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Shigella sonnei: epidemiology, evolution, pathogenesis, resistance and host interactions.
Get PDFShigella sonnei is a major cause of diarrhoea globally and is increasing in prevalence relative to other Shigella because of multiple demographic and environmental influences. This single-serotype species has traditionally received less attention in comparison to Shigella flexneri and Shigella dysenteriae, which were more common in low-income countries and more tractable in the laboratory. In recent years, we have learned that Shigella are highly complex and highly susceptible to environmental change, as exemplified by epidemiological trends and increasing relevance of S. sonnei. Ultimately, methods, tools and data generated from decades of detailed research into S. flexneri have been used to gain new insights into the epidemiology, microbiology and pathogenesis of S. sonnei. In parallel, widespread adoption of genomic surveillance has yielded insights into antimicrobial resistance, evolution and organism transmission. In this Review, we provide an overview of current knowledge of S. sonnei, highlighting recent insights into this globally disseminated antimicrobial-resistant pathogen and assessing how novel data may impact future vaccine development and implementation
Estimating future variant Creutzfeldt-Jakob disease cases in the UK: a cohort-based probabilistic model
Get PDFBackground: Variant Creutzfeldt–Jakob disease (vCJD) is a fatal prion disorder linked to dietary exposure to bovine spongiform encephalopathy (BSE). The epidemic peaked in the early 2000s, and no new cases have been reported in the UK since 2016. However, uncertainties remain regarding potential future cases, particularly in individuals with non-MM prion protein gene codon 129 genotypes, and possible secondary transmission via blood transfusion. We aimed to update risk estimates with recent data, informed by a probabilistic modelling approach.
Methods: We developed a cohort-based probabilistic model for variant CJD incidence incorporating genotype-specific attack rates and incubation periods, accounting for competing mortality risks. Model parameters were calibrated using historical case data and life-table analyses. We explored multiple scenarios, including sensitivity analyses with alternative incubation period distributions and potential missed diagnoses. Secondary transmission risk was assessed using historical transfusion-linked cases and epidemiological data.
Findings: In the base-case scenario, our model estimates a 48% probability that no further vCJD cases will occur, with a mean forecast of 2.7 additional cases. Allowing for missed past cases, estimates increased to a mean of 3.0 cases (one missed case) and 4.9 cases (four missed cases). Sensitivity analysis using a Cauchy incubation period distribution rather than a log-normal distribution increased estimates to 6.6, 9.4, and 17.9 cases, respectively. A plausible worse-case scenario, assuming very long incubation times and higher susceptibility in non-MM individuals, projected up to 65 cases of vCJD over coming decades, peaking in the 2030s. Secondary transmission risk remains negligible given transfusion safety measures, including leukodepletion since 1999.
Interpretation: Our findings suggest that vCJD is unlikely to re-emerge at significant levels. However, ongoing case ascertainment and scrutiny remains critical due to uncertainties in non-MM incubation and potentially, the emergence of previously unrecognised prion strains. Continued neuropathological case investigation, maintenance of core blood safety policies, and periodic risk reassessments are essential to ensure public health preparedness and avoid unnecessary restrictions.
Funding: No specific funding other than salaries of the authors
Composite endpoints in health technology assessment: Part 2 - expanding the evidence base with a framework for best modeling practice.
Get PDFThe first paper of this two-part series critically examined the role of composite endpoints in health technology assessments (HTAs) and outlined strategies for determining whether to employ the composite estimate of treatment effect or disaggregate into the component endpoints of the composite and apply separate treatment effects within a modeling framework. In this second paper, we expand the discussion beyond a pivotal trial and consider the way in which additional evidence from the same indication for different drugs in the same class, or the same drug for different indications, could be employed within HTAs. We offer a continuation of the case study of dapagliflozin for the treatment of heart failure with preserved or mildly reduced ejection fraction, where the evidence base was expanded to consider empagliflozin for the same indication, as well as both dapagliflozin and empagliflozin for heart failure with reduced ejection fraction. We conclude that, where there are multiple drugs in the same class and/or multiple indications for a class of drugs, HTAs should consider the exchangeability of the information that comes from additional evidence beyond the pivotal registration study. Further, we show how consideration of this additional evidence can support the decision concerning whether to disaggregate the components of a composite endpoint or employ the treatment effect from the composite for each endpoint
Does cytomegalovirus infection increase the risk of tuberculosis in UK children?
Get PDFThere is a hypothesized association between pre-existing cytomegalovirus (CMV) infection and risk of acquiring tuberculosis (TB). We aimed to explore if CMV seroprevalence and CMV IgG levels in children were associated with TB disease or Mycobacterium tuberculosis (Mtb) infection compared with children who were exposed to TB but remained well. In this cross-sectional analysis from an observational cohort study of children exposed to TB in their household in the UK, we examined samples from 75 participants, of whom 40 (53%) were male. Median age of the cohort was 6 years (interquartile range: 3-11 years). In total, 21 (28%) children had TB disease, 27 (36%) had Mtb infection and 27 (36%) had TB exposure only. There was no increased risk of TB in children who were CMV-seropositive (OR 2.18 [0.75-6.48]), and there were no differences in CMV IgG quantification by TB category. There was no detectable CMV viraemia in any of the children in our study. We found higher levels of CMV seroprevalence (49%) than previously described in the UK. In this small study of children exposed to TB, in a low-TB burden setting, we found no association between CMV serostatus or CMV IgG levels and TB status.This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'
Factors associated with stillbirth in São Paulo, Brazil: FetRiskS - a multidisciplinary case-control study.
Get PDFBACKGROUND: Stillbirth remains a significant public health issue, with socioeconomic, demographic, environmental, behavioral, healthcare, and biological factors influencing its occurrence. This study aimed to investigate the risk factors for stillbirths in São Paulo, Brazil. METHODS: This population-based case-control study included stillbirths (cases) and live births (controls) from 14 public hospitals in the city of São Paulo, Brazil. Data were obtained from interviews with women after delivery, hospital records, antenatal care registries, placental samples, and maternal blood samples for analysis of infection biomarkers. A logistic regression model was used to estimate the odds ratio (OR) with a 95% confidence interval. RESULTS: The study included 401 stillbirths (348 antepartum and 53 intrapartum) and 419 live births. The final model identified significant risk factors for stillbirth, including the absence of a partner (OR = 1.76; 95%CI: 1.15–2.68), smoking during pregnancy (OR = 1.94; 95%CI: 1.10–3.47), inadequate antenatal care access (OR = 2.15; 95%CI: 1.38–3.39), hyperglycemia (OR = 1.91; 95%CI: 1.21–3.03), the presence of placental lesions (OR = 3.15; 95%CI: 2.20–4.52), fetal growth restriction (OR = 6.16; 95%CI: 3.76–10.4), and congenital malformations (OR = 4.25; 95%CI: 2.42–7.67). CONCLUSIONS: This study identifies critical maternal and fetal factors associated with stillbirth risk in a middle-income country, showing its complex profile. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-025-08427-w
Case Reports of Human Monkeypox Virus Infections, Uganda, 2024.
Get PDFMpox is a zoonotic disease caused by the monkeypox virus. We report on human mpox cases in Uganda identified by PCR and confirmed by deep sequencing. Phylogenetic analysis revealed clustering with other clade Ib sequences associated with recent outbreaks in the Democratic Republic of the Congo
Impact of SPRING, an Integrated Mother-Child Focused Psychosocial Home-visiting Intervention, on Postpartum Depression in Rural India: A Cluster Randomized Controlled Trial.
Get PDFBACKGROUND: Post-partum depression (PPD) adversely affects maternal and child health, yet evidence for integrated mother-child interventions remains limited in low-resource settings. We evaluated the impact of SPRING (Sustainable Programme Incorporating Nutrition and Games), an integrated mother-child psychosocial home-visiting intervention, on PPD outcomes in rural India. METHOD: A cluster-randomized controlled trial evaluated the intervention's impact across 120 villages (24 clusters). Mother-infant dyads were identified through house-to-house surveillance, with PPD measured at 12 months post-partum using the Patient Health Questionnaire-9 (PHQ-9). While the intervention aimed to improve child growth and development by indirectly addressing maternal mental health, this article reports specifically on PPD outcomes. RESULTS: Among 2007 mothers completing assessments, PPD prevalence was 13.1%, with no significant difference between arms (RR = 0.98, 95% CI: 0.69-1.39, p = .90). No effect of intervention was found on PPD (mean PHQ-9 score 1.8 [SD 2.68] in the intervention group and 1.9 [SD 2.79] in the control group; effect size -0.02; 95% CI: -0.11, 0.07; p = .68). Analyses were intention-to-treat. CONCLUSIONS: The lack of measurable impact in our study highlights two key considerations. First, integrated mother-child psychosocial interventions may require more targeted strategies to address depressive symptoms and reduce PPD. Second, implementation challenges, such as coverage and uptake, likely influence effectiveness. Notably, at least one in eight mothers in our study experienced PPD at 12 months post-partum, aligning with other Indian studies. This persistent burden, alongside unmet mental health needs, emphasizes the urgency for future integrated mother-child interventions to include PPD-specific components and critically monitor implementation, especially in rural settings
Improving the Reporting on Health Equity in Observational Research (STROBE-Equity): Extension Checklist and Elaboration.
Get PDFIMPORTANCE: Observational studies can provide valuable insights to inform decisions on health equity. Existing guidelines for reporting such studies, such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, currently lack specific considerations for reporting on health equity. Health equity is defined as the absence of avoidable and unfair differences that may exist across individuals and populations due to structural and systematic inequities in living and working conditions, opportunities, and resources. To address this gap, the research team developed an extension of the STROBE statement (STROBE-Equity) that focuses on reporting health equity data and considerations.
OBSERVATIONS: This consensus statement followed steps for developing a consensus- and evidence-based guideline using an integrated knowledge translation approach to ensure engagement of knowledge users from diverse disciplines and perspectives. Selection criteria for the research team and steering committees prioritized diversity across age, gender, and geography. The STROBE checklist was extended to include 10 items specifically aimed at reporting health equity considerations. To develop these items, the research team drew on evidence from empirical studies including a scoping review of the literature, methodological review, key informant interviews, an online survey, and a global consensus meeting of experts. For each of the 10 equity-related items, the statement provides an explanation and example(s) of transparent reporting practices.
CONCLUSIONS AND RELEVANCE: Use of the STROBE-Equity extension alongside the STROBE statement when writing up completed reports of observational studies has the potential to advance the reporting of health equity data and considerations. Improved reporting of this information may help knowledge users better identify and apply evidence relevant to populations experiencing inequities
Prevalence and Causes of Blindness and Vision Impairment in the State of Qatar: Results of a Population-Based Cross-Sectional Study.
Get PDFINTRODUCTION: This study is a population-based investigation into the prevalence and causes of blindness and vision impairment (VI) among people aged 50 years and older living in the State of Qatar. METHODS: A Rapid Assessment of Avoidable Blindness (RAAB) methodology, applied from May 2022 to June 2023, utilized stratified two-stage cluster random sampling to select 5,060 persons aged 50 years and older resident in Qatar from 145 communities chosen by probability proportional to size. Communities were stratified by Qatari and non-Qatari nationality. Participants were examined by ophthalmologists in primary health centers. Data collection was through the RAAB7 Android application and supervised by a trainer using secure, encrypted cloud storage. RESULTS: Of the 3,206 participants examined, 14 (0.4%) had blindness and 10 (0.3%) had severe VI. Compared to a previous RAAB study in 2009, the prevalence of blindness (presenting visual acuity [VA] <3/60) decreased from 1.28% to 0.4% (95% confidence interval (CI): 0.2-0.7%). The age-sex-adjusted prevalence of all VI (presenting VA <6/12-NPL) was 9.7% (95% CI: 8.3-11.1), higher among females 12.6% (95% CI: 10.5-14.6), and Qataris 16.7% (95% CI: 14.4-19.1), compared to males 7.6% (95% CI: 6.3-9.0), and non-Qataris 6.3% (95% CI: 5.1-7.5). The principal causes of blindness included diabetic retinopathy (DR) (33.3%), cataract (20%), glaucoma (13%), and other posterior segment diseases (13%). All VI was mainly attributed to uncorrected refractive errors at 58% and cataract at 17%, with the former being more common among non-Qataris and cataract more prevalent among Qataris. CONCLUSION: Our findings show a low prevalence of VI compared with many countries that have published VI data. VI was mainly caused by DR, cataract, and uncorrected refractive error. Further reduction in vision loss can be achieved with early detection and improved access using innovation and technology
The Pandemic Agreement: What's Next?
Get PDFThe COVID-19 pandemic exposed critical weaknesses in global health governance, prompting the development of the WHO Pandemic Agreement, formally adopted by the World Health Assembly in May 2025. This landmark Agreement seeks to address the shortcomings of the 2005 International Health Regulations by establishing legally binding commitments to enhance pandemic preparedness, equity, and international solidarity. However, the negotiation process revealed deep geopolitical divisions, raising concerns about the Agreement's legitimacy and enforceability. Key provisions include improved surveillance, data sharing, protection for healthcare workers, and equitable access to medical countermeasures. Nevertheless, its effectiveness may be compromised by vague language, unresolved issues, and the absence or abstention of influential states. Implementation is further challenged by political fragmentation, sovereignty concerns, and disparities in national capacities. The Agreement's success will depend on sustained political will, robust accountability mechanisms, and meaningful national adoption. Ongoing debates over the definition of 'pandemic' and the WHO's limited enforcement powers underscore the tension between multilateral cooperation and national sovereignty. While the Agreement represents a significant step forward, it is not a panacea. Its promise lies in its potential to catalyse coordinated global action, but only if supported by genuine commitment and adaptive governance. As the world faces future health threats, the Pandemic Agreement must evolve into a practical tool for resilience, equity, and collective security