Rotavirus Vaccine Effectiveness Research Articles

Effects of the rotavirus vaccine program across age groups in the United States: analysis of national claims data, 2001\u20132016

BackgroundThe direct effectiveness of infant rotavirus vaccination implemented in 2006 in the United States has been evaluated extensively, however, understanding of population-level vaccine effectiveness (VE) is still incomplete.MethodsWe analyzed time series data on rotavirus gastroenteritis (RVGE) and all-cause acute gastroenteritis (AGE) hospitalization rates in the United States from the MarketScan® Research Databases for July 2001–June 2016. Individuals were grouped into ages 0–4, 5–9, 10–14, 15–24, 25–44, and 45–64 years. Negative binomial regression models were fitted to monthly RVGE and AGE data to estimate the direct, indirect, overall, and total VE.ResultsA total of 9211 RVGE and 726,528 AGE hospitalizations were analyzed. Children 0–4 years of age had the largest declines in RVGE hospitalizations with direct VE of 87% (95% CI: 83, 90%). Substantial indirect effects were observed across age groups and generally declined in each older group. Overall VE against RVGE hospitalizations for all ages combined was 69% (95% CI: 62, 76%). Total VE was highest among young children; a vaccinated child in the post-vaccine era has a 95% reduced risk of RVGE hospitalization compared to a child in the pre-vaccine era. We observed higher direct VE in odd post-vaccine years and an opposite pattern for indirect VE.ConclusionsVaccine benefits extended to unvaccinated individuals in all age groups, suggesting infants are important drivers of disease transmission across the population. Imperfect disease classification and changing disease incidence may lead to bias in observed direct VE.Trial registrationNot applicable.

Perinatal Risk Factors Associated With Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000-2012): A Record Linkage Cohort Study.

Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions associated with childhood gastroenteritis-related hospitalizations. We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia 2000-2012. We identified hospital admissions up to <15 years of age pertaining to these children, with a principal diagnosis code for infectious gastroenteritis. Cox regression was used to obtain the adjusted hazard ratios with 95% confidence intervals and the population attributable fractions associated with each risk factor in Aboriginal and non-Aboriginal children for their first gastroenteritis-related hospital admission. There were a total of 15,888 gastroenteritis-related hospital admissions (25.7% occurring among non-Aboriginal children). The overall gastroenteritis hospitalization rate for children <15 years of age was 4.6/1000 child-years for non-Aboriginal children and 21.5/1000 child-years for Aboriginal children. Male gender, <20 years of maternal age, preterm birth, low birth weight, residence in remote regions of Western Australia and birth in the pre-rotavirus vaccine era were significant independent risk factors for gastroenteritis hospitalization in both Aboriginal and non-Aboriginal children. Additionally, birth by caesarean section and low socioeconomic status were identified as being associated with gastroenteritis hospitalization in non-Aboriginal children. Population attributable fractions suggest that 39% of all gastroenteritis hospitalizations in non-Aboriginal children (38% in Aboriginal children) could be averted if all children receive the rotavirus vaccine. Given the beneficial effect of infant rotavirus vaccination in preventing all-cause gastroenteritis hospitalization, efforts should be taken to optimize rotavirus vaccine coverage in those at highest risk.

Infrequent Transmission of Monovalent Human Rotavirus Vaccine Virus to Household Contacts of Vaccinated Infants in Malawi.

Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8–10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi.

Genome constellations of 24 porcine rotavirus group A strains circulating on commercial Thai swine farms between 2011 and 2016.

Rotavirus A (RVA) infection is a major cause of diarrhea-related illness in young children. RVA is also one of the most common enteric viruses detected on pig farms and contributes to substantial morbidity and mortality in piglets. Long-term multi-site surveillance of RVA on Thai swine farms to determine the diversity of RVA strains in circulation is currently lacking. In this study, we characterized the 11 segments of the RVA genome from 24 Thai porcine RVA strains circulating between 2011 and 2016. We identified G9 (15/24) and P[13] (12/24) as the dominant genotypes. The dominant G and P combinations were G9P[13] (n = 6), G9P[23] (n = 6), G3P[13] (n = 5), G9P[19] (n = 3), G4P[6] (n = 2), G4P[19] (n = 1), and G5P[13] (n = 1). Genome constellation of the Thai strains showed the predominance of Wa-like genotype (Gx-P[x]-I1/I5-R1-C1-M1-A8-N1-T1/T7-E1/E9-H1) with evidence of reassortment between the porcine and human RVA strains (e.g., G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[19]-I5-R1-C1-M1-A8-N1-T7-E9-H1). To assess the potential effectiveness of rotavirus vaccination, the Thai RVA strains were compared to the RVA strains represented in the swine rotavirus vaccine, which showed residue variations in the antigenic epitope on VP7 and shared amino acid identity below 90% for G4 and G5 strain. Several previous studies suggested these variations might effect on virus neutralization specificity and vaccine efficacy. Our study illustrates the importance of RVA surveillance beyond the G/P genotyping on commercial swine farms, which is crucial for controlling viral transmission.

In Silico screening of T-cell and B-cell Epitopes of Rotavirus VP7 and VP4 proteins for Effective Vaccine Design

Rotavirus is one of the deadliest causative agents of childhood diarrhea which causes half a million child death across the globe, mostly in developing countries. However, effective vaccine strategies against rotavirus are yet to be established to prevent these unwanted premature deaths. In this regard, in silico vaccine design for rotavirus could be a promising alternative for developing countries due to its efficiency in shortening valuable time and cost. The present study described an epitope-based peptide vaccine design against rotavirus, using a combination of T-cell and B-cell epitope predictions and molecular docking approach. To perform this, sequences of rotavirus VP7 and VP4 proteins were retrieved from the NCBI database and subjected to different bioinformatics tools to predict most immunogenic T-cell and B-cell epitopes. From the identified epitopes, the sequence VMSKRSRSL of VP7 and TQFTDFVSL of VP4 was identified as the most potential epitopes based on their antigenicity, conservancy and interaction with major histocompatability complex I (MHC-I) alleles. Moreover, the peptide VMSKRSRSL interacted with human leukocyte antigen, HLA-B*08:01 and TQFTDFVSL interacted with HLA-A*02:06 with considerable binding energy and affinity score. Combined population coverage for our identified epitopes was found 70.53% and 45.64% for world population and South Asian population respectively. All these results suggest that, the epitopes identified in this study could be a very good vaccine candidate for the strains of rotavirus circulating in Bangladesh. However, as this study is completely dependent on computational prediction algorithms, further in vivo screening is required to come up in a precise conclusion about these epitopes for effective rotavirus vaccination.&#x0D; Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 45-55

Efectividad de la vacuna contra rotavirus frente a gastroenteritis grave por rotavirus: Estudio de casos-controles

Antecedentes: Desde el año 2006 las vacunas contra rotavirus tienen licencia y son utilizadas a nivel mundial, Rotarix® y Rotateq®. Ambas vacunas han demostrado una efectividad de 72-100% en la prevención de la enfermedad rotavírica severa en un período de seguimiento de 3 años. Objetivo: Evaluar la efectividad de la vacuna oral monovalente contra rotavirus en la reducción de la severidad de la diarrea aguda en niños menores de dos años atendidos en la emergencia pediátrica del Hospital Nacional Mario Catarino Rivas (HNMCR) del 1 de enero 2014 al 20 de mayo 2016. Pacientes y Métodos: Estudio de casos y controles en menores de 2 años ingresados en la sala de emergencia de pediatría del HNMCR en vigilancia por gastroenteritis por rotavirus. Tamaño de la muestra fue 83 casos y 83 controles. Las características sociodemográficas se analizaron por frecuencia y porcentaje y la efectividad de la vacuna a través del odd ratio. Resultados: la prevalencia de diarrea por rotavirus en los lactantes vacunados fue de 45%, en los no vacunados de 76% con un Xi2 de 7.95 (p= 0.005). La efectividad de la vacuna para los casos de diarrea severa vacunados con 1 dosis fue 86% (OR=0.14 [51.5-95.9]). Para 2 dosis fue de 98.99% (OR=0.011 [42-99.98]). Conclusiones: Los niños no vacunados contra el rotavirus presentaron casos más severos de diarrea, en contraste con los niños vacunados con 2 dosis, donde la vacuna fue efectiva (EV=98%), presentando en su mayoría casos de diarrea moderados.

Effectiveness of oral rotavirus vaccination in England against rotavirus-confirmed and all-cause acute gastroenteritis

BackgroundThe monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. MethodsWe used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. ResultsVE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40–84%) for one dose and 77% (95%CI: 66–85%) for two doses. Two-dose VE in children aged <12 months and ≥12 months was 85% (95%CI: 74–91%) and 54% (95%CI: 15–75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE = −20%, 95%CI: −36% to −5%), or against AGE hospitalisations (VE = 35%, 95% CI: −86% to 77%). ConclusionsIn this first detailed assessment of VE of the Rotarix® vaccine in the English national programme, we show that Rotarix® was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine’s performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios.

Incidence of Rotavirus Infection among Under-Five Children Attending Health Centres in Selected Communities of Ndola, Copperbelt Province, Zambia

Rotavirus infection is a highly infectious public health concern among under-five children characterized mainly by diarrhoea, vomiting and fever spread through oral fecal route from contaminated water, food and objects. Diarrhoea ranks third among the common causes of mortality in Zambia among under-fives which accounts for about 9%. Statistics obtained at Ndola District Health Management Office revealed that in spite of high coverage of rotavirus vaccine, diarrhoea incidence had risen over the years from 2011 to 2015 by 32.9/1000. Currently stool is not routinely tested for rotavirus infection, making it difficult to determine its incidence and effectiveness of rotavirus vaccine (RotarixTM), an intervention that was put in place on 27th November 2013 to mitigate diarrhoea disease. The objective of this study is to determine incidence of rotavirus infection among under-fives attending health centres in selected communities of Ndola. Purposive sampling was used to select 380 under-fives aged 3 months - 36 months who presented at health facilities with diarrhoea, vomiting and fever. Stool specimen was tested for rotavirus infection using Combi-Strip Rapid Diagnostic Test. The study was conducted at specified period in time from 1st March 2017 to 28th September 2017 to determine relationships and associations among suspected variables using cross-sectional analytic community based study design. Statistical Package for Social Science software was used for data analysis. Tests used included Pearson’s Chi-square and logistic regression. Results have revealed 11% incidence rate of rotavirus infection and significant statistical association among severity categories of rotavirus infection with uptake of rotavirus vaccine (p ≤ 0.001). Children who took two recommended doses of the vaccine 185 (59.5%) were more likely to have mild category (<7 score) of rotavirus infection. In conclusion, results clearly indicate that rotavirus vaccine reduces incidence and if a child has diarrhoea it is less severe which yields good outcomes.

Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe.

Rotavirus is a leading cause of mortality among children <5 years old. We evaluated monovalent rotavirus vaccine effectiveness (VE) under conditions of routine use at 2 surveillance sites in Harare, Zimbabwe, after vaccine introduction in May 2014. Children aged <5 years hospitalized or treated in the accident and emergency department (A&E) for acute watery diarrhea were enrolled for routine surveillance. Copies of vaccination cards were collected to document vaccination status. Among children age-eligible to receive rotavirus vaccine, we estimated VE, calculated as 1 - odds ratio, using a test-negative case-control design. We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in the analysis; 99% had verified vaccination status. Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases and 46% of controls had a Vesikari score ≥11 (P < .01). Among cases and controls, 31% and 37%, respectively, were stunted for their age (P < .01). Among children 6-11 months old, adjusted 2-dose VE against hospitalization or treatment in A&E due to rotavirus of any severity was 61% (95% confidence interval [CI], 21%-81%) and 68% (95% CI, 13%-88%) against severe rotavirus disease. Stratified by nutritional status, adjusted VE was 45% (95% CI, -148% to 88%) among stunted infants and 71% (95% CI, 29%-88%) among infants with a normal height for age. Monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants in Zimbabwe, providing additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in high-child-mortality settings.

Nonsecretor Histo-blood Group Antigen Phenotype Is Associated With Reduced Risk of Clinical Rotavirus Vaccine Failure in Malawian Infants.

BackgroundHisto–blood group antigen (HBGA) Lewis/secretor phenotypes predict genotype-specific susceptibility to rotavirus gastroenteritis (RVGE). We tested the hypothesis that nonsecretor/Lewis-negative phenotype leads to reduced vaccine take and lower clinical protection following vaccination with G1P[8] rotavirus vaccine (RV1) in Malawian infantsMethodsA cohort study recruited infants receiving RV1 at age 6 and 10 weeks. HBGA phenotype was determined by salivary enzyme-linked immunosorbent assay (ELISA). RV1 vaccine virus shedding was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in stool collected on alternate days for 10 days post-immunization. Plasma rotavirus–specific immunoglobulin A was determined by ELISA pre- and post-immunization. In a case-control study, HBGA phenotype distribution was compared between RV1-vaccinated infants with RVGE and 1:1 age-matched community controls. Rotavirus genotype was determined by RT-PCR.ResultsIn 202 cohort participants, neither overall vaccine virus fecal shedding nor seroconversion differed by HBGA phenotype. In 238 case-control infants, nonsecretor phenotype was less common in infants with clinical vaccine failure (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.20–0.75). Nonsecretor phenotype was less common in infants with P[8] RVGE (OR, 0.12; 95% CI, 0.03–0.50) and P[4] RVGE (OR, 0.17; 95% CI, 0.04–0.75). Lewis-negative phenotype was more common in infants with P[6] RVGE (OR, 3.2; 95% CI, 1.4–7.2).ConclusionsNonsecretor phenotype was associated with reduced risk of rotavirus vaccine failure. There was no significant association between HBGA phenotype and vaccine take. These data refute the hypothesis that high prevalence of nonsecretor/Lewis-negative phenotypes contributes to lower rotavirus vaccine effectiveness in Malawi.

Prevalence and genotypes of group A rotavirus among outpatient children under five years old with diarrhea in Beijing, China, 2011\u20132016

BackgroundRotavirus is a leading cause of severe diarrheal disease, and one of the common causes of death in children aged under five years old. The dominant epidemic strains may change in different years in the same area. In order to provide evidence for rotavirus epidemic control and inform vaccine development, we analyzed epidemiological patterns and genetic characteristics of rotavirus in Beijing during 2011–2016.MethodsStool specimens of outpatient children under five years old were collected from three children’s hospitals on a weekly basis. Group A rotavirus antigens were detected using enzyme-linked immunosorbent assay (ELISA) kit. The partial VP4 genes and VP7 genes of rotavirus were both amplified and sequenced. Genotyping and phylogenetic analyses were performed. Logistic regression and Chi-square tests were performed to determine differences across age groups, districts and years in rotavirus prevalence and genotype distribution.ResultsA total of 3668 stool specimens from children with acute diarrhea identified through hospital-based surveillance were collected from 2011 to 2016 in Beijing. A total of 762 (20.8%) specimens tested positive for rotavirus. The rotavirus-positive rate was highest among the 1–2 years old age group (29.0%, 310/1070). November, December and January were the highest rotavirus-positive rate months each year. G9 was the most common G genotype (64.4%, 461/716), and P [8] was the most common P genotype (87.0%, 623/716) among the 716 rotavirus-positive specimens. G9P [8], G3P [8] and G2P [4] were the most common strains. The rotavirus-positive rates of samples in 2012 and 2013 were higher than that in 2011, and the dominant genotype changed from G3P [8] to G9P [8] in 2012 and 2013. VP7 gene sequences of G9 strains in this study clustered into two main lineages. Most of the G9 strains exhibited the highest nucleotide similarity (99.1%~ 100.0%) to the strain found in Japan (MI1128). VP4 gene sequences of P [8] strains were almost P[8]b.ConclusionsRotavirus accounted for more than one fifth of childhood diarrhea in Beijing during the study period. Targeted measures such as immunization with effective rotavirus vaccines should be carried out to reduce the morbidity and mortality due to rotavirus.

Mitigating bias in observational vaccine effectiveness studies using simulated comparator populations: Application to rotavirus vaccination in the UK

BackgroundMeasuring vaccine effectiveness (VE) relies on the use of observational study designs. However, achieving robust estimates of direct and indirect VE is frequently compromised by bias, particularly when using syndromic diagnoses of low-specificity. MethodsIn order to mitigate confounding between the measured outcome and vaccine uptake, we developed a method to balance comparator populations using individual-level propensity scoring derived from the vaccine-exposed population, and applied it to the unexposed comparator population. Indirect VE was estimated by comparing the unvaccinated vaccine-exposed group with a propensity score-simulated unvaccinated, unexposed group. Direct VE was derived by removing indirect VE from the overall VE.We applied this method to an evaluation of the effectiveness of infant rotavirus vaccination in the UK. Using a general practice cohort of 45,259 live births between May 2010 and December 2015, we calculated indirect and direct VE against consultations for acute gastroenteritis using conventional and vaccination-propensity adjustment comparator populations. ResultsThe overall VE during the rotavirus-season (January-May) calculated using mixed-effects Cox regression was 30% [95% confidence intervals (95% CI: 25,35%)]. Use of conventional comparator populations resulted in implausible VE estimates −14% (95% CI: −41,7%) for direct and 29% (95% CI: 14,42%) for indirect effects. Applying our alternative method, direct VE was 26% (95% CI: 1,45%) and indirect VE was 8% (95% CI: −19,29%). ConclusionsEstimating VE using propensity score simulated comparator populations, particularly for studies using routine health data with syndromic, low-specificity endpoints will aid accurate measurement of the broader public health impact of a vaccine programme.

Effectiveness of monovalent rotavirus vaccine in the Philippines

Rotavirus (RV) is an important cause of diarrheal disease particularly in children aged under 5 years. Monovalent RV vaccine (RVV) was selectively introduced in 2012 in the Philippines and in July 2014 was introduced in the public health program of a province. Two RVV doses are recommended at 6 and 10 weeks of age. We conducted a test negative case-control evaluation to assess the effectiveness of RVV when given in a routine public health program in the Philippines. From September 2014 to August 2017, 967 children aged <5 years were hospitalized with diarrhea and of these, we enrolled 600 who were eligible to have received RVV and provided stool specimens for testing. Among children ≥8 months of age who were age-eligible to have received RVV, at least one dose of RVV had an adjusted vaccine effectiveness (VE) against RV hospitalization of 60% (95% confidence interval, CI: 24%, 79%), and against severe rotavirus diarrhea, VE was 64% (95% CI: 11%, 85%). These findings support the introduction of RVV into routine public health use in the Philippines. However, other factors such as costs, cost-effectiveness and operational issues must be considered prior to adoption of the vaccine into the countries’ public immunization program.

Effectiveness of rotavirus vaccine against rotavirus-coded hospitalisations among Australian Aboriginal and non-Aboriginal children

IntroductionRotavirus vaccine, RV1 (Rotarix), was included in the immunisation programs in Western Australia (WA) and New South Wales from mid-2007. In WA, RV1 was replaced with RV5 (RotaTeq) in mid-2009. Marked declines in rotavirus-related hospitalisations in both Aboriginal and non-Aboriginal children have been demonstrated following the implementation of the program.&#x0D; Objectives and ApproachWe aimed to assess RV1 vaccine effectiveness (VE) against rotavirus-coded hospitalisations among Aboriginal and non-Aboriginal children aged (1-hazard ratio*100) were obtained from Cox proportional hazards models (adjusted for infant, maternal and demographic factors and stratified by state of birth) for Aboriginal and non-Aboriginal children.&#x0D; ResultsThere were a total of 623 rotavirus-coded hospitalisations among the cohort children aged &lt;2 years. Rotavirus hospitalisation rates were 143.0/100,000 child-years (95% confidence interval [CI]: 113.3-180.4) among Aboriginal children and 49.0/100,000 child-years (95% CI: 44.8-53.5) among non-Aboriginal children.&#x0D; Compared to unvaccinated children, 1-dose VE among Aboriginal children against rotavirus-coded hospitalisations was 52.1% (95% CI: -0.02-77.1%) and 2-dose VE was 62.4% (95% CI: 26.9-80.7%) adjusting for birthweight, region of residence, socio-economic status, and year of birth. Among non-Aboriginal children, 1-dose VE was 39.0% (95% CI: 13.1-57.2%) and 2-dose VE was 53.4% (95% CI: 38.1-65.1%) adjusting for birth weight, mode of delivery and maternal age at birth and year of birth.&#x0D; Conclusion/ImplicationsBurden of rotavirus gastroenteritis remains significant in Aboriginal children. Given the previously demonstrated declines in rotavirus-related hospitalisations in this population following vaccine introduction, our lower-than-expected VE estimates might represent bias introduced by differences in health-seeking behaviour between the vaccinated and unvaccinated, herd immunity and/or possible non-differential misclassification of the outcome.

Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study.

SummaryBackgroundRotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10–51 weeks.MethodsIn this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression.FindingsBetween Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1–52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI –28 to 66; p=0·22).InterpretationRV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes.FundingWellcome Trust and GlaxoSmithKline Biologicals.

Effect of Rotavirus Vaccination on Acute Diarrheal Hospitalizations Among Low and Very Low Birth Weight US Infants, 2001-2015.

The effectiveness of rotavirus vaccines in low and very low birth weight infants (LBW and VLBW) weighing <2500 and <1500 g at birth, respectively, a high-risk population for severe rotavirus gastroenteritis, has not been well examined. We analyzed inpatient commercial claims data for US children <5 years of age from July 2001 to June 2015. Claims for acute gastroenteritis (AGE) and rotavirus-coded hospitalizations and LBW, VLBW and normal birth weight (NBW) infants were identified. Receipt of rotavirus vaccine was defined using Current Procedural Terminology. Rate reductions were calculated using prevaccine (2001-2006) and postvaccine (2007-2015) annual AGE and rotavirus hospitalization rates. As of December 2014, rotavirus vaccine coverage was 87%, 82% and 64%, for NBW, LBW and VLBW infants, respectively. For 2014-2015, among NBW, LBW and VLBW children <5 years of age, AGE hospitalization rate reductions relative to the prevaccine introduction period were 60% [95% confidence interval (CI): 58%-61%], 64% (95% CI: 57%-70%) and 55% (95% CI: 39%-67%), respectively. Rotavirus hospitalization rate reductions were 91% (95% CI: 90%-92%), 98% (95% CI: 93%-100%) and 93% (95% CI: 70%-98%). Rotavirus vaccines resulted in a 62% (95% CI: 51%-71%), 72% (95% CI: 44%-86%) and 71% (95% CI: 7%-91%) reduction in AGE hospitalization rates comparing vaccinated versus unvaccinated NBW, LBW and VLBW children 3-23 months of age, respectively. Rotavirus vaccines have substantially reduced AGE hospitalizations and are highly effective in LBW and VLBW infants, similar to NBW infants. Efforts to improve vaccination coverage, particularly in LBW and VLBW infants, should continue.

Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian Infants.

Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. Data were merged from 2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose, children were classified as receiving each dose "early," "on-time" or "late." Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 - odds ratio) × 100%. Models were adjusted for hospital, age and time since RV1 introduction (via including terms for month and year of birth). VE for 2 doses of RV1 tended to be higher in infants receiving the first dose early (VE, 92%; 95% confidence interval: 70%-98%), when compared with infants receiving their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE were not substantially different when comparing children by age at second dose [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)], including all children. Our results indicate that early administration may improve VE and support the current World Health Organization recommendations for the RV1 schedule.

Effectiveness of monovalent and pentavalent rotavirus vaccines in Japanese children

BackgroundRotavirus (RV) vaccination has been available in Japan since November 2011, but is not yet part of Japan’s national immunisation programs. There are insufficient data on vaccine effectiveness (VE) among Japanese children. MethodsBetween the months of January and May in 2014 and 2015, we conducted active surveillance of gastroenteritis among children at 14 medical facilities. Rectal swabs from all patients with diarrhoea or vomiting were tested for RV by immunochromatography, and positive specimens were genotyped. Demographic data and immunisation records were obtained from a questionnaire completed by their parents/guardians or medical records. A test-negative case-control design was used to examine vaccine effectiveness (VE) using unconditional logistic regression analysis adjusted for possible confounding factors. ResultsAmong the 1519 eligible subjects (children with acute gastroenteritis symptoms aged ≥2 months to <3 y visiting medical facilities) recruited, 487 cases and 925 controls were enrolled. Cases had more severe symptoms than controls, requiring more intensive treatment, including intravenous rehydration or hospitalisation. VE against all rotavirus gastroenteritis (RVGE) was 80.0% (95% confidence interval [CI], 72.8–85.5%), and VEs against RV1 and RV5 were similar, at 80.6% (95%CI, 70.7–87.1%) for RV1 and 80.4% (95% CI, 69.1–87.6%) for RV5. Although VEs of both vaccines decreased with age, VEs against all RVGE were >70% up to 2 years after vaccination. VEs increased with severity of RVGE, and VE against severe RVGE, requiring intravenous rehydration or hospitalisation, was 97.3% (95% CI, 88.8–99.3%). VEs of RV1 and RV5 against G1P[8] and G2P[4] were comparable, at RV1, 89.8% (95% CI, 78.2–95.5%) and 78.3% (95% CI, 23.6–93.8%); and RV5, 85.8% (95% CI, 72.8–92.6%) and 88.1% (95% CI, 10.1–98.4%), respectively. ConclusionsRotavirus vaccines were effective in preventing mild to severe RVGE, irrespective of vaccine type, time since vaccination, or RV genotype.

The effectiveness of rotavirus vaccine and its impact on demographic characteristics for children in Babylon city, Iraq

Gastroenteritis caused by rotavirus infection is one of the major healthcare problem affecting millions of children all over the world. WHO has recommended vaccine against rotavirus to be involved in the national immunisation programmes. In Iraq, rotavirus vaccine has been started since 2012 and in the current study, we aimed to estimate the effectiveness of rotavirus vaccine in Babylon city, Iraq. Faecal samples were obtained from children presented with diarrhoea during the period beginning in October 2016 until August 2017. The age range was 6-60 months and history of rotavirus vaccine was checked. Latex test for detection of Rotavirus analysed specimens. We examined 349 children with diarrhoea; the rotavirus antigen was detected in 169 faecal specimens from children with diarrhoea (48%). For those who are infected with rotavirus antigen, 44 (26%) were previously vaccinated against rotavirus and 125 (74%) were not. These results indicated that children who did not receive rotavirus vaccination have 4.679 folds increased the risk of having positive rotavirus antigen infected diarrhoea. Furthermore, low percentages of vaccinated children with positive rotavirus antigens detected in their stool were seen in most age groups except for those between 25–36 months with no gender differences. Additionally, more percentages were in the urban area and artificial feedings. The effectiveness of rotavirus vaccine, in the present study, has been confirmed in reducing the burden of rotavirus gastroenteritis in young children in Babylon city, Iraq. However, huge effort needs to be done in order to have more children received rotavirus vaccine.

A comparison of the test-negative and traditional case-control study designs with respect to the bias of estimates of rotavirus vaccine effectiveness

Estimation of the effectiveness of rotavirus vaccines via the test-negative control study design has gained popularity over the past few years. In this study design, children with severe diarrhea who test positive for rotavirus infection are considered as cases, while children who test negative serve as controls. We use a simple probability model to evaluate and compare the test-negative control and the traditional case-control designs with respect to the bias of resulting estimates of rotavirus vaccine effectiveness (VE). Comparisons are performed under two scenarios, corresponding to studies performed in high-income and low-income countries. We consider two potential sources of bias: (a) misclassification bias resulting from imperfect sensitivity and specificity of the test used to diagnose rotavirus infection, and (b) selection bias associated with possible effect of rotavirus vaccination on the probability of contracting severe non-rotavirus diarrhea.Our results suggest that both sources of bias may produce VE estimates with substantial bias. Particularly, lack of perfect specificity is associated with severe negative bias. For example, if the specificity of the diagnostic test is 90% then VE estimates from both types of case-control studies may under-estimate the true VE by more than 20%. If the vaccine protects children against non-rotavirus diarrhea then VE estimates from test-negative control studies may be close to zero even though the true VE is 50%. However, the sensitivity and specificity of the enzyme immunoassay test currently used to diagnose rotavirus infections are both over 99%, and there is no solid evidence that the existing rotavirus vaccines affect the rates of non-rotavirus diarrhea. We therefore conclude that the test-negative control study design is a convenient and reliable alternative for estimation of rotavirus VE.