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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 zaboratory workers might perceive TK insertion mutants as

ttenuated; 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, kecombinant strains of VACV commonly encode foreign ene products, and the possibility exists that resultant

ecombinant strains might have increased pathogenicity in mumans. C ACIP currently recommends VACV vaccination at least

very 10 years for laboratory workers who handle cultures ir animals infected with nonhighly attenuated erthopoxviruses (2), including the WR strain of VACV. easons the five persons described in this report failed to heet 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 formuition, which results in local infection at a predetermined te on the body, and resultant memory-immune response n subsequent exposure. Laboratory workers should adhere ) the vaccination schedule recommended by ACIP (2). ersons who have a contraindication to VACV vaccination hould consider carefully the possible consequences of a iboratory-acquired VACV infection in their decisions to 'ork with nonhighly attenuated VACV.

Laboratory directors, research staff, and institutional iosafety officials can further minimize the likelihood of nadvertent VACV exposure by reinforcing proper laborapry safety procedures, such as proper use of personal proctive equipment and safe needle-handling practices when andling VACV-infected cultures or animals. When a potential exposure occurs, the laboratory worker hould immediately and thoroughly wash the affected body art with water and the available cleaning product sanconed by their biosafety office; eyewash protocols should : followed for ocular exposures. The laboratory worker hould 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 clini

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

cination 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.

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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

Composition of the 2008–09 Influenza
Vaccine

The Food and Drug Administration's Vaccines an Related Biological Products Advisory Committee recommended that the 2008-09 trivalent influenza vaccine fo 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 thre: components from the 2007–08 influenza vaccine formula tion used in the United States. These recommendatior. were based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, post-vaccination serolog studies in humans, and the availability of candidate vaccine strains and reagents.

* 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.

Antigenic Characterization

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

ollaborating laboratories in the United States: 290 nfluenza A (H1N1), 161 influenza A (H3N2), and 157 afluenza B viruses. A total of 200 (69%) of 290 influenza (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 HiNl 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 he B/Victoria lineage were characterized as B/Malaysia/ 506/2004-like, the influenza B component of the 20078 influenza vaccine. One hundred forty-nine (95%) of ne 157 influenza B viruses characterized belong to the /Yamagata lineage.

State-Specific Activity Levels

During the week ending April 5, 2008, influenza activity was reported as widespreadTMS 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

Sutpatient Illness Surveillance
For the week ending April 5, 2008, the percentage

of utpatient visits for influenza-like illness (ILI)S 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 le 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 ecember 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

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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. SI 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. SS 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.

Defined as a temperature of 100.0°F (237.8°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.

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Network (NVSN). During November 4, 2007–March 2 2008, the preliminary laboratory-confirmed influenza associated hospitalization rate reported by NVSN for chidren aged 0-4 years was 5.61 per 10,000. During September 30, 2007–March 29, 2008, EIP sites reported a preliminary laboratory-confirmed influenza-associated hospitalization rate of 1.32 per 10,000 for children aged 0–17 years. For children aged 0-4 years, the rate was 3.11 per 10,000, and for children aged 5–17 years, the rate was 0.45 per 10,000. Differences in the rate estimates between the NVSN and the EIP systems likely result from the di ferent case-finding methods and the different population monitored.***

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*As of April 5, 2008. * 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 speciments 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. $. 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 national baseline for regional data is not appropriate.

Pneumonia and Influenza-Related
Mortality

Pneumonia and influenza (P&I) was listed as an under lying or contributing cause of death for 8.9% of all death reported through the 122 Cities Mortality Reporting System for the week ending April 5, 2008. This percentage was above the epidemic threshold of 6.9% for the week and marked the thirteenth consecutive week that the preportion of all deaths attributed to P&I was above the epi: demic threshold (Figure 4). The proportion of deaths from P&I exceeded the epidemic threshold during week ending January 5 and peaked at 9.1% during the week endir: March 15.

FIGURE 3. Estimated influenza activity levels reported by state epidemiologists, by state and level of activity – United States, week ending April 5, 2008

Influenza-Related Pediatric Mortality

During September 30, 2007–April 5, 2008, a total o 65 pediatric deaths among children aged <18 years assoc

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NVSN conducts surveillance in Monroe County, New York; Hamilton Cour Ohio; and Davidson County, Tennessee. NVSN provides population-base. estimates of laboratory-confirmed influenza hospitalization rates in children aged <5 years admitted to NVSN hospitals with fever or respiratory symptora Children are prospectively enrolled, and respiratory samples are collected 1.2 tested by viral culture and reverse transcription-polymerase chain reactie" (RT-PCR). EIP conducts surveillance in 60 counties associated with 12 metropolitan areas: San Francisco, California; Denver, Colorado; New Haver Connecticut; Atlanta, Georgia; Baltimore, Maryland; Minneapolis/St. I'd Minnesota; Albuquerque, New Mexico; Las Cruces, New Mexico; Alban New York; Rochester, New York; Portland, Oregon; and Nashville, Tenness EIP conducts surveillance for laboratory-confirmed, influenza-relare: hospitalizations in persons aged <18 years. Hospital laboratory and admission databases and infection-control logs are reviewed to identify children with a positive influenza test (i.e., viral culture, direct fluorescent antibody aways. RT-PCR, or a commercial rapid antigen test) from testing conducted as a par

of their routine care. # The expected seasonal baseline proportion of P&I deaths reported by the 12?

Cities Mortality Reporting System is projected using a robust regresar procedure in which a periodic regression model is applied to the observat percentage of deaths from P&I that occurred during the preceding 1 years The epidemic threshold is 1.645 standard deviations above the seasonal baseline.

* 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) locat 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) regionat

. 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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also has been detected, but at a lower level. Of 729 influenza A (H1N1) viruses tested, 81 (11.1%) were resistant to adamantanes. The adamantanes have no activity against influenza B viruses.

Based on the level of oseltamivir resistance observed in only one influenza A subtype (H1N1), persisting high levels of resistance to adamantanes in A (H3N2) viruses, and the predominance of A (H3N2) viruses circulating in the United States during the 2007–08 season with cocirculation of influenza B viruses, CDC continues to recommend the use of oseltamivir and zanamivir for the treatment or chemoprophylaxis of influenza (2). Use of amantadine or rimantadine is not recommended. Reported by: World Health Organization Collaborating Center for Surveillance, Epidemiology and Control of Influenza; C Dao, MPH, L Blanton, MPH, S Epperson, MPH, L Brammer, MPH, L Finelli, DrPH, T Wallis, MS, T Uyeki, MD, J Bresee, MD, A Klimov, PhD, N Cox, PhD, Influenza Div, National Center for Immunization and Respiratory Diseases, CDC Editorial Note: By some indicators, this influenza season has been more severe than the previous three seasons. Influenza activity in the United States remained low until January, peaked in mid-February, and decreased thereafter. For the week ending April 5, 2008, widespread activity was reported in six states, and regional activity was reported in 11 states, a decrease from mid-February, when 49 states reported widespread activity and one state reported regional activity. During peak activity of the previous three influenza seasons, the number of states reporting widespread or regional activity ranged from 41 to 49 states. During the 2007–08 season, the percentage of outpatient visits for ILI peaked at 5.9%, exceeded the national baseline for 13 consecutive weeks, and declined to 1.7% during the week ending April 5. During the previous three influenza seasons, the peak percentage of visits for ILI ranged from 3.2% to 5.4% and exceeded baseline levels for 14 to 16 consecutive weeks. To date, the percentage of deaths attributable to P&I peaked at 9.1% and exceeded the epidemic threshold for 13 consecutive weeks this season. For the week ending April 5, the proportion of deaths attributable to P&I was 8.9%. During the previous three seasons, the peak percentage of deaths attributable to P&I ranged from 7.7% to 8.9%, and the total number of weeks above the epidemic threshold ranged from 1 to 11 consecutive weeks. P&I mortality is higher this season than the previous three seasons, which were mild. The 2007-08 season is similar to the 2003–04 season, when the percentage of deaths attributable to P&I peaked at 10.4% and the number of consecutive weeks above the epidemic threshold was 9 weeks.

esistance to Antiviral Medications During this influenza season, an increase in the number influenza viruses resistant to the neuraminidase inhibior, oseltamivir, has been observed. Among the 1,153 Ifluenza A and B viruses tested during the 2007–08 fluenza season, to date, 84 (8.3%) have been found to be sistant to oseltamivir. All the oseltamivir-resistant viruses ave been influenza A (H1N1) viruses and have been etermined to share the same genetic mutation that conrs oseltamivir resistance. These 84 viruses represent 10.2% the 824 influenza A (H1N1) viruses that have been sted, an increase from four (0.7%) of 588 influenza A I1N1) viruses tested during the 2006–07 season. No sistance to oseltamivir has been identified among the 194 fluenza A (H3N2) or the 135 influenza B viruses tested, id no antiviral resistance to zanamivir has been detected

any influenza A or B viruses. Resistance to adamantanes mantadine and rimantadine) continues to be high among fluenza A viruses. Of 261 influenza A (H3N2) viruses sted, 260 (99.6%) were resistant to adamantanes. damantane resistance among influenza A (H1N1) viruses

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