Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections

Lotus L. Van Den Hoogen, Jona Walk, Tate Oulton, Isaie J. Reuling, Linda Reiling, James G. Beeson, Ross L. Coppel, Susheel K. Singh, Simon J. Draper, Teun Bousema, Chris Drakeley, Robert Sauerwein, Kevin K.A. Tetteh

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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.

Original languageEnglish
Article number03300
Number of pages11
JournalFrontiers in Microbiology
Publication statusPublished - 16 Jan 2019


  • antibodies
  • controlled human malaria infection (CHMI)
  • exposure
  • malaria
  • sero-epidemiology
  • sero-surveillance

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