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1.  Endothelial Protein C Receptor Gene Variants Not Associated with Severe Malaria in Ghanaian Children 
PLoS ONE  2014;9(12):e115770.
Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of Plasmodium falciparum-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering PROCR, the gene encoding EPCR, a promising candidate for an association study.
Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the PROCR gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1–156 months and 1,866 apparently healthy children aged 2–161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses.
A total of 41 genetic variants were detected in regulatory and coding regions of PROCR, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia.
Here we present the first analysis of genetic variation in the PROCR gene in the context of severe malaria in African subjects and show that genetic variation in the PROCR gene in our study population does not influence susceptibility to major severe malaria phenotypes.
PMCID: PMC4277309  PMID: 25541704
2.  Mapping Urban Malaria and Diarrhea Mortality in Accra, Ghana: Evidence of Vulnerabilities and Implications for Urban Health Policy 
Historic increase in urban population numbers in the face of shrinking urban economies and declining social services has meant that a large proportion of the urban population lives in precarious urban conditions, which provide the grounds for high urban health risks in low income countries. This study aims to identify, investigate, and contrast the spatial patterns of vulnerability and risk of two major causes of mortality, viz malaria and diarrhea mortalities, in order to optimize resource allocation for effective urban environmental management and improvement in urban health. A spatial cluster analysis of the observed urban malaria and diarrhea mortalities for the whole city of Accra was conducted. We obtained routinely reported mortality data for the period 1998–2002 from the Ghana Vital Registration System (VRS), computed the fraction of deaths due to malaria and diarrhea at the census cluster level, and analyzed and visualized the data with Geographic Information System (GIS, ArcMap 9.3.1). Regions of identified hotspots, cold spots, and excess mortalities were observed to be associated with some socioeconomic and neighborhood urban environmental conditions, suggesting uneven distribution of risk factors for both urban malaria and diarrhea in areas of rapid urban transformation. Case–control and/or longitudinal studies seeking to understand the individual level factors which mediate socioenvironmental conditions in explaining the observed excess urban mortalities and to establish the full range of risk factors might benefit from initial vulnerability mapping and excess risk analysis using geostatistical approaches. This is key to evidence-based urban health policy reforms in rapidly urbanizing areas in low income economies.
PMCID: PMC3531344  PMID: 22684425
Malaria; Diarrhea; Hotspots; Urban vulnerabilities; Health risk; Spatial autocorrelation; Cluster-level mortality
3.  Neighborhood Urban Environmental Quality Conditions Are Likely to Drive Malaria and Diarrhea Mortality in Accra, Ghana 
Background. Urbanization is a process which alters the structure and function of urban environments. The alteration in the quality of urban environmental conditions has significant implications for health. This applies both to the ecology of insect vectors that may transmit diseases and the burden of disease. Study Objectives. To investigate the relationship between malaria and infectious diarrhea mortality and spatially varied neighborhood environmental quality conditions in a low-income economy. Design. A one time point spatial analysis of cluster-level environmental conditions and mortality data using principal component analysis (PCA), one-way analysis of variance (ANOVA) and generalized linear models (GLMs). Methods. Environmental variables were extracted from the Ghana Census 2000 database while mortality data were obtained from the Ghana Births and Deaths Registry in Accra over the period 1998–2002. Results. Whereas there was a strong evidence of a difference in relative mortality of malaria across urban environmental zones of differing neighborhood environmental conditions, no such evidence of mortality differentials was observed for diarrhea. In addition, whereas bivariate analyses showed a weak to strong evidence of association between the environmental variables and malaria mortality, no evidence of association was found between diarrhea mortality and environmental variables. Conclusion. We conclude that environmental management initiatives intended for infectious disease control might substantially reduce the risk of urban malaria mortality and to a less extent that for urban diarrhea mortality in rapidly urbanizing areas in a low-income setting.
PMCID: PMC3136154  PMID: 21776438
4.  Comparative evaluation of two rapid field tests for malaria diagnosis: Partec Rapid Malaria Test® and Binax Now® Malaria Rapid Diagnostic Test 
BMC Infectious Diseases  2011;11:143.
About 90% of all malaria deaths in sub-Saharan Africa occur in children under five years. Fast and reliable diagnosis of malaria requires confirmation of the presence of malaria parasites in the blood of patients with fever or history suggestive of malaria; hence a prompt and accurate diagnosis of malaria is the key to effective disease management. Confirmation of malaria infection requires the availability of a rapid, sensitive, and specific testing at an affordable cost. We compared two recent methods (the novel Partec Rapid Malaria Test® (PT) and the Binax Now® Malaria Rapid Diagnostic Test (BN RDT) with the conventional Giemsa stain microscopy (GM) for the diagnosis of malaria among children in a clinical laboratory of a hospital in a rural endemic area of Ghana.
Blood samples were collected from 263 children admitted with fever or a history of fever to the pediatric clinic of the Agogo Presbyterian Hospital. The three different test methods PT, BN RDT and GM were performed independently by well trained and competent laboratory staff to assess the presence of malaria parasites. Results were analyzed and compared using GM as the reference standard.
In 107 (40.7%) of 263 study participants, Plasmodium sp. was detected by GM. PT and BN RDT showed positive results in 111 (42.2%) and 114 (43.4%), respectively. Compared to GM reference standard, the sensitivities of the PT and BN RDT were 100% (95% CI: 96.6-100) and 97.2% (95% CI: 92.0-99.4), respectively, specificities were 97.4% (95% CI: 93.6-99.3) and 93.6% (95% CI: 88.5-96.9), respectively. There was a strong agreement (kappa) between the applied test methods (GM vs PT: 0.97; p < 0.001 and GM vs BN RDT: 0.90; p < 0.001). The average turnaround time per tests was 17 minutes.
In this study two rapid malaria tests, PT and BN RDT, demonstrated a good quality of their performance compared to conventional GM. Both methods require little training, have short turnaround times, are applicable as well as affordable and can therefore be considered as alternative diagnostic tools in malaria endemic areas. The species of Plasmodium cannot be identified.
PMCID: PMC3118144  PMID: 21605401
5.  Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting 
In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities.
EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin.
Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no significant difference in the hemoglobin determined by the HemoCue compared to Cyanmethemoglobin (coef = -0.127, 95% CI: -0.379 - 0.634).
Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.
PMCID: PMC3095531  PMID: 21510885
6.  Assessing the Relationship between Socioeconomic Conditions and Urban Environmental Quality in Accra, Ghana 
The influence of socioeconomic status (SES) on health inequalities is widely known, but there is still poor understanding of the precise relationship between area-based socioeconomic conditions and neighborhood environmental quality. This study aimed to investigate the socioeconomic conditions which predict urban neighbourhood environmental quality. The results showed wide variation in levels of association between the socioeconomic variables and environmental conditions, with strong evidence of a real difference in environmental quality across the five socioeconomic classes with respect to total waste generation (p < 0.001), waste collection rate (p < 0.001), sewer disposal rate (p < 0.001), non-sewer disposal (p < 0.003), the proportion of households using public toilets (p = 0.005). Socioeconomic conditions are therefore important drivers of change in environmental quality and urban environmental interventions aimed at infectious disease prevention and control if they should be effective could benefit from simultaneous implementation with other social interventions.
PMCID: PMC2819780  PMID: 20195437
Ghana census data; area-based SES; Accra; socioeconomic inequalities
7.  Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi) 
Malaria Journal  2007;6:163.
Intermittent preventive antimalarial treatment in infants (IPTi) is currently evaluated as a malaria control strategy. Among the factors influencing the extent of protection that is provided by IPTi are the transmission intensity, seasonality, drug resistance patterns, and the schedule of IPTi administrations. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria.
One thousand seventy infants were enrolled in a registered controlled trial on the efficacy of IPTi with sulphadoxine-pyrimethamine (SP) in the Ashanti Region, Ghana, West Africa ( NCT00206739). Stratification for the village of residence and the month of birth of study participants demonstrated that the malaria incidence was dependent on spatial (range of incidence rates in different villages 0.6–2.0 episodes/year) and temporal (range of incidence rates in children of different birth months 0.8–1.2 episodes/year) factors. The range of spatio-temporal variation allowed ecological analyses of the correlation between malaria incidence rates, anti-Plasmodium falciparum lysate IgG antibody levels and protective efficacies provided by IPTi.
Protective efficacy of the first SP administration was positively correlated with malaria incidences in children living in a distinct village or born in a distinct month (R2 0.48, p < 0.04 and R2 0.63, p < 0.003, respectively). Corresponding trends were seen after the second and third study drug administration. Accordingly, IgG levels against parasite lysate increased with malaria incidence. This correlation was stronger in children who received IPTi, indicating an effect modification of the intervention.
The spatial and temporal variations of malaria incidences in a geographically and meteorologically homogeneous study area exemplify the need for close monitoring of local incidence rates in all types of intervention studies. The increase of the protective efficacy of IPTi with malaria incidences may be relevant for IPTi implementation strategies and, possibly, for other malaria control measures.
PMCID: PMC2234423  PMID: 18067679

Results 1-7 (7)