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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.

9. 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 immunization registry databases as supplemental sources of data to improve 1 ascertainment of vaccination coverage estimates in the National Immunization Survey. Arch Pediatr Adolesc Med 2006;160:838-42.

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 978. Smallpox was eradicated largely as the result of a orldwide 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, cluding laboratory workers who may be exposed to thopoxviruses, members of the military, selected healthɩre 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

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.

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

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dvisory Committee on Immunization Practices. Vaccinia vaccine is recommended for laboratory workers who directly handle cultures or animals fected 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). hymidine kinase.

Western Reserve

8 days

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 × 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 μL 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 vaccination in 2001, but immunization was unsuccessful (i... no lesion developed at the site of the vaccination). On the day of the incident, the laboratory worker went to the oc cupational health clinic and was revaccinated with VAC Vaccinia immunoglobulin was not administered. When the 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 at 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 recom binant WR VACV, which was being used for injecting mic The laboratory worker felt pain, but did not bleed, and 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 rec streaking appeared from the site of the scratch and extende into the axilla. Samples from the pustule were submitted to the state LRN laboratory, where VACV infection wa confirmed. The laboratory worker was afebrile and recovered without specific therapy.

Reported by: R Melchreit, MD, Connecticut Dept of Public Healt F Lewis, MD, Philadelphia Dept of Public Health, Pennsylvan P Quinlisk, MD, K Soyemi, MD, Iowa Dept of Public Health; L DesJard PhD, Univ of Iowa Hygienic Laboratory; LV Kirchhoff, MD, Unu & Iowa. EA Talbot, MD, Dartmouth Medical School; C Bean, PhD, No. Hampshire Dept of Health and Human Svcs. J Schmitt, MD, Nationa Institutes of Health. M Reynolds, PhD, W Davidson, MPH, S Smith, M 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 ACli vaccination recommendations (3,4). The total number e laboratories or researchers using nonhighly attenuated VACV strains is unknown; therefore, estimating the inc dence of VACV infection among at-risk laboratory worker is not possible. However, CDC does continue to receiv reports of laboratory-related VACV exposures (fewer tha 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 tha has a high risk of complications, such as ocular VAC infection (5). Recombinant strains of VACV are common

enerated by insertion of genetic material in the TK locus of the virus. Because inactivation of the TK locus has been ssociated with decreased VACV virulence in mice (6), some aboratory workers might perceive TK insertion mutants as attenuated; however, at least four of the infections and ttendant illnesses described in this report involved VACV trains that had insertions at the TK locus. Additionally, ecombinant strains of VACV commonly encode foreign ene products, and the possibility exists that resultant ecombinant strains might have increased pathogenicity in

umans.

ACIP currently recommends VACV vaccination at least very 10 years for laboratory workers who handle cultures r animals infected with nonhighly attenuated rthopoxviruses (2), including the WR strain of VACV. Reasons the five persons described in this report failed to neet ACIP recommendations included refusal of vaccinaon, absence of follow-through on a failed vaccination take, nd overdue revaccination. Because some laboratory workrs are hesitant to receive VACV vaccination for fear of side ffects, laboratory directors and occupational health prorams are encouraged to provide education regarding the sks and potential benefits of vaccination, including, for he latter, the prevention or reduction of severe complicaons from laboratory-acquired VACV infection. This benfit accrues from receiving a carefully measured (rather than ndetermined) dose of a well-characterized vaccine formution, which results in local infection at a predetermined te on the body, and resultant memory-immune response n subsequent exposure. Laboratory workers should adhere o the vaccination schedule recommended by ACIP (2). ersons who have a contraindication to VACV vaccination hould consider carefully the possible consequences of a boratory-acquired VACV infection in their decisions to ork with nonhighly attenuated VACV.

Laboratory directors, research staff, and institutional osafety officials can further minimize the likelihood of advertent VACV exposure by reinforcing proper laborary safety procedures, such as proper use of personal proctive equipment and safe needle-handling practices when indling VACV-infected cultures or animals.

When a potential exposure occurs, the laboratory worker ould immediately and thoroughly wash the affected body rt with water and the available cleaning product sanconed by their biosafety office; eyewash protocols should followed for ocular exposures. The laboratory worker ould then report the incident and strain to which they ight have been exposed to the laboratory director and

the occupational health clinic of the institution. VACV vaccination shortly after an exposure might help minimize the effects of inadvertent VACV infection. If severe illness or ocular infection occur, arrangements can be made with CDC for the administration of vaccinia immunoglobulin (2,3). The laboratory worker in case 4 immediately disinfected the wound and received prompt postexposure vaccination the day of the laboratory incident; this might have contributed to preventing infection at the site of the needlestick.

Secondary spread of VACV represents an additional public health concern. Patients with suspected VACV infection should be instructed by their caregivers in appropriate lesion care (2) as a precaution against spread of infection to another body site or to another person. Special care must be taken to avoid transmission to social contacts and persons in the health-care setting, particularly those with increased risk for severe illness from exposure to VACV, such as persons with atopic dermatitis, pregnant females, and immunocompromised persons.

Finally, occupational health clinics and health-care workers who might provide primary care for a laboratory worker exposed to VACV should become familiar with protocols for recognition and diagnosis of suspected poxvirus infections (3). Laboratory workers also should be instructed to seek care from appropriately trained health-care providers at their supporting institution. Appropriate infectioncontrol measures should be instituted at the time of presentation of a patient with a suspected case, and whenever possible, clinical care should be provided by persons who have been vaccinated with VACV. Clinics also should review procedures for communication with and confirmation of orthopoxvirus infection through the LRN or the Poxvirus Program (404-639-4129) at CDC.

References

1. CDC. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions. MMWR 2006;55(No. RR-1).

2. CDC. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR 2001;50(No. RR-10).

3. CDC. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR 2003;52(No. RR-4).

4. CDC. Recommendations for using smallpox vaccine in a pre-event vaccination program. MMWR 2003;52(No. RR-7).

5. Lewis FM, Chernak E, Goldman E, et al. Ocular vaccinia infection in laboratory worker, Philadelphia, 2004. Emerg Infect Dis 2006;12: 134-7.

6. Lee MS, Roos JM, McGuigan LC, et al. Molecular attenuation of vaccinia virus: mutant generation and animal characterization. J Virol 1992;66:2617-30.

Update: Influenza Activity United States, September 30, 2007-April 5, 2008, and Composition of the 2008-09

Influenza Vaccine

This report summarizes U.S. influenza activity* since September 30, 2007, the start of the 2007-08 influenza season, and updates the previous summary (1). Low levels of influenza activity were reported from October through early December. Activity increased from mid-December and peaked in mid-February.

Viral Surveillance

During September 30, 2007-April 5, 2008, World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories in the United States reported testing 185,938 specimens for influenza viruses, and 34,380 (18.5%) tested positive (Figure 1). Of these, 25,456 (74.0%) were influenza A viruses, and 8,924 (26.0%) were influenza B viruses. A total of 7,715 (30.3%) of the 25,456 influenza A viruses have been subtyped: 2,110 (27.3%) were influenza A (H1N1) viruses, and 5,605 (72.7%) were influenza A (H3N2) viruses. The percentage of specimens testing positive for influenza first exceeded 10% during the week ending January 12 and peaked at 32.0% during the week ending February 16. For the week ending April 5, 13.2% of specimens tested for influenza were positive. Although influenza A (H1N1) viruses predominated through mid-January, the proportion of reported influenza viruses that were A (H3N2) viruses increased rapidly during January, and during the week ending January 26, influenza A (H3N2) became the predominant virus for the season overall.

This season, more influenza A viruses than influenza B viruses have been identified in all surveillance regions. However, for weeks 13 and 14 (March 23-April 5), more influenza B than influenza A viruses were reported. Among

*The CDC influenza surveillance system collects five categories of information from 10 data sources. Viral surveillance: U.S. World Health Organization collaborating laboratories, the National Respiratory and Enteric Virus Surveillance System, and novel influenza A virus case reporting. Outpatient illness surveillance: U.S. Influenza Sentinel Provider Surveillance Network and the U.S. Department of Veterans Affairs/U.S. Department of Defense BioSense Outpatient Surveillance System. Mortality: 122 Cities Mortality Reporting System and influenzaassociated pediatric mortality reports. Hospitalizations: Emerging Infections Program and New Vaccine Surveillance Network. Summary of geographic spread of influenza: state and territorial epidemiologist reports.

* Data as of April 5, 2008.

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Composition of the 2008-09 Influenza
Vaccine

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recom mended that the 2008-09 trivalent influenza vaccine for the United States contain A/Brisbane/59/2007-lik (H1N1), A/Brisbane/10/2007-like (H3N2), and B/Florida 4/2006-like viruses. This represents a change in all three components from the 2007-08 influenza vaccine formula tion used in the United States. These recommendations were based on antigenic analyses of recently isolated influ enza viruses, epidemiologic data, post-vaccination serolog studies in humans, and the availability of candidate vaccine strains and reagents.

Antigenic Characterization

States are requested to submit a subset of their influenza virus isolates to CDC for further antigenic characteriza tion. Since September 30, 2007, CDC has antigenically characterized 608 influenza viruses submitted by WHO

Follaborating laboratories in the United States: 290 fluenza A (H1N1), 161 influenza A (H3N2), and 157 fluenza B viruses. A total of 200 (69%) of 290 influenza A(H1N1) viruses were characterized as A/Solomon Islands/ /2006-like, the influenza A (H1N1) component of the 007-08 influenza vaccine for the Northern Hemisphere, nd 70 (24%) were characterized as A/Brisbane/59/2007ke, the recommended H1N1 component of the 2008– 9 Northern Hemisphere vaccine. Thirty-five (22%) of the 61 influenza A (H3N2) viruses were characterized as /Wisconsin/67/2005-like, the influenza A (H3N2) comonent of the 2007-08 influenza vaccine for the Northern lemisphere. One hundred fifteen (71%) of the 161 ruses were characterized as A/Brisbane/10/2007-like, the commended influenza A (H3N2) component for the 2008 outhern Hemisphere and 2008–09 Northern Hemisphere accines. Influenza B viruses currently circulating can be ivided into two antigenically distinct lineages represented y B/Victoria/02/87 and B/Yamagata/16/88. Eight (5%) f the 157 influenza B viruses characterized belong to the Victoria lineage of viruses. Six (75%) of these viruses from e B/Victoria lineage were characterized as B/Malaysia/ 506/2004-like, the influenza B component of the 2007– 8 influenza vaccine. One hundred forty-nine (95%) of e 157 influenza B viruses characterized belong to the Yamagata lineage.

Outpatient Illness Surveillance

For the week ending April 5, 2008, the percentage of utpatient visits for influenza-like illness (ILI) reported y approximately 1,400 U.S. sentinel providers in 50 ates, Chicago, the District of Columbia, New York City, nd the U.S. Virgin Islands was 1.7%, which was below e national baseline of 2.2%. This season, the percentage f outpatient visits for ILI exceeded the national baseline or 13 consecutive weeks. The percentage of outpatient viss for ILI first exceeded baseline during the week ending December 29 and peaked at 5.9% during the week ending ebruary 16. The percentage of outpatient visits for acute spiratory illness (ARI)** reported by approximately 350

Defined as a temperature of ≥100.0°F (≥37.8°C), oral or equivalent, and cough and/or sore throat, in the absence of a known cause other than influenza. The national and regional baselines are the mean percentage of visits for ILI during noninfluenza weeks for the previous three seasons plus two standard deviations. A noninfluenza week is a week during which <10% of specimens tested positive for influenza. National and regional percentages of patient visits for ILI are weighted on the basis of state population. Use of the national baseline for regional data is not appropriate.

Based on International Classification of Diseases, Ninth Revision codes for ARI: 460-66 and 480-88.

U.S. Department of Defense (DoD) and 800 Department of Veterans Affairs (VA) BioSense outpatient treatment facilities for the week ending April 5 was 2.2%, which was below the national baseline of 3.2% (Figure 2).

State-Specific Activity Levels

During the week ending April 5, 2008, influenza activity was reported as widespread" in six states (Connecticut, Maine, Maryland, New York, Pennsylvania, and Vermont) (Figure 3). In addition, regional activity was reported by 11 states (Alaska, California, Colorado, Hawaii, Illinois, Iowa, Massachusetts, New Jersey, North Dakota, Oregon, and Washington); local influenza activity was reported by 23 states (Alabama, Arizona, Georgia, Idaho, Indiana, Kentucky, Louisiana, Michigan, Minnesota, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Carolina, Ohio, Rhode Island, South Carolina, South Dakota, Texas, Utah, Virginia, and Wyoming); and sporadic activity was reported by the District of Columbia and 10 states (Arkansas, Delaware, Florida, Kansas, Mississippi, Missouri, Oklahoma, Tennessee, West Virginia, and Wisconsin). Activity peaked during weeks 7 and 8 (February 10-23), when 49 states reported widespread influenza activity and one state reported regional activity.

Influenza-Associated Pediatric
Hospitalizations

Pediatric hospitalizations associated with laboratoryconfirmed influenza infections are monitored by two population-based surveillance networks, the Emerging Infections Program (EIP) and the New Vaccine Surveillance

BioSense is a national surveillance system that receives, analyzes, and evaluates health data from multiple sources, include 1) approximately 1,150 VA/DoD hospitals and ambulatory-care clinics; 2) multihospital systems, local hospitals, and state and regional syndromic surveillance systems in 37 states; and 3) Laboratory Corporation of America (LabCorp) test results.

$ The national, regional, and age-specific baselines are the mean percentage of visits for ARI during noninfluenza weeks for the previous three seasons plus two standard deviations. A noninfluenza week is a week during which <10% of specimens tested positive for influenza. Use of a national baseline for regional data is not appropriate.

Levels of activity are 1) no activity, 2) sporadic: isolated laboratory-confirmed influenza cases or a laboratory-confirmed outbreak in one institution, with no increase in activity; 3) local: increased ILI, or at least two institutional outbreaks (ILI or laboratory-confirmed influenza) in one region with recent laboratory evidence of influenza in that region (virus activity no greater than sporadic in other regions); 4) regional: increased ILI activity or institutional outbreaks (ILI or laboratory-confirmed influenza) in at least two but less than half of the regions in the state with recent laboratory evidence of influenza in those regions; and 5) widespread: increased ILI activity or institutional outbreaks (ILI or laboratory-confirmed influenza) in at least half the regions in the state with recent laboratory evidence of influenza in the state.

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