Parainfluenza Viruses
PIV infections are the most commonly recognized cause of croup, accounting for up to 75% of cases with a documented viral etiology, and they are a leading cause of lower respiratory tract disease resulting in hospitalization of infants. Infection with PIV induces partial immunity that moderates disease severity; reinfection in older children and adults produces milder respiratory illness and colds.
Classification and Pathogenesis
Human PIVs are medium-sized (120 to 150 nm), enveloped RNA viruses belonging to the Paramyxoviridae family and are classified into four antigenically stable types (1, 2, 3, and 4); type 4 is further classified into subtypes A and B. PIV replicates in epithelial cells of the upper and lower respiratory tract, and antibodies to the two major envelope surface glycoproteins—name-ly, the hemagglutinin-neuraminidase protein and the fusion protein—confer protection against infection. These proteins are necessary for attachment of virus to host cell receptors and membrane-fusing activity. PIV type 1 and type 2, which cause croup and laryngitis, probably replicate principally in the major airways, whereas PIV-3 causes lower respiratory tract infections.
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Table 4 Indications for Influenza Vaccination*21 |
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PERSONS AT INCREASED RISK FOR COMPLICATIONS |
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All adults 65 yr of age and older |
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Residents of nursing homes and other long-term care facilities that house persons of any age who have chronic medical conditions |
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Adults and children with chronic cardiopulmonary disorders, including asthma |
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Adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes), renal dysfunction, hemoglobinopathies, or immunosup-pression (including immunosuppression caused by medication or by HIV) |
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Children and teenagers (6 mo to 18 yr of age) who are receiving long-term aspirin therapy and therefore may be at risk for Reye syndrome |
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Women who will be pregnant during the influenza season |
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Children 6-23 mo of age |
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PERSONS 50-64 YR OF AGE+ |
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PERSONS WHO CAN TRANSMIT INFLUENZA TO THOSE AT HIGH RISK Physicians, nurses, and other personnel in both hospital and outpatient care settings, including medical emergency response workers (e.g., paramedics and emergency medical technicians) |
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Employees of nursing homes and long-term care facilities who have contact with patients or residents |
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Employees of assisted-living and other residences for persons in groups at high risk |
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Home care providers for persons at high risk |
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Household contacts of high-risk persons |
*Both the inactivated influenza vaccine and live, attenuated influenza vaccine (LAIV) can be used to reduce the risk of influenza. Healthy persons 5-49 yr of age who are not contacts of severely immunosuppressed persons can receive either LAIV or inactivated influenza vaccine; all other persons should receive inactivated influenza vaccine. In addition to persons for whom annual influenza vaccination is recommended, influenza vaccine should be given to any person who wishes to reduce the likelihood of becoming ill with influenza, if vaccine availability permits. +Vaccination is recommended for persons 50-64 yr of age because of the increased prevalence of persons with high-risk conditions in this group.
Epidemiology and Transmission
PIV infections occur initially during childhood; PIV-3 infections often occur during infancy and are an important cause of illness in infants younger than 6 months, as well as in immuno-compromised persons. The incidence of croup and respiratory disease caused by PIV-1 or PIV-2 infections is highest between the ages of 6 months and 5 years. PIV-1 typically causes epidemics lasting several months, peaking in October or November of alternating years, whereas PIV-2 activity is more sporadic. PIV-3 causes infections throughout the year, with outbreaks during the spring and summer.
PIVs are transmitted from person to person, either by direct contact with respiratory secretions or by large aerosol droplets. Transmission occurs readily in families, and reinfections in older children and adults are common. Outbreaks occur in nurseries, day care centers, and hospitals, with attack rates of 40% or higher in susceptible patients.
Diagnosis
Clinical features The incubation period of PIVs is approximately 3 to 6 days. Virus replication is generally limited to the respiratory tract, although viremia and CNS infections86 have been rarely documented. Initial infections cause fever, rhinitis, pharyngitis, laryngitis, croup, and bronchitis in children.
Laboratory tests Immunofluorescence testing of respiratory secretions and RT-PCR have been used for rapid PIV detection. Culture is generally slow, requiring days to weeks. Serologic assays, including complement fixation, ELISA, and hemagglutina-tion assays, are used for retrospective diagnosis.
Treatment
Specific antiviral therapy of proven value has not been established. Early treatment with aerosol ribavirin may benefit some immunocompromised patients with serious infections, and intravenous ribavirin has been used for treatment of PIV pneumonia in BMT patients.
Prevention
An effective PIV vaccine is not yet available, but live attenuated vaccines derived from either human or bovine PIV have been developed and appear to be safe and immunogenic in children. Infection control measures, with an emphasis on exclusion of sick caregivers and isolation protocols, may reduce the risk of nosocomial acquisition in compromised hosts.
Complications
In adults and older children, reinfections are often asymptomatic but may cause serious lower respiratory tract disease, including exacerbations of chronic airway disease and pneumonia. During periods of circulation, about 2% to 3% of cases of community-acquired pneumonia in adults are linked to PIV in-fection.88 Severe pneumonia, sometimes in the absence of upper respiratory tract illness, occurs in immunosuppressed adults and children, particularly after BMT.5
Respiratory Syncytial Virus
Classification and Pathogenesis
RSV is a paramyxovirus with surface glycoproteins that have neither hemagglutinin nor neuraminidase activity. The F protein is responsible for fusion of the viral envelope with the host cell membranes. Antibody against this protein neutralizes RSV in-fectivity and blocks syncytial cell formation. The G protein is responsible for attachment. Two major subgroups (A and B) are distinguished primarily by antigenic differences in the G glyco-protein, and multiple strains are recognized within each subgroup.
Epidemiology and Transmission
RSV is the major cause of lower respiratory tract disease in infants and young children, accounting for 45% to 90% of bronchi-olitis cases and up to 40% of pneumonia cases. Approximately 40% of infections in the first year of life cause lower respiratory tract illness and 1% to 2% result in hospitalization; about 10% of hospitalized infants require ventilatory support.
As many as 100,000 hospitalizations and 510 deaths of infants and children are attributed to RSV each year in the United States.89 RSV is also increasingly recognized as a cause of lower respiratory tract disease in older adults and immunocompro-mised persons.90,91 Mortality is usually less than 1% in previously healthy infants but is much higher in persons with primary immunodeficiency, persons undergoing cancer chemotherapy, and persons with preexisting pulmonary and heart disease.92 The number of RSV-related deaths in the elderly is estimated to be 10-fold higher than that in infants.93 In elderly persons, it is estimated that RSV is associated with 2% to 9% of hospitalizations or deaths caused by pneumonia90 and about 10% of hospitalizations for acute cardiopulmonary conditions.89 Each year, RSV is responsible for an estimated 11,321 excess deaths in the United States.
RSV causes prolonged outbreaks of infection from late fall to spring annually in temperate climates.94 Most outbreaks peak between January and March in the Northern Hemisphere, but sporadic cases can occur year-round. Epidemics are associated with increased pediatric hospitalizations and deaths from lower respiratory tract illness. Essentially all children are infected within several years after birth. Immunity is incomplete, and reinfections in children and adults are common. Higher titers of circulating and mucosal antibody occur with successive infections and appear to be associated with milder illness.
RSV appears to be spread by large-particle aerosols during close personal contact and by hand contamination with self-inoculation of the eye or nose. RSV is a major nosocomial pathogen, and high attack rates occur during outbreaks in hospitals, transplantation units, day care centers, and geriatric homes.95 Illness rates are commonly 20% to 50% among hospital staff and patients during epidemics. In households, secondary infection occurs in about one third of adults.
Diagnosis
Clinical features The incubation period of RSV averages 4 to 5 days but ranges up to 1 week. In infants and young children, almost all primary infections are symptomatic, and 40% or more are associated with bronchiolitis or pneumonia. Febrile upper respiratory tract illness and otitis media are common.
Most recurrent infections in adults are associated with upper respiratory tract illness. Adults typically experience coryza, pharyngitis, and cough, often with low-grade fever. Bronchitis, influenzalike illness, pneumonia, and exacerbations of asthma and chronic bronchitis also occur. In the elderly, the clinical manifestations and outcomes of RSV infections are similar to those of influenza.89,94 Elderly adults hospitalized with RSV commonly have dyspnea, wheezing, and sputum production. Viral bronchopneumonia or secondary bacterial pneumonia appears to complicate a high proportion of RSV infections in such patients.
RSV causes severe lower respiratory tract disease in immuno-suppressed patients, particularly BMT recipients and acute leukemia patients receiving chemotherapy.6 Most cases are noso-comial; mortality exceeds 60% when pneumonia develops. Rhinitis with sinusitis or otitis often precedes the development of pneumonia by several days and may provide a clue to diagnosis.
Laboratory tests Testing of bronchoalveolar lavage samples with RSV antigen or RNA detection provides rapid diagnosis in pneumonia cases. Commercially available ELISAs are sensitive to RSV in children, but nasopharyngeal samples are an insensitive means of detecting RSV antigen in adults, who have low titers of virus in the upper respiratory tract. RT-PCR is a reasonably sensitive technique to detect RSV infection, whereas culture of virus is slow and less sensitive. Serology is more sensitive than cell culture for diagnosis in adults but is slow because of the need for paired sera.89
Treatment
The value of aerosolized ribavirin in the management of RSV disease in hospitalized children remains controversial, and studies of its value in mechanically ventilated infants have yielded conflicting results.23 Aerosolized ribavirin should be considered for infants hospitalized with RSV infections who are at high risk for severe or complicated illness (e.g., those with congenital heart disease, bronchopulmonary dysplasia, cystic fibrosis, and immunodeficiency), for those who are already severely ill, and for those who are younger than 6 weeks. Treatment with poly-clonal or monoclonal RSV antibodies does not provide clear therapeutic benefit for RSV-infected infants and young children. Aerosol ribavirin may reduce progression from upper to lower respiratory tract disease in highly immunocompromised hosts. Early treatment with aerosolized ribavirin plus IVIg, RSV im-munoglobulin, or palivizumab appears to benefit immunosup-pressed patients with RSV pneumonia.
Prevention
Passive immunoprophylaxis by monthly administration of high-titer anti-RSV immunoglobulin or anti-F monoclonal antibody (palivizumab) reduces the risk of lower respiratory tract RSV disease and hospitalization in high-risk infants and children. Palivizumab is approved for prophylaxis in premature infants and children younger than 2 years with bronchopul-monary dysplasia and is appropriate for infants and young children with hemodynamically significant congenital heart disease.97 A phase 1 study has found that palivizumab appears to be safe and well tolerated in recipients of hematopoietic stem cell transplants.98 No vaccine against RSV is available yet, but studies of intranasal live-attenuated vaccine in children and injected subunit vaccine in elderly persons are ongoing.
Interruption of nosocomial transmission may be facilitated by thorough hand washing,99 decontamination of fomites, early identification and rapid isolation of infected infants and other potential RSV cases,100 and cohorting of staff with infected in-fants.101 Regular use of gowns, gloves, disposable eye-nose goggles, and possibly masks by hospital staff caring for infected children may further reduce the risk of nosocomial RSV spread.
Rhinovirus
Classification and Pathogenesis
Rhinoviruses are small (30 nm), nonenveloped viruses that belong to the Picornaviridae family. They have a single-stranded RNA genome and are composed of four structural proteins. Three of the proteins induce neutralizing antibodies and form the basis for serotyping. The large number of serotypes (> 110) makes the development of an effective vaccine unlikely. Nearly 90% of rhinovirus serotypes use intercellular adhesion mole-cule-1 as a common cellular receptor. Although replication of rhinovirus was thought to be limited to the upper respiratory tract, increasing data suggest that rhinovirus can replicate and cause disease in the lower airways.102
Epidemiology and Transmission
Rhinoviruses cause approximately one infection per person per year in adults, and rates are even higher in children. Rhi-novirus causes about 50% of colds in adults each year and up to 90% during the fall months.103 Immunity to rhinovirus is serotype specific and relatively enduring after infection, although reinfection can occur. Rhinoviruses cause infections year-round but are most prevalent in early fall and late spring. The relative importance of fomite spread with hand contamination and self-inoculation into the eyes or nose and aerosols in rhinovirus transmission is uncertain under natural conditions.
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Internet Resources for Respiratory Viral Infections |
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Adenovirus National Respiratory and Enteric Virus Surveillance System http://www.cdc.gov/ncidod/dvrd/revb/respiratory/eadfeat.htm |
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SARS Centers for Disease Control and Prevention www.cdc.gov/ncidod/sars |
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World Health Organization http://www.who.int/csr/sars/en/ |
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Influenza Virus World Health Organization http://www.who.int/csr/disease/influenza/en/ |
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Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm |
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National Foundation for Infectious Diseases http://www.nfid.org/library/influenza American Lung Association http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35426 |
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Parainfluenza Viruses National Respiratory and Enteric Virus Surveillance System http://www.cdc.gov/ncidod/dvrd/revb/respiratory/hpivfeat.htm |
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Respiratory Syncytial Virus National Respiratory and Enteric Virus Surveillance System http://www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htm American Lung Association http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35695 |
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Hantavirus |
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Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/diseases/hanta/hps/index.htm |
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Emerging Viruses Research Center Hantavirus Reference Laboratory |
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http://hsc.unm.edu/pathology/HjelleLab/ |
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American Lung Association http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35428 |
Diagnosis
Clinical features The incubation period of rhinoviruses averages about 2 days, with a range of 1 to 5 days. Rhinovirus colds vary in severity from mild episodes characterized by 1 to 2 days of coryza or scratchy throat to illnesses with profuse rhin-orrhea, pharyngitis, and tracheobronchitis. Symptoms usually peak on the second and third days of illness, and the median duration is 1 week.
Rhinovirus infections are associated with more frequent lower respiratory tract illness in the elderly and with bronchospasm and protracted cough in persons with preexisting airway dis-ease.104,105 Rhinovirus is the major infectious cause of asthma exacerbations in children and in adults. In addition, rhinovirus infections are associated with acute sinusitis,106 otitis media,107 exacerbations of chronic bronchitis, and lower respiratory tract disease in infants and young children. In BMT recipients, rhi- novirus infection has been associated with pneumonia and poor prognosis.1
Laboratory tests No rapid diagnostic test for rhinovirus infection is routinely available; detection is usually by virus isolation and, more recently, by RT-PCR.108
Treatment
No antiviral therapy of proven clinical value is currently available, but several approaches are under investigation. Oral administration of the capsid-binding antirhinoviral compound pleconaril reduces the severity and duration of uncomplicated rhinovirus colds in adults but is associated with risk of drug in-teractions.109 Nonselective regimens such as high-dose vitamin C, Echinacea preparations, inhalation of heated air, and zinc lozenges are of doubtful value.
Prevention
Barrier control measures may be beneficial, although tissues impregnated with virucides have proved disappointing in this regard. Hand washing and avoidance of finger-to-nose and finger-to-eye contact should reduce the risk of infection. Because of the risk of nosocomial transmission of rhinovirus infections, adherence to infection control precautions in cases of upper respiratory tract illness is important.
Hantavirus
Hantavirus causes hantavirus cardiopulmonary syndrome (HCPS).Most HCPS cases have occurred in young to middle-aged adults with no underlying disease. The largest number of cases have occurred in New Mexico, Arizona, and California, but cases have also been identified throughout western North America and sporadically in the eastern United States. HCPS is typically a zoonosis; the principal animal reservoir is the deer mouse. Human infections occur by inhalation of aerosols of infectious excreta. Detailed discussion of HCPS is provided elsewhere [see 7:XXXI Viral Zoonoses].
