Methodological Challenges in Estimating Trends and Burden of Cardiovascular Disease in Sub-Saharan Africa

Background. Although 80% of the burden of cardiovascular disease (CVD) is in developing countries, the 2010 global burden of disease (GBD) estimates have been cited to support a premise that sub-Saharan Africa (SSA) is exempt from the CVD epidemic sweeping across developing countries. The widely publicized perspective influences research priorities and resource allocation at a time when secular trends indicate a rapid increase in prevalence of CVD in SSA by 2030. Purpose. To explore methodological challenges in estimating trends and burden of CVD in SSA via appraisal of the current CVD statistics and literature. Methods. This review was guided by the Critical review methodology described by Grant and Booth. The review traces the origins and evolution of GBD metrics and then explores the methodological limitations inherent in the current GBD statistics. Articles were included based on their conceptual contribution to the existing body of knowledge on the burden of CVD in SSA. Results/Conclusion. Cognizant of the methodological challenges discussed, we caution against extrapolation of the global burden of CVD statistics in a way that underrates the actual but uncertain impact of CVD in SSA. We conclude by making a case for optimal but cost-effective surveillance and prevention of CVD in SSA

Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009

BACKGROUND: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. METHODS: As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006-2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. RESULTS: NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. CONCLUSIONS: NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa

A Comprehensive Analysis of Shared Loci between Systemic Lupus Erythematosus (SLE) and Sixteen Autoimmune Diseases Reveals Limited Genetic Overlap

In spite of the well-known clustering of multiple autoimmune disorders in families, analyses of specific shared genes and polymorphisms between systemic lupus erythematosus (SLE) and other autoimmune diseases (ADs) have been limited. Therefore, we comprehensively tested autoimmune variants for association with SLE, aiming to identify pleiotropic genetic associations between these diseases. We compiled a list of 446 non–Major Histocompatibility Complex (MHC) variants identified in genome-wide association studies (GWAS) of populations of European ancestry across 17 ADs. We then tested these variants in our combined Caucasian SLE cohorts of 1,500 cases and 5,706 controls. We tested a subset of these polymorphisms in an independent Caucasian replication cohort of 2,085 SLE cases and 2,854 controls, allowing the computation of a meta-analysis between all cohorts. We have uncovered novel shared SLE loci that passed multiple comparisons adjustment, including the VTCN1 (rs12046117, P = 2.02×10−06) region. We observed that the loci shared among the most ADs include IL23R, OLIG3/TNFAIP3, and IL2RA. Given the lack of a universal autoimmune risk locus outside of the MHC and variable specificities for different diseases, our data suggests partial pleiotropy among ADs. Hierarchical clustering of ADs suggested that the most genetically related ADs appear to be type 1 diabetes with rheumatoid arthritis and Crohn's disease with ulcerative colitis. These findings support a relatively distinct genetic susceptibility for SLE. For many of the shared GWAS autoimmune loci, we found no evidence for association with SLE, including IL23R. Also, several established SLE loci are apparently not associated with other ADs, including the ITGAM-ITGAX and TNFSF4 regions. This study represents the most comprehensive evaluation of shared autoimmune loci to date, supports a relatively distinct non–MHC genetic susceptibility for SLE, provides further evidence for previously and newly identified shared genes in SLE, and highlights the value of studies of potentially pleiotropic genes in autoimmune diseases

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (=3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has becomedominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies

External validation and cost effectiveness analysis of the non-LB Framingham cardiovascular disease risk assessment algorithm in the atherosclerosis risk in communities dataset

Background: In recent years, non-Laboratory based (non-LB) risk assessment algorithms have been developed to facilitate absolute cardiovascular disease (CVD) risk assessment in resource constrained primary care settings. The non-LB Framingham algorithm, which substitutes body mass index (BMI) for lipids, has the best discrimination and calibration among the published algorithms, but its external validity and cost-effectiveness have not been determined. Purpose: External validation and comparative effectiveness analysis of the non-LB versus laboratory based (LB) Framingham algorithm in a racially diverse population, and simulated cost-effectiveness analysis focusing on a black sample. Methods: Secondary data analysis was performed using the Atherosclerosis Risk in Communities (ARIC) dataset. Cox regression models including the non-LB and LB Framingham covariates were developed. Model discrimination was assessed using the C statistic, calibration using the goodness-of-fit test, and equivalence of regression coefficients using the z-test. Algorithms based on the models were developed and their performance assessed using the area under receiver operating characteristic curve (AUROC), and agreement using kappa statistics. Analyses using simulated incremental cost-effectiveness ratios (ICER) were focused on the black sample. IRB approval was obtained. Data were analyzed using Stata© software version 14. Results: Among 11,601 individuals (mean age 53.9 ± 5.7 years, 55% female, 24% black), the non-LB versus LB models performed as follows: C statistic (0.75 vs 0.76 for women, & 0.67 vs 0.68 for men); goodness-of-fit (14.2 vs 10.5 for women, & 25.8 vs 21.8 for men) respectively. In the black sample, regression coefficients of all covariates were similar to those generated in Framingham (z = ±1.96). The two algorithms based on the models had a kappa statistic of 0.76. When used to stratify risk in the entire ARIC sample, the non-LB and LB Framingham algorithms had AUROC of 0.706 vs 0.710 respectively. Prevention program guided by the non-LB Framingham dominated those guided by individual risk factors and LB Framingham algorithm. Conclusions: These results demonstrate the validity and cost-effectiveness of the non-LB Framingham algorithm. This approach could provide a valuable and efficient alternative to the traditional LB approaches in the ongoing efforts to address the high burden of CVD in underserved communitie

A scalable membrane electrode assembly architecture for efficient electrochemical conversion of CO2 to formic acid

Abstract The electrochemical reduction of carbon dioxide to formic acid is a promising pathway to improve CO2 utilization and has potential applications as a hydrogen storage medium. In this work, a zero-gap membrane electrode assembly architecture is developed for the direct electrochemical synthesis of formic acid from carbon dioxide. The key technological advancement is a perforated cation exchange membrane, which, when utilized in a forward bias bipolar membrane configuration, allows formic acid generated at the membrane interface to exit through the anode flow field at concentrations up to 0.25 M. Having no additional interlayer components between the anode and cathode this concept is positioned to leverage currently available materials and stack designs ubiquitous in fuel cell and H2 electrolysis, enabling a more rapid transition to scale and commercialization. The perforated cation exchange membrane configuration can achieve >75% Faradaic efficiency to formic acid at <2 V and 300 mA/cm2 in a 25 cm2 cell. More critically, a 55-hour stability test at 200 mA/cm2 shows stable Faradaic efficiency and cell voltage. Technoeconomic analysis is utilized to illustrate a path towards achieving cost parity with current formic acid production methods

Cross-cultural equivalence of the Kessler Psychological Distress Scale (K10) across four African countries in a multi-national study of adults

The Kessler Psychological Distress Scale (K10) has been widely used to screen psychological distress across many countries. However, its performance has not been extensively studied in Africa. The present study sought to evaluate and compare measurement properties of the K10 across four African countries: Ethiopia, Kenya, Uganda, and South Africa. Our hypothesis is that the measure will show equivalence across all.Data are drawn from a neuropsychiatric genetic study among adult participants (N = 9179) from general medical settings in Ethiopia (n = 1928), Kenya (n = 2556), Uganda (n = 2104), and South Africa (n = 2591). A unidimensional model with correlated errors was tested for equivalence across study countries using confirmatory factor analyses and the alignment optimization method. Results displayed 30 % noninvariance (i.e., variation) for both intercepts and factor loadings across all countries. Monte Carlo simulations showed a correlation of 0.998, a good replication of population values, indicating minimal noninvariance, or variation. Items “so nervous,” “lack of energy/effortful tasks,” and “tired” were consistently equivalent for intercepts and factor loadings, respectively. However, items “depressed” and “so depressed” consistently differed across study countries (R2 = 0) for intercepts and factor loadings for both items.The K10 scale likely functions equivalently across the four countries for most items, except “depressed” and “so depressed.” Differences in K10 items were more common in Kenya and Ethiopia, suggesting cultural context may influence the interpretation of some items and the potential need for cultural adaptations in these countries