Pediatric Annals

Viral Respiratory Infections

W Paul Glezen, MD

Abstract

The National Health Interview Survey for 1989 estimated that 19 million preschool children in the United States experienced about 45 million acute respiratory illnesses that altered their usual activities or caused their parents to seek medical consultation.1 On average, each child had 2-4 episodes that met these criteria. These illnesses included almost 14 million upper respiratory illnesses, 11.7 million acute ear infections, 11.6 million episodes of influenza-like illness, 1.8 million episodes of acute bronchitis, and 536 000 episodes of pneumonia. The vast majority of these illnesses were medically attended; overall, 72.8% were of sufficient severity to cause parents to take their child to a primary care facility. Physician encounters were recorded for virtually all acute ear infections and lower respiratory tract illnesses (LRIs). These estimates provide a measure of the severe morbidity associated with acute respiratory illness (ARI) in the United States and its impact on the health care system. More than one half of preschool children are in regular day care, and these children experience the larger proportion of the ARI burden. Many investigations have implicated respiratory viruses as the major causes of these illnesses - either by directly damaging the respiratory epithelium or by facilitating the invasion of bacterial pathogens into the middle ear and the lower respiratory tract.2"4

Most studies have shown that young children in group day care experience more ARIs than children in home care and that children in day care have illnesses of greater consequence. These studies have suggested that young children in day care are more likely to have LRIs, to be hospitalized for ARIs, and to need myringotomy and tube placement for persistent middle ear effusion. In a longitudinal study of infants followed from birth, Gardner et al5 found that children in day care had a significantly higher rate of LRIs. Bronchiolitis and pneumonia - but not croup - were more common among children in day care. Anderson et al6 examined risk factors associated with LRI hospitalizations of children under the age of 2; they found that regular attendance in group day care (more than six children in attendance) was significantly related to hospital ization. The duration of illness and the frequency of complications were compared for children in home care or day care by Wald and her associates.7,8 Children in day care had more severe illnesses of longer duration and were more likely to require myringotomy and tube placement for persistent middle ear effusion.

Table

Studies of infected children show that, on the average, virus excretion lasts for 7 to 10 days.18 Exclusion of children with ARIs would not be effective because viruses may be recovered from the upper respiratory tract 1 to 4 days before the onset of symptoms. The duration of virus excretion is related to the severity of the illness but may persist for a week or two after symptoms have subsided, especially for RSV, parainfluenza type 3, and adenoviruses.

For all of these reasons, transmission of respiratory viruses occurs readily in the day-care setting and is difficult to prevent. However, this does not mean that efforts to limit transmission would be futile. One interpretation of the comparison of outcome of RSV infection for children in day care and home care is that the virus inoculum is greater in the day-care setting. The higher frequency of LRIs observed among children in day care may be a consequence of the higher inoculum. Therefore, efforts to limit spread by careful handwashing and good hygiene practices are warranted. Infants should be segregated from toddlers and protected against exposure to older children with upperrespiratory illnesses. Infants less than 6 months of age…

The National Health Interview Survey for 1989 estimated that 19 million preschool children in the United States experienced about 45 million acute respiratory illnesses that altered their usual activities or caused their parents to seek medical consultation.1 On average, each child had 2-4 episodes that met these criteria. These illnesses included almost 14 million upper respiratory illnesses, 11.7 million acute ear infections, 11.6 million episodes of influenza-like illness, 1.8 million episodes of acute bronchitis, and 536 000 episodes of pneumonia. The vast majority of these illnesses were medically attended; overall, 72.8% were of sufficient severity to cause parents to take their child to a primary care facility. Physician encounters were recorded for virtually all acute ear infections and lower respiratory tract illnesses (LRIs). These estimates provide a measure of the severe morbidity associated with acute respiratory illness (ARI) in the United States and its impact on the health care system. More than one half of preschool children are in regular day care, and these children experience the larger proportion of the ARI burden. Many investigations have implicated respiratory viruses as the major causes of these illnesses - either by directly damaging the respiratory epithelium or by facilitating the invasion of bacterial pathogens into the middle ear and the lower respiratory tract.2"4

Most studies have shown that young children in group day care experience more ARIs than children in home care and that children in day care have illnesses of greater consequence. These studies have suggested that young children in day care are more likely to have LRIs, to be hospitalized for ARIs, and to need myringotomy and tube placement for persistent middle ear effusion. In a longitudinal study of infants followed from birth, Gardner et al5 found that children in day care had a significantly higher rate of LRIs. Bronchiolitis and pneumonia - but not croup - were more common among children in day care. Anderson et al6 examined risk factors associated with LRI hospitalizations of children under the age of 2; they found that regular attendance in group day care (more than six children in attendance) was significantly related to hospital ization. The duration of illness and the frequency of complications were compared for children in home care or day care by Wald and her associates.7,8 Children in day care had more severe illnesses of longer duration and were more likely to require myringotomy and tube placement for persistent middle ear effusion.

Table

TABLE 1Viruses Associated With Acute Respiratory Illness

TABLE 1

Viruses Associated With Acute Respiratory Illness

RESPIRATORY VIRUSES

More than 200 respiratory viruses have been associated with ARIs; most of these have been recovered from children in day care.3 Table 1 lists the principal viruses along with their types and subtypes.

Adenoviruses

Adenoviruses are a particular problem in the daycare setting. Studies have suggested that adenovirus infections are more frequent among children in day care than among children cared for at home.5 Adenovirus infections also are associated with development of acute otitis media.9 Their role in the pathogenesis of ear infections has not been fully explored, but as the name suggests, they were first isolated from adenoidal tissue removed during surgery. Viral invasion and inflammation of the lymphoid tissue of the nasopharynx could well lead to eustachian tube dysfunction and negative middle ear pressure, which appear to be important in the development of acute otitis media.

Table

TABLE 2Variants of Influenza Viruses Prevalent in the United States, 1978-1991

TABLE 2

Variants of Influenza Viruses Prevalent in the United States, 1978-1991

Influenza Viruses

Influenza viruses present a unique problem for day care. Allowing young, susceptible children from several households to congregate regularly provides optimal conditions for the spread of influenza viruses. Because a different influenza virus or viruses may be present each yean there is no opportunity for young children to acquire natural immunity that will protect against the prevalent viruses. Currently, there are three different influenza viruses circulating in the world, and antigenic variants may arise to each of these. Table 2 shows the major variants that have been active during the last 13 years since the reemergence of the influenza A (HlNl ) viruses. During that period, a total of 1 7 variants have produced epidemic disease - some variants have been active during more than one season. The unstable genome of the virus is sensitive to immune pressures - as soon as a large proportion of the population develops immunity to one variant, a new one arises. Therefore, the high attack rates in children can be accounted for readily. Children 5 years old or younger followed in the Houston Family Study experienced influenza virus infections at an annual rate of 40 per 100; 88% of these infections were associated with ARI. Hospitalization rates for children in this age group ranged from 3 to 7 per 1000 during influenza epidemics with the risk varying with the influenza type or subtype that was prevalent.10 The highest ARI hospitalizaron rates have occurred during influenza A (H3N2) epidemics. Influenza virus infection rates are particularly high in children in group day care, and an increase in episodes of AOM usually accompanies the influenza outbreaks.3,1 1

Table

TABLE 3Rates of Primary Infection With Respiratory Syncytial Virus, Chapel HlII Day Care Center (DCC)15 and Houston Family Study (HFS)12

TABLE 3

Rates of Primary Infection With Respiratory Syncytial Virus, Chapel HlII Day Care Center (DCC)15 and Houston Family Study (HFS)12

Respiratory Syncytial Virus

Respiratory syncytial vinos (RSV) is the most important cause of ARI in infants and young children.12 Infection rates are high during the first year of life, and virtually all children are infected by their second birthday. Reinfection is also common; in fact, about one half will have experienced a second infection by the end of their second year. Respiratory syncytial virus has a special trophism for the smallest airways; therefore, it is the major cause of bronchiolitis during the first year of life. In general, the severity of illness is related to the age of the infant at the time of infection - the younger the infant, the more severe the infection. Hospitalizations for RSV infection aie highest for infants in the second and third month of life.13 At least 1% of all infants require hospitalization for RSV disease. Respiratory syncytial virus is also the virus most frequently associated with acute otitis media.9,14 The virus is frequently recovered from the middle ear of infants with acute otitis media, and the occurrence of acute otitis media peaks when RSV is active in the day-care setting.

Overall, the infection rate for RSV is not higher for children in day care compared to children cared for at home; however, for children entered into day care at an early age, RSV infection is likely to be acquired at a younger age than observed for children in home care. Therefore, the consequences of infection may be more severe for infants in group day care. Table 3 compares the published RSV infection rates for infants and toddlers cared for in a day-care center15 with those of infants and young children cared for mostly at home.12 Although the methods of surveillance were slightly different and the groups were observed in different places at different times, the comparison is instructive. Forty-one of 42 day-care infants were infected during the first year, and 60 of 100 had clinical evidence of lower tract involvement. In contrast, only two thirds of infants cared for at home were infected, and only 22 of 100 had evidence of LRI. A higher rate of LRI was also observed for toddlers in day care; 42 of 100 had LRI compared to only 6 of 100 for toddlers at home. Infants entered the day-care center at 6 to 13 weeks of age in cohorts recruited in the summer. Therefore, the day-care infants were about 6 months old at the time of the RSV epidemic - beyond the age of greatest risk for the most serious outcome. If they had been recruited throughout the year so that their ages would have been staggered as were the children in the longitudinal home-care study in Houston, the difference in severity of illness might have been greater.

The differences in severity of illness were less pronounced for reinfection illnesses (Table 4)- Toddlers in day care had slightly higher reinfection rates and LRI rates.

Other Viruses

Infections with patainfluenza virus type 3 are as common as infections with RSV; however, the clinical manifestations of parainfluenza type 3 infections are usually milder.16 Rhinovirus infections appear to be more common in the day-care setting than at home.5 Rhinoviruses are usually associated with mild ARI and may trigger episodes of asthma in children. Infections with coronaviruses have the same clinical spectrum as rhinoviruses. Because of the complexities of diagnosing these viral infections, little is known about their prevalence in the day-care setting.

TRANSMISSION

The spread of respiratory viruses occurs readily in the day-care setting. Transmission may occur by aerosol, droplet nuclei, or direct contact. Varicella is difficult to control, but children with this diagnosis should be excluded from day caie foi at least 5 days. Influenza viruses are the best example of those that may spread by aerosol. Rhinoviruses are stable in the environment and may be picked up from shared toys and other objects. Even though RSV is relatively labile, it has been shown to survive on counter tops for as long as 6 hours.17 Day-care center personnel may participate in the spread of viruses through poor handwashing techniques. Self- inoculation may occur onto the mucosa of the eyes or nose, and transient asymptomatic carriage may result. Therefore, personnel are links in the chain of infections.

Table

TABLE 4Rates of Reinfection With Respiratory Syncytlal Virus, Chapel Hill Day Care Center (DCC)15 and Houston Family Study (HFS)12

TABLE 4

Rates of Reinfection With Respiratory Syncytlal Virus, Chapel Hill Day Care Center (DCC)15 and Houston Family Study (HFS)12

Studies of infected children show that, on the average, virus excretion lasts for 7 to 10 days.18 Exclusion of children with ARIs would not be effective because viruses may be recovered from the upper respiratory tract 1 to 4 days before the onset of symptoms. The duration of virus excretion is related to the severity of the illness but may persist for a week or two after symptoms have subsided, especially for RSV, parainfluenza type 3, and adenoviruses.

For all of these reasons, transmission of respiratory viruses occurs readily in the day-care setting and is difficult to prevent. However, this does not mean that efforts to limit transmission would be futile. One interpretation of the comparison of outcome of RSV infection for children in day care and home care is that the virus inoculum is greater in the day-care setting. The higher frequency of LRIs observed among children in day care may be a consequence of the higher inoculum. Therefore, efforts to limit spread by careful handwashing and good hygiene practices are warranted. Infants should be segregated from toddlers and protected against exposure to older children with upperrespiratory illnesses. Infants less than 6 months of age should not enter a group day-care setting during the respiratory season. Home-care arrangements with fewer than six children are preferred - especially for the first year of life.

SPECIFIC PROPHYLAXIS

Few vaccines or antiviral drugs that might be useful for otherwise healthy children in day care are available for respiratory viruses. Measles vaccine is recommended at 15 months of age for most children and at 1 year of age for children living in high-risk areas of the United States. A high-risk area is defined as: 1 ) a county with more than five cases among preschoolaged children during each of the last 5 years, 2) a county with a recent outbreak among unvaccinated preschool-aged children, and 3) cities with large unvaccinated populations. Failure to immunize a child against measles at the appropriate age is cause for exclusion from day care.

Inactivated influenza vaccine is recommended for children at risk for complications of influenza virus infection, such as those with asthma or other cardiopulmonary disorders. Influenza vaccine is also recommended for children who are household contacts of persons with these high-risk conditions. The vaccine is available for any child 6 months of age or older for whom the parents wish to decrease the risk of influenza virus infection. The inactivated vaccine does not produce a barrier to infection but serves to modify the consequences of infection. Therefore, it is not ideally suited for some of the purposes listed above. Two doses administered 4 weeks apart are required for the initial vaccination and annual injections are required thereafter.

The expense and discomfort of vaccination may not warrant routine use in healthy children; however, a recent study has demonstrated a significant reduction in the incidence of otitis media with the use of influenza vaccine among children in day care.19 The new live attenuated vaccine for intranasal administration may prove to be more effective and better accepted than the inactivated vaccine.20 The cold recombinant vaccine would probably have greatest usefulness for the universal immunization of children under the age of i O. Such a vaccine might be particularly effective for young children in day care. Universal immunization of children could also modify epidemic influenza for the community as a whole. Prevention of infection in the age group with highest attack rates could reduce the risk of exposure for all high-risk patients.

Amantadine is an antiviral drug that is effective as a treatment or as a prophylactic agent for influenza A virus infection. Unfortunately, this drug has a very narrow spectrum and is not effective for any other virus. The drug is available for use in children over the age of 1. During influenza A epidemics, it could be a useful tool for controlling infections of older children in day care by combining treatment of ill children with prophylaxis of children not yet ill. Amantadine does have side effects that are unpleasant, producing insomnia, loss of appetite, irritability, and dizziness in 5% to 10% of persons. These annoying side effects have limited its usefulness in healthy children. An analogue of amantadme, rimantadine, has the same effect as amantadine without the side effects. If this drug is licensed, it will be more useful in controlling influenza A infections in day care. Clover et al administered this drug to children for as long as 6 weeks and significantly reduced influenza A infections without side effects when compared to placebo in a randomized, double-blind study.21

REFERENCES

1. Current estimates from the National Health Interview Survey, United States, 1989. Vital Health Stat (10). 1990; 176: 14- 50.

2. Denny FW, Collier AM, Henderson FW. Acute respiratory infections in day care. Rev Infect Dis. 1986;8:527-532.

3. Loda FA, Gleien WP, Clyde WA Jr. Respiratory disease in group day cate. Pediatrics. 1972;49:12M37.

4. Strangert K, Carlstrum G, Jeansson S, Nord C-E. Infections in preschool children in group day care. Acta Paediair Scand. 1976;65:455-463.

5. Gardner G, Frank AL, Tabct LH. Effects of social and family factors on viral respiratory infection and illness in the first year of life. J Epidemial Community Health. 1984;38:42-48.

6. Andersen LJ, Parker RA, Strikes RA, et al. Day care center attendance and hospitalisation for lower respiratory tract illness. Pediatrics. 1908;82:300-308.

7. Wald ER. Dashefsky B. Byers C. Guerra N, Taylor F. Frequency and severity of infections in day care. J Pediatr. 1988;112:540-546.

8. Wald ER, Guerra N, Byers C. Upper respiratory tract infections in young childten; duration of and frequency of complications. Pediatrics. 1991;87:129-133.

9. Henderson FW, Collier AM, Sanyal MA. et al. A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. N Engl J Med. 1982;306: 1377- 1383.

10. Glezen WR Morbidity associated with the major respiratory viruses. Pediatr Ann. 199O; 19:535-542.

11. Klein JD; Collier AM, Glezen WP. An influenza B epidemic among children in day-care, Pediatrics. 1976; 58:3 40- 345.

12. Glezen WP, Taber LH, Frank AL, KaselJA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986; 140: 5 43 -546.

13. Glezen WP, Paredes A, Allison JE. Taber LH. Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr. 198l;98:707-715.

14. Klein BS, Dollete FR, Voliten RH. The role of respiratory syncytial virus and other viral pathogens in acute otitis media. J Pediatr. 1982i 101:16-20.

15. Henderson FW, Collier AM. Clyde WA Jr, Denny FW. Respiratory-syncyrial-virus infections, reinfections and immuniry. A prospective, longitudinal study in young children. N Engl J Med. 1979;300:530-534.

16. Gleien WR Frank AL, Taber LH, Kasel JA. Paratnfluenia viius type 3: seasonaliry and risk of infection and reinfection in young children. J Infect Res. 1934;150:851-857.

17 Hall CB, DoughlasRG Jr, Geiman JM. Possible transmission by fomites of respiratory syncytial virus. J Inject Dis. 1980;141:98-102.

18. Frank AL, Taber LH, Wells CR, Wells JM, Glezen WP, Paredes A. Patterns uf shedding of myxov iruses and paramyxoviruses in children. J Infect Dis. 198i;I44:433-441.

19. Heikkinan T, Ruuskanen O. Waris M. Ziegler T, Arola M, Halonen P. Influenza vaccination in the prevention of acute oticis media in children. Am J Dis Chad 1 991; 145:445-448.

20. Clover RD, Crawford S, Gleien WP, Taber LH, Maison CC, Couch RB. Comparison of heterolypic protection against influenza A/Taiwan/06 (H(Nl) hy attenuated and inactivated vaccines to A/Chile/83-like viruses. } infect Dis. 1991:163:300-304.

21. Clover RA Crawford SA, Abell TD, Ramsey CN Jr, Glezen WR Cyuch RB. Effectiveness of rimantadine prophylaxis of children within families. AmJ Dis Child. 1986; 140: 706- 709.

TABLE 1

Viruses Associated With Acute Respiratory Illness

TABLE 2

Variants of Influenza Viruses Prevalent in the United States, 1978-1991

TABLE 3

Rates of Primary Infection With Respiratory Syncytial Virus, Chapel HlII Day Care Center (DCC)15 and Houston Family Study (HFS)12

TABLE 4

Rates of Reinfection With Respiratory Syncytlal Virus, Chapel Hill Day Care Center (DCC)15 and Houston Family Study (HFS)12

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