640
MAJOR ARTICLES
Association between Respiratory Syncytial Virus Outbreaks and Lower Respiratory Tract Deaths of Infants and Young Children Larry J. Anderson, Robert A. Parker,* and Raymond L. Strilms*
From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia
Respiratory syncytial virus (RSV) is the single most important lower respiratory tract pathogen in infants and young children in developed countries [1-6]. In temperate climates, it usually causes outbreaks of infection each winter or early spring, and these outbreaks are often associated with increases in hospitalizations for acute respiratory illness. Studies of RSV infections and etiologic studies of acute respiratory illness deaths have demonstrated the RSV infections are also an important cause of deaths of infants and young children [6-12]. As candidate RSV vaccines are developed and move into clinical trials, it becomes increasingly important to determine the disease burden associated with outbreaks of RSV infections. One approach to estimating disease burden, used successfully for influenza, takes advantage of an increase in pneumonia and influenza deaths in adults associated with influenza outbreaks [13]. Since RSV is such an important cause of serious acute respiratory illness in infants and young children, it is possible that RSV outbreaks cause an increase in deaths from this illness in this age group; however outbreaks of other respiratory viruses may also be associated with increases in acute respiratory illness deaths in this age group. To study this possibility, we determined the temporal and geographic patterns of RSV and parainfluenza viruses 1, 2,
Received 20 April 1989; revised 29 September 1989. Reprints and correspondence: Dr. Larry J. Anderson, CDC, CID, DVD, 1600 Clifton Rd., Bldg. 7, Mailstop G17, Rm. B43, Atlanta, GA 30333. * Present addresses: Department of PreventiveMedicine, Vanderbilt University School of Medicine, Nashville, TN (R. A. P.); Center for Preventive Services, Division of Immunization (CDC), Atlanta, GA (R. L. S.). The Journal of Infectious Diseases 1990;161:640-646 This article is in the public domain. 0022-1899/90/6104-0007
and 3 and the temporal pattern of influenza A and B outbreaks in the USA and identifiedassociations between these outbreaks and deaths, by cause, of children 50 deaths per year and in which the peak number of deaths occurred in the autumn or winter was compared with the temporal patterns of virus isolations. The causes of death examined and the number of deaths in the 9-year period are listed in table 2. The data were coded according to the International Classification of Disease (ICD) eighth revision [15] for 1975-1978 and ninth revision [16] for 1979-1984. Definitions. A health year is the period from 1 July through 30 June of the following year; this treats the winter respiratory season (for this study, October-March) as a continuous period. An outbreak month was defined as any month with one-twelfth or more
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on June 18, 2015
The temporal patterns of respiratory virus isolations from 10 laboratories in the USA were compared with that of deaths of children .+-''---¥-.L-----''r'-'----'-', July 1975
July 1976
July 1977
July
July
July
July
July
July
July
1978
1979
1980
1981
1982
1983
1984
By Month
~ -0.10
~
~
. at
~
-0.10 :
--,----,----.---,--,....--.------.---+ -0.20
-0.20
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.
l:16
1~17 1~18
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By Month
Figure 3. Comparison of observed RSV isolations and observed deaths of infants 1-5 months old. Top, relationship between RSV isolations and LRI deaths; bottom, between RSV isolations and deaths from fires in private dwellings. Timing of peaks is similar to that for RSV for both lower respiratory illness (LRI) and fire deaths.
75 % of the individual health years for individual laboratories, the duration of outbreaks was 3-5 months. Associationbetweenvirusisolationand mortality. There were many significant temporal correlations between the percentage of deaths by cause and the percentage of monthly isolations for the six viruses; most of these associations, however, did not persist in the analysis of residual deaths and isolations. For example, in the 1-5 month age group, deaths from conflagrations (fire) in private dwellings and lower respiratory illness (LRI) were strongly associated with RSV (r = .615, P< .0001 and r = .875, P< .0001, respectively-figure 3). It is unlikely.however, that RSV isolations are causally related to deaths from fire: In the residual analysis, the association between RSV isolations and deaths from fire disappeared (r = .048, P> .5). The association between RSV and LRI deaths persisted (r = .412, P < .0001; figure 4). RSV and influenza virus were the isolations most often associated with specific causes of death (usually respiratory) in both the observed and the residual analyses (table 3). RSV isolations were most prominently associated with the respiratory deaths of children 1-11 months old; influenza virus isolations were most prominently associated with the respiratory deaths of children 24-59 months old. The correlation coefficient for the residual data for RSV and all LRI deaths for the 1-5 month group was r = .412 (P < .0001); for the 6-11 month group it was r = .245 (P < .05). RSV was also associated with all respiratory tract illness deaths in the 1-5 month group (for the residual data, r = .499, P < .0001). The correlation coefficients for influenza A and all LRI deaths and for influenza A plus B and all LRI deaths, for children 24-59 months old, are r = .228 (P < .05) and r = .350 (P < .001), respectively.
Figure 4. Comparison of residual RSV isolations and residual deaths of infants 1-5 months old. Top, relationship between RSV isolations and lower respiratory illness (LRI) deaths; bottom, between RSV isolations and deaths from fires in private dwellings. To better illustrate temporal patterns of residual LRI deaths, scale for residual LRI deaths is one-half that for residual RSV isolations and residual fire deaths. Timing of peaks and valleys in residual data for RSV isolations is similar to that for LRI deaths but not for fire deaths.
Over the 9 study years, the number of deaths associated with the winter peaks as measured by the difference in deaths between winter (October through March) and summer (April through September) ranged from 186 to 454 LRI deaths per year of children 1-11 months old and from 24 to 90 LRI deaths per year of children 24-59 months old . RSV or influenza virus isolations were also associated with deaths due to congenital anomalies of the heart and circulatory system, meningococcal disease, and septicemia and sudden deaths of unknown cause (table 3). Discussion In this study, we demonstrated for the first time an association between outbreaks of RSV infections and peaks in national respiratory deaths, especially LRI deaths, of infants and young children. To ensure that this association was not spurious, we required that the association be present in analyses of both observed data and residual data. Using residuals reduced the possibility that spurious associations were caused by seasonal factors. The residual analysis, for example, eliminated a spurious association between RSV isolations and deaths from fire. A casual relationship, however, should not be inferred solely from a temporal relationship. The relationship between RSV isolations and LRI deaths that we found is supported by published reports that show (1) serious RSV disease is most common in children 1-11 months old [19]; (2) serious RSV disease
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on June 18, 2015
II>
.§
Anderson et al.
644
JID 1990;161 (April)
Table 3. Residual virus isolations and death among children
MAJOR ARTICLES
Association between Respiratory Syncytial Virus Outbreaks and Lower Respiratory Tract Deaths of Infants and Young Children Larry J. Anderson, Robert A. Parker,* and Raymond L. Strilms*
From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia
Respiratory syncytial virus (RSV) is the single most important lower respiratory tract pathogen in infants and young children in developed countries [1-6]. In temperate climates, it usually causes outbreaks of infection each winter or early spring, and these outbreaks are often associated with increases in hospitalizations for acute respiratory illness. Studies of RSV infections and etiologic studies of acute respiratory illness deaths have demonstrated the RSV infections are also an important cause of deaths of infants and young children [6-12]. As candidate RSV vaccines are developed and move into clinical trials, it becomes increasingly important to determine the disease burden associated with outbreaks of RSV infections. One approach to estimating disease burden, used successfully for influenza, takes advantage of an increase in pneumonia and influenza deaths in adults associated with influenza outbreaks [13]. Since RSV is such an important cause of serious acute respiratory illness in infants and young children, it is possible that RSV outbreaks cause an increase in deaths from this illness in this age group; however outbreaks of other respiratory viruses may also be associated with increases in acute respiratory illness deaths in this age group. To study this possibility, we determined the temporal and geographic patterns of RSV and parainfluenza viruses 1, 2,
Received 20 April 1989; revised 29 September 1989. Reprints and correspondence: Dr. Larry J. Anderson, CDC, CID, DVD, 1600 Clifton Rd., Bldg. 7, Mailstop G17, Rm. B43, Atlanta, GA 30333. * Present addresses: Department of PreventiveMedicine, Vanderbilt University School of Medicine, Nashville, TN (R. A. P.); Center for Preventive Services, Division of Immunization (CDC), Atlanta, GA (R. L. S.). The Journal of Infectious Diseases 1990;161:640-646 This article is in the public domain. 0022-1899/90/6104-0007
and 3 and the temporal pattern of influenza A and B outbreaks in the USA and identifiedassociations between these outbreaks and deaths, by cause, of children 50 deaths per year and in which the peak number of deaths occurred in the autumn or winter was compared with the temporal patterns of virus isolations. The causes of death examined and the number of deaths in the 9-year period are listed in table 2. The data were coded according to the International Classification of Disease (ICD) eighth revision [15] for 1975-1978 and ninth revision [16] for 1979-1984. Definitions. A health year is the period from 1 July through 30 June of the following year; this treats the winter respiratory season (for this study, October-March) as a continuous period. An outbreak month was defined as any month with one-twelfth or more
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on June 18, 2015
The temporal patterns of respiratory virus isolations from 10 laboratories in the USA were compared with that of deaths of children .+-''---¥-.L-----''r'-'----'-', July 1975
July 1976
July 1977
July
July
July
July
July
July
July
1978
1979
1980
1981
1982
1983
1984
By Month
~ -0.10
~
~
. at
~
-0.10 :
--,----,----.---,--,....--.------.---+ -0.20
-0.20
l:~5
.
l:16
1~17 1~18
1i.u1/9 l:lro l:'11 l:lr2
1~lr3 1~lr4
By Month
Figure 3. Comparison of observed RSV isolations and observed deaths of infants 1-5 months old. Top, relationship between RSV isolations and LRI deaths; bottom, between RSV isolations and deaths from fires in private dwellings. Timing of peaks is similar to that for RSV for both lower respiratory illness (LRI) and fire deaths.
75 % of the individual health years for individual laboratories, the duration of outbreaks was 3-5 months. Associationbetweenvirusisolationand mortality. There were many significant temporal correlations between the percentage of deaths by cause and the percentage of monthly isolations for the six viruses; most of these associations, however, did not persist in the analysis of residual deaths and isolations. For example, in the 1-5 month age group, deaths from conflagrations (fire) in private dwellings and lower respiratory illness (LRI) were strongly associated with RSV (r = .615, P< .0001 and r = .875, P< .0001, respectively-figure 3). It is unlikely.however, that RSV isolations are causally related to deaths from fire: In the residual analysis, the association between RSV isolations and deaths from fire disappeared (r = .048, P> .5). The association between RSV and LRI deaths persisted (r = .412, P < .0001; figure 4). RSV and influenza virus were the isolations most often associated with specific causes of death (usually respiratory) in both the observed and the residual analyses (table 3). RSV isolations were most prominently associated with the respiratory deaths of children 1-11 months old; influenza virus isolations were most prominently associated with the respiratory deaths of children 24-59 months old. The correlation coefficient for the residual data for RSV and all LRI deaths for the 1-5 month group was r = .412 (P < .0001); for the 6-11 month group it was r = .245 (P < .05). RSV was also associated with all respiratory tract illness deaths in the 1-5 month group (for the residual data, r = .499, P < .0001). The correlation coefficients for influenza A and all LRI deaths and for influenza A plus B and all LRI deaths, for children 24-59 months old, are r = .228 (P < .05) and r = .350 (P < .001), respectively.
Figure 4. Comparison of residual RSV isolations and residual deaths of infants 1-5 months old. Top, relationship between RSV isolations and lower respiratory illness (LRI) deaths; bottom, between RSV isolations and deaths from fires in private dwellings. To better illustrate temporal patterns of residual LRI deaths, scale for residual LRI deaths is one-half that for residual RSV isolations and residual fire deaths. Timing of peaks and valleys in residual data for RSV isolations is similar to that for LRI deaths but not for fire deaths.
Over the 9 study years, the number of deaths associated with the winter peaks as measured by the difference in deaths between winter (October through March) and summer (April through September) ranged from 186 to 454 LRI deaths per year of children 1-11 months old and from 24 to 90 LRI deaths per year of children 24-59 months old . RSV or influenza virus isolations were also associated with deaths due to congenital anomalies of the heart and circulatory system, meningococcal disease, and septicemia and sudden deaths of unknown cause (table 3). Discussion In this study, we demonstrated for the first time an association between outbreaks of RSV infections and peaks in national respiratory deaths, especially LRI deaths, of infants and young children. To ensure that this association was not spurious, we required that the association be present in analyses of both observed data and residual data. Using residuals reduced the possibility that spurious associations were caused by seasonal factors. The residual analysis, for example, eliminated a spurious association between RSV isolations and deaths from fire. A casual relationship, however, should not be inferred solely from a temporal relationship. The relationship between RSV isolations and LRI deaths that we found is supported by published reports that show (1) serious RSV disease is most common in children 1-11 months old [19]; (2) serious RSV disease
Downloaded from http://jid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on June 18, 2015
II>
.§
Anderson et al.
644
JID 1990;161 (April)
Table 3. Residual virus isolations and death among children
