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Target Trial Emulation of the Modified Vaccinia Ankara-Bavarian Nordic Vaccine for Pre-Exposure Mpox Prevention in At-Risk Populations.
Get PDFBackground: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence ≥14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7-13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21-1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting
Understanding end-user preferences for hand hygiene enabling technologies: A mixed-methods study in peri-urban Lusaka, Zambia
Get PDFHandwashing facilities (HWFs) are associated with higher rates of handwashing with soap, and the presence of a HWF is the global proxy indicator of household handwashing behaviour. There is limited information on HWF attributes important to end-users with few comparative assessments of HWFs from a user-perspective. We aimed to identify HWF attributes important to end-users and determine how pre-manufactured HWFs ranked by these attributes. This two-phased study was conducted with a diverse group of targeted end-users in two peri-urban communities in Lusaka, Zambia. We identified eight pre-existing HWFs: two manufactured locally (Kalingalinga bucket and Tippy tap) and six industrially produced, imported designs (Jengu, SatoTap, SaniTap, HappyTap, SpaTap, and Kohler Cleanse). In the first phase, focus group discussions explored what participants liked and disliked about each HWF, and thematic analysis defined nine attributes for comparison. In the second phase, participants individually ranked each HWF by these attributes, their overall preference, and their preference once estimated retail prices were revealed. Participants also ranked attributes by importance. Ranking data were modelled using rank-ordered logistic regression. Discussions revealed nine attributes important to end-users: appearance, water management, hygienic use, convenience, water disposal, vulnerability to theft or breakage, ease of use, price and maintenance. Hygienic use and water management were considered most important attributes. Excluding price, facilities resembling a sink, such as the Happy Tap (34%) and Jengu (28%), had the highest probability of being ranked first. With consideration for price, participants preferred lower-cost HWFs such as the Kalingalinga bucket (44%), Tippy Tap (13%) and SATO Tap (10%). This study identified nine attributes important to end-users that can inform future design efforts. Future work will explore user preferences in situ by rotating households through specific HWFs for an extended period. Potential manufacturers should continue to iterate on HWF designs emphasizing reducing costs
Water, Health, and Social Technologies: One Million Cisterns Programme Case Study.
Get PDFBackground: This paper focuses on the impacts of climate change on vulnerable ecosystems and its implications for the health and well-being of populations. It specifically examines the semi-arid region of Brazil, where the introduction of a social climate adaptation tool, cisterns, has brought about significant positive changes. Cisterns, a low-cost climate adaptation technology, can be replicated globally, reducing the negative health impacts of frequent droughts, especially for vulnerable groups in remote rural areas. Objective: We analyze the impact of the "One Million Cisterns Program" (P1MC) on health by synthesizing the literature and modeling its interactions with climatic and environmental factors with the Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework. Methods: Our case study employs a multidisciplinary approach, focusing on two key objectives: (i) synthesizing the literature on the implementation of the P1MC and its association with health outcomes, using search criteria that specifically target articles linking the program to health impacts; and (ii) developing a conceptual framework to model the relationship between climatic and environmental factors, adaptive ecosystems, and health outcomes. The DPSEEA framework evaluates the structural connections between climate change and human health. Findings: The study found a significant gap in the literature concerning the relationship between P1MC and health outcomes. Cisterns target the pressure/state linkages related to contextual factors and health effects, addressing the root causes of drought-related health issues. This framework also provides a foundation for collaboration among health, environmental, and policy sectors to address shared challenges, such as water security and health outcomes. Conclusion: We offer a multidisciplinary analytical framework that can be used to explore various perspectives-environmental, social, and health-related-with experts and stakeholders to develop and improve adaptive social technology strategies for living in the era of climate change. This framework also facilitates the implementation of qualitative and quantitative well-being and health assessments
Geographical equity in Ethiopian infant feeding practices: a secondary analysis of a birth cohort study.
Get PDFOBJECTIVES: To assess the geographical equity in Ethiopian infants' exclusive breastfeeding at 5 months and dietary diversity at 12 months and whether social factors explained the spatial inequities.
DESIGN: Secondary analysis of a birth cohort study.
SETTING: Analysis of data from the Ethiopian Performance Monitoring for Action panel study conducted from July 2020 to August 2021 in five regions (ie, Oromia, Amhara, Afar and Southern Nations, Nationalities and Peoples regions and the Addis Ababa City administration). We analysed geographical autocorrelation to assess geographical variations in exclusive breastfeeding and dietary diversity. Areas with higher and lower coverage of appropriate infant feeding outcomes were analysed using hotspot analyses. We performed geographically weighted regression to investigate whether sociodemographic factors explained the geographical feeding differences.
PARTICIPANTS: 1850 infants were prospectively followed from birth to 12 months.
OUTCOME MEASURES: Exclusive breastfeeding at 5 months and minimum-level dietary diversity at 12 months.
RESULTS: Sixty-nine percent (95% CI 67 to 71) of infants were exclusively breastfed at 5 months, while at 12 months, only 16% (95% CI 13 to 19) had complementary feeding from five or more food groups. There were geographical variations in the coverage of exclusive breastfeeding and minimum dietary diversity. Higher proportions of infants were exclusively breastfed at 5 months in northern areas, and more 12-month-old infants in central parts of the country had complementary feeding from at least five food groups. Sociodemographic factors explained a quarter of the geographical variation in dietary diversity.
CONCLUSION: Most Ethiopian infants were exclusively breastfed, which was in line with global recommendations but with some geographical differences. There was prominent geographical variation in dietary diversity, partly explained by social factors, but overall, very few 12-month-old infants were fed from at least five food groups. This low dietary quality could impair Ethiopian children's physical growth, development and health
BonoboFlow: viral genome assembly and haplotype reconstruction from nanopore reads.
Get PDFSUMMARY: Viral genome sequencing and analysis are crucial for understanding the diversity and evolution of viruses. Traditional Sanger sequencing is limited by low sequence depth and is labor intensive. Next-Generation Sequencing (NGS) methods, such as Illumina, offer improved sequencing depth and throughput but face challenges with accurate reconstruction of viral genomes due to genome fragmentation. Third-generation sequencing platforms, such as PacBio and Oxford Nanopore Technologies (ONT), generate long reads with high throughput. However, PacBio is constrained by substantial resource requirements, while ONT suffers from inherently high error rates. Moreover, standardized pipelines for ONT sequencing encompassing basecalling to genome assembly remain limited. RESULTS: Here, we introduce BonoboFlow, a standardized Nextflow pipeline designed to streamline ONT-based viral genome assembly/haplotype reconstruction. BonoboFlow integrates key processing steps, including basecalling, read filtering, chimeric read removal, error correction, draft genome assembly/haplotype reconstruction, and genome polishing. The pipeline accepts raw POD5 or basecalled FASTQ files as input, produces FASTA consensus files as output, and uses a reference genome (in FASTA format) for contaminant read filtering. BonoboFlow's containerized implementation via Docker and Singularity ensures seamless deployment across diverse computing environments. While BonoboFlow excels in assembling small and medium viral genomes, it showed challenges when reconstructing large viral genomes. AVAILABILITY AND IMPLEMENTATION: BonoboFlow and corresponding containerized images are publicly available at https://github.com/nchis09/BonoboFlow and https://hub.docker.com/r/nchis09/bonobo_image. The test dataset is available at SRA repository Accession number: PRJNA1137155, http://www.ncbi.nlm.nih.gov/bioproject/1137155
Randomised controlled trial of topical combination therapy chlorhexidine 0.2% and natamycin 5% versus topical natamycin 5% alone for fungal keratitis in East Africa: study protocol.
Get PDFIntroductionFungal corneal infection (fungal keratitis [FK]) poses significant treatment challenges. The efficacy of current topical antifungals is inconsistent and often limited, especially in low and middle-income countries where the majority of FK cases occur. Topical natamycin 5% is the current primary treatment in many countries, however, a substantial proportion of cases develop progressive disease, even with intensive treatment. Given the limitations of existing antifungal treatments, there is a need for alternative treatment strategies to address this condition.Chlorhexidine, an antiseptic with both antibacterial and antifungal properties, has received attention as a potential therapeutic agent. While a recent randomized controlled trial (RCT) in Nepal demonstrated the superiority of natamycin over chlorhexidine, a pilot study in Uganda has indicated a possible role for adjunctive chlorhexidine 0.2% in FK treatment. The contrasting findings necessitate a comprehensive RCT to investigate the potential benefit of adding topical chlorhexidine 0.2% alongside natamycin 5% in the management of FK.MethodsWe will test the hypothesis that topical natamycin 5% in combination with chlorhexidine 0.2% is superior to topical natamycin 5% alone in a two-arm, single-masked RCT (ISRCTN, ISRCTN87195453, registered 27/08/2020, https://www.isrctn.com/ISRCTN87195453). Participants are adults with FK presenting to tertiary ophthalmic hospitals in Tanzania and Uganda. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and corneal scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients will be reviewed at days 2, 7 (with re-culture), 14, 21, month 2, and month 3. The primary outcome is best spectacle corrected visual acuity (BSCVA) at three months. Primary analysis (intention-to-treat) will be by linear regression, with treatment arm and baseline BSCVA pre-specified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty, and positive re-culture rate
Admission pattern and outcome of hypertensive disorders of pregnancy: a retrospective study of admitted cases at the Princess Christian Maternity Hospital in Freetown, Sierra Leone.
Get PDFBACKGROUND: Hypertensive disorders of pregnancy (HDP) are major contributors to maternal and neonatal mortality, particularly in low-resource settings. Pregnancy-induced hypertension accounted for 16% of maternal deaths in 2016, ranking as the second leading cause of maternal mortality in Sierra Leone. The country faces challenges of HDP management due to limited primary healthcare resources. This study investigated the admission patterns and outcomes of HDP at the Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone.
METHODS: A retrospective cross-sectional study was conducted, reviewing medical records of 572 pregnant women admitted with HDP at PCMH from January to December 2022. Hypertensive patients were classified according to established criteria for hypertensive pregnancy. Maternal and neonatal outcomes were categorised as favourable and unfavourable outcomes based on set criteria. The Chi-square Test and Fisher's exact test were performed to determine the association between admission patterns/management with maternal and neonatal outcomes using Statistical Package for Social Sciences version 27.
RESULTS: Out of the 572 HDP patients admitted cases reviewed, preeclampsia was the most common type of HDP 446 (78%). The majority of admissions occurred in the third trimester (95.6%) with common presenting symptoms including headache 64 (11.2%) and oedema 45 (7.9%). Most patients were treated with antihypertensive medications 547 (96%), predominantly combinations of two or more antihypertensive drugs 435 (76.0%). Maternal outcomes were favourable in 488 (85.3%), while neonatal outcomes were favourable in 396(69.2%). Gestational age on admission (p < 0.001), prolonged hospitalisation ≥ 7 days (p < 0.001), and elevated diastolic BP (p < 0.001) significantly predicted adverse neonatal outcomes, while gestational age on admission (p < 0.001) and prolonged hospitalisation ≥ 7 days (p < 0.001) were significantly associated with maternal outcome.
CONCLUSION: This study underscores the substantial burden of hypertensive disorders of pregnancy in Sierra Leone, with preeclampsia as the most common presentation, largely diagnosed in the third trimester. Despite favourable maternal outcomes, neonatal outcomes remain suboptimal. These findings underscore the need for improved antenatal screening, enhanced neonatal care, and adoption of predictive tools to support early detection and targeted intervention, particularly among younger, previously overlooked at-risk populations
Primary health care reforms: a scoping review.
Get PDFBACKGROUND: Demographic transitions, societal changes, and evolving population health needs are placing increasing pressure on healthcare systems, necessitating ongoing reforms. Primary health care (PHC) is a foundational component of Universal Health Coverage (UHC) and sustainable health systems. Many countries have undertaken PHC reforms aimed at improving population health. This review explores the objectives, implementation mechanisms, challenges, and outcomes of these reforms. METHODS: We conducted a systematic review of studies sourced from five databases (PubMed, Scopus, Proquest, Embase, and Science Direct), applying the World Health Organization's Health Systems Framework for deductive content analysis. The PRISMA guidelines were followed to ensure transparency and rigour in summarizing the published literature. RESULTS: A total of 147 types of interventions were identified, with most targeting service delivery and financing. Key reform objectives included expanding access to care, improving financing and payment systems, scaling up family physician programmes, increasing government health expenditure, leveraging private sector capacities, and strengthening the PHC workforce. These interventions resulted in expanded public health coverage, enhanced access to PHC, increased utilization of services among low-income populations, broader social insurance coverage, and improved service quality, contributing to better community health outcomes. CONCLUSION: The success of PHC reforms depends on their alignment with political, social, and cultural contexts, as well as consideration of the social determinants of health. Strong governmental support, managerial stability, decentralization, and regional capacity building are essential for sustainable implementation. Reforms should be gradual, supported by accurate forecasting, adequate and sustainable resources, and evidence-based strategies, drawing on international experiences
Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: A genomic and spatial analysis.
Get PDFDelays in identifying and treating individuals with infectious tuberculosis (TB) contribute to poor health outcomes and allow ongoing community transmission of M. tuberculosis (Mtb). Current recommendations for screening for tuberculosis specify community characteristics (e.g., areas with high local tuberculosis prevalence) that can be used to target screening within the general population. However, areas of higher tuberculosis burden are not necessarily areas with higher rates of transmission. We investigated the transmission of Mtb using high-resolution surveillance data in Blantyre, Malawi. We extracted and performed whole genome sequencing on mycobacterial DNA from cultured M. tuberculosis isolates obtained from culture-positive tuberculosis cases at the time of tuberculosis (TB) notification in Blantyre, Malawi between 2015-2019. We constructed putative transmission networks identified using TransPhylo and investigated individual and pair-wise demographic, clinical, and spatial factors associated with person-to-person transmission. We found that 56% of individuals with sequenced isolates had a probable transmission link to at least one other individual in the study. We identified thirteen putative transmission networks that included five or more individuals. Five of these networks had a single spatial focus of transmission in the city, and each focus centered in a distinct neighborhood in the city. We also found that approximately two-thirds of inferred transmission links occurred between individuals residing in different geographic zones of the city. While the majority of detected tuberculosis transmission events in Blantyre occurred between people living in different zones, there was evidence of distinct geographical concentration for five transmission networks. These findings suggest that targeted interventions in areas with evidence of localized transmission may be an effective local tactic, but will likely need to be augmented by city-wide interventions to improve case finding to have sustained impact
Surgical Risk and Long-Term Mortality With PCI and CABG in Ischemic Left Ventricular Systolic Dysfunction
Get PDFBackground: Coronary artery bypass grafting (CABG) improves survival compared with optimal medical therapy (OMT) alone in patients with ischemic left ventricular systolic dysfunction (iLVSD), but percutaneous coronary intervention (PCI) did not show clinical benefits in this population. However, the randomized controlled trials (RCT) evaluating these 2 revascularization modalities may differ in terms of baseline surgical risk. The aim is to investigate whether the treatment effects of PCI vs OMT, and of CABG vs OMT, are modified by baseline surgical risk. Methods: A post hoc analysis of the Revascularization for Ischemic Ventricular Dysfunction – British Cardiovascular Intervention Society 2 (REVIVED-BCIS2) and Surgical Treatment for Ischemic Heart Failure (STICH) RCT comparing PCI and CABG vs OMT, respectively, in patients with iLVSD, was conducted. The main outcome was all-cause mortality. Interaction between randomized treatment and baseline surgical risk, estimated by a modified European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II, was quantified. Results: A total of 666 participants from the REVIVED-BCIS2 trial and 1200 participants from the STICH trial were included. Participants from the REVIVED-BCIS2 trial were more likely to be in the highest tertile of baseline EuroSCORE-II (40.4% vs 29.4%, respectively; P < .001). In the REVIVED-BCIS2 trial, PCI had a consistent lack of effect on all-cause mortality vs OMT across baseline EuroSCORE-II tertiles (P for interaction = .79). In the STICH trial, CABG reduced mortality consistently vs OMT across baseline EuroSCORE-II tertiles (P for interaction = .64). Conclusions: In the 2 largest RCT evaluating the impact of revascularization in iLVSD and multivessel coronary disease, the treatment effect of PCI vs OMT, and of CABG vs OMT, was not modified by baseline surgical risk