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الانزيمات
Parainfluenza Virus Infections
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p599-602
2025-12-31
58
Parainfluenza viruses are ubiquitous and cause common respiratory illnesses in persons of all ages. They are major pathogens of severe respiratory tract disease in infants and young children. Reinfections with parainfluenza viruses are common.
Pathogenesis and Pathology
Parainfluenza virus replication in the immunocompetent host appears to be limited to respiratory epithelia. Viremia, if it occurs at all, is uncommon. The infection may involve only the nose and throat, resulting in a “common cold” syndrome. However, infection may be more extensive and, especially with types 1 and 2, may involve the larynx and upper trachea, resulting in croup (laryngotracheobronchitis). Croup is characterized by respiratory obstruction caused by swelling of the larynx and related structures. The infection may spread deeper to the lower trachea and bronchi, culminating in pneumonia or bronchiolitis, especially with type 3, but at a much lower frequency than that observed with RSV.
The duration of parainfluenza virus shedding is about 1 week after onset of illness; some children may excrete virus several days prior to symptoms. Type 3 may be excreted for up to 4 weeks after onset of primary illness. This persistent shedding from young children facilitates spread of infection. Prolonged viral shedding may occur in children with com promised immune function and in adults with chronic lung disease.
Factors that determine the severity of parainfluenza virus disease are unclear but include both viral and host properties, such as susceptibility of the protein to cleavage by different proteases, production of an appropriate protease by host cells, immune status of the patient, and airway hyperreactivity.
The production of virus-specific IgE antibodies during primary infections has been associated with disease severity. The mechanism may involve release of mediators of inflammation that alter airway function.
Clinical Findings
The relative importance of parainfluenza viruses as a cause of respiratory diseases in different age groups is indicated in Table 1. Their presence in lower respiratory tract infections in young children shows seasonal variation seen in Figure1.
Table1. Viral Infections of the Respiratory Tract
Fig1. Patterns of lower respiratory tract infections in infants and young children with paramyxoviruses and other viruses. Data from 25 years of surveillance (1976–2001) involving 2009 children from birth to age 5 years. (Reproduced with permission from Williams JV, Harris PA, Tollefson SJ, et al: Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 2004;350:443–450. Copyright © 2004 Massachusetts Medical Society.)
Primary infections in young children usually result in rhinitis and pharyngitis, often with fever and some bronchitis. However, children with primary infections caused by parainfluenza virus type 1, 2, or 3 may have serious illness, ranging from laryngotracheitis and croup (particularly with types 1 and 2) to bronchiolitis and pneumonia (particularly with type 3). The severe illness associated with type 3 occurs mainly in infants younger than the age of 6 months; croup or laryngotracheobronchitis is more likely to occur in older children between ages 6 months and 18 months. More than half of initial infections with parainfluenza virus type 1, 2, or 3 result in febrile illness. It is estimated that only 2–3% develop into croup. Parainfluenza virus type 4 does not usually cause serious disease, even on first infection.
The most common complication of parainfluenza virus infection is otitis media.
Immunocompromised children and adults are susceptible to severe infections. Mortality rates after parainfluenza infection in bone marrow transplant recipients range from 10% to 20%.
Newcastle disease virus is an avian paramyxovirus that produces pneumoencephalitis in young chickens and respiratory disease in older birds. In humans, it may produce inflammation of the conjunctiva. Recovery is complete in 10–14 days. Infection in humans is an occupational disease limited to workers handling infected birds.
Immunity Parainfluenza virus types 1, 2, and 3 are distinct serotypes that lack significant cross-neutralization. Virtually all infants have maternal antibodies to the viruses in serum, yet these antibodies do not prevent infection or disease. Reinfection of older children and adults also occurs in the presence of antibodies elicited by an earlier infection. However, those antibodies modify the course of disease; such reinfections usually present simply as nonfebrile upper respiratory infections (colds).
Natural infection stimulates appearance of immunoglobulin A (IgA) antibody in nasal secretions and concomitant resistance to reinfection. The secretory IgA antibodies are most important for providing protection against reinfection but disappear within a few months. Reinfections are thus common even in adults.
Serum antibodies are made to both HN and F viral sur face proteins, but their relative roles in determining resistance are unknown. As successive reinfections occur, the antibody response becomes less specific because of shared antigenic determinants among parainfluenza viruses and mumps virus. This makes it difficult to diagnose the specific paramyxovirus associated with a given infection using serologic assays.
Laboratory Diagnosis
Nucleic acid amplification tests are the preferred diagnostic methods because of their sensitivity and specificity, their ability to detect a broad range of viruses, and the rapidity of results.
Antigen detection methods are also useful for rapid diagnosis. The immune response to the initial parainfluenza virus infection in life is type specific. However, with repeated infections, the response becomes less specific, and cross reactions extend even to mumps virus. Definitive diagnosis relies on viral isolation from appropriate specimens.
A. Nucleic Acid Detection
Reverse transcription polymerase chain reaction (RT-PCR) assays can be used to detect viral RNA in nasopharyngeal swabs, washes or aspirates, or lower respiratory tract specimens such as bronchoalveolar lavage fluid. Sequence analyses are useful in molecular epidemiology studies of parainfluenza virus infections.
B. Antigen Detection
Detection of viral antigens can be done in exfoliated nasopharyngeal cells by direct or indirect immunofluorescence tests. These methods are fairly rapid and simple to perform but are limited by low sensitivity and the range of viruses detected.
C. Isolation and Identification of Virus
Rapid cell culture methods can detect a number of respiratory viruses able to be cultured in vitro but are slower to provide results than nucleic acid or antigen detection methods and are not able to easily detect mixed infections. A continuous monkey kidney cell line, LLC-MK2, is suitable for isolation of parainfluenza viruses. Prompt inoculation of samples into cell cultures is important for successful viral isolation because viral infectivity drops rapidly. For rapid diagnosis, samples are inoculated onto cells growing on coverslips in shell vials and are incubated. One to 3 days later, the cells are fixed and tested by immunofluorescence. Another way to detect the presence of virus is to perform hemadsorption using guinea pig erythrocytes. Depending on the amount of virus, 10 days or more of incubation may be necessary before the cultures become hemadsorption positive. Virus culture is necessary if a viral isolate is desired for research purposes.
D. Serology
Serodiagnosis should be based on paired sera. Anti body responses can be measured using neutralization, hemagglutination-inhibition (HI), or enzyme-linked immunosorbent assay (ELISA) tests. A fourfold rise in titer is indicative of infection with a parainfluenza virus, as is the appearance of specific IgM antibody. However, because of the problem of shared antigens, it is impossible to be confident of the specific virus type involved.
Epidemiology
Parainfluenza viruses are a major cause of lower respiratory tract disease in young children (see Figure 1). Parainfluenza viruses are widely distributed geographically. Type 3 is most prevalent, with about two-thirds of infants infected during the first year of life; virtually all have antibodies to type 3 by age 2 years. Infections with types 1 and 2 occur at a lower rate, reaching prevalences of about 75% and 60%, respectively, by 5 years of age.
Type 3 is endemic, with some increase during the spring; types 1 and 2 tend to cause epidemics during the fall or winter, frequently on a 2-year cycle.
Reinfections are common throughout childhood and in adults and result in mild upper respiratory tract illnesses. Reportedly, 67% of children are reinfected with parainfluenza type 3 during the second year of life. Reinfections may necessitate hospitalization of adults with chronic lung dis eases (eg, asthma).
Parainfluenza viruses are transmitted by direct person to-person contact or by large-droplet aerosols. Type 1 has been recovered from air samples collected in the vicinity of infected patients. Infections can occur through both the nose and the eyes.
Parainfluenza viruses are usually introduced into a group by preschool children and then spread readily from person to person. The incubation period appears to be from 5 to 6 days. Type 3 virus especially will generally infect all susceptible individuals in a semiclosed population, such as a family or a nursery, within a short time. Parainfluenza viruses are troublesome causes of nosocomial infection in pediatric wards in hospitals. Other high-risk situations include day-care centers and schools.
Treatment and Prevention
Contact isolation precautions are necessary to manage nosocomial outbreaks of parainfluenza virus. These include restriction of visitors, isolation of infected patients, and gowning and handwashing by medical personnel.
The antiviral drug ribavirin has been used with some benefit in treatment of immunocompromised patients with lower respiratory tract disease.
No vaccine is available.
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