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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 influ

enza 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.

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

To assess rotavirus vaccination coverage and adherence the vaccination schedule, CDC examined data from th:data systems: 1) immunization information systems (IIS: 2) IIS sentinel sites, and 3) the Vaccine Safety Datalin (VSD). IIS data are derived from confidential, compute ized records of vaccine administration collected from mi tiple health-care providers within a defined geographic ar: (e.g., a state or city). CDC funds the development ar. operations of IISs under the Public Health Service Act.**: 2006, approximately 65% of U.S. children aged <6 vez participated in an IIS (6). IIS data were used to measu: the number of rotavirus vaccine doses administered. Ado tional data were derived from the population-based IIS: Arizona, the District of Columbia, Michigan, Minnesot. Montana, and Oregon, which were participants in CDC IIS sentinel site project during 2004-2007. Sentinel sis. are a subset of the state IIS coverage area and represe.. 210,000 children aged <6 years in contiguous geograp: counties, postal code areas, or U.S. Census tracts. The surveillance areas have high health-care provider particip tion and child enrollment (>90%) in the IIS. Procedur are in place in these sites to increase completeness araccuracy of the data (e.g., routine comparisons of IIS record with health-care provider data) (7). IIS sentinel site da were used to assess rotavirus vaccination coverage anu adherence to the ACIP-recommended vaccination schedu

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Rotavirus Vaccination Coverage and Adherence to the

Advisory Committee on
Immunization Practices (ACIP)-

Recommended Vaccination
Schedule United States,

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 RotaTeq only be administered at the ages for which safety

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

(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

::VSD is a collaborative project involving CDC and eight edical-care organizations in the United States that vollect data on approximately 5.5 million persons annually

3). VSD data provide comprehensive immunization hisories and incorporate routine data-quality checks to probuote data accuracy (9). VSD data were used to assess

Therence to the ACIP-recommended vaccination schedcie. For the assessment of adherence to the vaccination hedule, data on rotavirus vaccine administration by age in weeks) and dose number in the series were reported by S sentinel sites through May 31, 2007, and by VSD trough 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 admin-tration 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 106 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 estilates of other infant vaccines. At IIS sentinel sites, 1-dose pverage at age 3 months ranged from 69.3% to 90.4%


TABLE. Number of rotavirus vaccine doses administered, by
data source and selected characteristics — immunization
information system (IIS) sentinel sites and Vaccine Safety
Datalink (VSD), United States, 2006–2007*

IIS sentinel sites
All infants
Total doses administered


90,151 First doses administered


41,583 First doses administered at age 6–12 wks 45,659 (85.9) 38,582 (92.8)

(% of first doses administered) Infants receiving >3 doses Doses administered


64,317 First doses administered


26,005 First doses administered at age 6–12 wks 21,395 (95.0) 25,629 (98.6)

(% of first doses administered) * Data reported through May 31, 2007, by IIS sentinel sites and through July 31, 2007, by VSD.

IGURE 1. First dose rotavirus vaccination coverage among hildren aged 3 months,* by quarter - immunization information ystem (IIS) sentinel sites, United States, 2006–20071

FIGURE 2. Administration of first dose of rotavirus vaccine, by age of child – immunization information system (IIS) sentinel sites and Vaccine Safety Datalink (VSD), United States, 2006-2007*




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No. of doses (in thousands)




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10,95 <6 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

Age (wks)

Approximate populations of children aged 3 months in IIS sentinel site registries: Arizona (n = 785), District of Columbia (n = 220), Michigan in = 7,299), Minnesota (n = 183), Montana (n = 506), and Oregon (n=510). Populations varied by quarter. Data reported through May 15, 2007.

* Data reported through May 31, 2007, by IIS sentinel sites and through July 31, 2007, by VSD.

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, MWang, MPH, LJ Stockman, MPH, U Parashar, MBBS, National Center for Immunization and Respiratory Diseases; ) 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 23 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 dara 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 repres sentative, which might limit the generalizability of thex findings. The National Immunization Survey (NIS) provides childhood vaccination coverage data that are natiorally representative. However, because the survey targe's children aged 19–35 months, NIS data on rotavirus vacanation coverage will not be available until 2009 or 2010 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 shou: continue to monitor vaccination coverage, identify poten tial barriers to vaccination, and increase vaccination coverage to levels similar to those for other recommended infari vaccines. In addition, health-care providers should remai vigilant in following the ACIP-recommended vaccinatio schedule for rotavirus vaccine and are reminded to repor 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 : Columbia Dept of Health; KS Enger, MPH, Michigan Dept of Com munity Health; K White, MPH, Minnesota Dept of Health; B Wehra Montana Dept of Public Health and Human Svcs; J Gaudino, MD Oregon Dept of Human Svcs; and E Belongia, MD, Vaccine Sater Datalink, CDC.

References 1. CDC. Prevention of rotavirus gastroenteritis among infants and e

dren: recommendations of the Advisory Committee on Immunizate

Practices. MMWR 2006;55(No. RR-12). 2. Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception amer

infants given an oral rotavirus vaccine. N Engl J Med 2001:37

564–72. 3. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy o:

pentavalent human-bovine (WC3) reassortant rotavirus vacciné

N Engl J Med 2006;354:23–33. 4. CDC. Postmarketing monitoring of intussusception after Rota Teq

vaccination-United States, February 1, 2006-February 15, 2017

MMWR 2007;56:218-22. 5. Haber P, Patel M, Hector IS, et al. Post-licensure monitoring of inte

susception 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.

7. CDC. Influenza vaccination coverage among children aged 6-23

months—six immunization information system sentinel sites, United

States, 2006–07 influenza season. MMWR 2007;56:963–5. 3. Chen RT, DeStefano F, Davis RL, et al. The Vaccine Safety Datalink:

immunization research in health maintenance organizations in the

USA. Bull World Health Organ 2000;78:186–94. --). Chen RT, Glasser JW, Rhodes PH, et al. The Vaccine Safety Datalink

project: a new tool for improving vaccine safety monitoring in the

United States. Pediatrics 1997;99:765–73. ). Khare M, Piccinino L, Barker LE, Linkins RW. Assessment of immu

nization registry databases as supplemental sources of data to improve ascertainment of vaccination coverage estimates in the National Immunization Survey. Arch Pediatr Adolesc Med 2006;160:838–42.

for various research purposes, including fundamental studies of orthopoxviruses and use as a vector for the expression of foreign proteins (often antigens or immunomodulators) in eukaryotic cells and animal models. The widespread use of VACV for research has resulted in laboratory-acquired VACV infections, some requiring hospitalization. The current Advisory Committee on Immunization Practices (ACIP) guidelines recommend VACV vaccination for laboratory workers who handle cultures or animals contaminated or infected with nonhighly attenuated VACV strains or other orthopoxviruses that infect humans (2). This report describes five recent occurrences of laboratory-acquired VACV infections and exposure and underscores the need for

proper vaccination, laboratory safety, infection-control practices, and rapid medical evaluation of exposures in the context of orthopoxvirus research.

Laboratory-Acquired Vaccinia
Exposures and Infections

United States, 2005-2007
- The last case of naturally acquired smallpox disease, caused

, the orthopoxvirus variola virus (VARV), occurred in -977, and the last laboratory-acquired case occurred in

278. Smallpox was eradicated largely as the result of a Corldwide vaccination campaign that used the related thopoxvirus, vaccinia virus (VACV), as a live virus vacne. Routine childhood vaccination for smallpox in the -nited States was terminated by 1972, but vaccination Ontinues or has been reintroduced for specific groups, Icluding laboratory workers who may be exposed to thopoxviruses, members of the military, selected healthire workers, and first responders. Severe complications of ACV infection can occur, particularly in persons with nderlying risk factors, and secondary transmission of VACV so can occur (1). VACV is used in numerous institutions

Case Reports

During 2005–2007, five cases of laboratory-acquired VACV infection were reported to CDC from state health departments and health-care providers in the United States. No national surveillance system exists to track laboratoryrelated VACV exposures, and the five cases were reported to CDC informally in the course of seeking consultation on treatment and prevention. All five cases involved the Western Reserve (WR) vaccinia strain. Cases 1-4 involved recombinant VACVs with an insertion at the thymidine kinase (TK) locus. Case 5 also involved a recombinant VACV, but details of the virus are not known (Table).

Case 1. In March 2005, a laboratory worker at an academic institution in Connecticut experienced a needlestick

ABLE. Characteristics of laboratory-acquired vaccinia virus (VACV) cases — United States, 2005–2007

Time from

incident to Location of vaccination


Type of


initial State a se


recommendations? strain vaccinia virus medical care medical care Connecticut Twice, most recently Questionable; due Western Recombinant,

3 days Occupational 10 years prior for revaccination Reserve insert in Tkt locus

health clinic Pennsylvania No previous vaccination No; declined

Western Recombinant,

6 days

Health-care vaccination Reserve insert in TK locus

provider lowa No previous vaccination No; declined

Western Recombinant,

11 days

Emergency vaccination Reserve insert in TK locus

department Maryland 6 years prior; no take No; failed take;

Western Recombinant,

Same day Occupational no follow-up

insert in TK locus

health clinic vaccination New Hampshire No previous vaccination No; declined

Western Recombinant,

8 days

Emergency vaccination Reserve details not known

department Advisory Committee on Immunization Practices. Vaccinia vaccine is recommended for laboratory workers who directly handle cultures or animals nfected with nonhighly attenuated vaccinia viruses. Revaccination is recommended at least every 10 years. CDC. Vaccinia (smallpox) vaccine: ecommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR 2001;50(No. RR-10). Thymidine kinase.

to a finger while injecting mice with recombinant VACV. The laboratory worker was admitted to a hospital 3 days later with fever, lymphadenopathy, lymphangitis, and a hemorrhagic bulla at the site of the injury. The laboratory worker had been vaccinated with VACV as a child, and a second time approximately 10 years before the incident. Symptoms improved rapidly, and the laboratory worker was released after one night in the hospital. Infection with an orthopoxvirus was confirmed by testing in the state's Laboratory Response Network (LRN) laboratory.

Case 2. In October 2006, a laboratory worker at an academic institution in Pennsylvania experienced a needlestick injury on the thumb while injecting a mouse with a recombinant WR VACV strain. The laboratory worker had previously declined VACV vaccination. Six days after the incident, the laboratory worker sought medical care, with a primary lesion at the site of the inoculation and a secondary lesion near the thumbnail. Nine days after inoculation, the laboratory worker reported malaise, and on the following day, had a fever of 102.0°F (38.9°C) and lymphadenopathy. By day 13, the laboratory worker was feeling better; on day 14, a surgeon debrided the lesion near the thumbnail. VACV infection was confirmed by polymerase chain reaction and viral culture at CDC.

Case 3. In May 2007, a laboratory worker at an academic institution in Iowa who had no previous history of VACV vaccination was unsheathing a sterile needle and received a needlestick in a finger. The laboratory worker continued with the experiments, which involved two recombinant VACVs, and did not change gloves or wash hands until finished. The typical challenge dose for this set of experiments was 3 x 106 plaque-forming units (pfu). Approximately 11 days after the needlestick, the laboratory worker developed symptoms of VACV infection, including fever and chills, and noted a lesion and swelling at the site of the needlestick. The laboratory worker sought medical attention at an urgent-care facility and informed the clinical staff of the incident. A diagnosis of VACV infection was confirmed by the state LRN laboratory. The laboratory worker recovered fully.

Case 4. In August 2007, a laboratory worker at a government facility in Maryland unintentionally inoculated a finger with approximately 5 uL of a solution containing VACV, after injection of a research animal. The inoculum contained up to 104 pfu of the virus, which was a recombinant strain of WR VACV. The laboratory worker did not wash the exposed area immediately, but instead immersed the wound in a disinfectant containing hypochlorite for a few minutes.

The laboratory worker had received a primary VACV vacci nation in 2001, but immunization was unsuccessful (i.c. no lesion developed at the site of the vaccination). On th: day of the incident, the laboratory worker went to the okcupational health clinic and was revaccinated with VAC). Vaccinia immunoglobulin was not administered. When th: worker was reevaluated on days 3, 4, and 5 postvaccination, no evidence of VACV infection was observed at the site of inoculation, and a characteristic lesion developed a the site of vaccination, evidence of a take.

Case 5. In September 2007, a laboratory worker at an academic institution in New Hampshire who had no his tory of vaccination incurred a minor scratch to a finger with a small-gauge needle containing 5 x 104 pfu/mL of recombinant WR VACV, which was being used for injecting mit The laboratory worker felt pain, but did not bleed, and so continued working. Seven days later, the laboratory worke noted a pustule at the site of the scratch, sought medical attention the following day, and was hospitalized when red streaking appeared from the site of the scratch and extende. into the axilla. Samples from the pustule were submitte. to the state LRN laboratory, where VACV infection wa confirmed. The laboratory worker was afebrile and recor. ered without specific therapy. Reported by: R Melchreit, MD, Connecticut Dept of Public Healt F Lewis, MD, Philadelphia Dept of Public Health, Pennsylvani. P Quinlisk, MD, K Soyemi, MD, Iowa Dept of Public Health; L Desjard: PhD, Univ of lowa Hygienic Laboratory; LV Kirchhoff, MD, Unu Iowa. EA Talbot, MD, Dartmouth Medical School; C Bean, PhD, V. Hampshire Dept of Health and Human Svcs. ) Schmitt, MD, Nation Institutes of Health. M Reynolds, PhD, W Davidson, MPH, S Smith, Y Li, PhD, I Damon, MD, PhD, Div of Viral and Rickettsial Disease National Center for Zoonotic, Vector-Borne, and Enteric Disease. A MacNeil, PhD, D Dufficy, DVM, EIS officers, CDC. Editorial Note: Although laboratory-related VACV expe sures are rare, the cases described in this report demor . strate the need for laboratory workers to comply with ACH vaccination recommendations (3,4). The total number ct laboratories or researchers using nonhighly attenuatedVACV strains is unknown; therefore, estimating the inu dence of VACV infection among at-risk laboratory worker is not possible. However, CDC does continue to recei: reports of laboratory-related VACV exposures (fewer thai five per year).

Laboratory-acquired exposure to VACV can lead to severe or atypical infections; exposures can be associated with a high inoculum or can occur through a route that has a high risk of complications, such as ocular VACV infection (5). Recombinant strains of VACV are common

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