Malaria transmission and antibody responses to Plasmodium falciparum

Malaria is a disease of public health concern. Globally, gains in malaria control seen over the last decades have recently stalled, with some areas experiencing a resurgence of malaria. Longitudinal studies in local areas provide valuable information about the changing epidemiology of malaria. This knowledge is crucial for surveillance and timely interventions.The aim of this thesis was to investigate trends in the prevalence of malaria and its influence on anaemia and antibody responses to P. falciparum in a previously highly endemic area in Tanzania. The population in Nyamisati, a coastal village in Tanzania, participated in a longitudinal epidemiology study with repeated cross- sectional surveys.In Study I, we assessed the prevalence of Plasmodium species from 1994 to 2016 using a species-specific real-time PCR assay targeting the Plasmodium 18S rRNA gene. We observed a reduction in the prevalence of P. falciparum, P. malariae, and P. ovale spp. until 2010. After 2010, P. falciparum prevalence decreased further, while P. ovale and P. malariae became relatively more common. In Study II, we further assessed the temporal trends of malaria using real-time PCR, microscopy, and rapid diagnostic tests, extending the analysis to include 11 surveys from 1986 to 2024. We also assessed the impact of malaria on anaemia. Over these four decades, malaria prevalence declined substantially, from 69.7% (95% CI 62.8-75.8) in 1986 to 3.5% (95% CI 2.1-5.7) in 2024 by real-time PCR. Anaemia prevalence decreased in parallel with malaria until 2016 but remained stable thereafter despite further reductions in malaria transmission.In Study III, we evaluated whether the antibody level to whole P. falciparum schizont extract is a marker of exposure as malaria transmission declines. We found that seropositivity and antibody levels against P. falciparum were higher in the high transmission period. Antibody levels and the odds of being seropositive were higher among individuals who were parasite positive at the survey, particularly during the low malaria transmission period. In Study IV, we assessed antibody function against P. falciparum merozoites as malaria transmission declined. Antibody-dependent respiratory burst (ADRB) activity was higher during the high malaria transmission period. Age was a significant predictor of ADRB activity in both malaria transmission periods. Ongoing infection significantly influenced ADRB activity during the low, but not the high, malaria transmission period.Collectively, these studies demonstrate a substantial decline in malaria transmission in Nyamisati, transitioning from very high to very low levels. Antibody responses, both in terms of levels and functional activity, were closely associated with parasite exposure, particularly as transmission waned. A deeper understanding of the factors contributing to reduced malaria transmission in this setting is essential. Overall, the findings highlight the importance of continuous monitoring of malaria epidemiology to guide control efforts and support future elimination strategies.List of scientific papersI. Persistent transmission of Plasmodium malariae and Plasmodium ovale species in an area of declining Plasmodium falciparum transmission in eastern Tanzania. Yman V, Wandell G, Mutemi D. D, Miglar A, Asghar M, Hammar U, Karlsson M, Lind I, Nordfjell C, Rooth I, Ngasala B, Homann M. V, Färnert A. PLOS Neglected Tropical Diseases, 13(5): e0007414 (2019). https://doi.org/10.1371/journal.pntd.0007414II. From high transmission to near elimination: Malaria trends in a rural village in coastal Tanzania from 1986 to 2024. Mutemi D. D, Yman V, Kinabo C, Makene T, Broumou I, Zerebinski J, Forsblom S, Miglar A, Ally J, Jesaja S, Mhoja L, Johansson M, Rooth I, Ngasala B, Färnert A. ManuscriptIII. Antibodies against Plasmodium falciparum schizont extract as a marker of malaria transmission intensity. Mutemi D. D, Yman V, Forsblom S, Foroogh F, Ribacke U, Vetter L, Tuju J, Nyamako L, Rooth I, Kinyanjui S, Ngasala B, Osier F, Färnert A. ManuscriptIV. Antibody-dependent respiratory burst against Plasmodium falciparum merozoites in individuals living in an area with declining malaria transmission. Mutemi D. D, Tuju J, Ogwang R, Nyamako L, Wambui K. M, Cruz I. R, Villner P, Yman V, Kinyanjui S. M, Rooth I, Ngasala B, Färnert A, Osier F. H. A. Vaccines, 12(2):203 (2024). https://doi.org/10.3390/vaccines12020203