As national malaria-control programs are intensifying and moving towards the goal of elimination, the primary focus has shifted from case management to the interruption of transmission. This will require the efficient and accurate identification of residual transmission foci that can be specifically targeted for elimination. Optimal surveillance systems should collect information on an ongoing basis to allow for a virtually real-time assessment of changes, while at the same time can be combined with other programmatic information to assist in planning, implementation, and modification/adjustment of malaria control activities to improve program performance. Whereas the current tools are not particularly suitable for this purpose, serological measurement, based on antibody prevalence, has been proposed as an alternative approach. Although this works well in areas of stable, low-level transmission, the vaccine antigens evaluated track changes in transmission very slowly and are thus of limited use in a rapidly changing environment where timely and actionable information is required. Thus there is an urgent need to identify a novel category of antigens with relatively short half-lives (6-8 weeks), and limited memory, for use in surveillance activitie. This need is particularly urgent for P. vivax, because well- characterized P. vivax candidate antigens are severely lacking. This study proposes to identify P. vivax proteins that can be used as antigens to screen for short half-life immune response, informing the recent history of parasite infection. Using multiplex bead assays, over 1,000 P. vivax proteins, produced by cell-free systems, will be screened against human plasma collected at different time intervals from P. vivax-infected subjects during clinical episodes and populations at risk in malaria endemic areas under a cohort epidemiological study with well-defined duration of new infection and post-treatment parasite clearance. The full kinetics profiles for antibodies to 100 selected antigens will be determined though analyzing the antibody titers at all time-points, to determine antibody half-lives. The 20 antigens with the best kinetic profiles (limited post-treatment antibody production, antibody half-life of 6-8 weeks, limited individual variation) will be selected for furher validation for use as surveillance candidate antigen to identify transmission hot-spots, using plasma from school-aged children in malaria-endemic and non-endemic areas. This study will result in the development of a novel serological assay to identify P. vivax transmission and its utility for detecting (residual) transmission 'hot-spots'among populations, and recent infections.

Public Health Relevance

Many nations are working towards the eventual elimination of malaria. In this process, it will be important to have a simple tool that can identify hotspots of residual transmission when control has been implemented, and malaria cases have declined. This study aims to identify Plasmodium vivax proteins that can be used as serological markers to identify new P. vivax infections with no history of previous infection. Once the protein markers are identified and validated for this purpose, monitoring of malaria transmission post-elimination can be performed in large scale more quickly and routinely than using other available methods, such as examination of blood smears for parasites, or amplification of parasite DNA using molecular-biological techniques.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-R (50))
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Rao, Malla R
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Mahidol University
Nakhon Pathom
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Longley, Rhea J; França, Camila T; White, Michael T et al. (2017) Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand. Malar J 16:178
Longley, Rhea J; Reyes-Sandoval, Arturo; Montoya-Díaz, Eduardo et al. (2016) Acquisition and Longevity of Antibodies to Plasmodium vivax Preerythrocytic Antigens in Western Thailand. Clin Vaccine Immunol 23:117-24
Longley, Rhea J; Sattabongkot, Jetsumon; Mueller, Ivo (2016) Insights into the naturally acquired immune response to Plasmodium vivax malaria. Parasitology 143:154-70
Longley, Rhea J; Sripoorote, Piyarat; Chobson, Pornpimol et al. (2016) High Efficacy of Primaquine Treatment for Plasmodium vivax in Western Thailand. Am J Trop Med Hyg 95:1086-1089