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Update: Influenza Activity --- United States and Worldwide, 2005--06 Season, and Composition of the 2006--07 Influenza Vaccine

During the 2005--06 influenza season, influenza A (H1N1), A (H3N2), and B viruses cocirculated worldwide. In the United States, influenza A (H3N2) viruses predominated overall, but influenza B viruses were isolated more frequently than influenza A viruses late in the season. Influenza activity in the United States peaked in early March, and the number of pneumonia and influenza deaths did not exceed the epidemic threshold. Worldwide, influenza B viruses were the most commonly reported influenza type in Europe; influenza A (H1N1) and influenza B viruses predominated in Asia. Through June 13, 2006, outbreaks of influenza A (H5N1) viruses (avian influenza) among migratory birds and poultry flocks were associated with severe human illness or death in 10 countries (Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey, and Vietnam). This report summarizes influenza activity in the United States and worldwide during the 2005--06 influenza season and describes composition of the 2006--07 influenza vaccine.

United States

The national percentage of respiratory specimens testing positive for influenza and the proportion of outpatient visits to sentinel providers for influenza-like illness (ILI)* peaked in early March 2006. Influenza A (H3N2) viruses were most commonly isolated overall, but influenza B viruses were more frequently identified than influenza A viruses during late April and May. A small number of influenza A (H1N1) viruses also were identified.

Viral Surveillance

During October 2, 2005--May 20, 2006, World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System collaborating laboratories in the United States tested 139,647 specimens for influenza viruses, and 17,414 (12.5%) were positive (Figure 1). Of these, 14,093 (80.9%) were influenza A viruses, and 3,321 (19.1%) were influenza B viruses. Among the influenza A viruses, 5,661 (40.2%) were subtyped; 5,231 (92.4%) of those were influenza A (H3N2) viruses, and 430 (7.6%) were influenza A (H1N1) viruses. The proportion of specimens testing positive for influenza first exceeded 10% during the week ending December 24, 2005 (week 51), peaked at 23.0% during the week ending March 11, 2006 (week 10), and declined to <10% during the week ending April 29, 2006 (week 17), for a total of 18 consecutive weeks during which more than 10% of specimens tested positive. Peak percentage of specimens testing positive for influenza ranged from 23.2% to 41.0% during the preceding five influenza seasons, and the peak occurred during early December to late February ([1]; CDC, unpublished data, 2006). Also during the preceding five seasons, the number of consecutive weeks during which more than 10% of specimens tested positive for influenza ranged from 11 to 15 weeks (CDC, unpublished data, 2006).

Composition of the Influenza Vaccine for the 2006--07 Season

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee has recommended that the 2006--07 trivalent influenza vaccine for the United States contain A/New Caledonia/20/99-like (H1N1), A/Wisconsin/67/2005-like (H3N2), and B/Malaysia/2506/2004-like viruses. This represents a change in the influenza A (H3N2) and influenza B components. For the A/Wisconsin/67/2005-like (H3N2) virus, U.S. vaccine manufacturers can use A/Wisconsin/67/2005 or the antigenically equivalent A/Hiroshima/52/2005 strain. For the influenza B component, either the B/Malaysia/2506/2004 or B/Ohio/1/2005 strain can be used. This recommendation is based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, and postvaccination serologic studies in humans.

Antigenic Characterization

Since October 1, 2005, CDC has antigenically characterized 828 influenza viruses collected by U.S. laboratories: 503 influenza A (H3N2) viruses, 88 influenza A (H1N1) viruses, and 237 influenza B viruses. Of the 503 influenza A (H3N2) viruses, 381 (75.7%) were characterized as A/California/07/2004-like, the influenza A (H3N2) component recommended for the 2005--06 influenza vaccine, and 122 (24.3%) viruses demonstrated reduced titers with antisera produced against A/California/07/2004. Of the 122 low-reacting viruses, 96 were tested with antisera produced against A/Wisconsin/67/2005, the H3N2 component selected for the 2006--07 vaccine, and 70 were A/Wisconsin-like. The hemagglutinin proteins of 85 (96.6%) of the 88 influenza A (H1N1) viruses were antigenically similar to the hemagglutinin of the vaccine strain A/New Caledonia/20/99, and three (3.4%) showed reduced titers with antisera produced against A/New Caledonia/20/99. Influenza B viruses currently circulating can be divided into two antigenically distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87 viruses. Fifty-two (21.9%) of the 237 influenza B viruses that have been characterized belong to the B/Yamagata lineage; eight were similar to B/Shanghai/361/2002, the recommended influenza B component for the 2005--06 influenza vaccine, 43 were characterized as B/Florida/07/2004-like (a minor antigenic variant of B/Shanghai/361/2002), and one showed reduced titers with antisera produced against both B/Shanghai/361/2002 and B/Florida/07/2004. A total of 185 (78.1%) of the 237 influenza B viruses were identified as belonging to the B/Victoria lineage; 184 were similar to B/Ohio/1/2005, the influenza B component selected for the 2006--07 vaccine, and one showed reduced titers with antisera produced against B/Ohio/1/2005.

ILI Surveillance

The weekly percentage of patient visits to U.S. sentinel providers for ILI exceeded baseline levels (2.2%) during the weeks ending December 17, 2005--April 1, 2006 (weeks 50--13) and peaked twice, once at 3.3% for the week ending December 31, 2005 (week 52), and again at 3.2% for the week ending March 4, 2006 (week 9) (Figure 2). During the preceding five influenza seasons, the peak percentage of patient visits for ILI ranged from 3.2% to 7.6%, and the peak occurred during late December to mid-February ([1]; CDC, unpublished data, 2006).

State-Specific Activity Levels

Influenza activity, as reported by state and territorial epidemiologists, peaked during the week ending March 11, 2006 (week 10), when 25 states reported widespread activity and 16 states reported regional activity.§ Thirty-eight states and New York City reported widespread influenza at least once during the 2005--06 season. No states reported widespread influenza activity during the weeks ending April 22--May 20, 2006 (weeks 16--20). The peak number of states reporting widespread or regional activity during the preceding five influenza seasons ranged from 45 to 50 states ([1]; CDC, unpublished data, 2006).

Pneumonia- and Influenza-Related Mortality

During the 2005--06 influenza season, the percentage of deaths attributed to pneumonia and influenza (P&I) as reported by the 122 Cities Mortality Reporting System did not exceed the epidemic threshold (Figure 3). The percentage of P&I deaths peaked twice at 7.8%, once during the week ending January 14, 2006 (week 2), and again during the week ending March 18, 2006 (week 11). During the preceding five influenza seasons, the peak percentage of P&I deaths ranged from 8.1% to 10.4%, and the total number of weeks above the epidemic threshold ranged from 4 to 16 ([1]; CDC, unpublished data, 2006).

Influenza-Associated Pediatric Hospitalization

Pediatric hospitalizations associated with laboratory-confirmed influenza infections are monitored in two population-based surveillance networks, the Emerging Infections Program (EIP) and the New Vaccine Surveillance Network (NVSN). During October 1, 2005--April 30, 2006, the preliminary influenza-associated hospitalization rate reported by EIP for children aged 0--17 years was 1.21 per 10,000. For children aged 0--4 and 5--17 years, the rates were 2.76 and 0.38 per 10,000, respectively. In NVSN, during October 30, 2005--April 29, 2006, the preliminary laboratory-confirmed influenza-associated hospitalization rate for children aged 0--4 years was 5.4 per 10,000. EIP and NVSN hospitalization data collection ended on April 30, 2006. Rate estimates are preliminary and might change as data are finalized.

During 2000--2005, the end-of-season hospitalization rate for NVSN ranged from 3.7 (2002--03) to 12.0 (2003--04) per 10,000 children aged 0--4 years. During the 2003--04 influenza season, the end-of-season hospitalization rate for EIP was 8.9 per 10,000 children aged 0--4 years and 0.8 per 10,000 children aged 5--17 years; during the 2004--05 season, the rates were 3.3 and 0.6, respectively. Differences in rate estimates between the NVSN and the EIP systems likely result from the different case-finding methods and the different populations monitored.**

Influenza-Related Pediatric Mortality

During October 2, 2005--June 3, 2006, a total of 35 deaths among children aged <18 years associated with laboratory-confirmed influenza infections during the 2005--06 influenza season were reported to CDC from 13 states (Arizona, California, Colorado, Connecticut, Kansas, New Jersey, New Mexico, Oklahoma, Pennsylvania, Rhode Island, Vermont, Virginia, and Wyoming) and New York City. Four (11.4%) of the children were aged <6 months, 11 (31.4%) were aged 6--23 months, four (11.4%) were aged 2--4 years, and 16 (45.7%) were aged 5--17 years. Of the 31 patients for whom influenza virus type was known, 23 had influenza A virus infection and eight had influenza B virus infection. All eight pediatric deaths attributed to influenza B infection occurred from late March through May. These data are provisional and subject to change as more information becomes available.

Worldwide

During the 2005--06 influenza season, influenza A (H1N1), A (H3N2), and B viruses cocirculated worldwide. In Africa, small numbers of influenza A and B viruses were reported. In Asia, influenza A (H1N1) and influenza B viruses predominated. Influenza A (H3N2) viruses circulated at lower levels overall in Asia but predominated in some countries. In Europe, influenza B viruses were most commonly reported, but influenza A (H1N1) and A (H3N2) viruses also were identified frequently.

Human Infections with Avian Influenza A (H5N1) Viruses

During December 1, 2003--June 13, 2006, a total of 225 human cases of avian influenza A (H5N1) infection were reported to WHO from 10 countries (2). Of these, 128 (57%) were fatal (Table). All cases were reported from Asia (Azerbaijan, Cambodia, China, Indonesia, Iraq, Thailand, Turkey, and Vietnam) or Africa (Djibouti and Egypt). To date, no human case of avian influenza A (H5N1) virus infection has been identified in the United States.

Reported by: WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza. L Blanton, MPH, L Brammer, MPH, S Wang, MPH, A Postema, MPH, T Wallis, MS, D Shay, MD, J Bresee, MD, A Klimov, PhD, N Cox, PhD, Influenza Div (proposed), National Center for Immunization and Respiratory Diseases (proposed), CDC.

Editorial Note:

During the 2005--06 influenza season, influenza activity in the United States peaked in early March and excess mortality was not detected. In the United States, influenza A (H3N2) viruses predominated during most of the season, but influenza B viruses were more frequently identified than influenza A viruses during late April through May. Worldwide, influenza B viruses were reported most commonly in many European countries, and influenza A (H1N1) and influenza B viruses predominated in Asia.

In the United States, the majority of influenza A (H3N2) and A (H1N1) viruses were characterized as A/California/07/2004-like and A/New Caledonia/20/99, respectively, the recommended influenza A components of the 2005--06 influenza vaccine. In the early months of the season, the majority of influenza B isolates matched the B/Shanghai/361/2002 strain (or its minor antigenic variant B/Florida/07/2004), the recommended influenza B component for the 2005--06 vaccine; however, later in the season, the majority of influenza B isolates matched the B/Ohio/1/2005 strain. The B/Ohio/1/2005 virus has been selected as the influenza B component for the 2006--07 influenza vaccine.

As a supplement to influenza vaccination, antiviral drugs have aided in the control and prevention of influenza. However, the 2005--06 influenza season was notable because of the emergence of a high level of resistance among circulating influenza A (H3N2) viruses to the antiviral adamantanes (i.e., amantadine and rimantadine). Of 209 influenza A (H3N2) virus isolates collected from 26 states and sent to CDC during October 1--December 31, 2005, a total of 193 (92.3%) were resistant to adamantanes (3). On the basis of these findings, in January 2006, CDC recommended against use of the adamantane class of antivirals for the treatment and prophylaxis of influenza in the United States until susceptibility to adamantanes has been reestablished among circulating influenza A isolates (4). A high level of resistance to adamantanes (>90%) by influenza A (H3N2) viruses continued to be observed among specimens tested through May 2006.

As of June 13, 2006, influenza A (H5N1) had been reported in migratory birds or poultry flocks in Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Djibouti, Egypt, Niger, Nigeria, and Sudan), Asia (Afghanistan, Azerbaijan, Cambodia, China, Georgia, Hong Kong, Kazakhstan, India, Indonesia, Iraq, Iran, Israel, Jordan, Malaysia, Mongolia, Myanmar, Palestinian Autonomous Territories, Pakistan, Thailand, Turkey, and Vietnam), and Europe (Albania, Austria, Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Poland, Romania, Russia, Serbia-Montenegro, Slovakia, Slovenia, Sweden, Switzerland, Ukraine, and the United Kingdom) (5). The spread of the virus can be associated, in part, with the movement of wild migratory birds from Asia (6), suggesting that apparently healthy birds can carry the virus over long distances (7). No evidence of sustained person-to-person transmission of influenza A (H5N1) viruses has been reported to date, but rare cases of person-to-person transmission likely have occurred (8).

In collaboration with local and state health departments, CDC continues to recommend enhanced surveillance for possible influenza A (H5N1) infection among travelers with severe unexplained respiratory illness returning from influenza A (H5N1)-affected countries (9). Additional information on influenza, including avian influenza, is available at http://www.cdc.gov/flu. Updates on the worldwide avian influenza situation are available from WHO at http://www.who.int/csr/disease/avian_influenza/en.

Acknowledgments

This report is based, in part, on data contributed by participating state and territorial health departments and state public health laboratories, WHO collaborating laboratories, National Respiratory and Enteric Virus Surveillance System collaborating laboratories, the U.S. Influenza Sentinel Provider Surveillance System, the New Vaccine Surveillance Network, the Emerging Infections Program, and the 122 Cities Mortality Reporting System. WHO National Influenza Centers, WHO Global Influenza Programme, Geneva, Switzerland. I Gust, MD, A Hampson, WHO Collaborating Center for Reference and Research on Influenza, Parkville, Australia. A Hay, PhD, WHO Collaborating Center for Reference and Research on Influenza, National Institute of Medical Research, London, England. M Tashiro, MD, WHO Collaborating Center for Reference and Research on Influenza, National Institute of Infectious Diseases, Tokyo, Japan.

References

  1. CDC. Update: influenza activity---United States and worldwide, 2004--05 season. MMWR 2005;54:631--4.
  2. World Health Organization. Confirmed human cases of avian influenza A (H5N1). Geneva, Switzerland: World Health Organization; 2006. Available at http://www.who.int/csr/disease/avian_influenza/en.
  3. Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005--2006 influenza season in the United States. JAMA 2006;295:891--4.
  4. CDC. High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents---United States, 2005--06 influenza season. MMWR 2006;55:44--6.
  5. World Organisation for Animal Health. Update on avian influenza in animals (type H5). Paris, France: World Organisation for Animal Health; 2006.
  6. World Health Organization. Avian influenza---new areas with infection in birds (update 34). Geneva, Switzerland: World Health Organization; 2005.
  7. Chen H, Smith GJ, Li KS, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci USA 2006;103:2845--50.
  8. Ungchusak K, Auewarakul P, Dowell SF, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005; 352:333--40.
  9. CDC. CDC health update: updated interim guidance for laboratory testing of persons with suspected avian influenza A (H5N1) virus in the United States. Atlanta, GA: US Department of Health and Human Services, CDC; 2006. Available at http://www.phppo.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00246.

* Defined as a temperature of >100.0ºF (>37.8ºC), oral or equivalent, and cough and/or sore throat in the absence of a known cause other than influenza.

The national baseline was calculated as the mean percentage of patient visits for ILI during noninfluenza weeks for the preceding three influenza seasons, plus two standard deviations. Noninfluenza weeks are those in which <10% of laboratory specimens are positive for influenza. Wide variability in regional data precludes calculating region-specific baselines; therefore, applying the national baseline to regional data is inappropriate. National and regional percentages of patient visits for ILI are weighted on the basis of state population.

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

The expected seasonal baseline proportion of P&I deaths reported by the 122 Cities Mortality Reporting System is projected using a robust regression procedure in which a periodic regression model is applied to the observed percentage of deaths from P&I during the preceding 5 years. The epidemic threshold is 1.645 standard deviations above the seasonal baseline.

** NVSN provides population-based estimates of laboratory-confirmed influenza hospitalization rates in children aged <5 years admitted to NVSN hospitals with fever or respiratory symptoms. Children are prospectively enrolled, and respiratory samples are collected and tested by viral culture and reverse transcription--polymerase chain reaction (RT-PCR). EIP conducts surveillance for laboratory-confirmed, influenza-related hospitalizations in children 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 assay, RT-PCR, or a commercial rapid antigen test) from testing conducted as a part of their routine care.

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Table

Table 4
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