Distinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure

Victor Yman,Timothy Chege,Faith H A Osier,Daniel Kiboi,Christopher Sundling,Anna Färnert,Michael T White,Patience Kiyuka,James Tuju,Emily Chepsat,Kennedy Mwai,Gathoni Kamuyu,Nelson Kibinge,Lydia Nyamako,Klara Sondén,Linda Murungi,Muhammad Asghar,Rinter Kimathi

doi:10.1038/s41467-021-27863-8

Abstract

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in 65 adult travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a combination of five serological markers that detect exposure within the previous three months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. Such serological exposure markers could be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.

Highlights

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden
Sixty-five adults diagnosed with P. falciparum malaria at Karolinska University Hospital in Sweden were enroled at the time of diagnosis and followed prospectively with repeated blood sampling for up to one year in complete absence of re-exposure
Antibody responses to 111 P. falciparum blood-stage antigens were quantified in all collected sample series using the KILchip protein microarray

Summary

Introduction

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. A serological tool that provides information on the magnitude of the individual-level exposure as well as the time frame within which the individual was last exposed is currently lacking and could improve surveillance by allowing for estimation of infection incidence from single timepoint cross-sectional data[15] Such information could be used to monitor transmission intensity and dynamics, trigger intensified surveillance with focused malaria testing and treatment, guide targeted interventions (e.g. using long-lasting insecticidal nets or other vector control measures) and subsequently evaluate their impact, or even to demonstrate the absence of transmission (reviewed in Greenhouse et al 2018 and 2019)[16,17]. It is possible that these uncontrolled factors may have impacted which candidate serological markers have previously been suggested[21,25,26,31]

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Conclusion