2 research outputs found
Socio-demographic determinants of dengue infection during an outbreak in Dar es Salaam City, Tanzania
AbstractBackground: In recent years, the eastern coast of Africa has witnessed a number of dengue outbreaks. This study was carried out to determine socio-demographic determinants of dengue infection during the 2014 outbreak in Dar es Salaam, Tanzania. Methods: Unmatched case-control analysis of secondary data from a cross-sectional dengue investigation in three districts of Dar es Salaam in June 2014 was conducted. Febrile patients seeking care at health facilities were recruited. Cases were serologically-confirmed dengue-positive while controls were serologically-confirmed dengue-negative patients. A questionnaire was used to collect sociodemographic information. The association between sociodemographic variables and dengue infection was examined using univariate analysis and multivariate logistic regression analysis. Results: A total of 81 cases and 281 controls were included in the analysis. Majority of the cases and controls were males (64.2% versus 54.1%; P=0.137) and were >15 years of age (88.9% versus 72.9%; P =0.003). Living in Kinondoni (aOR = 4.28; 95% CI: 1.74 - 10.53); being employed (aOR = 2.06; 95% CI: 1.06-4.04); having piped water at home (aOR = 2.63; 95% CI: 1.40 - 4.95) and a recent visit of health facility (aOR = 1.94; 95% CI: 1.11 - 3.38) were significantly associated with dengue infection.Conclusions: Dengue infection in Dar es Salaam varied between the three districts and was associated with being employed, having piped water at home and a recent visit to the health facility. These findings provide primary understanding of the influence of socio-demographic factors on dengue and may be used to develop appropriate preventive interventions
Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study
Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative