Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.

Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution.

Emergence of equine-like G3 and porcine-like G9 rotavirus strains in Sarawak, Malaysia: 2019-2021.

Rotavirus is the leading causative viral agent of pediatric acute gastroenteritis globally, infecting mostly children 5 years old and below. Data on rotavirus prevalence in Malaysia is scarce, despite the WHO's recommendation for continuous rotavirus surveillance, and has underestimated the need for national rotavirus vaccination. Characteristics of the current rotavirus strains in Malaysia have to be determined to understand the rotavirus epidemiology and vaccine compatibility. This study sought to determine the genetic relatedness of Sarawak rotavirus strains with global strains and to determine the antigenic coverage and epitope compatibility of Rotarix and RotaTeq vaccines with the Sarawak rotavirus strains via in silico analysis. A total of 89 stool samples were collected from pediatric patients (<5 years old) with acute gastroenteritis at private hospitals in Kuching, Sarawak. Rotavirus was detected using reverse transcription-polymerase chain reaction. Positive amplicons were analyzed using nucleotide sequencing before phylogenetic analyses and assessment of epitope compatibility. Genotyping revealed G1P[8] (1/13; 7.7%), G3P[8] (3/13; 23%), G9P[4] (1/13; 7.7%), and G9P[8] (3/13; 23%), G9P[X] (1/13; 7.7%), GXP[4] (1/13; 7.7%), and GXP[8] (3/13; 23%) in samples. All wild-type Sarawak rotavirus strains, with the exception of G1, showed variations in their phylogenetic and antigenic epitope characteristics.

The Full Impact of Rotavirus Vaccines in Africa Has Yet to Be Realized.

Africa bears the brunt of diarrheal mortality globally. Rotavirus vaccination rates are high across the continent and demonstrate impact on diarrheal disease reduction. Nevertheless, there is room for significant improvement in managing rotavirus vaccine coverage, in access to recognized public services such as appropriate medical care, including oral rehydration therapy and improved water and sanitation.

The Effect of Virus-Specific Vaccination on Laboratory Infection Markers of Children with Acute Rotavirus-Associated Acute Gastroenteritis.

OBJECTIVE: Rotavirus (RV) is one of the most common and important causes of acute gastroenteritis (AGE) in newborns and children worldwide. The aim of this study was to evaluate the effect of the RV vaccine on the natural history of RV infections using the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune inflammatory index (SII) as hematological indexes, clinical findings, and hospitalization. METHOD: Children aged 1 month to 5 years who were diagnosed with RV AGE between January 2015 and January 2022 were screened, and 630 patients were included in the study. The SII was calculated by the following formula: neutrophil × platelet/lymphocyte. RESULTS: Fever and hospitalization were significantly higher and breastfeeding was significantly lower in the RV-unvaccinated group than in the RV-vaccinated group. The NLR, PLR, SII, and CRP were significantly higher in the RV-unvaccinated group (p < 0.05). The NLR, PLR, and SII were significantly higher both in the non-breastfed group than in the breastfed group and in the hospitalized group than in the not hospitalized group (p < 0.05). CRP was not significantly different in either the hospitalization group or the breastfeeding group (p > 0.05). SII and PLR were significantly lower in the RV-vaccinated group than in the RV-unvaccinated group in both the breastfed and non-breastfed subgroups. For NLR and CRP, while there was no significant difference according to RV vaccination status in the breastfed group, there was a significant difference in the non-breastfed group (p value: <0.001; <0.001). CONCLUSIONS: Despite the low level of vaccine coverage, the introduction of RV vaccination had a positive impact on the incidence of RV-positive AGE and related hospitalizations in children. These results showed that breastfed and vaccinated children were less prone to inflammation because their NLR, PLR, and SII ratios were lower. The vaccine does not prevent the disease 100%. However, it can prevent severe disease with exsiccation or death.

14th International dsRNA Virus Symposium, Banff, Alberta, Canada, 10-14 October 2022.

This triennial International dsRNA Virus Symposium covered original data which have accrued during the most recent five years. In detail, the genomic diversity of these viruses continued to be explored; various structure-function studies were carried out using reverse genetics and biophysical techniques; intestinal organoids proved to be very suitable for special pathogenesis studies; and the potential of next generation rotavirus vaccines including use of rotavirus recombinants as vectored vaccine candidates was explored. 'Non-lytic release of enteric viruses in cloaked vesicles' was the topic of the keynote lecture by Nihal Altan-Bonnet, NIH, Bethesda, USA. The Jean Cohen lecturer of this meeting was Polly Roy, London School of Hygiene and Tropical Medicine, who spoke on aspects of the replication cycle of bluetongue viruses, and how some of the data are similar to details of rotavirus replication.

Impact of rotavirus vaccination on seizure hospitalizations in children: A systematic review.

BACKGROUND: Previous studies found conflicting results about the effect of rotavirus (RV) vaccination on seizure hospitalizations in children younger than 5 years old. OBJECTIVES: To evaluate the evidence of the impact of RV vaccination on the prevention of seizure hospitalizations in children. METHODS: A systematic review was conducted in the electronic database MEDLINE of all observational studies in children younger than 5 years old published since 2006. Two reviewers performed title/abstract, full-text review, and data extraction. RESULTS: Thirteen studies met eligibility criteria. Nine studies reported a significant reduction in seizure hospitalizations upon RV vaccine introduction, three studies reported an absence of significant impact, and one study reported a significant rise in seizure hospitalization after the introduction of RV vaccines. LIMITATIONS: The great variability between study designs, case definitions and potential biases prevent quantifying the impact of RV vaccination against seizure hospitalizations. CONCLUSIONS: RV vaccination might prevent seizure hospitalizations in children; however, robust, and well-designed studies are needed to better determine the strength of this association.

Systematic review of the effect of additional doses of oral rotavirus vaccine on immunogenicity and reduction in diarrhoeal disease among young children.

Background: Oral rotavirus vaccines have lower effectiveness in high child mortality settings. We evaluated the impact of additional dose(s) schedules of rotavirus vaccine on vaccine immunogenicity and reduction in episodes of gastroenteritis. Methods: We searched Medline (via PubMed), Cochrane databases and ClinicalTrials.gov for randomised controlled trials from 1973 to February 2022, evaluating the immunological and clinical impact of additional dose vs standard dose oral rotavirus vaccine schedules. We extracted immunogenicity - proportion of children with evidence of anti-rotavirus IgA seroresponse, and clinical - proportion of children with at least one episode of severe rotavirus gastroenteritis, outcome data and used random effects meta-analysis where appropriate. We assessed the methodological quality of the studies using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO (CRD42021261058). Findings: We screened 536 items and included 7 clinical trials. Our results suggest moderate to high level evidence that an additional dose rotavirus vaccine schedule improves IgA vaccine immune response, including additional doses administered as a booster dose schedule >6 months old; IgA vaccine seroresponse 74·3% additional dose schedule vs 56·1% standard dose schedule RR 1·3 (95%CI, 1·15 - 1·48), and when administered to children who were seronegative at baseline; IgA vaccine seroresponse 48.2% additional dose schedule vs 29.6% standard dose schedule RR 1.86 (95%CI 1.27 to 2.72). Only one study evaluated reduction in gastroenteritis episodes and found little benefit in first year of life, 1·8% vs 2·0% RR 0·88 (95% CI, 0·52 to 1·48), or second year of life, 1·7% vs 2·9% RR 0·62 (95%CI, 0·31 - 1·23). Interpretation: Administering an additional dose of oral rotavirus vaccines is likely to result in an improved vaccine immune response, including when administered as a booster dose to older children. Evidence of an impact on diarrhoeal disease is needed before additional dose rotavirus vaccine schedules can be recommended as vaccine policy. Funding: BM was funded by the National Health and Medical Research Council, the Royal Australasian College of Physicians Paediatrics and Child Health Division, and the Australian Academy of Science.

Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains.

Group A rotaviruses (RVAs) are the most common etiological agents of severe acute diarrhea among children under 5 years old worldwide. At present, two live-attenuated RVA vaccines, LLR (G10P[15]) and RotaTeq (G1-G4, G6 P[8], P[5]), have been introduced to mainland China. Although RVA vaccines can provide homotypic and partially heterotypic protection against several strains, it is necessary to explore the genetic and antigenic variations between circulating RVAs and vaccine strains. In this study, we sequenced viral protein VP7 and VP4 outer capsid proteins of 50 RVA strains circulating in China from 2016 to 2019. The VP7 and VP4 sequences of almost all strains showed high homology to those of previously reported human strains and vaccine strains of the same genotype. However, in the presumed antigenic epitopes of the VP7 and VP4, multiple amino acid variations were found, regardless of the G and P genotypes of these strains. Moreover, all circulating G3 RVA strains in China potentially possess an extra N-linked glycosylation site compared with the G3 strain of RotaTeq. The potential N-linked glycosylation site at residues 69-71 was found in all G9 strains in China but not in the G9 strain of the Rotavac or Rotasill vaccine. These variations in antigenic sites might result in the selection of strains that escape the RVA neutralizing-antibody pressure imposed by vaccines. Furthermore, the G4 and P[6] genotypes in this study showed high homology to those of porcine strains, indicating the transmission of G4 and P[6] genotypes from pigs to humans in China. More genetic surveillance with antigenic evaluation in prevalent RVAs is necessary for developing and implementing rotavirus vaccines in China.

Histo-blood group antigens and rotavirus vaccine virus shedding in Australian infants.

Rotavirus vaccine performance varies between high and low income countries. One possible explanation is inherited histo-blood group antigens (HBGAs) the expression of which differs between populations. HBGAs are polymorphic glycans on mucosal surfaces. Their presence indicates the secretor phenotype, while their absence identifies a non-secretor status. HBGAs can act as rotavirus receptors and might influence live-attenuated rotavirus vaccine virus replication and shedding. Studies in low and middle income countries of the human rotavirus vaccine Rotarix (RV1), suggest HBGA secretor phenotype is important for vaccine immunogenicity. We investigated in a high income country the association between HBGA phenotype (secretor and Lewis) and the bovine-human reassortment vaccine RotaTeq (RV5) vaccine shedding in the stools of infants following each vaccine dose. Eighty-two infants from an Australian birth cohort provided saliva and weekly stool samples after RV5 vaccination doses. Lewis and secretor HBGA phenotyping was identified from saliva samples and confirmed by genotyping. Vaccine virus strains were detected by real-time polymerase chain reaction assays. No significant association between secretor status and vaccine virus shedding was identified. The proportion of infants who shed rotavirus following the first RV5 dose for secretor and non-secretor infants was 57/64 (89%) and 17/18 (94%), respectively, decreasing to 24/64 (33%) and 9/18 (50%) after the second dose and 26/64 (42%) and 8/18 (44%) following the third vaccine dose, respectively. Similarly, no significant differences were observed in vaccine virus shedding by Lewis, or combined Lewis and secretor status, after each vaccine dose. We found HBGAs were not associated with RV5 vaccine virus shedding in Australian infants.

Changing distribution of rotavirus A genotypes circulating in Japanese children with acute gastroenteritis in outpatient clinic, 2014-2020.

BACKGROUND: Rotavirus A (RVA) is a major cause of severe acute gastroenteritis (AGE) in infants and children worldwide. In Japan, two kinds of rotavirus vaccines have been introduced as voluntary vaccines in 2011 and 2012, respectively, and launched into the national vaccine program in October 2020. METHODS: In this study, we investigated prevalence of RVA and their molecular characterization in the stool samples collected from infants and children with AGE who visited one outpatient clinic in Japan, from July 2014 to June 2020, during voluntary vaccination with two kinds of rotavirus vaccines. RESULTS: The RVA detection rates decreased from 44.7 % in 2014-2015 to 35.4 % in 2018-2019, whereas in 2019-2020 the numbers of samples collected were dramatically decreased and none of RVA was detected. During this study period, rotavirus vaccination rates in this area increased from 32.4 % to 62.2 %. Distribution of RVA VP7 (G), VP4 (P), and VP6 (I) genotypes in this area had changed year by year; the major genotype combinations were G1P[8]I1 and G1P[8]I2 in 2014-2015, G2P[4]I2 and G9P[8]I1 in 2015-2016, G1P[8]I1 and G8P[8]I2 in 2017-2018, and G8P[8]I2 in 2018-2019. Phylogenetic analysis demonstrated that VP7 nucleotide sequences of G1 were genetically diverse compared with those of other G genotypes in this study. Meanwhile, predominance of unusual G2P[8]I1, G2P[8]I2 and mixed P genotypes were observed only in 2016-2017, but did not carry on in 2017-2019. The equine-like G3 was detected only in 2016-2017. CONCLUSIONS: The results revealed diversity of RVA genotypes and the genotype combinations have changed year by year in Japan, during the study period of 2016-2020.

Impact and effectiveness of monovalent rotavirus vaccine in Tajik children.

BACKGROUND: In 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE). METHODS: Using surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 - 2019. Immunization records were obtained from clinics. RESULTS: Among enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 - 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 - 73%) among children 5 - 59 months of age and 64% (95% CI: 36 - 80%) among children 5 - 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 - 11 months of age, but CIs were wide and overlapping. CONCLUSIONS: Our data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.

Exploring the feasibility of integration of surveillance for intussusception into the routine monitoring of adverse events following immunization by countries of the WHO African Region for Africa.

Surveillance for intussusception (IS) post-rotavirus vaccine introduction in World Health Organization Africa Region (WHO/AFRO) has been restricted mainly to the large referral teaching hospitals. The choice of these facilities for surveillance was made to utilize the abundant expertise of specialists in paediatrics and surgery in these hospitals who can diagnose and manage such patients with IS. The surveillance has been well coordinated by the African Intussusception Surveillance Network established in 2012. This network has supported surveillance across the African region and has accumulated a huge database of IS cases in children < 1 year with findings that have demonstrated safety of the monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline). However, safety data on the pentavalent and RotaTeq (Merck Vaccine) is not yet available from the African region. Although, this network has provided much needed data, there is an inherent bias in monitoring and reporting of IS cases in only large tertiary hospitals. This time limited special project does not capture suspected intussusception cases with no access to hospital facilities used for monitoring IS. Additionally, the design requires extensive resources to support collection of high-quality data for monitoring IS, which is unsustainable. For these reasons suitable linkages between IS monitoring and routine Adverse Event Following Immunization (AEFI) should be established for continuity of monitoring of this condition. We propose alignment of the two systems that offers opportunity for high profile recognition and to enhance a sustainable system for diagnosis, treatment and continuous assessment of intussusception occurring in infancy.

Understanding Rotavirus Vaccine Efficacy and Effectiveness in Countries with High Child Mortality.

Rotavirus claims thousands of lives of children globally every year with a disproportionately high burden in low- and lower-middle income countries where access to health care is limited. Oral, live-attenuated rotavirus vaccines have been evaluated in multiple settings in both low- and high-income populations and have been shown to be safe and efficacious. However, the vaccine efficacy observed in low-income settings with high rotavirus and diarrheal mortality was significantly lower than that seen in high-income populations where rotavirus mortality is less common. Rotavirus vaccines have been introduced and rolled out in more than 112 countries, providing the opportunity to assess effectiveness of the vaccines in these different settings. We provide an overview of the efficacy, effectiveness, and impact of rotavirus vaccines, focusing on high-mortality settings and identify the knowledge gaps for future research. Despite lower efficacy, rotavirus vaccines substantially reduce diarrheal disease and mortality and are cost-effective in countries with high burden. Continued evaluation of the effectiveness, impact, and cost-benefit of rotavirus vaccines, especially the new candidates that have been recently approved for global use, is a key factor for new vaccine introductions in countries, or for a switch of vaccine product in countries with limited resources.

Vaccine hesitancy and receipt of mandatory and optional pediatric vaccines in Shanghai, China.

Given increased global concern about vaccine hesitancy, this study estimates coverage of mandatory vs non-mandatory vaccines in children, and assesses whether vaccine hesitancy among young parents relates to their child's eventual vaccination status in Shanghai, China. In a cohort study within Shanghai, China, we ascertained vaccine hesitancy among parents of young infants, and later abstracted their child's electronic immunization records. We measure full coverage of vaccines on the mandatory, and publicly funded Expanded Program on Immunization (EPI). Non-EPI vaccines included pneumococcal conjugate vaccine, Haemophilus influenzae type b vaccine, and rotavirus vaccine. Vaccine hesitancy was linked to vaccine uptake through mixed effects logistic regression models. Among 972 children, full coverage of all EPI vaccines by 15 months was 95%, compared to dose 1 coverage of pneumococcal conjugate vaccine at 13%, Haemophilus influenzae type b vaccine at 68%, and rotavirus vaccine at 52%. Vaccine hesitancy was not significantly linked with full coverage of all EPI vaccines (OR: 1.55, 95% CI: .89, 2.72), but coverage in the vaccine hesitant was lower for pneumococcal conjugate vaccine dose 1 (OR: .70, 95% CI: .53, .91), and rotavirus vaccine dose 1 (OR: .69, 95% CI: .56, .86). Disparities by education level were not significant for EPI vaccines, but were for dose 1 of pneumococcal conjugate vaccine rotavirus vaccine. Overall, vaccine hesitancy was related to lower uptake of non-EPI, but not EPI vaccines. Shanghai has a robust system for insurance equitable access to EPI vaccines, but if vaccine hesitancy grows, it could reduce coverage of non-EPI vaccines.

Potential impact and cost-effectiveness of injectable next-generation rotavirus vaccines in 137 LMICs: a modelling study.

While current live, oral rotavirus vaccines (LORVs) are reducing severe diarrhea everywhere, their effectiveness is lower in high burden settings. Alternative approaches are in advanced stages of clinical development, including injectable next-generation rotavirus vaccine (iNGRV) candidates, which have the potential to better protect children, be combined with existing routine immunizations and be more affordable than current LORVs. In an effort to better understand the real public health value of iNGRVs and to help inform decisions by international agencies, funders, and vaccine manufacturers, we conducted an impact and cost-effectiveness analysis examining 20 rotavirus vaccine use cases. We evaluated several currently licensed LORVs, one neonatal oral NGRV (oNGRV), one iNGRV, and one iNGRV-DTP (iNGRV comprising part of a DTP-containing combination) over a ten-year timeframe in 137 low- and middle-income countries. The most promising use case identified was a high efficacy iNGRV-DTP, predicted to have the lowest vaccine program cost (US$1.4 billion), the highest vaccine benefit (750,000 rotavirus deaths averted, 13 million rotavirus hospital admissions averted, US$ 2.7 billion health-care cost averted), and most favorable cost-effectiveness (cost-saving). iNGRV-DTP vaccine remained the most affordable, safe, and cost-effective option even when it was assumed to have equivalent efficacy to the current LORVs. This study shows that while the development of iNGRVs with superior efficacy to currently licensed LORVs would be ideal, iNGRVs with similar efficacy to LORVs would offer substantial public health value. It also highlights the economic value of accelerating the development of DTP-based combination vaccines that include iNGRV to provide rotavirus protection.

Direct and indirect costs of acute diarrhea in children under five years of age in Indonesia: Health facilities and community survey.

BACKGROUND: Diarrhea remains a major cause of child morbidity and mortality in low- and middle-income countries. Reliable data on the economic burden of diarrhea is required to support the selection of appropriate health intervention programs. This study aimed to estimate the costs of acute diarrhea in children under five years of age in Indonesia, a large middle-income country with a substantial diarrheal burden. METHODS: Direct medical cost data were extracted retrospectively for 1050 children under five years of age with acute diarrhea receiving inpatient care across 45 health facilities in seven Indonesian provinces during 2017-2020. Direct medical costs for children treated in outpatient settings were estimated by collecting unit costs associated with standard diarrhea case management in children. A structured interview of 240 caregivers of inpatients was also conducted retrospectively to estimate direct non-medical costs as well as indirect costs from caregiver income loss. RESULTS: The weighted average direct medical cost for treatment of acute diarrhea as an inpatient and outpatient across health facility types was US$99.8 (SD±$56.8)(35% room costs, 29% professional fees, 26% medication costs, 10% diagnostic costs) and US$7.6 (SD±$4.3) (34% diagnostic costs, 28% medication costs, 27% professional fees, 10% registration fees), respectively. The average direct non-medical household cost for an acute diarrheal admission was US$4.90 and the indirect cost was US$9.90. CONCLUSION: There is a significant economic burden associated with acute diarrhea in children in Indonesia. This study, based on a wide variety of health care settings and geographical regions, provides data to inform the economic evaluation of rotavirus vaccines and other diarrheal prevention programs. FUNDING: This work was supported by a research grant from the Murdoch Children's Research Institute (MCRI) and PATH; and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Established and new rotavirus vaccines: a comprehensive review for healthcare professionals.

Robust scientific evidence related to two rotavirus (RV) vaccines available worldwide demonstrates their significant impact on RV disease burden. Improving RV vaccination coverage may result in better RV disease control. To make RV vaccination accessible to all eligible children worldwide and improve vaccine effectiveness in high-mortality settings, research into new RV vaccines continues. Although current and in-development RV vaccines differ in vaccine design, their common goal is the reduction of RV disease risk in children <5 years old for whom disease burden is the most significant. Given the range of RV vaccines available, informed decision-making is essential regarding the choice of vaccine for immunization. This review aims to describe the landscape of current and new RV vaccines, providing context for the assessment of their similarities and differences. As data for new vaccines are limited, future investigations will be required to evaluate their performance/added value in a real-world setting.

PLAIN LANGUAGE SUMMARYThe diseaseRotaviruses are a leading cause of acute diarrhea, also called gastroenterities, among young children. They can lead to servere dehydration, hospitilization, and even death.Several vaccines against rotavirus disease have been developed. Their design is based on:weakened human rotavirus that mimic natural infection without causing disease, such as Rotarix, Rotavin-M1, Rotavac and RV3-BB (not yet marketed)non-infective animal viruses such as RotaTeq, Rotasiil or LLR.new concepts, such as inactivated vaccinesWhat is new?We reviewed the current, recently launched and soon-to-be-launched rotavirus vaccines and found that:Rotarix and RotaTeq have been used globally for more than a decade with demonstrated impact and favourable safety profileLimited data on the impact and safety profile are available to date for:Rotavin-M1 and LLR vaccines, locally marketed in Vietnam and China, respectivelyRotavac and Rotasiil, licensed in indiaNew vaccine concepts have been mainly investigated animal models with encouraging resultsWhat is the impact?Despite their different designs, the current rotavirus vaccines demonstrate effectiveness in protecting against rotairus gastroenterits.Data for most recent vacciness are currently limited, for which additional data are needed to demonstrate how they will perform on a larger scale, their added value in a real setting and ther safety profile.

Plasma VP8∗-Binding Antibodies in Rotavirus Infection and Oral Vaccination in Young Bangladeshi Children.

BACKGROUND: Despite the availability and success of live-attenuated oral vaccines, rotavirus (RV) remains the leading cause of pediatric gastroenteritis worldwide. Next-generation vaccines targeting RV VP8∗ are under evaluation, but the role of VP8∗-specific antibodies in human immunity to RV and their potential as immune correlates of protection remains underexplored. METHODS: We measured plasma RV VP8∗-binding antibodies in 2 cohorts of young children in Dhaka, Bangladesh. Plasma from a cohort study of 137 unvaccinated children aged 6-24 months old hospitalized with acute gastroenteritis was assessed for VP8∗ antibody seropositivity. VP8∗ antibodies were compared with the current standard for RV immunity, total RV-specific IgA (RV-IgA). Additionally, VP8∗ antibody responses were measured as part of an immunogenicity trial of a monovalent, oral, live-attenuated RV vaccine (Rotarix). RESULTS: Fewer children with acute RV gastroenteritis were seropositive for VP8∗-binding IgA or IgG antibodies at hospital admission compared with RV-IgA, suggesting that the absence of VP8∗-binding antibodies more accurately predicts susceptibility to RV gastroenteritis than RV-IgA in unvaccinated children. However, when present, these antibodies appeared insufficient to protect fully from disease and no threshold antibody level for protection was apparent. In vaccinated children, these antibodies were very poorly induced by Rotarix vaccine, suggesting that VP8∗-specific antibodies alone are not necessary for clinical protection following oral vaccination. CONCLUSIONS: This work suggests that VP8∗-binding antibodies may not be sufficient or necessary for protection from RV gastroenteritis following prior RV infection or oral vaccination; the role of VP8∗ antibodies induced by parenteral vaccination with non-replicating vaccines remains to be determined.

National stakeholder preferences for next-generation rotavirus vaccines: Results from a six-country study.

BACKGROUND: Currently available live, oral rotavirus vaccines (LORVs) have significantly reduced severe rotavirus hospitalizations and deaths worldwide. However, LORVs are not as effective in low- and middle-income countries (LMIC) where rotavirus disease burden is highest. Next-generation rotavirus vaccine (NGRV) candidates in development may have a greater public health impact where they are needed most. The feasibility and acceptability of possible new rotavirus vaccines were explored as part of a larger public health value proposition for injectable NGRVs in LMICs. OBJECTIVE: To assess national stakeholder preferences for currently available LORVs and hypothetical NGRVs and understand rationales and drivers for stated preferences. METHODS: Interviews were conducted with 71 national stakeholders who influence vaccine policy and national programming. Stakeholders from Ghana, Kenya, Malawi, Peru, Senegal, and Sri Lanka were interviewed using a mixed-method guide. Vaccine preferences were elicited on seven vaccine comparisons involving LORVs and hypothetical NGRVs based on information presented comparing the vaccines' attributes. Reasons for vaccine preference were elicited in open-ended questions, and the qualitative data were analyzed on key preference drivers. RESULTS: Nearly half of the national stakeholders interviewed preferred a highly effective standalone, injectable NGRV over current LORVs. When presented as having similar efficacy to the LORV, however, very few stakeholders preferred the injectable NGRV, even at substantially lower cost. Similarly, a highly effective standalone injectable NGRV was generally not favored over an equally effective oral NGRV following a neonatal-infant schedule, despite higher cost of the neonatal option. An NGRV-DTP-containing combination vaccine was strongly preferred over all other options, whether delivered alone with efficacy similar to current LORVs or co-administered alongside an LORV (LORV + NGRV-DTP) to increase efficacy. CONCLUSION: Results from these national stakeholder interviews provide valuable insights to inform ongoing and future NGRV research and development.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.