Pentavalent Rotavirus Vaccine Research Articles

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.

Community Diarrhea Incidence Before and After Rotavirus Vaccine Introduction in Nicaragua

We estimated the incidence of watery diarrhea in the community before and after introduction of the pentavalent rotavirus vaccine in León, Nicaragua. A random sample of households was selected before and after rotavirus vaccine introduction. All children < 5 years of age in selected households were eligible for inclusion. Children were followed every 2 weeks for watery diarrhea episodes. The incidence rate was estimated as numbers of episodes per 100 child-years of exposure time. A mixed effects Poisson regression model was fit to compare incidence rates in the pre-vaccine and vaccine periods. The pre-vaccine cohort (N = 726) experienced 36 episodes per 100 child-years, and the vaccine cohort (N = 826) experienced 25 episodes per 100 child-years. The adjusted incidence rate ratio was 0.60 (95% confidence interval [CI] 0.40, 0.91) during the vaccine period versus the pre-vaccine period, indicating a lower incidence of watery diarrhea in the community during the vaccine period.

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

Lack of Nonspecific Protection Against All‐Cause Nonrotavirus Gastroenteritis by Vaccination with Orally Administered Rotavirus Vaccine

Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens. Safety and efficacy of the pentavalent bovine-human reassortant rotavirus vaccine were studied in multiple populations, including children of the Navajo and White Mountain Apache tribes in the southwestern United States. Stool specimens were collected from children with AGE and tested for rotavirus using an enzyme immunoassay. Analyses were conducted to detect the presence or absence of a vaccine effect on incidence, severity, and duration of AGE in which rotavirus was not detected. The majority of AGE (N = 558: 472 nonrotavirus vs 86 rotavirus) occurred between August 2002 and March 2004 among children ranging from ages 4 to 23 months. The incidence of nonrotavirus AGE was similar by vaccine groups with an incidence rate ratio of 1.07 (incidence rate ratio = vaccinated/unvaccinated, 95% confidence interval 0.89-1.29). The hazards of first, second, third, or any AGE in which rotavirus was not detected differed little by vaccination status (P > 0.05). Duration of symptoms and severity of nonrotavirus AGE were similar by vaccine group. There was no vaccine effect on frequency or severity of nonrotavirus AGE.

Determining the effectiveness of the pentavalent rotavirus vaccine against rotavirus hospitalizations and emergency department visits using two study designs

The objective of this study is to determine the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) for preventing rotavirus-related hospitalizations and emergency department (ED) visits during the 2006–07 and 2007–08 rotavirus seasons using two study designs. Active, prospective population-based surveillance was conducted to identify cases of laboratory-confirmed rotavirus-related hospitalizations and ED visits to be used in case-cohort and case-control designs. VE was calculated using one comparison group for the case-cohort method and two comparison groups for the case-control method. The VE estimates produced by the three analyses were similar. Three doses of RV5 were effective for preventing rotavirus-related hospitalizations and ED visits in each analysis, with VE estimated as 92% in all three analyses. Two doses of RV5 were also effective, with VE ranging from 79% to 83%. A single dose was effective in the case-cohort analysis, but was not significant in either of the case-control analyses. The case-cohort and the case-control study designs produced the same VE point estimates for completion of the three dose series. Two and three doses of RV5 were effective in preventing rotavirus-related hospitalizations and ED visits.

Effectiveness of vaccination with the pentavalent rotavirus vaccine in Nicaragua as determined using the screening method

The screening method is a surveillance tool to evaluate vaccine effectiveness (VE) using coverage data on cases and available administrative estimates of vaccine coverage in the population. The aim of this analysis was to evaluate the utility and limitations of using the screening methodology to estimate VE, particularly in a developing world country with a high coverage rate, and to compare it with the VE estimates from 2 case-control studies. Using data from 2008, the screening method employed in this study estimated that VE for 3 doses of RV5 among children < 12 mo of age to prevent wild-type severe disease, resulting in hospitalization or emergency department visits, was 92% (95% confidence interval [CI]: 78–100%). Additional sensitivity analysis demonstrated that the point estimates of VE against severe disease ranged from 72% (95% CI: 62–83%) to 92% (95% CI: 78–100%); this range of VE estimates, although wide, is relatively consistent with results reported from 2 case-control studies in Nicaragua for the same time period. When the infrastructure is in place to collect reasonably robust case data, the use of the screening method to estimate VE is possible in the developing world setting. Cases of severe wild-type rotavirus gastroenteritis were obtained through an observational, hospital-based, prospective, surveillance program to assess rotavirus acute gastroenteritis. The proportion of cases vaccinated was estimated using the child’s vaccination card or health record. The proportion of the population vaccinated was estimated using administrative population-based vaccination coverage estimates provided by the Nicaraguan Ministry of Health.

Her İki (Monovalan ve Pentavalan) Rotavirus Aşısının Maliyet Etkinliği

Her İki (Monovalan ve Pentavalan) Rotavirus Aşısının Maliyet Etkinliği

Effectiveness of an Incomplete RotaTeq (RV5) Vaccination Regimen in Preventing Rotavirus Gastroenteritis in the United States

Effectiveness of the pentavalent rotavirus vaccine (RV5) after administration of the complete (3 dose) regimen has been demonstrated in a real-world setting. This study assessed the effectiveness of RV5 following partial completion of the 3-dose regimen. Using a large national health insurance claims database, 2 cohorts of infants (those who received RV5 and a concurrent group who received diphtheria-tetanus-acellular pertussis, but not RV5) were followed through the 2007 and 2008 rotavirus seasons (January 1 to May 31) to identify cases of rotavirus gastroenteritis and all-cause gastroenteritis resulting in medical care encounters. Vaccine effectiveness following the first and the second RV5 doses was estimated by quantifying reductions in hospitalizations, emergency department (ED) and physician office visits. A first RV5 dose was received by 42,306 infants whereas 28,417 infants in the concurrent comparison group received a first diphtheria-tetanus-acellular pertussis dose; 43,704 infants received a second RV5 dose, and 31,810 infants received a second diphtheria-tetanus-acellular pertussis dose. One dose of RV5 was associated with 88% effectiveness against rotavirus gastroenteritis hospitalizations and ED visits and 44% effectiveness against all-cause gastroenteritis hospitalizations and ED visits. A 2-dose regimen of RV5 was associated with 94% effectiveness against rotavirus gastroenteritis hospitalizations and ED visits and 40% effectiveness against all-cause gastroenteritis hospitalizations and ED visits. The RV5 vaccine exhibits effectiveness against rotavirus gastroenteritis even before completing the full 3-dose regimen. These results are of particular relevance when considering the benefits of a partially completed rotavirus vaccine series.

Immunogenicity and safety of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine (PRV) in Indian infants

Objective: To evaluate the immunogenicity and safety of a pentavalent rotavirus vaccine (PRV) in Indian infants.Study Design:Open-label, single-arm multicentric study.Setting:Hospital facilities (out patients)Subjects:One hundred and ten (110) healthy Indian infants were enrolled between the ages of 6 weeks and 12 weeks.Intervention:Three doses of oral pentavalent rotavirus vaccine (PRV) were administered with an interval of 4 to 10 weeks (28 to 70 days).Main Outcome Measures:Immunogenicity of PRV was based on the proportion of infants exhibiting a >3-fold rise in serum anti rotavirus IgA antibodies (from pre dose 1 to 14 days post dose 3). Safety was evaluated for 14 days after each dose. Results:Of the 110 infants enrolled, 83% exhibited at least a 3-fold rise (seroconversion) in serum anti rotavirus IgA antibodies. There were no clinically significant adverse events reported.Conclusions:A 3-dose regimen of PRV was found to be immunogenic and well tolerated in healthy Indian infants.Clinical trials registration:ClinicalTrials.gov; NCT00496054

Risk of Intussusception Following Administration of a Pentavalent Rotavirus Vaccine in US Infants

Risk of Intussusception Following Administration of a Pentavalent Rotavirus Vaccine in US Infants

Adoption of Rotavirus Vaccine by U.S. Physicians: Progress and Challenges

Pentavalent rotavirus vaccine (RV5) was recommended for routine use in 2006 followed by monovalent rotavirus vaccine (RV1) in 2008. To describe, among a U.S. sample of pediatricians (n=289 respondents) and family medicine physicians (n=243 respondents), (1) current practices regarding rotavirus vaccine (RV) and barriers to use with comparison to a 2007 survey and (2) knowledge of recent safety concerns regarding RV1 and their impact on its use. A mail and Internet survey was conducted with the physicians, from November 2010 to January 2011; analyses were conducted March-September 2011. Response rates were 70% (289/410) for pediatricians and 61% (243/401) for family medicine physicians; routine administration of RV was reported by 95% of pediatricians and 65% of family medicine physicians (2007: 85% and 45%). Almost all barriers to use of RV had decreased compared to 2007. For pediatricians and family medicine physicians, respectively, 94% and 70% were aware of the temporary suspension of RV1 due to presence of porcine circovirus; 49% and 45%, respectively, were aware of the addition to RV1 labeling regarding a possible increased risk of intussusception. Among physicians aware of the safety issues, <5% reported stopping giving RV as a result. After reading information about porcine circovirus, 35% of pediatricians and 59% of family medicine physicians reported it had increased their own concerns about the safety of RV; and 31% and 60%, respectively, reported this regarding intussusception. The acceptance of RV has increased, and barriers to use have decreased. Among physicians, recent safety questions about RV1 have not affected use of RV, although they have raised safety concerns.

Pharmacoeconomic Spotlight on Rotavirus Vaccine RIX4414 (Rotarix™) in Developed Countries

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated ‘real-world’ effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting.Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.

Pharmacoeconomic Spotlight on Rotavirus Vaccine RIX4414 (Rotarix™) in Developed Countries

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated ‘real-world’ effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.

The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales

Rotavirus vaccines have shown great potential for reducing the disease burden of the major cause of severe childhood gastroenteritis. The decision regarding whether rotavirus vaccination will be introduced into the national immunization program is currently being reviewed. The conclusions of previous evaluations of rotavirus vaccination cost-effectiveness contradict each other. This is the first analysis to incorporate a dynamic transmission model to assess the cost-effectiveness of rotavirus vaccination in England and Wales. Most previously reported models do not include herd protection, and thus may underestimate the cost-effectiveness of vaccination against rotavirus. We incorporate a dynamic model of rotavirus transmission in England and Wales into a cost-effectiveness analysis to determine the probability that the pentavalent rotavirus vaccination will be cost-effective over a range of full-course vaccine prices. This novel approach allows the cost-effectiveness analysis to include a feasible level of herd protection provided by a vaccination program. Our base case model predicts that pentavalent rotavirus vaccination is likely to be cost-effective in England and Wales at £60 per course. In some scenarios the vaccination is predicted to be not only cost-effective but also cost-saving. These savings could be generated within ten years after vaccine introduction. Our budget impact analysis demonstrates that for the realistic base case scenarios, 58–96% of the cost outlay for vaccination will be recouped within the first four years of a program. Our results indicate that rotavirus vaccination would be beneficial to public health and could be economically sound. Since rotavirus vaccination is not presently on the immunization schedule for England and Wales but is currently under review, this study can inform policymakers of the cost-effectiveness and budget impact of implementing a mass rotavirus vaccine strategy.

Symptomatic Infection and Detection of Vaccine and Vaccine-Reassortant Rotavirus Strains in 5 Children: A Case Series

Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient's illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections.

Duration of Protection of Pentavalent Rotavirus Vaccination in Nicaragua

To evaluate the duration of protection of pentavaent rotavirus vaccine (RV5) against rotavirus hospitalizations in Nicaragua, a developing country in Central America. We conducted a case-control study at 4 hospitals from 2007 through 2010, including 1016 children hospitalized with laboratory-confirmed rotavirus diarrhea, 4930 controls with nonrotavirus diarrhea (ie, "test-negative"), and 5627 controls without diarrhea. All cases and controls were aged ≥ 6 months and born after August 2006. Outcomes included odds of antecedent vaccination between case-patients and controls, and effectiveness of vaccination (1 - adjusted odds ratio [OR] × 100). Duration of protection was assessed by comparing effectiveness among children aged <1 year compared with ≥ 1 year. Indicators of socioeconomic conditions and nonrotavirus vaccination (oral polio vaccine and diphtheria/tetanus/pertussis/hepatitis A/hepatitis B) for test-negative controls were more comparable to the rotavirus case-patients than nondiarrhea controls. RV5 vaccination was associated with a significantly lower risk of rotavirus hospitalization by using test-negative controls (OR: 0.55; 95% confidence interval [CI]: 0.41-0.74) and nondiarrhea controls (OR: 0.30; 95% CI: 0.22-0.40). Risk of rotavirus hospitalization was twofold lower among RV5 vaccinated children aged <1 year (OR: 0.36; 95% CI: 0.22-0.57) compared with RV5 vaccinated children aged ≥ 1 year (OR: 0.70; 95% CI: 0.47-1.05). RV5 provided good protection against severe rotavirus disease in Nicaragua during the first year of life, when most severe and fatal rotavirus disease in developing countries occurs. However, the decline in protection with age warrants monitoring of disease among older children and consideration of a booster dose evaluation at the end of infancy.

Duration of Protection of Pentavalent Rotavirus Vaccination in Nicaragua

Duration of Protection of Pentavalent Rotavirus Vaccination in Nicaragua

Rotavirus Vaccine Trial in Jamaica

Worldwide, rotaviruses have been a significant cause of dehydrating gastroenteritis. This contributed to increased infant morbidity and mortality in Jamaica. We enrolled 1804 Jamaican infants in the international randomized, placebo-controlled, pentavalent (G1, G2, G3, G4 and P1) rotavirus vaccine trial. This pentavalent vaccine was found to significantly reduce rotavirus gastroenteritis attributable emergency room visits and hospitalizations, without increasing the rates of intussusception, or other serious adverse events in Jamaican infants. It is recommended that the rotavirus vaccine be included in Jamaica's National Immunization Programme in accordance with recommendations from the World Health Organization.

A study of RotaTeq™ (pentavalent rotavirus vaccine) in Chinese healthy adults, children and infants

A study of RotaTeq™ (pentavalent rotavirus vaccine) in Chinese healthy adults, children and infants

No Increased Risk of Intussusception After Rotavirus Vaccination

Source: Shui IM, Baggs J, Patel M, et al. Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants. JAMA. 2012; 307(6): 598– 604; doi: 10.1001/jama.2012.97In a collaboration between the US Centers for Disease Control and Prevention (CDC) and 8 managed care organizations (the Vaccine Safety Datalink [VSD]), investigators from multiple sites evaluated the risk of intussusception following administration of pentavalent rotavirus (RV5) vaccine to infants aged 4 to 34 weeks between 2006 and 2010. Rates of intussusception among RV5 recipients were compared to those of control infants who received age-appropriate recommended vaccines other than RV5 as well as to background rates among historical control infants from 2001 to 2005 (prior to licensure of RV5). Data on infants who received RV5 outside the recommended age guidelines were excluded. An intussusception episode was identified using International Classification of Diseases, Ninth Revision (ICD-9) codes from hospital, emergency department, and outpatient visits, and then validated through medical record review. Investigators focused on 2 time periods after each RV5 dose, or other vaccine doses in controls, to examine intussusception risk: days 1–7 and days 1–30 after immunization.During the study period, 309,844 first RV5 doses, 257,915 second doses, and 218,966 third doses were administered (total 786,725 doses). There were 389,026 total non-RV5 vaccine doses administered to infants in the control group during the same period. A total of 56 cases of intussusception were identified using ICD-9 codes during the study period in the 30 days following either an RV5 dose (n=30) or a comparison vaccine dose in control infants (n=26). Among the 22 confirmed cases of intussusception, 14 occurred in infants who received RV5 and 8 occurred in the comparison group (relative risk, 0.95; 95% CI, 0.37–2.63). Analysis by dose number (first, second, or third) and time after dose (1–7 or 1–30 days) revealed no significant differences between infants in the RV5 group and those in the comparison group.Compared to historical background rates established from 2001 to 2005, there were no significant increases in the expected rate of intussusception following any RV5 dose for 1–7 or 1–30 day risk windows.The authors conclude that there is no evidence of increased risk of intussusception in US infants receiving RV5 at the recommended ages.Dr Tolan has disclosed no financial relationship relevant to this commentary. Dr Tolan is on the Speaker’s Bureau for Novartis. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The first rotavirus vaccine was removed from the US market when an increased risk of intussusception, particularly in the first week after receipt of the first dose, was recognized during post-licensure monitoring. Subsequently, RV5 and a monovalent rotavirus vaccine were approved for use based upon pre-licensure evaluations of approximately 70,0001 and 60,0002 infants, respectively. Furthermore, an early post-licensure VSD evaluation following approximately 200,000 RV5 doses demonstrated no increased risk of intussusception.3 However, 2 recent international studies demonstrated an increased risk in their populations (Australia4 and Mexico5), raising concern that such a risk might, in fact, exist.With the inclusion of the additional 780,000 doses in this study, the total number of doses now included in US pre- and post-licensure rotavirus RV5 evaluations stands at more than 1 million. These evaluations have detected no evidence of an increased intussusception risk. One of the limitations of the current study is that it only evaluated RV5 doses given to infants with health insurance from one of the participating managed care organizations. It is conceivable that the evidence thus generated may not be generalizable to all US infants. Socioeconomic and demographic differences may help to explain the increased rate of intussusception observed in Mexico, for example.5 Additionally, only those doses given in the recommended time frames were analyzed, and therefore risk of intussusception following late doses cannot be addressed by this study. In the VSD population, 6.5% of first doses were given late.A predominant cause of intussusception is likely wild-type rotavirus infection. Perhaps the background rate will fall as uptake of rotavirus vaccine increases. As we wait for evidence of this, current data are nonetheless overwhelming that RV5 does not increase the risk of intussusception.This is good news. It is hard to ignore the fact that rotavirus vaccination prevented 42,000 to 62,000 infant hospitalizations in 2008.6 The public health impact of this decrease is enormous. The results of this study reinforce that the risk:benefit ratio of rotavirus vaccination is unequivocally positive.