Persistence of G10P[11] neonatal rotavirus infections in southern India.

BACKGROUND: Neonatal rotavirus infections are predominantly caused by distinct genotypes restricted to this age-group and are mostly asymptomatic. METHOD: Stool samples from neonates admitted for >48 h in neonatal intensive care units (NICUs) in Vellore (2014-2015) and Chennai (2015-2016) in southern India, and from neonates born at hospitals in Vellore but not admitted to NICUs (2015-2016) were tested for rotavirus by ELISA and genotyped by hemi-nested RT-PCR. RESULTS: Of 791 neonates, 150 and 336 were recruited from Vellore and Chennai NICUs, and 305 were born in five hospitals in Vellore. Positivity rates in the three settings were 49.3% (74/150), 29.5% (99/336) and 54% (164/305), respectively. G10P[11] was the commonly identified genotype in 87.8% (65/74), 94.9% (94/99) and 98.2% (161/164) of the neonates in Vellore and Chennai NICUs, and those born at Vellore hospitals, respectively. Neonates delivered by lower segment cesarian section (LSCS) at Vellore hospitals, not admitted to NICUs, had a significantly higher odds of acquiring rotavirus infection compared to those delivered vaginally [p = 0.002, OR = 2.4 (1.4-4.3)]. CONCLUSIONS: This report demonstrates the persistence of G10P[11] strain in Vellore and Chennai, indicating widespread neonatal G10P[11] strain in southern India and their persistence over two decades, leading to interesting questions about strain stability.

Geographically Weighted Regression Modeling of Spatial Clustering and Determinants of Focal Typhoid Fever Incidence.

BACKGROUND: Typhoid is known to be heterogenous in time and space, with documented spatiotemporal clustering and hotspots associated with environmental factors. This analysis evaluated spatial clustering of typhoid and modeled incidence rates of typhoid from active surveillance at 4 sites with child cohorts in India. METHODS: Among approximately 24 000 children aged 0.5-15 years followed for 2 years, typhoid was confirmed by blood culture in all children with fever >3 days. Local hotspots for incident typhoid cases were assessed using SaTScan spatial cluster detection. Incidence of typhoid was modeled with sociodemographic and water, sanitation, and hygiene-related factors in smaller grids using nonspatial and spatial regression analyses. RESULTS: Hotspot households for typhoid were identified at Vellore and Kolkata. There were 4 significant SaTScan clusters (P < .05) for typhoid in Vellore. Mean incidence of typhoid was 0.004 per child-year with the highest incidence (0.526 per child-year) in Kolkata. Unsafe water and poor sanitation were positively associated with typhoid in Kolkata and Delhi, whereas drinking untreated water was significantly associated in Vellore (P = .0342) and Delhi (P = .0188). CONCLUSIONS: Despite decades of efforts to improve water and sanitation by the Indian government, environmental factors continue to influence the incidence of typhoid. Hence, administration of the conjugate vaccine may be essential even as efforts to improve water and sanitation continue.

Factors Predicting Blood Culture Positivity in Children With Enteric Fever.

BACKGROUND: Blood culture, despite low sensitivity, is the gold standard for enteric fever diagnosis. Understanding predictors of blood culture positivity may help design strategies to optimize enteric fever diagnosis. METHODS: A cohort of 6760 children aged 0.5-15 years was followed for 3 years for enteric fever with blood cultures in an automated system, for fevers >3 days. Factors affecting test positivity in fevers and participant-level predictors for culture refusals were analyzed using regression models. RESULTS: Overall, 6097 suspected typhoid/paratyphoid fever (STF) episodes were reported, of which 5703 (93.5%) STFs had sampling for blood cultures, with 394 (6.5%) refusals. Salmonella enterica serovar Typhi/Paratyphi positivity was culture-confirmed in 3.8% (218/5703) of STF episodes. Older children (odds ratio [OR], 1.96 [95% CI, 1.39-2.77]), larger blood volume inoculated (OR, 2.82 [95% CI, 1.71-4.66]), higher temperatures during fever (OR, 3.77 [95% CI, 2.89-4.91]), and fevers diagnosed as suspected typhoid or acute undifferentiated fever (OR, 6.06 [95% CI, 3.11-11.78]) had a higher probability of culture positivity. Antibiotics before culture did not decrease culture positivity. Blood culture refusals were higher for children from wealthier households or with milder illness. CONCLUSIONS: Performing blood cultures in older children with fever, especially those fevers with toxic presentation and increasing blood volume for inoculation are strategies to improve enteric fever detection in surveillance settings.

Antibiotics for Fever Among Children: Findings From the Surveillance for Enteric Fever in India Cohorts.

BACKGROUND: Acute febrile illness in children is frequently treated with antibiotics. However, the inappropriate use of antibiotics has led to the emergence of multidrug-resistant pathogens. METHODS: We measured use of antibiotics for fever in 4 pediatric cohorts that were part of the Surveillance for Enteric Fever in India (SEFI) network. In this network, 24 062 children were followed up weekly, capturing information on fever and other morbidity between October 2017 and December 2019. RESULTS: An antibiotic was given in 27 183 of the 76 027 (35.8%) episodes of fever. The incidence of fever-related antibiotic use was 58.0 (95% confidence interval [CI], 57.2-58.6) per 100 child-years. The median time to initiation of antibiotics was 4 days, and in 65% of those who received an antibiotic it was initiated by the second day. Antibiotics were continued for <3 days in 24% of the episodes. Higher temperature, younger age, male sex, joint family, higher education, internet access, and availability of personal conveyance were associated with antibiotic treatment for fever. CONCLUSIONS: In developing countries where antibiotic use is not regulated, broad-spectrum antibiotics are initiated early, and often inappropriately, in febrile illness. Frequent and inappropriate use of antibiotics may increase risk of antimicrobial resistance.

Hospitalization Rates and Direct Medical Costs for Fever in a Pediatric Cohort in South India.

BACKGROUND: Primary data on causes and costs of hospitalization are necessary for costing and cost-effectiveness analysis. Data on incidence and causes of hospitalization and consequent expenses among Indian children are limited. METHODS: A cohort of 6000 children aged 0.5-15 years residing in urban Vellore was followed for 3 years, under the Vellore Typhoid Study, 2016-2017, and later under the Surveillance for Enteric Fever project, 2017-2019. Data on hospitalization events and associated antibiotic use, and direct medical costs for fever-related hospitalization of study children were obtained from caregivers through weekly follow-up by study field workers. RESULTS: The incidence of hospitalization was 33 per 1000 child-years of observation. Children aged 0.5-5 years had the highest incidence of hospitalization. The top 5 infectious causes for hospitalization were acute undifferentiated fevers, respiratory tract infections, acute gastroenteritis, enteric fever, and dengue. The overall median cost of hospitalization for fever was 4243 (interquartile range, 2502-7215) Indian rupees (INR). An episode of dengue had a median cost of 5627 INR, followed by acute undifferentiated fevers and enteric fever with median costs of 3860 and 3507 INR, respectively. CONCLUSIONS: Hospitalization for fever is common in young children and impacts household finances in low-income Indian households.

Impact of rotavirus vaccines in low and middle-income countries.

PURPOSE OF REVIEW: Rotavirus vaccines are playing a pivotal role in improving lives of infants and young children in low and middle-income countries (LMICs). Many of these countries have adopted the vaccine into their routine immunization, whereas others are considering introduction. This article provides an update on the impact of rotavirus vaccines in LMICs on morbidity and mortality in children aged less than 5 years, and their cost-effectiveness. RECENT FINDINGS: The WHO, in 2013, updated its recommendation to prioritize introduction of rotavirus vaccines in the routine immunization schedule, without age restrictions. Despite the decreased efficacy of the vaccines in LMICs, data from Sub-Saharan Africa have demonstrated a decrease in rotavirus-related morbidity, with some sites reporting an indirect protective effect on children age ineligible to receive the vaccine. Even with improvements in sanitation, nutritional status in children, and other health-related indices in LMICs, the use of rotavirus vaccines will play an important role in preventing rotavirus-related gastroenteritis. Economic models predict a reduction in economic burden because of rotavirus-related health costs, making vaccine introduction cost-effective in resource-constrained settings. SUMMARY: Increasing evidence from impact studies shows the significant impact of rotavirus vaccination on hospitalizations and economic burden because of rotavirus gastroenteritis in LMICs. Universal rotavirus vaccination is recommended, and introductions should be monitored by robust surveillance systems to measure effectiveness and impact.

Cryptosporidiosis in children in the Indian subcontinent.

Cryptosporidiosis is a leading cause of diarrheal disease among children under two in developing countries. Previous estimates have shown a high burden of cryptosporidial diarrhea in children from Sub-Saharan Africa and South Asia. Asymptomatic cryptosporidial infections which go undetected and untreated have been shown to result in significant malnutrition. In this review, we carried out a literature search of studies published on cryptosporidiosis in children in the Indian subcontinent from 1983 to 2016. Of the 154 publications identified, 54 were included for final analysis with both hospital-based and community-based studies. There were wide variations in reported prevalence rates from hospital studies and highlight the need to be carry out these studies with uniform sampling and molecular tools for detection, especially in countries with a dearth of information. Community-based studies, however, showed similarities in spite of differences in when (the late 1990s up until recently) and where (South India or Bangladesh) they were conducted. When more sensitive detection methods were used, cryptosporidial diarrhea accounted for 7%-9% of all diarrhea episodes and 20%-30% of children in these cohorts experienced at least one cryptosporidial diarrheal episode. High rates of asymptomatic infections with increased detection by serology and multiple infections (symptomatic and asymptomatic) were also documented in all cohorts. This overview brings to light the high burden of disease associated with cryptosporidiosis in children in the subcontinent and the gaps in knowledge to be addressed.