Update: Influenza Activity -- United States and Worldwide, 1996-97 Season, and Composition of the 1997-98 Influenza Vaccine

In collaboration with the World Health Organization (WHO), its international network of collaborating laboratories, and state and local health departments, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza viruses. This report summarizes surveillance for influenza in the United States and worldwide during the 1996-97 influenza season and describes the composition of the 1997-98 influenza vaccine. United States

Influenza activity began in October 1996, increased at the end of November, peaked during late December through early January 1997, and decreased slowly through March. The number of state and territorial epidemiologists who reported regional * or widespread activity peaked at 38 during the week ending January 4, 1997. Widespread activity was last reported for the week ending March 22; only two states (Alaska and Arizona) reported regional activity for the week ending April 5. The percentage of patient visits to sentinel physicians for influenza-like illness exceeded baseline levels (0-3%) for 5 consecutive weeks from December 1, 1996, through January 4, 1997, and peaked at 7% during the weeks ending December 14 and December 28.

From September 29, 1996, through April 5, 1997, WHO collaborating laboratories in the United States tested 35,623 specimens for respiratory viruses, and 6344 (18%) were positive for influenza. Of these, 5126 (81%) were influenza type A, and 1218 (19%) were type B (Figure_1). All of the subtyped influenza type A viruses were influenza A(H3N2). Influenza type A viruses predominated from October through the first week of February, but the number of influenza type B isolates began increasing during January and were more commonly reported than influenza type A after mid-February; 88% of all isolates during February 9-April 5, 1997, were influenza type B.

The proportion of deaths attributed to pneumonia and influenza (P&I) reported by 122 U.S. cities exceeded the epidemic threshold ** for 10 consecutive weeks from December 8, 1996, through February 15, 1997, before returning to baseline (Figure_2). This was the earliest sustained increase in P&I mortality since at least the 1986-87 influenza season, the earliest season for which these data were reviewed. Worldwide

Influenza activity was moderate to severe in the northern hemisphere from October 1996 through March 1997. Overall, influenza A(H3N2) viruses predominated in North America and Europe, but influenza type B was isolated frequently. In many countries, influenza type A viruses predominated during the early part of the season, but influenza type B isolates became more commonly isolated than influenza type A by the end of the season. Influenza type B predominated in most Asian countries, but epidemic influenza in Japan was due predominantly to influenza A(H3N2) viruses. Few laboratory-confirmed cases of influenza A(H1N1) were reported worldwide.

Influenza A(H3N2) viruses predominated in Canada, Colombia, Finland, France, Japan, Netherlands, Russia, Slovakia, Spain, and the United Kingdom. In Colombia, an influenza A(H3N2) epidemic during August-November was the most severe influenza epidemic reported in that country since the pandemic of 1968-69. Influenza A(H3N2) was the only influenza virus type/subtype reported in Greece and Poland. Influenza A(H3N2) activity also was reported in Bulgaria, China, French Guiana and Guadeloupe, Germany, Guam, Hong Kong, Hungary, Ireland, Jamaica, Korea, Madagascar, Norway, Portugal, Reunion, Romania, Saudi Arabia, Senegal, Singapore, Sweden, Switzerland, Taiwan, Thailand, Uruguay, and Former Yugoslavia. In Israel, influenza A(H3N2) activity was preceded by influenza type B activity.

Sporadic influenza A(H1N1) cases were reported in Argentina during October, in Belarus and Italy during January, in the southern half of France and Germany during February, and in Romania during January and February; an outbreak of influenza A(H1N1) occurred in a primary school in Romania during January. Other countries reporting isolation of influenza A(H1N1) viruses include Canada, China, Hungary, Russia, Singapore, Switzerland, and Taiwan. Influenza A(unsubtyped) activity was reported in Australia, Austria, Belarus, Belgium, Croatia, Czech Republic, Denmark, Iceland, Italy, Latvia, Malaysia, and New Zealand.

Influenza type B viruses were predominant in China, the Czech Republic, Denmark, Hong Kong, Iran, Israel, and Singapore. Increases in influenza type B activity followed earlier influenza A(H3N2) activity in Austria, Belgium, Canada, Finland, France, French Guiana and Guadeloupe, Netherlands, Portugal, Spain, the United Kingdom, and Former Yugoslavia. Both influenza type A and type B were reported in Belarus, Croatia, Germany, Hungary, Iceland, Italy, Latvia, Norway, Sweden, and Switzerland. Other countries reporting influenza type B activity included Australia, Chile, Fiji, Korea, Malaysia, Nepal, Romania, Russia, Senegal, Saudi Arabia, Slovakia, Taiwan, and Thailand. Composition of the 1997-98 Vaccine

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the 1997-98 trivalent influenza vaccine for the United States contain A/Wuhan/359/95-like (H3N2), A/Bayern/07/95-like (H1N1), and B/Beijing/184/93-like viruses. This recommendation was based on antigenic analyses of recently isolated influenza viruses and the antibody responses of persons vaccinated with the 1996-97 vaccine.

Although influenza A(H1N1) viruses were isolated only sporadically during the 1996-97 influenza season, during 1996 an increasing number of antigenically characterized isolates, represented by A/Bayern/07/95, demonstrated a reduction in titer to A/Texas/36/91 and A/Taiwan/01/86 ferret antisera (Table_1) (1). A second group of antigenically distinct influenza A(H1N1) viruses, represented by A/Wuhan/371/95, has been identified in China and Hong Kong since 1995 and in a single isolate in Singapore during 1996. Vaccines containing A/Texas/36/91 induced a good antibody response to the vaccine strain but less frequent and reduced antibody responses to recent influenza A(H1N1) isolates such as A/Bayern/07/95. Therefore, VRBPAC recommended changing the influenza A(H1N1) component for the 1997-98 season to an A/Bayern/07 /95-like virus. The antigenically equivalent strain that will be used by U.S. vaccine manufacturers is A/Johannesburg/82/96.

Most antigenically characterized influenza A(H3N2) viruses isolated worldwide were similar to the reference strain A/Wuhan/359/95 and the antigenically equivalent vaccine strain A/Nanchang/933/95. Vaccines containing A/Nanchang/933/95 induced antibodies with similar frequency and titer to the vaccine virus and to recently isolated influenza A(H3N2) strains. Therefore, VRBPAC recommended retaining A/Nanchang/ 933/95 in the 1997-98 influenza vaccine.

Most influenza type B viruses that have been antigenically characterized are similar to the reference strains B/Beijing/184/93 and B/Harbin/07/94. Although a small number are related to the antigenically distinct B/Victoria/02/87-like viruses, these viruses have not been isolated in the United States since 1991 and have circulated recently only in Asia. Vaccines containing B/Harbin/07/94 induced antibodies with similar frequency and titer to the vaccine virus and to influenza type B strains recently isolated in North America and Europe. Therefore, VRBPAC recommended retaining B/Harbin/07/94 in the 1997-98 vaccine.

Reported by: Participating state and territorial epidemiologists and state public health laboratory directors. World Health Organization collaborating laboratories. Sentinel Physicians Influenza Surveillance System. M Zambon, PhD, Central Public Health Laboratory, A Hay, PhD, National Institute for Medical Research, London; G Schild, DSc, J Wood, PhD, National Institute for Biological Standards and Control, Hertfordshire, England. I Gust, MD, A Hampson, Commonwealth Serum Laboratories, Parkville, Australia. K Nerome, PhD, National Institute of Health, Tokyo, Japan. Y Guo, Institute of Virology, National Center for Preventive Medicine, Beijing, People's Republic of China. Div of Emerging and Other Communicable Diseases Surveillance and Control, World Health Organization National Influenza Centers, Geneva, Switzerland. Div of Virology, Center for Biologics Evaluation and Research, Food and Drug Administration. Influenza Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: This was the fifth season since the 1986-87 season in which influenza A(H3N2) viruses have predominated; during the other 5 years, at least 7% of isolates were influenza A(H3N2). The pattern of influenza activity in the United States during the 1996-97 season was characterized by a sudden, sharp increase in morbidity followed by a sustained increase in P&I-related deaths. Although outbreaks were reported among all age groups, most outbreaks reported to CDC occurred among elderly nursing-home residents. Since mid-February, more influenza type B than influenza type A has been isolated (Figure_1), suggesting that type B viruses may circulate more widely next winter. Although no influenza A(H1N1) viruses have been isolated in the United States during the 1996-97 season, both influenza A(H1N1) and A(H3N2) viruses may circulate during the 1997-98 season.

Strains to be included in the influenza vaccine usually are selected during the preceding January through March because of scheduling requirements for production, quality control, packaging, and distribution of vaccine for administration before onset of the next influenza season. Recommendations of the Advisory Committee on Immunization Practices for the use of vaccine and antiviral agents for prevention and control of influenza will be published in an MMWR Recommendations and Reports on April 25, 1997 (2).

References

1. World Health Organization. Recommended composition of influenza virus vaccines for use in the 1997-1998 season. Wkly Epidemiol Rec 1997;72:57-61.

2. CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(no. RR-9) (in press).

• Levels of activity are 1) no activity; 2) sporadic -- sporadically occurring influenza-like illness (ILI) or culture-confirmed influenza, with no outbreaks detected; 3) regional -- outbreaks of ILI or culture-confirmed influenza in counties with a combined population of less than 50% of the state's total population; and 4) widespread -- outbreaks of ILI or culture-confirmed influenza in counties with a combined population of greater than or equal to 50% of the state's total population. ** The epidemic threshold is 1.645 standard deviations above the seasonal baseline. The expected seasonal baseline is projected using a robust regression procedure in which a periodic regression model is applied to observed percentages of deaths from P&I since 1983.

  
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  Table_1
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  TABLE 1. Hemmagglutination-inhibition titers of influenza A(H1N1) viruses with serum
  specimens from infected ferrets *
  =================================================================================================
                                                        Ferret antiserum
                                  -----------------------------------------------------------------
  Viral antigen                   A/Taiwan/01/86   A/Texas/36/91   A/Bayern/07/95   A/Wuhan/371/95
  -------------------------------------------------------------------------------------------------
  Reference antigen
   A/Taiwan/01/86                     1280             320              640              <40
   A/Texas/36/91                       640            1280              640               40
   A/Bayern/7/95                       640             640             1280               40
   A/Wuhan/371/95                      <40             <40              <40              640
  
  Recent isolates
   A/Auckland/6/96                     640             320             1280               40
   A/Brazil/140/96                     640             160             1280               40
   A/Chile/2110/96                     320             160             1280               40
   A/Nagasaki/37/96                    160             640              640              <40
   A/Poiniers/191/96                   320             320              640              <40
   A/Zambia/546/96                     320             320              640               80
                                       320             320              640               40
  A/Switzerland/6081/97
   A/Beijing/262/95                     40             <40               80              640
   A/Singapore/15/96                   <40              40              <40              640
   A/Nanchang/1/96                     <40             <40               80              320
  -------------------------------------------------------------------------------------------------
  * A fourfold difference in hemagglutination-inhibition titer between two viruses usually
    indicates antigenic variation between viruses.
  =================================================================================================
  

  
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