Pentavalent Human-bovine Reassortant Vaccine Research Articles

The Apparent Lack of the Risk of Intussusception Immediately After Rotavirus Vaccination Among Japanese Infants.

Rotavirus vaccines carry a small risk of intussusception mainly 1-7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market. Between 2011 and 2018, an estimated 21,677 infants (46%) were vaccinated and 54% were not. Through a retrospective survey of medical records in 18 hospitals in the prefecture, we identified 58 infants, 28 of whom were vaccinated and 30 of whom were unvaccinated, as having intussusception that met level 1 of the Brighton criteria. Thus, the intussusception rate was 123 per 100,000 infant-years (95% confidence interval [CI]: 94-160). Despite the high rate, none developed intussusception 1-7 days after the first dose of either the monovalent human rotavirus vaccine (GSK) or the pentavalent human-bovine reassortant vaccine (MSD). The incidence rate ratio of vaccinated to unvaccinated infants between 42 and 245 days of life was estimated at 0.96 (95%CI: 0.43-2.1; p = 0.92). Given that over 95% of infants received the first dose before 15 weeks of age, the risk of intussusception associated with the rotavirus vaccines in high-incidence-rate countries can be reduced to a minimum by adhering to the recommended schedule at 2, 3, and 4 months of age.

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.

Public health impact of accelerated immunization against rotavirus infection among children aged less than 6 months in the United States

We developed a cohort model to evaluate the expected public health impact of accelerated regimens for immunization against rotavirus gastroenteritis (RVGE). Alternative strategies for vaccination with the pentavalent human-bovine reassortant vaccine, Rotateq® (RV5, Merck) and the oral live attenuated human rotavirus vaccine, Rotarix® (RV1, GlaxoSmithKline Vaccines) were considered, including acceleration of the 1st dose only (by 2 weeks) as well as acceleration of the 1st (by 2 weeks) and subsequent doses (by up to 10 weeks). Assuming vaccine coverage levels consistent with current US clinical practice, accelerated regimens would be expected to reduce annual numbers of RVGE-related hospitalizations by 300–400, emergency department visits by 3000–4000, and outpatient visits by 3000–4000 (i.e., by 9–14%) among US children aged <6 months. Accordingly, accelerating the immunization of children against RVGE may yield substantive reductions in the number of RV-related encounters in US clinical practice.

Rotavirus vaccines

Group A rotavirus is the most common cause of severe gastroenteritis in young children globally, estimated to cause approximately 500,000 deaths each year, mainly in low-income countries. Two oral vaccines are currently licensed, a monovalent attenuated human rotavirus strain (Rotarix®, GSK Biologicals) and a pentavalent human-bovine reassortant vaccine (Rotateq®, Sanofi Pasteur MSD). On the basis of efficacy data from Europe and America, these vaccines were first recommended for routine immunization by WHO in 2006 in these countries. Studies reporting on the impact of rotavirus vaccination in early-introducer countries are now available, they suggest that these vaccines may have a major effect on burden of severe diarrhoea. In 2009, the WHO recommendation was expanded to all infants worldwide. The remaining questions are the vaccine efficacy in Africa and Asia, recent data from clinical trials showing a lower efficacy in these settings, the possible evolution of strains under the pression of selection of vaccination, and the real risk of intussusception after vaccination. In France, rotavirus vaccination has not yet been introduced into the routine immunization program in infants less than 6 months.

Rotavirus vaccines: entering a new stage of deployment

Rotavirus is the single most important cause of severe diarrhoea in infants and young children. This review provides updated information concerning three rotavirus vaccines that are being evaluated and introduced globally. Two large, phase III clinical trials, each involving more than 60,000 infants in both developing and developed countries, demonstrated that both RotaTeq (Merck & Co., Whitehouse Station, New Jersey, USA), the pentavalent human-bovine reassortant vaccine, and Rotarix (GlaxoSmithKine Biologicals, Rixensart, Belgium), the monovalent live-attenuated human rotavirus vaccine, are safe with respect to intussusception when the first dose is administered between 6 and 12 weeks of age, and that both vaccines are 90-95% efficacious in preventing severe rotavirus gastroenteritis including hospitalization. The bovine (UK)-human rotavirus reassortant tetravalent (BRV-TV) vaccine, developed at the National Institutes of Health (USA), was licensed for local production in several developing countries. Rotavirus vaccines are entering a new stage of deployment toward the goal of reducing morbidity and mortality attributed to rotavirus infection in developing countries, and hospitalizations and emergency visits caused by rotavirus in developed countries. High vaccine prices appear to offset cost savings, and may make policymakers even in wealthy countries hesitate to introduce a rotavirus vaccine into their childhood immunization programmes.

Letters to the Editor

4 October 2006 Dear Editor, NOSOCOMIAL ROTAVIRUS INFECTION IN AN AUSTRALIAN CHILDREN’S HOSPITAL There have been some exciting developments in the field of rotavirus vaccination with the successful completion of large phase III trials demonstrating the safety and efficacy of both an attenuated human rotavirus vaccine (Rotarix, GlaxoSmithKline, Boronia, Australia)1 and a pentavalent human-bovine reassortant vaccine (RotaTeq, CSL Limited/Merck & Co Inc, Melbourne, Australia).2 These vaccines were licensed in Australia by the Therapeutic Goods Administration in the first half of 2006 and applications made to the Pharmaceutical Benefits Advisory Committee have resulted in a recommendation for funding under the National Immunisation Program. Rotavirus vaccination is likely to have an impact on community and hospital-treated episodes of rotavirus gastroenteritis in Australia and elsewhere. Vaccination of infants is estimated to prevent around 85–100% of hospitalisations due to rotavirus gastroenteritis in the first year following vaccination.1, 2 Studies from other countries have shown that a significant burden of hospital-treated rotavirus infection is acquired in hospital nosocomially. Nosocomial infection rates have not been studied in Australia since a 1989 report that 14% of children <3 years old admitted to general paediatric wards at the Adelaide Children’s Hospital developed nosocomial rotavirus infection.3 We have collected data on nosocomial rotavirus infections at the Children’s Hospital at Westmead since 1996. Since 1999, all faecal specimens from inpatients with diarrhoea sent for microbiological analysis have been tested for rotavirus using the Rotazyme enzyme-linked immunosorbent assay (ELISA), whether requested or not. Between 1999 and 2004, the incidence density of proven nosocomial rotavirus infection (defined as rotavirus diarrhoea with onset at least 72 h after admission and up to 24 h after discharge) in children <2 years old admitted during the winter rotavirus season, varied between 6.7 and 14.8 cases per 10 000 rotavirus-free days in hospital. When cases of possible nosocomial infection (defined as rotavirus diarrhoea with onset between 24 and 72 h after admission or between 24 and 72 h after discharge) were added to the proven cases, the incidence density for the study period varied between 9.2 and 19.3 cases per 10 000 rotavirus-free days in hospital. Over the study period, 14.5% of all ELISA confirmed rotavirus infections were proven to be hospital-acquired, and 19.4% were either proven or probably hospital-acquired. These ratios of nosocomially acquired compared with all confirmed rotavirus infections are at the lower end of the range reported in a systematic review of 14–51%,4 although these values are likely to be dependent upon the age ranges studied and the institutional referral patterns for hospital and community stool specimens. Because we did not attempt to systematically test stools from all hospitalised children or to follow-up children after discharge, it is likely that the true rates of nosocomial infection may be significantly higher than the rates reported here. In one report, 39.3% of nosocomial infections were asymptomatic and 67.6% occurred after discharge.5 Asymptomatic infection is important in that it probably contributes to the subsequent transmission of the virus. In other institutions, nosocomial rotavirus infection has been found to contribute significantly to patient length of stay and to the costs of care,6 although we have not attempted to directly calculate these parameters. Despite careful attention to infection control practices, nosocomial rotavirus infections remain a significant problem in paediatric hospitals. Universal rotavirus vaccination in infancy is likely to reduce the number of hospitalised children with community-acquired rotavirus and may have a significant impact on reducing nosocomial infection rates in Australian paediatric hospitals.

Vaccines against rotavirus and human papillomavirus (HPV)

To briefly review strategies aimed at the development of rotavirus and HPV vaccines, with emphasis on the current status of studies assessing the safety, reactogenicity, immunogenicity and efficacy of recently developed vaccines. This review focuses on articles published from 1996 to 2006, mainly those from the last five years, with special emphasis on data obtained from recently completed studies involving a new live attenuated human rotavirus vaccine and a virus-like particle (HPV) vaccine. Strategies for developing rotavirus vaccines ranged from Jennerian approaches to the new human-derived rotavirus vaccine. Currently, two rotavirus vaccines are recognized as both efficacious and safe: a pentavalent human-bovine reassortant vaccine and a vaccine derived from an attenuated rotavirus of human origin. The second of these has been evaluated in more than 70,000 infants all over the world. Prophylactic vaccines against HPV have been tested in more than 25,000 young individuals around the world. Results from phase II and III clinical studies indicate that such vaccines against the most common types of HPV, those linked to both genital warts and 70% of cervical cancers, are safe and highly efficacious. A future rotavirus immunization program covering 60 to 80% of infants worldwide is likely to reduce by at least 50% the number of rotavirus-associated hospitalizations and deaths. It is also reasonable to expect that implementation of HPV prophylactic vaccines will reduce the burden of the HPV-related diseases that presently impact millions of people around the world.