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Effectiveness of the RTS,S/AS01E malaria vaccine in a real-world setting over 1 year of follow-up after the three-dose primary schedule: an interim analysis of a phase 4 study in Ghana, Kenya, and Malawi.
Get PDFBACKGROUND: RTS,S/AS01E was first introduced within the Malaria Vaccine Implementation Programme in selected areas in Ghana, Kenya, and Malawi. A series of post-introduction observational studies were initiated in these areas to assess RTS,S/AS01E safety and effectiveness in real-world settings. Here, we report the results of the interim analysis of the EPI-MAL-003 study secondary objectives related to vaccine effectiveness. METHODS: EPI-MAL-003 was a phase 4, disease surveillance study with prospective cohort event monitoring. The study was performed in routine medical practice settings at 12 sites (four per country) in Ghana, Kenya, and Malawi. Children younger than 18 months were enrolled in exposed clusters (sites where RTS,S/AS01E was introduced) and unexposed clusters; data were collected via active surveillance. In an interim analysis, we estimated the effect of vaccination on the incidence of malaria, all-cause hospitalisations, and malaria-related hospitalisations, the prevalence of anaemia among hospitalised children, and mortality over 1 year of follow-up after primary vaccination with three RTS,S/AS01E doses. These endpoints were analysed in the effectiveness analysis set. The primary endpoints are reported elsewhere, together with secondary safety endpoints. This study is registered with ClinicalTrials.gov, NCT03855995, and is completed. FINDINGS: The first child was enrolled on March 21, 2019, and the cutoff date for the current analysis was Nov 2, 2023. 45 000 children were enrolled (22 426 [49·8%] were female and 22 574 [50·25%] were male). 39 463 children were included in the analyses. When comparing vaccinated children from exposed clusters with unvaccinated children from unexposed clusters, country-adjusted incidence rate ratios were 0·70 (95% CI 0·67-0·73; p<0·001) for any malaria, 0·42 (0·30-0·60; p<0·001) for severe malaria, 0·64 (0·56-0·72; p<0·001) for malaria-related hospitalisations, 0·79 (0·74-0·84; p<0·001) for all-cause hospitalisations, and 0·83 (0·64-1·09; p=0·18) for all-cause mortality. The adjusted odds ratio for the prevalence of anaemia among children who were hospitalised (vaccinated children from exposed clusters vs unvaccinated children from unexposed clusters) was 0·81 (95% CI 0·73-0·90; p<0·001). Similar trends were observed in a before-after comparison with unvaccinated children enrolled in the EPI-MAL-002 study conducted before the RTS,S/AS01E introduction. INTERPRETATION: Over 1 year of follow-up after the third vaccine dose, vaccination with RTS,S/AS01E in real-world settings showed significant reductions in malaria burden. These findings reinforce the continued use of RTS,S/AS01E vaccination in children as an effective public health measure to reduce malaria-related illness and mortality in endemic regions, and highlight its relevance for future malaria control strategies. FUNDING: GSK
Unpacking postpartum depression in rural India: an integrated analysis of risk factors at 12 months and child development outcomes at 18 months of age - findings from the SPRING study.
Get PDFBACKGROUND: Postpartum depression (PPD) negatively affects maternal well-being and early child development (ECD). While research often focuses on the early postpartum depression, symptoms can emerge or persist later in the first year, potentially affecting mothers and children differently at this stage. Yet, the 12-month postpartum period remains understudied globally, particularly in low-resourced settings where contextual stressors are pronounced. This study addresses the urgent need to understand later-stage postpartum depression and how it influences child development at 18 months, a critical period for identifying early developmental delays. METHODS: We analysed longitudinal data from a cluster randomised trial of an integrated mother-child intervention in rural India (Haryana). Mother-child dyads enrolled between 18 June 2015 and 1 July 2017 were assessed for PPD at 12 months using Patient Health Questionnaire-9 (PHQ-9) and for child development at 18 months with Bayley Scales of Infant and Toddler Development-III. We examined PPD risk factors using logistic regression and the association between PPD and ECD through multinomial regression models, accounting for covariates and clustering. RESULTS: Among 2007 mothers assessed at 12 months, PPD prevalence was 13.1% (PHQ-9 ≥ 5). Maternal adverse events (OR = 1.53, CI: 1.35-1.73, p < 0.001) and psychosocial stress (OR = 1.10, 95% CI: 1.08-1.12, p < 0.001) increased PPD odds, while psychosocial support (OR = 0.97, 95% CI: 0.96-0.98, p < 0.001) and higher socio-economic status (OR = 0.72, 95% CI: 0.64-0.79, p < 0.001) reduced them. Among 1250 dyads assessed at 18 months, PPD predicted mild-to-moderate (RRR = 1.63, 95% CI: 1.13-2.36, p < 0.01) and severe (RRR = 1.64, 95% CI: 1.03-2.61, p < 0.05) language delays, but not cognitive or motor delays. These associations were not significant after adjustment. CONCLUSIONS: This is among the first Indian studies to longitudinally examine the association between postpartum depression at 12 months and child development at 18 months, addressing a major evidence gap in rural settings. The study identified a distinct risk profile for postpartum depression shaped by socioeconomic and maternal adversity. Postpartum depression showed domain-specific associations with language delays, explained by contextual factors. These findings highlight the need to integrate evidence-based mental health screening and support for at-risk mothers and children into existing maternal and child health services in rural contexts
Associations of menstrual health with school absenteeism and examination performance among Ugandan secondary school students: A prospective study.
Get PDFBACKGROUND: Relatively few studies have quantified the amount of school missed due to poor menstrual health, or the impact of poor menstrual health on examination performance. METHODS: We conducted secondary observational analyses from data nested within a cluster-randomised trial of a menstrual health intervention in 60 Ugandan secondary schools (The trial is registered as ISRCTN45461276). We used baseline data from trial participants in both arms, and endline data from the control arm participants. School absenteeism was estimated as the self-reported number of days absent due to menstruation per month and examination performance was assessed by an independently set assessment by the Uganda National Examination Board. We estimated adjusted incidence rate ratios (aIRR) for associations with school absenteeism, using negative binomial regression adjusted for school-level clustering. We estimated adjusted standardised mean differences (aSMD) in examination scores using mixed-effects linear regression. RESULTS: Of the 3312 participants who reported menstruating in the past 6 months at baseline, 323 (9.8%) reported missing at least one day of school per month due to menstruation (mean days missed = 0.30 per month, 95%CI 0.27-0.34). Similarly, of the 1192 participants in the trial control arm seen at endline, 135 (11.3%) reported missing at least one day due to menstruation (mean days missed = 0.31 per month (95%CI 0.27-0.37)). There was evidence that menstrual-related absenteeism and poorer examination performance at endline were both associated with baseline use of inadequate menstrual materials, negative menstrual attitudes, unmet menstrual practice needs, and experience of menstrual-related teasing. In addition, absenteeism due to menstruation was associated with menstrual pain, and poorer examination performance was associated with poorer baseline menstrual knowledge. CONCLUSION: Among Ugandan students, multiple dimensions of menstrual health are associated with school absenteeism and examination performance. TRIAL REGISTRATION AND RECRUITMENT DETAILS: ISRCTN ISRCTN45461276
Integrated indicators for tracking climate mitigation and adaptation: a protocol for a rapid review with a focus on health co-benefits and trade-offs
Get PDFBackground Climate mitigation and adaptation policies influence a wide range of climate-sensitive health determinants, yet current monitoring systems often treat these domains separately. Integrated indicators capable of capturing co-benefits and trade-offs across climate and health, and the synergies between mitigation and adaptation, could strengthen accountability and support coherent policymaking. This rapid review aims to identify how health-related indicators used in climate adaptation and mitigation intersect, and to assess their potential for integrated monitoring frameworks. Methods This protocol outlines a rapid review conducted in accordance with established rapid-review guidance. The review builds on existing indicator sets from national climate–health assessments and additional evidence from mitigation-focused syntheses. A multi-layered search strategy will be applied in PubMed and targeted grey literature sources, limited to studies published from 2000 onward in high- and upper-middle-income settings relevant to the United Kingdom. Screening will follow an adapted Population–Intervention–Outcome framework, with dual-reviewer piloting and single-reviewer screening thereafter. Data extraction will capture study characteristics; indicator details; health-related exposures and outcomes; evidence of co-benefits or trade-offs; equity considerations; and policy relevance. Quality appraisal will use the STROBE checklist for observational studies and an adapted GHEMMS tool for modelling studies. Findings will be synthesised narratively and summarised in tables, informing a long list of candidate indicators for subsequent assessment by policy partners. Results As this is a protocol, no results are yet available. Planned outputs include coded evidence on cross-domain indicator usage, consistency of health pathways, equity gaps, and the strength and feasibility of candidate indicators. Conclusions This rapid review will provide the first structured synthesis of health-related indicators that bridge climate mitigation and adaptation. The findings will support the development of integrated monitoring approaches that better reflect the interdependencies of climate action and health, with direct relevance for ongoing national and international indicator-setting efforts.</ns3:p
Single genome amplification and molecular cloning of HIV-1 populations in acute HIV-1 infection: implications for studies on HIV-1 diversity and evolutionary rate.
Get PDFBACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is one of the fastest-evolving human pathogens. Understanding HIV-1 transmission, within-host adaptation, and evolutionary dynamics is pivotal for development of interventions and vaccines. HIV-1 infection is generally caused by a single transmitted founder virus (TFV), and TFV sequences are typically obtained using single genome amplification (SGA). However, suboptimal sample quality can cause sequencing failures, representing considerable losses considering the scarcity of acute HIV-1 infection (AHI) samples. Sequencing failures may be mitigated by molecular cloning (MC), which can be less vulnerable to sample quality but more susceptible to polymerase chain reaction (PCR) errors. Here, we explore the feasibility of supplementing SGA with MC data using samples from clinical and research cohorts to determine whether sequence diversity and evolutionary rate estimates are comparable between the techniques.
METHODS: Plasma samples were selected from participants with documented AHI from an East African research cohort (the International AIDS Vaccine Initiative, 2006-2011) and a clinical cohort from Sweden (1983-2011). SGA and MC sequencing were done on the HIV-1 env V1-V3 region (~940 base pairs). Within-host sequence diversity was determined from maximum likelihood phylogenetic trees, and evolutionary rate by Bayesian phylogenetic analysis. Highlighter plots, Hamming distances, and assessment of star phylogenies were used to quantify TFVs.
RESULTS: One hundred participants (median age 30.3 years, 15% female), contributing 350 samples from four longitudinal time points, 10-540 days post-infection, met the inclusion criteria. SGA succeeded on 90% of research cohort and 48% of clinical cohort samples. Comparative analysis of linked SGA and MC data from 10 samples indicated that approximately eight sequences were necessary for diversity estimates. Consistently higher sequence diversity was observed among MC relative to SGA sequences (median [IQR]: 0.009 [0.003, 0.015] and 0.004 [0.001, 0.012] substitutions/site, P = .002), whereas evolutionary rates were comparable between the two methods (0.016 [0.012, 0.019] and 0.011 [0.008, 0.020] substitutions/site/year, P = .232). Five participants with samples obtained within 45 days post-infection were eligible for TFV quantification, and all found to have one TFV using both techniques.
CONCLUSION: MC data is a suitable supplement for SGA-based HIV-1 studies to preserve the value of precious samples for analysis of evolutionary rate, but not for sequence diversity
Trends in Median Age at First Sex and Age at First Marriage Among Youth in Tanzania: Accelerated Failure Time Model (1994-2016).
Get PDFUnderstanding trends in age of first sex and first marriage is vital for interventions addressing sexually transmitted infections (STIs/HIV) and youth sexual behavior. Shifts in these milestones affect fertility, contraceptive use, and STI/HIV dynamics. Traditional descriptive statistics often overlook younger populations, leading to inaccurate trend assessments. This study analyzed trends in median age at first sex and first marriage using survival analysis. Data from eight surveys within Magu Health and Demographic Surveillance System (1994-2016) were analyzed, focusing on individuals aged 15-24 years. The accelerated failure time (AFT) model with log-logistic distribution estimated these medians. Results showed an increase in median age at first sex by one year for both sexes and in first marriage by one year for females and two years for males. The AFT model captured gradual increases from 2003-2004 to 2015-2016 for females and 2003-2004 to 2010 for males, while standard descriptive statistics showed no changes in specific periods: age at first sex, 1996-1997 to 2012-2013 (females) and 2003-2004 to 2012-2013 (males); first marriage, 1994-1995 to 2015-2016 (females) and 2003-2004 to 2010 (males). Individuals with no education had lower median age at first sex (males: 17.1 vs. 18.3 years; females: 16.2 vs. 18.2) and first marriage (females: 18.0 vs. 21.3) than those with secondary or higher education. HIV-positive individuals experienced slightly earlier age at first sex and first marriage than negative individuals. Education plays a pivotal role in delaying these events. The AFT model enriches trend assessment
Clinical and cost-effectiveness of medical management versus surgery for deep infiltrating endometriosis: synopsis from the DIAMOND RCT.
Get PDFBACKGROUND: Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments. OBJECTIVE(S): To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis. DESIGN AND METHODS: A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis. SETTING AND PARTICIPANTS: Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres. INTERVENTIONS: Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone. MAIN OUTCOME MEASURES: The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes. RESULTS: Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation. LIMITATIONS: The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group. CONCLUSIONS: The clinical question regarding the effectiveness of surgical removal or optimised medical treatment for deep endometriosis remains relevant. It remains unanswered because of the early closure of the trial due to failure to recruit participants. To deliver important surgical studies in this area will require potentially different study designs with new and innovative strategies to educate, enthuse and incentivise both patients and clinicians. There is a need for simplified processes to expedite study site set up, along with increased accountability and funding to motivate local research and development departments and principal investigators. FUTURE WORK: The DIAMOND trial has shed light on some of the obstacles preventing the successful delivery of robust trials in deep endometriosis thereby informing future study designs. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR130310
Developing guidance on assessing and managing conflicts of interest for a complex public health research consortium
Get PDFWhat is new?
Conflicts of interest in public health research are often addressed through disclosure alone, which is insufficient to protect research integrity. This paper reflects on the process of developing and implementing a conflict of interest policy for a complex, multi-institutional and multi-sector research consortium.
What was the approach?
The research uses a reflective case study approach, drawing on documents and reflexive notes to document the development and implementation of a COI policy in a research consortium on the commercial determinants of health.
What is the academic impact?
The paper identifies practical steps and considerations for managing conflicts of interest in complex collaborative research settings, reflecting on key questions and challenges encountered during this process. It details an empirically grounded framework for governing conflicts of interest in research and advances understanding of how such policies can be operationalised in practice.
What is the wider impact?
The paper offers actionable guidance on designing and embedding conflict of interest policies in complex collaborations, supporting more robust research governance and helping to safeguard the integrity of public health research
Weaponizing Kinship: A Demographic Analysis of Bereavement in the Colombian Conflict
Get PDFThe ongoing Colombian armed conflict has produced widespread homicides and enforced disappearances, as armed actors used violence to terrorize communities and consolidate power. Family bereavement—one of the most pervasive and enduring consequences of this violence—remains critically understudied from a quantitative perspective. We quantify the population burden of bereavement—ever having lost a family member to conflict—using kinship demographic models applied to 1985–2018 data compiled by the Truth Commission and the Special Jurisdiction for Peace, corrected for under‐registration. By 2018, an estimated 7.5% of Colombians had lost a close relative and about 40% had lost at least one family member to conflict. Even assuming an over‐optimistic scenario with no post‐2018 violence, demographic projections indicate that conflict‐related bereavement will remain visible well into the 2080s. Results are robust to subnational heterogeneity and alternative “bereavement memory” specifications. Reading these estimates alongside the Commission's qualitative record underscores bereavement as a strategic mechanism of repression aimed at fracturing kin networks and community cohesion rather than a collateral by‐product. Our demographic profiling of the bereaved informs population‐health and psychosocial responses, including support for relatives of the disappeared, and can guide reparations and community‐based programs that rebuild kin and neighborhood ties while strengthening guarantees of non‐repetition
Spatial and temporal inequalities in malaria incidence and mortality among children aged 0-4 years in Nigeria: a subnational analysis, 2010-2019.
Get PDFBACKGROUND: Malaria remains a leading cause of morbidity and mortality among children under five in Nigeria, with pronounced subnational disparities. This study analyzed the temporal and spatial inequalities in malaria incidence and mortality among children aged 0-4 years across Nigeria's 36 states and the Federal Capital Territory from 2010 to 2019.
METHODS: Estimates from the Institute for Health Metrics and Evaluation (IHME) were analyzed using the WHO Health Equity Assessment Toolkit (HEAT). Subnational inequalities were quantified using five metrics: coefficient of variation (COV), difference (D), ratio (R), population-attributable risk (PAR), and population-attributable fraction (PAF).
RESULTS: From 2010 to 2019, national malaria incidence declined from 103 to 74.5 cases (27.7% reduction), while mortality fell from 477.3 to 237.6 deaths per 100,000 (50.2% reduction). However, progress was uneven. Northern states such as Zamfara, Kano, and Katsina had the highest baseline burden in 2010 (incidence > 150 per 1000; mortality > 700 per 100,000) and, despite declines, remained among the most affected in 2019. Southern states including Lagos, Delta, and Anambra consistently recorded lower burdens (incidence < 60 per 1000; mortality < 300 per 100,000). Subnational inequality narrowed over time, with incidence COV peaking at 46.3% in 2013 before falling to 28.1% in 2019, and mortality COV declining from a 2013 peak of 42.9% to 22.3% in 2019.
CONCLUSION: Nigeria's malaria incidence and mortality among under-five children have decreased, but subnational disparities persist, particularly in northern states, although a reduction in D and R values indicates modest progress in equity, necessitating geographically targeted interventions