† By reverse transcription-polymerase chain reaction.

1 Confidence interval.

Statistically significant.

A/Wisconsin/76/2005 strain. All 18 influenza B viruses were B/Florida/04/2006-like, belonging to the B/Yamagata/ 16/88 lineage of viruses. B/Yamagata-like viruses are antigenically distinct from the B/Victoria-like lineage virus that was included in the 2007-08 influenza vaccine. Reported by: E Belongia, MD, B Kieke, L Coleman, PhD, J Donahue, DVM, PhD, S Irving, J Meece, PhD, M Vandermause, Marshfield Clinic Research Foundation, Marshfield, Wisconsin. D Shay, MD, P Gargiullo, PhD, A Balish, A Foust, MA, L Guo, MD, S Lindstrom, PhD, XXu, MD, A Klimov, PhD, J Bresee, MD, N Cox, PhD Influenza Div, National Center for Immunization and Respiratory Disease, CDC.

Editorial Note: Influenza infections result in substantial morbidity and mortality each year in the United States (4,5). Because of the sizeable burden of influenza-associated disease, annual influenza vaccination was recommended by ACIP for the 2007-08 season for children aged 6-59 months, adults aged ≥50 years, persons with chronic medical conditions that place them at high risk for serious influenza-related complications, and close contacts of these groups and of children aged <6 months (6).

Viral data reported to World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories in the United States during the 2007-08 influenza season through April 5, 2008, demonstrated that influenza A and B viruses accounted for 74% and 26%, respectively, of influenza viruses characterized in the United States (7). Of influenza A viruses subtyped,

27% were influenza A (H1N1) viruses, and 73% w: influenza A (H3N2) viruses. Antigenic characterization a subset of these viruses by CDC indicated that 69% A (H1N1) viruses were A/Solomon Islands/3/2006-lik the A (H1N1) vaccine component, but that 71% A (H3N2) viruses were A/Brisbane/10/2007-like, a rece antigenic variant of the A/Wisconsin/67/2005-like vir the A (H3N2) vaccine component. In addition, 95% c antigenically characterized B viruses belonged to the B/Yamagata lineage. Viruses in this lineage are antigen cally distinct from the B/Malaysia/2506/2004-like com ponent of the 2007-08 vaccine, which is in the B/Victor lineage. These viral surveillance data suggested that t. effectiveness of the 2007-08 influenza vaccine might b reduced against circulating influenza A (H3N2) and viruses. However, in this analysis, preliminary VE result indicated that, despite the antigenic differences between vaccine and circulating H3N2 strains, the effectiveness vaccine in preventing medically attended respiratory i nesses from influenza A infections was 58%. In contrast no VE could be demonstrated against influenza B.

Multiple previous studies of the effectiveness of influenza vaccines have been reported (i.e., observational studies d the clinical effects of vaccination as opposed to randomize clinical trials) (8). VE varies from influenza season to sea son, based in part on the degree of antigenic match

ween vaccine and circulating influenza strains. VE pre-usly has been assessed sporadically in different populans and by using different methods. Annual systematic essments of VE using laboratory-confirmed outcomes ve not been available within an influenza season. FurDermore, antigenic characterization data rarely have been ilable for influenza viruses isolated from participants of studies, and not previously from the population for 10m annual vaccination is recommended by ACIP. spite a mismatch between the vaccine influenza A 3N2) strain and seven of nine influenza A (H3N2) uses isolated from study participants, the data in this ort are consistent with results obtained in seasons with noderate antigenic mismatch between vaccine and circuing strains of H3N2 viruses (1,8).

Based on preliminary analyses of A/Brisbane/10/2007e (H3N2) viruses and the 2007-08 vaccine H3N2 strain ng the method of antigenic mapping (9), an average irfold difference was observed between the homologous er for the vaccine strain and average titers for circulating ains. These differences were measured with hemagglutition inhibition tests by using a panel of reference stinfection ferret antisera. The degree of mismatch tween the A/Wisconsin/67/2005 vaccine strain and 3N2 viruses tested at CDC thus far during the U.S. 07-08 influenza season can be described as moderate in ation to antigenic distances seen over time for H3N2 uses (10). By contrast, all the influenza B viruses isoed in the Marshfield Clinic study this season and antinically characterized thus far belong to the B lineage not ntained in this season's vaccine. Viruses from the Victoria-like lineage and B/Yamagata-like lineage are subntially more antigenically distinct from each other than Wisconsin/67/2005-like and A/Brisbane/10/2007-like 3N2 viruses are from each other.

The findings in this report are subject to at least four nitations. First, analyses were conducted while enrollment d laboratory testing were ongoing, and not all RT-PCR sitive samples had yet been confirmed by culture. Thus, e preliminary subtype distribution and antigenic charterization results might not be representative of all tients in the study with influenza. Second, VE was estiated only for prevention of influenza among persons who ught care for acute respiratory illness, comparing patients 10 tested positive for influenza with patients who tested gative. Certain patients who tested negative for influza might actually have had influenza virus infections, hough RT-PCR is the most sensitive diagnostic test availle. In addition, although simulation models have monstrated that VE estimated with test-negative

controls was close to the actual VE when test specificity was high, as is also the case with RT-PCR (3), this method is only beginning to be used in studies. VE was assessed against medically attended influenza and not against more severe outcomes of influenza infection, such as influenza hospitalizations; VE might vary with severity of the outcome studied. Third, if the antigenic characteristics of influenza viruses circulating in other regions of the United States differ substantially from viruses isolated from the Marshfield, Wisconsin, study participants, VE might vary by region. Finally, enrollment of patients continued in this study thorough March 28, and final analyses might differ from these interim assessments of VE.

These preliminary data based on study enrollment during January 21-February 8 suggest several conclusions. First, when assessing VE, laboratory data on antigenic characterization of circulating influenza viruses compared with vaccine strains should be interpreted together with data on the clinical effectiveness of vaccination in preventing laboratory-confirmed influenza illnesses. Although two of three vaccine strains were not optimally matched with circulating viruses this season, an interim VE estimate suggests that vaccination provided substantial protection against medically attended acute respiratory illness in this study population. In addition, intraseason estimates of VE, such as those from this analysis, might be useful to public health authorities and medical practitioners in their communications about the benefits of vaccination, especially late in the influenza season. Such data also might be helpful to practitioners when evaluating the need for antiviral treatment and prophylaxis for their patients. Therefore, creating systems that enable collection and dissemination of timely VE data during an influenza season are a priority for CDC. Finally, health-care providers should be aware of the types and subtypes of influenza circulating in their communities over the course of each influenza season. If influenza B strains predominate during the remainder of this season, providers can anticipate an increased risk for vaccine failures and should consider early use of antiviral medications for treatment and prophylaxis of persons at high risk for complications from influenza infection.

Acknowledgments

The findings in this report are based, in part, on contributions from V Allison, J Anderson, E Bergmann, C Beyer, L Bennetti, N Berger, C Becker, A Bernitt, A Brockman, K Buedding, D Cole, A Deedon, J Frahmann, D Gamble, L Gavigan, D Gentz, G Greenwald, N Hartl, J Herr, D Hilgemann, L Ivacic, D Johnson, D Kempf, T KronenwetterKoeppel, D Marx, C Meyer, C Reis, S Reisner, J Salzwedel, S Strey, P Siegler, P Stockwell, L Verhagen, D York, J Zygarlicke, Marshfield Clinic Research Foundation, Marshfield, Wisconsin.

References

1. Edwards KM, DuPont WD, Westrich MK, Plummer WD, Palmer PS, Wright PF. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis 1994;169:68-76.

2. Bridges CB, Thompson WW, Meltzer MI, et al. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: a randomized controlled trial. JAMA 2000;284:1655–63.

3. Orenstein EW, De Serres G, Haber MJ, et al. Methodologic issues regarding the use of three observational study designs to assess influenza vaccine effectiveness. Int J Epidemiol 2007;36:623–31. 4. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179–86.

5. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333-40.

6. CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR 2007;56(No. RR-6).

7. CDC. Update: influenza activity-United States, September 30, 2007– April 5, 2008, and composition of the 2008-09 influenza vaccine. MMWR 2008;57:404-9.

8. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 2007;357:1373-81.

9. Smith DJ, Lapedes AS, de Jong JC, et al. Mapping the antigenic and genetic evolution of influenza virus. Science 2004;305:371–6.

10. Russell CA, Jones TC, Barr IG, et al. The global circulation of seasonal influenza A(H3N2) viruses. Science. In press 2008.

February 2006-May 2007

Worldwide, rotavirus is the leading cause of severe gastroenteritis in children aged <5 years. In February 2006, a new human-bovine rotavirus vaccine, Rota Teq® (Merck & Co., Inc., Whitehouse Station, New Jersey), was recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of U.S. infants. Three doses of RotaTeq are recommended at ages 2, 4, and 6 months (1). The first dose should be administered between ages 6 and 12 weeks, and vaccination should not be initiated for infants aged >12 weeks. Subsequent doses should be administered at 4-10 week intervals, with all doses administered by age 32 weeks. This schedule is consistent with the ages at which RotaTeq was administered during prelicensure trials (1), and ACIP has recommended that Rota Teq only be administered at the ages for which safety

and efficacy data are available. In 1999, a previous rhest human rotavirus vaccine, RotaShield® (Wyeth Labora:ries, Inc., Marietta, Pennsylvania), was withdraw voluntarily from the U.S. market by the manufacture because it was associated with intussusception, a form : bowel obstruction. The greatest risk for intussusception w noted after the first dose of RotaShield (2). Data from. large-scale, prelicensure safety trial and postlicensure mon toring do not indicate an association between the curren RotaTeq vaccine and intussusception (3-5). CDC assess rotavirus vaccination coverage among U.S. infants duri February 2006-May 2007 and examined adherence to ACIP-recommended vaccination schedule. This report su marizes the results of that assessment, which indicated the by May 15, 2007, nearly half of infants aged 3 mont had received 1 dose of rotavirus vaccine, with the majer of doses administered according to ACIP recommendation. Health-care providers should remain vigilant in followi the ACIP-recommended vaccination schedule for rotavit vaccine.

To assess rotavirus vaccination coverage and adherence the vaccination schedule, CDC examined data from the data systems: 1) immunization information systems (IIS 2) IIS sentinel sites, and 3) the Vaccine Safety Datali (VSD). IIS data are derived from confidential, compute ized records of vaccine administration collected from m

tiple health-care providers within a defined geographic are (e.g., a state or city). CDC funds the development an: operations of IISS under the Public Health Service Act. 2006, approximately 65% of U.S. children aged <6 year participated in an IIS (6). IIS data were used to measur the number of rotavirus vaccine doses administered. Ada tional data were derived from the population-based IISS Arizona, the District of Columbia, Michigan, Minnesot Montana, and Oregon, which were participants in CDC IIS sentinel site project during 2004-2007. Sentinel sit are a subset of the state IIS coverage area and represe ≥10,000 children aged <6 years in contiguous geograph counties, postal code areas, or U.S. Census tracts. The surveillance areas have high health-care provider participa tion and child enrollment (>90%) in the IIS. Procedure are in place in these sites to increase completeness and accuracy of the data (e.g., routine comparisons of IIS record with health-care provider data) (7). IIS sentinel site dat were used to assess rotavirus vaccination coverage and adherence to the ACIP-recommended vaccination schedu

* 42 USC Sect. 247b (project grants for preventive health services).

VSD is a collaborative project involving CDC and eight edical-care organizations in the United States that ollect data on approximately 5.5 million persons annually 3). VSD data provide comprehensive immunization hispries and incorporate routine data-quality checks to proote data accuracy (9). VSD data were used to assess dherence to the ACIP-recommended vaccination schede. For the assessment of adherence to the vaccination hedule, data on rotavirus vaccine administration by age n weeks) and dose number in the series were reported by S sentinel sites through May 31, 2007, and by VSD rough July 31, 2007. Some children might be enrolled both IISS and VSD; however, this overlap is not anticiated to affect the estimates of adherence in either system, hich were analyzed separately. In both systems, the date vaccine administration was used to determine the dose umber in the series, with the first date of vaccine admintration counting as dose 1.

During February 2006-May 2007, a total of 1,120,239 iministered doses that were recorded by IISS in 27 states porting rotavirus vaccine administration by dose numer in the series. The monthly number of doses adminisred increased from approximately 4,000 doses in May 006 to nearly 134,000 in March 2007. At the six IIS ntinel sites, vaccination coverage increased from the third uarter of 2006 to the second quarter of 2007 (Figure 1). s of May 15, 2007, 1-dose rotavirus vaccination coverage nong infants aged 3 months at IIS sentinel sites ranged om 40.1% to 65.4% (mean: 49.1%). Rotavirus vaccinaon coverage estimates were compared with coverage estiates of other infant vaccines. At IIS sentinel sites, 1-dose overage at age 3 months ranged from 69.3% to 90.4%

GURE 1. First dose rotavirus vaccination coverage among hildren aged 3 months,* by quarter-immunization information /stem (IIS) sentinel sites, United States, 2006-2007+

(mean: 84.1%) for pneumococcal conjugate vaccine (PCV7) and from 69.5% to 92.3% (mean: 85.7%) for diphtheria, tetanus, and acellular pertussis (DTaP) vaccine.

A total of 107,128 doses were reported by IIS sentinel sites, and 90,151 doses were reported by VSD (Table). At IIS sentinel sites, 45,659 (85.9%) of 53,143 first doses were administered within the recommended age range of 6-12 weeks, whereas in VSD, 38,582 (92.8%) of 41,583 first doses were administered within the recommended age range (Figure 2). For the respective 7,484 (14.1%) and 3,001 (7.2%) first doses administered outside the recommended age range, small peaks were observed at ages 17 and 26 weeks. When analysis of IIS sentinel site and VSD data was restricted to infants who received ≥3 doses, 21,395 (95.0%) of 22,526 first doses at IIS sentinel sites and 25,629 (98.6%) of 26,005 first doses in VSD were

administered within the recommended age range. Small peaks in administration of the first dose were noted at age 17 weeks in both data sources.

A small percentage of doses were reported as administered completely outside the recommended age range of 6-32 weeks. Of all doses reported by IISS, IIS sentinel sites, and VSD, 0.1%, 0.2%, and 0.04%, respectively, were administered at age <6 weeks, and 1.8%, 1.6%, and 0.7%, respectively, were administered at age >32 weeks. Reported by: HA Clayton, MPH, MM Cortese, MD, DC Payne, PhD, DL Bartlett, MPH, LA Zimmerman, MPH, WG Williams, MPH, M Wang, MPH, LJ Stockman, MPH, U Parashar, MBBS, National Center for Immunization and Respiratory Diseases; J Baggs, PhD, Immunization Safety Office, Office of the Chief Science Officer, CDC.

Editorial Note: Routine vaccination of infants with rotavirus vaccine is anticipated to be the most effective public health intervention for reducing the substantial burden of rotavirus disease in children. Rotavirus vaccination coverage in the United States increased during the year after the February 2006 ACIP recommendation, and by May 2007, nearly half of infants aged 3 months in IIS sentinel sites had received 1 dose of rotavirus vaccine. Although the majority of health-care providers in these systems appear to be administering the vaccine as recommended, the findings in this report suggest that some infants are receiving their first dose of rotavirus vaccine outside of the ACIPrecommended schedule.

The findings in this report are subject to at least three limitations. First, in each data source, the date of vaccine administration was used to determine the dose number in the series, with the first date of vaccine administration counted as dose 1. Thus, doses counted as first doses but administered at approximately ages 17 and 26 weeks (i.e.,

the ages when second and third doses of vaccine are recommended) might actually represent second or third doses for infants whose previous doses were not recorded in these systems. Alternatively, the late first doses might represent infants receiving rotavirus vaccine during routine well-child visits at ages 4 and 6 months. To explore these hypotheses, analysis of IIS sentinel site and VSD data was restricted to infants who received >3 doses (i.e., infants who were more likely to have a first dose recorded); that analysis determined that a lower percentage of first doses were administered outside the recommended age range. However, small peaks in administration of first doses were still noted at age 17 weeks in both data sources, indicating that some children received rotavirus vaccine outside of the recommended schedule. The decrease in the percentage of first doses administered outside of the schedule might be attributable,

in part, to the possibility that infants who receive all 3 dose are more likely to be vaccinated on schedule than other infants. Second, although IIS sentinel site and VSD dat are monitored for accuracy and completeness, some vacc nations might not be entered into a child's electronic record potentially resulting in an underestimation of vaccination coverage levels (10). Finally, the populations captured in IIS sentinel sites and VSD might not be nationally rep sentative, which might limit the generalizability of thes findings. The National Immunization Survey (NIS) provides childhood vaccination coverage data that are nationally representative. However, because the survey targe children aged 19–35 months, NIS data on rotavirus vacci nation coverage will not be available until 2009 or 2015 nearly 2 to 3 years after the February 2006 ACIP recom mendation for rotavirus vaccination.

Although these initial findings on rotavirus vaccination coverage are encouraging, public health professionals shoul continue to monitor vaccination coverage, identify poter tial barriers to vaccination, and increase vaccination coverage to levels similar to those for other recommended infa:: vaccines. In addition, health-care providers should remain vigilant in following the ACIP-recommended vaccinatio: schedule for rotavirus vaccine and are reminded to reper any adverse events to the Vaccine Adverse Events Reporting System.

Acknowledgments

The findings in this report are based, in part, on contributions R Volp, Arizona Dept of Health Svcs; RP McLaren, MS, District t Columbia Dept of Health; KS Enger, MPH, Michigan Dept of Com munity Health; K White, MPH, Minnesota Dept of Health; B Wehre Montana Dept of Public Health and Human Svcs; J Gaudino, MD Oregon Dept of Human Svcs; and E Belongia, MD, Vaccine Safet Datalink, CDC.

References

1. CDC. Prevention of rotavirus gastroenteritis among infants and chidren: recommendations of the Advisory Committee on Immunizatio Practices. MMWR 2006;55(No. RR-12).

2. Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception amers infants given an oral rotavirus vaccine. N Engl J Med 2001;34564-72.

3. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of pentavalent human-bovine (WC3) reassortant rotavirus vaccine N Engl J Med 2006;354:23–33.

4. CDC. Postmarketing monitoring of intussusception after RotaTeq vaccination-United States, February 1, 2006-February 15, 2007

MMWR 2007;56:218-22.

5. Haber P, Patel M, Hector IS, et al. Post-licensure monitoring of intussusception after RotaTeq vaccination in the United States, Februar 1, 2006-September 25, 2007. Pediatrics. In press 2008.

6. CDC. Immunization information systems progress-United State 2006. MMWR 2008;57:289–91.