Distinct kinetics in antibody responses to 111 Plasmodium falciparum antigens identifies novel serological markers of recent malaria exposure

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could dramatically 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 travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a novel combination of five serological markers (GAMA, MSP1, MSPDBL1 C- and N-terminal, and PfSEA1) that detect exposure within the previous 3-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. These serological exposure markers can be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Swedish Research Council [grant no 2015-02977 and 2018-02688 to AF] and by the Stockholm County Council [ALF project grant no. 20130207 and 20150135 to AF]. FHAO is supported by a Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation (3.2 - 1184811 - KEN -SKP) and an EDCTP Senior Fellowship supported by the European Union (TMA 2015 SF1001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethical Review Board in Stockholm, Sweden (Dnr 2006/893-31/4 and 2013/550-32/4, 2018/2354-32, 2019-03436) and written informed consent was obtained from all study participants. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets used and analysed during the current study are available from the corresponding author on reasonable request.