Adverse outcomes in patients hospitalized with pneumonia at age 60 or more: A prospective multi-centric hospital-based study in India.

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

Prevalence of undernutrition among migrant, refugee, internally displaced children and children of migrated parents in lower-middle-income countries: A meta-analysis of published studies from last twelve years.

BACKGROUND AND AIMS: This review aims to estimate the prevalence of undernutrition among migrants, refugees, internally displaced children, and children of migrated parents living in lower-middle-income countries. METHODS: PubMed, Scopus, Science-Direct, CINAHL-Plus, & Google Scholar were searched for peer-reviewed evidence published between January 2010 to March 2023. Two researchers independently examined the studies and retrieved the data. The internal and external validity of the studies was assessed using the NIH quality assessment tool, and a checklist adapted from Downs & Black, Bracht & Glass, and Del Siegle's guidelines. A random effect model was chosen to pool the estimates. Subgroup analysis, Meta-regression, and sensitivity analysis were done to explore the source of heterogeneity and the robustness of estimates. RESULTS: Among the 1978 records initially searched, 21 studies were selected for analysis. The pooled prevalence estimates for stunting, wasting, and underweight were estimated to be 29.39% (Confidence Interval [CI] 21.69-37.73; I2 99%; p < 0.01), 12.76% (CI 7.84-18.68; I2 99%; P < 0.01), and 24.05% (CI 16.17-32.94; I2 100%; p < 0.001) respectively. Among different WHO regions, all three undernutrition estimates were higher in LMICs belonging to the Southeast Asian region (Stunting 37.62%; wasting 14.28% and underweight 31.24%). Undernutrition among migrant Indian children was 43.55%, 18.71%, and 37.45% respectively. High heterogeneity was noted across all estimates with I2-value >90%. Sensitivity analysis across indicators showed the stability of our estimates. CONCLUSIONS: The extent of undernutrition, particularly wasting was high among migrant/refugee children living in lower-middle-income countries. Measures should be taken to strengthen the government-subsidized public food distribution system, increase healthcare outreach, and ensure public health insurance coverage among the migrant population.

Do Oral Cholera Vaccine and Water, Sanitation, and Hygiene Combine to Provide Greater Protection Against Cholera? Results From a Cluster-Randomized Trial of Oral Cholera Vaccine in Kolkata, India.

Background: Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods: We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results: Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001). Conclusions: These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.

Cost of acute respiratory illness episode and its determinants among community-dwelling older adults: a four-site cohort study from India.

Introduction: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. Methods: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. Results: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. Conclusion: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted.

Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India.

Background: Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings. Methods: Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected "training subpopulation" (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous ("better" vs "not better") composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive "validation population" (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation. Results: Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval, .49-.99]; P = .048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0-4 years) and this effect progressively declined with age. Conclusions: The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224.

Towards a Resilient Post-Pandemic Health System: Lessons through the Spectacles of Indian Health Policy Scenario.

A resilient health system necessitates strong governance, political commitment, effective administrative entities and inter-organisational collaboration. This paper examines India's current health policy landscape and explores the analytical and operational capacities required to establish a robust post-pandemic health system using the policy capacity framework described by Wu et al. (2015). We emphasised the need for a coordinated policy response to strengthen health information systems, health service management, human resource management and healthcare financing. The role that the planned implementation of Indian public health management cadres would play in the coming era, the importance of a comprehensive health information management system and the need for operational coordination between government and non-governmental organisations has also been emphasised.

The changing relationship between Cholera and interannual climate variables in Kolkata over the past century.

BACKGROUND: In the Bengal Delta, research has shown that climate and cholera are linked. One demonstration of this is the relationship between interannual ocean-atmospheric oscillations such as the El Niño Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD). What remains unclear in the present literature is the nature of this relationship in the specific context of Kolkata, and how this relationship may have changed over time. RESULTS: In this study, we analyse the changing relationship between ENSO and IOD with cholera in Kolkata over recent (1999-2019) and historical (1897-1941) time intervals. Wavelet coherence analysis revealed significant non-stationary association at 2-4 year and 4-8 year periods between cholera and both interannual timeseries during both time intervals. However, coherence was notably weakened in the recent interval, particularly with regards to ENSO, a result supported by a complementary SARIMA analysis. Similar coherence patterns with temperature indicate it could be an important mediating factor in the relationship between cholera and oscillating climate phenomena in Kolkata. CONCLUSIONS: This study reveals a shifting relationship between cholera and climate variables (ENSO and IOD) in Kolkata, suggesting a decoupling between environmental influences and cholera transmission in recent years. Our results therefore do not suggest that an intensification of ENSO is likely to significantly influence cholera in the region. We also find that the relationship between cholera and interannual climate variables is distinct to Kolkata, highlighting the spatial heterogeneity of the climate-cholera relationship even within the Bengal Delta.

Seasonality of cholera in Kolkata and the influence of climate.

BACKGROUND: Cholera in Kolkata remains endemic and the Indian city is burdened with a high number of annual cases. Climate change is widely considered to exacerbate cholera, however the precise relationship between climate and cholera is highly heterogeneous in space and considerable variation can be observed even within the Indian subcontinent. To date, relatively few studies have been conducted regarding the influence of climate on cholera in Kolkata. METHODS: We considered 21 years of confirmed cholera cases from the Infectious Disease Hospital in Kolkata during the period of 1999-2019. We used Generalised Additive Modelling (GAM) to extract the non-linear relationship between cholera and different climatic factors; temperature, rainfall and sea surface temperature (SST). Peak associated lag times were identified using cross-correlation lag analysis. RESULTS: Our findings revealed a bi-annual pattern of cholera cases with two peaks coinciding with the increase in temperature in summer and the onset of monsoon rains. Variables selected as explanatory variables in the GAM model were temperature and rainfall. Temperature was the only significant factor associated with summer cholera (mean temperature of 30.3 °C associated with RR of 3.8) while rainfall was found to be the main driver of monsoon cholera (550 mm total monthly rainfall associated with RR of 3.38). Lag time analysis revealed that the association between temperature and cholera cases in the summer had a longer peak lag time compared to that between rainfall and cholera during the monsoon. We propose several mechanisms by which these relationships are mediated. CONCLUSIONS: Kolkata exhibits a dual-peak phenomenon with independent mediating factors. We suggest that the summer peak is due to increased bacterial concentration in urban water bodies, while the monsoon peak is driven by contaminated flood waters. Our results underscore the potential utility of preventative strategies tailored to these seasonal and climatic patterns, including efforts to reduce direct contact with urban water bodies in summer and to protect residents from flood waters during monsoon.

The gut microbiome of the healthy population in Kolkata, India, is a reservoir of antimicrobial resistance genes emphasizing the need of enforcing antimicrobial stewardship.

Antimicrobial resistance (AMR) alleviation warrants antimicrobial stewardship (AS) entailing the indispensability of epidemiological surveillance. We undertook a small-scale surveillance in Kolkata to detect the presence of antimicrobial resistance genes (ARGs) in the healthy gut microbiome. We found that it was a reservoir of ARGs against common antibiotics. A targeted Polymerase Chain Reaction (PCR) and sequencing-based ARGs detection against tetracyclines, macrolides, trimethoprim, sulfamethoxazole, aminoglycosides, amphenicol, and mobile genetic element (MGE) markers were deployed in 25 fecal samples. Relative abundance and frequency of ARGs were calculated. We detected markers against all these classes of antibiotics. 100% samples carried aminoglycoside resistance marker and int1U. A comparison with our previously published diarrheal resistome from the same spatial and temporal frame revealed that a higher diversity of ARGs were detected in the community and a higher rate of isolation of tetC, msrA, tmp, and sul-2 was found. The presence of common markers in the two cohorts proves that the gut microbiome has been contaminated with ARGs and which are being disseminated among different ecosystems. This is an issue of discerning concern for public health. The study raises an alarming picture of the AMR crisis in low-middle and emergent economies. It emphasizes the strict enforcement of AS in the community.

Burden of Typhoid and Paratyphoid Fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).

Evolutionary dynamics of influenza A/H1N1 virus circulating in India from 2011 to 2021.

Influenza A viruses (IAV) are fast-evolving pathogens with a very high mutation rate (2.0 × 10-6 to 2.0 × 10-4) compared to the influenza B (IBV) and influenza C (ICV) viruses. Generally, the tropical regions are considered as the reservoir for the IAV's genetic and antigenic evolutionary modification to be reintroduced into the temperate region. Therefore, in connection to the above facts, the present study emphasized on the evolutionary dynamic of the pandemic-2009 H1N1 (pdmH1N1) influenza virus in India. A total of Ninety-two whole genome sequences of pdmH1N1 viruses circulating in India during the 2009 post-pandemic era were analysed. The temporal signal of the study, indicating strict molecular clock evolutionary process and the overall substitution rate is 2.21 × 10-3/site/year. We are using the nonparametric Bayesian Skygrid coalescent model to estimates the effective past population dynamic or size over time. The study exhibits a strong relation between the genetic distances and collection dates of the Indian pdmH1N1 strain. The skygrid plot represents the highest exponential growth of IAV in rainy and winter seasons. All the genes of Indian pdmH1N1 were under purifying selective pressure. The Bayesian time-imprinted phylogenetic tree represents the following clade distributions in the country within the last 10 years; I) clade 6, 6C, and 7 were co-circulating between the 2011 to 2012 flu season; II) the clade 6B was introduced into circulation in the late seasons of 2012; III) lastly, the clade 6B remain existing in the circulation and segregated into subclade 6B.1 with five different subgroup (6B.1A, 6B.1A.1, 6B.1A.5a, 6B.1A.5a.2, 6B.1A.7). The recent circulating strain of Indian H1N1 strain represent the insertion of basic-amino acid arginine (R) in the cleavage site (325/K-R) of HA protein and amino acid mutation (314/I-M) on the lateral head surface domain of NA protein. Moreover, the study indicates the sporadic presence of the oseltamivir-resistant (275/H-Y) H1N1 variant in circulation. The present study suggests the purifying selective pressure and stochastic ecological factors for the existence and adaptation of a certain clade 6B in the host populations and additional information on the emergence of mutated strains in the circulation.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Rationality of Prescriptions by Rational Use of Medicine Consensus Approach in Common Respiratory and Gastrointestinal Infections: An Outpatient Department Based Cross-Sectional Study from India.

BACKGROUND: Drug utilisation studies are relevant for the analysis of prescription rationality and are pertinent in today's context of the increasing burden of antimicrobial resistance. Prescriptions for patients with diarrhoea or Acute Respiratory Infection (ARI) have been analysed in this study to understand the prescription pattern among various categories of prescribers in two tertiary care centers. METHODS: This cross-sectional study was conducted from August 2019 to December 2020 in the medicine and pediatrics outpatient departments of two government teaching hospitals in West Bengal, India. A total of 630 prescriptions were evaluated against WHO standards. Prescriptions were assessed by a 'Rational Use of Medicine Consensus committee' approach. RESULTS: The Fixed Dose Combination (FDC) was used in half of the patients (51%). Both the generic prescription (23.3%) and adherence to hospital formulary rates (36.5%) were low. The antibiotics prescription rate was high (57%), and it was higher for diarrhoea than ARI. Deviations from the standard treatment guidelines were found in 98.9% of prescriptions. Deviations were commonly found with prescriptions written by the junior doctors (99.6%). CONCLUSION: Irrational prescribing patterns prevail in tertiary care centers and indicate the necessity of awareness generation and capacity building among prescribers regarding AMR and its unseen consequences.

Safety and immunogenicity of the Rotavac and Rotasiil rotavirus vaccines administered in an interchangeable dosing schedule among healthy Indian infants: a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial.

BACKGROUND: Rotavirus is the leading cause of severe dehydrating gastroenteritis among children younger than 5 years in low-income and middle-income countries. Two vaccines-Rotavac and Rotasiil-are used in routine immunisation in India. The safety and immunogenicity of these vaccines administered in a mixed regimen is not documented. We therefore aimed to compare the safety and seroresponse of recipients of a mixed regimen versus a single regimen. METHODS: We did a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial at two sites in India. We recruited healthy infants aged 6-8 weeks. Infants with systemic disorders, weight-for-height Z scores of less than minus three SDs, or a history of persistent diarrhoea were excluded. Eligible infants were randomly allocated to six groups in equal numbers to receive either the single vaccine regimen (ie, Rotavac-Rotavac-Rotavac [group 1] or Rotasiil-Rotasiil-Rotasiil [group 2]) or the mixed vaccine regimen (ie, Rotavac-Rotasiil-Rotavac [group 3], Rotasiil-Rotavac-Rotasiil [group 4], Rotavac-Rotasiil-Rotasiil [group 5], or Rotasiil-Rotavac-Rotavac [group 6]). Randomisation was done using an online software by site in blocks of at least 12. The primary outcome was seroresponse to rotavirus vaccine, measured using rotavirus-specific serum IgA antibodies 4 weeks after the third dose. The seroresponse rates were compared between recipients of the four mixed vaccine regimens (consisting of various combinations of Rotavac and Rotasiil) with recipients of the single vaccine regimens (consisting of Rotavac or Rotasiil only for all three doses). The non-inferiority margin was set at 10%. Safety follow-ups were done for the duration of study participation. This trial was registered with the Clinical Trials Registry India, number CTRI/2018/08/015317. FINDINGS: Between March 25, 2019, and Jan 15, 2020, a total of 1979 eligible infants were randomly assigned to receive a single vaccine regimen (n=659; 329 in group 1 and 330 in group 2) or a mixed vaccine regimen (n=1320; 329 each in groups 3 and 4, and 331 each in groups 5 and 6). All eligible participants received the first dose, 1925 (97·3%) of 1979 received the second dose, and 1894 (95·7%) received all three doses of vaccine. 1852 (93·6%) of 1979 participants completed the follow-up. The immunogenicity analysis consisted of 1839 infants (1238 [67·3%] in the mixed vaccine regimen and 601 [32·7%] in the single vaccine regimen; 13 samples were insufficient in quantity) who completed vaccination and provided post-vaccination sera. The seroresponse rate in the mixed vaccine regimen group (33·5% [95% CI 30·9-36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1-33·4]); the seroresponse rate difference was 3·9% (95% CI -0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4-93·0) in the single vaccine regimen group and 91·1% (89·5-92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study. INTERPRETATION: Rotavac and Rotasiil can be safely used in an interchangeable manner for routine immunisation since the seroresponse was non-inferior in the mixed vaccine regimen compared with the single vaccine regimen. These results allow for flexibility in administering the vaccines, helping to overcome vaccine shortages and supply chain issues, and targeting migrant populations easily. FUNDING: Ministry of Health and Family Welfare, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Cholera.

Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Utilization of dental care services among adult Indian population: A meta-analysis of evidence from 2011-2022.

Background: This study aimed to generate a pooled national estimate on dental health care services utilization by the adult population in India from any public or private facility in an effort to highlight the demand and usage for oral health care. Methods: In this meta-analysis, PubMed, ScienceDirect, DOAJ, and Google Scholar were searched using a search strategy that combined MeSH headings and keywords (e.g., "Oral Health", "Dental Health Services", utilization, India, etc.) for articles on dental utilization among Indian adults, published between January 2011 and June 2022. Study quality was assessed using the NIH Quality assessment tool, and a random-effects inverse-variance method was used for pulling utilization proportions. Meta-regression and sub-group analyses were conducted to identify the sources of heterogeneity. Heterogeneity is reported as I2. To examine publication bias, the funnel plot, egger's test, and trim-and-fill analysis were performed. Results: From 4012 identified articles, 21 were eligible for inclusion. The pooled dental care utilization amongst Indian adults were found to be 23.96% (confidence interval [CI]: 16.81%- 31.11%, P<0.001, I2=98.93%), and the highest estimate was in South Zone (30.02%, CI: 19.14-40.90, P<0.01, I2=98.63%). Visual inspection of the funnel plot revealed the presence of publication bias (egger's P value 0.02). A mild decrease in utilization estimate was noted through trim and fill analysis (adjusted estimate 17.65%, CI: 8.97-26.33, P=0.03). No significant subgroup effect was found for the variables study zone and conduction years (P value: 0.09 & 0.34 respectively). Conclusion: Future studies should be undertaken to focus on the demand and supply of oral health care services since an evidential gap has been identified due to the uneven distribution of studies available from various regions of India. The heterogeneity can be attributed to the diverse socioeconomic, literacy, and inherent health system performance status.

Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial.

BACKGROUND: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). FINDINGS: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. INTERPRETATION: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. FUNDING: Bharat Biotech International and Indian Council of Medical Research.

Cohort profile: Indian Network of Population-Based Surveillance Platforms for Influenza and Other Respiratory Viruses among the Elderly (INSPIRE).

PURPOSE: We describe here a multicentric community-dwelling cohort of older adults (>60 years of age) established to estimate incidence, study risk factors, healthcare utilisation and economic burden associated with influenza and respiratory syncytial virus (RSV) in India. PARTICIPANTS: The four sites of this cohort are in northern (Ballabgarh), southern (Chennai), eastern (Kolkata) and western (Pune) parts of India. We enrolled 5336 participants across 4220 households and began surveillance in July 2018 for viral respiratory infections with additional participants enrolled annually. Trained field workers collected data about individual-level and household-level risk factors at enrolment and quarterly assessed frailty and grip strength. Trained nurses surveilled weekly to identify acute respiratory infections (ARI) and clinically assessed individuals to diagnose acute lower respiratory infection (ALRI) as per protocol. Nasal and oropharyngeal swabs are collected from all ALRI cases and one-fifth of the other ARI cases for laboratory testing. Cost data of the episode are collected using the WHO approach for estimating the economic burden of seasonal influenza. Handheld tablets with Open Data Kit platform were used for data collection. FINDINGS TO DATE: The attrition of 352 participants due to migration and deaths was offset by enrolling 680 new entrants in the second year. All four sites reported negligible influenza vaccination uptake (0.1%-0.4%), low health insurance coverage (0.4%-22%) and high tobacco use (19%-52%). Ballabgarh had the highest proportion (54.4%) of households in the richest wealth quintile, but reported high solid fuel use (92%). Frailty levels were highest in Kolkata (11.3%) and lowest in Pune (6.8%). The Chennai cohort had highest self-reported morbidity (90.1%). FUTURE PLANS: The findings of this cohort will be used to inform prioritisation of strategies for influenza and RSV control for older adults in India. We also plan to conduct epidemiological studies of SARS-CoV-2 using this platform.

Challenges for Programmatic Implementation of Oral Cholera Vaccine in India.

Cholera remains a major contributor of diarrheal diseases and leads to substantial morbidity and mortality, particularly in low socioeconomic settings. Nonavailability of a national cholera control plan in India, compounded by underreporting of cholera cases and deficient accurate cholera hotspot estimates, has made cholera control a challenge. Obstacles in the programmatic introduction of oral cholera vaccine (OCV) lie within the infrastructure-stockpile, costing, distribution system, cold-chain mechanism, vaccine logistics, and lack of strengthened surveillance systems for adverse events following immunization. Sustained political commitment along with collaboration of people working in the media will also determine the policy outcome of OCV introduction in India.