Implementation Of Rotavirus Vaccination Research Articles

Diarrhea-Associated Hospitalizations Among US Children Over 2 Rotavirus Seasons After Vaccine Introduction

After implementation of rotavirus vaccination in 2006, large decreases in rates of severe diarrhea among US children occurred in 2007-2008. We ascertained whether these decreases were sustained in 2008-2009. We examined hospital discharge data from a national network of pediatric hospitals and compared all-cause diarrhea-related and rotavirus-specific hospitalizations in 3 prevaccine rotavirus seasons (2003-2006) with those in 2 postvaccine seasons (2007-2008 and 2008-2009) among children <5 years of age. We defined rotavirus seasons using data from a national laboratory surveillance network. At 62 consistently reporting hospitals, a median of 15 645 diarrhea-related hospitalizations (range: 14 881-16 884 hospitalizations) occurred each rotavirus season among children <5 years of age in 2003-2006. Compared with this median, all-cause diarrhea-related hospitalizations decreased by 50% (n = 7760) in 2007-2008 and by 29% (n = 11 039) in 2008-2009. In 2007-2008, reductions of 47% to 55% were seen for all age groups, including vaccine-ineligible children ≥2 years of age (48%). In 2008-2009, these reductions decreased in magnitude, especially among children ≥2 years of age (17%). Decreases in 2007-2008 and 2008-2009 were similar in the Northeast and West, but decreases were smaller in 2008-2009, compared with 2007-2008, in the Midwest and South. Compared with prevaccine seasons, decreases in diarrhea- and rotavirus-associated hospitalizations seen in 2007-2008 were sustained in 2008-2009 but were somewhat smaller. Given the variability in diarrhea-related hospitalization trends over the 2 postvaccine seasons according to age group and region, continued surveillance is required for full assessment of the impact of rotavirus vaccination.

Characterization of Rotavirus Strains Detected in Windhoek, Namibia during 1998–1999

Namibia, located on the southwestern coast of southern Africa, is characterized by vast deserts, limited fresh water, and low population density. Mortality estimates among children <5 of age are 63 deaths per 1000 live-births, with diarrheal diseases contributing to 3% of these deaths. Data on the burden of rotavirus disease and circulating serotypes in Namibia are currently not available. From May 1998 through December 1999, 815 stool specimens were collected from children <5 years of age who attended the Windhoek State Hospital, Windhoek, Namibia, for diarrhea. Specimens were screened for the presence of rotavirus antigens. Rotavirus-positive specimens were further analyzed to determine electropherotype, subgroup (SG) specificity, and G and P genotypes. Rotavirus was detected in 113 (13.8%) of 815 specimens, with the majority of infections occurring in children <18 months of age. Strains bearing 1 long electropherotype, SGII, and G1P[8] or G1P[6] specificity predominated during the 20-month study period. In addition to the typical winter rotavirus season, a peak in rotavirus infection was also observed during the summer. Serotypes G1P[8], G1P[6], G1P[4], and G2P[4] were found throughout the study period, predominantly in children <18 months of age. The observed summer rotavirus peak coincided with increased rainfall in Namibia and an increase in the diversity of detected serotypes. During the October to December 1999 peak, 2 G9P[6] strains and 1 G8P[4] strain were identified. Expanded and updated information on prevalence of rotavirus infection, circulating serotypes, and burden of disease will be required to enable local government to make decisions on the implementation of rotavirus vaccination in Namibia.

Genetic and Antigenic Diversity of Human Rotaviruses: Potential Impact on Vaccination Programs

The successful development and implementation of rotavirus vaccines will have a significant impact on rotavirus-induced gastroenteritis in children worldwide. However, this introduction will increase the immune pressure against wild-type rotavirus strains circulating in the community, altering the forces and balances that drive rotavirus evolution. There is concern that antigenically distinct novel or rare strains may be selected and spread, decreasing vaccine efficacy. This review describes the diversity of rotavirus strains and the mechanism by which wild-type rotavirus strains can evolve, including genetic drift and genetic reassortment.

Reduction in hospitalizations for diarrhea and rotavirus infections in New York state following introduction of rotavirus vaccine

Objectives To monitor trends and costs of diarrhea and rotavirus-associated hospitalizations in New York before and after rotavirus vaccine implementation in 2006. To examine rotavirus test results from sentinel hospital-associated laboratories. Methods Hospital discharge data and laboratory rotavirus testing data were analyzed for children 1 month up to 18 years of age for 10 sentinel and all statewide hospitals from January 1, 2003 through December 31, 2008. Results Among children 1–23 months of age, a 40% reduction in diarrhea-associated hospitalizations and 85% decrease in rotavirus-coded hospitalizations at the 10 sentinel hospitals was observed in 2008 compared with the average of pre-vaccine seasons from 2003 through 2006. For both sentinel and statewide hospitals, the percent of diarrhea admissions due to rotavirus was reduced at least 83% among children 1–23 months (vaccine eligible) and 70% for older unimmunized children. Statewide hospital costs for rotavirus hospitalizations in children <2 years of age were reduced $10 million. Sentinel hospital laboratory data validated the declining trends seen in hospitalizations. Conclusions In 2008, New York hospital data showed significant reductions in rotavirus hospitalizations and costs among children aged 1–23 months who were eligible for vaccine. Reductions also occurred among unimmunized older children suggesting the importance of continue monitoring in future seasons to fully assess vaccine impact.

Assessment of Postlicensure Safety of Rotavirus Vaccines, with Emphasis on Intussusception

The global implementation of rotavirus vaccines will result in a major step toward limiting the disease burden of rotavirus infection. However, as history has shown with the experience of Rotashield (Wyeth Lederle Vaccines), the introduction of a new vaccine should occur in parallel with a postmarketing surveillance strategy to detect any unexpected or rare adverse events. Two new rotavirus vaccines (Rotarix [GSK Biologicals] and RotaTeq [Merck]) have been found to be safe and effective in large clinical trials involving >60,000 infants in the Americas and Europe. However, given that intussusception is an extremely rare event, some risk could be detected as the vaccine is administered to a larger number of infants. In response to a recommendation of the World Health Organization Global Advisory Committee for Vaccine Safety, a standardized approach to the postmarketing surveillance of rotavirus vaccine safety has been developed. We review the principal safety issues requiring further evaluation in postlicensure use of rotavirus vaccines. For intussusception, we also discuss challenges and approaches to monitoring.

Implementation of Rotavirus Immunization in Philadelphia, Pennsylvania: High Levels of Vaccine Ineligibility and Off-Label Use

Our goal was to predict, using delayed diphtheria-tetanus-acellular pertussis vaccination as an indicator, whether the current narrowly defined age limits for pentavalent rotavirus vaccine exclude a substantial proportion of children from complete immunization against rotavirus and to assess adherence of providers to recommended age limits by examining the first 6 months of use of pentavalent rotavirus vaccine in Philadelphia, Pennsylvania. Data from a computerized children's immunization registry in Philadelphia were analyzed. Demographics and age at immunization with first 3 diphtheria-tetanus-acellular pertussis doses were examined from 2001 to 2005. Similar characteristics were evaluated for children who received pentavalent rotavirus vaccine doses during the first 6 months of its availability (August 2006 through January 2007). During the 5-year period, 24 403 of 103 967 recipients of first diphtheria-tetanus-acellular pertussis vaccine were >12 weeks of age; only 56 411 of 79 564 first diphtheria-tetanus-acellular pertussis recipients <or=12 weeks of age received the first 3 doses at ages that they could have completed the pentavalent rotavirus vaccine series if vaccines were given at the same visit. Children using public providers were more likely to have delayed immunization. During the first 6 months of pentavalent rotavirus vaccine implementation, 5566 pentavalent rotavirus vaccine doses were recorded in the Kids Immunization Database/Tracking System: 3912 first doses, 1419 second doses, and 235 third doses. Of 3912 first-dose pentavalent rotavirus vaccine recipients, 770 were >12 weeks of age. Hospital-based providers were less likely to administer pentavalent rotavirus vaccine off-label. With the current level of vaccine implementation and current pentavalent rotavirus vaccine recommendations for series initiation, a substantial proportion of children are expected to be excluded from receiving any pentavalent rotavirus vaccine or completing the series. In the first 6 months of availability, pentavalent rotavirus vaccine frequently was used off-label for age, underscoring the importance of education of immunization providers. Current outreach programs for finding 10-month-old toddlers delinquent for immunizations will not improve the possibility of protection against rotavirus.

Implementing rotavirus vaccination in Asia

At the 2006 meeting of the Asian Pacific Pediatric Association (APPA), the Asia Pacific regional rotavirus community and international experts strongly recommended that rotavirus vaccines be used in National Immunization Programmes (NIP) in countries in Asia. Two rotavirus vaccine candidates are currently licensed and have been demonstrated to be safe, well tolerated and highly efficacious. Several additional vaccines are in the late stages of development. The conference participants agreed that decisions on the introduction of rotavirus vaccines may require additional disease burden data in some countries and that economic evaluations will help policymakers reach decisions on nationwide rotavirus vaccine implementation. Other potential issues that arise with vaccine implementation, for example, the concomitant use of rotavirus vaccines with other vaccines, were also discussed. Rotavirus vaccines have the potential to substantially reduce morbidity and mortality from rotavirus disease and impact children's health in Asia.

Molecular Epidemiology of Rotavirus in Central and Southeastern Europe

A surveillance network was implemented by the Istituto Superiore di Sanità of Rome in collaboration with laboratories of virology in Czech Republic, Slovenia, Croatia, Albania, and Bulgaria. About 1,500 rotavirus-positive stool samples were collected from children with severe gastroenteritis admitted to hospitals or outpatient wards between 2004 and 2006. The G and P genotypes were determined by reverse transcription-nested PCR. Significant differences were found in the geographical distributions of rotavirus genotypes between countries participating in the study. The prevalence of "common" G/P combinations, G1P[8], G3P[8], G4P[8], and G2P[4], ranged between 50 and 85%. The G9 genotype, which is emerging worldwide, was identified in 2 to 35% of all samples depending on the country. Unusual combinations, such as G1 or G4 associated with P[4] or G2 with P[8], which may have arisen by reassortment between human strains, were found in samples from 3 to 20% of patients. The uncommon genotypes G8P[8] and G10P[6], which may have an animal origin, were also identified. Double infections with two rotavirus strains were observed in between 1.7 and 14% of cases studied. Our findings might implicate challenges for rotavirus vaccine implementation in a wide geographic area of the Balkans and Central-Eastern Europe and underscore the importance of extensive strain surveillance for success in vaccine development.

Rotavirus gastroenteritis: epidemiological data from a regional hospital in Belgium

The Belgian Institute of Public Health registered from 2000 to 2005 a yearly average of 6,790 hospital admissions for rotavirus gastroenteritis in children less than 5 years of age. Very efficacious rotavirus vaccines are available nowadays. The surveillance of hospitalisation due to rotavirus gastroenteritis is a good target for the follow-up of vaccine-related prevention. In a large regional Belgian hospital, rotavirus is associated with 12% to 21% of all hospitalisation days among children less than 2 years of age. The general implementation of rotavirus vaccination could dramatically reduce the hospitalisation of young children due to rotavirus gastroenteritis in developed countries.

Rotavirus vaccines: considerations for successful implementation in Europe

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.

Reply

On behalf of the large number of investigators who participated in the monumental trial designed to evaluate the safety and efficacy of the human attenuated rotavirus vaccine Rotarix, I would like to thank Drs Kamal-Udin and Croft for their accurate summary of our study. Also, I completely agree with their appreciation of the significant disease burden associated with rotavirus worldwide, as well as the impact that the implementation of rotavirus vaccination can have in both the developing and industrialized world.

Active hospital-based surveillance of rotavirus diarrhea in Austrian children, period 1997 to 2003

Rotavirus is the most common pathogen causing severe dehydrating diarrhea in infants and young children worldwide. Any decision on implementation of rotavirus vaccination will be strongly influenced by the expected reduction in severe and therefore costly outcomes associated with rotavirus infection. The aim of this study was to provide data on hospitalization of young children with rotavirus infection in Austria. The data were derived from active hospital-based sentinel surveillance for rotavirus during the period 1997 to 2003. During this period 25,600 children<15 years of age were hospitalized with acute laboratory-confirmed rotavirus gastroenteritis, the infection showing seasonal peaks between February and March. In 5 % of the cases first symptoms of diarrhea occurred at a minimum of 48 hours after hospital admission, indicating healthcare-associated origin of infection. The mean annual incidence of hospitalization per 100,000 population for the age group<5 years was 766 and for those<2 years 1742, the latter meaning that 1 in 60 Austrian children up to 2 years of age required hospitalization. An average peak incidence was observed between 8 and 14 months of age, with an average of 68% of the reported cases occurring in children aged<or=24 months. The mean length of hospital stay was 4.7 days, resulting in 17,200 rotavirus-associated hospital days per year. The observed incidence of hospitalization due to rotavirus in Austria is slightly higher than that reported in other industrialized countries. Our results reflect the considerable number of rotavirus-associated pediatric hospital in-patient days per year and the substantial annual direct costs of hospital care.

Rotavirus Types in Europe and Their Significance for Vaccination

The degree of diversity of cocirculating human rotavirus wild-type strains is high. This article reviews the occurrence and frequency of rotavirus types in European children younger than 5 years of age during the past 10-15 years. To enable greater understanding of the overall epidemiologic situation, rotavirus types found in animals in Europe are described. In addition, rotavirus types occurring in children outside Europe are considered. Taken together, these data provide an essential background to the development of rotavirus vaccines. The different concepts of immunization with the 2 main rotavirus candidate vaccines are briefly discussed, and their potential impact on the epidemiology of cocirculating rotavirus wild-type viruses is considered. A case is made for comprehensive surveillance of cocirculating human rotavirus types in Europe after the implementation of rotavirus vaccination.

Rotavirus VP7, and VP4 Types circulating in Plateau State Nigeria

Objective: To determine the rotavirus genotypes circulating in Plateau State using RT – PCR. Materials and Methods: Thirty one rotavirus isolates recovered from diarrhoeic stools in 1998 and 1999 were analyzed using nested multiplex RT – PCR technique for the determination of VP7 and VP4 genotypes Results: VP7 typing revealed the presence of the global epidemiologically important VP7 strains G1-G3 except genotype G4. ‘Mosaic' rotaviruses G1/3 were also found. The VP4 types identified were P (6), P(8) and P(4). Mixed genotypes of P(4)/P(6) were also detected. The predominant strains circulating during 1988 and 1999 were P(6) G1, P(6) G3, P(8)G1 and P(8)G3. Some strains could not be typed by the primers used. Conclusion: The application of molecular techniques of PCR to detect and characterize rotavirus strains circulating, contributes to the knowledge and burden of rotavirus strain diversity even though some strains could not be typed. This provides fundamental data necessary for rotavirus vaccine design and implementation in Africa. Key words: Rotavirus, genotypes, circulating in Plateau State, Nigeria. Highland Medical Research Journal Vol.1(4) 2003: 62-66

Characterization of Rotavirus Strains in a Danish Population: High Frequency of Mixed Infections and Diversity within the VP4 Gene of P[8] Strains

We characterized the G and P types from 162 rotavirus-positive stool specimens collected from 162 persons in Denmark (134 children and 28 adults) with acute diarrhea in 1998, 2000, and 2002. Samples were obtained during outpatient consultations (73%) and from hospitalized patients (27%). Although more than 20 different G-P combinations were identified, only 52% represented the globally most common types G1P[8], G2P[4], and G4P[8]. The G9 genotype, which is emerging worldwide, was identified in 12% of all samples. Twenty-one percent of the samples were of mixed genotypic origin, which is the highest frequency reported in any European population. The standard reverse transcription-PCR methods initially failed to identify a considerable fraction of the rotavirus P strains due to mutations at the VP4 primer-binding sites of P[8] strains. The application of a degenerate P[8] primer resulted in typing of most VP4 strains. There was considerable year-to-year variation among the circulating G-P types, and whereas G1P[8] was predominant in 1998 (42% of samples) and 2002 (26%), G2P[4] was the strain that was most frequently detected in 2000 (26% of samples). Our findings might implicate challenges for rotavirus vaccine implementation in a European population and underscore the importance of extensive strain surveillance prior to, during, and after introduction of any vaccine candidate.