ACUTE RESPIRATORY DISEASES

Most acute respiratory diseases are viral infections. They may be complicated by bacterial
superinfections in which a bacterial infection develops after a viral infection. In such a situation,
however, an illness would be of longer duration and not be considered acute. Acute respiratory
infections (ARIs) are the most frequent illnesses experienced by most people globally. Young
children have between five and seven of these illnesses per year, with a general decrease in
frequency with increasing age. Adults will have about two such illnesses per year. It has been shown
that among adults women have a higher frequency of respiratory disease than men do, and women
who do not work outside the home have more frequent illnesses than those who do. This indicates
that children are responsible for spreading illnesses in the family. Further evidence for this
conclusion comes from the seasonal occurrence of the illnesses. While these acute infections occur
year-round, in the temperate zones most begin in the colder season, and the first peak of illnesses
follows the opening of schools by about two weeks.

Table 1

Infectious Agents Causing Common Respiratory Infections

Virus Number of Types Illness Syndrome

source: Courtesy of author.

Rhinoviruses 110+ Common cold

Coronavirus 2+ (?) Common cold

Parainfluenza 4 Croup or pneumonia in children Colds in adults

Respiratory Syncytial 2 Bronchiolitus or pneumonia in children

Virus (RSV) Common cold in adults

Adenovirus Acute Respiratory Disease, Pharyngoconjunctival fever, pneumonia, etc.

One reason why there are so many acute illnesses experienced throughout life is the large number
of viruses that can cause the common cold and other similar syndromes (see Table 1). In addition,
when infection with one of these agents occurs it does not result in lifetime immunity. Since the
actual infection is on the surface of the respiratory tract rather than disseminated in the blood, it is
much more affected by secretory IgA antibodies than circulatory IgG antibodies. As a result,
immunity produced by past experience with the same virus is relative rather than absolute. This
means there may be protection from reinfection over a period of months rather than years, and if
reinfection occurs, it may produce an inapparent infection or milder illness than would be
experienced without prior infection. This situation is most dramatic with agents such as respiratory
syncytial virus (RSV) and parainfluenza viruses. The initial infection can produce potentially life-
threatening illnesses in young children, such as bronchitis or croup, but later in life reinfection will
produce only a common cold-like syndrome.

AGENTS CAUSING RESPIRATORY INFECTION

A wide variety of viruses, containing both RNA and DNA, cause ARIs. The most important viruses are
listed in Table 1. Rhinoviruses are the most frequent cause of the common cold. They circulate all
year, along with the other viruses listed in the table, and are the major cause for the major autumn
increase in respiratory illness. Multiple types of virus cause this rhinovirus outbreak, which is
different from the typical outbreak of an infectious disease, in which only one viral type is
responsible. It is thought that children are responsible for spreading the different types of virus in
schools, and that they are then introduced into families.

Coronaviruses are also important agents of the common cold. Scientists have had difficulty in the
laboratory working with these viruses, and the usual methods of virus detection have not yielded
complete results. For this reason, less is known about them than the others listed in Table 1. There
are at least two major types of coronaviruses, each of which appears to occur over a limited period
of time, usually in winter and spring.

While significantly different virologically, parainfluenza viruses and RSVs will be considered together
because of similarities in overall behavior. There are four types of parainfluenza viruses.
Parainfluenza type 4 is an agent that is sporadic in occurrence, producing little more than the
common cold. As such, its activity is rarely described except when the virus is encountered as part of
a comprehensive investigation in which a variety of different agents are sought. In contrast,
whenever the severe respiratory illnesses causing hospitalization of young children are studied,
parainfluenza types 1, 2, and 3, and RSV, are identified. Both types 1 and 2 most typically cause
laryngotracheobronchitis, more commonly called croup. First infection with these viruses is
essentially universal by three to four years of age, and, based on the number of infants and young
children requiring medical attention, it can be estimated that well over 10 percent of children first
encountering these viruses require medical attention specific for this syndrome. Like all respiratory
viruses, these agents reinfect repeatedly throughout life, with later infections becoming milder or
asymptomatic. Parainfluenza type 3 does not produce this syndrome, but rather one of pneumonia,
often with features of obstruction. Again, first infection is universal at an early age, but only
occasionally results in the most severe of the potential manifestations of the disease. Reinfection
with or without symptoms also recurs throughout life.
RSV was formerly thought to comprise only one viral type, but recent work has identified two groups
that are not as distinctively different as the types of parainfluenza virus. There are suggestions that
group A viruses are more virulent in the illnesses they produce and more frequent in occurrence, but
these differences are not dramatic. RSV produces what is undoubtedly the most severe respiratory
illness in a small proportion of young children infected for the first time in life. The typical syndrome
is usually bronchiolitis, but pneumonia is sometimes diagnosed as well. Because of the severity of
this illness, a vaccine to prevent RSV has been identified as a high priority for development. The
purpose of the vaccine would not be to prevent the disease, since absolute immunity is not possible,
but rather to modify the disease expression so that initial illness becomes similar in characteristics to
a reinfection.

Adenoviruses are different in many respects from the viruses described above. First, they are DNA
viruses, and as such have been examined in terms of issues such as the induction of tumors in
humans. The ability of these viruses to produce tumors has been demonstrated in laboratory
animals, but never in humans. The viruses themselves are divided into many types that produce
distinctly different syndromes. While childhood pneumonia does occur, it is not a major public
health problem except in East Asia, where reports of epidemics have come from North China. Types
4, 7, and others produce a syndrome called acute respiratory disease, which becomes epidemic in
military recruits worldwide. A vaccine has been developed, but because of the limited target
population, maintaining supplies has been an issue.

There are nonviral agents that cause acute respiratory infections, but not with the same frequency
as the viruses, at least not in developed countries. Legionella pneumophila causes Legionaires'
disease, a bacterial pneumonia, sporadically in adults, and reported outbreaks have been associated
with contaminated water supplies in hospitals and other institutions. Chlamydia pneumoniae causes
lower respiratory illnesses in a small proportion of older children and adults. However, the most
important role of this agent may be as a risk factor for development of atherosclerosis. Evidence for
the association of the infection with coronary artery disease is not yet conclusive.

GLOBAL ASPECTS AND PROSPECTS OF PREVENTION

ARIs are a leading cause of death in children under age five in developing countries. While the viral
agents occur in a similar pattern as in developed countries, it is certain bacteria, particularly
Streptococcus pneumoniae and Haemophilus influenzae, once prominent worldwide in lower
respiratory infections, that are the causes of death. The likely scenario is that the viruses initiate the
acute illness, followed by a superinfection caused by the bacteria. However, certain of the viruses,
such as RSV, may alone be responsible for life-threatening illness. Antibiotics can be used to treat
the bacterial infections, but resistance of S. pneumoniae, also called pneumococcus, is becoming
widespread. Vaccines should be an important approach to control. A vaccine is already in use for H.
influenzae type B, and conjugated vaccines are either licensed or being tested for S. pneumoniae.
Vaccines, aside from influenza, have been more difficult to develop for the viral pathogens. RSV
remains at the top of the priority list for development, but as yet no such vaccine is available.

Arnold Monto

(see also: Contagion; Influenza )

Bibliography

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Glezen, W. P., and Denny, F. W. (1973). "Epidemiology of Acute Lower Respiratory Disease in
Children." New England Journal of Medicine 288:498–505.

Grayson, J. T.; Campbell, L. A.; and Kuo, C. C. et al. (1990). "A New Respiratory Tract Pathogen:
Chlamydia Pneumniae Strain TWAR." Journal of Infectious Diseases 161:618–625.

Hendley, J. O.; Wenzel, R. P., and Gwaltnew, J. M. Jr. (1973). "Transmission of Rhinovirus Colds by
Self-Inoculation." New England Journal of Medicine 288:1361–1364.

McNaughton, M. R. (1982). "Occurrence and Frequency of Coronavirus Infections in Humans as

Monto, A. S. (1973). "The Tecumseh Study of Respiratory Illness. V. Patterns of Infection with the
Parainfluenzaviruses." American Journal of Epidemiology 97:338–348.
Monto, A. S., and Sullivan, K. M. (1993). "Acute Respiratory Illness in the Community. Frequency of
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Monto, A. S., and Ullman, B. M. (1974). "The Tecumseh Study. Acute Respiratory Illness in an
American Community." Journal of the American Medical Association 227:164–169.

Mufson, M. A.; Levine, H. D.; Wasil, R. E. et al. (1973). "Epidemiology of Respiratory Syncytial Virus
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