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This study examined the relative proportion of enteric pathogens associated with severe gastroenteritis (GE) among children younger than 2 years in a phase III efficacy trial of the ROTASIIL® vaccine in India, evaluated the impact of co-infections on vaccine efficacy (VE), and characterized the association between specific pathogens and the clinical profile of severe GE. Stored stool samples collected from cases of severe GE in the phase III trial were tested by quantitative polymerase chain reaction using TaqMan™ Array Cards. Etiology was attributed by calculating the adjusted attributable fraction (AF) for each pathogen. A test-negative design was used to estimate VE. The pathogens with the highest AFs for severe diarrhea were rotavirus (23.5%), adenovirus 40/41 (17.0%), Shigella spp./enteroinvasive Escherichia coli, norovirus GII, enterotoxigenic E. coli, and Cryptosporidium spp. A considerable proportion of the disease in these children could not be explained by the pathogens tested. Severe GE cases associated with rotavirus and Shigella spp. were more likely to have a longer duration of vomiting and diarrhea, respectively. Cases attributed to Cryptosporidium spp. were more severe and required hospitalization. In the intention-to-treat population, VE was estimated to be 43.9% before and 46.5% after adjustment for co-infections; in the per-protocol population, VE was 46.7% before and 49.1% after adjustments. Rotavirus continued to be the leading cause of severe GE in this age group. The adjusted VE estimates obtained did not support co-infections as a major cause of lower vaccine performance in low- and middle-income countries.

Background: Histology forms an important component of first-year medical education. Unfortunately, it is limited to the practical laboratory due to the need for a microscope and good quality slides. Virtual microscopy is a recent advancement, which uses computers as an alternative to microscopes. The aim of the study was to compare virtual microscopy (VM)-based practical classes with traditional microscopy (TM)-based practical classes for two cohorts of first-year medical students, by comparing learning achieved using two different test scores as well as a qualitative assessment of student and faculty perspectives regarding the feasibility and usefulness of VM., Methods: Each cohort of students was divided into two equal batches and each batch underwent eight histology modules of which, four utilised traditional microscopes and four utilised virtual microscopes. Quantitative analysis was performed using a theory test (which assessed preparation, theory knowledge and understanding) as well as a spotter test (which assessed identification skills, reasoning, and recall). Qualitative analysis was performed using a structured questionnaire and focus group discussions., Results: Modules using VM were better when compared with those using TM, showing statistically significant and better grades. Qualitative analysis performed, yielded important information as to how this technology can serve as a good adjunct to traditional histology classes in the competency-based curriculum by increasing student interest, enabling self-study, and reducing students dependence on the tutor., Conclusions: VM forms a good adjunct as well as a standalone modality of learning to TM, as it improves accessibility to slides and promotes self-learning., Competing Interests: The authors have none to declare., (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Introduction/aims: In Guillain-Barré syndrome (GBS), the sensitivity and specificity of phrenic compound muscle action potential (CMAP) measurements to predict endotracheal mechanical ventilation are unknown. Hence, we sought to estimate sensitivity and specificity., Methods: We performed a 10-year retrospective analysis of adult GBS patients from our single-center laboratory database (2009 to 2019). The phrenic nerve amplitudes and latencies before ventilation were recorded along with other clinical and demographic features. Receiver operating curve (ROC) analysis with area under the curve (AUC) was used to determine the sensitivity and specificity with 95% confidence interval (CI) for phrenic amplitudes and latencies in predicting the need for mechanical ventilation., Results: Two hundred five phrenic nerves were analyzed in 105 patients. The mean age was 46.1 ± 16.2 years, with 60% of them being male. Fourteen patients (13.3%) required mechanical ventilation. The average phrenic amplitudes were lower in the ventilated group (P = .003), but average latencies did not differ (P = .133). ROC analysis confirmed that phrenic amplitudes could predict respiratory failure (AUC = 0.76; 95% CI, 0.61 to 0.91; P < .002), but phrenic latencies could not (AUC = 0.60; 95% CI, 0.46 to 0.73; P = .256). The best threshold for amplitude was ≥0.6 mV, with sensitivity, specificity, and positive and negative predictive values of 85.7%, 58.2%, 24.0%, and 96.4%, respectively., Discussion: Our study suggests that phrenic CMAP amplitudes can predict the need for mechanical ventilation in GBS. In contrast, phrenic CMAP latencies are not reliable. The high negative predictive value of phrenic CMAP amplitudes ≥0.6 mV can preclude mechanical ventilation, making these a useful adjunct to clinical decision-making., (© 2023 Wiley Periodicals LLC.)

Background and Objective: India, a highly heterogeneous country, has no common reference standards for predicting spirometry values, with very few recent studies from south India. This study aimed to create reference equations for rural south Indian adults, based on a population-based survey in Vellore, south India and compare it with other equations from India., Methods: The data from 583 non-smoking, asymptomatic participants (30 years and older) from a spirometry-based survey for airflow obstruction (rural Vellore, 2018), were used to develop equations for FEV1, FEV1/FVC, and FVC. The dataset was divided for development (70%) and validation (30%), by gender. Differences between observed and predicted values were assessed using the new equations and comparisons made with other equations from India., Results: Predictions with Vellore rural equations were closest to the previous south Indian equations from urban Bangalore. However, the Bangalore equations led to overestimation of FVC values in males, and of both FEV1 and FVC values in females. Using the rural Vellore equations also led to a higher percent of males being classified as having airflow obstruction, compared to the Bangalore equations which underestimated airflow obstruction in this rural population. Comparison with previously derived Indian equations from other parts of the country showed pronounced variations., Conclusions: Our study reiterates the need for representative rural and urban studies of adults from various parts of India, to obtain region specific reference equations, given the wide variations in spirometry values in "normal" individuals, due to social heterogeneities of the Indian population and resulting complexities in defining normal.

Purpose: Identifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI)., Methods: This retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied., Results: In our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1-3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p < 0.001). Appropriate initial empirical therapy was given to 70.9%. Recovery from neutropenia occurred in 57.4% while 25.8% had prolonged or profound neutropenia. Sixty-nine percent (107/155) had septic shock and needed intensive care; 12.2% of patients required dialysis. Non-recovery from neutropenia (aHR, 4.28; 95% CI 2.53-7.23), presence of septic shock (aHR, 4.42; 95%CI 1.47-13.28), requirement of intensive care (aHR,3.12;95%CI 1.23-7.93), and persistent bacteremia (aHR,1.74; 95%CI 1.05-2.89) significantly predicted poor outcomes in multivariable analysis., Conclusion: FUBC showing persistent bacteremia predicted poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections (CRGNBSI) and should be routinely reported., (© 2023. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants., (© 2022 Wiley Periodicals LLC.)

Purpose: Dose-dense chemotherapy improves survival but with increased toxicity and treatment-related cost. We report the prevalence of anemia and the possible risk factors associated with chemotherapy-related anemia and determine the cost and time-delay associated with transfusion requirement in Indian patients with non-metastatic breast cancer on dose-dense preoperative chemotherapy., Methods: In this study, triple-negative breast cancer (TNBC) patients were treated preoperatively with docetaxel and cyclophosphamide alternating with epirubicin and cisplatin every 2 weeks. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the red cell indices, transfusion requirement, time to transfusion, as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred., Results: A total of 116 consecutive women with nonmetastatic TNBC were treated with preoperative chemotherapy. The median age was 44.5 years. 56.1% of patients had stage III disease. Anemia was detected at baseline in 54 (46.5%) patients with mild anemia (10-12 g/dl) in 42 (36.2%) patients and moderate anemia (8-10 g/dl) in 12 (10.3%) patients. During the course of treatment, all patients developed anemia. A total of 44 patients (37.9%) required transfusion during chemotherapy, with 55(47.4%) patients developing grade 1-2 anemia and 40 (34.5%) patients developing grade 3 anemia. The factors associated with anemia requiring transfusion were a steeper decline in hemoglobin after two cycles (OR 1.65, p = 0.02), low-grade tumor (OR 2.48, p = 0.03), and thrombocytopenia grade 3 or 4 (OR 4.35, p = 0.034), of which tumor grade and thrombocytopenia remained significant in multivariate analysis. Nearly one-fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of INR 7000 was incurred among those requiring blood transfusion., Conclusion: Anemia is a common toxicity associated with dose-dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low-grade tumor, grade 3 or 4 thrombocytopenia, and grade 2 or higher anemia after two cycles of chemotherapy are risk factors for blood transfusions during treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Longitudinal studies are important to understand patterns of growth in children and limited in India. It is important to identify an approach for characterising growth trajectories to distinguish between children who have healthy growth and those growth is poor. Many statistical approaches are available to assess the longitudinal growth data and which are difficult to recognize the pattern. In this research study, we employed functional principal component analysis (FPCA) as a statistical method to find the pattern of growth data. The purpose of this study is to describe the longitudinal child growth trajectory pattern under 3 years of age using functional principal component method., Methods: Children born between March 2002 and August 2003 (n = 290) were followed until their third birthday in three neighbouring slums in Vellore, South India. Field workers visited homes to collect details of morbidity twice a week. Height and weight were measured monthly from 1 month of age in a study-run clinic. Longitudinal child growth trajectory pattern were extracted using Functional Principal Component analysis using B-spline basis functions with smoothing parameters. Functional linear model was used to assess the factors association with the growth functions., Results: We have obtained four FPCs explained by 86.5, 3.9, 3.1 and 2.2% of the variation respectively for the height functions. For height, 38% of the children's had poor growth trajectories. Similarly, three FPCs explained 76.2, 8.8, and 4.7% respectively for the weight functions and 44% of the children's had poor growth in their weight trajectories. Results show that gender, socio-economic status, parent's education, breast feeding, and gravida are associated and, influence the growth pattern in children., Conclusions: The FPC approach deals with subjects' dynamics of growth and not with specific values at given times. FPC could be a better alternate approach for both dimension reduction and pattern detection. FPC may be used to offer greater insight for classification., (© 2022. The Author(s).)

Background: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden., Methods: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting., Results: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure., Conclusions: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1-4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11-0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06-0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

Background: Conditional cash transfers are widespread and effective for utilization of targeted health services, but there is little evidence of their influence on the utilization of non-targeted or extended general healthcare services. Using data from a population-based health utilization survey, we evaluated the influence of conditional cash transfers for maternal and immunization services on the utilization of healthcare services for acute childhood illnesses., Methods: Participants included mothers or primary caretakers of children <2 y of age residing in 2407 households in urban Vellore, Tamil Nadu, India. Mothers of children with illness in the preceding month were interviewed on presenting symptoms, provider choice and beneficiary status of maternal and immunization-based conditional cash transfer programs., Results: Of 2407 children <2 y of age, about 48% reported being beneficiaries of maternal and immunization-based conditional cash transfers. Beneficiary status was associated with an increased use of public services (adjusted relative risk [aRR] 3.14 [95% confidence interval {CI} 1.96 - 5.02]) but not the use of private services (aRR 1.42 [95% CI 0.97 - 2.08]) relative to home or informal care., Conclusions: Our findings indicate financial incentives for use of maternal and immunization services could have an indirect, non-targeted effect on utilization of formal healthcare for acute childhood illnesses., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Perturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved., Methods: Patients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters., Results: Patients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter-1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 μg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 μg/dL., Conclusions: In patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease., Competing Interests: Declaration of Competing Interest All the authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Purpose: To prospectively evaluate whether time to debridement has any correlation with union, infection, and quality of life in high-grade lower limb fractures in a tropical setting., Methods: A prospective cohort study was conducted at a tertiary care center in South India. Two hundred fifty-four adult skeletally mature patients with 301 grade 3 fractures involving the femur, tibia, or fibula were recruited. The cohort was empirically divided into two groups (early and late) based on the time to debridement (less than or more than 12 h from injury)., Outcome: The primary outcome was nonunion. Secondary outcomes were deep infection rates and patients' quality of life. Short form-36 (SF-36) and short musculoskeletal functional assessment (SMFA) questionnaires were also used. Patients were followed up for 9 months., Results: The follow-up rate was 93%. The late group had a significantly higher risk of nonunion (odds ratio(OR): 6.5, 95% confidence interval (CI): 2.82-14.95) and infections (OR: 6.05, 95% CI: 2.85-12.82). There was a 4% increase in the infection risk for each hour of delay for the initial 50 h ( p < 0.0001). SF-36 and SMFA scores were superior in the early group ( p < 0.0001)., Conclusion: The study contradicts findings reported in the literature from the West. Our study was in agreement with our hypothesis and proved that debridement within 12 h resulted in significantly lower rates of nonunion and infections and an overall improved quality of life in high-grade open lower limb fractures in a developing country., Level of Evidence: Level II., Trial Registration: German Clinical Trials Register DRKS00015186.

Introduction: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians., Methods and Analysis: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes., Ethics and Dissemination: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals., Trial Registration Number: ISRCTN13432279; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Schizophrenia, a chronic psychiatric disorder, can affect one's productivity and psychosocial functioning. In Indian context, the responsibility of caring persons with schizophrenia is increasingly on their spouses. Spousal caregiver experience and its relation with disability in schizophrenia need to be studied., Materials and Methods: We conducted a cross-sectional study among 52 outpatients with schizophrenia and their spouses attending a tertiary psychiatric center. The objectives were: (a) to explore spousal caregiver burden in schizophrenia and (b) to assess the relation between disability and spousal caregiver burden. The study adopted recommended ethical principles. Scales such as Burden Assessment Schedule, Indian Disability Evaluation and Assessment Scale (IDEAS), and Positive and Negative Syndrome Scale were used to collect appropriate data. Descriptive analysis, bivariate analysis, and multivariate analysis were done in SPSS software version 16.0., Results: The mean spousal caregiver burden score was 73.5 (standard deviation: 14.0). In bivariate analysis, disability, duration of schizophrenia, severity of schizophrenia, place of residence, and socioeconomic status had statistically significant relation with spousal caregiver burden. Adjusted for spouses' age, gender, and other significant factors in bivariate analysis, the IDEAS global disability score (2.6, [confidence interval 0.5-3.8, P = 0.013]) retained statistically significant association with spousal caregiver burden., Conclusion: Spouses of persons with schizophrenia experience significant caregiver burden. Disability was found to be the most powerful determinant of spousal caregiver burden in the sample. Focus on disability alleviation in the management of schizophrenia may help reduce spousal caregiver burden., Competing Interests: There are no conflicts of interest.

Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest.

Objectives: Conditioning child growth measures on baseline accounts for regression to the mean (RTM). Here, we present the "conditional random slope" (CRS) model, based on a linear-mixed effects model that incorporates a baseline-time interaction term that can accommodate multiple data points for a child while also directly accounting for RTM., Methods: In two birth cohorts, we applied five approaches to estimate child growth velocities from 0 to 12 months to assess the effect of increasing data density (number of measures per child) on the magnitude of RTM of unconditional estimates, and the correlation and concordance between the CRS and four alternative metrics. Further, we demonstrated the differential effect of the choice of velocity metric on the magnitude of the association between infant growth and stunting at 2 years., Results: RTM was minimally attenuated by increasing data density for unconditional growth modeling approaches. CRS and classical conditional models gave nearly identical estimates with two measures per child. Compared to the CRS estimates, unconditional metrics had moderate correlation (r = 0.65-0.91), but poor agreement in the classification of infants with relatively slow growth (kappa = 0.38-0.78). Estimates of the velocity-stunting association were the same for CRS and classical conditional models but differed substantially between conditional versus unconditional metrics., Conclusion: The CRS can leverage the flexibility of linear mixed models while addressing RTM in longitudinal analyses., (© 2017 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.)

Background: The World Health Organization (WHO) recommends six months of exclusive breastfeeding. Despite documented health, social and economic benefits, the practice of exclusive breastfeeding is quite low and information on influencing factors is limited especially from slum settlements. Our goal is to assess the prevalence and evaluate factors associated with early cessation of exclusive breastfeeding in the first six months of life among mothers in urban slums of Vellore, Southern India., Methods: We pooled data from three similar birth cohort studies ( n = 1088) conducted between 2002 and 2009. Breastfeeding information was obtained soon after birth and then from follow-up home visits conducted once every two weeks by the field workers. Multivariable Cox regression analyses were used to assess factors associated with early cessation of exclusive breastfeeding., Results: The prevalence of exclusive breastfeeding for the first six months was 11.4%, based on prospective data since birth. Results from multivariable analyses revealed maternal education (Adjusted Hazard Ratio [AHR] 1.18 , 95% CI 1.03, 1.35), pucca type of house (AHR 1.25 , 95% CI 1.10, 1.43), two or more number of children in the family (AHR 1.26 , 95% CI 1.10, 1.43), joint family structure (AHR 1.20 , 95% CI 1.02, 1.40) and birth during summer (AHR 1.16, 95% CI 1.01, 1.31) were associated with early cessation of exclusive breastfeeding in the first six months., Conclusions: Our results indicate that exclusive breastfeeding rates are well below the recommended levels. Educational interventions providing comprehensive breastfeeding information to mothers and their families can be evaluated to assess its effect on improving infant feeding practices.

Objective: To determine the prevalence and risk factors of scrub typhus in Tamil Nadu, South India., Methods: We performed a clustered seroprevalence study of the areas around Vellore. All participants completed a risk factor survey, with seropositive and seronegative participants acting as cases and controls, respectively, in a risk factor analysis. After univariate analysis, variables found to be significant underwent multivariate analysis., Results: Of 721 people participating in this study, 31.8% tested seropositive. By univariate analysis, after accounting for clustering, having a house that was clustered with other houses, having a fewer rooms in a house, having fewer people living in a household, defecating outside, female sex, age >60 years, shorter height, lower weight, smaller body mass index and smaller mid-upper arm circumference were found to be significantly associated with seropositivity. After multivariate regression modelling, living in a house clustered with other houses, female sex and age >60 years were significantly associated with scrub typhus exposure., Conclusions: Overall, scrub typhus is much more common than previously thought. Previously described individual environmental and habitual risk factors seem to have less importance in South India, perhaps because of the overall scrub typhus-conducive nature of the environment in this region., (© 2017 John Wiley & Sons Ltd.)

Aim: The aim of the study was to measure patient's satisfaction level and acceptance of conscious sedation as a method of pain relief following transvaginal oocyte retrieval (TVOR) during assisted reproduction technology treatment. We also evaluated the factors that may influence the efficacy of conscious sedation method., Setting and Design: A prospective cross-sectional study., Materials and Methods: Prospective study was conducted from October 2015 to January 2016 at a university-level hospital and 100 women were recruited. Variables for analysis included woman age, duration of procedure, number of oocytes retrieved, and transmyometrial passage of the needle. Pain assessment was done by visual analog scale (VAS). Medical complications, and patient satisfaction score [Likert's score and client satisfaction questionnaire (CSQ)] were recorded., Results: There was a moderate positive correlation between age and pain score on day 1 post-procedure. When the duration of procedure was >12 min, immediate post-procedure pain score was significantly higher compared to those whose procedure where duration was <12 min. There was no correlation between pain score and the number of oocytes retrieved (≤5, 6-15, and ≥16) and transmyometrial passage of needle. The VAS 10-point score immediately post-procedure, after 6 and 24 h post-procedure, and on day of embryo transfer was 2.83 (±1.67), 0.78 (±1.04), 0.39 (±1.09), and 0.14 (±0.58), respectively. The Likert's score was 3.65 (±0.82) and mean CSQ was 27.04 (±3.01). Majority of the women (86%) preferred the same pain relief method for future analgesia. There were no major complications., Conclusion: Conscious sedation was associated with high satisfaction level and acceptance rate among patients undergoing TVOR., Competing Interests: There are no conflicts of interest.

Background: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention., Methods: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera., Results: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection., Conclusions: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Diarrhea causes significant morbidity and mortality in Indian children under 5 years of age. Flies carry enteric pathogens and may mediate foodborne infections. In this study, we characterized fly densities as a determinant of infectious diarrhea in a longitudinal cohort of 160 urban and 80 rural households with 1,274 individuals (27% under 5 years of age) in Vellore, India. Household questionnaires on living conditions were completed at enrollment. Fly abundance was measured during the wet and dry seasons using fly ribbons placed in kitchens. PCRs for enteric bacteria, viruses, and protozoa were performed on 60 fly samples. Forty-three (72%) fly samples were positive for the following pathogens: norovirus (50%), Salmonella spp. (46.7%), rotavirus (6.7%), and Escherichia coli (6.7%). Ninety-one episodes of diarrhea occurred (89% in children under 5 years of age). Stool pathogens isolated in 24 of 77 (31%) samples included E. coli, Shigella spp., Vibrio spp., Giardia, Cryptosporidium, and rotavirus. Multivariate log-linear models were used to explore the relationships between diarrhea and fly densities, controlling for demographics, hygiene, and human-animal interactions. Fly abundance was 6 times higher in rural than urban sites (P < 0.0001). Disposal of garbage close to homes and rural living were significant risk factors for high fly densities. The presence of latrines was protective against high fly densities and diarrhea. The adjusted relative risks of diarrheal episodes and duration of diarrhea, associated with fly density at the 75th percentile, were 1.18 (95% confidence interval [CI], 1.03 to 1.34) and 1.15 (95% CI, 1.02 to 1.29), respectively. Flies harbored enteric pathogens, including norovirus, a poorly documented pathogen on flies., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Recent emphasis on eye care in intensive care unit (ICU) patients has translated to eye assessment being part of routine care. In this setting, we determined the incidence, risk factors, and resolution time of exposure keratopathy., Methods: In this prospective cohort study, 301 patients were examined within 24 hours of ICU admission and subsequently daily by an ophthalmologist till death or discharge. Eyelid position, conjunctival and corneal changes, treatment, and outcome data were collected., Results: Admission diagnoses included febrile illnesses (35.2%) and respiratory failure (32.6%); 84.1% were ventilated. Forty-nine patients had exposure keratopathy (bilateral = 35, unilateral = 14) at admission; 35 patients developed new onset keratopathy (incidence 13.2%) 4.6 ± 2.6 days after ICU admission. In 67 patients, keratopathy was mild (punctate epithelial erosions). Macroepithelial defects (n = 9), stromal whitening with epithelial defect (n = 3), and stromal scar (n = 3) were infrequent. None developed microbial keratitis. On multivariate logistic regression analysis, eyelid position (odds ratio, 2.93; 95% confidence interval, 1.37-6.25), and ventilation duration (odds ratio, 1.11; 95% confidence interval, 1.04-1.19) were strongly associated with the development of keratopathy after ICU admission. Keratopathy resolved in 3.6 ± 4.5 days., Conclusions: Severe exposure keratopathy is infrequent in a protocolized ICU setting. Eyelid position and duration of ventilation are associated with exposure keratopathy., (Copyright © 2014 Elsevier Inc. All rights reserved.)