Background Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. Methods We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Results Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Conclusions Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR.
In January 2006, the Journal published two landmark articles reporting the safety and efficacy of two different vaccines - RotaTeq (Merck), a pentavalent vaccine (RV5)(1) and Rotarix (GlaxoSmithKline), a monovalent vaccine (RV1)(2) - to prevent rotavirus, the most common cause of severe childhood diarrhea worldwide and of deaths from diarrhea in low-income countries. Each trial enrolled more than 60,000 infants to determine whether these live oral vaccines caused intussusception, the rare complication that in 1999 forced the withdrawal of the first licensed rotavirus vaccine, RotaShield (Wyeth Lederle), less than a year after it was recommended for routine immunization of U.S. . . .
Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p=0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p=0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p<0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p<0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score≥16) was 60.5% (95% CI 17.7, 81, p=0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p=0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).
Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.
A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine.
INTRODUCTION: Hospital discharge records and laboratory data have shown a substantial early impact from the rotavirus vaccination program that commenced in 2007 in Australia. However, these assessments are affected by the validity and reliability of hospital discharge coding and stool testing to measure the true incidence of hospitalised disease. The aim of this study was to assess the validity of these data sources for disease estimation, both before and after, vaccine introduction. METHODS: All hospitalisations at a major paediatric centre in children aged <5 years from 2000 to 2009 containing acute gastroenteritis (AGE) ICD 10 AM diagnosis codes were linked to hospital laboratory stool testing data. The validity of the rotavirus-specific diagnosis code (A08.0) and the incidence of hospitalisations attributable to rotavirus by both direct estimation and with adjustments for non-testing and miscoding were calculated for pre- and post-vaccination periods. RESULTS: A laboratory record of stool testing was available for 36% of all AGE hospitalisations (n=4948) the rotavirus code had high specificity (98.4%; 95% CI, 97.5-99.1%) and positive predictive value (96.8%; 94.8-98.3%), and modest sensitivity (61.6%; 58-65.1%). Of all rotavirus test positive hospitalisations only a third had a rotavirus code. The estimated annual average number of rotavirus hospitalisations, following adjustment for non-testing and miscoding was 5- and 6-fold higher than identified, respectively, from testing and coding alone. Direct and adjusted estimates yielded similar percentage reductions in annual average rotavirus hospitalisations of over 65%. CONCLUSION: Due to the limited use of stool testing and poor sensitivity of the rotavirus-specific diagnosis code routine hospital discharge and laboratory data substantially underestimate the true incidence of rotavirus hospitalisations and absolute vaccine impact. However, this data can still be used to monitor vaccine impact as the effects of miscoding and under-testing appear to be comparable between pre and post vaccination periods.
Background: There are no studies on clinically significant transaminase elevation due to rotavirus gastroenteritis in the literature. Also, there are significant discrepancies among previous studies regarding the prevalence of increased serum transaminase levels in rotavirus infection. Methods: Patients investigated for rotavirus by stool antigen testing, who were followed between January 2005 and May 2012, were retrospectively enrolled in this study. Patients were divided into 2 groups according to their rotavirus results: rotavirus-positive acute gastroenteritis (RPAG) and rotavirus-negative acute gastroenteritis (RNAG) groups. Results: A total of 4317 children who presented with acute gastroenteritis were assessed. The study was completed with 642 patients who met the inclusion criteria. In the RPAG group (n = 272), elevated alanine aminotransferase (ALT) was found in 42 (15.4%) patients and elevated aspartate aminotransferase (AST) in 69 (25.4%), while in the RNAG group (n = 370), these numbers were 25 (6.8%) and 44 (11.9%), respectively. The elevated ALT and AST levels were found to be significantly higher in the RPAG group than in the RNAG group (both p < 0.001). The prevalence of elevated transaminase levels was found to be similar with respect to gastroenteritis severity score (p > 0.05). The high serum transaminase levels normalized uneventfully in all patients in the RPAG and RNAG groups during follow-up. Conclusions: In this study, our results clearly signify a liver influence in rotavirus infections. Therefore, rotavirus infections should be kept in mind when evaluating the aetiology of transaminase elevation in patients with acute gastroenteritis.
Transmission of rotavirus vaccine or vaccine-reassortant strains to unvaccinated contacts has been reported. Therefore, it is essential to evaluate and characterize the nature of vaccine-virus shedding among rotavirus vaccine recipients. Two groups of healthy infants who received a complete course of RotaTeq (RV5) or Rotarix (RV2) were enrolled (between March 2010 and June 2011) to compare fecal shedding for one month after each vaccine dose. Shedding was assessed using both enzyme immunoassay (EIA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Eighty-seven infants (34 girls and 53 boys) were enrolled in the study. After the first vaccine dose, the peak time of virus shedding occurred between day 4 and day 7, with positive detection rates of 80-90% by real-time RT-PCR and 20-30% by EIA. In both groups, vaccine shedding occurred as early as one day and as late as 25-28 days. Mixed effects logistic regression analysis of real-time RT-PCR data showed no significant differences between two groups when shedding rates were compared after the first vaccine dose (odds ratio [OR] 1.26; P=0.71) or after the second vaccine dose (odds ratio [OR] 1.26; P=0.99). However, infants receiving RV2 shed significantly higher viral loads than those receiving RV5 when compared after the first vaccine dose (P=0.001) and after the second dose (P=0.039). In terms of shedding rates detected by real-time RT-PCR, vaccine uptake of RV5 or RV2 among infants in Taiwan was comparable. Clinical significance of higher shedding viral loads in RV2 should be further observed.
Introduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme.