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Application of a high-resolution melt assay for monitoring SARS-CoV-2 variants in Burkina Faso and Kenya.
Get PDFThe rapid emergence and global dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a need for robust, adaptable surveillance systems. However, financial and infrastructure requirements for whole-genome sequencing mean most surveillance data have come from higher-resource geographies, despite unprecedented investment in sequencing in low- and middle-income countries (LMICs). Consequently, the molecular epidemiology of SARS-CoV-2 in some LMICs is limited, and there is a need for more cost-accessible technologies to help close data gaps for surveillance of SARS-CoV-2 variants. To address this, we have developed two high-resolution melt (HRM) curve assays that target variant-defining mutations in the SARS-CoV-2 genome, which give unique signature profiles that define different SARS-CoV-2 variants of concern (VOCs). Extracted RNA from SARS-CoV-2-positive samples collected from 205 participants (112 in Burkina Faso, 93 in Kenya) enrolled in the MALCOV study (Malaria as a Risk Factor for COVID-19) between February 2021 and February 2022 were analyzed using our optimized HRM assays. With next-generation sequencing on Oxford Nanopore MinION as a reference, two HRM assays, HRM-VOC-1 and HRM-VOC-2, demonstrated sensitivity/specificity of 100%/99.29% and 92.86%/99.39%, respectively, for detecting Alpha, 90.08%/100% and 92.31%/100% for Delta, and 93.75%/100% and 100%/99.38% for Omicron BA.1. The assays described here provide a lower-cost approach to conducting molecular epidemiology, capable of high-throughput testing. We successfully scaled up the HRM-VOC-2 assay to screen a total of 506 samples from which we were able to show the replacement of Alpha with the introduction of Delta and the replacement of Delta by the Omicron variant in this community in Kisumu, Kenya.IMPORTANCEThe rapid evolution of the severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) demonstrated the need for accessible surveillance tools so all communities can conduct viral surveillance. Sequencing, the gold standard, is still a largely inaccessible methodology in low-resource settings. Here, we present a quick, low-cost tool to screen for the common VOCs, designed to support surveillance efforts in low-resource settings. This tool was used to screen samples from Burkina Faso and Western Kenya throughout the pandemic. We show through comparison to sequencing that our assay can generate highly similar data on the different variants circulating in a population, therefore showing the effectiveness of our tool. While not a replacement for sequencing, we present a method of screening and prioritizing samples for further investigation and reduce overburdening sequencing capacity. Our findings provide insight into one potential tool that could be further applied to pathogen screening in the absence of robust sequencing infrastructure
Previous or current infection with SARS-CoV-2 virus and its impact on maternal and neonatal health outcomes in Benin: a sero-epidemiological study in pregnant women.
Get PDFBACKGROUND: SARS-CoV-2 (COVID-19) has emerged as a significant global public health challenge, revealing critical vulnerabilities within health systems worldwide. While extensive data on COVID-19 is available from high-income countries, information remains scarce in lower-income regions, particularly regarding its impact on pregnant women. This study aims to evaluate the burden of COVID-19 among pregnant women and its effects on maternal and birth outcomes during the third wave in Benin. METHODS: A cross-sectional, hospital-based survey was conducted from May 19 to September 19, 2022, at the Lagune Mother and Child Teaching Hospital. A standardized questionnaire was administered, and nasal swabs along with serological analysis were performed on 437 pregnant women. Multivariate logistic regression was used to assess risk factors and evaluate the impact of previous or current COVID-19 exposure on maternal and birth adverse outcomes. RESULTS: SARS-CoV-2 was detected in less than 1% of pregnant women through PCR testing of nasal swab samples. Among the study population, 14.4% of women were vaccinated against COVID-19. A total of 81.1% of women tested positive for antibodies, suggesting prior exposure or infection to SARS-CoV-2 or vaccination. Notably, 78.6% of unvaccinated women had detectable antibodies, which serves as a more accurate proxy for infection prevalence. No significant association was found between prior COVID-19 exposure and adverse maternal and birth outcomes (aOR: 0.48, 95% CI 0.15-1.51). CONCLUSIONS: Although PCR testing revealed a low incidence of active SARS-CoV-2 infection, the high prevalence of IgG antibodies among pregnant women suggests widespread prior exposure or infection. Vaccination was identified as a strong predictor of detectable IgG antibodies. Notably, despite the presence of antibodies, no significant association was found between prior COVID-19 exposure and adverse maternal or birth outcomes. These findings highlight the need for further research to explore the potential long-term effects of COVID-19 infection on pregnancy outcomes and to better understand the relationship between antibody presence and maternal and fetal health
Development and Validation of Polygenic Risk Scores for Blood Pressure Traits in Continental African Populations.
Get PDFBACKGROUND: Most polygenic risk scores (PRS) have been developed in European populations, frequently leading to limited transferability across diverse ancestry populations. This study aimed to develop and evaluate PRS for blood pressure (BP) traits in continental African populations and investigate how African genetic diversity influences PRS performance. METHODS: We generated PRS for systolic BP, diastolic BP, pulse pressure, and hypertension. We used a pan-African cohort as the target population and compared single-ancestry and multi-ancestry PRS methods. We compared the performance of African ancestry-derived PRS against multi-ancestry PRS on the entire data set and within South, East, and West African subpopulations. RESULTS: Multi-ancestry PRS demonstrated significantly higher predictive accuracy compared with single-ancestry PRS models. PRS predictive accuracy varied across different African regions, with the highest performance observed in East Africa. In the combined population, the difference in mean BP values between the first multi-ancestry PRS quartile and the top quartile was 6.53 (95% CI, 5.3-7.74), 3.81 (95% CI, 3.9-4.52), and 3.59 (95% CI, 2.4-4.32) mm Hg for systolic BP, diastolic BP, and pulse pressure, respectively. Individuals in the highest PRS risk quartile had odds of hypertension that were 1.47 (95% CI, 1.7-1.69) times greater than those in the lowest risk quartile. CONCLUSIONS: These findings highlight the importance of integrating diverse ancestries in PRS development and accounting for subpopulation genetic variation to improve the predictive accuracy of BP PRS in African populations
Comparative effectiveness of alternative second-line oral glucose-lowering therapies for type 2 diabetes: a precision medicine approach applied to routine data.
Get PDFAIMS/HYPOTHESIS: National clinical guidelines recommend that second-line treatment for type 2 diabetes mellitus is chosen according to individuals' characteristics but there is limited evidence available to inform this choice. This paper's aim is to compare the effects on HbA1c of sulfonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) added to metformin as second-line oral glucose-lowering treatments according to an individual's age, baseline HbA1c and presence of multiple long-term conditions (MLTCs). METHODS: We accessed primary care-hospital linked data for 41,790 individuals from the Clinical Practice Research Datalink (CPRD) in England who initiated second-line treatment after metformin between 2015 and 2021. We combined target trial emulation with instrumental variable analysis to reduce the risk of confounding. The outcome was change in HbA1c between baseline and 1 year follow-up. We reported results stratified by age (18-49 years, 50-69 years and ≥70 years), baseline HbA1c (77 mmol/mol [>9.2%]) and presence of MLTCs. RESULTS: The mean (95% CI) difference in HbA1c change for SGLT2i vs SU was larger for people aged 18-49 years (-5.74 mmol/mol [-7.47, -4.01]) (-0.5% [-0.7, -0.4]) than for those aged 50-69 years (-4.03 mmol/mol [-5.61, -2.44]) (-0.4% [-0.5, -0.2]) and for those aged 70 years or over (-2.68 mmol/mol [-4.50, -0.86]) (-0.3% [-0.4, -0.07]). The mean (95% CI) difference in HbA1c change for SGLT2i vs DPP4i was -5.80 mmol/mol (-7.60, -4.00) (-0.5% [-0.7, -0.4]) for those aged 18-49 years, -4.13 mmol/mol (-5.82, -2.45) (-0.4% [-0.5, -0.2]) for those aged 50-69 years and -3.13 mmol/mol (-5.01, -1.24) (-0.3% [-0.4, -0.1]) for those aged ≥70 years. The mean difference (improvement) in HbA1c was similar across subgroups defined by baseline HbA1c or presence of MLTCs. For SGLT2i vs SU, the mean (95% CI) difference was -5.37 mmol/mol (-7.13, -3.62) (-0.5% [-0.6, -0.3]) for people without MLTC and -3.72 mmol/mol (-5.34, -2.10]) (-0.3% [-0.5, -0.2]) for people with MLTC. For SGLT2i vs DPP4i the corresponding estimated differences (95% CI) were -5.44 mmol/mol (-7.27, -3.61) (-0.5% [-0.7, -0.3]) for those without MLTC and -3.93 mmol/mol (-5.64, -2.21) (-0.3% [-0.5, -0.2]) for those with MLTC. CONCLUSIONS/INTERPRETATION: Second-line treatment with SGLT2i is more effective than SU or DPP4i in reducing HbA1c across subgroups of people defined by age, baseline HbA1c and presence of MLTCs. Our evidence complements RCTs in using routinely available information on demographic characteristics, biomarkers and comorbidities to inform an individualised approach
Can nutrition-sensitive agriculture interventions address intersectional inequalities in women's diets? A mediation analysis using cross-sectional trial data from Odisha, India.
Get PDFBACKGROUND: Improving nutrition for all requires understanding how interventions influence nutrition inequalities within society. Intersectionality, which considers how multiple disadvantages intersect, may offer more precise insight into the equity of these interventions. OBJECTIVES: Using an intersectionality-informed approach and mediation with exposure-mediator interaction, we investigated how participation in nutrition-sensitive agriculture interventions tested in the UPAVAN trial affected inequalities in women's diets in Odisha, India. METHODS: We analyzed cross-sectional endline data from 3294 mothers of children aged 0-23 months in 111 UPAVAN intervention villages. We estimated dietary inequalities as excess relative risk of minimum dietary diversity (MDD-W) according to scheduled tribe (ST) identity (ST or non-ST), education (≥5, <5 y), or wealth (higher, lower) and comparing intersectional groups that combine ST/non-ST with education or wealth group. We used a 4-way decomposition to estimate whether these MDD-W inequalities were affected by social group differences in intervention participation rates (mediation only), participation benefits (interaction only), or both combined (mediated interaction). RESULTS: Intervention participation and MDD-W were greater among the more advantaged groups of non-ST, higher education, or higher wealth. Often, the more disadvantaged groups had greater participation benefits (interaction only), which narrowed MDD-W inequalities. However, intersectional groups with 2 disadvantaged characteristics (e.g., poorer ST) had smaller participation benefits than those with 1 disadvantaged characteristic (e.g., wealthier ST), which widened MDD-W inequalities. Differences in participation rates had negligible effects on MDD-W inequalities. Often, any marginal widening of MDD-W inequalities due to disadvantaged groups participating less (mediation only) was suppressed by their greater participation benefits (mediated interaction). CONCLUSIONS: To our knowledge, this is the first intersectionality-informed analysis of nutrition interventions. UPAVAN interventions mostly had equitable impacts, reducing several inequalities in maternal diet quality. We demonstrate how intersectionality-informed analyses can help identify inequities in nutrition interventions and inform the design of inclusive interventions that reach and benefit the most marginalized groups
Container-based sanitation delivers better service
Get PDFAn alternative to sewers and pit latrines, container-based systems are increasingly used in informal settlements. Weekly surveys show users are generally satisfied, but their sanitation-related quality of life falls when service problems arise
Disability inclusion in the Brazilian health system: results of a health system assessment.
Get PDFBACKGROUND: People with disabilities face more barriers accessing healthcare and on average experience worse health outcomes. Strengthening health access for people with disabilities requires coordinated action across the health system. The Missing Billion Inclusive Health System Framework is a new tool to support policy makers to assess levels of disability inclusion within health systems. OBJECTIVES: This study uses the Missing Billion framework in Brazil to i) contribute to the further testing and development of the framework and ii) assess the level of disability inclusion within the Unified Health System. METHODS: Information sources used to complete the assessment included Brazilian laws and policies, publicly available data, published literature, literature reviews and interviews with people with disabilities and service providers in São Paulo, Santos, Brasília and Arcoverde. A workshop with stakeholders was held to co-develop key recommendations. RESULTS: Overall, the Missing Billion framework was comprehensive and feasible to complete. It highlighted key strengths in terms of disability inclusion in the Brazilian health system as well as gaps and leverage points for action. CONCLUSIONS: The Missing Billion framework can identify progress and opportunities to strengthen disability inclusion in health systems. In Brazil, key promotive factors include supportive policies, leadership and financing structures. There are also opportunities for strengthening data and evidence, healthcare worker training on disability and health service accessibility. Actions must be centered on and informed by people with disabilities
Association of Water, Sanitation, Hygiene and Animal Ownership With Relapse to Acute Malnutrition Among Children Aged 6-59 Months in Mali, South Sudan and Somalia: A Multi-Site Prospective Cohort Study.
Get PDFChildren successfully treated through community-based management of acute malnutrition (CMAM) frequently relapse to acute malnutrition (AM) following recovery and discharge. This prospective cohort study examined associations between relapse and household water, sanitation and hygiene (WASH) conditions, as well as animal ownership, in Mali, South Sudan and Somalia. Between April 2021 and June 2022, 1115 children were enrolled, with 964 children followed for 6 months, 242 in Mali, 488 in South Sudan and 234 in Somalia. Relapse to AM occurred in 32%, 63% and 21% of children in Mali, South Sudan and Somalia, respectively. In Mali, relapse risk was higher in households using multiple drinking water sources (aRR 1.71, 95% CI: 1.21-2.43, p = 0.003) or lacking soap (aRR 1.71, 95% CI: 1.03-2.82, p = 0.037). In South Sudan, inadequate drinking water sources, open defecation and the presence of animal faeces in the compound were associated with an increased risk of relapse (aRR 1.20, 95% CI: 1.04-1.38, p = 0.010; aRR 1.16, 95% CI: 1.03-1.30, p = 0.016; aRR 1.13, 95% CI: 1.02-1.26, p = 0.019, respectively). Sheep ownership in Mali (aRR 0.57, 95% CI: 0.40-0.81, p = 0.002) and cattle ownership in South Sudan (aRR 0.78, 95% CI: 0.71-0.85, p = < 0.001) were protective. No significant WASH or animal-related factors were associated with relapse in Somalia. As nearly all household drinking water samples were contaminated across settings and time points, no association could be detected between measured water quality and relapse. While many WASH indicators were not associated with relapse, some inadequate WASH conditions were identified as risk factors for relapse, although heterogeneous across contexts. These findings may help to identify at-risk children during treatment and inform strategies to reduce relapse post-recovery
To what extent does Together with Gloria! expand the reach of SASA! Together community programming? A mixed methods evaluation of an edutainment intervention in Kasese, Uganda.
Get PDFBACKGROUND: Community-level interventions to prevent violence against women (VAW), though potentially efficacious, are challenging to implement at scale, requiring intensive long-term engagement. There is thus interest in the potential for mass-media strategies, including 'edutainment', to complement and extend the reach of in-person community programming. While edutainment interventions can demonstrably reach large audiences at relatively low cost, little is known about who they reach/exclude, nor about barriers/facilitators to engagement. This paper describes the extent to which 'Together with Gloria!' (TWG), a 33-episode radio-drama, expanded the reach of SASA! Together, a community-level VAW prevention intervention in Western Uganda. METHODS: As part of a broader mixed-methods evaluation, we conducted two cross-sectional community surveys: baseline (6-weeks into broadcasting); and endline (6-weeks after final broadcast). Qualitative data collection included focus group discussions and in-depth interviews with community members, local leaders and SASA! Together Community Activists. We present descriptive data on TWG's reach, and the extent to which people listened/discussed TWG with others. We use logistic regression to explore variation in reach by socio-demographic characteristics. Barriers/facilitators to engagement are explored using survey and qualitative data. RESULTS: At endline (n = 1018), 52% of survey respondents reported having listened to TWG. Across all demographic sub-groups, exposure to TWG considerably exceeded exposure to in-person SASA! Together programming, with TWG listening more uniformly spread across villages. Among men, listening was positively associated with increasing age, having a partner and children, and radio ownership. Among women, listening was positively associated with secondary education, being childless, and owning a radio. Most listeners (74% men; 64% women) reported usually listening with others (most commonly a partner), and 41% had discussed TWG with other community members. Communal listening and multiple broadcast stations/timeslots were noted to facilitate listening. Barriers included lack of radio access (particularly among women), and lack of time. CONCLUSIONS: TWG expanded overall reach of in-person SASA! Together programming, and reduced geographical disparities in access. Use of multiple radio-stations/broadcasting timeslots allowed many to listen despite competing time-commitments. Future revisions to broaden access and appeal could include communal broadcasts in public places, and the incorporation of characters and storylines to resonate with younger childless men