Severe Rotavirus Gastroenteritis In Children Research Articles

Comparison of Vesikari and Clark scales regarding the definition of severe rotavirus gastroenteritis in children

Background: Two clinical severity scales, the Vesikari scale and the Clark scale, are commonly used to assess the efficacy of rotavirus vaccines. The results obtained using the two severity scales differ significantly and hamper comparisons. The aim of this study was to compare the Clark and Vesikari scales and to determine whether modified classifications would provide a better correlation between the two scales. Methods: The severity of rotavirus gastroenteritis was assessed for each child using both the Vesikari and Clark scales. To make a statistical comparison between the two scales, the classifications were modified. Results: In total, 200 children with rotavirus gastroenteritis were evaluated. Of these, 57% were classified as severe by the Vesikari scale, and only 1.5% by the Clark scale (p < 0.001). When the Clark three-category scale was transformed into a two-category scale by merging mild and moderate categories as non-severe, a good correlation with the Vesikari scale still could not be found. Using the median of the severity scores as the severity threshold did not provide a better correlation between the two scales. Transforming the Vesikari two-category scale into a three-category scale by further subdividing the severe category into two parts, as moderate and severe (≥ 16), provided a better correlation between the two severity scales, but still did not achieve a good level of agreement. Conclusions: The Clark and Vesikari scales differ significantly in the definition of severe gastroenteritis. Even the attempts at reclassifying the scales did not achieve a good correlation.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life

Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age.In a double-blind placebo controlled multicenter trial, 6799 infants aged 6–7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. The number of infants needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0). Serious adverse events were observed at the same rates in the two groups. None of the eight intussusception events occurred within 30 days of a vaccine dose and all were reported only after the third dose.The sustained efficacy of the 116E in the second year of life is reassuring. Clinical Trial RegistryThe trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109).

The occurrence of severe rotavirus gastroenteritis in children under 3 years of age before and after the introduction of rotavirus vaccine: a prospective observational study in three pediatric clinics in Shibata City, Niigata Prefecture, Japan.

The occurrence of severe rotavirus gastroenteritis (RVGE) in children under 3 years of age before and after the introduction of rotavirus vaccine was prospectively surveyed in three pediatric clinics in Shibata City, Niigata Prefecture, Japan, during the 2011 and 2012 RVGE epidemic seasons. In this observational study, a significantly lower occurrence of severe RVGE among severe gastroenteritis cases was observed in 2012. The incidence rate of severe RVGE among outpatients in 2012 was significantly lower than that in 2011. Despite the significant reduction in severe RVGE, the results must be interpreted with caution because the surveillance period is short and requires extension to conclude whether the reduction in the incidence of severe RVGE is a direct effect of rotavirus vaccination. Therefore, we will continue the survey to evaluate the impact of vaccination.

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial

BackgroundA phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix™) against severe rotavirus gastroenteritis in children up to three years of age. MethodsHealthy infants aged 6–12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1–2 months post-Dose 2 using ELISA (cut-off=20U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. ResultsIn children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%–99.9%) and 96.1% (95% CI: 76.5%–99.9%), respectively. The seroconversion rate 1–2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%–99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. ConclusionRIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children.

Rotavirus vaccine-derived shedding and viral reassortants

Evaluation of: Donato CM, Ch’ng LS, Boniface KF et al. Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination. J. Infect. Dis. 206(3), 377–383 (2012).Two live, attenuated rotavirus vaccines, RotaTeq® (Merck) and Rotarix® (GlaxoSmithKline), have been used in Australia since July 2007 to prevent severe rotavirus gastroenteritis in children. Using active postvaccination monitoring, passive surveillance and state-of-the-art laboratory techniques, Donato et al. report that RotaTeq rotavirus vaccine and vaccine-derived strains were detected actively in stool samples from 13 out of 61 (21.3%) infants having diarrhea within 2 weeks of rotavirus vaccination, and among three out of 460 (0.7%) cases with acute gastroenteritis captured via the Australian Rotavirus Surveillance Program. Six (37.5%) of these 16 vaccine-derived viral specimens were associated with a G1P[8] strain thought to be the result of genetic reassortment between two component RotaTeq strains. Although nearly half of these reassortant-associated cases had underlying medical conditions, such as severe combined immunodeficiency disorder, further study is needed to understand the relationship between shedding, viral reassortants and underlying medical conditions.

Population-based surveillance for severe rotavirus gastroenteritis in children in Karachi, Pakistan

The incidence of rotavirus-associated severe diarrhoea and distribution of rotavirus genotypes in children less than five years of age was determined in two low-income communities in Karachi, Pakistan. Over a two-year period, 717 children met eligibility criteria for severe diarrhoea and stools were obtained from 575 (80%) with 97 (17%) being rotavirus positive. Adjusted annual rates of severe rotavirus diarrhoea in children less than five years and less than one year were respectively 5.7 and 16.9 per 1000 in community A, and 8.1 and 25.4 per 1000 child years of observation in community B. An estimated 1 in 40 infants experience a severe episode of rotavirus gastroenteritis annually in Pakistan. The most common rotavirus strains were G9P[8] (15%), G1P[8] (13%) and G1[P4] (8.4%). This information will inform policy decisions about the introduction of rotavirus vaccines.

Active, Population-Based Surveillance for Severe Rotavirus Gastroenteritis in Children in the United States

Routine vaccination of US infants against rotavirus was implemented in 2006, prompting the Centers for Disease Control and Prevention New Vaccine Surveillance Network to begin population-based acute gastroenteritis surveillance among US children<3 years of age. This surveillance system establishes baseline estimates of rotavirus disease burden and allows for the prospective monitoring of rotavirus vaccination impact. Eligible children with acute gastroenteritis (>or=3 episodes of diarrhea and/or any vomiting in a 24-hour period) who were hospitalized, were seen in emergency departments, or visited selected outpatient clinics in 3 US counties during the period of January through June 2006 were enrolled. Epidemiological and clinical information was obtained through parental interview and medical chart review, and stool specimens were tested for rotavirus with enzyme immunoassays. Rotavirus-positive specimens were genotyped by using reverse transcription-polymerase chain reaction assays. Stool specimens were collected from 516 of the 739 enrolled children with acute gastroenteritis (181 inpatient, 201 emergency department, and 134 outpatient) and 44% tested positive for rotavirus (227 of 516 specimens). The most common strain was P[8]G1 (84%), followed by P[4]G2 (5%) and P[6]G12 (4%). None of the 516 children had received rotavirus vaccine. The rotavirus detection rate was 50% for hospitalized acute gastroenteritis cases, 50% for emergency department visits, and 27% for outpatient visits. Rotavirus-related acute gastroenteritis cases were more likely than non-rotavirus-related acute gastroenteritis cases to present with vomiting, diarrhea, fever, and lethargy. Directly calculated, population-based rates for rotavirus hospitalizations and emergency department visits were 22.5 hospitalizations and 301.0 emergency department visits per 10 000 children<3 years of age, respectively. A sentinel outpatient clinic visit rate of 311.9 outpatient visits per 10,000 children<3 years of age was observed. Population-based, laboratory-confirmed rotavirus surveillance in the final rotavirus season before implementation of the US rotavirus vaccine program indicated a considerable burden of disease on the US health care system.

Impacto de gastroenteritis severa por rotavirus en niños chilenos menores de 3 años de edad

Rotavirus infections account every year in Chile, for approximately 53,000 emergency consultations and 8,000 hospital admissions among children under three years of age. To estimate incidence rates of severe rotavirus gastroenteritis in children <3 years of age, living in the V and VIII Regions and to identify the predominant viral serotypes. A prospective hospital-based surveillance for severe gastroenteritis was implemented in public and private hospitals of Viña del Mar and Valparaiso (Region V) and of Chiguayante, Concepción, Penco, San Pedro de la Paz, Talcahuano and Tomé (Region VIII). All children <3 years of age residing in the districts, who consulted for severe gastroenteritis requiring oral or intravenous rehydration (equivalent to WHO plan B or C), or who were admitted to the hospital, were enrolled. Demographic and clinical information and a stool sample were obtained. Rotavirus was detected by ELISA and positive samples were serotyped by ELISA or real time PCR. Between January 23 and June 30, 2003, a total of 760 children were recruited. Among these, 343 (45%) were admitted to the hospital. Stool samples were collected from 433 children. Among these, 214 were positive for rotavirus (49.4%). Overall, monthly disease incidence rates were 124/100,000 in V Region, and 114/100,000 in VIII Region. The predominant serotype was G4. Rotavirus was responsible for nearly half of the severe gastroenteritis episodes among children <3 years, during a predominantly G4 serotype season. Every year, approximately one every 70 children <3 years will have a severe rotavirus gastroenteritis episode.

A Rotavirus Vaccine for Infants: The Asian Experience

Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented. Completed RIX4414 trials have been reviewed. Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated. These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.