The incidence and direct medical cost of hospitalization due to rotavirus gastroenteritis in Kyoto, Japan, as estimated from a retrospective hospital study.

Anticipating imminent licensure of rotavirus vaccine for use in Japan, we estimated the incidence of rotavirus hospitalization and calculated the direct medical cost associated with rotavirus hospitalization in a hospital that provided virtually exclusive pediatric beds to the local community adjacent to the northern outskirts of metropolitan Kyoto, Japan. For a 2 year period between September, 2008 and August, 2010, there were 103 hospitalizations due to acute gastroenteritis among children less than 5 years of age. Stool specimens from 77 (75%) of the 103 hospitalized patients were tested for rotavirus antigen, and 46 (60%) were positive. The proportion of rotavirus positives was 65% in the peak-season months (January-June) and 17% in the off-season months (July-December). By extrapolating the test results to those patients with acute gastroenteritis who were not tested, 13 additional cases were estimated to be rotavirus positive. Assuming that all patients with rotavirus gastroenteritis less than 5 years of age in the catchment (5532 according to the 2005 census) were admitted to this hospital, the annual incidence of rotavirus hospitalization was estimated to be 4.1 (testing-unadjusted)-5.3 (adjusted) per 1000 child-years. Thus, it was estimated that one child in 48 or one child in 37 born in this area would be hospitalized due to rotavirus gastroenteritis by the age of 5 years. The incidence of rotavirus hospitalization was similar to the rate in Ise city (4.9 per 1000 child-years), also in central Japan, and lower than the rate in Honjo city in northern Japan (13 per 1000 child-years). Nevertheless, the burden of rotavirus hospitalization was substantial, and the total direct medical cost was estimated to be 6.6 billion Japanese Yen (US$ 57 million). While economic analysis and comparisons with alternative preventive procedures may be necessary, this study provides the policymakers and pediatricians with further evidence that is necessary to decide whether to introduce rotavirus vaccines into the routine childhood immunization schedule in Japan.

Cost-effectiveness analysis of a universal rotavirus immunization program in Japan.

In anticipation of the imminent licensure of rotavirus vaccine, we evaluated the cost-effectiveness of rotavirus vaccine in Japan by taking into account the considerable variations in the incidence of rotavirus-associated hospitalizations previously reported in the literature. We assumed that the variation was due to local differences in healthcare utilization practices rather than a true difference in the incidence of severe rotavirus gastroenteritis. Thus, a Markov model was constructed such that the sum of rotavirus-associated hospitalizations and outpatient visits was set a constant value of 129 cases per 1,000 child-years. We calculated the direct medical cost, the indirect cost, and the quality-adjusted life year (QALY) loss in children aged less than 5 years. For the base case scenario, the incremental cost-effectiveness ratio (ICER) per QALY gained was 9.8 million Japanese yen from the healthcare perspective, but it was 900,000 Japanese yen from the societal perspective, making the program of universal immunization against rotavirus highly cost-effective. Furthermore, the universal immunization program was found to be cost-effective from the societal perspective for any of the previously reported incidence rates of rotavirus-associated hospitalization. Thus, the introduction of the rotavirus vaccine into the childhood immunization schedule and its co-administration with other childhood vaccines will be a cost-effective public health intervention in Japan.

Issues with reducing the rotavirus-associated mortality by vaccination in developing countries.

More than 65% of the global rotavirus deaths were estimated to occur in 11 countries in Asia and Africa, claiming 345,000 children less than 5 years of age in 2004. While efficacious rotavirus vaccines are at hand, inequity in health delivery system within and between these countries was found to be the major hurdle against achieving the goal of rotavirus vaccine. When the coverage of currently used vaccines was applied to a rotavirus vaccine, a maximum of 202,550 deaths would be averted. Even if the coverage reached 80%, there would remain 96,841 children dying because of rotavirus diarrhea in these 11 countries. Studies are therefore encouraged to develop comprehensive strategies to resolve inequity in health delivery system enabling the increase in the immunization coverage.

Rotavirus vaccines: entering a new stage of deployment.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study.

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

A critical time for rotavirus vaccines: a review.

Universal introduction of rotavirus vaccines into childhood immunization programs is expected to substantially reduce the mortality from rotavirus gastroenteritis in developing countries (currently estimated at 702,000 annual deaths among children less than 5 years of age). In addition, it is expected to virtually eliminate hospitalizations due to rotavirus gastroenteritis in developed countries. Two rotavirus vaccines, Rotarix (GlaxoSmithKline Biologicals, Belgium) and RotaTeq (Merck & Co., USA) have recently completed Phase III clinical trials, each involving more than 60,000 children. Both vaccines appear safe with respect to intussusception, and are highly efficacious in preventing severe gastroenteritis due to rotavirus strains carrying predominantly serotype G1. The monovalent human rotavirus vaccine Rotarix, possessing serotype P1A[8],G1, is being first introduced into developing countries, whereas the pentavalent bovine-human reassortant rotavirus vaccine RotaTeq, comprising G-types G1, G2, G3, G4 and P-type P1A[8], will be initially introduced into the USA and Europe. Current disease burden estimates and economic justification will be required wherever the vaccines are introduced. Confirmation of the safety of both vaccines will require extensive postlicensure evaluation in which it will be key to assure adherence to administration of the first dose of either vaccine before 3 months of age. Assessment of the ability of each vaccine to provide protection against an increasingly diverse population of rotavirus strains will crucially depend on continuous global strain surveillance. Finally, efforts to improve existing rotavirus vaccines and to develop alternative vaccines should continue, so as to ensure that the prerotavirus vaccine era is consigned to a historical context.