were mild to moderate and no study-related severe AEs were observed in any study participants. The majority of symptoms were transient, resolving within 48 hours. Molecular diagnostic methods detected parasitemia in 100% of study participants before malaria diagnosis using microscopy. Of reported AEs, microscopy detected 67%-100%, quantitative PCR 79%-100%, and quantitative real-time reverse-transcription PCR 96%-100% of study participants prior to appearance of symptoms. Almost all symptoms appeared after initiation of treatment, likely as known consequence of drug treatment. CONCLUSIONS: PvCHMI is safe with the majority of infections being detected prior to appearance of clinical symptoms, which can be further alleviated by using sensitive molecular methods for clinical diagnosis. Clinical Trials Registration. NCT01157897. Published by Oxford University Press for the Infectious Diseases Society of America 2021.
Authors: Angela M Minassian; Yrene Themistocleous; Sarah E Silk; Jordan R Barrett; Alison Kemp; Doris Quinkert; Carolyn M Nielsen; Nick J Edwards; Thomas A Rawlinson; Fernando Ramos Lopez; Wanlapa Roobsoong; Katherine Jd Ellis; Jee-Sun Cho; Eerik Aunin; Thomas D Otto; Adam J Reid; Florian A Bach; Geneviève Mc Labbé; Ian D Poulton; Arianna Marini; Marija Zaric; Margaux Mulatier; Raquel Lopez Ramon; Megan Baker; Celia H Mitton; Jason C Sousa; Nattawan Rachaphaew; Chalermpon Kumpitak; Nongnuj Maneechai; Chayanut Suansomjit; Tianrat Piteekan; Mimi M Hou; Baktash Khozoee; Kirsty McHugh; David J Roberts; Alison M Lawrie; Andrew M Blagborough; Fay L Nugent; Iona J Taylor; Kimberly J Johnson; Philip J Spence; Jetsumon Sattabongkot; Sumi Biswas; Julian C Rayner; Simon J Draper Journal: JCI Insight Date: 2021-12-08