High seroprevalence of SARS-CoV-2 in Burkina-Faso, Ghana and Madagascar in 2021: a population-based study.

BACKGROUND: The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. METHODS: A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. RESULTS: Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. CONCLUSIONS: High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk.

Limited Reliability of the Molecular Detection of Plasmodium spp. from Incubated Blood Culture Samples for Forensic Purposes.

The suitability of incubated blood culture material for forensic molecular malaria diagnosis was assessed for non-endemic settings for cases in which the differential diagnosis malaria was initially overlooked. For the proof-of-principle assessment, residual blood culture materials from febrile patients from tropical Ghana were investigated by real-time PCR and compared with available historic microscopic results. In 2114 samples, for which microscopical results and real-time PCR results were available, microscopical results comprised 711 P. falciparum detections, 7 P. malariae detections, 1 microscopically not-further-discriminable Plasmodium spp. detection as well as 13 detections of mixed infections comprising 12 cases of P. falciparum/P. malariae co-infections and 1 case of a P. falciparum/P. ovale complex co-infection, while real-PCR indicated 558 P. falciparum detections, 95 P. malariae detections, 10 P. ovale complex detections, 1 P. vivax detection and 4 detected P. falciparum/P. malariae co-infections. Concordance of routine microscopy and real-time PCR was imperfect. Using routine microscopy as reference was associated with a seemingly low agreement of positive real-time PCR results of 90.9%. However, if positive samples, either by routine microscopy or real-time PCR or both, were applied as a combined reference, the agreement of positive results obtained with real-time PCR was increased from 74.0% to 77.9%, while the agreement of positive results obtained with routine microscopy was decreased from 100% to 85.3%. The predictive value of routine microscopy for negative results in the reference was slightly better with 90.9% compared to real-time PCR with 86.9%; the concordance between routine microscopy and real-time PCR was imperfect. In conclusion, even suboptimal sample materials such as incubated blood culture materials can be applied for forensic malaria diagnosis, if more suitable sample materials are not available, but the molecular detection rate of positive results in routine microscopy is much lower than previously reported for non-incubated blood.

Human genetic variant E756del in the ion channel PIEZO1 not associated with protection from severe malaria in a large Ghanaian study.

Recently, a common genetic variant E756del in the human gene PIEZO1 was associated with protection from severe malaria. Here, we performed a genetic association study of this gain-of-function variant in a large case-control study including 4149 children from the Ashanti Region in Ghana, West Africa. The statistical analysis did not indicate an association with protection from severe malaria and, thus, providing evidence against a strong protective effect of the PIEZO1 E756del variant on severe malaria susceptibility.

Seroprevalence of SARS-CoV-2 in urban settings in three sub-Saharan African countries (SeroCoV): a study protocol for a household-based cross-sectional prevalence study using two-stage cluster sampling.

INTRODUCTION: The current COVID-19 pandemic has impacted the entire world with increasing morbidity and mortality and has resulted in serious economic and social consequences. Assessing the burden of COVID-19 is essential for developing efficient pandemic preparedness and response strategies and for determining the impact of implemented control measures. Population-based seroprevalence surveys are critical to estimate infection rates, monitor the progression of the epidemic and to allow for the identification of persons exposed to the infection who may either have been asymptomatic or were never tested. This is especially important for countries where effective testing and tracking systems could not be established and where non-severe cases or under-reported deaths might have blurred the true burden of COVID-19. Most seroprevalence surveys performed in sub-Saharan Africa have targeted specific high risk or more easily accessible populations such as healthcare workers or blood donors, and household-based estimates are rarely available. Here, we present the study protocol for a SARS-CoV-2 seroprevalence estimation in the general population of Burkina Faso, Ghana and Madagascar in 2021. METHODS AND ANALYSIS: The SeroCoV study is a household-based cross-sectional prevalence investigation in persons aged 10 years and older living in urban areas in six cities using a two-stage geographical cluster sampling method stratified by age and sex. The presence of anti-SARS-CoV-2 IgG antibodies will be determined using a sensitive and specific SARS-CoV-2 IgG ELISA. In addition, questionnaires will cover sociodemographic information, episodes of diseases and history of testing and treatment for COVID-like symptoms, travel history and safety measures. We will estimate the seroprevalence of SARS-CoV-2, taking into account test performance and adjusting for the age and sex of the respective populations. ETHICS AND DISSEMINATION: Ethical approval was received for all participating countries. Results will be disseminated through reports and presentations at the country level as well as peer-reviewed publications and international scientific conferences presentations.

The East African Community (EAC) mobile laboratory networks in Kenya, Burundi, Tanzania, Rwanda, Uganda, and South Sudan-from project implementation to outbreak response against Dengue, Ebola, COVID-19, and epidemic-prone diseases.

BACKGROUND: East Africa is home to 170 million people and prone to frequent outbreaks of viral haemorrhagic fevers and various bacterial diseases. A major challenge is that epidemics mostly happen in remote areas, where infrastructure for Biosecurity Level (BSL) 3/4 laboratory capacity is not available. As samples have to be transported from the outbreak area to the National Public Health Laboratories (NPHL) in the capitals or even flown to international reference centres, diagnosis is significantly delayed and epidemics emerge. MAIN TEXT: The East African Community (EAC), an intergovernmental body of Burundi, Rwanda, Tanzania, Kenya, Uganda, and South Sudan, received 10 million € funding from the German Development Bank (KfW) to establish BSL3/4 capacity in the region. Between 2017 and 2020, the EAC in collaboration with the Bernhard-Nocht-Institute for Tropical Medicine (Germany) and the Partner Countries' Ministries of Health and their respective NPHLs, established a regional network of nine mobile BSL3/4 laboratories. These rapidly deployable laboratories allowed the region to reduce sample turn-around-time (from days to an average of 8h) at the centre of the outbreak and rapidly respond to epidemics. In the present article, the approach for implementing such a regional project is outlined and five major aspects (including recommendations) are described: (i) the overall project coordination activities through the EAC Secretariat and the Partner States, (ii) procurement of equipment, (iii) the established laboratory setup and diagnostic panels, (iv) regional training activities and capacity building of various stakeholders and (v) completed and ongoing field missions. The latter includes an EAC/WHO field simulation exercise that was conducted on the border between Tanzania and Kenya in June 2019, the support in molecular diagnosis during the Tanzanian Dengue outbreak in 2019, the participation in the Ugandan National Ebola response activities in Kisoro district along the Uganda/DRC border in Oct/Nov 2019 and the deployments of the laboratories to assist in SARS-CoV-2 diagnostics throughout the region since early 2020. CONCLUSIONS: The established EAC mobile laboratory network allows accurate and timely diagnosis of BSL3/4 pathogens in all East African countries, important for individual patient management and to effectively contain the spread of epidemic-prone diseases.

Needs for an Integration of Specific Data Sources and Items - First Insights of a National Survey Within the German Center for Infection Research.

State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an online survey to determine prioritization of requests for data integration and exchange in ID research. The survey was designed with three sub-surveys, including a ranking of 15 data categories and 184 specific data items and a query of available 51 data collecting systems. A total of 84 researchers from 17 fields of ID research participated in the survey (predominant research fields: gastrointestinal infections n=11, healthcare-associated and antibiotic-resistant infections n=10, hepatitis n=10). 48% (40/84) of participants had experience as medical doctor. The three top ranked data categories were microbiology and parasitology, experimental data, and medication (53%, 52%, and 47% of maximal points, respectively). The most relevant data items for these categories were bloodstream infections, availability of biomaterial, and medication (88%, 87%, and 94% of maximal points, respectively). The ranking of requests of data integration and exchange is diverse and depends on the chosen measure. However, there is need to promote discipline-related digitalization and data exchange.

A cross-sectional study on risk factors for infection with Parvovirus B19 and the association with anaemia in a febrile paediatric population in Ghana.

Parvovirus B19 (B19V) occurs globally and can cause severe anaemia. The role of co-infections with Plasmodium falciparum (P. falciparum) has been controversially discussed. The study aimed to determine prevalence and severity of B19V infection, and the effect of co-infections on the risk for anaemia. Between November 2013 and April 2015 a total of 1186 hospital visits of children with fever admitted to a hospital in Ghana were recorded. Malaria, B19V and additional diagnostics for fever causes were performed. Recent B19V infection was defined as PCR and/or IgM positivity. Risk factors for a B19V infection and for anaemia were analysed. The prevalence of anaemia was compared between children with/without B19V infection, stratified for the presence of malaria. B19V IgM/PCR was positive in 6.4% (n = 76; 40 IgM + , 30 PCR + , 6 IgM + and PCR +). Among the B19V cases 60.5% had a simultaneous P. falciparum infection. B19V IgM positivity but not PCR positivity was associated with moderate-severe anaemia (OR = 2.6; 95%-CI: 1.3-5.3; P < 0.01 vs. OR = 0.9; 95%-CI: 0.4-1.8; P = 0.70). P. falciparum and IgM positive B19V infection were independent risk factors for anaemia with no evidence of effect modification. Our data show a significant association between B19V infection, defined as IgM but not PCR positivity, and moderate-severe anaemia. A multiplicative effect of B19V and P. falciparum infection was not found.

Correction: Gastrointestinal infections and diarrheal disease in ghanaian infants and children: an outpatient case-control study.

[This corrects the article DOI: 10.1371/journal.pntd.0003568.].

Clinical indicators for bacterial co-infection in Ghanaian children with P. falciparum infection.

Differentiation of infectious causes in severely ill children is essential but challenging in sub- Saharan Africa. The aim of the study was to determine clinical indicators that are able to identify bacterial co-infections in P. falciparum infected children in rural Ghana. In total, 1,915 severely ill children below the age of 15 years were recruited at Agogo Presbyterian Hospital in Ghana between May 2007 and February 2011. In 771 (40%) of the children malaria parasites were detected. This group was analyzed for indicators of bacterial co-infections using bivariate and multivariate regression analyses with 24 socio-economic variables, 16 terms describing medical history and anthropometrical information and 68 variables describing clinical symptoms. The variables were tested for sensitivity, specificity, positive predictive value and negative predictive value. In 46 (6.0%) of the children with malaria infection, bacterial co-infection was detected. The most frequent pathogens were non-typhoid salmonellae (45.7%), followed by Streptococcus spp. (13.0%). Coughing, dehydration, splenomegaly, severe anemia and leukocytosis were positively associated with bacteremia. Domestic hygiene and exclusive breastfeeding is negatively associated with bacteremia. In cases of high parasitemia (>10,000/µl), a significant association with bacteremia was found for splenomegaly (OR 8.8; CI 1.6-48.9), dehydration (OR 18.2; CI 2.0-166.0) and coughing (OR 9.0; CI 0.7-118.6). In children with low parasitemia, associations with bacteremia were found for vomiting (OR 4.7; CI 1.4-15.8), severe anemia (OR 3.3; CI 1.0-11.1) and leukocytosis (OR 6.8 CI 1.9-24.2). Clinical signs of impaired microcirculation were negatively associated with bacteremia. Ceftriaxone achieved best coverage of isolated pathogens. The results demonstrate the limitation of clinical symptoms to determine bacterial co-infections in P. falciparum infected children. Best clinical indicators are dependent on the parasitemia level. Even with a moderate sensitivity of >60%, only low positive predictive values can be obtained due to low prevalence of bacteremia. Rapid testing for distinguishing parasitemia and bacteremia is essential.

Gastrointestinal infections and diarrheal disease in Ghanaian infants and children: an outpatient case-control study.

INTRODUCTION: Diarrheal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in resource-poor areas. This case-control study assessed the associations between gastrointestinal infections and diarrhea in children from rural Ghana. METHODS: Stool samples were collected from 548 children with diarrhea and from 686 without gastrointestinal symptoms visiting a hospital from 2007-2008. Samples were analyzed by microscopy and molecular methods. RESULTS: The organisms most frequently detected in symptomatic cases were Giardia lamblia, Shigella spp./ enteroinvasive Escherichia coli (EIEC), and Campylobacter jejuni. Infections with rotavirus (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI]: 4.3-16.6), C. parvum/hominis (aOR = 2.7; 95% CI: 1.4-5.2) and norovirus (aOR = 2.0; 95%CI: 1.3-3.0) showed the strongest association with diarrhea. The highest attributable fractions (AF) for diarrhea were estimated for rotavirus (AF = 14.3%; 95% CI: 10.9-17.5%), Shigella spp./EIEC (AF = 10.5%; 95% CI: 3.5-17.1%), and norovirus (AF = 8.2%; 95% CI 3.2-12.9%). Co-infections occurred frequently and most infections presented themselves independently of other infections. However, infections with E. dispar, C. jejuni, and norovirus were observed more often in the presence of G. lamblia. CONCLUSIONS: Diarrheal diseases in children from a rural area in sub-Saharan Africa are mainly due to infections with rotavirus, Shigella spp./EIEC, and norovirus. These associations are strongly age-dependent, which should be considered when diagnosing causes of diarrhea. The presented results are informative for both clinicians treating gastrointestinal infections as well as public health experts designing control programs against diarrheal diseases.

Geographically weighted regression of land cover determinants of Plasmodium falciparum transmission in the Ashanti Region of Ghana.

BACKGROUND: Malaria is a mosquito-borne parasitic disease that causes severe mortality and morbidity, particularly in Sub-Saharan Africa. As the vectors predominantly bite between dusk and dawn, risk of infection is determined by the abundance of P. falciparum infected mosquitoes in the surroundings of the households. Remote sensing is commonly employed to detect associations between land use/land cover (LULC) and mosquito-borne diseases. Due to challenges in LULC identification and the fact that LULC merely functions as a proxy for mosquito abundance, assuming spatially homogenous relationships may lead to overgeneralized conclusions. METHODS: Data on incidence of P. falciparum parasitaemia were recorded by active and passive follow-up over two years. Nine LULC types were identified through remote sensing and ground-truthing. Spatial associations of LULC and P. falciparum parasitaemia rate were described in a semi-parametric geographically weighted Poisson regression model. RESULTS: Complete data were available for 878 individuals, with an annual P. falciparum rate of 3.2 infections per person-year at risk. The influences of built-up areas (median incidence rate ratio (IRR): 0.94, IQR: 0.46), forest (median IRR: 0.9, IQR: 0.51), swampy areas (median IRR: 1.15, IQR: 0.88), as well as banana (median IRR: 1.02, IQR: 0.25), cacao (median IRR: 1.33, IQR: 0.97) and orange plantations (median IRR: 1.11, IQR: 0.68) on P. falciparum rate show strong spatial variations within the study area. Incorporating spatial variability of LULC variables increased model performance compared to the spatially homogenous model. CONCLUSIONS: The observed spatial variability of LULC influence in parasitaemia would have been masked by traditional Poisson regression analysis assuming a spatially constant influence of all variables. We conclude that the spatially varying effects of LULC on P. falciparum parasitaemia may in fact be associated with co-factors not captured by remote sensing, and suggest that future studies assess small-scale spatial variation of vegetation to circumvent generalised assumptions on ecological associations that may in fact be artificial.

Mental health related determinants of parenting stress among urban mothers of young children--results from a birth-cohort study in Ghana and Côte d'Ivoire.

BACKGROUND: There are limited data on the parenting stress (PS) levels in sub-Saharan African mothers and on the association between ante- and postnatal depression and anxiety on PS. METHODS: A longitudinal birth cohort of 577 women from Ghana and Côte d'Ivoire was followed from the 3rd trimester in pregnancy to 2 years postpartum between 2010 and 2013. Depression and anxiety were assessed by the Patient Health Questionnaire depression module (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) at baseline, 3 month, 12 month and 24 month postpartum. PS was measured using the Parenting Stress Index-Short Form (PSI-SF) at 3, 12 and 24 month. The mean total PS score and the subscale scores were compared among depressed vs. non-depressed and among anxious vs. non-anxious mothers at 3, 12 and 24 month postpartum. The proportions of clinical PS (PSI-SF raw score > 90) in depressed vs. non-depressed and anxious vs. non-anxious mothers were also compared. A generalized estimating equation (GEE) approach was used to estimate population-averaged associations between women's depression/anxiety and PS adjusting for age, child sex, women's anemia, education, occupation, spouse's education, and number of sick child visits. RESULTS: A total of 577, 531 and 264 women completed the PS assessment at 3 month, 12 month and 24 month postpartum across the two sites and the prevalences of clinical PS at each time point was 33.1%, 24.4% and 14.9% in Ghana and 30.2%, 33.5% and 22.6% in Côte d'Ivoire, respectively. At all three time points, the PS scores were significantly higher among depressed mothers vs. non-depressed mothers. In the multivariate regression analyses, antepartum and postpartum depression were consistently associated with PS after adjusting for other variables. CONCLUSIONS: Parenting stress is frequent and levels are high compared with previous studies from high-income countries. Antepartum and postpartum depression were both associated with PS, while antepartum and postpartum anxiety were not after adjusting for confounders. More quantitative and qualitative data are needed in sub-Saharan African populations to assess the burden of PS and understand associated mechanisms. Should our findings be replicated, it appears prudent to design and subsequently evaluate intervention strategies.

No association between antenatal common mental disorders in low-obstetric risk women and adverse birth outcomes in their offspring: results from the CDS study in Ghana and Côte D'Ivoire.

BACKGROUND: Evidence linking common mental disorders (CMD) in pregnant women to adverse birth outcomes is inconsistent, and studies often failed to control for pregnancy complications. This study aimed to explore the association between antenatal depression and anxiety symptoms and birth outcomes in a low-obstetric risk sample of mother/child dyads in Ghana and Côte d'Ivoire. METHODS: In 2010-2011, a prospective cohort of 1030 women in their third trimester in Ghana and Côte d'Ivoire was enrolled. Depression and anxiety were assessed in the third trimester using the Patient Health Questionnaire depression module and the 7-item Generalized Anxiety Disorder scale. 719 mother/child dyads were included in the analysis. We constructed multivariate regression models to estimate the association between CMD and low birth weight (LBW), and preterm birth (PTB) to control for potential confounders. RESULTS: The prevalence of depression and anxiety symptoms were 28.9% and 14.2% respectively. The mean birth weight was 3172.1g (SD 440.6) and the prevalence of LBW was 1.7%. The mean gestational age was 39.6 weeks and the proportion of PTB was 4%. Multivariate linear regression revealed no significant association between maternal depression (B=52.2, 95% CI -18.2 122.6, p=0.15) or anxiety (B=17.1, 95% CI -74.6 108.7, p=0.72) and birth weight. Yet, low socio-economic status, female sex of the child, and younger maternal age were associated with lower birth weight. Multivariate logistic regression suggested no significant association between maternal depression (OR: 2.1, 95% CI 0.8 5.6, p=0.15) or anxiety (OR: 1.8, 95% CI 0.6 5.5, p=0.29) with PTB. CONCLUSIONS: Our data suggests that depression and/or anxiety in the 3(rd) trimester of pregnancy are not independent predictors of adverse birth outcomes in low obstetric risk women. The role of pregnancy complications as confounders or effect modifiers in studies of maternal CMD and their impact on birth outcomes should be investigated.

Health care utilization and symptom severity in Ghanaian children--a cross-sectional study.

The aim of this study was to identify factors influencing health care utilization behavior for children with mild or severe disease symptoms in rural Ghana. Between March and September 2008 a cross-sectional health care utilization survey was conducted and 8,715 caregivers were interviewed regarding their intended behavior in case their children had mild or severe fever or diarrhea. To show associations between hospital attendance and further independent factors (e.g. travel distance or socio-economic status) prevalence ratios were calculated for the four disease symptoms. A Poisson regression model was used to control for potential confounding. Frequency of hospital attendance decreased constantly with increasing distance to the health facility. Being enrolled in the national health insurance scheme increased the intention to attend a hospital. The effect of the other factors diminished in the Poisson regression if modeled together with travel distance. The observed associations weakened with increasing severity of symptoms, which indicates that barriers to visit a hospital are less important if children experience a more serious illness. As shown in other studies, travel distance to a health care provider had the strongest effect on health care utilization. Studies to identify local barriers to access health care services are important to inform health policy making as they identify deprived populations with low access to health services and to early treatment.

Incidence and characteristics of bacteremia among children in rural Ghana.

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data.Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior.Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9-52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1-29.4) for NTS, 6.3 (CI 4.1-8.4) for S. aureus, 4.3 (CI 2.5-6.1) for S. pneumoniae and 3.3 (CI 1.8-4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malaria-endemic areas should be considered.

Genome-wide association study indicates two novel resistance loci for severe malaria.

Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

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.

Predictive value of fever and palmar pallor for P. falciparum parasitaemia in children from an endemic area.

INTRODUCTION: Although the incidence of Plasmodium falciparum malaria in some parts of sub-Saharan Africa is reported to decline and other conditions, causing similar symptoms as clinical malaria are gaining in relevance, presumptive anti-malarial treatment is still common. This study traced for age-dependent signs and symptoms predictive for P. falciparum parasitaemia. METHODS: In total, 5447 visits of 3641 patients between 2-60 months of age who attended an outpatient department (OPD) of a rural hospital in the Ashanti Region, Ghana, were analysed. All Children were examined by a paediatrician and a full blood count and thick smear were done. A Classification and Regression Tree (CART) model was used to generate a clinical decision tree to predict malarial parasitaemia a7nd predictive values of all symptoms were calculated. RESULTS: Malarial parasitaemia was detected in children between 2-12 months and between 12-60 months of age with a prevalence of 13.8% and 30.6%, respectively. The CART-model revealed age-dependent differences in the ability of the variables to predict parasitaemia. While palmar pallor was the most important symptom in children between 2-12 months, a report of fever and an elevated body temperature of ≥37.5°C gained in relevance in children between 12-60 months. The variable palmar pallor was significantly (p<0.001) associated with lower haemoglobin levels in children of all ages. Compared to the Integrated Management of Childhood Illness (IMCI) algorithm the CART-model had much lower sensitivities, but higher specificities and positive predictive values for a malarial parasitaemia. CONCLUSIONS: Use of age-derived algorithms increases the specificity of the prediction for P. falciparum parasitaemia. The predictive value of palmar pallor should be underlined in health worker training. Due to a lack of sensitivity neither the best algorithm nor palmar pallor as a single sign are eligible for decision-making and cannot replace presumptive treatment or laboratory diagnosis.

A -436C>A polymorphism in the human FAS gene promoter associated with severe childhood malaria.

Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS. Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.-436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58-0.88, p(empirical) = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62-0.80, p = 1.8×10⁻7, n = 6035). The association applied to c.-436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36-0.60) and to a lesser extent to c.-436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63-0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Spatial analysis of land cover determinants of malaria incidence in the Ashanti Region, Ghana.

Malaria belongs to the infectious diseases with the highest morbidity and mortality worldwide. As a vector-borne disease malaria distribution is strongly influenced by environmental factors. The aim of this study was to investigate the association between malaria risk and different land cover classes by using high-resolution multispectral Ikonos images and Poisson regression analyses. The association of malaria incidence with land cover around 12 villages in the Ashanti Region, Ghana, was assessed in 1,988 children <15 years of age. The median malaria incidence was 85.7 per 1,000 inhabitants and year (range 28.4-272.7). Swampy areas and banana/plantain production in the proximity of villages were strong predictors of a high malaria incidence. An increase of 10% of swampy area coverage in the 2 km radius around a village led to a 43% higher incidence (relative risk [RR] = 1.43, p<0.001). Each 10% increase of area with banana/plantain production around a village tripled the risk for malaria (RR = 3.25, p<0.001). An increase in forested area of 10% was associated with a 47% decrease of malaria incidence (RR = 0.53, p = 0.029). Distinct cultivation in the proximity of homesteads was associated with childhood malaria in a rural area in Ghana. The analyses demonstrate the usefulness of satellite images for the prediction of malaria endemicity. Thus, planning and monitoring of malaria control measures should be assisted by models based on geographic information systems.