Antibody Responses to Antigenic Targets of Recent Exposure Are Associated With Low-Density Parasitemia in Controlled Human Plasmodium falciparum Infections

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van den Hoogen, Lotus L
Walk, Jona
Oulton, Tate
Reuling, Isaie J
Reiling, Linda
Beeson, James G
Coppel, Ross L
Singh, Susheel K
Draper, Simon J
Bousema, Teun
Drakeley, Chris
Sauerwein, Robert
Tetteh, Kevin KA
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2019
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Abstract

The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman’s ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.

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FRONTIERS IN MICROBIOLOGY
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© 2019 van den Hoogen, Walk, Oulton, Reuling, Reiling, Beeson, Coppel, Singh, Draper, Bousema, Drakeley, Sauerwein and Tetteh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Soil sciences
Microbiology
Medical microbiology
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