Abstract
BACKGROUNDNaturally acquired immunity to malaria is incompletely understood. We used controlled human malaria infection (CHMI) to study the impact of past exposure on malaria in Kenyan adults in relation to infection with a non-Kenyan parasite strain.METHODSWe administered 3.2 × 103 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (Sanaria PfSPZ Challenge, NF54 West African strain) by direct venous inoculation and undertook clinical monitoring and serial quantitative PCR (qPCR) of the 18S ribosomal RNA gene. The study endpoint was met when parasitemia reached 500 or more parasites per μL blood, clinically important symptoms were seen, or at 21 days after inoculation. All volunteers received antimalarial drug treatment upon meeting the endpoint.RESULTSOne hundred and sixty-one volunteers underwent CHMI between August 4, 2016, and February 14, 2018. CHMI was well tolerated, with no severe or serious adverse events. Nineteen volunteers (11.8%) were excluded from the analysis based on detection of antimalarial drugs above the minimal inhibitory concentration or parasites genotyped as non-NF54. Of the 142 volunteers who were eligible for analysis, 26 (18.3%) had febrile symptoms and were treated; 30 (21.1%) reached 500 or more parasites per μL and were treated; 53 (37.3%) had parasitemia without meeting thresholds for treatment; and 33 (23.2%) remained qPCR negative.CONCLUSIONWe found that past exposure to malaria, as evidenced by location of residence, in some Kenyan adults can completely suppress in vivo growth of a parasite strain originating from outside Kenya.TRIAL REGISTRATIONClinicalTrials.gov NCT02739763.FUNDINGWellcome Trust.
Highlights
Humans become immune to Plasmodium falciparum malaria following repeated exposure [1]
The aim of this study was to investigate how the in vivo parasite growth in controlled human malaria infection (CHMI) would be modified by preexisting immunity, where qPCR was used to quantify parasite growth and PfNF54 parasites were used for challenge
All 161 volunteers were inoculated with 3.2 × 103 PfSPZ of Sanaria PfSPZ Challenge NF54 by direct venous inoculation (DVI) and monitored for outcomes by clinical assessment and qPCR
Summary
Humans become immune to Plasmodium falciparum malaria following repeated exposure [1]. Immunoepidemiological studies show associations between immune responses and protection against malaria in the field [2], but their interpretation is complicated by heterogeneity of exposure [3]. Malaria is genetically diverse, and vaccines that protect against heterologous parasites are required for sustained public health impact. Exposure in the field is usually with parasites of unknown genotype, further complicating inferences on protective immunity. An experimental design with controlled exposure to parasites, such as the controlled human malaria infection (CHMI) model, is needed for greater confidence in inferring causality and to directly test for heterologous immunity. Human infection studies in which investigators intentionally infect healthy volunteers have been used to understand pathogenesis, immunity, and genetic resistance to infection and to measure the efficacy of drugs and vaccines [4]. We used controlled human malaria infection (CHMI) to study the impact of past exposure on malaria in Kenyan adults in relation to infection with a non-Kenyan parasite strain
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