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Asymptomatic school-age children carry the majority of transmissible Plasmodium falciparum infections
No full textBackgroundPersistent human-to-mosquito parasite transmission hinders malaria control in high burden settings. Understanding the human transmission reservoir can support the design of targeted interventions to reduce transmission.MethodsIn a year-long cohort study in rural Malawi, we used molecular methods to detect all Plasmodium falciparum (Pf) infections and those containing gametocytes, the parasite stage required for transmission, longitudinally at routine surveillance and sick visits. Using population-level analyses, we determined the demographic, temporal, and spatial clustering of infections containing gametocytes and gametocyte density, which predicts transmission.ResultsHere we show that gametocytes are not randomly distributed among the population or among individuals with Pf infections; gametocytes are detected in only 23% of the population. Among all participants, school-age children have significantly higher incidence of gametocyte-containing infections and high-density gametocyte infections compared to other groups. The presence of school-age children is a key driver of gametocyte frequencies and densities within households, even after adjusting for Pf infection levels. Based on the total gametocyte abundance in the population, we estimate that clearing infections from asymptomatic school-age children in the rainy season would decrease gametocyte abundance by 67% in the population.ConclusionsSchool-age children are the primary driver of ongoing Pf transmission in Malawi and interventions targeting school-age children are needed to effectively reduce Pf infection risk at a population level
Adapting health systems to men’s realities: An intersectional exploration of men’s barriers to TB care in Nigeria’s peri-urban communities
Full text linkAlthough men bear the brunt of TB morbidity and mortality globally and in Nigeria, understanding of men’s barriers to TB care is limited, including in peri-urban settlements where the risk of TB exposure is high. This research explored how masculinities combine with layers of disadvantage among men in peri-urban communities to limit their access to TB services. We conducted 20 in-depth interviews among 12 men and 8 women with presumptive or confirmed TB, 3 focus group discussions among 24 men in their workplaces, and interviews with 12 key informants exploring experiences of TB symptoms and care seeking. Audio recordings were transcribed and analysed using a reflexive thematic approach. Findings suggest many men in peri-urban settlements could not afford to show TB symptoms due to strict masculine gender expectations and norms (Theme 1), while official TB information was not tailored to reach them (Theme 2). When developing symptoms presumptive of TB, men negotiated the least disruptive way to wellbeing (Theme 3). After TB diagnosis, female healthcare workers used strategies such as baiting and negotiating to engage and retain men in care (Theme 4). In conclusion, health systems need to address the compounded barriers facing different groups of men in high-burden peri-urban settlements in Nigeria highlighted by this study and leverage existing community resources to create scalable adaptations to care that make services more responsive to their realities
Approximate Bayesian estimation of time to clinical benefit using Frequentist approaches:an application to an intensive blood pressure control trial
No full textBackground: Time to Benefit (TTB) is a critical metric in clinical practice, reflecting the duration required to achieve therapeutic goals post-treatment. Traditionally, TTB estimation has relied on Bayesian Weibull regression, which, despite its merits, can be computationally intensive. To address this, we propose and evaluate Frequentist methods as efficient alternatives to approximate Bayesian TTB estimation. Methods: We evaluated three Frequentist methods, parametric delta, Monte Carlo, and nonparametric bootstrap, for TTB estimation, comparing their performance with the Bayesian approach. Results: Extensive simulations demonstrated that the proposed Frequentist methods outperformed the Bayesian method in efficiency. Real-world data applications further validated these findings, with the Monte Carlo (MC) method exhibiting significantly faster computational speed compared to the nonparametric bootstrap, while the Bayesian method was the least efficient. Conclusions: The proposed Frequentist methods offer significant advantages to approximate the Bayesian approach for TTB estimation, particularly in efficiency and practicality. The Monte Carlo method, with its median point estimate and percentile confidence intervals, is the recommended choice for its balance of efficacy and expedience.</p
Visceral fat-to-muscle mass ratio to predict cardiovascular events and mortality in patients with chronic obstructive pulmonary disease A prospective cohort study
No full textBackground: Chronic obstructive pulmonary disease (COPD) patients can have increased cardiovascular events risk, which might be impacted by an imbalance between fat and muscle mass. This study explores the relationships between visceral fat-to-muscle mass ratio (VMR) and cardiovascular events and mortality in COPD patients. Methods: A prospective cohort study was performed on COPD patients from May 2018 to December 2023. Baseline information and VMR were collected. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, stroke, and exacerbation of congestive heart failure. Secondary outcomes were non-fatal cardiovascular events and mortality. Cox regression models, Kaplan–Meier curves, and restricted cubic splines were applied to assess the relationship between VMR and outcomes. Results: Of 1045 COPD patients, 138 (13.2 %) experienced MACE, and 169 (16.2 %) experienced non-fatal cardiovascular events and mortality during an average of 62-month follow-up period. VMR was nonlinearly associated with MACE (P = 0.023), with one-standard-deviation VMR increase leading to a 50 % increase in MACE risk (hazard ratio, HR, = 1.50, 95 % confidence interval, CI = 1.17–1.93) and 20 % increase in non-fatal cardiovascular event and mortality risk (HR = 1.20, 95 % CI = 1.08–1.34). The cumulative MACE incidence rose with higher VMR categories (log-rank P < 0.0001). In the fully adjusted model, the highest VMR quartile was significantly associated with a greater MACE risk than the lowest VMR (HR = 5.18, 95 % CI = 2.75–9.75). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses indicated a more significant VMR impact in those below 60. Conclusions: Elevated VMR was associated with increased MACE among COPD patients.</p
Introduction of confidential enquiry into maternal deaths in Ethiopia: Implementation and methodological considerations
Full text linkBackground: Despite having high maternal mortality, no recent confidential enquiry into maternal deaths (CEMD) has been implemented in Ethiopia. This paper outlines the introduction of the CEMD, major findings, and key methodological considerations. Methods: We embedded this CEMD in the ongoing Ethiopian Obstetric Surveillance System (EthOSS), a regional system that monitors a range of major obstetric conditions in eastern Ethiopia. Multiple methods (both qualitative and quantitative) were used to collect, analyse and report the data. A multidisciplinary committee was established and trained on principles and methodology of CEMD by international experts. The CEMD committee conducted two plenary CEMD sessions to review maternal deaths reported from April 1, 2021, to March 31, 2022, from 13 hospitals in the EthOSS consortium. Each case was assessed for causes, contributing factors, delays in care using the three-delays model, preventability, and recommendations for improving care. Results: Out of 70 maternal deaths, in 59 there was enough information to enable a review by the committee; 27/59 (46%) and 15/59 (25%) were caused by obstetric haemorrhage and hypertensive disorders of pregnancy respectively. In 55/59 (93%), at least one of the three delays was identified: delay one (seeking care) in 48 (81%), delay two (reaching an appropriate facility) in 52 (88%), and delay three (receiving adequate care) in 54 (92%). The review indicated that almost all reported deaths could have been prevented with better care. Conclusions: Almost all the maternal deaths in the region were considered preventable. Training for improving providers’ clinical skills, improving availability of blood and basic supplies, strengthening postpartum monitoring, and referrals were recommended for saving lives through reducing preventable maternal deaths.</p
Patient and public involvement, engagement, and participation in practice: co-production of a creative health approach and theory of change through the ReCITE consortium-building project in Liverpool
Full text linkBackgroundCo-production with public stakeholders is increasingly recognised as an important approach to ensuring health research is relevant to communities and interventions and likely to generate sustainable change. Ideally, co-production needs to be sustained throughout different stages of research and allow stakeholders ownership of the research agenda. We explore a case study of iterative co-production conducted over a nine-month period with a wide range of disparate stakeholders that transformed into a research-ready consortium able to design and obtain funding for a creative health research programme.Main bodyThe ReCITE consortium is comprised of academics, creatives, and specialists in capacity development and community engagement in Liverpool, UK. Its main focus is health equity and coming up with new ways of working to tackle entrenched, avoidable and unfair differences in health. ReCITE led a series of six workshops in 2023 to co-produce a research programme to investigate creative approaches for improving health equity. Fifty-six stakeholders from the academic, creative and arts, health, community and voluntary sectors participated across six workshops that sought broad engagement and consolidated stakeholder input to develop a research agenda and expand the consortium. Common emerging themes were: (1) understanding complexities in funding creative health; (2) investigating storytelling as a catalyst for change; (3) achieving change through collective action; (4) the role of creative advocacy to change societal and funding structures; (5) evidencing the impact of community-led creative health interventions on health equity. These formed multiple co-produced outputs, including five pillars of a theory of change for the research that underpinned the research questions and determined five interventions to take forward by the research-ready consortium to securing funding for future work.ConclusionThe iterative process of gaining stakeholder input, consolidating it, and seeking further input, helped to incorporate the perspectives of different stakeholder groups into different project outputs. Equitable power-sharing guided decision-making over what to prioritise was important in building ownership of the research agenda and trust among stakeholders. However, this was a lengthy iterative process and sustaining time commitment was difficult for those stakeholders who were not fully funded to participate
Cluster minimal sufficient balance (CMSB) an efficient covariate balancing randomization method for cluster randomized trials
Full text linkBACKGROUND: Cluster randomized trials (CRTs) require balanced baseline covariates to yield unbiased estimates of treatment effects. Existing approaches such as constrained randomization can improve balance but may compromise allocation randomness. We introduce Cluster Minimal Sufficient Balance (CMSB), a cluster randomization method designed to enhance covariate balance while preserving allocation randomness and computational efficiency. METHODS: CMSB integrates dynamic imbalance monitoring with conditional biased randomization into a single procedure. The method accommodates both continuous and categorical covariates and was evaluated through simulation studies comparing its performance with constrained randomization, simple randomization, block randomization, stratified randomization, and minimization across varying numbers of clusters and covariate dimensions. An empirical application further assessed its practical utility. RESULTS: In high-dimensional settings with 10 covariates, CMSB achieved a 45% greater improvement in covariate balance compared to constrained randomization, while maintaining near-optimal allocation randomness (correct guess probability: 49.79% versus 61.03% for minimization). CMSB reduced mean allocation time from over 100 s under constrained randomization to 0.116 s per allocation, even when simulating up to 2,000 randomization schemes. In the empirical application, CMSB demonstrated a 76% improvement in covariate balance relative to simple randomization. CONCLUSIONS: CMSB effectively balances the competing demands of covariate balance, allocation randomness, and computational efficiency in cluster randomized trials. Its ability to handle high-dimensional covariates makes it particularly suitable for large-scale trials.</p
Optimizing insecticide deployment strategies to delay quantitative resistance in mosquito populations
Full text linkThe large-scale use of insecticides remains a cornerstone of malaria vector control, but its long-term effectiveness is undermined by the evolution of quantitative insecticide resistance (qIR) in mosquito populations. We develop and analyze a mathematical model to identify optimal deployment strategies for two insecticides that differ only in their relative efficacy against target mosquito populations. Resistance is represented as a continuous phenotypic trait influencing mosquito fecundity and mortality, and the model accounts for successive deployment periods. Our results show that when mutational variance is high, the optimal strategy is to deploy the most effective insecticide at full coverage, regardless of its relative efficacy or pre-deployment exposure history. By contrast, when mutational variance is low, optimal deployment requires a transient reduction in coverage during early periods, with a threshold effect driven by both relative efficacy and initial exposure rates. Crucially, we find that, under the hypothesis that the first insecticide is ineffective against mosquitoes, simultaneous use of both insecticides is rarely optimal. Instead, sequential deployment–using one insecticide until resistance reaches a critical threshold, followed by optimal use of the second–delays resistance evolution and improves long-term control. These findings provide a theoretical foundation for adaptive qIR management strategies aimed at prolonging the effectiveness of insecticides in malaria vector control.</p
Adiposity and reproductive characteristics across the lifespan: a multi-ethnic population-based study in Northwest China
Full text linkBackground: Reproductive characteristics significantly shape physiological adaptations, little is known about how they relate to adiposity in women of multi-ethnic regions undergoing a rapid increase in obesity burden. This study aims to address this gap by assessing how reproductive patterns correlate with adiposity and identifying potential moderating factors among Chinese adults. Methods: In 2018–2019, 107,679 participants from the Regional Ethnic Cohort Study in China were included in this cross-sectional analysis. Restricted cubic spline and generalized linear regression models were used to assess the association of reproductive characteristics such as age at menarche and menopause, number of children, menopause status, duration of post-menopause, and reproductive years, as well as reproductive pattern with adiposity using body mass index (BMI). Reproductive pattern was characterized using a Higher-Risk Reproductive Score (HRRS), which incorporates key landmarks such as early menarche (≤ 12 years), having ≥ 3 children, and later age at menopause (≥ 51 years). Results: Females’ mean BMI was 24.4 (standard deviation, SD 3.8) kg/m2, with the median age at menarche and menopause of 15.0 (interquartile range, IQR 2.0) and 49.0 (IQR 5.0), median number of children and reproductive years of 2.0 (IQR 1.0) and 34.0 (IQR 6.0). Age at menarche was non-linearly associated with an average drop of 0.13 kg/m2 in BMI, particularly in Uyghur ethnic and younger adults. Age at menopause and reproductive years was non-linearly related to higher BMI by 0.05 and 0.07 kg/m2 per year delay. Adiposity exhibited an inverted U-shape with number of children. The duration of post-menopause correlated with a BMI reduction of 0.08 kg/m² on average. The HRRS was associated with an increase of 0.56 kg/m2 in BMI. Conclusions: Among Chinese women, earlier age at menarche and later age at menopause were associated with increased adiposity. Adiposity showed an inverted U-shaped relationship with number of children, and a higher-risk reproductive pattern was linked to increased adiposity.</p
Incorporating findings from a vaccine refusal study to develop a community play to improve understanding of maternal vaccines in rural Kilifi, Kenya
Full text linkInnovative approaches are urgently needed to address the growing concern of vaccine hesitancy. Used effectively, community theatre has the potential to promote health knowledge and attitude change as it encourages community dialogues and information sharing. We used research findings from a vaccine hesitancy study to develop a community play on maternal vaccines. The development of the script for the play was an iterative process between a local community theatre group and the research team. Outreaches in three community open spaces were held. Evaluation comprised notes and observations from outreaches and group discussions among community audiences. Discussions were recorded, transcribed and translated to English and analysed using thematic approach. We produced an entertaining and culturally relevant performance that conveyed key messages about maternal vaccines in a clear and accessible manner in the local language. Community feedback highlighted its effectiveness in dispelling rumours and correcting misinformation while enhancing knowledge and understanding of maternal vaccination. Community members appreciated that it was informative and educational, demonstrating how research-based theatre can serve as an innovative tool for public health communication. Researchers working in comparable contexts may adapt this approach to address vaccine hesitancy in their own settings.</p