Rotavirus Vaccine Effectiveness Research Articles

Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study

Objective To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national...

A mathematical model of the indirect effects of rotavirus vaccination

Rotavirus (RV) infections progressively confer natural immunity against subsequent infection. Similarly to natural infection, vaccination with a live attenuated vaccine potentially reduces RV transmission and induces herd protection. A mathematical transmission model was developed to project the impact of a vaccination programme on the incidence of RV infection and disease for five countries in the European Union. With vaccination coverage rates of 70%, 90% and 95% the model predicted that, in addition to the direct effect of vaccination, herd protection induced a reduction in RV-related gastroenteritis (GE) incidence of 25%, 22% and 20%, respectively, for RV-GE of any severity, and of 19%, 15%, and 13%, respectively, for moderate-to-severe RV-GE, 5 years after implementation of a vaccination programme.

Update on Rotarix™: an oral human rotavirus vaccine

Worldwide, rotaviruses are the single most important agents of severe gastroenteritis in infants and young children. Globally, it is estimated that every year rotavirus gastroenteritis causes more than 125 million episodes of diarrhea and nearly 527,000 deaths, mainly in developing countries. The development of new effective and safe rotavirus vaccines was recognized as the most effective intervention strategy that could yield a significant impact on the burden of rotavirus disease. Rotarix™ is an oral live-attenuated human rotavirus vaccine containing a single G1P[8] strain. The first oral dose may be administered as early as 6 weeks of age, with a minimum interval of 4 weeks prior to second dose; the vaccination course should be completed by the age of 24 weeks according to the manufacturer. In the USA, the upper age limit for the second dose has recently been recommended at 32 weeks of age by the Advisory Committee on Immunization Practices. The development program for Rotarix including Phase I, II and III multicenter studies involving over 100,000 infants has been established in Latin America, Europe, Asia and Africa. The vaccine proved to be well tolerated, immunogenic, efficacious, safe and not associated with intussusception. It provided 85–96% protection against severe rotavirus gastroenteritis caused by G1 and non-G1 serotypes in Latin American and European clinical trials; and of public health importance, Rotarix reduced hospitalizations of all-cause gastroenteritis by 40 and 75%, respectively. Efficacy against G2P[4] strains ranged from 41% in Latin America to 81% in Europe. In the former, Rotarix afforded sustained high protection (80.5%; 95% CI: 71.3–87.1) against severe rotavirus gastroenteritis during the first 2 years of life in a region with a changing pattern of wild-type rotavirus circulation. In a recently completed vaccine trial in South Africa and Malawi, Rotarix showed an overall efficacy of 61.2% (95% CI: 44.0–73.2) by 1 year of age. Although these rates are lower than those from developed and middle-income countries, they look promising given the lack of other effective interventions. With the expanding introduction of rotavirus vaccines into national immunization programs, postmarketing surveillance should be conducted to measure the impact of rotavirus vaccination, as well as continued monitoring of circulating rotavirus strains.

Assessing the Effectiveness and Public Health Impact of Rotavirus Vaccines after Introduction in Immunization Programs

Two new vaccines against severe rotavirus gastroenteritis that have high efficacy in middle- and high-income countries have recently been licensed in many countries worldwide. Clinical trials in low-income countries in Africa and Asia are ongoing. Experience gained through studies of natural rotavirus infection and the clinical trials for the current and previous rotavirus vaccines indicate that, as countries begin to introduce these newly approved vaccines into routine childhood immunization programs, monitoring their performance in real world settings should be a high priority. Key epidemiological considerations in the postlicensure period include (1) how the vaccine will perform against severe rotavirus disease under routine public health use; (2) how routine vaccination will impact the epidemiology of disease with regard to the burden of severe disease and death, age distribution of cases, seasonality, and serotype distribution; (3) whether vaccination will have a sufficient impact on transmission to reduce disease burden in unvaccinated age groups; and (4) whether vaccine will confer protection through the first 3 years of life, when most severe disease and mortality associated with rotavirus occur. Monitoring of impact with focus on these public health considerations will allow parents, health care providers, and decision makers to appreciate the health benefits of vaccination in reducing the burden of severe rotavirus disease. It will also allow assessment of the effectiveness of rotavirus vaccines in programmatic use and the need for modifying vaccination schedules or vaccine formulations to enhance the performance of immunization. In this article, we review data for the protective efficacy of the 2 new rotavirus vaccines, with emphasis on issues particularly important for consideration as these vaccines are introduced in routine infant immunization programs.

How Much Could Rotavirus Vaccines Reduce Diarrhea‐Associated Mortality in Northern Ghana? A Model to Assess Impact

Effective rotavirus vaccines could substantially reduce the approximately 500,000 deaths due to rotavirus disease per year worldwide, although the impact will depend on vaccine effectiveness, timing of administration, and coverage. We modeled vaccine impact on rotavirus-associated mortality in rural Ghana. All deaths due to acute diarrhea among children during 1998-2004 in the Kassena-Nankana District of Ghana were identified, and the number of deaths due to rotavirus disease was estimated using hospital laboratory surveillance data. Assuming rotavirus vaccine would be included in the current Expanded Program on Immunization schedule, we estimated the reduction in rotavirus-associated mortality with use of the current coverage and timing of diphtheria, tetanus, and pertussis vaccine administration and various age-restricted schedules. Of the 381 deaths due to diarrhea, 131 (34%) were estimated to be caused by rotavirus infection. On the basis of current diphtheria, tetanus, and pertussis vaccine coverage and timing, a 90% efficacious 3-dose rotavirus vaccine would prevent 70% of deaths due to rotavirus infection if administered without age restrictions, 53% if only initiated among children <12 weeks of age, and 52% if the course also was completed by 32 weeks of age. Rotavirus vaccine has the potential to substantially reduce rotavirus-associated mortality in rural Ghana. Although timely vaccination should be encouraged, extending the current age recommendation for initiation of rotavirus vaccination could increase the coverage and impact of vaccination.

Hospital‐Based Surveillance of Rotavirus Diarrhea in the People’s Republic of China, August 2003–July 2007

Rotaviruses cause acute diarrhea worldwide. Previous studies of rotavirus diarrhea in China found that rotavirus infection is the most common cause of severe diarrhea in young children. In the present study, surveillance of rotavirus diarrhea was conducted involving 9549 children aged <5 years who were admitted for treatment of diarrhea at 11 sentinel hospitals in China from August 2003 through July 2007. Group A rotavirus was detected in 3749 (47.8%) of the 7846 fecal specimens by using enzyme-linked immunosorbent assay. Rotavirus isolates were characterized by reverse-transcriptase polymerase chain reaction to determine G and P genotypes. All the strains that are common worldwide were detected; G3P[8] was the most common. An unusual G5 strain was detected in 2 specimens. Of all episodes of rotavirus diarrhea, 94% occurred during the first 2 years of life, peaking at 6-23 months of age. Our findings indicate that globally common rotavirus strains continue to be a major cause of severe childhood diarrhea in China. Introduction of routine immunization with effective rotavirus vaccines would substantially reduce this burden.

Sentinel Hospital‐Based Surveillance of Rotavirus Diarrhea in Iran

Rotavirus is the most common causes of severe, acute diarrhea during childhood and is an important cause of morbidity and mortality in developing countries. We established active hospital-based surveillance of childhood diarrhea to assess the scope of severe rotavirus disease in Iran. From May 2006 through April 2007, prospective surveillance of rotavirus diarrhea among children aged <5 years was conducted in 5 sentinel hospitals in Iran. Stool samples were tested for rotavirus using a commercially available enzyme immunoassay, and rotavirus-positive samples were genotyped using reverse-transcriptase polymerase chain reaction. Of 2198 children admitted to the hospital for acute gastroenteritis, 1298 (59.1%) had stool samples test positive for rotavirus by enzyme immunoassay. Of the rotavirus episodes, 85% occurred during the first 2 years of life, with the peak prevalence of severe rotavirus disease occurring from September through January. Among the 110 rotavirus-positive samples that were genotyped, G4P[8] was the most commonly detected rotavirus genotype (30.9% of strains). Other commonly detected genotypes included P[8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1[P8] (10.9%), and G2[P4] (5.5%). Rotavirus is the most common cause of severe diarrhea in Iran, which indicates that safe and effective rotavirus vaccination in Iran is a public health priority.

Rotavirus Vaccination: Cost‐Effectiveness and Impact on Child Mortality in Developing Countries

Rotavirus is the leading cause of severe gastroenteritis in children <5 years of age and is responsible for >500,000 deaths annually; approximately 85% of this burden is in low-income countries eligible for financial support from the GAVI Alliance. We projected the uptake, health impact, and cost-effectiveness of introducing rotavirus vaccination in GAVI-eligible countries to help policy makers in prioritizing resources to gain the greatest health improvements for their constituencies. A demand forecast model was used to predict adoption of rotavirus vaccine in the poorest countries in the world. We then modeled health outcomes and direct costs of a hypothetical birth cohort in the target population for scenarios with and without a rotavirus vaccine with use of data on health outcomes of rotavirus infection, vaccine effectiveness, and immunization rates. Vaccination would prevent 2.4 million rotavirus deaths and >82 million disability-adjusted life-years (DALYs) in 64 of the 72 GAVI-eligible countries introducing vaccine from 2007 through 2025. The cost per DALY averted decreases over time, from a high of US$450 per DALY averted in the first year to a sustained low of $30 per DALY during 2017-2025, with a cumulative figure of $43 per DALY averted during 2008-2025. By applying the baseline scenario with an initial vaccine price of $7 per dose for a 2-dose vaccine, with a gradual decrease beginning in 2012 and stabilizing at $1.25 per dose by 2017, vaccination was very cost-effective in all GAVI-eligible countries with use of each country's gross domestic product per DALY averted as a threshold. Introduction of rotavirus vaccines into the world's poorest countries is very cost-effective and is projected to substantially reduce childhood mortality.

Molecular epidemiology of rotavirus among children under 5 years old hospitalized for diarrhea in China

To study molecular epidemiology of Rotavirus among children under 5 years of age in china. Stool specimens were collected from 4047 inpatients under 5 years of age with diarrhea in our 9 hospital-based surveillance sites from January 2006 to December 2007 following the WHO Rotavirus surveillance protocol. Rotavirus were detected by ELISA, Further strain characterization of rotavirus was carried out with RT-PCR. A total of 4047 stool samples were collected and 3862 of total stools were tested among which 1700 was positive. The Rotavirus positive rate is 44.0%. A peak admission of rotavirus diarrhea was observed from November to next January. More than 95.4% of viral diarrhea patients occurred in their first 2 years. The incidence rates of rotavirus diarrhea were highest in 12-17 months of age. The most common rotavirus strain was P[8]G3(58.3%); followed by P[8] G1(22.1%), P[4]G1 (3.0%), P[8]G9 (2.4%). G4 was not detected in this study. The four common strains were 80.8% in the world. Rotavirus diarrhea was an important infectious disease among children under 5 years of age in China. Safe and effective rotavirus vaccines for the prevention of rotavirus diarrhea and reduction of treatment costs are of significant importance to China.

Estimates of the economic burden of rotavirus‐associated and all‐cause diarrhoea in Vellore, India

To determine the cost of rotavirus and all-cause diarrhoea in Vellore, India. Parents of children <5 years of age accessing clinics, emergency rooms, or hospitals for acute diarrhoea completed a questionnaire detailing healthcare utilisation, medical and non-medical expenditures, and lost income. Faecal samples were screened for rotavirus and medical records were examined. Costs were estimated for inpatient and outpatient resource consumption, stratified by facility. Total societal costs of a hospitalised diarrhoeal episode were Rs 3278.50 (US$ 80.80) at a large referral hospital and Rs 1648.60 (US$ 40.60) at a smaller community hospital. Costs for rotavirus positive or negative gastroenteritis were similar. Median household expenditures per diarrhoeal episode at the referral and the community hospitals equalled 5.8% and 2.2% of the annual household income, respectively. Diarrhoeal disease in children constitutes a considerable economic burden. An appropriately priced and effective rotavirus vaccine may provide significant economic savings for the Indian household and healthcare system.

Immunogenicity of a thermally inactivated rotavirus vaccine in mice

Current approaches to the prevention of severe rotavirus diarrhea and deaths in children have all been through the use of live oral vaccines. To develop a safe and effective inactivated rotavirus vaccine (IRV), a new simple, rapid and robust method for the inactivation is critical and essential because chemical inactivation commonly used for a number of killed vaccines has been a challenge and problematic for rotavirus. We have examined an array of thermal conditions and demonstrated that purified YK-1 rotavirus in diluent buffer can be completely inactivated by heat treatment, as evidenced by the lack of virus growth in 2 successive passages in cell culture. Unlike chemical treatment that often causes physical and biochemical damages to viruses, thermally inactivated rotavirus particles maintained their structural, biochemical and antigenic integrity. A two-dose intramuscular administration of thermally inactivated YK-1 rotavirus without adjuvant resulted in high titers of total and neutralizing antibody in serum of mice. Adjuvant Al(OH)3 further led to enhanced antibody titers and also dramatically lowered the amount of antigens in the vaccine formulation. Our results demonstrate the potential of heat inactivation as a novel approach to the manufacture of a safe and efficacious parenteral rotavirus vaccine, which should serve as an important addition to and back up for live oral rotavirus vaccine in children.

Clinical ep idemiologic profile of rotavirus infections in Korea

Primary rotavirus gastroenteritis infection usually occurs in infants under 2 years of age worldwide regardless of level of hvgiene, quality of water, food or sanitation or type of behavior. In Korea, the diseases mostly occurred in infants under 2 years old, and usually in late fall to early winter with the highest incidence shown in November until early 1990s. However, since then, relatively the age incidence of this infection has increased in children over 2 years old, and it has mainly occurred in late winter to early spring with the highest incidence shown between February and March. And rotavirus gastroenteritis serotypes varied year to year as well as varied by year within the same region in our country. The comparison of severity scores between age groups in Korea showed that severity score was lowest in infants less than 3 months and highest in infants more than 6 months and less than 12 months, and hospitalization period between age groups was longest in infants older than 3 months and less than 6 months, In this aspect, rotavirus vaccines should be given to infants less than 2 years of age in whom the incidence of rotavirus gastroenteritis is the highest, and vaccination should be ideally started before 3 months considering hospitalization period and severity of rotavirus gastroenteritis. However, It should be careful for the introduction of new rotavirus vaccine, and the effectiveness of rotavirus Vaccines should be assessed by long-term post marketing surveillance. And we guess a multivalent vaccine may be an ideal rotavirus vaccine to prevent primary infection caused by variable rotavirus strains in Korea. In addition, clinical epidemiology studies on rotavivus gastroenteritis which evluate the age and serotypes related severity should be continuously conducted in various regions.(Korean J Pediatr Infect Dis 2008;15:5-11)

LITERATURE REVIEW OF ROTAVIRUS PREVALENCE IN AFRICA

INTRODUCTION: Diarrhea kills 1.6 million children younger than 5 years annually, with rotavirus causing 600 000 of those deaths. Eighty-five percent of these deaths occur in sub-Saharan Africa and southeast Asia. OBJECTIVE: We aimed to review rotavirus prevalence studies of children in Africa from 1975 to 2006. METHODS: Three multilingual Medline searches (limited to humans) were performed: “RV,” country/Africa, and epidemiology/diarrhea. Additional inclusion criteria included children &amp;lt;5 years of age, conducted over &amp;gt;3 months, and including &amp;gt;50 children. Data were analyzed in 4 periods. RESULTS: Of the initial 189 studies identified, 75 in 18 countries met the additional inclusion criteria (Table 1). More than half of the studies were hospital based. In all studies the most common serotypes were G1 (25%), G4 (16%), G2 (13%), G3 (12%), P[8] (37%), P[6] (35%), and P[4] (11%). From 1996 to 2006 the common serotypes were G1 (22%), G4 (17%), G2 (13%), G3 (13%), P[6] (37%), P[8] (35%), and P[4] (11%). CONCLUSIONS: The current prevalence rate is 30% (range: 17%–38%). Present serotypes include G1 through G4, G8, G9, P[8], P[6], and P[4]. Rotavirus diarrhea represents a significant disease burden. Current rotavirus prevalence studies are important, because there are effective rotavirus vaccines available to prevent mortality and severe disease. TABLE 1.Results of 75 Studies on Rotavirus Prevalence in Children &amp;lt;5 Years Old in AfricaAll Studies1976–19851986–19951996–2006Total No. of studies75123924Duration, mo12 (8.0–15.5)12 (8.0–12.5)12 (8.0–12.5)14 (11–24)Rotavirus-positive, %26252530Studies with serotyping, n180216Rotavirus-positive with serotyping, %24—567— indicates that data were not available.

Rotavirus vaccines: an overview.

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.

Effectiveness of Lanzhou lamb rotavirus vaccine against rotavirus gastroenteritis requiring hospitalization: A matched case-control study

We sought to determine the vaccine effectiveness (VE) of Lanzhou lamb rotavirus (LLR) vaccine against rotavirus gastroenteritis in children <5 requiring hospitalization. Children hospitalized 2002–2004 with rotavirus gastroenteritis were matched by gender, age and community to 838 controls. VE was calculated for one or more doses of LLR vaccine with 95% confidence intervals (CI). For one dose versus zero doses, LLR vaccine VE was 73.3% (95% CI, range 61.2–81.6%). VE of one dose versus zero doses was higher in children 12–23 months than in children 2–11 months (80.9% versus 60.0%). We found one dose moderately effective in preventing rotavirus gastroenteritis requiring hospitalization.

Gastroenteritis by rotavirus in Spanish children. Analysis of the disease burden

Rotavirus is one of the most common causes of gastroenteritis worldwide. With the commercialisation of effective rotavirus vaccines in Europe in sight, it is necessary to provide studies which evaluate the disease burden. The aim of this study is two-fold, on one hand, to determine the burden of the rotavirus disease in Spanish children under the age of five, and on the other, to estimate the economic cost of these hospitalizations. The study was undertaken during a 5 year period (2000-2004). The rotavirus hospitalization rate was determined using the Minimum Basic Data Set of the national hospital discharge register. The observed data were compared with those expected by applying a model developed by the Centers for Disease Control and Prevention (CDC) adapted for European Countries. The financial expense of these hospitalizations was estimated. Of all admissions coded as gastroenteritis, 31.6% were due to rotavirus. The hospitalization rate by rotavirus was 480 cases per 100,000 children under five. These data are within the confidence range proposed by the adapted CDC model. The financial expense due to hospitalizations reaches 123,262 euros yearly in a Spanish University Hospital. In conclusion, rotavirus contributes significantly to the hospitalization of acute gastroenteritis. The rate of hospitalization by rotavirus is higher compared to other studies carried out in Spain. In view of future commercialisation of rotavirus vaccines, more in-depth analysis considering direct and indirect costs are necessary.

New vaccines to boost child care in developing countries

By the age of three years most children in the world have been infected with rotavirus. In the developed world many cases need nothing more than attentive treatment and rest at home but in about 5-10% of cases children become so dehydrated due to gastro-enteritis they may need hospital care. The picture is more grim in developing countries where three-quarters of infants have had their first clinically serious rotavirus infection by their first birthday. Worldwide rotavirus accounts for an estimated two-fifths of all severe diarrhoea cases and causes up to a third of the 1.9 million deaths a year among under-fives due to diarrhoea. Ninety percent of these deaths occur in the developing countries where access to lifesaving treatment is limited and where a vaccine would offer the best hope for preventing countless deaths. Finding a safe and effective rotavirus vaccine has been a priority for the World Health Organization (WHO) in the 1990s. But the search got off to a false start. In mid-1998Wyeths RotaShield was licensed for sale in the United States of America (USA) and rapidly introduced into routine childhood vaccination programmes. Within nine months cases of vaccine-related intussusception a serious condition that causes bowel obstruction were reported among some one million children who had been vaccinated. The manufacturer voluntarily withdrew the vaccine and the US Advisory Committee for Immunization Practices withdrew its recommendation for its use. (excerpt)

RIX4414 (Rotarix™): a live attenuated human rotavirus vaccine

Rotaviruses are recognized as the single most important cause of severe infantile gastroenteritis worldwide. On a world scale rotaviruses are estimated to be responsible for over 600000 deaths annually. For these reasons rotaviruses have received a high priority as a target for vaccine development. Incorporation of an effective rotavirus vaccine into the infant immunization schedule in developed countries could reduce hospitalizations due to dehydrating diarrhea in young children by 40 to 60%. More important the worldwide use of such vaccine could decrease the total number of deaths caused by diarrhea by approximately 10 to 20%. Transmission of rotaviruses occurs by the fecal-oral route providing a highly efficient mechanism for universal exposure that has circumvented regional and national cultural practice differences. The symptoms associated with rotavirus disease typically are diarrhea and vomiting accompanied by fever nausea anorexia cramping and malaise that can be mild and of shortduration or produce severe dehydration. Severe disease occurs primarily in young children most commonly among those aged 6 to 24 months. Approximately 90% of children in both developed and developing countries experience a rotavirus infection by the time they reach 3 years of age. (excerpt)

Hospital-based study of the economic burden associated with rotavirus diarrhea in Taiwan

Rotavirus infection is the most important cause of diarrheal illness in small children in both developed and developing countries. In addition to causing morbidity and mortality in children, the treatment of rotavirus gastroenteritis is a major economic burden on the health care system and families. The purpose of this study was to estimate the economic burden associated with rotavirus infection in Taiwan. To do this, we combined data on the disease burden of a rotavirus-associated hospital admission with detailed cost data for a sample of 2,600 children with diarrhea who were admitted to the hospital. The annual total social and hospital costs for rotavirus-associated admission calculated from data collected during April 1, 2001 to March 31, 2003 was US $13.3 million and US $10.4 million, respectively. On average, families spent US $294 when their child's admission was associated with rotavirus infection; this cost represents ∼40% of the monthly salary of an unskilled or service worker. In conclusion, these data emphasize the potential for a safe and effective rotavirus vaccine to reduce the economic burden associated with rotavirus disease.

Rotavirus vaccines—An update

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. Rotavirus disease prevention efforts suffered a severe setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccines have been developed and have proven to be safe and efficacious. 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.