Rotavirus Vaccine Effectiveness Research Articles

Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study

The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH).

Effectiveness of rotavirus vaccine against hospital admission for rotavirus diarrhoea in Brazilian children: a case-control study

BackgroundIn Brazil, before the introduction of the monovalent rotavirus vaccine in 2006, between 22% and 38% of children younger than age 5 years admitted to hospital with diarrhoea had positive stool samples for rotavirus. Rotavirus vaccine effectiveness against hospital admission caused by the G2[P4] genotype in Brazil is estimated to be 40–85%. We estimated overall and genotype-specific vaccine effectiveness and the effect of time since vaccination on hospital admission for Brazilian children with rotavirus diarrhoea. MethodsWe did a case-control study of ten general hospitals from the Rotavirus Diarrhoea Surveillance System of five regions of Brazil, from July 2008, to August 2011. 215 patients (aged 4–24 months) with confirmed rotavirus diarrhoea were recruited and 1961 controls (admitted to hospital without diarrhoea) were frequency matched to cases by sex and age group. We estimated vaccine effectiveness with multivariable logistic regression adjusted for year of birth; sex and age; variance estimation of Jackknife (crude) and confounders (adjusted). FindingsTwo-dose crude vaccine effectiveness was 76% (95% CI 58–86), lasting for 2 years. Two-dose adjusted effectiveness was 72% (44–85), suggesting no noticeable confounding. 80 (51%) patients had genotype G2[P4] and 24 (15%) had G1[P8]. Two-dose vaccine effectiveness was 89% (78–95) for G1[P8] and 76% (64–84) for G2[P4]; 74% (35–90) for all G1, 76% (63–84) for all G2, and 63% (27–99) for all non-G1 or non-G2. One dose vaccine effectiveness for all genotypes was 62% (39–97). InterpretationTwo-dose vaccine effectiveness for prevention of hospital admission with rotavirus diarrhoea was high, lasted for at least 2 years, and was similar for both G1[P8] and G2[P4]. On the basis of these findings we recommend the continued use of this vaccine in the Brazilian Immunization Program and monitoring of the emergence of unusual and novel rotavirus genotypes. FundingHealth Surveillance of the Ministry of Health of Brazil.

Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses

The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher’s exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by GIP[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

Impact of rotavirus vaccine on premature infants.

Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. NCT00740935.).

Distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after its introduction: a systematic review and meta-analysis

Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80-98) against homotypic strains, 71% (39-86) against partly heterotypic strains, and 87% (76-93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36-73), 72% (58-81), and 47% (28-61). In high-income countries, RV5 vaccine effectiveness was 83% (78-87) against homotypic strains, 82% (70-89) against single-antigen vaccine type strains, 82% (70-89) against partly heterotypic strains, and 75% (47-88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58-78) against single-antigen vaccine type strains, 37% (10-56) against partly heterotypic strains, and 87% (38-97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P[4] (2198 of 4428, 50%) and G1P[8] (953, 22%), and those in countries using RV5 were G1P[8] (1280 of 3875, 33%) and G2P[4] (1169, 30%). Sustained predominance of a single strain was not recorded. RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. None.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

BackgroundRotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in OmanMethodsA Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives.ResultsA universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective.ConclusionsUniversal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

Epidemiology of rotavirus diarrhoea in Albania.

The aim of the study was to estimate the prevalence of rotavirus disease in children<5 years old in Tirana, Albania, and to monitor and characterize the rotavirus genotypes. Rotavirus was detected in 21% of samples, more frequently in children under 2 years of age, which accounted for 80.8% of all positive cases. Among all rotavirus-positive samples collected, G4P[8] was the most prevalent genotype (38%), followed by G1P[8] (36.6%). The use of safe and effective rotavirus vaccines for the prevention of severe diarrhoea and the reduction of treatment costs will be of great importance for Albania.

Intussusception risk after rotavirus vaccination in U.S. infants

To the Editor: Yih et al. (Feb. 6 issue)1 report that a rotavirus vaccine was associated with approximately 1.5 excess cases of intussusception per 100,000 recipients of the first dose among infants in the United States. Changes in temporal trends in the incidence of intussusception have been described in a few studies based on hospitalization data.2-5 This surveillance allows a historical baseline view of the incidence of intussusception. Five-year data from the network of regional emergency departments in southern France included more than 1 million visits by patients younger than 18 years of age. These data showed an increase in the incidence of intussusception, defined according to the diagnosis code,2 from 31.9 cases per 100,000 visits in 2009 to 74.1 cases per 100,000 visits in 2013 (odds ratio, 2.32; 95% confidence interval, 1.74 to 3.11) (Fig. 1). The vaccine coverage among less than 10% of the population in France could not explain this variation. During the same 2009–2013 period, the global incidence of intussusception was highest among children between 1 and 2 years of age (average incidence in this age group, 97.7 cases per 100,000 visits) and the increase in the incidence among children in this age group was similar to the increase among all children. Emergency department databases permit real-time surveillance of the incidence of intussusception, but because of natural changes in incidence, information obtained from these databases should be interpreted with caution. These data alone are not sufficient in pharmacovigilance for adverse effects of rotavirus vaccine. Guilhem Noel, M.D.

Effectiveness of the monovalent rotavirus vaccine in Colombia: A case-control study

ObjectiveTo assess the effectiveness of the monovalent rotavirus vaccine (RV1) to prevent rotavirus diarrhea admissions to emergency departments (ED) in Colombia. MethodsA multicenter case-control study was carried out in six Colombian cities from 2011 to January, 2013. Cases were laboratory confirmed rotavirus diarrhea patients admitted to ED of selected health centers. Controls were patients with non-rotavirus diarrhea. Vaccination status was card-confirmed. Vaccine effectiveness and 95% confidence intervals (CI) were calculated from the conditional logistic regression models using the formula 1−adjusted odds ratio×100. Results1051 fecal samples were collected from 193 cases and 858 controls. Vaccination history was confirmed on 173 cases (90%) and 801 controls (93%). Among the rotavirus-positive samples with vaccination history, 57% were G2P[4], 9.8% G9P[8], 6% G9P[6]. Median age of cases (17 months) was greater than controls (15 months) (P<0.001), and mothers of cases had lower level of education (P=0.025). The adjusted effectiveness was 79.19% (95% CI, 23.7 to 94.32) among children 6–11 months of age and −39.75% (95% CI, −270.67 to 47.24) among those >12 months of age. Against overnight rotavirus hospitalizations, RV1 provided protection of 84.42% (95% CI, 22.68 to 96.86) among children 6–11 months of age, and −79.49% (95% CI, −555.8 to 51.08) among those >12 months. ConclusionsRV1 provided significant protection against rotavirus hospitalization among children under 1 year of age in the Colombian setting. The observation of lower effectiveness in children >12 months requires further assessment.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial

Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

A sham case-control study of effectiveness of DTP-Hib-hepatitis B vaccine against rotavirus acute gastroenteritis in Kenya.

BackgroundIn many GAVI-eligible countries, effectiveness of new vaccines will be evaluated by case-control methodology. To inform the design and assess selection bias of a future case-control study of rotavirus vaccine effectiveness (VE) in western Kenya, we performed a sham case-control study evaluating VE of pentavalent vaccine (DTP-Hib-HepB) against rotavirus acute gastroenteritis (AGE).MethodsFrom ongoing rotavirus surveillance, we defined cases as children 12 weeks to 23 months old with EIA-confirmed rotavirus AGE. We enrolled one community-based and two hospital-based control groups. We collected vaccination status from cards at enrollment, or later in homes, and evaluated VE by logistic regression.ResultsWe enrolled 91 cases (64 inpatient, 27 outpatient), 252 non-rotavirus AGE facility-based controls (unmatched), 203 non-AGE facility-based controls (age-matched) and 271 community controls (age-matched). Documented receipt of 3 pentavalent doses was 77% among cases and ranged from 81-86% among controls. One percent of cases and 0-2% of controls had no pentavalent doses. The adjusted odds ratio of three versus zero doses for being a case was 3.27 (95% CI 0.01-1010) for community controls and 0.69 (95% CI 0.06-7.75) for non-rotavirus hospital-based AGE controls, translating to VE of -227% and 31%, respectively, with wide confidence intervals. (No facility-based non-AGE controls were unvaccinated.) Similar results were found for ≥2 pentavalent doses and for severe rotavirus AGE.ConclusionsThe study showed that it is feasible to carry out a real case control in the study area, but this needs to be done as soon as the vaccine is introduced to capture the real impact. Sham case-control or pilot studies before vaccine introduction can be useful in designing case-control VE studies.

Effectiveness of rotavirus vaccine against hospitalized rotavirus diarrhea: A case–control study

Rotavirus is one of the leading cause of hospitalization and outpatients visits among children under five years. This study evaluated overall and genotype-specific vaccine effectiveness of oral monovalent rotavirus vaccine (G1P[8] strain) in preventing hospital admission of Brazilian children with rotavirus acute diarrhea.A hospital based case–control study was conducted in five Regions of Brazil using the National Rotavirus Acute Diarrhea Surveillance System from July 2008 to August 2011. A total of 215 cases (aged 4–24 months) admitted with confirmed rotavirus diarrhea were recruited and 1961 controls hospitalized without diarrhea were frequency matched by sex and age group to cases.Two-dose adjusted vaccine effectiveness (adjusted by year of birth and the frequency matching variables) was 76% (95%CI: 58–86) lasting for two years. Effectiveness controlled by the available potential confounders was 72% (95%CI: 44–85), suggesting no appreciable confounding by those factors for which adjustment was made. In a half of the cases the rotavirus genotype was G2P[4] and in 15% G1P[8]. Genotype-specific VE (two doses) was 89% (95%CI: 78–95), for G1P[8] and 76% (95%CI: 64–84) for G2P[4]. For all G1, it was 74% (95%CI: 35–90), for all G2, 76% (95%CI: 63–84), and for all non G1/G2 genotypes, 63% (95%CI: −27–99). Effectiveness for one dose was 62% (95%CI: 39–97).Effectiveness of two-dose monovalent rotavirus vaccine in preventing hospital admission with rotavirus diarrhea was high, lasted for two years and it was similar against both G1P[8] and G2P[4]. Based on the findings of the study we recommend the continued use of rotavirus in the Brazilian National Immunization Program and the monitoring of the early emergence of unusual and novel rotavirus genotypes.

Molecular Epidemiology of Contemporary G2P[4] Human Rotaviruses Cocirculating in a Single U.S. Community: Footprints of a Globally Transitioning Genotype

Group A rotaviruses (RVs) remain a leading cause of childhood gastroenteritis worldwide. Although the G/P types of locally circulating RVs can vary from year to year and differ depending upon geographical location, those with G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] specificities typically dominate. Little is known about the evolution and diversity of G2P[4] RVs and the possible role that widespread vaccine use has had on their increased frequency of detection. To address these issues, we analyzed the 12 G2P[4] RV isolates associated with a rise in RV gastroenteritis cases at Vanderbilt University Medical Center (VUMC) during the 2010-2011 winter season. Full-genome sequencing revealed that the isolates had genotype 2 constellations typical of DS-1-like viruses (G2P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Phylogenetic analyses showed that the genome segments of the isolates were comprised of two or three different subgenotype alleles; this enabled recognition of three distinct clades of G2P[4] viruses that caused disease at VUMC in the 2010-2011 season. Although the three clades cocirculated in the same community, there was no evidence of interclade reassortment. Bayesian analysis of 328 VP7 genes of G2 viruses isolated in the last 39 years indicate that existing G2 VP7 gene lineages continue to evolve and that novel lineages, as represented by the VUMC isolates, are constantly being formed. Moreover, G2 lineages are characteristically shaped by lineage turnover events that introduce new globally dominant strains every 7 years, on average. The ongoing evolution of G2 VP7 lineages may give rise to antigenic changes that undermine vaccine effectiveness in the long term. Little is known about the diversity of cocirculating G2 rotaviruses and how their evolution may undermine the effectiveness of rotavirus vaccines. To expand our understanding of the potential genetic range exhibited by rotaviruses circulating in postvaccine communities, we analyzed part of a collection of rotaviruses recovered from pediatric patients in the United States from 2010 to 2011. Examining the genetic makeup of these viruses revealed they represented three segregated groups that did not exchange genetic material. The distinction between these three groups may be explained by three separate introductions. By comparing a specific gene, namely, VP7, of the recent rotavirus isolates to those from a collection recovered from U.S. children between 1974 and 1991 and other globally circulating rotaviruses, we were able to reconstruct the timing of events that shaped their ancestry. This analysis indicates that G2 rotaviruses are continuously evolving, accumulating changes in their genetic material as they infect new patients.

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.

Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice

BackgroundConflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy. MethodsWe randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams’ diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA. ResultsRBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (P<.0001). RRV vaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (P<.0001). Vaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (P<.05), however we detected no effects of undernutrition on viral clearance nor of infection on bodyweight. EDIM infection provoked higher anti-RV serum IgA levels in RBD vs. CD mice, regardless of vaccination (P<.0001). Last, RRV vaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (P<.0001). ConclusionsDespite modulated IgA responses to vaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings.

Comparison of 2 Assays for Diagnosing Rotavirus and Evaluating Vaccine Effectiveness in Children with Gastroenteritis

We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%–91%]) in EIA-positive children but offered no significant protection (14% [95% CI −105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients.

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.

Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study

Objective To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia.Design Case-control study.Setting Six hospitals in Bolivia, between March 2010...

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

PRM184 - The influence of choice task layout on the outcomes of a discrete choice experiment

Objectives To empirically test to what extent the layout of choice tasks (i.e., displayed in words or graphics) in a Discrete Choice Experiment (DCE) influences the attribute estimates and the conclusions drawn from the DCE. Methods A DCE questionnaire was sent to the parents of 2500 newborn babies aged 6 weeks at maximum. Each questionnaire contained two times the same 9 choice tasks, ones words were used to describe the attributes and levels and ones graphics were used. The DCE consisted of five attributes related to the decision of parents to vaccinate their newborn baby against the rotavirus (vaccine effectiveness, frequency of severe side effects, protection duration, location, costs). Mixed logit models were conducted to estimate the relative importance of the attributes. Results Preliminary results are based on 279 observations from 31 parents. In February 2013 data collection will be completed and analyzed. When comparing the choices of every respondent per choice tasks, 58% chose inconsistent at 1 or more choice tasks and 35% chose inconsistent in two or more choice tasks. In both datasets (layout in words and graphics), vaccine effectiveness (βeffects code 1=0.64 and βeffects code 1=1.00, βeffects code 2=0.67 and βeffects code 2=0.01), frequency of severe side effects (βeffects code 1=0.26 and βeffects code 1=0.41, βeffects code 2=1.22 and βeffects code 2=0.89) protection duration (β=0.37, β=0.17) and costs (β=-0.10, β=-0.11) showed significant attribute estimates (P<.05). However, the relative importance of these attributes differed between both datasets. Conclusions For now it can be concluded that the presentation of the choice sets (by either using words or graphics) in a DCE influences study outcomes. Besides extensive pilot testing to ensure the choice tasks are understood and interpreted as intended, it might be worthwhile to include discussions about the layout of the choice tasks in the focus group stage of the DCE designing process