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Objective To develop a framework and index for measuring universal health coverage (UHC) at the district level in India and to assess progress towards UHC in the districts. Methods We adapted the framework of the World Health Organization and World Bank to develop a district-level UHC index ([UHC.sub.d]). We used routinely collected health survey and programme data in India to calculate [UHC.sub.d] for 687 districts from geometric means of 24 tracer indicators in five tracer domains: reproductive, maternal, newborn and child health; infectious diseases; noncommunicable diseases; service capacity and access; and financial risk protection. [UHC.sub.d] is on a scale of 0% to 100%, with higher scores indicating better performance. We also assessed the degree of inequality within districts using a subset of 14 tracer indicators. The disadvantaged subgroups were based on four inequality dimensions: wealth quintile, urban-rural location, religion and social group. Findings The median [UHC.sub.d] was 43.9% (range: 26.4 to 69.4). Substantial geographical differences existed, with districts in southern states having higher [UHC.sub.d] than elsewhere in India. Service coverage indicator levels were greater than 60%, except for noncommunicable diseases and for service capacity and access. Health insurance coverage was limited, with about 10% of the population facing catastrophic and impoverishing health expenditure. Substantial wealth-based disparities in UHC were seen within districts. Conclusion Our study shows that UHC can be measured at the local level and can help national and subnational government develop prioritization frameworks by identifying health-care delivery and geographic hotspots where limited progress towards UHC is being made. Objectif Elaborer un cadre et un Indice servant a mesurer la couverture sanitaire universelle (CSU) a l'echelle des districts en Inde, et evaluer les progres effectues dans ce domaine. Methodes Nous avons adapte le cadre de l'Organisation mondiale de la Sante et de la Banque mondiale pour mettre au point un indice de CSU par district ([CSU.sub.d]). Nous avons utilise des donnees recueillies systematiquement dans le cadre d'un programme et d'une enquete sur la sante en Inde pour calculer le [CSU.sub.d] de 687 districts, en partant des moyennes geometriques de 24 indicateurs tracants relevant de cinq categories: sante reproductive, maternelle, neonatale et infantile; maladies infectieuses; maladies non transmissibles; capacite et acces aux services; et enfin, protection contre les risques financiers. Le [CSU.sub.d] est compris entre 0 et 100%, les scores les plus eleves indiquant de meilleures performances. Nous avons egalement evalue le degre d'inegalite au sein des districts a l'aide d'un sous-ensemble de 14 indicateurs tracants. Les sous-groupes defavorises reposaient sur quatre formes d'inegalite: quintiles de richesse, implantation urbaine ou rurale, groupe religieux et groupe social. Resultats Le [CSU.sub.d] median etait de 43,9% (ecart: 26,4 a 69,4). Nous avons observe des variations geographiques considerables, les districts des Etats du sud affichant un meilleur [CSU.sub.d] que partout ailleurs en Inde. Lindicateur relatif a la couverture des services depassait les 60%, saufpour les maladies non transmissibles ou encore la capacite et l'acces aux services. De son cote, la couverture d'assurance-maladie etait limitee, environ 10% de la population etant confrontee a des depenses de sante catastrophiques entrainant un appauvrissement. Enfin, d'importantes disparites dans la CSU ont ete constatees a l'interieur des districts. Conclusion Notre etude montre que la CSU peut etre mesuree a l'echelle locale, ce qui peut aider les autorites locales et nationales a hierarchiser les priorites en identifiant les prestations de soins de sante et les zones geographiques a risque ou l'evolution vers une CSU se fait attendre. Objetivo Desarrollar un marco y un indice para medir la cobertura sanitaria universal (CSU) a nivel de distrito en India y evaluar los avances hacia la CSU en los distritos. Metodos Se adapto el marco de la Organizacion Mundial de la Salud y del Banco Mundial para desarrollar un indice de cobertura sanitaria universal a nivel de distrito ([CSU.sub.d]). Se utilizaron datos de encuestas y programas de salud recopilados sistematicamente en India para calcular el [CSU.sub.d] de 687 distritos a partir de medias geometricas de 24 indicadores de seguimiento en cinco ambitos de seguimiento: salud reproductiva, materna, neonatal e infantil; enfermedades infecciosas; enfermedades no transmisibles; capacidad y acceso a los servicios; y proteccion contra riesgos financieros. El CSU, esta en una escala de 0 a 100%, y los puntajes mas altos indican un mejor desempeno. Tambien se evaluo el grado de desigualdad dentro de los distritos utilizando un subconjunto de 14 indicadores de seguimiento. Los subgrupos desfavorecidos se basaron en cuatro dimensiones de desigualdad: quintil de riqueza, ubicacion urbano-rural, religion y grupo social. Resultados El promedio de [CSU.sub.d] fue del 43,9% (rango: 26,4 a 69,4). Existian diferencias geograficas significativas: los distritos de los estados del sur tenian un [CSU.sub.d] mas alto que los del resto de India. Los niveles de los indicadores de cobertura de servicios eran superiores al 60%, excepto para las enfermedades no transmisibles y para la capacidad y el acceso a los servicios. La cobertura del seguro sanitario era limitada, y alrededor del 10% de la poblacion se enfrentaba a gastos sanitarios catastroficos y empobrecedores. Se observaron disparidades significativas en la CSU segun el nivel de riqueza dentro de los distritos. Conclusion Este estudio demuestra que la CSU puede medirse a escala local y puede ayudar a los gobiernos nacionales y subnacionales a desarrollar marcos de priorizacion mediante la identificacion de los puntos criticos geograficos y de prestacion de asistencia sanitaria en los que los avances hacia la CSU son limitados., Introduction Universal health coverage (UHC) has emerged as a major goal in global health within the post-2015 millennium development agenda. (1) The objectives of UHC are typically defined by three [...]

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

BackgroundAssessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels.MethodsWe assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH.FindingsWe estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH.InterpretationWASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns.FundingWHO and Foreign, Commonwealth & Development Office.

Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.

Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE.

India had just under 150,000 reported coronavirus disease (COVID-19) deaths in 2020, fewer per 1 million persons than many other countries, such as Spain, France, the United Kingdom, and the [...]

BackgroundObservational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE.MethodsWe reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models.ResultsRisk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels.ConclusionsDissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE.