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Heritability of Plasmodium parasite density in a rural Ugandan community.

ABSTRACT: Many factors influence variation in Plasmodium infection levels, including parasite/host genetics, immunity, and exposure. Here, we examine the roles of host genetics and exposure in determining parasite density, and test whether effects differ with age. Data for 1,711 residents of an eastern Ugandan community were used in pedigree-based variance component analysis. Heritability of parasite density was 13% (P < 0.001) but was not significant after controlling for shared household. Allowing variance components to vary between children (< 16 years) and adults (≥ 16 years) revealed striking age differences; 26% of variation could be explained by additively acting genes in children (P < 0.001), but there was no genetic involvement in adults. Domestic environment did not explain variation in children and explained 5% in adults (P = 0.09). Genetic effects are an important determinant of parasite density in children in this population, consistent with previous quantitative genetic studies of Plasmodium parasitaemia, although differences in environmental exposure play a lesser role.

SUBMITTER: Pullan RL

PROVIDER: S-EPMC2963957 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Heritability of Plasmodium parasite density in a rural Ugandan community.

Pullan Rachel L RL Bukirwa Hasifa H Snow Robert W RW Brooker Simon S

The American journal of tropical medicine and hygiene 20101101 5

Many factors influence variation in Plasmodium infection levels, including parasite/host genetics, immunity, and exposure. Here, we examine the roles of host genetics and exposure in determining parasite density, and test whether effects differ with age. Data for 1,711 residents of an eastern Ugandan community were used in pedigree-based variance component analysis. Heritability of parasite density was 13% (P < 0.001) but was not significant after controlling for shared household. Allowing varia ...[more]

PMID: 21036825

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Project description:Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR?=?1.34, 95% CI 1.20-1.50, p?<?0.001), having a temperature ?38.0°C vs?<?37.0°C (RR?=?1.19, 95% CI 1.05-1.35, p?=?0.007) and having a parasite density >20,000/?L vs <4,000/?L (RR?=?3.37, 95% CI 2.44-4.49, p?<?0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.Current Controlled Trials Identifier NCT00527800.

Project description:Background: Market vendors occupy a strategic position in the fight against the spread of SARS CoV-2 in rural Uganda. To successfully contain the spread of the virus, special attention needs to be given to this set of people by assessing the type of information, source of information, and practices they inculcate as regards adherence to WHO guidelines in the fight against COVID-19 in Uganda. The study aimed to assess the role of information sources, education level, and phone internet connectivity in influencing COVID-19 knowledge among the rural market vendors; and the relationship existing between knowledge, attitude, and practices among them. Methods: The study was a descriptive cross-sectional study among rural market vendors (n = 248) in southwestern Uganda. Information was collected using a questionnaire and descriptively presented as frequency and percentages. Results: The study showed that the majority of the rural market vendors had sufficient information regarding COVID-19 with the majority being female individuals and have attained a secondary level of education, The general percentage score for knowledge, attitude, and practices were (75.57, 82.6, and 76.50% respectively). There was a positive correlation between attitude and practices (r = 0.17, p = 0.007), as well as their knowledge with practices (r = 0.29, p < 0.001). The majority of the people in the population did not have their phones connected to the internet (OR = 1.96, 95%CI: 1.16-3.31, P = 0.01). The majority of people received their information regarding COVID-19 from one source (radio) (OR = 1.55). Conclusion: Where and how the rural market vendors get their information and education level are vital in breaking COVID 19 infection circle in line with WHO guidelines. Therefore, sources of information and education level played a key role in molding their knowledge and practices. However, the level of knowledge on COVID 19 among our respondents was not linked with phone internet connectivity.

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Project description:Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant surface antigen family expressed on infected red blood cells that plays a role in immune evasion and mediates adhesion to vascular endothelium. PfEMP1s are potential targets of protective antibodies as suggested by previous seroepidemiology studies. Here, we used previously reported proteomic analyses of PfEMP1s of clinical parasite isolates collected from Malian children to identify targets of immunity. We designed a peptide library representing 11 PfEMP1 domains commonly identified on clinical isolates by membrane proteomics and then examined peptide-specific antibody responses in Malian children. The number of previous malaria infections was associated with development of PfEMP1 antibodies to peptides from domains CIDRα1.4, DBLγ11, DBLβ3, and DBLδ1. A zero-inflated negative binomial model with random effects (ZINBRE) was used to identify peptide reactivities that were associated with malaria risk. This peptide selection and serosurvey strategy revealed that high antibody levels to peptides from DBLγ11 and DBLδ1 domains correlated with decreased parasite burden in future infections, supporting the notion that specific PfEMP1 domains play a role in protective immunity. IMPORTANCE Plasmodium infection causes devastating disease and high mortality in young children. Immunity develops progressively as children acquire protection against severe disease, although reinfections and recrudescences still occur throughout life in areas of endemicity, partly due to parasite immunoevasion via switching of variant proteins such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the infected erythrocyte surface. Understanding the mechanisms behind antibody protection can advance development of new therapeutic interventions that address this challenge. PfEMP1 domain-specific antibodies have been linked to reduction in severe malaria; however, the large diversity of PfEMP1 domains in circulating parasites has not been fully investigated. We designed representative peptides based on B cell epitopes of PfEMP1 domains identified in membranes of clinical parasite isolates and surveyed peptide-specific antibody responses among young Malian children in a longitudinal birth cohort. We examined previous infections and age as factors contributing to antibody acquisition and identified antibody specificities that predict malaria risk.

Dataset Information

Heritability of Plasmodium parasite density in a rural Ugandan community.

Publications

Heritability of Plasmodium parasite density in a rural Ugandan community.

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