Assuntos
Política de Saúde , United States Dept. of Health and Human Services , Saúde da Mulher/tendências , Feminino , História do Século XX , História do Século XXI , Humanos , Estados Unidos , United States Dept. of Health and Human Services/história , Saúde da Mulher/história , Saúde da Mulher/legislação & jurisprudênciaRESUMO
Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Æ4, Æ3 and Æ2 with APOE Æ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Æ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Æ4 children for Plasmodium spp. densities compared to non-APOE Æ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Æ4 allele compared to those without an APOE Æ4 allele. When considering non-APOE Æ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Æ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Æ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Æ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.
Assuntos
Apolipoproteínas E/genética , Epistasia Genética , Hemoglobina Falciforme/genética , Malária/genética , Parasitemia/genética , Polimorfismo Genético , Alelos , Criança , Pré-Escolar , Feminino , Gabão , Genótipo , Hemoglobina A/genética , Interações Hospedeiro-Parasita , Humanos , Lactente , Malária/sangue , Malária/parasitologia , Masculino , Parasitemia/sangue , Parasitemia/parasitologia , Plasmodium falciparum/fisiologia , Plasmodium malariae/fisiologia , Isoformas de Proteínas/genética , Especificidade da EspécieAssuntos
Acessibilidade aos Serviços de Saúde , Cobertura do Seguro/legislação & jurisprudência , Patient Protection and Affordable Care Act , Saúde Reprodutiva/legislação & jurisprudência , Saúde da Mulher , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Cobertura do Seguro/economia , Saúde Reprodutiva/economia , Estados UnidosRESUMO
BACKGROUND: The protection afforded by human erythrocyte polymorphisms against the malaria parasite, Plasmodium falciparum, has been proposed to be due to reduced ability of the parasite to invade or develop in erythrocytes. If this were the case, variable levels of parasitaemia and rates of seroconversion to infected-erythrocyte variant surface antigens (VSA) should be seen in different host genotypes. METHODS: To test this hypothesis, P. falciparum parasitaemia and anti-VSA antibody levels were measured in a cohort of 555 asymptomatic children from an area of intense malaria transmission in Papua New Guinea. Linear mixed models were used to investigate the effect of alpha+-thalassaemia, complement receptor-1 and south-east Asian ovalocytosis, as well as glucose-6-phosphate dehydrogenase deficiency and ABO blood group on parasitaemia and age-specific seroconversion to VSA. RESULTS: No host polymorphism showed a significant association with both parasite prevalence/density and age-specific seroconversion to VSA. CONCLUSION: Host erythrocyte polymorphisms commonly found in Papua New Guinea do not effect exposure to blood stage P. falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms.