Correspondence
Influenza and Hospitalizations in Children
N Engl J Med 2000; 342:1752-1753June 8, 2000
- Article
To the Editor:
The quantitation of mortality and morbidity caused by influenzavirus infections has traditionally relied on estimates of the number of infections that occur in excess of the number expected for the season. The sharp seasonality of the annual influenza epidemics allows such estimates. Two reports in the January 27 issue of the Journal, one by Neuzil et al.1 and one by Izurieta et al.,2 assessed the serious morbidity that might be attributed to influenzavirus infections in children. These estimates of morbidity are substantial but conservative. Both groups of investigators limited their estimates because of concern about overlap of respiratory syncytial virus infections. In their Tennessee study, Neuzil et al.1 used rates for the “peri-influenza season” as the main base-line values. The rate for the peri-influenza season was subtracted from the rate for the epidemic period of influenza. This method relies on a false assumption that all of the respiratory pathogens involved in the winter respiratory-disease season are layered proportionally, with influenzavirus added on top.3 The activity of both respiratory syncytial virus and parainfluenza virus peaks in the peri-influenza season. Therefore, subtracting the rate for the peri-influenza season leads to a large underestimate of the rate of influenza-attributable disease. Furthermore, this study combined data for the period from 1973 to 1984, a period when influenza epidemics were less intense and less frequent.4 Limiting the analysis to the epidemics that occurred from 1984–1985 to 1992–1993 would provide information that is more representative of the current situation.
The survey of morbidity performed by Izurieta et al.2 in a large West Coast population of patients in managed care is limited because it does not include lower-income populations, which have the highest rates of hospitalizations. Furthermore, the method of separating the periods of respiratory syncytial virus activity from periods in which influenza virus activity predominated is flawed by the difference in sensitivity of the diagnostic tests used for the viruses. Tests for respiratory syncytial virus — either culture or antigen detection — are more sensitive than those for influenzavirus or parainfluenza virus. My colleagues and I found that only 25 percent of infections with the latter viruses among hospitalized children who were younger than five years of age were identified by culture or antigen detection, as compared with 63 percent of respiratory syncytial virus infections.5 The remainder of infections were detected by increases in antibody titers only in serum specimens obtained from patients during convalescence.
Finally, both studies should have presented annualized rates so that one could compare current rates with earlier rates. Because of the variability in the occurrence of infections with the major viruses, it is difficult to standardize the expected base-line rate of morbidity. Use of the rate during the summer nadir for estimates of serious morbidity would avoid underestimation.
5 ReferencesW. Paul Glezen, M.D.
Baylor College of Medicine, Houston, TX 770301
Neuzil KM ,Mellen BG ,Wright PF ,Mitchel EF ,Griffin MR . The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000;342:225-231
Full Text | Web of Science | Medline2
Izurieta HS ,Thompson WW ,Kramarz P , et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-239
Full Text | Web of Science | Medline3
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
CrossRef | Web of Science | Medline4
Glezen WP . Influenza control -- unfinished business. JAMA 1999;281:944-945
CrossRef | Web of Science | Medline5
Glezen WP ,Paredes A ,Taber LH . Influenza in children: relationship to other respiratory agents. JAMA 1980;243:1345-1349
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Dr. Glezen that it may be difficult to distinguish hospitalizations that are secondary to influenzavirus infections from those that are due to respiratory syncytial virus infections in young children on the basis of epidemiologic criteria. However, by using prospective surveillance methods for both viruses, we attempted to minimize any confounding effect of respiratory syncytial virus infections. When we excluded the periods of peak respiratory syncytial virus activity from our analysis, our influenza-attributable estimates were similar to estimates that included these periods, suggesting that over the 19 years of the study, respiratory syncytial virus infections contributed equally to disease rates in peri-influenza and influenza seasons. In Nashville, there was greater overlap of respiratory syncytial virus and influenzavirus seasons from 1984–1985 to 1992–1993 than from 1973 to 1984. Confining the analysis to these later years would have exaggerated the influenza-associated morbidity. Likewise, confounding by parainfluenza virus was most likely minimal. During the period of the study, the activity of parainfluenza virus types 1 and 2 peaked during October, which we defined as part of the “summer season” in our study. Parainfluenza virus type 3 infections occurred throughout the year, with two peaks — in March, during our influenza–peri-influenza seasons, and in May, during our summer season.1
We estimated that, each year in Tennessee, influenzavirus infections were responsible for 2.6 hospitalizations per 1000 previously healthy children who were younger than five years of age and who were enrolled in Medicaid, with rates of 7.5 per 1000 among children who were younger than one year of age and of 0.9 per 1000 among those who were three to four years old. Using different methods, Mullooly and Barker estimated that 1 per 1000 children who were younger than five years of age and who were enrolled in a health maintenance organization were hospitalized for influenzavirus infections.2 The rates reported by Izurieta et al. indicated that the influenza-associated rate of hospitalization was 1 to 2 per 1000 children who were younger than two years of age. The sociodemographic characteristics of the Medicaid population may contribute to our higher estimates. However, all three studies are consistent in their findings of substantial influenza-related morbidity in young children, and the results warrant further efforts to prevent influenza-associated illness.
2 ReferencesKathleen M. Neuzil, M.D., M.P.H.
University of Washington School of Medicine, Seattle, WA 98195Marie R. Griffin, M.D., M.P.H.
Peter F. Wright, M.D.
Vanderbilt University School of Medicine, Nashville, TN 372321
Reed G ,Jewett PH ,Thompson J ,Tollefson S ,Wright PF . Epidemiology and clinical impact of parainfluenza virus infections in otherwise healthy infants and young children <5 years old. J Infect Dis 1997;175:807-813
CrossRef | Web of Science | Medline2
Mullooly JP ,Barker WH . Impact of type A influenza on children: a retrospective study. Am J Public Health 1982;72:1008-1016
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with Dr. Glezen that our estimates of the rates of influenza-related hospitalization among young children were “substantial but conservative.” The conservative estimates resulted from our attempts to reduce the effect of infections with other respiratory viruses, including respiratory syncytial virus and parainfluenza virus types 1 and 3, on the estimates of influenza-related rates of hospitalization. Dr. Glezen suggests that the use of a summer base-line value to estimate the rate of influenza-attributable hospitalizations would avoid an underestimation of the effect of influenzavirus infections, but the use of such a base line runs the risk of producing overinflated estimates. Because of these competing concerns and because various base lines have been used by others for such estimates,1-3 we used a summer base-line value to produce a high estimate of the rate of influenza-attributable hospitalization among children in addition to our use of a periseason base-line value to produce a conservative estimate.
Dr. Glezen also states that our findings were limited because the study population did not include lower-income populations. A study using 1990 U.S. Census data found that the proportion of members of Northern California Kaiser Permanente who lived in predominantly working-class census-block groups was similar to that in the general U.S. population.4 Although the proportion of members in impoverished and undereducated census-block groups was somewhat lower than the proportion in the general population,4 these members were not excluded from our analyses.
Finally, we disagree with Dr. Glezen's assertion that our method of separating the periods of influenzavirus activity and respiratory syncytial virus activity was flawed by differences in the sensitivity of the diagnostic tests used to detect these viruses. Although various tests were used with differing sensitivities, the large number of positive results (3638 in the San Francisco Bay area and 4883 in the Seattle area) from persons of all ages allowed us to make an accurate determination of the periods when each virus was in circulation and to define appropriately the periods in which each virus predominated.
4 ReferencesHéctor S. Izurieta, M.D., M.P.H.
Pan American Health Organization, Washington, DC 20037William W. Thompson, Ph.D.
David K. Shay, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 303331
Mullooly JP ,Barker WH . Impact of type A influenza on children: a retrospective study. Am J Public Health 1982;72:1008-1016
CrossRef | Web of Science | Medline2
Glezen WP ,Decker M ,Perrotta DM . Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978-1981. Am Rev Respir Dis 1987;136:550-555
CrossRef | Web of Science | Medline3
Neuzil KM ,Reed GW ,Mitchel EF ,Simonsen L ,Griffin MR . Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094-1102
Web of Science | Medline4
Krieger N . Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 1992;82:703-710
CrossRef | Web of Science | Medline
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