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Update: Influenza Activity --- United States and Worldwide, 2002--03 Season, and Composition of the 2003--04 Influenza Vaccine

In collaboration with the World Health Organization (WHO), its collaborating laboratories, state and local health departments, health-care providers, and vital statistic registries, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza viruses. During the 2002--03 influenza season, influenza A (H1)*, A (H3N2), and B viruses co-circulated in the Northern Hemisphere. Human infections with avian influenza A (H5N1) and A (H7N7) viruses were reported in Hong Kong and the Netherlands, respectively. In the United States, the 2002--03 influenza season was mild; influenza A (H1) and B viruses circulated widely, and the predominant virus varied by region and time of season. This report summarizes influenza activity in the United States and worldwide during the 2002--03 influenza season and describes the composition of the 2003--04 influenza vaccine.

United States

The percentage of respiratory specimens testing positive for influenza and the proportion of outpatient visits to physicians for influenza-like illness (ILI)§ began to increase in mid-January and peaked during early February. Both influenza A (H1) and B viruses circulated widely this season, with some regions reporting more influenza A viruses than influenza B viruses and others reporting more B viruses than A viruses. Nationally, influenza B viruses predominated during the first half of the season, but after the week ending February 1, influenza A viruses were reported more frequently than influenza B viruses.

During September 29, 2002--May 17, 2003, the WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories in the United States tested 94,966 specimens for influenza viruses, of which 11,027 (11.6%) were positive. Of these, 6,324 (57%) were influenza A viruses, and 4,703 (43%) were influenza B viruses. Among the influenza A viruses, 3,381 (53%) were subtyped; of these, 2,534 (75%) were influenza A (H1) viruses, and 847 (25%) were influenza A (H3N2) viruses. Influenza A viruses were reported more frequently (range: 58%--86%) than influenza B viruses in the New England, East North Central, Pacific, Mountain, and Mid-Atlantic regions, and influenza B viruses were reported more frequently (range: 53%--78%) than influenza A viruses in the West North Central, West South Central, South Atlantic, and East South Central regions. The proportion of specimens testing positive for influenza first increased to >10% during the week ending January 18 (week 3), peaked at 25% during the week ending February 8 (week 6), and declined to <10% during the week ending April 5 (week 14). The peak percentage of specimens testing positive for influenza during the previous three seasons (1999--00, 2000--01, and 2001--02) ranged from 23% to 31% (1; CDC, unpublished data, 2003).

CDC has antigenically characterized 626 influenza viruses submitted by U.S. laboratories since September 29, 2002: 267 influenza A (H1) viruses, 105 influenza A (H3N2) viruses, and 254 influenza B viruses. Of the 267 influenza A (H1) viruses, 193 (72%) had an N1 neuraminidase, 66 (25%) had an N2 neuraminidase, and the neuraminidase typing for eight (3%) H1 viruses is pending. The hemagglutinin proteins of all 267 influenza A (H1) viruses were similar antigenically to the hemagglutinin of the vaccine strain A/New Caledonia/20/99 (H1N1). Of the 105 influenza A (H3N2) isolates that have been characterized, 98 (93%) were similar to A/Panama/2007/99, the H3N2 component of the 2002--03 influenza vaccine, and seven (7%) had reduced titers to ferret antisera produced against A/Panama/2007/99. Of the 254 influenza B viruses that have been characterized, 253 (99%) belonged to the B/Victoria lineage and were similar antigenically to the vaccine strain B/Hong Kong/330/01, and one (1%) belonged to the B/Yamagata lineage and was similar to B/Shizuoka/15/01, a B/Sichuan/379/99-like virus.

During the week ending December 28, 2002 (week 52) and each consecutive week during the weeks ending January 25--March 8, 2003 (weeks 4--10), the weekly percentage of patient visits for ILI to U.S. sentinel providers exceeded baseline levels (0--1.9%). The peak percentage of patient visits for ILI was 3.2% during the week ending February 8 (week 6). During the previous three seasons (1999--00, 2000--01, and 2001--02), the peak percentage of patient visits for ILI ranged from 3.2% to 5.7% (1; CDC, unpublished data, 2003).

On the basis of data reported by state and territorial epidemiologists, influenza activity peaked during the week ending February 22 (week 8), when 35 states reported regional or widespread influenza activity**. One or more states reported regional influenza activity each week during the weeks ending October 26, 2002--May 17, 2003. Widespread influenza activity was reported by one or more states for the weeks ending December 7--21, 2002 (weeks 49--51), and for all but 1 week during the weeks ending January 18--April 19, 2003 (weeks 3--16). The peak number of states reporting widespread or regional activity during the previous three seasons ranged from 38 to 44 states.

As measured by the 122 Cities Mortality Reporting System, the percentage of deaths in the United States attributed to pneumonia and influenza (P&I) did not exceed the epidemic threshold†† during the 2002--03 season. During the previous three seasons, the number of consecutive weeks during which the percentage of deaths attributed to P&I exceeded the epidemic threshold ranged from 0 to13 weeks.

Worldwide

During October 2002--May 2003, influenza A and B viruses co-circulated in Asia, Europe, and North America. In Europe and Asia, the majority of influenza A viruses subtyped were A (H3N2), but A (H1) was the most frequently reported influenza A subtype in North America. Within countries or regions, the predominant virus type or subtype varied and changed frequently as the season progressed.

In Europe, influenza A (H3N2) viruses predominated in the Czech Republic, Germany, Italy, the Netherlands, Poland, Russia, and Switzerland; in Asia, these viruses predominated in Japan, Hong Kong, and the Republic of Korea. Influenza A (H3N2) viruses also were reported in Africa (Egypt, Madagascar, Senegal, and Tunisia), other countries in Asia (China, Guam, India, Israel, Malaysia, the Philippines, Singapore, Thailand, and Turkey), other countries in Europe (Bulgaria, France, Norway, Portugal, Romania, and Slovakia), Latin America (Argentina, Brazil, French Guiana, Mexico, and Peru), and Oceania (Australia).

Influenza A (H1) viruses predominated in Canada and Mexico. In the United States, influenza A (H1) and B viruses were reported at approximately the same frequency. Influenza A (H1) viruses also were reported in Africa (Senegal), Asia (China, Hong Kong, and Israel), Europe (the Czech Republic, France, Italy, the Netherlands, Norway, Poland, Russia, Slovakia, Spain, and Switzerland), and Latin America (Argentina, Brazil, and Peru). Countries reporting unsubtyped influenza A viruses include Belgium, Chile, Lithuania, and Slovenia.

Influenza B viruses predominated in Belgium, the United Kingdom, France, Portugal, Romania, and Spain. Influenza B viruses also were reported in Africa (Egypt, Madagascar, Morocco, and Tunisia), Asia (India, China, Guam, Japan, Hong Kong, Israel, the Philippines, Thailand, and Taiwan), Europe (the Czech Republic, Germany, Italy, the Netherlands, Norway, Poland, Russia, Slovakia, Slovenia, and Switzerland) and Latin America (Argentina, Brazil, Chile, French Guiana, Mexico, and Peru).

In February 2003, two human infections with avian influenza A (H5N1) virus were confirmed in a family of Hong Kong residents who had traveled recently to Fujian Province in mainland China (2). The first patient, a boy aged 9 years, was hospitalized in Hong Kong and recovered; the second patient, the boy's father, died in a Hong Kong hospital on February 17. Other family members had respiratory symptoms, and the boy's sister, aged 8 years, died while the family was in mainland China. The cause of her death and of the other respiratory illnesses in the family is not known. As of June 4, 2003, no additional human cases of influenza A (H5N1) infection had been identified in Hong Kong or elsewhere.

Since the end of February 2003, the Netherlands has reported outbreaks of highly pathogenic avian influenza A (H7N7) in poultry on several farms. Subsequently, H7N7 infections have been reported among pigs and humans in the Netherlands and among birds in Belgium and Germany. As of April 25, the National Influenza Center in the Netherlands had confirmed 83 cases of H7N7 influenza virus infections among poultry workers and their families since the end of February 2003; 79 had conjunctivitis, but six also reported ILI symptoms (e.g., fever, cough, and muscle aches). One person reported only ILI, and two persons reported mild illness that could not be classified as ILI or conjunctivitis. A veterinarian aged 57 years who visited one of the affected farms in early April died on April 17 of acute respiratory distress syndrome and complications related to H7N7 infection. Dutch authorities reported that transmission of H7N7 influenza from two poultry workers to three family members possibly occurred. All three family members had conjunctivitis, and one also had ILI.

Composition of the 2003--04 Influenza Vaccine

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the 2003--04 trivalent influenza vaccine for the United States contain A/New Caledonia/20/99-like (H1N1), A/Moscow/10/99-like (H3N2), and B/Hong Kong/330/01-like viruses. This recommendation was based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, and postvaccination serologic studies in humans.

The hemagglutinin proteins of the majority of influenza A (H1N1) and A (H1N2) viruses isolated worldwide were similar to A/New Caledonia/20/99 (H1N1). Antibodies produced following vaccination with the 2002--03 vaccine containing A/New Caledonia/20/99 (H1N1) virus reacted equally well with recent influenza A (H1N1) and A (H1N2) viruses and the vaccine strain (3).

The majority of influenza A (H3N2) viruses isolated during the 2002--03 season were similar to A/Panama/2007/99 and A/Moscow/10/99-like (H3N2) viruses. A small number of influenza A (H3N2) viruses had reduced titers to ferret antisera produced against A/Panama/2007/99 (H3N2)-like viruses. Because the majority of viruses were similar to A/Panama/2007/99, an influenza A/Moscow/10/99-like (H3N2) virus was retained in the 2003--04 vaccine. Because of its growth properties, U.S. vaccine manufacturers will use an antigenically equivalent virus, A/Panama/2007/99, as the influenza A component (4).

The majority of influenza B isolates worldwide were from the B/Victoria/2/87 lineage and were similar to the 2002--03 vaccine strain, B/Hong Kong/330/01. U.S. manufacturers will use either B/Hong Kong/330/01 or the antigenically equivalent virus, B/Hong Kong/1434/02, in the 2003--04 vaccine.

Reported by: WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza. L Brammer, MPH, A Postema, MPH, S Harper, MD, A Klimov, PhD, K Fukuda, MD, N Cox, PhD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note:

Overall, the 2002--03 influenza season was mild, and the predominant virus type/subtype varied by region in the United States and in Europe. In many areas, the predominant circulating virus type changed within a region or country as the season progressed. For example, influenza B viruses predominated in the United States during October--January, but after January, influenza A viruses were identified more frequently.

Human infections with avian influenza viruses A (H5N1) and A (H7N7) were reported during 2002--03 influenza season in Hong Kong and the Netherlands, respectively. These are the first human infections with avian influenza viruses reported since 1999, when two children were infected with influenza A (H9N2) in Hong Kong (5), and the first human influenza A (H5N1) infections reported since 1997 (6,7). Since 1997, influenza A (H5N1) virus has been detected periodically in chickens and ducks, and more recently, in wild birds in Hong Kong. Human H7N7 infections were associated previously with conjunctivitis (8,9), but the cases in the Netherlands are the first virologically confirmed respiratory infections with this virus subtype and include the first recorded human fatality associated with this virus.

Transmission of avian influenza viruses directly from animals to humans is unusual. Humans typically have little or no antibody protection against these viruses. If an avian or other animal influenza virus infected humans and spread efficiently from person to person, an influenza pandemic could result.

As a result of the human A (H5N1) infections, in February 2003, CDC issued recommendations for enhanced influenza surveillance for state health departments (http://www.cdc.gov/ncidod/diseases/flu/hanH5N1.htm). Recommendations for enhanced influenza surveillance include 1) year-round laboratory testing for influenza and sentinel provider surveillance for ILI; 2) subtyping of all influenza A viruses identified by U.S. WHO/NREVSS collaborating laboratories; and 3) strengthening of sentinel provider surveillance in states with <75% of their sentinel provider goal (i.e., one regularly reporting site per 250,000 population, or a minimum of 10 sites in smaller, less populous states).

Considerable overlap exists between the clinical presentation and travel history of persons who might have severe acute respiratory syndrome (SARS) and those who should be evaluated for infection with influenza A (H5N1). Influenza A infection should be considered in the differential diagnosis along with SARS when evaluating patients with febrile respiratory illness. Priority should be given to subtyping influenza A viruses isolated from potential SARS patients with recent travel to Asia and the contacts of such persons. Any influenza viruses that cannot be subtyped should be reported immediately to CDC.

Influenza vaccine manufacturers project that approximately 80--85 million doses of influenza vaccine will be available for distribution during the 2003--04 season, approximately 10--15 million doses below last year's production level, but more than the estimated total number of doses sold in 2002. This projection could change as the season progresses.

Acknowledgments

This report is based on data contributed by participating state and territorial epidemiologists and state public health laboratory directors, World Health Organization collaborating laboratories, National Respiratory and Enteric Virus Surveillance System collaborating laboratories, U.S. Influenza Sentinel Provider Surveillance System. WHO National Influenza Centers, Communicable Diseases, Surveillance and Response, Geneva, Switzerland. A Hay, PhD, WHO Collaborating Center for Reference and Research on Influenza, National Institute for Medical Research, London, England. I Gust, MD, A Hampson, WHO Collaborating Center for Reference and Research on Influenza, Parkville, Australia. M Tashiro, MD, WHO Collaborating Center for Reference and Research on Influenza, National Institute of Infectious Diseases, Tokyo, Japan. R Fouchier, PhD, T Kuiken, DVM, A Osterhaus, DVM, Dept of Virology, Erasmus Medical Center, Rotterdam, the Netherlands. JSM Peiris, DPhil, Depts of Microbiology and Pathology, Queen Mary Hospital, Univ of Hong Kong, Hong Kong Special Administrative Region (SAR). W Lim, FRCPA, Government Virus Unit, Dept of Health, Hong Kong SAR. Div of Public Health Surveillance and Informatics, Epidemiology Program Office, CDC.

References

  1. CDC. Surveillance for influenza---United States 1997--98, 1998--99, and 1999--00. In: CDC surveillance summaries (October 25). MMWR 2002;51(No. SS-7).
  2. Update: influenza activity---United States, 2002--03 season. MMWR 2003;52:224--5.
  3. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2003--2004 influenza season. Wkly Epidemiol Rec 2002;78:58--62.
  4. World Health Organization. Addendum to the recommended composition of influenza virus vaccines for use in the 2003--2004 influenza season. Wkly Epidemiol Rec 2002;78:77.
  5. CDC. Update: influenza activity---United States and worldwide, 1998--99 season, and composition of the 1999--2000 influenza vaccine. MMWR 1999;48:374--8.
  6. Buxton Bridges C, Katz JM, Seto WH, et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis 2000;181:344--8.
  7. Mounts AW, Kwong H, Izurieta HS, et al. Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997. J Infect Dis 1999;180:505--8.
  8. Kurtz J, Manvell RJ, Banks J. Avian influenza virus isolated from a woman with conjunctivitis. Lancet 1996;348:901--2.
  9. Webster RG, Geraci J, Petursson G, Skirnisson K. Conjunctivitis in human beings caused by influenza A virus of seals. N Engl J Med 1981;304:911.

* Includes both the A (H1N1) and A (H1N2) influenza virus subtypes.

As of May 22, 2003.

§ Defined as temperature of >100º F (>37.8º C) and either cough 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 plus two standard deviations. A noninfluenza week is a week during which <10% of specimens tested positive for influenza. Wide variability in regional data precludes calculating region-specific baselines and makes it inappropriate to apply the national baseline to regional data.

** Levels of activity are 1) no activity, 2) sporadic---sporadically occurring ILI or laboratory-confirmed influenza with no outbreaks detected, 3) regional---outbreaks of ILI or laboratory-confirmed influenza in counties with a combined population of <50% of a state's total population, and 4) widespread---outbreaks of ILI or laboratory-confirmed influenza in counties with a combined population of >50% of a state's total population.

†† The expected seasonal baseline proportion of P&I deaths reported by the 122 Cities Mortality Reporting System is projected by using a robust regression procedure in which a periodic regression model is applied to the observed percentage of deaths from P&I during the previous 5 years. The epidemic threshold is 1.654 standard deviations above the seasonal baseline (1).



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