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.

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.

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.

Global Experience With Rotavirus Vaccines.

Rotavirus is a major cause of severe pediatric diarrhea worldwide. In 2006, 2 live, oral rotavirus vaccines, Rotarix and RotaTeq, were licensed for use in infants and were rapidly adopted in many high- and middle-income settings where efficacy had been demonstrated in clinical trials. Following completion of successful trials in low-income settings, the World Health Organization (WHO) recommended rotavirus vaccination for all infants globally in 2009. In 2018, 2 new rotavirus vaccines, Rotasiil and Rotavac, were prequalified by WHO, expanding global availability. As of March 2021, rotavirus vaccines have been introduced nationally in 106 countries. Since, Rotavirus vaccines have demonstrated effectiveness against severe disease and mortality, even among age groups in eligible for vaccination. Cross-genotypic protection has been demonstrated, and the favorable benefit-risk profile of these vaccines continues to be confirmed. Ongoing research seeks to better understand reasons for the geographic disparities in effectiveness observed, in order to optimize vaccine strategies worldwide.

[Population impact of rotavirus vaccination in Mexico after 10 years]. / Impacto poblacional a 10 años de la vacunación contra rotavirus en México.

OBJECTIVE: To evaluate the impact of rotavirus (RV) vaccination after 10 years of it´s universalization on morbidity and mortality from Acute Diarrheal Disease (ADD) in mexican children under five years of age. MATERIALS AND METHODS: Annual median numbers for ADD new cases, hospitalizations and deaths were compared between pre and post universalization periods; absolute and relative reductions were calculated, considering p<0.05 values as significant. RESULTS: Mortality, hospitalizations and new cases from ADD in children under five decreased 52.6, 46, and 15.5% respectively, in the posuniversalization period. During rotavirus seasons, reduction in mortality, hospitalizations and new cases was 66.9, 64.7, and 28.7% respectively. CONCLUSIONS: As of the universal introduction of RV vaccination in Mexico, significant and sustained reductions are appreciated for mortality and hospitalizations from ADD, less so for incidence. A most prominent effect is observed during the winter season.

OBJETIVO: Evaluar el impacto de la vacunación contra rotavirus (RV) a 10 años de su universalización sobre la morbimortalidad por enfermedad diarreica aguda (EDA) en niños mexicanos menores de cinco años. MATERIAL Y MÉTODOS: Se compararon las medianas anuales de casos nuevos, defunciones y hospitalizaciones por EDA del periodo pre y posuniversalización; se calcularon reducciones absolutas y relativas, considerando significativos valores de p<0.05. RESULTADOS: La mortalidad, hospitalizaciones y casos nuevos por EDA en menores de cinco años disminuyeron 52.6, 46 y 15.5% respectivamente, en el periodo posuniversalización. Durante la temporada de RV las reducciones en la mortalidad, hospitalizaciones y casos nuevos fueron de 66.9, 64.7 y 28.7%, respectivamente. CONCLUSIONES: A partir de la universaliza- ción de la vacuna de RV en México, se aprecian reducciones importantes y sostenidas en la mortalidad, hospitalizaciones e incidencia por EDA, con menor impacto en esta última. El mayor impacto se observa durante la temporada de RV.

[A systematic review of the risk of oral rotavirus vaccine and intussusception].

In 1999, since the Rotashield, the first generation of oral Rotavirus vaccine has been confirmed that there is a link to intussusception, mainly occurs in 7 days after first dose. With the second generation of RV vaccine has been listed globally and intussusception monitoring has continued. This study reviewed the current phase Ⅲ clinical and post-marketing studies of rotavirus vaccines on the market and found that the two most widely used rotavirus vaccines, RV1 and RV5, were found the risk of intussusception increased within 7 days of ORV. The Lanzhou lamb rotavirus vaccine (LLR), which manufactured by Lanzhou Institute of Biological Products Co, also lacks Epidemiological surveies. With the introduction of RV5 in 2018, the role of rotavirus vaccine in the prevention and efforts of severe rotavirus diarrhea is increasing. It is urgent to establish an intussusception active monitoring system to monitor the incidence of intussusception after rotavirus vaccine and provide more evidence for the post-marketing evaluation of the rotavirus vaccine.

[Expert consensus on the prevention, diagnosis and treatment of rotavirus gastroenteritis (RVGE) in children (2020)].

Rotavirus is the leading cause of acute gastroenteritis in children under 5 years worldwide. Every child aged 3 to 5 years has experienced at least one episode of rotavirus gastroenteritis (RVGE). In China, RVGE accounts for approximately 40% and 30% of diarrhea-related hospitalizations and outpatient visits in children under 5 years, and about 90% of RVGE occur in the children under 2 years. RVGE imposes heave burden to health care system and family and has gained wide attention from public health. World Health Organization ranked RVGE as the high priority vaccine-preventable disease. As of October 2019, 102 countries and regions have incorporated rotavirus vaccine into national immunization program, which has remarkably reduced disease burden and death associated with RVGE in children under 5 years worldwide. For this purpose, the Yangtze River Delta Immunization Integration Working Group, Chinese Medical Association Infectious Diseases Branch Pediatric Infection and Hepatology Group formulated the 'Expert consensus on the prevention, diagnosis and treatment of rotavirus gastroenteritis in children' based on the latest and important English and Chinese literatures. This consensus will be briefly described in the perspective of epidemiology, disease burden, clinical characteristics, laboratory diagnosis, prevention and treatment to comprehensively landscape the epidemiology of rotavirus, scientifically evaluate the clinical symptoms and disease burden of rotavirus infection, comprehensively consider the vaccination prevention and treatment measures, and further construct and improve the integrated prevention and control strategy of RVGE in the region of Yangtze River Delta.

Long-term impact of suboptimal rotavirus vaccines on acute gastroenteritis in hospitalized children in Northern Taiwan.

BACKGROUND/PURPOSE: Rotavirus vaccines were launched in Taiwan since early 2006. Our study was aimed to figure out long-term extended molecular epidemiology in acute gastroenteritis (AGE) in hospitalized young children after rotavirus vaccination in Taiwan. METHODS: During the 10-year period from January 2007 to December 2016, fecal samples from children under 5 years old with AGE hospitalized in Chang Gung Children's Hospital (CGCH) were examined for enteric pathogens and they were divided into two time intervals: early post-vaccine (Jan. 2007 to Dec. 2011; EPV) and late post-vaccine (Jan. 2012 to Dec. 2016; LPV). RESULTS: In total, 837 patients with AGE were enrolled with complete study. In the EPV period, 106 (26.7%) rotavirus and 65 (16.4%) norovirus infections were identified as major pathogens. In the LPV period, 79 (17.9%) rotavirus and 98 (22.2%) norovirus infections were diagnosed. Statistical analyses showed a significantly decreased prevalence of rotavirus infection (P = 0.002) and a significantly increased prevalence of norovirus (P = 0.034) and enteric bacterial infections (P < 0.001). A substantial decrease of rotavirus G1 (P = 0.079) in the LPV period and norovirus GII.4 prevailed through the decade. CONCLUSION: In Taiwan, under a suboptimal rotavirus vaccination policy, there was a marked decrease in the rate of rotavirus AGE of hospitalized young children. Significantly increased norovirus infection has replaced rotavirus as the leading cause. Expansion of rotavirus vaccine coverage, development of a norovirus prevention strategy, and sustained bacterial infection control are important for AGE containment in children in Taiwan.

A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants.

BACKGROUND: The recommended schedule for receipt of 2-dose human rotavirus vaccine (HRV) coincides with receipt of the first and second doses of diphtheria, pertussis, and tetanus vaccine (ie, 6 and 10 weeks of age, respectively). Alternative schedules and additional doses of HRV have been proposed and may improve vaccine performance in low-income countries. METHODS: In this randomized trial in rural Ghana, HRV was administered at ages 6 and 10 weeks (group 1), 10 and 14 weeks (group 2), or 6, 10, and 14 weeks (group 3). We compared serum antirotavirus immunoglobulin A (IgA) seroconversion (≥20 U/mL) and geometric mean concentrations (GMCs) between group 1 and groups 2 and 3. RESULTS: Ninety-three percent of participants (424 of 456) completed the study per protocol. In groups 1, 2, and 3, the IgA seroconversion frequencies among participants with IgA levels of <20 U/mL at baseline were 28.9%, 37.4%, and 43.4%, respectively (group 1 vs group 3, P = .014; group 1 vs group 2, P = .163). Postvaccination IgA GMCs were 22.1 U/mL, 26.5 U/mL, and 32.6 U/mL in groups 1, 2, and 3, respectively (group 1 vs group 3, P = .038; group 1 vs group 2, P = .304). CONCLUSIONS: A third dose of HRV resulted in increased seroconversion frequencies and GMCs, compared with 2 doses administered at 6 and 10 weeks of age. Since there is no correlate of protection, a postmarketing effectiveness study is required to determine whether the improvement in immune response translates into a public health benefit in low-income countries. CLINICAL TRIALS REGISTRATION: NCT015751.

Sustained Reduction of Childhood Diarrhea-Related Mortality and Hospitalizations in Mexico After Rotavirus Vaccine Universalization.

BACKGROUND: Mexico implemented routine childhood vaccination against rotavirus in 2007. We describe trends in hospitalization and deaths from diarrhea among children aged <5 years in Mexico before and 7 years after implementation of rotavirus vaccination. METHODS: We obtained data on deaths and hospitalizations from diarrhea, from January 2003 through December 2014, in Mexican children <5 years of age. We compared diarrhea-related mortality and hospitalizations in the postvaccine era with the prevaccine baseline from 2003 to 2006. RESULTS: Compared with the prevaccine baseline, we observed a 53% reduction (95% confidence interval [CI], 47%-58%) in diarrhea-related mortality and a 47% reduction (95% CI, 45%-48%) in diarrhea-related hospitalizations in postvaccine years, translating to 959 deaths and 5831 hospitalizations averted every year in Mexican children aged <5 years. Prevaccine peaks in diarrhea-related mortality and hospitalizations during the rotavirus season months were considerably diminished in postvaccine years, with greater declines observed during the rotavirus season compared with non-rotavirus season months. CONCLUSIONS: We document a substantial and sustained decline in diarrhea-related hospitalizations and deaths in Mexican children associated with implementation of rotavirus vaccination. These results highlight the public health benefits that could result in countries that adopt rotavirus vaccination into their national immunization programs.

Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward.

Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.

Reduced rotavirus vaccine effectiveness among children born during the rotavirus season: a pooled analysis of 5 case-control studies from the Americas.

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.

Parental views on childhood vaccination against viral gastroenteritis-a qualitative interview study.

BACKGROUND: Gastroenteritis (GE) causes significant morbidity, especially in young children. A vaccine against rotavirus, a common cause of viral GE (vGE), was added to the childhood immunization schedule in the UK in July 2013 and further related vaccines are under development. AIM: To explore parents' beliefs about vGE and their attitudes towards vaccinating. DESIGN AND SETTING: Qualitative interview study with parents of children who had recently experienced an episode of GE. METHOD: Twenty-eight semi-structured interviews were conducted over the phone with parents. Interviews were audio-recorded, transcribed and analysed using standard thematic approaches. RESULTS: Parents varied in their perception of the threat posed by GE, and parents who did not perceive GE as serious were less enthusiastic about vaccines. Other parents were supportive of vaccines in general and considered benefits to their child, their family and the wider community. Many parents said that they lacked knowledge about efficacy and effectiveness of GE vaccines but their underlying belief about the seriousness of illness motivated their attitudes. CONCLUSION: Acceptability of GE vaccines to parents could be improved by providing more information on both the burden of illness and the impact of rotavirus vaccine in other comparable countries.

Direct, indirect, total, and overall effectiveness of the rotavirus vaccines for the prevention of gastroenteritis hospitalizations in privately insured US children, 2007-2010.

We demonstrate how direct, indirect, total, and overall effectiveness estimates and absolute benefits of rotavirus vaccines vary through the years following vaccine introduction. Privately insured US children in a large claims database were followed from age 8 months until they 1) experienced a hospitalization for rotavirus or acute gastroenteritis; 2) lost continuous health plan enrollment; 3) turned 20 months of age; or 4) reached the end of the study period. Vaccine effectiveness estimates in preventing rotavirus and acute gastroenteritis hospitalizations were estimated using Cox proportional hazards regression, stratified by calendar year and adjusted for birth month. Incidence rate differences were estimated to determine the absolute number of gastroenteritis hospitalizations prevented in the cohort. Among 905,718 children, 51%, 66%, 80%, and 86% received 1 or more doses of rotavirus vaccine in each year from 2007 to 2010. The direct vaccine effectiveness of 1 or more doses of rotavirus vaccine in preventing rotavirus gastroenteritis hospitalizations ranged from 87% to 92% each year. Accounting for indirect protection increased estimates of vaccine effectiveness by an additional 3%-8% among those vaccinated. Failing to account for population-level vaccine benefits in 2010, when circulation of rotavirus was low, could underestimate the sustained impact of the vaccine program.

Estimating the costs of implementing the rotavirus vaccine in the national immunisation programme: the case of Malawi.

OBJECTIVES: Worldwide, rotavirus infections cause approximately 453,000 child deaths annually. Two licensed vaccines could be life- and cost-saving in low-income countries where the disease burden is highest. The aim of our study was to estimate the total cost of implementing the rotavirus vaccine in the national immunisation programme of a low-income country. Furthermore, the aim was to examine the relative contribution of different components to the total cost. METHODS: Following the World Health Organization guidelines, we estimated the resource use and costs associated with rotavirus vaccine implementation, using Malawi as a case. The cost analysis was undertaken from a governmental perspective. All costs were calculated for a 5-years period (2012-2016) and discounted at 5%. The value of key input parameters was varied in a sensitivity analysis. RESULTS: The total cost of rotavirus vaccine implementation in Malawi amounted to US$ 18.5 million over a 5-years period. This translated into US$ 5.8 per child in the birth cohort. With GAVI Alliance financial support, the total cost was reduced to US$ 1.4 per child in the birth cohort. Approximately 83% of the total cost was attributed to vaccine purchase, while 17% was attributed to system costs, with personnel, transportation and cold chain as the main cost components. CONCLUSION: The total cost of rotavirus vaccine implementation in Malawi is high compared with the governmental health budget of US$ 26 per capita per year. This highlights the need for new financing opportunities for low-income countries to facilitate vaccine implementation and ensure sustainable financing.

Monitoring of children with acute gastroenteritis in Madrid, Spain, during 2010-2011: rotavirus genotype distribution after the vaccines introduction.

BACKGROUND AND OBJECTIVES: A structured surveillance study was conducted on children with diarrhea who were hospitalized in Madrid (Spain) during 2010-2011, in order to describe temporal, geographic, and age-related trends in rotavirus (RV) strains after the introduction of the RV vaccines in our country. STUDY DESIGN AND RESULTS: A total of 370 children were enrolled, with RV being detected in 117 (31.6%) cases. Coinfections were detected mainly with rotavirus, astrovirus and norovirus. The most prevalent rotavirus G type was G1 (60.7%) followed by G2 (16.09%), G9 (5.9%), and G12 (5.1%). The G12 genotype appeared for the first time in 2008 in Spain, and it has increased to 5.1% of the cases in this report. Some uncommon P genotypes, such as P[14] and P[6], both with a low percentage, were found. The samples with G1 G2, G9 and G12 genotypes appeared in all ages, but were significantly higher in children under 2 years old. CONCLUSION: A long-term structured surveillance is required in the Spanish post vaccine era, in order to determine the prevalence and variability of RV genotypes. This will especially be needed to distinguish between changes occurring as a result of natural fluctuation in genotype or those (changes) that could be mediated by population immunity to the vaccines. In addition, it will be necessary to study the impact of the current vaccines on the circulating rotavirus strains and on the overall reduction in the prevalence of rotavirus disease among children in Spain.

High cost is the primary barrier reported by physicians who prescribe vaccines not included in India's Universal Immunization Program.

Haemophilus influenzae type B (Hib) vaccine, pneumococcal conjugate vaccine (PCV) and rotavirus (RV) vaccine are available in the private market in India, but, except for Hib in eight states, are not included in India's Universal Immunization Program (UIP). Pediatricians were surveyed about administering non-UIP vaccines. Most give these vaccines to some of their patients (73-83%, depending on vaccine), but few give them to all patients (7-18%). High cost was the most frequently cited barrier (93-96%). Only 10-12% of respondents had concerns about the efficacy of PCV or RV vaccine, and concerns about Hib vaccine efficacy or any vaccine safety issues were rare (1-3%). Practice varied by type of healthcare facility, with pediatricians at government hospitals least likely to administer non-UIP vaccines. Support for the inclusion of all three in the UIP was high (83-95%). Including Hib vaccine, PCV and RV vaccine in India's UIP would be supported by pediatricians and help eliminate the current barrier of high cost of these immunizations.

Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period.

BACKGROUND: Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. METHODS: In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. RESULTS: In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. CONCLUSIONS: RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

The Frequency of Rotavirus Gastroenteritis in Children from West of Iran and Genotyping of Rotavirus Isolates: A Suggestion for Further Changes in Childhood Immunization Program.

BACKGROUND: Rotavirus is the most common cause of gastroenteritis among children. Currently, four oral live-attenuated vaccines are available to prevent rotavirus infection. The World Health Organization (WHO) has recommended including rotavirus vaccination in national immunization programs; however, it has not been introduced to the Iranian national immunization program. The study aimed to assess the frequency of rotavirus gastroenteritis in the west of Iran and investigate the necessity of rotavirus vaccination. Study Design: A case series study. METHODS: In this case series study, 284 cases under six years of age who presented with acute gastroenteritis from March 2021 to 2022 to a referral hospital in the west of Iran were evaluated. Data on baseline characteristics, clinical manifestations, results of stool test, ELISA for rotavirus detection, and polymerase chain reaction (PCR) test for genotyping of rotavirus-positive samples were recorded. RESULTS: Results showed that the prevalence of rotavirus infection was 36.6%. The highest frequency was observed among children aged 6-12 months and during the autumn. According to the PCR results, G1P[8], G9P[8], G9P[4], and G1P [4] were the dominant genotypes, and 33.75% of samples were infected with multiple rotavirus genotypes. CONCLUSION: The study highlights the considerable prevalence of rotavirus infection among cases of acute gastroenteritis in children under six years of age who were referred to a referral hospital in the west of Iran and the high diversity of rotavirus genotypes in the targeted community. Consequently, physicians and health policymakers should prioritize strategies for the prevention and control of this infection, particularly by considering the rotavirus vaccine as a priority for the Iranian national immunization program.

Corrigendum: 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.

[This corrects the article DOI: 10.3389/fcimb.2022.927490.].