Influenza Control
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《新英格兰医药杂志》
Influenza is an uncontrolled epidemic disease that occurs every winter. Epidemics, which vary in severity, are measured by excess mortality, but influenza is always the leading cause of acute respiratory tract infections that lead to health care visits or hospitalization. Therefore, when an epidemic is classified as "mild," this comparison is only with other flu epidemics; even mild flu epidemics result in the highest rates of health care encounters for the season. The effect on health care facilities is magnified by the usual sharp seasonality of influenza outbreaks. Many patients, particularly young children, experience a sudden onset of symptoms that include a high fever. These symptoms are alarming, and a medical consultation is sought. Hospitals and emergency services may be overtaxed and may have to turn away new patients at the peak of an epidemic. This phenomenon was the primary reason why the province of Ontario, Canada, has offered free vaccinations against influenza for all its citizens for the past five years.
Influenza is not a reportable disease, and most of the measures of the effect of influenza examine medical events — mortality, hospitalizations, and health care visits — that coincide with defined epidemics, but without specific etiologic studies of cases. The quantification of the effect of influenza by nonspecific measures has become increasingly difficult. Previously, the outbreaks of respiratory viruses were relatively discrete, and estimates could be made in an easily defined period.1 Currently, extended outbreaks of respiratory syncytial virus (RSV) usually encompass outbreaks of influenza and make nonspecific estimates difficult. The alarming consequence of these changes is that since 1979, the rates of hospitalization for infants with RSV have doubled and the rates of hospitalization attributable to influenza have continued to rise for adults 50 years of age or older despite a substantial increase in vaccination against influenza for the most vulnerable patients.2
In anticipation of the new recommendation that all toddlers 6 to 23 months of age be vaccinated against influenza, the New Vaccine Surveillance Network (NVSN) was organized by the Centers for Disease Control and Prevention in 1999 as reported in this issue of the Journal by Poehling and colleagues.3 The NVSN has prospectively tested children from a defined population for respiratory virus infection — specifically influenza — between 2000 and 2004. These children were younger than five years of age and were admitted to the hospital for acute respiratory tract infection or fever. Influenza virus infection was confirmed by laboratory culture and reverse-transcriptase–polymerase-chain-reaction assay. The rates determined were substantial — 4.5 per 1000 for children up to five months of age and almost 1 per 1000 for the total number of children younger than five years of age. These rates represent the minimum burden of influenza for preschool children.
To extrapolate these rates to the U.S. population, several factors should be considered. The NVSN protocol identified influenza virus infection only for patients admitted during the acute stage of the infection when the virus was detectable in respiratory secretions. A patient admitted at a later stage with complications such as bacterial pneumonia might be missed because the virus would no longer be present. Such patients can be identified by testing acute-phase and convalescent-phase serum samples for a significant antibody rise to influenza antigens. The number of patients with respiratory virus infection identified may be doubled if paired serum samples are tested.4 Furthermore, complications of influenza virus infection may involve organ systems other than the respiratory tract; these complications include encephalopathy, myocarditis, and myositis. Thus, it is clear that influenza causes more deaths and hospitalizations than all other diseases that are preventable by vaccine combined and that universal immunization against influenza should be considered. The NVSN provides an efficient platform for evaluating the effectiveness of universal immunization against influenza among preschool children.
The NVSN sites did not include appreciable numbers of uninsured families, who compose almost 20 percent of the U.S. population. The demographics of this uninsured group include many young families whose income is too high to qualify for Medicaid and too low to afford health insurance. The rates of hospitalization of children in these households are several times as high as those of children in families with health care coverage.5 The provision of annual seasonal vaccination for these children will test the public health infrastructure. Current recommendations regarding the influenza vaccine also include the household contacts of persons who are given priority for vaccination. The priority list now includes children younger than five years of age. Many of the household contacts are schoolchildren, who have the highest annual rates of infection with the influenza virus and are the main transmitters of infection. Currently, rates of immunization for healthy household contacts are low because no system exists for identifying and vaccinating these persons each year. A reasonable adjunct to current strategies for influenza control would be to extend the recommendation for vaccination to all schoolchildren and to reach them through school-based clinics.6 These clinics would affect all segments of the school-aged population — even the uninsured. Not only could school-based vaccination clinics improve control of seasonal influenza epidemics, but they would provide venues for rapid deployment of vaccine during a pandemic — an important consideration.
The NVSN group reported that outpatient visits attributable to influenza infection confirmed by laboratory culture were 10 to 250 times as common as hospitalizations for the target age groups. However, they stress that recognition of influenza infection by the treating clinician was low. As a consequence, few patients were offered specific therapy for infection with the influenza virus. This lack of recognition represents a missed opportunity to intervene to reduce both the risk of complications and the spread of the virus to contacts. Young children excrete greater concentrations of virus for longer periods of time than do older patients. Treatment of these younger patients even three to four days after the onset of infection may at least reduce the spread of infection to contacts. Identification of infection in the index child is also an opportunity to treat or extend prophylaxis against influenza to family contacts. Antiviral medications are likely to be a central defense against the first wave of the next pandemic. Surveillance networks such as the NVSN group, coupled with effective treatment of patients and their contacts, will contribute to the control of seasonal influenza and may provide a valuable rehearsal for the next pandemic.
Dr. Glezen reports having received consulting fees from MedImmune, Chiron, and GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.
Source Information
From the Department of Molecular Virology and Microbiology and the Department of Pediatrics, Baylor College of Medicine, Houston.
References
Glezen WP. The changing epidemiology of respiratory syncytial virus and influenza: impetus for new control measures. Pediatr Infect Dis J 2004;23:Suppl:S202-S206.
Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333-1340.
Poehling KA, Edwards KM, Weinberg GA, et al. The underrecognized burden of influenza in young children. N Engl J Med 2006;355:31-40.
Munoz FM. The impact of influenza in children. Semin Pediatr Infect Dis 2002;13:72-78.
Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 2000;283:499-505.
Glezen WP, Simonsen L. Benefits of influenza vaccine in US elderly -- new studies raise questions. Int J Epidemiol 2006;35:352-353.(W. Paul Glezen, M.D.)
Influenza is not a reportable disease, and most of the measures of the effect of influenza examine medical events — mortality, hospitalizations, and health care visits — that coincide with defined epidemics, but without specific etiologic studies of cases. The quantification of the effect of influenza by nonspecific measures has become increasingly difficult. Previously, the outbreaks of respiratory viruses were relatively discrete, and estimates could be made in an easily defined period.1 Currently, extended outbreaks of respiratory syncytial virus (RSV) usually encompass outbreaks of influenza and make nonspecific estimates difficult. The alarming consequence of these changes is that since 1979, the rates of hospitalization for infants with RSV have doubled and the rates of hospitalization attributable to influenza have continued to rise for adults 50 years of age or older despite a substantial increase in vaccination against influenza for the most vulnerable patients.2
In anticipation of the new recommendation that all toddlers 6 to 23 months of age be vaccinated against influenza, the New Vaccine Surveillance Network (NVSN) was organized by the Centers for Disease Control and Prevention in 1999 as reported in this issue of the Journal by Poehling and colleagues.3 The NVSN has prospectively tested children from a defined population for respiratory virus infection — specifically influenza — between 2000 and 2004. These children were younger than five years of age and were admitted to the hospital for acute respiratory tract infection or fever. Influenza virus infection was confirmed by laboratory culture and reverse-transcriptase–polymerase-chain-reaction assay. The rates determined were substantial — 4.5 per 1000 for children up to five months of age and almost 1 per 1000 for the total number of children younger than five years of age. These rates represent the minimum burden of influenza for preschool children.
To extrapolate these rates to the U.S. population, several factors should be considered. The NVSN protocol identified influenza virus infection only for patients admitted during the acute stage of the infection when the virus was detectable in respiratory secretions. A patient admitted at a later stage with complications such as bacterial pneumonia might be missed because the virus would no longer be present. Such patients can be identified by testing acute-phase and convalescent-phase serum samples for a significant antibody rise to influenza antigens. The number of patients with respiratory virus infection identified may be doubled if paired serum samples are tested.4 Furthermore, complications of influenza virus infection may involve organ systems other than the respiratory tract; these complications include encephalopathy, myocarditis, and myositis. Thus, it is clear that influenza causes more deaths and hospitalizations than all other diseases that are preventable by vaccine combined and that universal immunization against influenza should be considered. The NVSN provides an efficient platform for evaluating the effectiveness of universal immunization against influenza among preschool children.
The NVSN sites did not include appreciable numbers of uninsured families, who compose almost 20 percent of the U.S. population. The demographics of this uninsured group include many young families whose income is too high to qualify for Medicaid and too low to afford health insurance. The rates of hospitalization of children in these households are several times as high as those of children in families with health care coverage.5 The provision of annual seasonal vaccination for these children will test the public health infrastructure. Current recommendations regarding the influenza vaccine also include the household contacts of persons who are given priority for vaccination. The priority list now includes children younger than five years of age. Many of the household contacts are schoolchildren, who have the highest annual rates of infection with the influenza virus and are the main transmitters of infection. Currently, rates of immunization for healthy household contacts are low because no system exists for identifying and vaccinating these persons each year. A reasonable adjunct to current strategies for influenza control would be to extend the recommendation for vaccination to all schoolchildren and to reach them through school-based clinics.6 These clinics would affect all segments of the school-aged population — even the uninsured. Not only could school-based vaccination clinics improve control of seasonal influenza epidemics, but they would provide venues for rapid deployment of vaccine during a pandemic — an important consideration.
The NVSN group reported that outpatient visits attributable to influenza infection confirmed by laboratory culture were 10 to 250 times as common as hospitalizations for the target age groups. However, they stress that recognition of influenza infection by the treating clinician was low. As a consequence, few patients were offered specific therapy for infection with the influenza virus. This lack of recognition represents a missed opportunity to intervene to reduce both the risk of complications and the spread of the virus to contacts. Young children excrete greater concentrations of virus for longer periods of time than do older patients. Treatment of these younger patients even three to four days after the onset of infection may at least reduce the spread of infection to contacts. Identification of infection in the index child is also an opportunity to treat or extend prophylaxis against influenza to family contacts. Antiviral medications are likely to be a central defense against the first wave of the next pandemic. Surveillance networks such as the NVSN group, coupled with effective treatment of patients and their contacts, will contribute to the control of seasonal influenza and may provide a valuable rehearsal for the next pandemic.
Dr. Glezen reports having received consulting fees from MedImmune, Chiron, and GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.
Source Information
From the Department of Molecular Virology and Microbiology and the Department of Pediatrics, Baylor College of Medicine, Houston.
References
Glezen WP. The changing epidemiology of respiratory syncytial virus and influenza: impetus for new control measures. Pediatr Infect Dis J 2004;23:Suppl:S202-S206.
Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333-1340.
Poehling KA, Edwards KM, Weinberg GA, et al. The underrecognized burden of influenza in young children. N Engl J Med 2006;355:31-40.
Munoz FM. The impact of influenza in children. Semin Pediatr Infect Dis 2002;13:72-78.
Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 2000;283:499-505.
Glezen WP, Simonsen L. Benefits of influenza vaccine in US elderly -- new studies raise questions. Int J Epidemiol 2006;35:352-353.(W. Paul Glezen, M.D.)