Abstract
Malaria represents a major public health problem in Africa. In the East African highlands, the high-altitude areas were previously considered too cold to support vector population and parasite transmission, rendering the region particularly prone to epidemic malaria due to the lack of protective immunity of the population. Since the 1980’s, frequent malaria epidemics have been reported and these successive outbreaks may have generated some immunity against Plasmodium falciparum amongst the highland residents. Serological studies reveal indirect evidence of human exposure to the parasite, and can reliably assess prevalence of exposure and transmission intensity in an endemic area. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasite’s antigens. We surveyed and compared the antibody response profiles of age-stratified sera from residents of two endemic areas in the western Kenyan highlands with differing malaria transmission intensities, during two distinct seasons, against 854 polypeptides of P. falciparum using high-throughput proteomic microarray technology. We identified 107 proteins as serum antibody targets, which were then characterized for their gene ontology biological process and cellular component of the parasite, and showed significant enrichment for categories related to immune evasion, pathogenesis and expression on the host’s cell and parasite’s surface. Additionally, we calculated age-fitted annual seroconversion rates for the immunogenic proteins, and contrasted the age-dependent antibody acquisition for those antigens between the two sampling sites. We observed highly immunogenic antigens that produce stable antibody responses from early age in both sites, as well as less immunogenic proteins that require repeated exposure for stable responses to develop and produce different seroconversion rates between sites. We propose that a combination of highly and less immunogenic proteins could be used in serological surveys to detect differences in malaria transmission levels, distinguishing sites of unstable and stable transmission.
Highlights
Malaria represents a major public health problem in Africa [1]
The work we present here is an expansion of the study published by Badu et al [20], in which the antibody response to the 19kDa fragment of merozoite surface protein-1 (MSP-119) of P. falciparum was examined in populations from two endemic areas in the western Kenyan highlands
The 8 var gene products (PfEMP1) recognized by sera were present in the enriched categories for both Component (‘host cell-related’) and Process (‘antigenic variation’); merozoite surface protein 1 (MSP1), MSP7, duffy binding-like merozoite surface protein (DBLMSP), MTRAP, DBLlike protein Pf332 and the conserved P. falciparum (Pf) protein PF3D7_1136200 were represented in the enriched categories for both Cellular Component and Biological Process
Summary
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], where there is a marked gradient of parasite prevalence along the altitude transect [5,6,7]. Malaria transmission monitoring in the East African highlands is an important public health problem. The repertoire of targets of the antibody response expands after multiple infections, with the number of recognized antigens being correlated to parasite prevalence, the host’s age and immunity to clinical malaria [14,15,16]. The vast majority of serological surveys for malaria infection have been, hereto, limited to a small number of the parasite’s antigens
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