Rotavirus and adenovirus infections in children with acute gastroenteritis after introducing the Rotasiil® vaccine in Kisangani, Democratic Republic of the Congo.

BACKGROUND: Although rotavirus vaccination has reduced the global burden of the virus, morbidity and mortality from rotavirus infection remain high in Sub-Saharan Africa. This study aimed to determine the prevalence of rotavirus and adenovirus infections in children under five years with acute gastroenteritis and to identify factors associated with rotavirus infection after the introduction of the Rotasiil® vaccine in 2019 in Kisangani, Democratic Republic of the Congo (DRC). METHODS: This study consisted of a cross-sectional hospital-based survey conducted from May 2022 to April 2023 in four health facilities in Kisangani, using a fecal-based test (rapid antigenic immuno-chromatographic diagnostic test, BYOSYNEX adenovirus/rotavirus BSS, Biosynex SA, Illkirch-Graffenstaden, France) of rotavirus and adenovirus infections among children under five years of age with acute gastroenteritis. RESULTS: A total of 320 children under five years of age with acute gastroenteritis were included. The prevalence of rotavirus infection was 34.4%, that of adenovirus was 6.3%, and that of both rotavirus and adenovirus coinfection was 1.3%. The prevalence of rotavirus was significantly higher in unvaccinated children than in vaccinated children (55.4% versus 23.1%; P < 0.001). This difference was observed only in children who received all three vaccine doses. Multivariate logistic regression analysis shows that the rate of rotavirus infection was significantly reduced in vaccinated children (adjusted OR: 0.31 [95% confidence intervals (CI): 0.19-0.56]; P < 0.001) and those whose mothers had an average (adjusted OR: 0.51 [95% CI: 0.25-0.91]; P = 0.018) or high level (adjusted OR: 0.34 [95% CI: 0.20-0.64]; P < 0.001) of knowledge about the rotavirus vaccine. CONCLUSIONS: The prevalence of rotavirus infection remains high in Kisangani despite vaccination. However, the prevalence of adenovirus infections was low in our series. Complete vaccination with three doses and mothers' average and high level of knowledge about the rotavirus vaccine significantly reduces the rate of rotavirus infection. It is, therefore, essential to strengthen the mothers' health education, continue with the Rotasiil® vaccine, and ensure epidemiological surveillance of rotavirus infection.

Prediction of effectiveness of universal rotavirus vaccination in Southwestern Vietnam based on a dynamic mathematical model.

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.

Immunogenicity and safety of a new hexavalent rotavirus vaccine in Chinese infants: A randomized, double-blind, placebo-controlled phase 2 clinical trial.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Rotavirus infections and their genotype distribution in Rwanda before and after the introduction of rotavirus vaccination.

Rotavirus vaccination has reduced mortality and hospital admissions due to rotavirus diarrhoea, but its effect on rotavirus infections and the impact of rotavirus genotypes are still unclear. Real-time PCR was used to detect rotavirus and other pathogens in faeces samples from children below five years of age with acute diarrhoea, collected before (n = 827) and after (n = 807, 92% vaccinated) the introduction of vaccination in Rwanda in 2012. Rotavirus was genotyped by targeting VP7 to identify G1, G2, G3, G4, G9 and G12 and VP4 to identify P[4], P[6] and P[8]. In vaccinated children, rotavirus infections were rarer (34% vs. 47%) below 12 months of age, severe dehydration was less frequent, and rotavirus was more often found as a co-infecting agent. (79% vs 67%, p = 0.004). Norovirus genogroup II, astrovirus, and sapovirus were significantly more often detected in vaccinated children. The predominant rotavirus genotypes were G2P[4] and G12P[6] in 2009-2010 (50% and 12%), G9P[8] and G1P[8] in 2011-2012 (51% and 22%), and G12P[8] in 2014-2015 (63%). Rotavirus vaccination in Rwanda has reduced the severity of rotavirus gastroenteritis and rotavirus infection frequency during the first year of life. Rotavirus infections were frequent in vaccinated children with diarrhoea, often as co-pathogen. Rotavirus genotype changes might be unrelated to vaccination because shifts were observed also before its introduction.

The economic impact of the introduction of universal rotavirus vaccination on rotavirus gastroenteritis related hospitalisations in children in Ireland.

BACKGROUND: Rotavirus gastroenteritis (RVGE), a vaccine preventable disease, remains a common cause of severe gastroenteritis in children globally. Ireland introduced the universal rotavirus vaccination to the national immunisation programme in 2016. In this paper the economic impact on RVGE related hospitalisations amongst children under 5 years is examined. METHODS: Using national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5 years, pre- and post-vaccine introduction. Costs are estimated and ITSA results are compared to the counterfactual to estimate the economic impact of the vaccine. A probit model examines patient characteristics pre- and post-vaccine introduction. RESULTS: Vaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1 year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2 years (p = 0.001) and length of stay was lower on average (p = 0.095). The counterfactual analysis revealed 492 RVGE hospitalisations were avoided on average annually since the introduction of the vaccine. This has an estimated economic value of €0.92 million per annum. CONCLUSIONS: Following the introduction of the rotavirus vaccine in Ireland, hospitalisations for RVGE decreased significantly and those hospitalised were older and with a reduced length of stay on average. This has the potential for significant cost savings for the Irish healthcare system.

Introducing ROTAVAC® to the occupied Palestinian Territories: Impact on diarrhea incidence, rotavirus prevalence and genotype composition.

BACKGROUND: Rotavirus infection remains an important cause of morbidity and mortality in children. The introduction of vaccination programs in more than 100 countries has contributed to a decrease in hospitalizations and mortality. This study investigates the epidemiological impact of the rotavirus vaccine ROTAVAC® in the Palestinian Territories, the first country to switch from ROTARIX® to this new vaccine. METHODS: Clinical surveillance data was collected fromchildren younger than 5attendingoutpatient clinics throughout Gaza withdiarrhea between 2015 and 2020. The incidence of all-cause diarrhea was assessed using an interrupted time-series approach. Rotavirus prevalence was determined at the Caritas Baby Hospital in the West Bank usingELISA on stool specimen of children younger than 5with diarrhea. Genotyping was performed on 325 randomly selected rotavirus-positive samples from January 2015 through December 2020 using multiplex PCR analysis. RESULTS: Average monthly diarrhea casesdropped by 16.7% annually fromintroduction of rotavirus vaccination in May 2016 to the beginning of the SARS-CoV-2 epidemic in March 2020 for a total of 53%. Case count declines were maintained afterthe switchto ROTAVAC® in October 2018. Rotavirus positivity in stool samples declined by 67.1% over the same period without change followingthe switch to ROTAVAC®. The distribution of predominant genotypes in rotavirus-positive stool samples changed from a pre-vaccination G1P [8] to G9P[8] and G12P[8] during the ROTARIX® period and G2P[4] after the introduction of ROTAVAC®. CONCLUSION: ROTAVAC® has shown epidemiological impact on par with ROTARIX® after its introduction to the national immunization schedule in the Palestinian Territories. A molecular genotype shift from a pre-vaccination predominance of G1P[8] to a current predominance of G2P[4] requires more long-term surveillance.

Impact and cost-effectiveness of rotavirus vaccination in Niger: a modelling study evaluating alternative rotavirus vaccines.

OBJECTIVES: To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model. SETTING: The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger. PARTICIPANTS: The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age. INTERVENTIONS: We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021. RESULTS: We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold. CONCLUSIONS: This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis.

BACKGROUND: Rotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries. METHODS: Beginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars. RESULTS: Vaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147-$38,993) and ranged from $85 per DALY averted (95% UI: $13-$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030-$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39-$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382-$3,118). CONCLUSION: Our findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.

Rotaviruses: From Pathogenesis to Disease Control-A Critical Review.

Since their first recognition in human cases about four decades ago, rotaviruses have remained the leading cause of acute severe dehydrating diarrhea among infants and young children worldwide. The WHO prequalification of oral rotavirus vaccines (ORV) a decade ago and its introduction in many countries have yielded a significant decline in the global burden of the disease, although not without challenges to achieving global effectiveness. Poised by the unending malady of rotavirus diarrhea and the attributable death cases in developing countries, we provide detailed insights into rotavirus biology, exposure pathways, cellular receptors and pathogenesis, host immune response, epidemiology, and vaccination. Additionally, recent developments on the various host, viral and environmental associated factors impacting ORV performance in low-and middle-income countries (LMIC) are reviewed and their significance assessed. In addition, we review the advances in nonvaccine strategies (probiotics, candidate anti-rotaviral drugs, breastfeeding) to disease prevention and management.

Long-term surveillance of rotavirus vaccination after implementation of a national immunization program in Finland (2008-2018).

BACKGROUND: Rotavirus (RV) vaccination was included in the Finnish National immunization Program (NIP) in 2009. RotaTeq (RV5) has been used exclusively with a national average vaccination coverage rate (VCR) of > 90%. While previous studies have demonstrated that inpatient rotavirus gastroenteritis (RVGE) admissions declined by as much as 96% in Finnish children ≤ 5 years old following RV vaccination introduction, no study has evaluated long-term protection after vaccination in Finland. In this study, we analyze incidence of hospital outpatient visits and inpatient admissions of gastroenteritis in children up to 7 years of age. METHODS: We first describe the incidence of RVGE, viral gastroenteritis (VGE), and acute gastroenteritis (AGE) for all Finnish children born during 2008-2011. Children were stratified by the year of birth into not-eligible, partially eligible and rotavirus vaccine-eligible (born in 2008, 2009, 2010 and 2011, respectively). Hospital inpatient and outpatient data was collected from the National Care Register for all children from birth until December 31st, 2018. We also studied RVGE incidence during 2014-2017 for children<3 years of age in municipalities with VCRs of 90% and above and municipalities with VCRs below 90%. RESULTS: RVGE incidence decreased significantly soon after implementation of RV vaccination in the NIP. In vaccine-eligible cohorts, no clear peak incidence in the youngest age groups could be observed, and no RVGE cases were observed beyond 6 years after vaccination, in contrast to vaccine ineligible and partially eligible cohorts. Despite an overall high VCR in Finland, regions with high VCR had lower incidence of RVGE than regions with lower VCR. CONCLUSION: Incidence of RVGE has remained low in all age groups during the 10 years following introduction of RV vaccine in the Finnish NIP. Differences in RVGE incidence were observed in regions with high as compared with lower VCR, highlighting the importance of maintaining high vaccination coverage.

Does the Choice of Health Metric, DALY or QALY, Influence Conclusions of Health Economic Evaluation? A Case Study of Rotavirus Vaccine in Burundi.

BACKGROUND: Two metrics, quality-adjusted life-year (QALY) and disability-adjusted life-year (DALY), have been commonly used to measure health benefits associated with health interventions. This study aimed to explore the effect of the choice of health metric (DALY or QALY) on economic evaluation conclusion. METHODS: A previous published model for a cost-utility analysis (CUA) of rotavirus vaccine was adapted to estimate the QALYs gained and DALYs averted from four rotavirus vaccines: Rotarix, RotaTeq, Rotavac, and Rotasiil. The study was conducted in both Burundi provider and societal perspectives over a five-year time horizon. Disability weights (DW) were derived from the Global Burden of Disease (GBD) study. Scenario analysis was performed to evaluate the impact of age weights and source of utility weight. RESULTS: In base-case analysis, the QALYs gained ranged from 46 to 78% of the DALYs averted. The incremental cost-effectiveness ratios (ICER) per QALY gained were higher than ICER per DALY averted by 28 to 113%, leading to less favorable cost effectiveness. The QALYs gained from using 1-DW as utility weight were slightly higher than those using EQ-5D utility weight obtained from previous literature, yet less likely to alter CUA conclusions. When age-weighting was incorporated in the DALY calculation, the ICERs per DALY averted were reduced leading to more favorable cost effectiveness. CONCLUSION: In case of rotavirus diarrhea, in which mortality burden is considered larger than morbidity due to short duration of disease, although the use of DALY consistently led to more favorable cost-effective result than the use of QALY such effects were considered small and less likely to affect the EE conclusion under current CET of 1 GDP per capita.

Effect of early life antibiotic use on serologic responses to oral rotavirus vaccine in the MAL-ED birth cohort study.

BACKGROUND: Oral rotavirus vaccine efficacy is lower in low- and middle-income countries (LMICs) than in high-income countries. The degree to which antibiotic use impacts rotavirus vaccine immunogenicity in LMICs is unknown. Using data from a multisite prospective birth cohort study of malnutrition and enteric disease, MAL-ED, we examined the effect of early life antibiotic use on the immune response to rotavirus vaccine. METHODS: We assessed whether antibiotic use from birth up to 7 days following rotavirus vaccine series completion was associated with rotavirus seropositivity at 7 months of age in Brazil, Peru, and South Africa using a modified Poisson regression. We then used parametric g-computation to estimate the impact of hypothetical interventions that treated all children and alternatively prevented inappropriate antibiotic treatments on seropositivity. RESULTS: Of 537 children, 178 (33%) received at least one antibiotic course during the exposure window. Probability of seropositivity was 40% higher among children who had at least one course of antibiotics compared with those with no antibiotic exposure (PR: 1.40, 95% CI: 1.04, 1.89). There was no significant difference by the number of antibiotic courses received or total duration of antibiotics. Treating all children with antibiotics would be associated with a 19% (95% CI: 18%, 21%) absolute increase in seropositivity at 7 months. In contrast, removing inappropriate antibiotics would result in a 4% absolute reduction (95% CI: -5%, -2%) in seropositivity. CONCLUSIONS: Early life antibiotic use was associated with increased seropositivity. However, a hypothetical intervention to remove inappropriate antibiotics would have little effect on overall seropositivity. Further investigation into the underlying mechanisms of antibiotic use on the infant gut microbiome and immune response are needed.

Rotavirus epidemiology and genotype distribution in hospitalised children, Greece, 2008 to 2020: A prospective multicentre study.

BackgroundTwo rotavirus (RV) vaccines were licensed in Greece in late 2006 and included in the national immunisation programme in 2012.AimTo study the epidemiology and genotype distribution of RV in children during the post-vaccination period and assess the impact of increased vaccination coverage.MethodsIn a prospective multicentre hospital-based study, hospitalised children (≤ 16 years) with an RV-positive faecal sample were recruited. Epidemiological and genotyping analyses were performed; periods of low (2008-12) and moderate (2012-20) RV vaccination coverage were compared. Statistical analysis was performed with a chi-squared or Mann-Whitney U test and logistic regression.ResultsA total of 3,874 children (55.6% male; n = 2,153) with median age of 1.4 years (IQR: 0.5-3.3) were studied during 2008-20. Most RV-infected children were aged ≤ 3 years (72.2%) and hospitalised during December-May (69.1%). Common RV genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], G12P[8]) were detected in 92.2% of samples; G-P combinations with prevalence above 1% were G4P[8] (44.1%), G1P[8] (25.4%), G2P[4] (14.9%), G9P[8] (3.5%), G12P[8] (2.2%), G3P[8] (2.1%), other (4.3%) and mixed (3.5%). Of all samples, 97.6% were homotypic or partially heterotypic to vaccines' genotypes. With moderate vaccination coverage, the seasonal peak was detected earlier, children were older and partially or fully heterotypic genotypes were increased (p < 0.001).ConclusionsIn the era of moderate RV vaccination coverage in Greece, epidemiology of RV in hospitalised children seemed to change. However, most circulating genotypes remain homotypic or partially heterotypic to RV vaccines. Continuous epidemiological surveillance and genotyping are important to monitor possible changes arising from RV vaccines' implementation.

Global Estimates of Rotavirus Hospitalizations Among Children Below 5 Years in 2019 and Current and Projected Impacts of Rotavirus Vaccination.

BACKGROUND: Rotavirus vaccine impact on rotavirus hospitalizations is not well documented globally. We performed a systematic review to estimate the number of rotavirus hospitalizations that (1) occur annually, (2) are currently prevented by rotavirus vaccines, and (3) could be prevented with improved vaccine coverage and universal vaccine introduction. METHODS: We systematically reviewed articles indexed in the PubMed database published from January 1, 2000, to December 31, 2019. We included all primary peer-reviewed studies with rotavirus hospitalization rates for children below 5 years that reported data prior to vaccine introduction, utilized at least one continuous year of data collection, and collected hospitalization data after 2000 using active surveillance. We grouped pre-vaccine country estimates by childhood mortality strata and calculated the median rate among each group. We then assigned the mortality stratum-specific hospitalization rates to each country and calculated the number of rotavirus hospitalizations by country, mortality strata, and World Health Organization region. RESULTS: Our search strategy identified 4590 manuscripts, of which 32 were included in the final dataset. In 2019, an estimated 1 760 113 (interquartile range [IQR]: 1 422 645-2 925 372) rotavirus hospitalizations occurred globally, with 524 871 (IQR: 415 987-814 835) prevented by rotavirus vaccination. With universal introduction of rotavirus vaccines and increased vaccine coverage, we estimate that an additional 751 609 (IQR: 607 671-1 318 807) rotavirus hospitalizations can be prevented annually. CONCLUSIONS: This analysis highlights the continued burden of rotavirus hospitalizations among children below 5 years. A large, preventable proportion of this burden could be eliminated by expanding introductions to new countries and increasing rotavirus vaccine coverage to levels seen with other childhood vaccinations.

Why Aren't We Achieving High Vaccination Rates for Rotavirus Vaccine in the United States?

BACKGROUND: Rotavirus vaccine (RV) coverage levels for US infants are <80%. METHODS: We surveyed nationally representative networks of pediatricians by internet/mail from April to June, 2019. Multivariable regression assessed factors associated with difficulty administering the first RV dose (RV#1) by the maximum age. RESULTS: Response rate was 68% (303/448). Ninety-nine percent of providers reported strongly recommending RV. The most common barriers to RV delivery overall (definite/somewhat of a barrier) were: parental concerns about vaccine safety overall (27%), parents wanting to defer (25%), parents not thinking RV was necessary (12%), and parent concerns about RV safety (6%). The most commonly reported reasons for nonreceipt of RV#1 by 4 to 5 months (often/always) were parental vaccine refusal (9%), hospitals not giving RV at discharge from nursery (7%), infants past the maximum age when discharged from neonatal intensive care unit/nursery (6%), and infant not seen before maximum age for well care visit (3%) or seen but no vaccine given (4%). Among respondents 4% strongly agreed and 25% somewhat agreed that they sometimes have difficulty giving RV#1 before the maximum age. Higher percentage of State Child Health Insurance Program/Medicaid-insured children in the practice and reporting that recommendations for timing of RV doses are too complicated were associated with reporting difficulty delivering the RV#1 by the maximum age. CONCLUSIONS: US pediatricians identified multiple, actionable issues that may contribute to suboptimal RV immunization rates including lack of vaccination prior to leaving nurseries after prolonged stays, infants not being seen for well care visits by the maximum age, missed opportunities at visits and parents refusing/deferring.

Assessing Vaccine Coverage and Timeliness in Bamako, Mali after the Introduction of Rotavirus Vaccine: A Modified Immunization Cluster Survey.

Vaccine coverage and timeliness are critical metrics for evaluating the performance of immunization programs. Following the introduction of rotavirus vaccine in Bamako, Mali, we conducted two cluster surveys spaced approximately 1 year apart to evaluate these metrics among children 9 to 20 months of age. Using the child's immunization card or the medical record at the center of administration, each selected child's immunization status was determined at 9 and 12 months of age. Deviations from the WHO-recommended immunization schedule were described by the median delay and fraction of children receiving doses outside of recommended age ranges. Overall, 1,002 children were enrolled in the two surveys combined; 80.1% of children born 7 to 12 months after introduction (survey 1) received three doses of pentavalent rotavirus vaccine (ROTA3) by 9 months of age, which increased to 86.1% among children born 17 to 26 months after introduction (survey 2). Concomitantly, coverage with the third dose of diphtheria-pertussis-tetanus-containing vaccine (DPT3) by age 9 months was 86.5% (survey 1) and 88.9% (survey 2); by age 12 months, 61.3% and 72.4% of children, respectively, had received all scheduled immunizations. The median delay in ROTA3 and DPT3 administration were similar at about 3.4 weeks. Within 3 years of introduction, coverage of rotavirus vaccine among Bamako infants achieved coverage similar to DPT3 and is approaching the Global Vaccine Action Plan goal of 90% coverage by 2020. However, timeliness of coverage remains a concern.

Global Rotavirus and Pneumococcal Conjugate Vaccine Introductions and the Association With Country Disease Surveillance, 2006-2018.

BACKGROUND: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. METHODS: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. RESULTS: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. CONCLUSIONS: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.

Phylogenetic analysis of VP7 and VP4 genes of the most predominant human group A rotavirus G12 identified in children with acute gastroenteritis in Himachal Pradesh, India during 2013-2016.

G12 strains are now considered to be the sixth most prevalent human rotaviruses globally. India has introduced rotavirus vaccine Rotavac® into the national immunization program in 2016 and Himachal Pradesh (HP) is the first state to launch it. During epidemiological rotavirus surveillance in HP, predominance of G12 rotaviruses was observed. This study investigated the genetic variability and evolution of HP G12 strains (n = 15) associated with P-genotypes P[6], P[4], and P[8] identified between 2013 and 2016. Phylogenetic analysis of VP7 gene revealed that all characterized G12 strains clustered in lineage-III and diversified into three subclusters indicating that these strains may have originated from three different ancestral G12 strains. The comparative sequence analysis of HP strains with Rotavac® and Rotarix® vaccine strains revealed various amino acid substitutions in epitope regions of VP7 and VP4 proteins especially at the antibody neutralization sites. Only 12/29 VP7 epitope residues and 2/25 VP4 epitope residues were found to be conserved between HP rotavirus strains and vaccine strains. Both long and short electropherotypes were observed in G12P[4] strains, while a single long electropherotype was observed in G12P[6] strains. Children of ≤11 months were significantly infected with G12 rotaviruses. The frequency of vomiting episodes (≥5/day) was significantly higher in children infected with G12 rotavirus strains as compared to non-G12 rotaviruses (p = 0.0405). Our study provides the comprehensive data on clinical characteristics and evolutionary pattern of the G12 rotavirus, the most prevalent strain in HP and emphasizes the need to monitor these strains for inclusion in future vaccine.