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Clinical Microbiology Reviews Jan 2008Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood... (Review)
Review
Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.
Topics: Administration, Oral; Animals; Cattle; Child, Preschool; Clinical Trials as Topic; Europe; Humans; Infant; Intussusception; Latin America; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; United States; Vaccination; Vaccines, Attenuated
PubMed: 18202442
DOI: 10.1128/CMR.00029-07 -
Vaccine Apr 2018More than 10 years after the authorisation of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, uptake in Europe... (Review)
Review
BACKGROUND
More than 10 years after the authorisation of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, uptake in Europe remains low. Only 13 countries in Europe provide a fully-funded rotavirus universal mass vaccination (UMV) programme, three provide a partially-funded programme, and one provides full funding for a reduced programme targeting at-risk infants. Around 40% of countries in Europe currently have no existing recommendations for rotavirus vaccine use in children from the national government.
METHODS
We provide an overview of the status of rotavirus vaccine recommendations across Europe and the factors impeding uptake. We consider the evidence for the benefits and risks of vaccination, and argue that cost-effectiveness and cost-saving benefits justify greater access to rotavirus vaccines for infants living in Europe.
RESULTS
Lack of awareness of the direct and indirect burden caused by rotavirus disease, potential cost-saving from rotavirus vaccination including considerable benefits to children, families and society, and government/insurer cost constraints all contribute to complacency at different levels of health policy in individual countries.
CONCLUSIONS
More than 10 years after their introduction, available data confirm the benefits and acceptable safety profile of infant rotavirus UMV programmes. Europe serves to gain considerably from rotavirus UMV in terms of reductions in healthcare resource utilization and related costs in both vaccinated subjects and their unvaccinated siblings through herd protection.
Topics: Cost-Benefit Analysis; Europe; Humans; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 29576308
DOI: 10.1016/j.vaccine.2018.02.080 -
Scientific Reports Jul 2019ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion...
ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (≤3, 4-7 and ≥8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at ≥4 days post vaccination (DPV). At ≥4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (>13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.
Topics: ABO Blood-Group System; Blood Group Antigens; Humans; Infant; Lewis Blood Group Antigens; Nicaragua; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; Vaccines, Attenuated; Virus Shedding
PubMed: 31341254
DOI: 10.1038/s41598-019-47166-9 -
Human Vaccines & Immunotherapeutics 2014Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal... (Review)
Review
Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq(®) and Rotarix(®) are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis.
Topics: Gastroenteritis; Humans; Immunity, Mucosal; Incidence; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 25424826
DOI: 10.4161/hv.29605 -
Human Vaccines & Immunotherapeutics 2018An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and...
An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and lower-middle income countries. Since 2009 the World Health Organization (WHO) recommends the use of rotavirus vaccines in all national immunization programs. This review compares rotavirus vaccine (RV) introductions and vaccine coverage by region, country income status and Gavi-eligibility from 2006-2016. Gross National Income data from the World Bank and surviving infant population from United Nations Population Division was obtained for 2016. Data from WHO were collected on rotavirus vaccine coverage, national immunization schedules, and new vaccine introductions for 2016 while estimated rotavirus deaths were collected for 2013, the last year of available WHO data. As of December 2016, the majority of countries (57%, 110/194) had not introduced universal rotavirus vaccine despite WHO's 2009 recommendation to do so. Countries in the WHO African region had the greatest proportion of introductions (37%, 31/84) by December 2016 and a great majority of these (77%, 24/31) were supported by new vaccine introduction (NVI) grants from Gavi. Almost half (48%) of global introductions were in low and lower-middle income Gavi-eligible and Gavi-graduating countries. Conversely, countries in the Southeast Asia WHO region and those not eligible for Gavi NVI support have been slow to introduce rotavirus vaccine. High-income countries, on average, had poorer rotavirus vaccine coverage compared to low and lower-middle income countries. The over-representation of African countries within the Gavi subset and high estimated rotavirus deaths in these African countries, likely explains why introduction efforts have been focused in this region. While much progress has been made with the integration and implementation of rotavirus vaccine into national immunization programs, 110 countries representing 69% of the global birth cohort had yet to introduce the vaccine by December 2016.
Topics: Capital Financing; Disease Transmission, Infectious; Global Health; Humans; Immunization Programs; Infant; Rotavirus Infections; Rotavirus Vaccines; Vaccination Coverage
PubMed: 29787334
DOI: 10.1080/21645515.2018.1470725 -
Human Vaccines & Immunotherapeutics Jul 2021Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective... (Randomized Controlled Trial)
Randomized Controlled Trial
Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity. This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6-12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA). The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups. The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.
Topics: Adult; Antibodies, Viral; China; Double-Blind Method; Humans; Immunogenicity, Vaccine; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated; Vaccines, Combined
PubMed: 33545015
DOI: 10.1080/21645515.2020.1861874 -
PloS One 2020Recent studies have reported that after the introduction of rotavirus vaccine the incidence of intussusception did not change among infants, or slightly increased at the...
BACKGROUND
Recent studies have reported that after the introduction of rotavirus vaccine the incidence of intussusception did not change among infants, or slightly increased at the age immediately after the first dose. The rotavirus vaccines were introduced in Korea for private market use in 2007-2008. We investigated the incidence of intussusception before (2002-2006) and after (2009-2015) the vaccine introduction in Korea.
METHODS
We conducted an interrupted time series study that used data from the Korean National Health Insurance database to identify infants (<12 months of age) who were diagnosed with intussusception and underwent non-invasive or invasive reduction from 2002 to 2015. According to the recommended ages for immunization, the annual intussusception incidence and the incidence rate ratios were calculated among three age groups, 6-14, 15-24, and 25-34 weeks.
RESULTS
The annual incidences in infants have decreased over time from 241.7 per 100,000 infants (pre-vaccine period) to 160.1-205.2 per 100,000 infants (post-vaccine period). The incidence rate ratio during the post-vaccine period ranged from 0.66 to 0.85. The incidences of intussusception in all three infant age groups have decreased in post-vaccine period compared to pre-vaccine period (incidence rate ratio range: 0.31-0.65, 0.47-0.75, and 0.68-0.94 in 6-14, 15-24, and 25-34 weeks, respectively).
CONCLUSIONS
The incidence of intussusception in infants did not increase after the rotavirus vaccine introduction in Korea, but rather decreased over the past decades. Since the incidence of intussusception varies according to country or region, continuous monitoring the incidence of intussusception in infants is necessary in each county or region.
Topics: Humans; Incidence; Infant; Intussusception; Republic of Korea; Rotavirus Infections; Rotavirus Vaccines
PubMed: 32857776
DOI: 10.1371/journal.pone.0238185 -
Pediatrics Feb 2016Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone.
METHODS
Randomized, multicenter, open-label study. Healthy infants (6-14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A ≥20 U/mL) were compared in all the vaccine groups.
RESULTS
Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated.
CONCLUSIONS
Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone.
Topics: Antibodies, Viral; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunization Schedule; Infant; Male; Patient Safety; Rotavirus; Rotavirus Vaccines
PubMed: 26823540
DOI: 10.1542/peds.2015-2603 -
Human Vaccines & Immunotherapeutics 2019Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations... (Review)
Review
Rotavirus vaccines have been introduced into over 95 countries globally and demonstrate substantial impact in reducing diarrheal mortality and diarrheal hospitalizations in young children. The vaccines are also considered by WHO as "very cost effective" interventions for young children, particularly in countries with high diarrheal disease burden. Yet the full potential impact of rotavirus immunization is yet to be realized. Large countries with big birth cohorts and where disease burden is high in Africa and Asia have not yet implemented rotavirus vaccines at all or at scale. Significant advances have been made demonstrating the impact of the vaccines in low- and lower-middle income countries, yet the modest effectiveness of the vaccines in these settings is challenging. Current research highlights these challenges and considers alternative strategies to overcome them, including alternative immunization schedules and host factors that may inform us of new opportunities.
Topics: Child, Preschool; Clinical Trials as Topic; Cost-Benefit Analysis; Developing Countries; Diarrhea; Gastroenteritis; Humans; Immunization Schedule; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 30735087
DOI: 10.1080/21645515.2018.1553593 -
Vaccine Aug 2022Rotavirus infections remain a leading cause of morbidity and mortality among infants residing in low- and middle-income countries. To address the large need for...
Rotavirus infections remain a leading cause of morbidity and mortality among infants residing in low- and middle-income countries. To address the large need for protection from this vaccine-preventable disease we are developing a trivalent subunit rotavirus vaccine which is currently being evaluated in a multinational Phase 3 clinical trial for prevention of serious rotavirus gastroenteritis. Currently, there are no universally accepted in vivo or in vitro models that allow for correlation of field efficacy to an immune response against serious rotavirus gastroenteritis. As a new generation of non-replicating rotavirus vaccines are developed the lack of an established model for evaluating vaccine efficacy becomes a critical issue related to how vaccine potency and stability can be assessed. Our previous publication described the development of an in vitro ELISA to quantify individual vaccine antigens adsorbed to an aluminum hydroxide adjuvant to address the gap in vaccine potency methods for this non-replicating rotavirus vaccine candidate. In the present study, we report on concordance between ELISA readouts and in vivo immunogenicity in a guinea pig model as it relates to vaccine dosing levels and sensitivity to thermal stress. We found correlation between in vitro ELISA values and neutralizing antibody responses engendered after animal immunization. Furthermore, this in vitro assay could be used to demonstrate the effect of thermal stress on vaccine potency, and such results could be correlated with physicochemical analysis of the recombinant protein antigens. This work demonstrates the suitability of the in vitro ELISA to measure vaccine potency and the correlation of these measurements to an immunologic outcome.
Topics: Animals; Antibodies, Viral; Gastroenteritis; Guinea Pigs; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccine Potency; Vaccines, Subunit
PubMed: 35871866
DOI: 10.1016/j.vaccine.2022.07.017