Antibody Responses to Antigenic Targets of Recent Exposure Are Associated With Low-Density Parasitemia in Controlled Human Plasmodium falciparum Infections
Authorvan den Hoogen, LL; Walk, J; Oulton, T; Reuling, IJ; Reiling, L; Beeson, JG; Coppel, RL; Singh, SK; Draper, SJ; Bousema, T; ...
Source TitleFrontiers in Microbiology
PublisherFRONTIERS MEDIA SA
University of Melbourne Author/sBeeson, James
Document TypeJournal Article
Citationsvan den Hoogen, L. L., Walk, J., Oulton, T., Reuling, I. J., Reiling, L., Beeson, J. G., Coppel, R. L., Singh, S. K., Draper, S. J., Bousema, T., Drakeley, C., Sauerwein, R. & Tetteh, K. K. A. (2019). Antibody Responses to Antigenic Targets of Recent Exposure Are Associated With Low-Density Parasitemia in Controlled Human Plasmodium falciparum Infections. FRONTIERS IN MICROBIOLOGY, 9 (JAN), https://doi.org/10.3389/fmicb.2018.03300.
Access StatusOpen Access
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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