Estimated dengue force of infection and burden of primary infections among Indian children.

BACKGROUND: Comprehensive, age-stratified dengue surveillance data are unavailable from India and many more dengue cases occur than are reported. Additional information on dengue transmission dynamics can inform understanding of disease endemicity and infection risk. METHODS: Using age-stratified dengue IgG seroprevalence data from 2556 Indian children aged 5-10 years, we estimated annual force of infection (FOI) at each of 6 sites using a binomial regression model. We estimated the ages by which 50 and 70% of children were first infected; and predicted seroprevalence in children aged 1-10 years assuming constant force-of-infection. Applying these infection rates to national census data, we then calculated the number of primary dengue infections occurring, annually, in Indian children. RESULTS: Annual force-of-infection at all sites combined was 11.9% (95% CI 8.8-16.2), varying across sites from 3.5% (95% CI 2.8-4.4) to 21.2% (95% CI 18.4-24.5). Overall, 50 and 70% of children were infected by 5.8 (95% CI 4.3-7.9) and 10.1 (95% CI 7.4-13.7) years respectively. In all sites except Kalyani, > 70% of children had been infected before their 11th birthday, and goodness-of-fit statistics indicated a relatively constant force-of-infection over time except at two sites (Wardha and Hyderabad). Nationwide, we estimated 17,013,527 children (95% CI: 14,518,438- 19,218,733), equivalent to 6.5% of children aged < 11 years, experience their first infection annually. CONCLUSIONS: Dengue force-of-infection in India is comparable to other highly endemic countries. Significant variation across sites exists, likely reflecting local epidemiological variation. The number of annual primary infections is indicative of a significant, under-reported burden of secondary infections and symptomatic episodes. TRIAL REGISTRATION: Registered retrospectively with clinicaltrials.gov ( NCT01477671 ; 18/11/2011) and clinical trials registry of India (ctri.nic.in; CTRI/2011/12/002243 ; 15/12/2011). Date of enrollment of 1st subject: 22/9/2011.

Impact of prepregnancy body mass index on adverse pregnancy outcomes: analysis from the Longitudinal Indian Family hEalth cohort study.

BACKGROUND: Both high and low maternal prepregnancy body mass index can lead to suboptimal fetal growth and risk of pregnancy complications. In developed countries, nearly half of all women of childbearing age are either overweight or obese, and most data linking maternal body mass index and adverse pregnancy complications are limited to these populations. OBJECTIVE: This study aimed to prospectively evaluate the relationships between prepregnancy body mass index and adverse pregnancy outcomes using the Longitudinal Indian Family hEalth (LIFE) study. STUDY DESIGN: We modeled the relationships between prepregnancy body mass index and adverse pregnancy outcomes such as low birthweight, preterm birth, cesarean delivery, intrauterine growth restriction, miscarriage, and fetal death among 675 women aged 15 to 35 years with singleton pregnancies in the Longitudinal Indian Family hEalth study, a population-based prospective pregnancy cohort study conducted in Telangana, India. Prepregnancy body mass index was calculated as weight in kilograms divided by height in meters squared and was classified into 4 categories using the World Health Organization recommendations for Asian adults. Prepregnancy body mass index was assessed at a mean of 12.3 months before pregnancy. Odds ratios and 95% confidence intervals of adverse pregnancy outcomes were modeled and adjusted for confounders. RESULTS: Obese women had a 3-fold increased risk of cesarean delivery (odds ratio, 3.13; 95% confidence interval, 1.56-6.29) compared with normal-weight women. Those who were overweight also had a marginally increased risk of cesarean delivery, albeit not statistically significant (odds ratio, 1.17; 95% confidence interval, 0.61-2.24). Underweight women had a modestly increased risk of low birthweight, compared with normal-weight women (odds ratio, 1.12; 95% confidence interval, 0.71-1.77), although results were not significant. Conversely, obese (odds ratio, 0.71; 95% confidence interval, 0.28-1.77) and overweight (odds ratio, 0.61; 95% confidence interval, 0.24-1.51) women had a marginally decreased risk of low birthweight. CONCLUSION: Our data suggest that women with elevated prepregnancy body mass index may have a higher risk of adverse pregnancy outcomes, especially cesarean delivery. Although this study has limited generalizability, our findings are generalizable to rural to periurban regions of India. Further studies exploring the translatability of these findings to other populations are needed. In addition, targeted prepregnancy intervention studies and programs that include counseling on optimization of preconception health and lifestyle modification for improvement of subsequent pregnancy outcomes among overweight and obese women are needed.

Adverse birth outcomes among women with 'low-risk' pregnancies in India: findings from the Fifth National Family Health Survey, 2019-21.

Background: Despite substantial progress in improving maternal and newborn health, India continues to experience high rates of newborn mortality and stillbirths. One reason may be that many births happen in health facilities that lack advanced services-such as Caesarean section, blood transfusion, or newborn intensive care. Stratification based on pregnancy risk factors is used to guide 'high-risk' women to advanced facilities. To assess the utility of risk stratification for guiding the choice of facility, we estimated the frequency of adverse newborn outcomes among women classified as 'low risk' in India. Methods: We used the 2019-21 Fifth National Family Health Survey (NFHS-5)-India's Demographic and Health Survey-which includes modules administered to women aged 15-49 years. In addition to pregnancy history and outcomes, the survey collected a range of risk factors, including biomarkers. We used national obstetric risk guidelines to classify women as 'high risk' versus 'low risk' and assessed the frequency of stillbirths, newborn deaths, and unplanned Caesarean sections for the respondent's last pregnancy lasting 7 or more months in the past five years. We calculated the proportion of deliveries occurring at non-hospital facilities in all the Indian states. Findings: Using data from nearly 176,699 recent pregnancies, we found that 46.6% of India's newborn deaths and 56.3% of stillbirths were among women who were 'low risk' according to national guidelines. Women classified as 'low risk' had a Caesarean section rate of 8.4% (95% CI 8.1-8.7%), marginally lower than the national average of 10.0% (95% CI 9.8-10.3%). In India as a whole, 32.0% (95% CI 31.5-32.5%) of deliveries occurred in facilities that were likely to lack advanced services. There was substantial variation across the country, with less than 5% non-hospital public facility deliveries in Punjab, Kerala, and Delhi compared to more than 40% in Odisha, Madhya Pradesh, and Rajasthan. Newborn mortality tended to be lower in states with highest hospital delivery rates. Interpretation: Individual risk stratification based on factors identified in pregnancy fails to accurately predict which women will have delivery complications and experience stillbirth and newborn death in India. Thus a determination of 'low risk' should not be used to guide women to health facilities lacking key life saving services, including Caesarean section, blood transfusion, and advanced newborn resuscitation and care. Funding: Bill and Melinda Gates Foundation and the World Bank. The findings, interpretations and conclusions expressed in the paper are entirely those of the authors, and do not represent the views of the Gates Foundation or of the World Bank, its Executive Directors, or the countries they represent.

Peripheral bone structure, geometry, and strength and muscle density as derived from peripheral quantitative computed tomography and mortality among rural south Indian older adults.

Multiple studies have observed a relationship of bone mineral density (BMD) measured by Dual energy X-ray absorptiometry (DXA) and mortality. However, areal BMD (aBMD) measured by DXA is an integrated measure of trabecular and cortical bone and does not measure the geometry of bone. Peripheral Quantitative Computed Tomography (pQCT) provides greater insights on bone structure, geometry and strength. To examine whether higher bone phenotypes and muscle density as measured by pQCT are associated with a lower all-cause mortality, we studied 245 men and 254 women (all age >60) recruited in the Mobility and Independent Living among Elders Study in rural south India. Cox proportional hazards models estimated hazard ratios (HR [95% Confidence Intervals]). After an average follow-up of 5.3 years, 73 men and 50 women died. Among men, trabecular volumetric bone mineral density (vBMD) of radius (HR per SD increase in parameter = 0.59 [0.43, 0.81]) and tibia (0.60[0.45, 0.81]), cortical vBMD of radius (0.61, [0.47, 0.79]) and tibia (0.62, [0.49, 0.79]), cortical thickness of radius (0.55, [0.42, 0.7]) and tibia (0.60, [0.47, 0.77]), polar strength strain index (SSIp) of tibia (0.73 [0.54, 0.98]), endosteal circumference of radius (1.63, [1.25, 2.12]) and tibia (1.54, [1.19, 1.98]) were associated with all-cause mortality. Muscle density (0.67, [0.51, 0.87]) was associated with lower mortality in men. Among women cortical vBMD of radius (0.64, [0.47, 0.87]) and tibia (0.60 [0.45, 0.79]), cortical thickness of radius (0.54, [0.37, 0.79]) and tibia (0.43, [0.30, 0.61]), SSIp of radius (0.70 [0.48,1.01]) and tibia (0.58 [0.37, 0.90]) and endosteal circumference of radius (1.33 [0.97, 1.82]) and tibia (1.83, [1.37, 2.45]) were associated with all-cause mortality. Among men, gait speed mediated the association of muscle density and mortality but there was no mediation for any bone parameters. Conclusion: pQCT bone measures and muscle density were independently associated with mortality among rural south Indian elders.

Sero-Surveillance to Monitor the Trend of SARS-CoV-2 Infection Transmission in India: Study Protocol for a Multi Site, Community Based Longitudinal Cohort Study.

Introduction: Large-scale sero-prevalence studies with representation from all age groups are required to estimate the true burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the community. Serial serological surveys in fixed cohorts enable study of dynamics of viral transmission and correlates of immune response over time in the context of gradual introduction of COVID-19 vaccines and repeated upsurge of cases during the pandemic. Methods: This longitudinal study will involve follow-up of a cohort of 25,000 individuals (5,000 per site) aged 2 years and above recruited from five existing demographic surveillance sites in India. The cohort will be tested for the presence of IgG antibodies against S1/S2 spike protein subunits of SARS-CoV-2 in four rounds; once at baseline and subsequently, at intervals of 4 months for a year between January 2021 and January 2022. Neutralization assays will be carried out in a subset of seropositive samples in each round to quantify the antibody response and to estimate the durability of antibody response. Serial serological surveys will be complemented by fortnightly phone based syndromic surveillance to assess the burden of symptomatic acute febrile illness/ influenza like illness in the same cohort. A bio-repository will also be established to store the serum samples collected in all rounds of serological surveys. Discussion: The population based sero-epidemiological studies will help to determine the burden of COVID-19 at the community level in urban and rural Indian populations and guide in monitoring the trends in the transmission of SARS-CoV-2 infection. Risk factors for infection will be identified to inform future control strategies. The serial serological surveys in the same set of participants will help determine the viral transmission dynamics and durability of neutralizing immune response in participants with or without symptomatic COVID infection.

Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men.

Peripheral quantitative computed tomography (pQCT) provides biomechanical estimates of bone strength. Rural South Indian men have reduced biomechanical indices of bone strength compared to US Caucasian and Afro-Caribbean men. This suggests an underlying higher risk of osteoporotic fractures and greater future fracture burden among the rural South Indian men. INTRODUCTION: Geographical and racial comparisons of bone mineral density (BMD) have largely focused on DXA measures of areal BMD. In contrast, peripheral quantitative computed tomography (pQCT) measures volumetric BMD (vBMD), bone structural geometry and provides estimates of biomechanical strength. To further understand potential geographical and racial differences in skeletal health, we compared pQCT measures among US Caucasian, Afro-Caribbean, and rural South Indian men. METHODS: We studied men aged ≥ 60 years enrolled in the Mobility and Independent Living among Elders Study (MILES) in rural south India (N = 245), Osteoporotic Fractures in Men Study (MrOS) in the US (N = 1148), and the Tobago Bone Health Study (N = 828). RESULTS: The BMI (kg/m2) of rural South Indian men (21.6) was significantly lower compared to the US Caucasians (28) and Afro-Caribbean men (26.9). Adjusting for age, height, body weight, and grip strength; rural South Indian men compared to US Caucasians had significantly lower trabecular vBMD [- 1.3 to - 1.5 standard deviation (SD)], cortical thickness [- 0.8 to - 1.2 SD]; significantly higher endosteal circumference [0.5 to 0.8 SD]; but similar cortical vBMD. Afro-Caribbean men compared to US Caucasians had similar trabecular vBMD but significantly higher cortical vBMD [0.9 to 1.2 SD], SSIp [0.2 to 1.4 SD], and tibial endosteal circumference [1 SD], CONCLUSIONS: In comparison to US Caucasians, rural South Indian men have reduced bone strength (lower trabecular vBMD) and Afro-Caribbean men have greater bone strength (higher cortical vBMD). These results suggest an underlying higher risk of osteoporotic fractures and greater future fracture burden among rural South Indian men.

Sex Steroid Hormones and Fracture in a Multiethnic Cohort of Women: The Women's Health Initiative Study (WHI).

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone. Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03. Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.

Design of the Mobility and Independent Living in Elders Study: An older adult cohort in rural India.

AIM: The Mobility and Independent Living in Elders Study (MILES) was established in 2012 to estimate the prevalence, incidence, and risk factors for disability and age-related disease in rural older Indians. Here we describe the main goals of MILES, the essential elements of its design and examinations, and the initial findings from the baseline visit. METHODS: A random sample of 562 men and women aged ≥60 years was enrolled from the Medchal region in Telangana State. Baseline examination consisted of two separate clinical visits, and included measurements of blood pressure, anthropometry, physical function, peripheral artery disease, cognitive function, bone and muscle quality, knee osteoarthritis, carotid intima-media thickness, and blood biomarkers. A comprehensive interview was carried out for demographics, disability and disease history. Annual follow-up visits are ongoing to collect information on incident disability and disease. RESULTS: The median age of participants was 66 years (range 60-92 years); median body mass index 21.7 kg/m2 , median gait speed 0.67 m/s and 55% self-reported their health status as fair or poor. CONCLUSIONS: These findings suggest a more frail population in the MILES cohort compared with older adults in USA cohorts. MILES will provide estimates of burden of disease, and disability and risk factors in older adults. Findings will be used to identify potential interventions to prevent disability in this rural Indian population. Geriatr Gerontol Int 2017; 17: 31-40.

Dengue serotype-specific seroprevalence among 5- to 10-year-old children in India: a community-based cross-sectional study.

BACKGROUND: Dengue surveillance data in India are limited and probably substantially underestimate the burden of disease. A community-based study was undertaken to assess the prevalence of dengue-specific immunoglobulin G (IgG) antibodies in children across India and to examine historical dengue exposure rates. Potential associations between socio-economic factors and dengue seroprevalence were also assessed (registered at ctri.nic.in: CTRI/2011/12/002243). METHODS: A convenience sample of 2609 healthy children aged 5-10 years was enrolled; these children were registered at or were living in the vicinity of eight centres located at six geographically distinct sites across India. Blood samples were drawn to test for the presence of dengue IgG antibodies using ELISA. Serotype-specific neutralizing antibody titres were measured in dengue IgG-positive children using dengue plaque reduction neutralization tests. Socio-demographic and household information was collected using a questionnaire. RESULTS: Overall, 2558/2609 children had viable samples with laboratory results for dengue IgG. Dengue IgG seroprevalence across all sites was 59.6% (95% confidence interval 57.7-61.5%): the lowest (23.2%) was in Kalyani, West Bengal, and the highest (80.1%) was in Mumbai. Seroprevalence increased with age. Multivariate analysis suggested associations with household water storage/supply and type of housing. Half of the subjects with positive IgG results presented a multitypic profile, indicating previous exposure to more than one serotype. CONCLUSIONS: The overall dengue seroprevalence suggests that dengue endemicity in India is comparable to that in highly endemic countries of Southeast Asia. Additional prospective studies are required to fully quantify the disease burden, in order to support evidence-based policies for dengue prevention and control in India.