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Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness.We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355.From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes.This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses.BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Background The burden of cardiovascular disease (CVD) in Ghana is rising, but details on its epidemiology are scarce. We sought to quantify mortality due to CVD in two districts in rural Ghana using verbal post-mortem (VPM) data. Methods We conducted a proportional sub-hazards analysis of 10 232 deaths in the Kassena-Nankana East and West districts from 2005 to 2012, to determine adult mortality attributed to CVD over time. We stratified results by age, gender and socio-economic status (SES), and compared CVD mortality among SES and gender strata over time. A competing risk model estimated the cumulative effect of eliminating CVD from the area. Results From 2005 to 2012, CVD mortality more than doubled overall, from 0.51 deaths for every 1000 person-years in 2005 to 1.08 per 1000 person-years in 2012. Mortality peaked in 2008 at 1.23 deaths per 1000 person-years. Increases were comparable in men (2.0) and women (2.3), but greater among the poorest residents (3.3) than the richest (1.3), and among persons aged 55–69 years (2.1) than those aged ≥70 years (1.8). By 2012, male and female CVD mortality was highest in middle-SES persons. We project that eliminating CVD would increase the number of individuals reaching age 73 years from 35% to 40%, adding 1.6 years of life expectancy. Conclusions The burden of CVD on overall mortality in the Upper East Region is substantial and markedly increasing. CVD mortality has especially increased in lower-income persons and persons in middle age. Further initiatives for the surveillance and control of CVD in these vulnerable populations are needed.

Carotid atherosclerosis and microalbuminuria are associated with atherosclerotic cardiovascular disease (ASCVD) but are understudied in sub-Saharan Africa.To evaluate the association of carotid atherosclerosis and microalbuminuria with 10-year ASCVD risk in middle-aged sub-Saharan African individuals.This cross-sectional study conducted analyses of baseline data from the African-Wits-INDEPTH (International Network for the Demographic Evaluation of Populations and Their Health in Low- and Middle-Income Countries) genomic study (AWI-Gen). Women and men aged 40 to 60 years without baseline CVD and drawn from Burkina Faso, Ghana, Kenya, and South Africa were included.Hypotheses for the analyses were formulated after data collection. The main exposures were carotid atherosclerosis, assessed using carotid intima-media thickness (CIMT) using B-mode ultrasonography, and microalbuminuria, measured using spot urine albumin (SUA) and urine albumin-creatinine ratio (uACR). The main outcome was high ASCVD risk, defined as a 2018 Pooled Cohort Equations score of 7.5% or greater. Associations were estimated using adjusted multivariable logistic regression analyses.A total of 9010 participants with a mean (SD) age of 50 (6) years and 4533 (50.3%) women were included. High CIMT, SUA, and uACR were each associated with older age (eg, mean [SD] age of participants with high vs reference range CIMT: 55 [5] years vs 50 [6] years; P .001) and high prevalence of both diabetes and hypertension (eg, hypertension among those with high vs reference range SUA: 213 of 1117 [19.1%] vs 356 of 2549 [14.0%]; P .001). Smokers were likely to have higher vs reference range SUA (210 [18.8%] vs 407 [16.0%]) and uACR (138 of 707 [19.5%] vs 456 of 2797 [16.3%]). Carotid atherosclerosis was common in Burkina Faso (82 of 262 [31.3%]) and Ghana (91 [34.7%]), while microalbuminuria, measured by SUA, was common in Kenya (272 [24.4%]) and South Africa (519 [46.5%]). SUA was associated with higher odds of carotid atherosclerosis (odds ratio [OR], 1.77; 95% CI, 1.04-3.01) compared with uACR (OR, 0.51; 95% CI, 0.27-0.95). Common CIMT, SUA, and uACR were associated with 10-year ASCVD risk, with CIMT having a stronger association with 10-year ASCVD risk in both women (OR, 1.95; 95% CI, 1.78-2.14) and men (OR, 1.73; 95% CI, 1.55-1.93) than SUA (women: OR, 1.29; 95% CI, 1.12-1.43; men: OR, 1.46; 95% CI, 1.26-1.55) and uACR (women: OR, 1.32; 95% CI, 1.10-1.54; men: OR, 1.35; 95% CI, 1.15-1.46).The presence of microalbuminuria measured by SUA may indicate risk of subclinical carotid atherosclerosis and high 10-year ASCVD risk in middle-aged residents of sub-Saharan Africa. These data should be confirmed in longitudinal studies of cardiovascular events.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid‐intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross‐sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B‐mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 1‐stage individual participant data meta‐analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09–0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01–0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06–0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High‐density lipoprotein‐cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race‐ ethnicity‐specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

The current global malaria control and elimination agenda requires development of additional effective disease intervention tools. Discovery and characterization of relevant parasite antigens is important for the development of new diagnostics and transmission monitoring tools and for subunit vaccine development. This study assessed the natural antibody response profile of seven novel Plasmodium falciparum pre-erythrocytic antigens and their potential association with protection against clinical malaria. Antigen-specific antibody levels in plasma collected at six time points from a longitudinal cohort of one-to-five year old children resident in a seasonal malaria transmission area of northern Ghana were assessed by ELISA. Antibody levels were compared between parasite-positive and parasite-negative individuals and the association of antibody levels with malaria risk assessed using a regression model. Plasma antibody levels against five of the seven antigens were significantly higher in parasite-positive children compared to parasite-negative children, especially during low transmission periods. None of the antigen-specific antibodies showed an association with protection against clinical malaria. The study identified five of the seven antigens as markers of exposure to malaria, and these will have relevance for the development of disease diagnostic and monitoring tools. The vaccine potential of these antigens requires further assessment.

Few studies have compared the utility of serum levels of lipid fractions in cardiovascular disease (CVD) risk assessment in sub-Saharan Africa (SSA). The current study interrogated this question among men and women aged 40–60 years in rural northern Ghana. This was a cross-sectional study in which data was collected on socio-demography, behaviour, health history, anthropometry and lipid levels. Adjusted multivariable logistic regression models were used to assess the association of various lipid metrics with CVD. All tests were considered statistically significant at P

Immunity to Plasmodium falciparum is non-sterilising, thus individuals residing in malaria-endemic areas are at risk of infection throughout their lifetime. Here we seek to find a genomic epidemiological explanation for why residents of all ages harbour blood stage infections despite lifelong exposure to P. falciparum in areas of high transmission. We do this by exploring, for the first known time, the age-specific patterns of diversity of variant antigen encoding (var) genes in the reservoir of infection. Microscopic and submicroscopic P. falciparum infections were analysed at the end of the wet and dry seasons in 2012-2013 for a cohort of 1541 residents aged from 1 to 91 years in an area characterised by high seasonal malaria transmission in Ghana. By sequencing the near ubiquitous Duffy-binding-like alpha domain (DBLα) that encodes immunogenic domains, we defined var gene diversity in an estimated 1096 genomes detected in sequential wet and dry season sampling of this cohort. Unprecedented var (DBLα) diversity was observed in all ages with 42,399 unique var types detected. There was a high degree of maintenance of types between seasons (40% seen more than once), with many of the same types, especially upsA, appearing multiple times in isolates from different individuals. Children and adolescents were found to be significant reservoirs of var DBLα diversity compared with adults. Var repertoires within individuals were highly variable, with children having more related var repertoires compared to adolescents and adults. Individuals of all ages harboured multiple genomes with var repertoires unrelated to those infecting other hosts. High turnover of parasites with diverse isolate var repertoires was also observed in all ages. These age-specific patterns are best explained by variant-specific immune selection. The observed level of var diversity for the population was then used to simulate the development of variant-specific immunity to the diverse var types under conservative assumptions. Simulations showed that the extent of observed var diversity with limited repertoire relatedness was sufficient to explain why adolescents and adults in this community remain susceptible to blood stage infection, even with multiple genomes.

Background: African populations are characterised by diversity at many levels including: demographic history, genetic ancestry, language, wealth, socio-political landscape, culture and behaviour. Several of these have a profound impact on body fat mass. Obesity, a key risk factor for cardiovascular and metabolic diseases, in the wake of the epidemiological and health transitions across the continent, requires detailed analysis together with other major risk factors. Objective: To compare regional and sex-specific body mass index (BMI) distributions, using a cross-sectional study design, in adults aged 40–60 years across six study sites in four sub-Saharan African (SSA) countries and to compare the determinants of BMI at each. Methods: Anthropometric measurements were standardised across sites and BMI calculated. Median BMI and prevalence of underweight, lean, overweight and obesity were compared between the sexes and across sites. Data from multivariable linear regression models for the principal determinants of BMI were summarised from the site-specific studies. Results: BMI was calculated in 10,702 participants (55% female) and was significantly higher in women than men at nearly all sites. The highest prevalence of obesity was observed at the three South African sites (42.3–66.6% in women and 2.81–17.5% in men) and the lowest in West Africa (1.25–4.22% in women and 1.19–2.20% in men). Across sites, higher socio-economic status and educational level were associated with higher BMI. Being married and increased dietary intake were associated with higher BMI in some communities, whilst smoking and alcohol intake were associated with lower BMI, as was HIV infection in the regions where it was prevalent. Conclusion: In SSA there is a marked variation in the prevalence of obesity both regionally and between men and women. Our data suggest that the drive for social upliftment within Africa will be associated with rising levels of obesity, which will require the initiation of targeted sex-specific intervention programmes across specific African communities.

Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55.4%) to the dry (20.7%) season (P < 0.001). Combining detection methods, 74.4% and 42.5% of the population in the wet and dry seasons, respectively, had evidence of a P. falciparum infection. Interestingly in those > 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of West Africa.

Several associations between specific HLA alleles and susceptibility or resistance to Plasmodium falciparum malaria have been previously reported, but no associations have been confirmed in multiple populations. We studied associations between HLA-A, -B, and DRB1 alleles and severe malaria in northern Ghana. We analyzed HLA-DRB1*04 in 4,032 subjects from a severe malaria case-control study, 790 severe malaria cases, 1,611 mild malaria controls, and 1631 asymptomatic controls. The presence of HLA-DRB1*04 was associated with severe malaria (OR = 2.42, 95% CI = 1.64, 3.58). The allele frequency of DRB1*04 was similar in the two major ethnic groups in the study population, Kassem (4.4%) and Nankam (4.7%), and the OR for the association between DRB1*04 and severe malaria was similar in both ethnic groups. These findings are consistent with results from Gabon suggesting that DRB1*04 is a risk factor for severe malaria.