Successful Human Infection with P. falciparum Using Three Aseptic Anopheles stephensi Mosquitoes: A New Model for Controlled Human Malaria InfectionReport as inadecuate




Successful Human Infection with P. falciparum Using Three Aseptic Anopheles stephensi Mosquitoes: A New Model for Controlled Human Malaria Infection - Download this document for free, or read online. Document in PDF available to download.

Controlled human malaria infection CHMI is a powerful method for assessing the efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5 Plasmodium falciparum Pf sporozoite SPZ-infected mosquitoes to reliably induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected mosquitoes reared aseptically in compliance with current good manufacturing practices cGMP was successful in 6 participants. Here, we report results from a subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to validate the initial clinical trial. We also compare results of safety, tolerability, and transmission dynamics in participants undergoing CHMI using 3 PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5 mosquitoes. Nineteen adults aged 18–40 years were bitten by 3 Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19 participants developed malaria 100%; 12 of 19 63% on Day 11. The mean pre-patent period was 258.3 hours range 210.5–333.8. The geometric mean parasitemia at first diagnosis by microscopy was 9.5 parasites-µL range 2–44. Quantitative polymerase chain reaction qPCR detected parasites an average of 79.8 hours range 43.8–116.7 before microscopy. The mosquitoes had a geometric mean of 37,894 PfSPZ-mosquito range 3,500–152,200. Exposure to the bites of 3 aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for CHMI in malaria-naïve adults. The aseptic model should be considered as a new standard for CHMI trials in non-endemic areas. Microscopy is the gold standard used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites earlier. If qPCR continues to be shown to be highly specific, and can be made to be practical, rapid, and standardized, it should be considered as an alternative for diagnosis.

Trial Registration

ClinicalTrials.gov NCT00744133 NCT00744133



Author: Matthew B. Laurens, Peter Billingsley, Adam Richman, Abraham G. Eappen, Matthew Adams, Tao Li, Sumana Chakravarty, Anusha Gunasek

Source: http://plos.srce.hr/



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