Nov/Dec 2000, Volume 3, No.9, pp. 5758, 61-62.
These rapid genetic changes are the reason that one or more new virus strains are usually incorporated into each years influenza vaccine. Since 1977, influenza A(H1N1) viruses, influenza A(H3N2) viruses, and influenza B viruses have been in global circulation. A persons immunity to the surface antigens, especially hemagglutinin, reduces the likelihood of infection and the severity of disease if infection occurs.
An antibody against one influenza virus type or subtype, however, confers little or no protection against another virus type or subtype; thus, an unvaccinated individual can succumb to the disease more than once in a given flu season.
The influenza incubation period is one to four days, with an average of two days. Persons can be infectious starting the day before symptoms begin through about five days after illness onset. Children can be infectious for a longer period. Uncomplicated influenza is characterized by the abrupt onset of fever, myalgia, headache, severe malaise, nonproductive cough, sore throat, and rhinitis. Typically, the illness runs its course after several days; however, cough and malaise can persist for two or more weeks. In some people, influenza can exacerbate underlying medical conditions such as pulmonary or cardiac disease or lead to secondary bacterial pneumonia or primary influenza viral pneumonia.
The flu vaccine and its benefits
Influenza vaccine contains two type A and one type B influenza virus strains. These represent the influenza viruses likely to circulate in the United States in the upcoming winter (see the next section). The vaccine is made from highly purified, chicken-egg-grown viruses that have been made noninfectious by adding a surfactant to disrupt the virus particle. Whole-virus, subvirion, and purified-surface-antigen preparations are available.
Most vaccinated children and young adults develop high post-vaccination hemagglutination-inhibition antibody titers. These antibody titers are protective against illness caused by strains similar to those in the vaccine. The effectiveness of influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient and the degree of similarity between the viruses in the vaccine and those in circulation. When the antigenic match between vaccine and circulating viruses is close, influenza vaccine prevents illness in 7090% of healthy persons younger than 65.
The elderly and people with certain chronic diseases, such as heart disease, asthma, and diabetes, might develop lower postvaccination antibody titers than healthy adults and remain susceptible to influenza-related upper respiratory tract infection. For these individuals, the vaccine still can be effective in preventing secondary complications and reducing the risk of influenza-related hospitalization and death. Among older persons who do not live in nursing homes or similar chronic-care facilities, influenza vaccine is 3070% effective in preventing hospitalization for pneumonia and influenza. Among elderly persons residing in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications, and deaths. In this population, the vaccine can be 5060% effective in preventing hospitalization or pneumonia and 80% effective in preventing death, even though the effectiveness in preventing influenza illness often ranges from 30 to 40%.
The decision process
WHO made its recommendation for the composition of the 20002001 trivalent influenza vaccine for the Northern Hemisphere on Feb. 16, 2000, after an annual conference by influenza experts at WHOs Geneva headquarters. WHO recommended that the trivalent influenza vaccine prepared for the 20002001 season include A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Beijing/184/93-like antigens. National control authorities in each country approve the specific influenza vaccines used in their countries. National health authorities are responsible for recommendations about the use of the vaccine.
Scientists at the U.S. FDA make the actual recommendation for the composition of each flu seasons vaccine on the basis of antigenic and molecular analyses of recently isolated influenza viruses, epidemiologic data, and postvaccination serologic studies in humans provided by the CDC and WHO. Typically, the FDAs Vaccines and Related Biologic Products Advisory Committee (VRBPAC) determines its recommended influenza vaccine composition within days of the WHO decision and communicates it to vaccine manufacturers.
For the 20002001 U.S. trivalent influenza vaccine, VRBPAC specified that U.S. manufacturers use the antigenically equivalent A/Panama/2007/99 (H3N2) virus instead of the A/Moscow/10/99 (H3N2)-like antigen recommended by WHO. For the WHO-recommended B/Beijing/184/93-like antigen, they will use the antigenically equivalent B/Yamanashi/166/98 virus. These antigenically equivalent viruses will be used because of their better growth properties and because they are representative of currently circulating A(H3N2) and B viruses. U.S. virus manufacturers will also use the A/New Caledonia/20/99-like (H1N1) virus.
Influenza type B viruses were isolated sporadically in the United States and worldwide and were antigenically similar to the 19992000 vaccine strain B/Beijing/184/93 and to the widely used equivalent vaccine strain B/Yamanashi/166/98. Therefore,
WHO made its recommendations for the composition of vaccines intended for the May to October 2001 period in the Southern Hemisphere in September 2000. Their experts recommended the following strains for inclusion: A/Moscow/10/99 (H3N2)- like virus, A/New Caledonia/20/99 (H1N1)-like virus, and B/Sichavan/379/99-like virus.
Who should be immunized?
ACIP reports that targeting this age group should not only protect more high-risk people, but will also result in higher vaccination rates. This strategy also probably help to increase vaccination rates among people without high-risk conditions but for whom annual vaccination is recommended because they live with people at increased risk of influenza-related complications.
For the 20002001 influenza season in the United States, lower-than-anticipated production yields for this years influenza A(H3N2) vaccine component and other manufacturing problems were encountered. As of September 28, the CDC announced that it expected vaccine amounts should be approximately what was distributed last year although a substantial amount of vaccine will reach providers later than usual.
ACIP has advised delaying at least some large, organized vaccination campaigns until later in the season as availability of vaccine becomes assured. In previous years, ACIP recommended that organized vaccination campaigns take place during October through mid-November. Normally, these timing recommendations balance several considerations other than availability, including the desirability of administering vaccine before significant seasonal influenza activity has begun but not vaccinating so early that vaccine antibody titers might substantially decrease in some persons, nor so late that the vaccine will have insufficient time to become effective. But given this years delays, ACIP recommends that vaccination efforts should first focus on health care workers and people at high risk for complications. It advises that these efforts should continue into December and later as long as influenza vaccine is available and that special efforts should also continue into December and later to vaccinate the 5064 age class and others who are not at high risk.
Potential new vaccines
Possible advantages of LAIVs include their potential to induce a broad mucosal and systemic immune response, ease of administration, and the acceptability of an intranasal route of administration compared with injectable vaccines. In a five-year study comparing conventional trivalent inactivated vaccine and bivalent LAIVs (administered by nose drops) that used related but different vaccine strains, the two vaccines were found to be approximately equivalent in effectiveness. In a recent study of children age 1571 months, an intranasally administered trivalent LAIV was 93% effective in preventing culture-positive influenza A(H3N2) and B infections.
In a follow-up study during the 19971998 season, the trivalent LAIV was 86% effective in preventing culture-positive influenza in children, despite a poor match between the vaccines influenza A(H3N2) component and the predominant circulating influenza A(H3N2) virus. A study conducted among healthy adults during the same season found a 924% reduction in febrile respiratory illnesses and a 1328% reduction in lost workdays. No study has directly compared the efficacy or effectiveness of trivalent inactivated vaccine and trivalent LAIV.