Margaret M. Cortese

Decline and Change in Seasonality of US Rotavirus Activity After the Introduction of Rotavirus Vaccine

BACKGROUND: In 2006, routine immunization of US infants against rotavirus was initiated. We assessed national, regional, and local trends in rotavirus testing and detection before and after vaccine introduction. METHODS: We examined data for July 2000 through June 2008 from a national network of ∼70 US laboratories to compare geographical and temporal aspects of rotavirus season timing and peak activity. To assess trends in rotavirus testing and detection, we restricted the analyses to 33 laboratories that reported for ≥26 weeks per season from 2000 to 2008. RESULTS: Nationally, the onset and peak of the 2007–2008 rotavirus season were delayed 15 and 8 weeks, respectively, compared with prevaccine seasons from 2000–2006. Delays were observed in each region. The 2007–2008 rotavirus season lasted 14 weeks compared with a median of 26 weeks during the prevaccine era. Of 33 laboratories, 32 reported fewer positive results and a lower proportion of positive test results in 2007–2008 compared with the median in 2000–2006, with a 67% decline in the number and a 69% decline in the proportion of rotavirus-positive test results. The proportion of positive test results in 2007–2008 compared with the median in 2000–2006 declined >50% in 79% of the laboratories and >75% in 39% of the laboratories. CONCLUSIONS: The 2007–2008 US rotavirus season seems substantially delayed, shorter, and diminished in magnitude compared with seasons before vaccine implementation. The extent of change seems greater than expected on the basis of estimated vaccine coverage, suggesting indirect benefits to unvaccinated individuals. Monitoring in future seasons is needed to confirm these trends.

Rotavirus Vaccine and Health Care Utilization for Diarrhea in U.S. Children

BACKGROUND Routine vaccination of U.S. infants with pentavalent rotavirus vaccine (RV5) began in 2006. METHODS Using MarketScan databases, we assessed RV5 coverage and diarrhea-associated health care use from July 2007 through June 2009 versus July 2001 through June 2006 in children under 5 years of age. We compared the rates of diarrhea-associated health care use in unvaccinated children in the period from January through June (when rotavirus is most prevalent) in 2008 and 2009 with the prevaccine rates to estimate indirect benefits. We estimated national reductions in the number of hospitalizations for diarrhea, and associated costs, by extrapolation. RESULTS By December 31, 2008, at least one dose of RV5 had been administered in 73% of children under 1 year of age, 64% of children 1 year of age, and 8% of children 2 to 4 years of age. Among children under 5 years of age, rates of hospitalization for diarrhea in 2001-2006, 2007-2008, and 2008-2009 were 52, 35, and 39 cases per 10,000 person-years, respectively, for relative reductions from 2001-2006 by 33% (95% confidence interval [CI], 31 to 35) in 2007-2008 and by 25% (95% CI, 23 to 27) in 2008-2009; rates of hospitalization specifically coded for rotavirus infection were 14, 4, and 6 cases per 10,000 person-years, respectively, for relative reductions in the rate from 2001-2006 by 75% (95% CI, 72 to 77) in 2007-2008 and by 60% (95% CI, 58 to 63) in 2008-2009. In the January-June periods of 2008 and 2009, the respective relative rate reductions among vaccinated children as compared with unvaccinated children were as follows: hospitalization for diarrhea, 44% (95% CI, 33 to 53) and 58% (95% CI, 52 to 64); rotavirus-coded hospitalization, 89% (95% CI, 79 to 94) and 89% (95% CI, 84 to 93); emergency department visits for diarrhea, 37% (95% CI, 31 to 43) and 48% (95% CI, 44 to 51); and outpatient visits for diarrhea, 9% (95% CI, 6 to 11) and 12% (95% CI, 10 to 15). Indirect benefits (in unvaccinated children) were seen in 2007-2008 but not in 2008-2009. Nationally, for the 2007-2009 period, there was an estimated reduction of 64,855 hospitalizations, saving approximately

Uptake, impact, and effectiveness of rotavirus vaccination in the United States: review of the first 3 years of postlicensure data.

278 million in treatment costs. CONCLUSIONS Since the introduction of rotavirus vaccine, diarrhea-associated health care utilization and medical expenditures for U.S. children have decreased substantially.

United States rotavirus strain surveillance from 2005 to 2008: genotype prevalence before and after vaccine introduction.

Background: Rotavirus vaccine was recommended for routine use in US infants in 2006. Before the introduction of vaccine, rotavirus was the most common cause of severe gastroenteritis in children <5 years of age in the United States. Methods: We reviewed published data to summarize the US experience during the first 3 years of its rotavirus vaccination program. Results: Rotavirus seasons have been delayed and diminished in magnitude during the postvaccine era compared with the prevaccine era. Hospitalizations, emergency department visits, and outpatient visits due to gastroenteritis have declined dramatically in children <5 years of age including in children age-ineligible to have received vaccine, suggesting indirect benefits of vaccination. Rotavirus vaccine has been widely accepted by pediatricians. Vaccine coverage is steadily increasing but remains lower than coverage levels of other routine infant immunizations. Conclusions: The implementation of routine childhood immunization against rotavirus has rapidly and dramatically reduced the large health burden of rotavirus gastroenteritis in US children. Continued monitoring of rotavirus diarrhea is needed to determine if immunity wanes as vaccinated children get older and to better quantify the indirect benefits of vaccination. Ongoing surveillance will also enable monitoring of the long-term impact of vaccination on rotavirus epidemiology.

Sustained decline in rotavirus detections in the United States following the introduction of rotavirus vaccine in 2006.

Background: A live, attenuated rotavirus vaccine, RotaTeq®, was approved in 2006 for immunization of infants in the United States. To monitor the distribution of rotavirus genotypes before and after vaccine introduction, the Centers for Disease Control and Prevention conducted strain surveillance with the National Rotavirus Strain Surveillance System. Methods: Over 3 rotavirus seasons, 2005–2006, 2006–2007, and 2007–2008, National Rotavirus Strain Surveillance System laboratories collected rotavirus-positive stool specimens and submitted them to the Centers for Disease Control and Prevention. Rotavirus strains were G- and P-genotyped by multiplex reverse transcription-polymerase chain reaction or nucleotide sequencing. Results: During 2005–2006 and 2006–2007 seasons, G1 was the dominant G-type but in the 2007–2008 season, G3 replaced G1 as the most frequently detected strain. Four genotypes, G1P[8], G2P[4], G3P[8], and G9P[8] were detected in every season. Uncommon strains observed during the study period were G2P[8], G1P[6], G2P[6], G4P[6], G1P[4], G3P[9], G12P [6], and G12P[8]. The mean age of rotavirus cases in the 2007–2008 season increased significantly in patients less than 3 years old compared with the 2 previous seasons. Conclusions: The increased overall prevalence of G3P [8] strains in 2007–2008, the first rotavirus season with reasonable rotavirus vaccine coverage, was consistent with Australian reports of G3 dominance following RotaTeq introduction. However, these strain changes in both countries have occurred in the context of large declines in severe rotavirus disease and we cannot rule out that they are simply the result of naturally occurring changes in rotavirus strain prevalence. These findings underscore the need for careful monitoring of strains to assess possible vaccine pressure-induced changes and vaccine effectiveness against various rotavirus genotypes.

Postlicensure Monitoring of Intussusception After RotaTeq Vaccination in the United States, February 1, 2006, to September 25, 2007

Background: Following implementation of the rotavirus vaccination program in 2006, rotavirus activity in the United States declined dramatically in 2007–2008 but increased slightly in 2008–2009, despite greater vaccine uptake. To further evaluate impact of the vaccine program, we assessed trends in rotavirus testing and detection during 2009–2010. Methods: We examined rotavirus testing data from July 2000 to June 2010 from the National Respiratory and Enteric Viruses Surveillance System to compare rotavirus season timing and peak activity in the pre- and postvaccine introduction eras. Rotavirus season onset was defined as the first of 2 consecutive weeks during which the percentage of specimens testing positive for rotavirus was ≥10%. To assess trends in rotavirus testing and detection, we restricted the analyses to 25 laboratories that reported for ≥26 weeks per season from 2000 to 2010. Results: During 2009–2010, the threshold for the start of the rotavirus season was never achieved nationally or in the North, Midwest, or West. Activity in the South met this threshold but the season duration was substantially shorter and of lower magnitude than in all previous pre- and postvaccine introduction seasons. Nationally and within each region, the peak week was more delayed and the peak proportion of positive tests was substantially lower than all previous seasons. The total number of tests performed declined by 23%, and the number of positive tests declined by 86%. Conclusions: Rotavirus activity was substantially diminished during the 2009–2010 rotavirus season compared with the prevaccine baseline and the 2 previous postvaccine introduction seasons. These sustained declines over 3 rotavirus seasons reaffirm the health benefits of the US rotavirus vaccination program.

Reduction in gastroenteritis in United States children and correlation with early rotavirus vaccine uptake from national medical claims databases.

BACKGROUND. In 1999, a previous rotavirus vaccine (RotaShield; Wyeth Laboratories, Marietta, PA) was withdrawn from the US market after postlicensure monitoring identified an association with intussusception. Although the new rotavirus vaccine (RotaTeq; Merck, West Point, PA) introduced in 2006 was not associated with intussusception in prelicensure trials, additional monitoring is important to ensure a complete safety profile. METHODS. We assessed intussusception reports after RotaTeq vaccination by using data from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink, a cohort of children enrolled in managed care. Observed versus expected rate ratios were determined by using vaccine dose distribution data and Vaccine Safety Datalink background intussusception rates. RESULTS. Between February 1, 2006, and September 25, 2007, the Vaccine Adverse Event Reporting System received 160 intussusception reports after RotaTeq vaccination. With the assumptions that reporting completeness was 75% and that 75% of the distributed doses of RotaTeq were administered, the observed versus expected rate ratios were 0.53 and 0.91 for the 1–21 and 1–7 day interval after vaccination, respectively. In the Vaccine Safety Datalink, 3 intussusception cases occurred within 30 days after 111521 RotaTeq vaccinations, compared with 6 cases after 186722 non–RotaTeq vaccinations during the same period. If, like RotaShield, RotaTeq had a 37-fold increased risk of intussusception within 3 to 7 days after vaccination, then 8 intussusception cases would be expected within 3 to 7 days among the ∼84000 infants vaccinated with the first dose of RotaTeq in the Vaccine Safety Datalink (N = 49902) and the prelicensure trial (N = 34035) combined, whereas no cases have been observed. CONCLUSIONS. Available data do not indicate that RotaTeq is associated with intussusception. Although an intussusception risk similar in magnitude to that of RotaShield can be excluded, continued monitoring is necessary for complete assessment of the safety profile of RotaTeq.

Economic Evaluation of the Routine Childhood Immunization Program in the United States, 2009

Background: We sought to estimate rotavirus disease reduction among children in hospital and office settings in the 4 US regions following rotavirus vaccine introduction and to estimate vaccine uptake. Methods: Two national third-party payer medical claims databases were used to examine the number of visits for gastroenteritis per annual nongastroenteritis visits among children aged <5 years during July 2003 to June 2008 in hospital and office settings. The gastroenteritis burden attributable to rotavirus was computed as the excess of all gastroenteritis visits during rotavirus seasons above the baseline of visits during nonrotavirus periods. Rotavirus vaccine uptake was estimated by comparing claims for rotavirus vaccine with those for diphtheria-tetanus-acellular pertussis vaccines. Results: In the South, Northeast, and Midwest, the typical winter-spring gastroenteritis peak due to rotavirus was markedly dampened in 2007–2008. Compared with the mean for 3 prevaccine seasons, the excess gastroenteritis visits that occurred during the 2007–2008 rotavirus season was reduced by >90% among infants in all care settings in 3 regions and by >70% among children aged 1 to 4 years. In the West, disease reductions were lower (53%–63% reduction among hospitalized infants). At the onset of the 2007–2008 season, coverage with ≥1 rotavirus vaccine dose was an estimated 57% among infants, 17% among children aged 1 year, and 0 among those aged 2 to 4 years. Conclusions: The rotavirus burden in 2007–2008 was markedly reduced in all US regions and exceeded that explained by only direct protection of the youngest vaccinated children.

Pertussis Hospitalizations Among Infants in the United States, 1993 to 2004

OBJECTIVES: To evaluate the economic impact of the 2009 routine US childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate, hepatitis A, and rotavirus vaccines; influenza vaccine was not included. METHODS: Decision analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported during 2005 to 2009. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and work time lost. All costs were inflated to 2009 dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2009 US birth cohort of 4 261 494 infants over their lifetime was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine childhood immunization were calculated. RESULTS: Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent ∼42 000 early deaths and 20 million cases of disease, with net savings of

Mumps Vaccine Performance among University Students during a Mumps Outbreak

13.5 billion in direct costs and