Publications by authors named "Umesh Parashar"

Background: The underlying causes for lower rotavirus vaccine effectiveness (VE) in high-child-mortality settings are not well understood. Uganda introduced the human monovalent G1P[8] rotavirus vaccine (Rotarix) in June 2018. We determined the effectiveness of Rotarix against rotavirus diarrhea requiring hospital care among Ugandan children.

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Norovirus is the leading cause of acute gastroenteritis (AGE) globally. Few longitudinal studies have assessed norovirus-associated AGE incidence across age groups in community settings in Latin America. During April 2015-April 2019, active surveillance for AGE among community members of all ages was conducted through household visits two to three times per week in San Jeronimo, Cusco, Peru.

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Post rotavirus vaccine introduction in Mozambique (September 2015), we documented a decline in rotavirus-associated diarrhoea and genotypes changes in our diarrhoeal surveillance spanning 2008-2021. This study aimed to perform whole-genome sequencing of rotavirus strains from 2009 to 2012 (pre-vaccine) and 2017-2018 (post-vaccine). Rotavirus strains previously detected by conventional PCR as G2P[4], G2P[6], G3P[4], G8P[4], G8P[6], and G9P[6] from children with moderate-to-severe and less-severe diarrhoea and without diarrhoea (healthy community controls) were sequenced using Illumina MiSeq platform and analysed using bioinformatics tools.

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Background And Objectives: Many neonatal intensive care units (NICUs) do not give rotavirus vaccines to inpatients due to a theoretical risk of horizontal transmission of vaccine strains. We aimed to determine incidence and clinical significance of vaccine-strain transmission to unvaccinated infants in a NICU that routinely administers pentavalent rotavirus vaccine (RV5).

Methods: This prospective cohort study included all patients admitted to a 100-bed NICU for 1 year.

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Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide. Vaccination offers the best protection against this disease, and two rotavirus vaccines were developed in India and included in its routine immunization program. The Government of India's decision to adopt this intervention was supported by a solid base of evidence from clinical trials, as well as substantial research regarding rotavirus disease burden and the potential health and economic value of immunization.

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Background: Rotavirus vaccines are moderately protective against illness in high mortality settings compared with low mortality settings. Vaccine effectiveness (VE) evaluations may clarify our understanding of these disparities, but estimates among key subpopulations and against rare outcomes are not available in many analyses due to sample size. We combined 25 datasets from test-negative design case-control evaluations in 24 countries that enrolled children with medically-attended diarrhea, laboratory-confirmed rotavirus stool testing, and documented vaccination status.

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Background: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens.

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Background: Monovalent rotavirus vaccine substantially reduced rotavirus disease burden after introduction (May 2014) in Madagascar. We examined the effectiveness and long-term impact on acute watery diarrhea and rotavirus-related hospitalizations among children <5 years old at two hospitals in Antananarivo, Madagascar (2010-2022).

Methods: We used a test-negative case-control design to estimate monovalent rotavirus vaccine effectiveness (VE) against laboratory-confirmed rotavirus hospitalizations among children age 6-23 months with documented vaccination status adjusted for year of symptom onset, rotavirus season, age group, nutritional status, and clinical severity.

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Article Synopsis
  • Rotavirus was a major cause of gastroenteritis in US children until the introduction of vaccines in 2006, which led to significant reductions in severe cases.
  • A study from 2009 to 2022 analyzed vaccine effectiveness (VE) using data from children with acute gastroenteritis, revealing a 78% effectiveness rate against severe rotavirus-related medical visits.
  • The effectiveness varied by severity of disease, showing 94% effectiveness against very severe cases, with younger children benefiting the most from vaccination.
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Introduction: Rotavirus vaccines may provide indirect protection by reducing transmission in the population and thus reducing disease burden.

Methods: This systematic review summarizes estimates of indirect protection from rotavirus vaccines and the methods used to obtain these estimates.

Results: We identified 71 studies published between 2009 and 2022 that provided 399 estimates of indirect protection from rotavirus vaccine.

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Background: Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan.

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Article Synopsis
  • Enteric viruses are the main cause of diarrhea in children under 5, with rotavirus being a well-researched culprit in Mozambique, though other viruses lack data post-vaccine.
  • The study investigated the prevalence of norovirus GI and GII, adenovirus 40/41, astrovirus, and sapovirus in children with varying severity of diarrhea before and after the introduction of the rotavirus vaccine.
  • Results showed that all viruses, except norovirus GI, were detected more frequently after the vaccine's introduction, highlighting the importance of ongoing monitoring for these viruses to improve disease prevention strategies.
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Background: Quantitative molecular assays are increasingly used for detection of enteric viruses.

Methods: We compared the clinical severity using the modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIAs] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (Ct) cutoffs.

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Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition.

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During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness.

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Background: In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants.

Methods: Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan.

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Rotavin-M1 (POLYVAC) was licensed in Vietnam in 2012. The association of Rotavin-M1 with intussusception, a rare adverse event associated with rotavirus vaccines, and with adverse events following immunization (AEFI) have not been evaluated and monitored under conditions of routine use. From February 2017 to May 2021, we conducted a pilot introduction of Rotavin-M1 into the routine vaccination program in two provinces.

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Background: Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort.

Methods: Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017-2018 and followed for 2 years.

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Article Synopsis
  • Rotavirus group A (RVA) is a leading cause of serious diarrhea in children worldwide, but vaccination programs have significantly reduced hospitalizations and deaths related to it.
  • From 2016 to 2021, a study in Nam Dinh and Thua Thien Hue provinces of Vietnam monitored RVA prevalence, revealing significant shifts in dominant strains.
  • The G9, G3, and G8 strains were the most common, with G3 prevalence notably decreasing, while G1 strains re-emerged, underscoring the complexity of genotype changes and the ongoing need to evaluate vaccine effectiveness.
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Despite the 2009 World Health Organization recommendation that all countries introduce rotavirus vaccines (RVV) into their national immunization programs, just 81 countries had introduced RVV by the end of 2015, leaving millions of children at risk for rotavirus morbidity and mortality. In response, the Rotavirus Accelerated Vaccine Introduction Network (RAVIN) was established in 2016 to provide support to eight Gavi-eligible countries that had yet to make an RVV introduction decision and/or had requested technical assistance with RVV preparations: Afghanistan, Bangladesh, Benin, Cambodia, Democratic Republic of Congo, Lao People's Democratic Republic, Myanmar, and Nepal. During 2016-2020, RAVIN worked with country governments and partners to support evidence-based immunization decision-making, RVV introduction preparation and implementation, and multilateral coordination.

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Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network.

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Rotavirus (RV), norovirus (NoV), sapovirus (SaV), and human astrovirus (HAstV) are the most common viral causes of gastroenteritis in children worldwide. From 2016 to 2021, we conducted a cross-sectional descriptive study to determine the prevalence of these viruses in hospitalized children under five years old in Nam Dinh and Thua Thien Hue provinces in Vietnam during the pilot introduction of the RV vaccine, Rotavin-M1 (POLYVAC, Hanoi, Vietnam). We randomly selected 2317/6718 (34%) acute diarrheal samples from children <5 years of age enrolled at seven sentinel hospitals from December 2016 to May 2021; this period included one year surveillance pre-vaccination from December 2016 to November 2017.

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Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries.

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Article Synopsis
  • Adenovirus has been linked to hepatitis in immunocompromised children, but not typically in healthy ones; this changed in April 2022 when unexplained hepatitis cases surfaced in the USA and UK, prompting national surveillance by the CDC.
  • The study focused on children under 10 with unexplained hepatitis and elevated liver enzymes, collecting detailed medical data, caregiver interviews, and specimen testing to identify causes.
  • A total of 377 cases were documented from October 2021 to September 2022, with a median patient age of 2.8 years and a fairly equal distribution of males and females.
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Background: Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear.

Methods: We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023.

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