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Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso.

ABSTRACT: BACKGROUND: There is accumulating evidence that host heparan sulphate proteoglycans play an important role in the life cycle of Plasmodium through their heparan sulphate chains, suggesting that genetic variations in genes involved in heparan sulphate biosynthesis may influence parasitaemia. Interestingly, Hs3st3a1 and Hs3st3b1 encoding enzymes involved in the biosynthesis of heparan sulphate are located within a chromosomal region linked to Plasmodium chabaudi parasitaemia in mice. This suggests that HS3ST3A1 and HS3ST3B1 may influence P. falciparum parasitaemia in humans. METHODS: Polymorphisms within HS3ST3A1 and HS3ST3B1 were identified in 270 individuals belonging to 44 pedigrees and living in Burkina Faso. Linkage and association between parasitaemia and the polymorphisms were assessed with MERLIN and FBAT. A genetic interaction analysis was also conducted based on the PGMDR approach. RESULTS: Linkage between P. falciparum parasitaemia and the chromosomal region containing HS3ST3A1 and HS3ST3B1 was detected on the basis of the 20 SNPs identified. In addition, rs28470223 located within the promoter of HS3ST3A1 was associated with P. falciparum parasitaemia, whereas the PGMDR analysis revealed a genetic interaction between HS3ST3A1 and HS3ST3B1. Seventy-three significant multi-locus models were identified after correcting for multiple tests; 37 significant multi-locus models included rs28470223, whereas 38 multi-locus models contained at least one mis-sense mutation within HS3ST3B1. CONCLUSION: Genetic variants of HS3ST3A1 and HS3ST3B1 are associated with P. falciparum parasitaemia. This suggests that those variants alter both the function of heparan sulphate proteoglycans and P. falciparum parasitaemia.

SUBMITTER: Atkinson A

PROVIDER: S-EPMC3364897 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso.

Atkinson Alexandre A Garnier Séverine S Afridi Sarwat S Fumoux Francis F Rihet Pascal P

Malaria journal 20120404

<h4>Background</h4>There is accumulating evidence that host heparan sulphate proteoglycans play an important role in the life cycle of Plasmodium through their heparan sulphate chains, suggesting that genetic variations in genes involved in heparan sulphate biosynthesis may influence parasitaemia. Interestingly, Hs3st3a1 and Hs3st3b1 encoding enzymes involved in the biosynthesis of heparan sulphate are located within a chromosomal region linked to Plasmodium chabaudi parasitaemia in mice. This s ...[more]

PMID: 22475533

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Project description:BackgroundInvestigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso.MethodsBlood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction.ResultsIn the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation.ConclusionsIn high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.

Project description:BackgroundAsymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season.MethodsA sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21 HBA and 22 HBB mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression.ResultsMalaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI95: 2.45-19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed.ConclusionsAccording to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions.

Project description:BackgroundMalaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region.MethodsTwo cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis.ResultsA total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine-pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14-0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39-0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31-4.91, p = 0.006).ConclusionsThe prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.

Project description:BACKGROUND: Malaria during pregnancy remains a serious public health problem. The aim of this study was to determine the prevalence and possible risk factors for malaria in pregnant women attending antenatal clinic at two primary health facilities in Bobo-Dioulasso. METHODS: We conducted a cross sectional study from September to December 2010 in two primary health facilities located in the periurban area of Bobo-Dioulasso. Pregnant women attending antenatal clinic (ANC) were included in the study after signing informed consent. For each participant, the social-demographic profile, malaria and obstetric histories were investigated through a questionnaire. Peripheral blood was collected and thick and thin blood smears were prepared to check Plasmodium falciparum parasitaemia. Hemoglobin concentration was measured. The associations between age, parity, gestational age, schooling, number of ANC visits, use of IPTp-SP, use of insecticide-treated nets (ITN) and anemia with the occurrence of P. falciparum malaria infection during pregnancy were analyzed through logistic regression. RESULTS: During the period of study, 105 (18.1%) out of 579 pregnant women were infected by P. falciparum. The hemoglobin concentration mean was 10.5?±?1.7/dL and was significantly lower in pregnant women with malaria infection (9.8 g/dL ±1.6) than in those who had no malaria infection (10.6 g/dL ±1.7) (P?<?0.001). Multivariate analysis indicated that, education (AOR 1.9, 95% CI?=?[1.2-3.2]), parity [primigravidae (AOR 5.0, 95% CI?=?[2.5-9.8]) and secundigravidae (AOR 2.1, 95% CI?=?[1.2-3.8])], and anaemia (AOR 2.1, 95% CI?=?[1.3-3.5]) were significantly associated with P. falciparum malaria infection. The use of IPTp-SP was not associated with P. falciparum malaria infection. CONCLUSIONS: P. falciparum malaria infection is common in pregnant women attending antenatal clinic and anaemia is an important complication. The results show that the use of IPTp-SP does not reduce the risk of malaria incidence during pregnancy.

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Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso.

Publications

Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso.

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