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Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.

ABSTRACT: Long-term planning to prevent malaria epidemics requires in-depth understanding of immunity to Plasmodium falciparum in areas of unstable transmission. Cytokine responses to immunodominant epitope peptides from liver stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) were evaluated over a nine-month interval in adults and children in Kenya from a malaria epidemic-prone highland area after several years of low transmission. The proportion and magnitude of interferon-gamma ELISPOT responses and the proportion of interleukin-10 responders to LSA-1 and TRAP peptides tended to be higher in adults than children. Frequencies of interferon-gamma responders to these peptides were similar at the two time points, but responses were not consistently generated by the same persons. These results suggest that T cell memory to pre-erythrocytic stage malaria antigens is maintained but may be unavailable for consistent detection in peripheral blood, and that these antigens induce both pro-inflammatory and anti-inflammatory cytokine responses in this population.

SUBMITTER: Moormann AM

PROVIDER: S-EPMC3634720 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.

Moormann Ann M AM Sumba Peter Odada PO Tisch Daniel J DJ Embury Paula P King Charles H CH Kazura James W JW John Chandy C CC

The American journal of tropical medicine and hygiene 20090901 3

Long-term planning to prevent malaria epidemics requires in-depth understanding of immunity to Plasmodium falciparum in areas of unstable transmission. Cytokine responses to immunodominant epitope peptides from liver stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) were evaluated over a nine-month interval in adults and children in Kenya from a malaria epidemic-prone highland area after several years of low transmission. The proportion and magnitude of interferon-gamma ...[more]

PMID: 19706920

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Project description:BackgroundAn. funestus is a major Afrotropical vector of human malaria. This study sought to investigate the larval ecology, sporozoite infection rates and blood meal sources of An. funestus in western Kenya.MethodsLarval surveys were carried out in Bungoma (Highland) and Kombewa (lowland) of western Kenya. Aquatic habitats were identified, characterized, georeferenced and carefully examined for mosquito larvae and predators. Indoor resting mosquitoes were sampled using pyrethrum spray catches. Adults and larvae were morphologically and molecularly identified to species. Sporozoite infections and blood meal sources were detected using real-time PCR and ELISA respectively.ResultsOf the 151 aquatic habitats assessed, 62/80 (78%) in Bungoma and 58/71(82%) in Kombewa were positive for mosquito larvae. Of the 3,193 larvae sampled, An. funestus larvae constitute 38% (1224/3193). Bungoma recorded a higher number of An. funestus larvae (85%, 95%, CI, 8.722-17.15) than Kombewa (15%, 95%, CI, 1.33-3.91). Molecular identification of larvae showed that 89% (n = 80) were An. funestus. Approximately 59%, 35% and 5% of An. funestus larvae co-existed with An. gambiae s.l, Culex spp and An. coustani in the same habitats respectively. Of 1,221 An. funestus s.l adults sampled, molecular identifications revealed that An. funestus constituted 87% (n = 201) and 88% (n = 179) in Bungoma and Kombewa, respectively. The Plasmodium falciparum sporozoite rate of An. funestus in Bungoma and Kombewa was 2% (3/174) and 1% (2/157), respectively, and the human blood index of An. funestus was 84% (48/57) and 89% (39/44) and for Bungoma and Kombewa, respectively.ConclusionMan-made ponds had the highest abundance of An. funestus larvae. Multiple regression and principal component analyses identified the distance to the nearest house as the key environmental factor associated with the abundance of An. funestus larvae in aquatic habitats. This study serves as a guide for the control of An. funestus and other mosquito species to complement existing vector control strategies.

Project description:BackgroundPersons with submicroscopic malaria infection are a major reservoir of gametocytes that sustain malaria transmission in sub-Saharan Africa. Despite recent decreases in the national malaria burden in Kenya due to vector control interventions, malaria transmission continues to be high in western regions of the country bordering Lake Victoria. The objective of this study was to advance knowledge of the topographical, demographic and behavioral risk factors associated with submicroscopic malaria infection in the Lake Victoria basin in Kisumu County.MethodsCross-sectional community surveys for malaria infection were undertaken in three eco-epidemiologically distinct zones in Nyakach sub-County, Kisumu. Adjacent regions were topologically characterized as lakeshore, hillside and highland plateau. Surveys were conducted during the 2019 and 2020 wet and dry seasons. Finger prick blood smears and dry blood spots (DBS) on filter paper were collected from 1,777 healthy volunteers for microscopic inspection and real time-PCR (RT-PCR) diagnosis of Plasmodium infection. Persons who were PCR positive but blood smear negative were considered to harbor submicroscopic infections. Topographical, demographic and behavioral risk factors were correlated with community prevalence of submicroscopic infections.ResultsOut of a total of 1,777 blood samples collected, 14.2% (253/1,777) were diagnosed as submicroscopic infections. Blood smear microscopy and RT-PCR, respectively, detected 3.7% (66/1,777) and 18% (319/1,777) infections. Blood smears results were exclusively positive for P. falciparum, whereas RT-PCR also detected P. malariae and P. ovale mono- and co-infections. Submicroscopic infection prevalence was associated with topographical variation (χ2 = 39.344, df = 2, p<0.0001). The highest prevalence was observed in the lakeshore zone (20.6%, n = 622) followed by the hillside (13.6%, n = 595) and highland plateau zones (7.9%, n = 560). Infection prevalence varied significantly according to season (χ2 = 17.374, df = 3, p<0.0001). The highest prevalence was observed in residents of the lakeshore zone in the 2019 dry season (29.9%, n = 167) and 2020 and 2019 rainy seasons (21.5%, n = 144 and 18.1%, n = 155, respectively). In both the rainy and dry seasons the likelihood of submicroscopic infection was higher in the lakeshore (AOR: 2.71, 95% CI = 1.85-3.95; p<0.0001) and hillside (AOR: 1.74, 95% CI = 1.17-2.61, p = 0.007) than in the highland plateau zones. Residence in the lakeshore zone (p<0.0001), male sex (p = 0.025), school age (p = 0.002), and living in mud houses (p = 0.044) increased the risk of submicroscopic malaria infection. Bed net use (p = 0.112) and occupation (p = 0.116) were not associated with submicroscopic infection prevalence.ConclusionTopographic features of the local landscape and seasonality are major correlates of submicroscopic malaria infection in the Lake Victoria area of western Kenya. Diagnostic tests more sensitive than blood smear microscopy will allow for monitoring and targeting geographic sites where additional vector interventions are needed to reduce malaria transmission.

Project description: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.

Dataset Information

Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.

Publications

Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.

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