Rotavirus Vaccine Effectiveness Research Articles

Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years

Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after introduction are noteworthy. To evaluate the comparative benefit, risk, and immunogenicity of different rotavirus vaccines by synthesizing randomized clinical trials (RCTs) and observational studies. Relevant studies published in 4 databases: Embase, PubMed, the Cochrane Library, and Web of Science were searched until July 1, 2020, using search terms including "rotavirus" and "vaccin*." Randomized clinical trials and cohort and case-control studies involving more than 100 children younger than 5 years that reported the effectiveness, safety, or immunogenicity of rotavirus vaccines were included. A random-effects model was used to calculate relative risks (RRs), odds ratios (ORs), risk differences, and 95% CIs. Adjusted indirect treatment comparison was performed to assess the differences in the protection of Rotarix and RotaTeq. The primary outcomes were RVGE, severe RVGE, and RVGE hospitalization. Safety-associated outcomes involved serious adverse events, intussusception, and mortality. A meta-analysis of 20 RCTs and 38 case-control studies revealed that Rotarix (RV1) significantly reduced RVGE (RR, 0.316 [95% CI, 0.224-0.345]) and RVGE hospitalization risk (OR, 0.347 [95% CI, 0.279-0.432]) among children fully vaccinated; RotaTeq (RV5) had similar outcomes (RVGE: RR, 0.350 [95% CI, 0.275-0.445]; RVGE hospitalization risk: OR, 0.272 [95% CI, 0.197-0.376]). Rotavirus vaccines also demonstrated higher protection against severe RVGE. Additionally, no significant differences in the protection of RV1 and RV5 against rotavirus disease were noted in adjusted indirect comparisons. Moderate associations were found between reduced RVGE risk and Rotavac (RR, 0.664 [95% CI, 0.548-0.804]), Rotasiil (RR, 0.705 [95% CI, 0.605-0.821]), and Lanzhou lamb rotavirus vaccine (RR, 0.407 [95% CI, 0.332-0.499]). All rotavirus vaccines demonstrated no risk of serious adverse events. A positive correlation was also found between immunogenicity and vaccine protection (eg, association of RVGE with RV1: coefficient, -1.599; adjusted R2, 99.7%). The high protection and low risk of serious adverse events for rotavirus vaccines in children who were fully vaccinated emphasized the importance of worldwide introduction of rotavirus vaccination. Similar protection provided by Rotarix and RotaTeq relieves the pressure of vaccines selection for health care authorities.

Estimating the Effectiveness of Rotavirus Vaccine Schedules.

Important questions exist regarding the comparative effectiveness of alternative childhood vaccine schedules; however, optimal approaches to studying this complex issue are unclear. We applied methods for studying dynamic treatment regimens to estimate the comparative effectiveness of different rotavirus vaccine (RV) schedules for preventing acute gastroenteritis-related emergency department (ED) visits or hospitalization. We studied the effectiveness of six separate protocols: one- and two-dose monovalent rotavirus vaccine (RV1); one-, two-, and three-dose pentavalent rotavirus vaccine (RV5); and no RV vaccine. We used data on all infants to estimate the counterfactual cumulative risk for each protocol. Infants were censored when vaccine receipt deviated from the protocol. Inverse probability of censoring-weighted estimation addressed potentially informative censoring by protocol deviations. A nonparametric group-based bootstrap procedure provided statistical inference. The method yielded similar 2-year effectiveness estimates for the full-series protocols; weighted risk difference estimates comparing unvaccinated children to those adherent to either full-series (two-dose RV1, three-dose RV5) corresponded to four fewer hospitalizations and 12 fewer ED visits over the 2-year period per 1,000 children. We observed dose-response relationships, such that additional doses further reduced risk of acute gastroenteritis. Under a theoretical intervention to fully vaccinate all children, the 2-year risk differences comparing full to observed adherence were 0.04% (95% CI = 0.03%, 0.05%) for hospitalizations and 0.17% (95% CI = 0.14%, 0.19%) for ED visits. The proposed approach can generate important evidence about the consequences of delaying or skipping vaccine doses, and the impact of interventions to improve vaccine schedule adherence.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56–29.4% in pre-vaccine years to 34–12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.

Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine

Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log10 FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log10 FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.

Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction

Children in low-and middle-income countries, including Rwanda, experience a greater burden of rotavirus disease relative to developed countries. Evolutionary mechanisms leading to multiple reassortant rotavirus strains have been documented over time which influence the diversity and evolutionary dynamics of novel rotaviruses. Comprehensive rotavirus whole-genome analysis was conducted on 158 rotavirus group A (RVA) samples collected pre- and post-vaccine introduction in children less than five years in Rwanda. Of these RVA positive samples, five strains with the genotype constellations G4P[4]-I1-R2-C2-M2-A2-N2-T1-E1-H2 (n = 1), G9P[4]-I1-R2-C2-M2-A1-N1-T1-E1-H1 (n = 1), G12P[8]-I1-R2-C2-M1-A1-N2-T1-E2-H3 (n = 2) and G12P[8]-I1-R1-C1-M1-A2-N2-T2-E1-H1 (n = 1), with double and triple gene reassortant rotavirus strains were identified. Phylogenetic analysis revealed a close relationship between the Rwandan strains and cognate human RVA strains as well as the RotaTeq® vaccine strains in the VP1, VP2, NSP2, NSP4 and NSP5 gene segments. Pairwise analyses revealed multiple differences in amino acid residues of the VP7 and VP4 antigenic regions of the RotaTeq® vaccine strain and representative Rwandan study strains. Although the impact of such amino acid changes on the effectiveness of rotavirus vaccines has not been fully explored, this analysis underlines the potential of rotavirus whole-genome analysis by enhancing knowledge and understanding of intergenogroup reassortant strains circulating in Rwanda post vaccine introduction.

Novel antigen panel for modern broad-spectrum recombinant rotavirus A vaccine.

PurposeRecombinant rotavirus A vaccines are being developed as an alternative to existing live oral attenuated vaccines. One of the main problems in the production of such vaccines is the genetic diversity of the strains that are in circulation. The goal of this study was to create an antigen panel for modern broad-spectrum recombinant rotavirus A vaccine.Materials and MethodsThe antigens of rotavirus were cloned and expressed in Escherichia coli. Antigenic specificity was investigated by Western blot analysis, which was performed using commercial polyclonal antisera to several RVA strains. Phylogenetic analysis was based on the amino acid sequences of the VP8* protein fragment of human RVA isolates representing genotypes P[4], P[6], and P[8].ResultsA universal panel of antigens was established, including consensus and conserved sequences of structural proteins VP8*, VP5*, and VP7, which are the main targets of neutralizing antibodies. For the first time, a consensus approach was used in the design of extended antigens based on VP8* (genotypes P[4], P[6], and P[8]) and VP5* (genotype P[8]) proteins' fragments. In addition, a gene coding the protein (ep-875) containing several copies of conserved short neutralizing epitopes of VP8*, VP7, and VP5* was created. Western blot analysis demonstrated that three synthetic VP8*-based antigens were not recognized by commercial antiserum against rotavirus strains isolated more than 35 years ago, but the specific activity of the VP5* and ep-875 antigens was confirmed. The problems of serological mismatch of vaccine strains and antigens with currently circulating strains are discussed.ConclusionFive antigens representing sequences of structural proteins belonging to different genotypes can be used in various combinations (from mono- to pentavalent mixtures) for the development of an effective broad-spectrum rotavirus vaccine.

Effectiveness of rotavirus vaccine in preventing transmission of rotavirus from children to household contacts in Malawi

Effectiveness of rotavirus vaccine in preventing transmission of rotavirus from children to household contacts in Malawi

Community transmission of rotavirus infection in a vaccinated population in Blantyre, Malawi: a prospective household cohort study

Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.

Retrospective Case-Control Study of 2017 G2P[4] Rotavirus Epidemic in Rural and Remote Australia.

Background: A widespread G2P[4] rotavirus epidemic in rural and remote Australia provided an opportunity to evaluate the performance of Rotarix and RotaTeq rotavirus vaccines, ten years after their incorporation into Australia’s National Immunisation Program. Methods: We conducted a retrospective case-control analysis. Vaccine-eligible children with laboratory-confirmed rotavirus infection were identified from jurisdictional notifiable infectious disease databases and individually matched to controls from the national immunisation register, based on date of birth, Aboriginal status and location of residence. Results: 171 cases met the inclusion criteria; most were Aboriginal and/or Torres Strait Islander (80%) and the median age was 19 months. Of these cases, 65% and 25% were fully or partially vaccinated, compared to 71% and 21% of controls. Evidence that cases were less likely than controls to have received a rotavirus vaccine dose was weak, OR 0.79 (95% CI, 0.46–1.34). On pre-specified subgroup analysis, there was some evidence of protection among children <12 months (OR 0.48 [95% CI, 0.22–1.02]), and among fully vs. partially vaccinated children (OR 0.65 [95% CI, 0.42–1.01]). Conclusion: Despite the known effectiveness of rotavirus vaccination, a protective effect of either rotavirus vaccine during a G2P[4] outbreak in these settings among predominantly Aboriginal children was weak, highlighting the ongoing need for a more effective rotavirus vaccine and public health strategies to better protect Aboriginal children.

Cost estimates of diarrhea hospitalizations among children

IntroductionDiarrhoea is a leading killer of children <5 years old, accounting for 480,000 deaths in 2017.Zimbabwe introduced Rotarix into its vaccination program in 2014. In this evaluation, we estimate direct medical, direct non-medical, and indirect costs attributable to a diarrhea hospitalization in Zimbabwe after rotavirus vaccine introduction. MethodsChildren <5 years old admitted to Harare Central Hospital from June 2018 to April 2019 with acute watery diarrhea were eligible for this evaluation. A 3-part structured questionnaire was used to collect data by interview from the child’s family and by review of the medical record. A stool specimen was also collected and tested for rotavirus. Direct medical costs were the sum of medications, consumables, diagnostic tests, and service delivery costs. Direct non-medical costs were the sum of transportation, meals and lodging for caregivers. Indirect costs are the lost income for household members. ResultsA total of 202 children were enrolled with a median age of 12 months (IQR: 7–21) and 48 (24%) had malnutrition. Children were sick for a median of 2 days and most had received outpatient medical care prior to admission. The median monthly household income was higher for well-nourished children compared to malnourished children (p < 0.001). The median total cost of a diarrhea illness resulting in hospitalization was $293.74 (IQR: 188.42, 427.89). Direct medical costs, with a median of $251.74 (IQR: 155.42, 390.96), comprised the majority of the total cost. Among children who tested positive for rotavirus, the median total illness cost was $243.78 (IQR: 160.92, 323.84). The median direct medical costs were higher for malnourished than well-nourished children (p < 0.001). ConclusionDirect medical costs are the primary determinant of diarrhea illness costs in Zimbabwe. The descriptive findings from this evaluation are an important first step in calculating the cost effectiveness of rotavirus vaccine.

Effect of childhood rotavirus vaccination on community rotavirus prevalence in rural Ecuador, 2008-13.

Although live attenuated monovalent human rotavirus vaccine (Rotarix) efficacy has been characterized through randomized studies, its effectiveness, especially in non-clinical settings, is less clear. In this study, we estimate the impact of childhood Rotarix® vaccination on community rotavirus prevalence. We analyse 10 years of serial population-based diarrhoea case-control study, which also included testing for rotavirus infection (n = 3430), and 29 months of all-cause diarrhoea active surveillance from a child cohort (n = 376) from rural Ecuador during a period in which Rotarix vaccination was introduced. We use weighted logistic regression from the case-control data to assess changes in community rotavirus prevalence (both symptomatic and asymptomatic) and all-cause diarrhoea after the vaccine was introduced. We also assess changes in all-cause diarrhoea rates in the child cohort (born 2008-13) using Cox regression, comparing time to first all-cause diarrhoea case by vaccine status. Overall, vaccine introduction among age-eligible children was associated with a 82.9% reduction [95% confidence interval (CI): 49.4%, 94.2%] in prevalence of rotavirus in participants without diarrhoea symptoms and a 46.0% reduction (95% CI: 6.2%, 68.9%) in prevalence of rotavirus infection among participants experiencing diarrhoea. Whereas all age groups benefited, this reduction was strongest among the youngest age groups. For young children, prevalence of symptomatic diarrhoea also decreased in the post-vaccine period in both the case-control study (reduction in prevalence for children <1 year of age = 69.3%, 95% CI: 8.7%, 89.7%) and the cohort study (reduction in hazard for receipt of two Rotarix doses among children aged 0.5-2 years = 57.1%, 95% CI: 16.6, 77.9%). Rotarix vaccination may suppress transmission, including asymptomatic transmission, in low- and middle-income settings. It was highly effective among children in a rural community setting and provides population-level benefits through indirect protection among adults.

Real-world effectiveness of rotavirus vaccines, 2006–19: a literature review and meta-analysis

Since licensure in 2006, rotavirus vaccines have been introduced in more than 100 countries. The efficacy of rotavirus vaccines is variable in settings with different child mortality levels. We did an updated review of the published literature to assess the real-world effectiveness of rotavirus vaccines in a range of settings. In this literature review and meta-analysis, we included observational, post-licensure studies of rotavirus vaccines, published from Jan 1, 2006, to Dec 31, 2019, in English, with laboratory-confirmed rotavirus as the endpoint. In addition to product-specific results for Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) or RotaTeq (Merck, West Point, PA, USA), we included Rotarix and RotaTeq mixed series, and non-product-specific vaccine effectiveness estimates from countries where Rotarix and RotaTeq are both available. Studies of other infant rotavirus vaccines were excluded because little or no post-licensure data were available. We fitted random-effects regression models to estimate vaccine effectiveness among children younger than 12 months and aged 12-23 months. On the basis of 2017 UNICEF mortality estimates for children younger than 5 years, countries were stratified as having low (lowest quartile), medium (second quartile), or high mortality (third and fourth quartiles). We identified and screened 1703 articles, of which 60 studies from 32 countries were included. 31 studies were from countries with low child mortality, eight were from medium-mortality countries, and 21 were from high-mortality countries. Rotarix vaccine effectiveness against laboratory-confirmed rotavirus among children younger than 12 months old was 86% (95% CI 81-90) in low-mortality countries, 77% (66-85) in medium-mortality countries, and 63% (54-70) in high-mortality countries. Rotarix vaccine effectiveness among children aged 12-23 months was 86% (81-90) in low-mortality countries, 54% (23-73) in medium-mortality countries, and 58% (38-72) in high-mortality countries. RotaTeq vaccine effectiveness among children younger than 12 months was 86% (76-92) in low-mortality countries and 66% (51-76) in high-mortality countries. RotaTeq vaccine effectiveness among children aged 12-23 months was 84% (79-89) in low-mortality countries. There was no substantial heterogeneity (I2 range: 0-36%). Median vaccine effectiveness in low-mortality countries was similar for Rotarix (83%; IQR 78-91), RotaTeq (85%; 81-92), mixed series (86%; 70-91), and non-product-specific (89%; 75-91) vaccination. Rotavirus vaccines were effective in preventing rotavirus diarrhoea, with higher performance in countries with lower child mortality. None.

Rotavirus vaccine effectiveness and impact in Uzbekistan, the first country to introduce in central Asia

ABSTRACT Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005−2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%−15% of infants and 10%−16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%−68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2–75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries. MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%. ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls. ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.

Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines.

Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix®, RotaTeq®, Rotavac®, and RotaSIIL®) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines.

Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014\u20132018

Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1st/2nd RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a−b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.

Rotavirus Vaccine Is Effective Against Rotavirus Gastroenteritis Resulting in Outpatient Care: Results From the Medically Attended Acute Gastroenteritis (MAAGE) Study.

Rotavirus is a common cause of severe pediatric acute gastroenteritis. Two vaccines are licensed in the United States and have demonstrated high effectiveness against moderate to severe disease. However, fewer data are available on rotavirus vaccine effectiveness (VE) against milder disease. We leveraged active surveillance data from Kaiser Permanente Northwest to calculate rotavirus VE against medically attended rotavirus illness among age-eligible children. We utilized a test-negative case-control design and applied 4 distinct case definitions based on reverse transcription-quantitative real-time PCR (qRT-PCR) assay and enzyme immunoassay (EIA) test results. VE was calculated as 100 × (1 - odds ratio), and models were adjusted for age group. The VE analysis population comprised 842 children, 799 (95%) of whom had mild disease requiring at most a clinic visit and 698 (83%) of whom were fully vaccinated against rotavirus. Age-adjusted VE was 70% (95% confidence interval [CI], 37-86%) against disease defined solely by qRT-PCR results, 72% (95% CI, 31-89%) against disease as defined by qRT-PCR with a quantification cycle (C q ) value <27, 73% (95% CI, 32-90%) against disease that was qRT-PCR positive but EIA negative, and 62% (95% CI, -20-88%) against disease defined solely by EIA. Results were similar when restricting to disease resulting in at most an ambulatory clinic or emergency department visit. These results support the effectiveness of rotavirus vaccination in protecting US children from mild to moderate and severe disease. Our findings are also useful to show the effectiveness of rotavirus vaccination against qRT-PCR-defined illness.

Rotavirus and Type 1 Diabetes—Is There a Connection? A Synthesis of the Evidence

Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Furthermore, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear.

Quantitative Benefit-Risk Models Used for Rotavirus Vaccination: A Systematic Review.

BackgroundAlthough rotavirus vaccines have proven to prevent the risk of rotavirus gastroenteritis (RVGE) in children under 5 years old, they are also associated with an increased transient risk of intussusception (IS). Several quantitative benefit-risk models (qBRm) are performed to measure this balance in hospitalizations and deaths prevented versus the ones induced.MethodIn this study, our objective was to provide a complete overview of qBRm used for rotavirus vaccination. We systematically searched 3 medical literature databases to identify relevant articles, in English, that were published between 2006 and 2019.ResultsOf the 276 publications screened, 14 studies using qBRm for rotavirus vaccination were retained, based on preselected criteria. Four were performed in low- and middle-income countries. Almost all (13 of 14) displayed the following characteristics: force of infection assumed to be constant over time (static model), indirect effect of rotavirus vaccination (herd effect) not considered, closed model (individuals not allowed to enter and/or exit the model over time), and aggregated level (no tracking of individual’s behavior). Most of the models were probabilistic (9 of 14) and reported sensitivity and/or scenario analyses (12 of 14). Input parameter values varied across studies. Selected studies suggest that, depending on the models used, for every IS hospitalization and death induced, vaccination would prevent, respectively, 190–1624 and 71–743 RVGE-related hospitalizations and deaths.ConclusionsThe benefits of rotavirus vaccination were shown to largely exceed the increased risk of IS, across all studies. Future research aiming to harmonize qBRm for rotavirus vaccination should ensure the comparability of studies and provide additional information for regulatory authorities, physicians, and patients.

Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective review

BackgroundKiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken.MethodsInpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010–December 2013 (pre-rotavirus vaccine) and January 2016–September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction.ResultsThe incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12·8% vs. 7·2%, p < 0·001) and all-cause under-five mortality (15·9% vs. 5·7%, p = 0·006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction.ConclusionsAGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.