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JAMA Pediatrics Jul 2021Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after... (Meta-Analysis)
Meta-Analysis
Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years: A Systematic Review and Meta-analysis of Randomized Clinical Trials and Observational Studies.
IMPORTANCE
Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after introduction are noteworthy.
OBJECTIVE
To evaluate the comparative benefit, risk, and immunogenicity of different rotavirus vaccines by synthesizing randomized clinical trials (RCTs) and observational studies.
DATA SOURCES
Relevant studies published in 4 databases: Embase, PubMed, the Cochrane Library, and Web of Science were searched until July 1, 2020, using search terms including "rotavirus" and "vaccin*."
STUDY SELECTION
Randomized clinical trials and cohort and case-control studies involving more than 100 children younger than 5 years that reported the effectiveness, safety, or immunogenicity of rotavirus vaccines were included.
DATA EXTRACTION AND SYNTHESIS
A random-effects model was used to calculate relative risks (RRs), odds ratios (ORs), risk differences, and 95% CIs. Adjusted indirect treatment comparison was performed to assess the differences in the protection of Rotarix and RotaTeq.
MAIN OUTCOMES AND MEASURES
The primary outcomes were RVGE, severe RVGE, and RVGE hospitalization. Safety-associated outcomes involved serious adverse events, intussusception, and mortality.
RESULTS
A meta-analysis of 20 RCTs and 38 case-control studies revealed that Rotarix (RV1) significantly reduced RVGE (RR, 0.316 [95% CI, 0.224-0.345]) and RVGE hospitalization risk (OR, 0.347 [95% CI, 0.279-0.432]) among children fully vaccinated; RotaTeq (RV5) had similar outcomes (RVGE: RR, 0.350 [95% CI, 0.275-0.445]; RVGE hospitalization risk: OR, 0.272 [95% CI, 0.197-0.376]). Rotavirus vaccines also demonstrated higher protection against severe RVGE. Additionally, no significant differences in the protection of RV1 and RV5 against rotavirus disease were noted in adjusted indirect comparisons. Moderate associations were found between reduced RVGE risk and Rotavac (RR, 0.664 [95% CI, 0.548-0.804]), Rotasiil (RR, 0.705 [95% CI, 0.605-0.821]), and Lanzhou lamb rotavirus vaccine (RR, 0.407 [95% CI, 0.332-0.499]). All rotavirus vaccines demonstrated no risk of serious adverse events. A positive correlation was also found between immunogenicity and vaccine protection (eg, association of RVGE with RV1: coefficient, -1.599; adjusted R2, 99.7%).
CONCLUSIONS AND RELEVANCE
The high protection and low risk of serious adverse events for rotavirus vaccines in children who were fully vaccinated emphasized the importance of worldwide introduction of rotavirus vaccination. Similar protection provided by Rotarix and RotaTeq relieves the pressure of vaccines selection for health care authorities.
Topics: Child, Preschool; Gastroenteritis; Humans; Infant; Infant, Newborn; Randomized Controlled Trials as Topic; Rotavirus Infections; Rotavirus Vaccines
PubMed: 33970192
DOI: 10.1001/jamapediatrics.2021.0347 -
Expert Opinion on Biological Therapy Mar 2022Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths... (Review)
Review
INTRODUCTION
Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths annually. There are six licensed oral, live-attenuated rotavirus vaccines: four vaccines pre-qualified for global use by WHO, and two country-specific vaccines. Expansion of rotavirus vaccines into national immunization programs worldwide has led to a 59% decrease in rotavirus hospitalizations and 36% decrease in diarrhea deaths due to rotavirus in vaccine-introducing countries.
AREAS COVERED
This review describes the current rotavirus vaccines in use, global coverage, vaccine efficacy from clinical trials, and vaccine effectiveness and impact from post-licensure evaluations. Vaccine safety, particularly as it relates to the risk of intussusception, is also summarized. Additionally, an overview of candidate vaccines in the pipeline is provided.
EXPERT OPINION
Considerable evidence over the past decade has demonstrated high effectiveness (80-90%) of rotavirus vaccines at preventing severe rotavirus disease in high-income countries, although the effectiveness has been lower (40-70%) in low-to-middle-income countries. Surveillance and research should continue to explore modifiable factors that influence vaccine effectiveness, strengthen data to better evaluate newer rotavirus vaccines, and aid in the development of future vaccines that can overcome the limitations of current vaccines.
Topics: Child; Diarrhea; Humans; Immunization Programs; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 34482790
DOI: 10.1080/14712598.2021.1977279 -
Human Vaccines & Immunotherapeutics 2019The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher... (Review)
Review
The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher standards of hygiene. Overcoming these obstacles will require great investment and also time, therefore more effective vaccines should be developed to meet the needs of those who would benefit the most from them. Increasing our current knowledge of mucosal immunity, response to Rotavirus infection and its modulation by circadian rhythms could point at actionable pathways to improve vaccination efficacy, especially in the case of individuals affected by environmental enteropathy. Also, a better understanding and validation of Rotavirus entry factors as well as the systematic monitoring of dominant strains could assist in tailoring vaccines to individual's needs. Another aspect that could improve vaccine efficiency is targeting to M cells, for which new ligands could potentially be sought. Finally, alternative mucosal adjuvants and vaccine expression, storage and delivery systems could have a positive impact in the outcome of Rotavirus vaccination.
Topics: Clinical Trials as Topic; Developing Countries; Enterocytes; Gastroenteritis; Humans; Immunity, Mucosal; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination; Vaccine Potency; Vaccines, Attenuated
PubMed: 30215578
DOI: 10.1080/21645515.2018.1520583 -
Human Vaccines & Immunotherapeutics Dec 2023Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine...
Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.
Topics: Animals; Rotavirus; Macaca mulatta; Antibodies, Viral; Rotavirus Vaccines; Leukocytes, Mononuclear; Rotavirus Infections; Antibodies, Neutralizing; Vaccines, Inactivated
PubMed: 36994772
DOI: 10.1080/21645515.2023.2189598 -
Vaccine Nov 2019Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus... (Review)
Review
Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest. New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development.
Topics: Animals; Developing Countries; Humans; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Virus Replication
PubMed: 28396207
DOI: 10.1016/j.vaccine.2017.03.076 -
The Pediatric Infectious Disease Journal Oct 2021Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared with high child mortality. Among several... (Review)
Review
Live, oral rotavirus vaccines are more effective at preventing rotavirus disease in countries with low child mortality compared with high child mortality. Among several hypotheses, poorer protection in malnourished children, who are more prevalent in countries with high child mortality, may partially explain this difference. We conducted a literature search to identify articles with a laboratory-confirmed rotavirus endpoint that evaluated differences by malnutrition status in rotavirus vaccine effectiveness and vaccine efficacy (VE) or the prevalence of rotavirus infection or illness among children <5 years old. We identified 7 analyses from 11 countries published from 2007 to 2019 that stratified rotavirus VE by malnutrition status. Among well-nourished children, VE point estimates ranged from 71% to 84% in observational studies and 26% to 61% in clinical trials. Among malnourished children, they ranged from -28% to 45% in observational studies and -3% to 61% in clinical trials. The relative difference between VE in well-nourished and malnourished children by length-for-age ranged from 37% to 64%, by weight-for-age ranged from 0% to 107%, and by weight-for-height ranged from -65% to 137%. We identified 3 cohort and 6 cross-sectional studies of natural rotavirus infection and illness and none reported that malnourished children were more susceptible to rotavirus infection or illness than well-nourished children. Overall, rotavirus vaccines may offer less protection to children with malnutrition than well-nourished children. As malnourished children often have worse outcomes from diarrhea, high rotavirus vaccine coverage and a better understanding of the performance of oral rotavirus vaccines in this population is important, though our finding that malnourished children may be less susceptible to rotavirus provides important context and information for vaccine evaluation design.
Topics: Child; Child Nutrition Disorders; Clinical Trials as Topic; Cross-Sectional Studies; Gastroenteritis; Global Health; Hospitalization; Humans; Malnutrition; Observational Studies as Topic; Rotavirus Infections; Rotavirus Vaccines; Vaccine Efficacy
PubMed: 34117200
DOI: 10.1097/INF.0000000000003206 -
The Milbank Quarterly Jun 2012Vaccination in the United States is a frequent source of controversy, with critics alleging failures by public health officials to adequately identify, monitor, and... (Review)
Review
CONTEXT
Vaccination in the United States is a frequent source of controversy, with critics alleging failures by public health officials to adequately identify, monitor, and respond to risks associated with vaccines. In response to these charges, the case of RotaShield, a vaccine withdrawn in 1999 following confirmation of a serious adverse event associated with its use, is regularly invoked as evidence of the effectiveness of current vaccine safety activities.
METHODS
This article examines the history of RotaShield, with particular attention paid to decision making regarding its use in the United States and internationally. I reviewed and analyzed federal advisory committee meeting transcripts, international conference reports, government and scientific publications, media coverage, and other primary and secondary source materials. I also conducted six semistructured interviews with former senior officials and advisory committee members at the U.S. Centers for Disease Control and Prevention who participated in decisions regarding the vaccine.
FINDINGS
Decision making regarding RotaShield, including the ultimate withdrawal of its recommendation for use, was shaped significantly by government health officials' concern for preserving public confidence in overall U.S. vaccination efforts amid several unrelated vaccine risk controversies ongoing at that time. This attention to public perception and external pressures occurred in tandem with the evaluation of the quantitative evidence regarding the magnitude and severity of the risk associated with the vaccine. The decisions made in the United States resulted in foreseen but unintended consequences for international use of the vaccine, including in nations where the profile of risks and potential benefits was dramatically different.
CONCLUSIONS
As enthusiasm for evidence-based decision making grows throughout medicine and public health, greater explicit attention should be directed to the processes by which decision makers and their expert advisers evaluate such evidence and translate it into regulation and policy by means of qualitative judgments.
Topics: Developing Countries; Health Policy; Humans; Intussusception; Policy Making; Politics; Risk Assessment; Rotavirus Infections; Rotavirus Vaccines; United States
PubMed: 22709389
DOI: 10.1111/j.1468-0009.2012.00664.x -
Current Opinion in Infectious Diseases Oct 2019As of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available,... (Review)
Review
PURPOSE OF REVIEW
As of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline.
RECENT FINDINGS
Data generated from use of currently available products supports their effectiveness and impact in diverse settings. Rotavirus vaccines have a favorable risk-benefit profile, but previous associations of rotavirus vaccination with intussusception necessitate continued monitoring for this rare but serious adverse event. Implementation of rotavirus vaccines was jeopardized in late 2018 and 2019 by a shortage of vaccine supply. Fortunately, with the prequalification of two additional vaccines in 2018, countries have increased choice in products with different characteristics, pricing, and implementation strategies. Other vaccines currently in development may open up further immunization strategies, such as neonatal vaccination schedules or parenteral administration.
SUMMARY
Rotavirus vaccines have demonstrated impact in reducing diarrheal morbidity and mortality worldwide. As countries begin to introduce the newly prequalified vaccines, additional data will become available on the safety and effectiveness of those products. Products in the pipeline have distinct profiles and could be an essential part of the expansion of rotavirus vaccine use worldwide.
Topics: Diarrhea; Drug Development; Drug-Related Side Effects and Adverse Reactions; Humans; Intussusception; Rotavirus Infections; Rotavirus Vaccines; Survival Analysis; Treatment Outcome
PubMed: 31305493
DOI: 10.1097/QCO.0000000000000572 -
The Pediatric Infectious Disease Journal Dec 2021Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Concerns exist that a monovalent vaccine (RV1) and a pentavalent vaccine (RV5) may be less... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Concerns exist that a monovalent vaccine (RV1) and a pentavalent vaccine (RV5) may be less effective against rotavirus strains not contained in the vaccines. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against severe rotavirus gastroenteritis caused by vaccine (homotypic) and nonvaccine (partially and fully heterotypic) strains.
METHODS
After conducting a systematic review, we meta-analyzed 31 case-control studies (N = 27,293) conducted between 2006 and 2020 using a random-effects regression model.
RESULTS
In high-income countries, RV1 VE was 10% lower against partially heterotypic (P = 0.04) and fully heterotypic (P = 0.10) compared with homotypic strains (homotypic VE: 90% [95% confidence intervals (CI): 82-94]; partially heterotypic VE: 79% [95% CI: 71-85]; fully heterotypic VE: 80% [95% CI: 65-88]). In middle-income countries, RV1 VE was 14-16% lower against partially heterotypic (P = 0.06) and fully heterotypic (P = 0.04) compared with homotypic strains (homotypic VE: 81% [95% CI: 69-88]; partially heterotypic VE: 67% [95% CI: 54-76]; fully heterotypic VE: 65% [95% CI: 51-75]). Strain-specific RV5 VE differences were less pronounced, and primarily derived from high-income countries. Limited data were available from low-income countries.
CONCLUSIONS
Vaccine effectiveness of RV1 and RV5 was somewhat lower against nonvaccine than vaccine strains. Ongoing surveillance is important to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited.
Topics: Case-Control Studies; Child; Diarrhea; Hospitalization; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccine Efficacy; Vaccines, Attenuated
PubMed: 34870393
DOI: 10.1097/INF.0000000000003286 -
Human Vaccines & Immunotherapeutics Jun 2021In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs,... (Review)
Review
In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs, significant yet incomplete progress has been made toward reducing the burden of rotavirus in low- to middle-income countries (LMIC). ORVs continue to demonstrate effectiveness and impact in LMIC, yet numerous factors hinder optimal performance and evaluation of these vaccines. This review will provide an update on ORV performance in LMIC, the increasing body of literature regarding factors that affect ORV response, and the status of newer and next-generation rotavirus vaccines as of early 2020. Fully closing the gap in rotavirus prevention between LMIC and high-income countries will likely require a multifaceted approach accounting for biological and methodological challenges and evaluation and roll-out of newer and next-generation vaccines.
Topics: Developing Countries; Humans; Immunization Programs; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 33327868
DOI: 10.1080/21645515.2020.1844525