Antibody responses to Plasmodium falciparum as markers of exposure and tools to monitor malaria transmission

Plasmodium falciparum malaria has the highest death toll of all human parasitic diseases and nearly half of the global population is living at risk of infection. Reducing the malaria burden with the goal of achieving elimination will require sustained commitment for control and better monitoring tools that can guide efforts to limit transmission. An effective malaria vaccine could significantly accelerate progress towards elimination but incomplete understanding of malaria immunity hampers vaccine development. Antibodies are key components of immunity to malaria and can also serve as sensitive markers of exposure. Data on the dynamics and specificity of the antibody response in natural P. falciparum infection could improve our understanding of the acquisition and maintenance of immunity, and be used to develop better serological tools for transmission surveillance.

In study I, we examined the temporal trends in malaria transmission over a period of 25 years in a closely monitored population in a rural area in Tanzania. We detected a gradual reduction in parasite prevalence starting prior to large-scale interventions and found that evaluation of spleen rate and haemoglobin levels were complementary to microscopy and molecular methods for estimates of malaria burden in this area of initially very high transmission. In study II, we developed new models for serological surveillance of malaria transmission based on cross-sectional data on age-specific antibody levels and evaluated their performance by further examining the transmission trends observed in study I. We demonstrated that these models are robust and improve precision in serological transmission estimates based on cross-sectional antibody data. In study III, we conducted a longitudinal follow-up of travellers treated for malaria in Sweden. We provided quantitative estimates of the dynamics and the longevity of malaria-specific antibodies and antibody secreting cells in absence of reexposure. In study IV, we examined the antibody responses to 111 P. falciparum antigens in the longitudinally followed travellers and identified novel candidate serological markers of recent exposure that warrant further evaluation.

Together these studies contribute to our overall understanding of the acquisition and maintenance of the antimalarial antibody response. The results help to improve current methods for serological malaria transmission surveillance and provide new information on antibody responses to P. falciparum that should be explored as markers of exposure.

List of scientific papers

I. Färnert A, Yman V, Vafa Homann M, Wandell G, Mhoja L, Johansson M, Jesaja S, Sandlund J, Tanabe K, Hammar U, Botai M, Premji Z G, Björkman A, Rooth I. Epidemiology of malaria in a village in the Rufiji River Delta, Tanzania: declining transmission over 25 years revealed by different parasitological metrics. Malaria Journal. 2014, 13, 459.
https://doi.org/10.1186/1475-2875-13-459

II. Yman V, White MT, Rono J, Arcà B, Osier F H A, Troye-Blomberg M, Boström S, Ronca R, Rooth I, Färnert A. Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity. Scientific Reports. 2016, 6, 19472.
https://doi.org/10.1038/srep19472

III. Yman V, White M T, Asghar M, Sundling C, Sondén K, Draper S J, Osier F H A, Färnert A. Dynamics of antibody responses to Plasmodium falciparum merozoite antigens after a single infection: Longevity explained by previous exposure and antibody secreting cell profiles. [Submitted]

IV. Yman V, Tuju J, White M T, Kamuyu G, Mwai K, Kibinge N, Asghar M, Sundling C, Sondén K, Bottai M, Murungi L, Kiboi D, Kimathi R, Chege T, Chepsat E, Kiyuka P, Nyamako L, Osier F H A, Färnert A. Serological signatures of recent and cumulative exposure to Plasmodium falciparum infection. [Manuscript]