Accelerated approval process used in flu vaccine approval
The U.S. Food and Drug Administration today approved Fluzone High-Dose, an inactivated influenza virus vaccine for people ages 65 years and older to prevent disease caused by influenza virus subtypes A and B.
People in this age group are at highest risk for seasonal influenza complications, which may result in hospitalization and death. Annual vaccination remains the best protection from influenza, particularly for people 65 and older.
Fluzone High-Dose was approved via the accelerated approval pathway. FDA’s accelerated approval pathway helps safe and effective medical products for serious or life-threatening diseases become available sooner. In clinical studies, Fluzone High-Dose demonstrated an enhanced immune response compared with Fluzone in individuals 65 and older.
2008-09 INFLUENZA PREVENTION & CONTROL RECOMMENDATIONS
Clinical Signs and Symptoms of Influenza
On this page:
- Signs and Symptoms
- Hospitalizations & Deaths from Influenza
- Figure 1: Month of Peak Influenza Activity
Influenza viruses are spread from person to person primarily through large-particle respiratory droplet transmission (e.g., when an infected person coughs or sneezes near a susceptible person). Transmission via large-particle droplets requires close contact between source and recipient persons, because droplets do not remain suspended in the air and generally travel only a short distance (less than or equal to 1 meter) through the air. Contact with respiratory-droplet contaminated surfaces is another possible source of transmission. Airborne transmission (via small-particle residue [less than or equal to 5µm] of evaporated droplets that might remain suspended in the air for long periods of time) also is thought to be possible, although data supporting airborne transmission are limited. The typical incubation period for influenza is 1–4 days (average: 2 days). Adults shed influenza virus from the day before symptoms begin through 5–10 days after illness onset. However, the amount of virus shed, and presumably infectivity, decreases rapidly by 3–5 days after onset in an experimental human infection model. Young children also might shed virus several days before illness onset, and children can be infectious for 10 or more days after onset of symptoms. Severely immunocompromised persons can shed virus for weeks or months.
Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms (e.g., fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis). Among children, otitis media, nausea, and vomiting also are commonly reported with influenza illness. Uncomplicated influenza illness typically resolves after 3–7 days for the majority of persons, although cough and malaise can persist for >2 weeks. However, influenza virus infections can cause primary influenza viral pneumonia; exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease); lead to secondary bacterial pneumonia, sinusitis, or otitis media; or contribute to coinfections with other viral or bacterial pathogens. Young children with influenza virus infection might have initial symptoms mimicking bacterial sepsis with high fevers, and febrile seizures have been reported in 6%–20% of children hospitalized with influenza virus infection. Population-based studies among hospitalized children with laboratory-confirmed influenza have demonstrated that although the majority of hospitalizations are brief (2 or fewer days), 4%–11% of children hospitalized with laboratory-confirmed influenza required treatment in the intensive care unit, and 3% required mechanical ventilation. Among 1,308 hospitalized children in one study, 80% were aged <5 years, and 27% were aged <6 months. Influenza virus infection also has been uncommonly associated with encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome.
Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. Sensitivity and predictive value of clinical definitions vary, depending on the prevalence of other respiratory pathogens and the level of influenza activity. Among generally healthy older adolescents and adults living in areas with confirmed influenza virus circulation, estimates of the positive predictive value of a simple clinical definition of influenza (acute onset of cough and fever) for laboratory-confirmed influenza infection have varied (range: 79%–88%).
Young children are less likely to report typical influenza symptoms (e.g., fever and cough). In studies conducted among children aged 5–12 years, the positive predictive value of fever and cough together was 71%–83%, compared with 64% among children aged <5 years. In one large, population-based surveillance study in which all children with fever or symptoms of acute respiratory tract infection were tested for influenza, 70% of hospitalized children aged <6 months with laboratory-confirmed influenza were reported to have fever and cough, compared with 91% of hospitalized children aged 6 months–5 years. Among children who subsequently were shown to have laboratory-confirmed influenza infections, only 28% of those hospitalized and 17% of those treated as outpatients had a discharge diagnosis of influenza.
Clinical definitions have performed poorly in some studies of older patients. A study of nonhospitalized patients aged 60 and older years indicated that the presence of fever, cough, and acute onset had a positive predictive value of 30% for influenza. Among hospitalized patients aged 65 years and older with chronic cardiopulmonary disease, a combination of fever, cough, and illness of <7 days had a positive predictive value of 53% for confirmed influenza infection. In addition, the absence of symptoms of influenza-like illness (ILI) does not effectively rule out influenza; among hospitalized adults with laboratory-confirmed infection in two studies, 44%–51% had typical ILI symptoms. A study of vaccinated older persons with chronic lung disease reported that cough was not predictive of laboratory-confirmed influenza virus infection, although having both fever or feverishness and myalgia had a positive predictive value of 41%. These results highlight the challenges of identifying influenza illness in the absence of laboratory confirmation and indicate that the diagnosis of influenza should be considered in patients with respiratory symptoms or fever during influenza season.
In the United States, annual epidemics of influenza typically occur during the fall or winter months, but the peak of influenza activity can occur as late as April or May (Figure 1). Influenza-related complications requiring urgent medical care, including hospitalizations or deaths, can result from the direct effects of influenza virus infection, from complications associated with age or pregnancy, or from complications of underlying cardiopulmonary conditions or other chronic diseases. Studies that have measured rates of a clinical outcome without a laboratory confirmation of influenza virus infection (e.g., respiratory illness requiring hospitalization during influenza season) to assess the effect of influenza can be difficult to interpret because of circulation of other respiratory pathogens (e.g., respiratory syncytial virus) during the same time as influenza viruses.
During seasonal influenza epidemics from 1979–1980 through 2000–2001, the estimated annual overall number of influenza-associated hospitalizations in the United States ranged from approximately 55,000 to 431,000 per annual epidemic (mean: 226,000). The estimated annual number of deaths attributed to influenza from the 1990–91 influenza season through 1998–99 ranged from 17,000 to 51,000 per epidemic (mean: 36,000). In the United States, the estimated number of influenza-associated deaths increased during 1990–1999. This increase was attributed in part to the substantial increase in the number of persons aged 65 years and older who were at increased risk for death from influenza complications. In one study, an average of approximately 19,000 influenza-associated pulmonary and circulatory deaths per influenza season occurred during 1976–1990, compared with an average of approximately 36,000 deaths per season during 1990–1999. In addition, influenza A (H3N2) viruses, which have been associated with higher mortality (54), predominated in 90% of influenza seasons during 1990–1999, compared with 57% of seasons during 1976–1990.
Influenza viruses cause disease among persons in all age groups. Rates of infection are highest among children, but the risks for complications, hospitalizations, and deaths from influenza are higher among persons aged 65 years and older, young children, and persons of any age who have medical conditions that place them at increased risk for complications from influenza. Estimated rates of influenza-associated hospitalizations and deaths varied substantially by age group in studies conducted during different influenza epidemics. During 1990–1999, estimated average rates of influenza-associated pulmonary and circulatory deaths per 100,000 persons were 0.4–0.6 among persons aged 0–49 years, 7.5 among persons aged 50–64 years, and 98.3 among persons aged 65 years and older.
NOTE: The text above is taken from Prevention & Control of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP) 2008. MMWR 2008 Jul 17; Early Release:1-60. (Also available as PDF, 586K)
FOR IMMEDIATE RELEASE
The U.S. Food and Drug Administration (FDA) today announced that it has approved this year’s seasonal influenza vaccines that include new strains of the virus likely to cause flu in the United States during the 2008-2009 season.
The six vaccines and their manufacturers are: CSL Limited, Afluria; GlaxoSmithKline Biologicals, Fluarix; ID Biomedical Corporation of Quebec, FluLaval; MedImmune Vaccines Inc., FluMist; Novartis Vaccines and Diagnostics Limited, Fluvirin; and Sanofi Pasteur Inc., Fluzone.
Approval information and specific indications can be found at http://www.fda.gov/cber/flu/flu2008.htm.
This season’s vaccines contain three strains of the influenza virus that disease experts expect to be the most likely cause of the flu in the United States.
Each season’s vaccines are modified to reflect the virus strains most likely to be circulating. The closer the match between the circulating strains and the strains in the vaccines, the better the protection.
There is always a possibility of a less than optimal match between the virus strains predicted to circulate and what virus strains end up causing the most illness. Even if the vaccines and the circulating strains are not an exact match, they will provide some protection and may reduce the severity of the illness or prevent flu-related complications.
“One of the biggest challenges in the fight against influenza is producing new vaccines every year,” said Jesse L. Goodman, M.D., M.P.H., director of FDA’s Center for Biologics Evaluation and Research. “There is no other instance where new vaccines must be made every year. The approval of flu vaccines is a part of FDA’s mission to promote the health of Americans throughout the year.”
The FDA changed all three strains for this year’s influenza vaccine—an unusual occurrence, as usually only one or two strains are updated from year to year. A list of the strains included in the 2008-2009 vaccine can be found at http://www.fda.gov/cber/flu/flu2008.htm. Of note, two of the three strains recommended for the U.S. this year are now in use for the Southern Hemisphere’s 2008 influenza season, which is currently underway.
Each year, experts from the FDA, World Health Organization, U.S. Centers for Disease Control and Prevention (CDC), and other institutions study virus samples and patterns collected throughout the year from around the world in an effort to identify strains that may cause the most illness in the upcoming season.
Based on those forecasts and on the recommendations of its Advisory Committee, the FDA each February decides on the three strains that manufacturers should include in their vaccines for the U.S. population. The FDA makes this decision early in the year so that manufacturers have enough time to produce the new vaccines.
Vaccination remains the cornerstone of preventing influenza, a contagious respiratory illness caused by influenza viruses. According to the CDC, every year an average of 5 to 20 percent of the U.S. population gets the flu, more than 200,000 are hospitalized from flu complications and there are about 36,000 flu-related deaths. Some individuals—the elderly, young children, and people with chronic medical conditions —are at higher risk for flu-related complications. Vaccination of these groups and of health care personnel is critical.
“Currently, only 40 percent of health care workers in the United States are vaccinated against influenza,” said Department of Health and Human Services’ Assistant Secretary of Health Joxel Garcia, M.D., M.B.A.
“Increasing the number of vaccinated health care personnel can be a strong front in the annual battle against the flu,” said Garcia. “Health care workers can set an example for the patients they serve as well as decrease the likelihood of contracting and transmitting the virus.”