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Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia: A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage.
Get PDFBACKGROUND: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. METHODS AND FINDINGS: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. CONCLUSIONS: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development
The effects of war on digital adherence technology engagement for TB treatment in Ukraine.
Get PDFBACKGROUND: The Russian invasion of Ukraine in February 2022 has disrupted TB care. We examine the effects of the war on people with drug-susceptible TB (PWTB) and health care worker (HCW) engagement with a digital adherence technology (DAT). METHODS: We conducted a cluster-randomised trial of a DAT intervention in Ukraine. In the intervention arm, PWTB received a pillbox with a daily treatment reminder. Pillbox openings were captured real-time onto a platform, accessed by HCWs who could add manual doses where relevant. We compared DAT engagement in pre-, early-, and later-war periods. RESULTS: From June 2021 to 2022, 816 PWTB (32% women, median age 44 years) were enrolled. DAT engagement varied across regions and time period, with a decline in engagement post-February 2022. PWTB DAT engagement was 78%-84% of treatment-days. There was a three- to four-fold increase in unknown dose or delays in manual reporting of adherence (>7 days) post-February 2022 versus pre-war in Mykolaivska and Donetska oblasts and a two-fold increase in Odeska, Lvivska, and Zakarpatska oblasts. CONCLUSION: The war significantly disrupted DAT engagement, particularly in regions heavily affected by the conflict. Reduced engagement was likely due to migration and communication challenges. There is a critical need for resilient TB care in conflict settings
Integration of a WASH Component in the Standard National Protocol for Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months in Northern Senegal-A Costing Study.
Get PDFSevere acute malnutrition (SAM) affects 12.2 million children globally. Integrating a water, sanitation and hygiene (WASH) kit in outpatient SAM treatment can improve recovery rates by preventing WASH-related diseases and complications, but its cost at scale remains unknown. This study estimates the cost of integrating a WASH kit, composed of chlorine-based water treatment, safe water storage with a lid, soap, and a hygiene promotion component into Senegal's national protocol for treating uncomplicated SAM. This costing study was nested within the TISA randomised controlled trial, which evaluated the addition of a WASH component to standard SAM treatment for children aged 6-59 months. Cost data were collected from 660 participants enroled between December 2020 and December 2021. We took a societal perspective and used a micro-costing approach to estimate direct medical, non-medical and indirect costs. The WASH component led to a 2021 international 33.03. Sensitisation to hygiene and water treatment cost 29.63 for two at-home visits. No additional out-of-pocket expenses were incurred by households, but 338.77, ranging from 517.29 in sensitivity analysis, with the SAM treatment representing 69% (154.39). The absence of additional costs for households induced by the WASH component is encouraging, as it suggests that it would not represent an obstacle to integration into the national protocol. We produced a robust and comprehensive cost estimate for integrating a WASH kit and hygiene promotion into Senegal's SAM treatment protocol. This increased the treatment cost by 45% which was lower than estimates from a previous study. Results inform budget planning and support future cost-effectiveness analyses of integrating WASH interventions into SAM protocols
Protocol for the development of the WHO gestational weight gain charts.
Get PDFINTRODUCTION: Gestational weight gain (GWG) is an important indicator of maternal nutrition to be monitored during pregnancy. However, there is no evidence-based tool that can be used to monitor it across all geographic locations and pre-pregnancy body mass index (BMI) categories. The WHO is undertaking a project to develop GWG charts by pre-pregnancy BMI category, and to identify GWG ranges associated with the lowest risks of adverse maternal and infant outcomes. This protocol describes all the steps that will be used to accomplish the development of these GWG charts.
METHODS AND ANALYSIS: This project will involve the analysis of individual participant data (researcher-collected or administrative). To identify eligible datasets with GWG data, a literature review will be conducted and a global call for data will be launched by the WHO. Eligible individual datasets obtained from multiple sources will be harmonised into a pooled database. The database will undergo steps of cleaning, data quality assessment and application of individual-level inclusion criteria. Heterogeneity of maternal weight and GWG will be assessed to verify the possibility of combining datasets from multiple sources and regions into a single database. Generalized Additive Models for Location, Scale and Shape will be applied for the construction of the centile curves. Diagnostic measures, internal and external validation procedures will also be performed.
ETHICS AND DISSEMINATION: This project will include an analysis of existing study de-identified data. To be included in the pooled database, each included study should have received ethics approvals from relevant committees. Manuscripts will be submitted to open-access journals and a WHO document will be published, including the GWG charts and cut-offs for application in antenatal care
Exploring the interactions between climate change, chemical exposures and public health
Get PDFAbstract
Climate change impacts human exposure to chemicals through multiple pathways. This article discusses the interaction between chemicals, climate change and public health, presenting the outcomes of discussions on gaps and opportunities for progressing scientific knowledge to support positive action in this area. These discussions were held at a workshop hosted by the National Institute of Health Research (NIHR) Health Protection Research Unit in Environmental Change and Health (HPRU ECH) and organised in collaboration between the London School of Hygiene and Tropical Medicine (LSHTM) and the UK Health Security Agency (UKHSA). The workshop focused on the UK, but future work would benefit from broadening the analysis to other countries
Harmonising definitions of multiple long term conditions for inflammation research: a co-production approach.
No full textOBJECTIVE: Inflammation is implicated in many chronic diseases, but its role in driving multiple long-term conditions (MLTCs) remains unclear. The InflAIM programme aims to explore this potential link. Existing MLTC codelists are valuable but have not been designed for inflammation-focused research and often lack harmonisation across coding systems. This work aimed to develop a transparent, co-produced MLTC framework with harmonised codelists for epidemiological research, focusing on inflammatory conditions within the InflAIM programme. RESULTS: Using a systematic, co-produced approach, we combined literature review, clinical consensus, and patient input. From 8 sources, 363 candidate conditions were identified, refined to 60 validated MLTCs. Patients informed terminology and diagnostic experiences. Codelists were drawn from CALIBER (43), HDR UK Phenotype Library (4), MULTIPLY (8), with 7 developed de novo. Harmonisation covered Read v2, SNOMED CT, and Medcodeids. Quality assurance excluded 16.5% of codes and resolved 92 overlaps.We produced harmonised codelists for 60 MLTCs, comprising 7,426 validated MedCodeids. Clinical consensus identified 17 conditions with significant inflammatory components. Additional lists were developed for autoimmune and infectious diseases to support inflammation-focused analyses. This framework extends existing resources to meet the needs of inflammation-focused research, offering a transparent, harmonised, and patient-informed foundation for the InflAIM programme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-025-07626-0
Health-promoting housing policy in a changing climate: integrating affordability, security, and resilience.
Get PDFHousing is a fundamental determinant of health, yet many housing systems fail to promote well-being or address growing challenges such as climate change, inequality, and urbanization. It is increasingly treated as an investment vehicle and as a commercial product supporting the construction industry, with substantial interactions with climate change, rather than its fundamental role providing shelter. This perspective addresses this gap by proposing an integrated framework for health-promoting housing policy that combines affordability, security, and quality, paying particular attention to their interdependence and the growing influence of climate, adopting a systems-thinking approach. The framework was developed through an iterative literature synthesis and interdisciplinary dialogue, designed to overcome the disciplinary fragmentation of existing evidence. We conducted structured searches in PubMed, Scopus, and Web of Science, supplemented by grey literature, concentrating on materials published since 2010, reflecting the increasing relevance of climate resilience and equity. Inclusion criteria focused on sources examining housing-health interactions, policy interventions, and systemic challenges; purely technical engineering studies were excluded. Themes were mapped against four policy levers, legal, financial, planning, and community-based measures. The resulting framework offers policymakers a flexible menu of options to strengthen housing systems and advance health equity. By integrating climate resilience and social inclusion into housing policy, this approach provides a foundation for coordinated action across sectors. Aligning housing policy with public health goals is essential for building equitable, sustainable, and resilient communities
Epidemiology and Risk Modelling of Influenza A Virus Within and Between Pig Herds in Northern Lao PDR.
Get PDFAnimal-origin influenza A virus (IAV) is a perennial candidate for causing the next pandemic. With high risk for interspecies IAV transmission but limited resources for surveillance, particularly in rural areas of low- and middle-income countries (LMICs) such as Laos, there is a need to develop targeted, risk-based strategies for early detection of novel IAVs that may emerge in pigs. We conducted (1) a cross-sectional survey to characterise pig producer types, management practices and pig movement patterns; (2) sampling among pigs in slaughterhouses to quantify IAV seroprevalence and infection; and (3) within- and between-herd disease modelling exploring the relative importance of farm type for the IAV epidemiology. Overall, 31.3% (100/319) of sera and 1.4% (7/515) of nasal swab samples from pigs tested positive for IAV antibodies (ELISA) and viral RNA (PCR detection of IAV M-gene), respectively. Most pigs sampled were exotic breeds and supplied by commercial farms. Using hierarchical Bayesian logistic regression models, seropositivity was significantly higher among exotic breeds compared with local breeds and higher among pigs originating from provinces outside of our study area. Stochastic, individual-based models of within- and between-herd transmission were developed and calibrated for five pig producer types using the cross-sectional data from 202 study participants. The modelling results suggested sustained IAV transmission between farms was unlikely unless the probability of local transmission, independent of pig movement, was relatively high, and the initial infection was seeded in areas with higher densities of smallholders. Between-herd IAV transmission was only sustained in scenarios where persistently infected commercial farms were present to continuously seed infection among the pig smallholder network. Together, these factors underscore risks associated with livestock intensification in commercial and smallholder productions. A larger study is warranted to fully characterise the interprovincial pig movement and evaluate IAV transmission within Laos to inform the national surveillance strategy
Malaria-MOI: A flexible and scalable tool for predicting multiplicity of infection in malaria parasites.
No full textBACKGROUND: Estimating the multiplicity of infection (MOI) is critical for understanding malaria transmission dynamics and within-host Plasmodium parasite diversity. We developed Malaria-MOI, a fast, flexible, and species-agnostic Python tool that infers MOI directly from standard genomics files (e.g., BAM, VCF format) derived from whole genome sequencing (WGS), without requiring prior training data, curated panels or complex parameter tuning.
RESULTS: When benchmarked on 27 Plasmodium falciparum mixed-clone samples with known MOI, Malaria-MOI matched or outperformed leading methods, achieving a root mean squared error of 0.38, mean absolute error of 0.15, and a correlation of 0.78 using genomic variants across 165 diverse loci. These results exceeded the median performance of existing Bayesian and likelihood-based approaches. Applied to 8,208 P. falciparum field samples, Malaria-MOI showed a strong negative correlation with FWS (ρ = − 0.76), consistent with its accurate capture of within-host diversity. It demonstrated high sensitivity for detecting monoclonal infections (0.99) and superior specificity (0.76) compared to estMOI (0.58), particularly at lower sequencing coverage. The tool also identified regional MOI differences aligned with transmission intensity, detecting more polyclonal infections in high-transmission areas such as West Africa, where estMOI underestimated complexity.
CONCLUSIONS: Overall, Malaria-MOI accommodates diverse input types, including whole-genome data and diversity loci, and is compatible with both Illumina and Nanopore sequencing platforms. It is integrated into the Malaria-Profiler framework and is well-suited for genomic surveillance of Plasmodium and other pathogens, especially when elucidating transmission intensity for disease elimination activities. SOFTWARE: https://github.com/LSHTMPathogenSeqLab/Malaria-MOI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-026-01600-6
Strategies, interventions, and uptake of catch-up vaccination among adolescent and adult migrants, refugees, and internally displaced persons (IDPs) in low- and middle-income countries (LMICs): A systematic review.
Get PDFBACKGROUND: Catch-up vaccination helps close immunity gaps among migrants, refugees and internally displaced people (IDPs) in low- and middle-income countries (LMICs). Despite immunisation life-course policies and global guidelines promoting catch-up vaccination of arriving migrants, vaccination strategies for adolescent and adult populations are poorly described. We synthesised evidence on catch-up vaccination strategies and interventions, delivery platforms, uptake and coverage, and contextual barriers and enablers in LMICs.
METHODS: We searched Embase, Medline, PsycINFO, Global Health, Web of Science and grey literature sources (including websites of international and national public health organisations and agencies) for primary studies and reports on catch-up vaccination strategies and interventions, delivery platforms, uptake and coverage, and contextual barriers and enablers targeting adolescents (9-18 years) and, or adults (≥19 years) in migrants (foreign-born, including refugees) and internally displaced people (IDPs; displaced within national borders) across 136 LMICs, (from January 1st 2000 to February 1st 2025; all languages). Study quality was accessed using ROBINS-I, CASP, AACODS and, AGREE II tools.
RESULTS: Thirty-seven records met the inclusion criteria (13 peer-reviewed, 24 grey literature), reporting catch-up vaccination activities across 16 LMICs. Most studies were conducted in Uganda (n = 6), Bangladesh (n = 4), Lebanon (n = 3), and Kenya (n = 3). Interventions reached ≥48,000 migrants, refugees, and IDPs (primarily Rohingya refugees in Bangladesh during COVID-19 catch-up campaigns). Populations targeted included mostly refugees (n = 16 studies; 43.2%), general migrants (n = 14; 37.8%), and IDPs (n = 5; 13.5%), with a smaller number involving mixed or other migrant groups (n = 4; 10.8%). The most frequently delivered vaccines were measles-rubella (n = 12; 32.4%), COVID-19 primary-series catch-up (n = 9; 24.3%), HPV (n = 6; 16.2%), polio OPV/IPV (n = 5; 13.5%), and Hepatitis B (n = 3; 8.1%). Catch-up vaccine delivery most commonly occurred through primary care via opportunistic offers (n = 11) and mobile/outreach delivery (n = 11), with additional implementation in fixed posts in camps/settlements (n = 7), supplemental immunisation activities (SIAs) (n = 6), school-linked delivery (n = 5), and hospital/outpatient opportunistic vaccination (n = 4). High uptake (≥85%) was reported where access barriers were minimised (e.g., walk-in availability, extended hours) was paired with community or peer engagement and simple recall systems (SMS or e-booking). Reported barriers included documentation/entitlement checks, language barriers, and fragmented or non-interoperable vaccination records.
CONCLUSIONS: Migrants remain at risk of under-immunisation, and greater emphasis must be placed on promotion of vaccination across the life-course for missed vaccines, doses, and boosters. Strengthening catch-up vaccination in adolescents and adults, and improving migration-disaggregated data and delivery systems, are urgently needed