Project description:Malaria represents a major public health problem in Africa [1]. In the East African highlands, even in high-altitude areas previously considered too cold to support vector population and parasite transmission [2], frequent malaria epidemics have been reported since the 1980M-bM-^@M-^Ys [3]. Plasmodium falciparum infections have been detected in areas as high as 1,600-2,400m above sea level in Africa [4], albeit there is a marked gradient of parasite prevalence along the altitude transect [5-7]. Both the historical absence of malaria in the African highlands and now the intensive malaria control efforts put in place after the recent outbreaks have reduced malaria prevalence and incidence [8], rendering the East African highlands particularly prone to epidemic malaria due to the lack of the protective immunity, and causing significant human mortality amongst all age groups [9]. Therefore, malaria transmission monitoring in the East African highlands becomes a particularly important public health issue.Despite the overall lower immunity of the population in these historically malaria-free areas, the many successive outbreaks since the 1980M-bM-^@M-^Ys may have generated some level of immunity against P. falciparum amongst highland residents. The antibody response to Plasmodium is cumulative and long lasting, developing after repeated exposures to the parasite and persisting for months or years after infection was resolved. The antibody response to Plasmodium varies amongst individuals of different age groups (i.e. toddlers, children and adults) as well as amongst individuals of same age groups from areas of different parasite prevalence [10]. The repertoire of targets of the antibody response also expands after multiple infections, with the number of recognized antigens being correlated to parasite prevalence, age and immunity to clinical malaria [11,12]. Serological studies bring forth indirect evidence of human exposure to the parasite, and can reliably assess its prevalence and transmission intensity in an endemic area [13-15]. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasiteM-bM-^@M-^Ys antigens. The work we present here is an expansion of the study published by Badu et al. [16], in which the antibody response to the 19kDa fragment of merozoite surface protein 1 (MSP-119) was examined in populations from two endemic areas in the western Kenyan highlands. There, the tremendous variations of malaria transmission intensity in a small spatial scale are caused by substantial differences in altitude, topography and other environmental conditions [6,7,17,18]. We now expand our antibody profiling survey to include 854 P. falciparum proteins by using high-throughput proteomic microarray technology. Protein microarrays have been used to explore the humoral response to P. falciparum in other African settings [19-24], but this is the broadest characterization of the antibody responses of the population of western Kenyan highlands to date. In the present study we: i) determined the serological reactivity against P. falciparum (Pf) in subjects residing in a low transmission area, and detected hotspots of transmission; ii) examined the dynamics of antibody response to hundreds of Pf proteins generated by sera from toddlers, older children and adults residing in two endemic areas differing in transmission intensities, during two distinct malaria seasons, and compared the intensity, breadth and antigenic targets of these responses; and iii) identified candidate Pf antigenic markers that could provide more sensitive serological surveillance to detect micro-geographic variations in malaria transmission levels and differentiate hotspots of infection in low endemic areas. (references provided in the 'readme.txt') Antibody profiling was performed on sera from residents of western Kenyan highlands against Plasmodium falciparum. One-hundred and ten age-stratified serum samples collected during the dry and the wet seasons, from residents of two locations with differing parasite transmission levels (uphill and valley bottom), and 10 unexposed USA controls were probed on a protein microarray displaying 854 unique proteins of P. falciparum.

Project description:Plasmodium vivax is the most geographically widespread human malaria parasite causing approximately 130-435 million infections annually. It is an economic burden in many parts of the world and poses a public health challenge along with the other Plasmodium sp. The biology of this parasite is very little understood. Emerging evidences of severe complications due to infections by this parasite provides an impetus to focus research on the same. Investigating this parasite directly from the infected patients is the most feasible way to study its biology and any pathogenic mechanisms which may exist. Gene expression studies of this parasite directly obtained from the patients has provided evidence of gene regulation resulting in varying amount of transcript levels in the different blood stages. However, the mechanisms regulating gene expression in malaria parasites are not well understood. Discovery of natural antisense transcripts (NATs) in P. falciparum has suggested that these might play an important role in regulating gene expression. We report here the genome-wide occurrence of NATs in P. vivax parasites from patients with differing clinical symptoms. A total of 1348 NATs against annotated gene loci have been detected using a custom designed strand specific microarray. Majority of NATs identified from this study shows positive correlation with the expression pattern of the sense transcript. Our data also shows condition specific expression patterns of varying S and AS transcript levels. Genes with AS transcripts enrich to various biological processes. This is the first report detailing the presence of NATs from clinical isolates of P. vivax. The data suggests differential regulation of gene expression in diverse clinical conditions and would lead to future detailed investigations of genome regulation. Plasmodium vivax isolates were collected from patients (n = 8) with differing clinical conditions.The patients exhibited symptoms categorized as un-complicated (n =1) or complicated malaria (n = 7). Criteria for determination of complicated disease were based on World Health Organization year 2010 guidelines. Microarray array based transcriptional profiling was carried out to detect prevalence of natural antisense transcripts.

Project description:Malaria represents a major public health problem in Africa [1]. In the East African highlands, even in high-altitude areas previously considered too cold to support vector population and parasite transmission [2], frequent malaria epidemics have been reported since the 1980’s [3]. Plasmodium falciparum infections have been detected in areas as high as 1,600-2,400m above sea level in Africa [4], albeit there is a marked gradient of parasite prevalence along the altitude transect [5-7]. Both the historical absence of malaria in the African highlands and now the intensive malaria control efforts put in place after the recent outbreaks have reduced malaria prevalence and incidence [8], rendering the East African highlands particularly prone to epidemic malaria due to the lack of the protective immunity, and causing significant human mortality amongst all age groups [9]. Therefore, malaria transmission monitoring in the East African highlands becomes a particularly important public health issue.Despite the overall lower immunity of the population in these historically malaria-free areas, the many successive outbreaks since the 1980’s may have generated some level of immunity against P. falciparum amongst highland residents. The antibody response to Plasmodium is cumulative and long lasting, developing after repeated exposures to the parasite and persisting for months or years after infection was resolved. The antibody response to Plasmodium varies amongst individuals of different age groups (i.e. toddlers, children and adults) as well as amongst individuals of same age groups from areas of different parasite prevalence [10]. The repertoire of targets of the antibody response also expands after multiple infections, with the number of recognized antigens being correlated to parasite prevalence, age and immunity to clinical malaria [11,12]. Serological studies bring forth indirect evidence of human exposure to the parasite, and can reliably assess its prevalence and transmission intensity in an endemic area [13-15]. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasite’s antigens. The work we present here is an expansion of the study published by Badu et al. [16], in which the antibody response to the 19kDa fragment of merozoite surface protein 1 (MSP-119) was examined in populations from two endemic areas in the western Kenyan highlands. There, the tremendous variations of malaria transmission intensity in a small spatial scale are caused by substantial differences in altitude, topography and other environmental conditions [6,7,17,18]. We now expand our antibody profiling survey to include 854 P. falciparum proteins by using high-throughput proteomic microarray technology. Protein microarrays have been used to explore the humoral response to P. falciparum in other African settings [19-24], but this is the broadest characterization of the antibody responses of the population of western Kenyan highlands to date. In the present study we: i) determined the serological reactivity against P. falciparum (Pf) in subjects residing in a low transmission area, and detected hotspots of transmission; ii) examined the dynamics of antibody response to hundreds of Pf proteins generated by sera from toddlers, older children and adults residing in two endemic areas differing in transmission intensities, during two distinct malaria seasons, and compared the intensity, breadth and antigenic targets of these responses; and iii) identified candidate Pf antigenic markers that could provide more sensitive serological surveillance to detect micro-geographic variations in malaria transmission levels and differentiate hotspots of infection in low endemic areas. (references provided in the 'readme.txt')

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