A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination. Despite the need to target all Plasmodium species, current focus is mainly directed towards Plasmodium falciparum , and to a lesser extent P . vivax . There is a substantial lack of data on both global and local transmission patterns of the neglected malaria parasites P . malariae and P . ovale spp. We used a species-specific real-time PCR assay targeting the Plasmodium 18s rRNA gene to evaluate temporal trends in the prevalence of all human malaria parasites over a 22-year period in a rural village in Tanzania.We tested 2897 blood samples collected in five cross-sectional surveys conducted between 1994 and 2016. Infections with P . falciparum , P . malariae , and P . ovale spp. were detected throughout the study period, while P . vivax was not detected. Between 1994 and 2010, we found a more than 90% reduction in the odds of infection with all detected species. The odds of P . falciparum infection was further reduced in 2016, while the odds of P . malariae and P . ovale spp. infection increased 2- and 6-fold, respectively, compared to 2010. In 2016, non-falciparum species occurred more often as mono-infections. The results demonstrate the persistent transmission of P . ovale spp., and to a lesser extent P . malariae despite a continued decline in P . falciparum transmission. This illustrates that the transmission patterns of the non-falciparum species do not necessarily follow those of P . falciparum , stressing the need for attention towards non-falciparum malaria in Africa. Malaria elimination will require a better understanding of the epidemiology of P . malariae and P . ovale spp. and improved tools for monitoring the transmission of all Plasmodium species, with a particular focus towards identifying asymptomatic carriers of infection and designing appropriate interventions to enhance malaria control.
Serology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. It has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. Seroconversion rates, based on antibody prevalence to Plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation rates but lack precision in settings where seroprevalence is still high. Here we present a new and widely applicable method, based on cross-sectional data on individual antibody levels. We evaluate its use as a sero-surveillance tool in a Tanzanian setting with declining malaria prevalence. We find that the newly developed mathematical models produce more precise estimates of transmission patterns, are robust in high transmission settings and when sample sizes are small, and provide a powerful tool for serological evaluation of malaria transmission intensity.In order to reduce the global malaria burden and achieve control, or even elimination, robust estimates of malaria transmission intensity are required for the strategic planning, implementation and evaluation of interventions [1][2][3][4] . Efficient monitoring of malaria transmission intensity depends on tools that produce reliable estimates across a wide range of transmission settings 5,6 . Such tools should preferably integrate information about both parasite and vector populations to capture the current level of transmission intensity as well as the transmission potential in areas where parasite carriage has decreased but vector populations persist [6][7][8][9] . Traditionally, transmission intensity has been estimated by a variety of techniques such as spleen rates, parasite prevalence or entomological inoculation rates (EIR) 2 . EIR has been considered the gold standard among metrics 10 , but is expensive and labour intensive to evaluate and estimates are often imprecise (especially when transmission is low) due to marked heterogeneity of both malaria transmission and vector distribution [10][11][12] . In addition, single-time point evaluation of parasite prevalence or EIR provides limited information about past transmission intensity 13,14 . Cumulative exposure to P. falciparum, however, can be estimated by evaluation of antibody responses to P. falciparum blood-stage antigens [15][16][17] . In addition, exposure to Anopheles mosquitoes can be evaluated through antibody responses to An. gambiae salivary gland protein 6 (gSG6) [18][19][20] . Existing methods for serological evaluation of malaria transmission have largely been based on cross-sectional data on antibody prevalence and on estimation of seroconversion rates (SCR) using serocatalytic models as shown by Drakeley et al. 15 . Although SCR based estimates have been extended to evaluate temporal changes 21-23 and provide robust information about medium and long-term trends of transmission intensity, they ...
BackgroundAntibodies against merozoite antigens are key components of malaria immunity. The naturally acquired antibody response to these antigens is generally considered short-lived; however, the underlying mechanisms remain unclear. Prospective studies of travellers with different levels of prior exposure, returning to malaria-free countries with Plasmodium infection, offer a unique opportunity to investigate the kinetics and composition of the antibody response after natural infection.MethodsAdults diagnosed with P. falciparum malaria in Stockholm, Sweden (20 likely malaria naïve and 41 with repeated previous exposure during residency in sub-Saharan Africa) were sampled at diagnosis and 10 days and 1, 3, 6, and 12 months after treatment. Total and subclass-specific IgG responses to P. falciparum merozoite antigens (AMA-1, MSP-119, MSP-2, MSP-3, and RH5) and tetanus toxoid were measured by multiplex bead-based immunoassays and ELISA. Mathematical modelling was used to estimate the exposure-dependent longevity of antibodies and antibody-secreting cells (ASCs).ResultsA majority of individuals mounted detectable antibody responses towards P. falciparum merozoite antigens at diagnosis; however, the magnitude and breadth were greater in individuals with prior exposure. In both exposure groups, antibody levels increased rapidly for 2 weeks and decayed thereafter. Previously exposed individuals maintained two- to ninefold greater antibody levels throughout the 1-year follow-up. The half-lives of malaria-specific long-lived ASCs, responsible for maintaining circulating antibodies, ranged from 1.8 to 3.7 years for merozoite antigens and were considerably short compared to tetanus-specific ASCs. Primary infected individuals did acquire a long-lived component of the antibody response; however, the total proportion of long-lived ASCs generated in response to infection was estimated not to exceed 10%. In contrast, previously exposed individuals maintained substantially larger numbers of long-lived ASCs (10–56% of total ASCs).ConclusionThe short-lived nature of the naturally acquired antibody response, to all tested merozoite antigens, following primary malaria infection can be attributed to a combination of a poor acquisition and short half-life of long-lived ASCs. Greater longevity is acquired with repeated infections and can be explained by the maintenance of larger numbers of long-lived ASCs. These insights advance our understanding of naturally acquired malaria immunity and will guide strategies for further development of both vaccines and serological tools to monitor exposure.Electronic supplementary materialThe online version of this article (10.1186/s12916-019-1255-3) contains supplementary material, which is available to authorized users.
SummaryAccelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real‐time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)–qPCR. Our results show that acute malaria infection affects cellular aging as reflected by elevated levels of CDKN2A expression, lower telomerase activity, and substantial telomere shortening during the first three months postinfection. After that CDKN2A expression declined, telomerase activity increased and telomere length was gradually restored over one year, reflecting that cellular aging was reversed. These findings demonstrate that malaria infection affects cellular aging and the underlying cellular mechanism by which pathogens can affect host cellular aging and longevity need to be elucidated. Our results urge the need to investigate whether repeated malaria infections have more pronounced and long‐lasting effects on cellular aging and lifespan (similarly to what was observed in birds) in populations living in malaria endemic areas.
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