AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Parainfluenza viruses (PIVs) are paramyxoviruses. Over the last decade, both the nomenclature and the taxonomic relationships of human parainfluenza viruses (HPIVs) have changed considerably.

The first HPIV discovered was the Sendai virus in 1952 in Japan. In 1955, HPIV type 2 (HPIV-2) was isolated from children with acute laryngotracheobronchitis (croup). In 1985, HPIV type 3 (HPIV-3) was isolated from children with respiratory tract infection. In 1960, HPIV type 4 (HPIV-4) was isolated from children with mild respiratory tract infections. HPIV-4 consists of A and B subtypes. Thus, HPIVs are now classified under 2 genera: the genus Respirovirus (HPIV-1, HPIV-3) and the genus Rubulavirus (HPIV-2, HPIV-4).

HPIVs are pathogens that primarily affect young children, in whom the pathogenic spectrum includes upper and lower respiratory tract infections. HPIVs are responsible for 30-40% of all acute respiratory tract infections in infants and children. These conditions include common cold with fever, croup, bronchiolitis, and pneumonia. HPIVs are also a cause of community-acquired respiratory tract infections of variable severity in adults. HPIV-1 is most commonly associated with croup. HPIV-2 is also associated with croup. HPIV-3 is second only to respiratory syncytial virus (RSV) as a cause of pneumonia and bronchiolitis in infants and young children. HPIV-4 is detected in patients less often, perhaps because HPIV-4 causes less severe disease.

Reinfection with HPIV can occur throughout life, with elderly and immunocompromised persons being at a greater risk of serious complications of infections.

The seasonal patterns of HPIV-1, HPIV-2, and HPIV-3 are curiously interactive. HPIV-1 causes the largest, most defined outbreaks, which are marked by sharp biennial rises in croup cases in the autumn of odd-numbered years. Outbreaks of infection with HPIV-2, although erratic, usually follow HPIV-1 outbreaks. Outbreaks of HPIV-3 infections occur yearly, mainly in spring and summer, and last longer than outbreaks of HPIV-1 and HPIV-2. HPIV-4 is infrequently isolated and, hence, relatively unknown and uncharacterized.¹

The following are clinical conditions caused by the various HPIV types:

• Croup - HPIV-1, HPIV-2, HPIV-3
• Bronchitis - HPIV-1, HPIV-3
• Minor upper respiratory tract disease - HPIV-1, HPIV-3, HPIV-4

In recent years, various aspects of the viruses, such as genomic organization, replication, and host immunity evasion mechanisms have been the subjects of intense study, as this knowledge will be crucial for development of intervening strategies (including vaccines) in the future.

Taxonomy

As noted above, the taxonomy of HPIVs has recently changed. HPIVs are now composed of 5 serotypes—HPIV-1, HPIV-2, HPIV-3, HPIV-4a, and HPIV-4b. These serotypes display substantial serologic cross-reactivity. Presently, these viruses are included in the order Mononegavirales, the family Paramyxoviridae, and the subfamily Paramyxovirinae. They belong to 2 different genera: HPIV-1 and HPIV-3 belong to the Respirovirus genus, and HPIV-2 and HPIV-4 belong to the Rubulavirus genus.

Pathophysiology

Structural organization

HPIVs are pleomorphic viruses whose envelope is derived from the host cell they last infected. These viruses are 150-200 nm in diameter and possess a single-stranded, nonsegmented, negative-sense RNA genome with nucleoprotein P and L proteins. A lipid bilayer covered with glycoprotein spikes surrounds a helical nucleocapsid that measures 12-17 nm in diameter. These glycoproteins are hemagglutinin-neuraminidase (HN) and fusion (F) proteins, which play a major role in the pathogenesis of the disease caused by the viruses.

Pathogenesis

Viral transmission occurs via direct inoculation of contagious secretions from the hands or via large-particle aerosols into the eyes and nose. Prolonged survival of HPIV on skin, cloth, and other objects emphasizes the importance of fomites in nosocomial spread. Respiratory epithelium appears to be the major site of virus binding and subsequent infection. The viruses attach to the host cells through hemagglutinin, which specifically combines with neuraminic acid receptors in the host cells. Subsequently, the viruses enter the cell via fusion with the cell membrane mediated by F1 and F2 receptors.

When HPIV infects a cell, the first observable morphologic changes may include focal rounding and growing of the cytoplasm and nucleus and decreased host-cell mitotic activity. Other observable changes include single or multilocular cytoplasmic vacuoles, basophilic or eosinophilic inclusions, and formation of multinucleated giant cells. These giant cells (fusion cells) usually develop late in the infection, and each giant cell contains between 2 and 7 nuclei.

Mechanisms of airway inflammation

HPIV infection in the respiratory tract leads to secretion of high levels of inflammatory cytokines such as interferon (IFN)–alpha, interleukin (IL)–2, IL-6, and tumor necrosis factor (TNF)–alpha. The peak duration of secretion is 7-10 days after initial exposure. Increasing levels of certain chemokines such as RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein (MIP)–K are detected in the nasal secretion of pediatric patients. These are responsible for pathological changes in the respiratory tract and clinical manifestations of this condition.

The chief pathological features include airway inflammation, necrosis and sloughing of respiratory epithelium, edema, excessive mucus production, and interstitial infiltration of lung. Edema of the mucus layer causes swelling in the vocal cords, larynx, trachea, and bronchi. These changes lead to obstruction of the airway inflow and subsequent stridor, which is characteristic of croup.

In animal models, increased levels of histamine and eosinophils are detected in bronchoalveolar lavage (BAL) samples following infection with HPIV, suggesting a state of hyperresponsiveness of the respiratory tract.

HPIV-2 and HPIV-3 infection in humans is known to induce expression of intercellular adhesion molecule-1 (ICAM-1) in tracheal and other cells of the respiratory tract. These molecules serve as receptors for rhinoviruses, thus paving the way for rhinoviral superinfection.

The virus continues to be excreted in respiratory exudates for 3-16 days following primary infection and 1-4 days following infection.

Immunology

Host defense against HPIVs is mediated largely by humoral immunity to both surface glycol proteins of the virus—HN and F. Most children are born with neutralizing antibodies to all 4 types of HPIV, but these titers quickly fall during the first 6 months of life. Most antibody response appears to involve serum immunoglobulin G1 (IgG1), but levels of serum immunoglobulin G3 (IgG3), immunoglobulin G4 (IgG4), serum immunoglobulin A (IgA), and immunoglobulin M (IgM) rise significantly in 30% of adults. Secretory IgA plays an important but not fully defined role in the protection against natural HPIV infections.

After natural infection with HPIV, most children and adults develop measurable levels of these antibodies in the serum; these antibodies have been shown to be correlated with disease prevention and amelioration in adults. Local interferon production has been noted in about 30% of children with HPIV infection. Although immunity to HPIV infection is long-lasting, reinfection may occur many times throughout life and at variable intervals, even in the presence of neutralizing antibodies. This cannot be explained merely based on the relatively stable antigenic determinants of HPIVs; thus, more research is needed.

In recent years, interesting facts regarding cell-mediated immunity have emerged. HPIV infections tend to be more severe in individuals with defective cell-mediated immunity, indicating that T cells may have a greater role in containing the disease.

Epidemiology

Respiratory secretions from infected humans are the source of infection. Transmission is via respiratory droplets or via direct person-to-person contact with infected secretions. The inoculating dose is very small.

HPIVs are common community-acquired respiratory pathogens without ethnic, socioeconomic, gender, age, or geographic boundaries. Many factors have been found that predispose individuals to these infections, including malnutrition, overcrowding, vitamin A deficiency, lack of breastfeeding, and environmental smoke or toxins.

Frequency

United States

Infections with HPIV-1 and HPIV-2 occur during autumn months. Infections with HPIV-3 occur throughout the year but appear to peak in the spring. HPIV-3 is the second most common cause of lower respiratory tract infections treated in the United States, second only to RSV. HPIV-4 infection patterns are not well-defined.

HPIV-3 infections occur earliest and most frequently. Based on seroepidemiological studies, 50% of US children aged 1 year and almost all US children aged 6 years have been infected by HPIV-3. Antibodies against HPIV-1 and HPIV-2 develop less rapidly, but 80% of children have antibodies against these types by age 10 years. HPIV-4 induces few clinical illnesses, but infections with this type are common nonetheless, as 70-80% of children aged 10 years have antibodies against HPIV-4.

International

Internationally, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 have worldwide distribution, and epidemics are known to occur, particularly with HPIV-1.

Parainfluenza viruses are responsible for disease throughout the year, but winter outbreaks of respiratory tract infections, especially croup, in children throughout the temperate zones of the northern and southern hemispheres represent peak periods of prevalence. Most infections are endemic, but sharp small epidemics involving HPIV-1 and HPIV-2 occasionally occur. The first reported outbreak of HPIV-4 infection occurred in Hong Kong in autumn of 2004. The outbreak involved 38 institutionalized children and 3 staff members during a 3-week period in a developmental disabilities unit.²

Mortality/Morbidity

Mortality induced by HPIV is unusual in developed countries and occurs almost exclusively in young infants or immunocompromised or elderly people. However, the preschool population in developing countries is at considerable risk for HPIV-induced death. Whether because of primary viral disease or because of facilitating secondary bacterial infections in malnourished children, lower respiratory tract infection causes 25-30% of the death in this age group, and HPIV causes at least 10% of lower respiratory tract infections.

Race

HPIVs have no predilection for any race.

Sex

HPIVs have no predilection for either sex.

Age

HPIV-1 can cause lower respiratory tract infection in young infants but is rare in those younger than 1 month. The full burden of HPIV-1 in adults and elderly persons has not been determined, but studies have shown that this virus causes yearly hospitalizations in healthy adults and may play a role in bacterial pneumonias and death in nursing-home residents.

HPIV-2 accounts for 60% of all infections that develop in children younger than 5 years, with peak incidence between ages 1 and 2 years.

Young infants (<6 mo) are particularly vulnerable to infection with HPIV-3. Unlike other HPIVs, 40% of HPIV-3 infections occur in the first year of life.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Human parainfluenza viruses (HPIVs) have been associated with every type of upper and lower respiratory tract illness. However, all HPIV types strongly correlate with specific clinical syndromes, age, and time of year. Lack of epidemiological data on HPIV-4 has so far prevented a clear understanding of the true clinical significance of the virus.

• Croup: Croup is a generic term that encompasses a heterogeneous group of illnesses that affect the larynx, the trachea, and the bronchi. HPIV-1, HPIV-2, and HPIV-3 are the most frequent causes of croup, accounting for almost 75% of all cases. HPIV-1 is the most common and is estimated to cause 18% of all croup cases. Symptoms of croup include fever, hoarse barking cough, laryngeal obstruction, and inspiratory stridor.
• Bronchiolitis: All 4 types of HPIV can cause bronchiolitis, but HPIV-1 and HPIV-3 have been reported most commonly. Each of these 2 groups appears to cause 10-15% of bronchiolitis cases in nonhospitalized children. The peak incidence of bronchiolitis occurs during the first year of life (81% of cases during this period) and then dramatically declines until it virtually disappears by school age. Predominant symptoms include fever, expiratory wheezing, tachypnea, retractions, rales, and air trapping.
• Pneumonias: HPIV-1 and HPIV-3 each cause about 10% of outpatient pneumonia cases, but, similar to bronchiolitis, HPIV-3 causes a larger percentage of cases in hospitalized patients. HPIV-2 and HPIV-4 can both cause pneumonia, but the incidence of disease is not well described. HPIV-1 infection has been associated with secondary bacterial pneumonias in elderly persons. Symptoms of pneumonias include fever, rales, and evidence of pulmonary consolidation.
• Tracheobronchitis: More than 25% of the agents identified to cause tracheobronchitis have been HPIVs. (HPIV-3 is more commonly associated with tracheobronchitis than HPIV-1 or HPIV-2.) Tracheobronchitis is the most common feature seen in persons with HPIV-4 infections.
• Other infections: HPIVs routinely cause otitis media, pharyngitis, and conjunctivitis coryza, and these can occur singly or in combination with a lower respiratory tract infection. HPIV-3 is the most frequently reported HPIV associated with otitis media.
• Infections in immunocompromised patients: The increasing number of patients who receive intense immunosuppression after undergoing transplantation of bone marrow and solid organs has highlighted the role of HPIVs as potential opportunistic pathogens. HPIV-2 causes giant cell pneumonia in persons with severe combined immunodeficiency diseases (SCIDs), and HPIV-3 has been found in persons with SCIDS and acute myeloid leukemia (AML) and in patients who have undergone bone marrow transplantation (BMT). The natural history of HPIV in patients infected with HIV is generally less severe than that in transplant recipients.

Physical

A broad range of findings is observed and may include fever, nasal congestion, pharyngeal erythema, nonproductive to minimally productive cough, inspiratory stridor, rhonchi, rales, and wheezing.

• The epiglottis is sometimes grossly swollen and reddened because of viral infection. Severe airway obstruction may ensue, requiring emergency tracheotomy.
• In serious cases, children should be quickly hospitalized (generally within 3-24 h). In immunocompromised hosts, upper respiratory tract symptoms are similar to those observed in healthy hosts, but the incidence of lower respiratory tract symptoms and sinusitis is much higher. In these groups, especially bone marrow transplant recipients, lower respiratory tract infection can lead to respiratory failure and death.

Causes

HPIV infection is acquired through inhalation of infected droplet nuclei or indirectly through contact with infected secretions. The incubation period is generally 2-6 days. See Pathophysiology.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bacterial superinfections
Bronchiolitis
Coronavirus
Foreign body aspiration (if croup or bronchiolitis is present)
Epiglottitis
Pneumonia
Respiratory syncytial virus
Retropharyngeal abscess
Rhinovirus

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The CBC count is usually within the reference range. Lymphocytosis may be present.
• Virus antigen detection and isolation
• • Collection and preparation of clinical specimens: Nasopharyngeal aspirations, nasal washings, and nasal aspirations are optimum specimens for collection. Throat swabs and nasal swabs can also be used. Specimens should be collected and placed in viral transport media (VTM), preferably at 4°C; if a delay of more than 24 hours is anticipated, specimens should be frozen. Nonrespiratory specimens such as CSF, rectal swabs, and stool, though rare, can be used. Paired sera (acute and convalescent phase) should be collected, separated quickly, and stored at either -20°C or -70°C; both samples should be tested simultaneously.
  • Electron microscopy: Microdrops of secretions or garglings are placed directly on carbon-coated electron microscopy grids and stained with phosphotungstic acid. Virions typical of the Paramyxoviridae may be observed. However, this study yields poor sensitivity.
  • Immunofluorescence: Indirect immunofluorescence is normally used with antisera against each serotype of parainfluenza virus. However, immunofluorescence findings cannot be used as the sole diagnostic criterion, as it also yields poor sensitivity. A study carried out in Arizona between 1983 and 1985 showed that immunofluorescence revealed HPIV-1 in only 63% of throat specimens from which this serotype was isolated in tissue cultures. HPIV-3 was revealed in only 31% of virus-culture–positive throat secretions.
  • Direct detection of viral antigens: HPIV antigen can be detected with enzyme-linked immunoassay (ELISA), radioimmunoassay, fluoroimmunoassay, and immunofluorescence. Synthesized recombinant HPIV-1 and HPIV-3 nucleocapsid proteins in the yeast Saccharomyces cerevisiae are used as a source of antigens.³ The latter two tests are both rapid and specific. Shell vial assay is another method for rapid identification of HPIV. Shell vials have yielded an average sensitivity of 84% in testing against standard tissue culture–positive HPIV cases.
  • Virus isolation: HPIV grows best in primary monkey kidney (PMK) cells (rhesus monkey kidney cells, cynomolgus, and African green monkeys). The LLC-MK2 strain is also excellent for continued passage and is almost as good as PMK cells for primary isolation. Trypsin (2-3 mg/mL) must be added to the maintenance medium of LLC-MK2 cells to recover all HPIV serotypes. Proteases are necessary for parainfluenza virus to replicate, and it is hypothesized that proteases present in primary cell cultures are absent in continuous cell lines.
  • Detection and typing: Cytopathic effects (CPEs) are rarely demonstrated during primary isolation of HPIV in tissue culture except with HPIV-2, which, when cultured, shows syncytia formation. All HPIVs demonstrate greater cytopathic effects upon adaptation to a particular cell line, with HPIV-3 being the most aggressive, destroying more than 50% of tissue culture monolayer by the third day. Virus growth is detected with hemadsorption inhibition using guinea pig erythrocytes within 3-10 days of incubation. However, the prolonged incubation time (3-10 d) required for virus isolation severely restricts the usefulness of virus isolation in short-term management.
  • Serologic diagnosis: A 4-fold rise or drop in titer is generally thought to signify acute infection if the testing is performed at the same time on paired acute- and convalescent-phase serum pimples. Hemagglutination inhibition, neutralization, complement fixation, ELISA, radioimmune assays, and Western blotting are frequently used antibody-based serological tests for diagnosis of HPIV infections.
  • Genomic detection: HPIV RNA can be detected directly with Northern hybridization or a dot blot analysis using virus-specific DNA probes. Polymerase chain reaction (PCR) assay is sensitive and specific in detecting HPIV. A multiplex reverse-transcriptase PCR (RT-PCR) assay for detecting HPIV-1, HPIV-2, and HPIV-3 has been developed. RT-PCR enzyme hybridization assay (RT-PCR-EHA) is available for detecting HPIV types 1-4, respiratory syncytial viruses A and B, and influenza A and B virus, with a reported sensitivity of 95-100% and specificity of 97-100% when compared with results of tissue culture. The RT-PCR-EHA yields results in approximately 7 hours. A multiplex RT-PCR assay kit under dual priming oligonucleotide system (DPO) that is used to detect 12 common viruses causing respiratory tract infections in children has recently become available.⁴

Imaging Studies

• Radiographs of the neck or chest are important if epiglottitis, croup, or pneumonia is a possibility.
• Anteroposterior views of the neck may demonstrate subglottic swelling with narrowing of the air shadow of the trachea (steeple sign) with croup; in patients with epiglottitis, lateral views may demonstrate enlargement of the epiglottis and ballooning of the hypopharynx.

Histologic Findings

The epithelium of the respiratory tract may show inflammation and necrosis. Subglottic tissues in particular may appear to be involved.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Supportive care is mandatory. Antiviral agents are of uncertain benefit. Anecdotal reports of possible benefit have been published, but controlled studies are lacking.
• Treatment of croup
• • Prehospital care
  • • It is paramount to control fever and to relieve respiratory symptoms.
    • Respiratory symptoms are improved by exposing children to cool night air or by inhalation of vapor droplets to soothe inflamed airways.
    • Antipyretics may be administered to control fever.
    • Moderate or severe croup requires medical evaluation in the office or ED.
  • ED care
  • • Mild croup: Cool oxygen mist and control of fever are effective in the treatment of mild croup.
    • Moderate croup: Therapy includes cool oxygen mist and, possibly, orally administered glucocorticoids. If patients fail to improve, racemic epinephrine nebulization has been shown to be beneficial. Hydration must be maintained with oral fluids or with intravenous fluids, when necessary.
    • Severe croup: In cases of impending respiratory failure, intensive-care monitoring is required in addition to repeat racemic epinephrine nebulization at 1- to 2-hour intervals. Endotracheal intubation followed by a tracheotomy may be required in patients with severe respiratory obstruction.

Consultations

Consultations may include pulmonologists and infectious diseases specialists.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Ribavirin is a broad-spectrum antiviral agent that has been shown to be effective against HPIV-3 infection in vitro and possibly in vivo. Although results are mixed, ribavirin aerosol or systemic therapy has been used to treat HPIV infections in children and adults who are severely immunocompromised. Use at this time is of uncertain clinical benefit.

Antibiotics are used only if bacterial complications (eg, otitis, sinusitis) develop. Corticosteroids and nebulizers are used to treat respiratory symptoms and to help reduce the inflammation and airway edema of croup.

Drug Category: Corticosteroids

Prednisone, prednisolone, and dexamethasone are commonly used glucocorticoids. Dexamethasone, because of its high potency and prolonged intramuscular half-life, is the preferred anti-inflammatory drug for croup.

Drug Category: Sympathomimetics

Epinephrine is highly effective when delivered via nebulizer. Nebulizers are air- or oxygen-powered devices that deliver medications directly to mucosal surfaces of respiratory tract and smooth muscles.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Indications for hospitalization
• • Respiratory distress
  • Dehydration
  • Stridor at rest, even after receiving therapy

Further Outpatient Care

• Bed rest
• Use of vaporizers producing moist air

Deterrence/Prevention

• Field trials of formalin-killed whole HPIV-1, HPIV-2, and HPIV-3 vaccines failed to protect children against natural infections in the late 1960s. Current approaches to HPIV vaccines include intranasal administration of live attenuated strains, subunit strategies using HN and F proteins, recombinant bovine human viruses, and strains engineered using reverse genetics.
• At present, antigenically and genetically stable attenuated stains of HPIV-3 have been developed with cold adaptation (CA), whose stability is enhanced because of multiple markers of attenuation in tissue culture. Cold adaptation strains of HPIV-1 and HPIV-2 have been developed, and attenuation in tissue culture and animal models has been demonstrated.
• Reverse genetics has produced an attenuated chimeric HPIV-1 that contains type 3 internal proteins with type 1 surface glycoproteins F and HN.⁵

Complications

• Adult respiratory distress syndrome and exacerbation of nephritic syndrome
• Serious morbidity in immunocompromised hosts (eg, transplant recipients)
• Rare complications, including Guillain-Barré syndrome and meningitis

Prognosis

• HPIV infections in older children and adults are generally mild. Occasionally, bronchiolitis or viral pneumonia in children and tracheobronchitis in adults has been reported.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Clinically distinguishing pneumonia caused by HPIV from pneumonia caused by bacteria is difficult; hence, patients with pneumonia are sometimes inappropriately treated with antibacterial antibiotics.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Fry AM, Curns AT, Harbour K, et al. Seasonal trends of human parainfluenza viral infections: United States, 1990-2004. Clin Infect Dis. Oct 15 2006;43(8):1016-22. [Medline].
2. Lau SK, To WK, Tse PW, et al. Human parainfluenza virus 4 outbreak and the role of diagnostic tests. J Clin Microbiol. Sep 2005;43(9):4515-21. [Medline].
3. Juozapaitis M, Zvirbliene A, Kucinskaite I, Sezaite I, Slibinskas R, Coiras M, et al. Synthesis of recombinant human parainfluenza virus 1 and 3 nucleocapsid proteins in yeast Saccharomyces cerevisiae. Virus Res. May 2008;133(2):178-86. [Medline].
4. Yoo SJ, Kuak EY, Shin BM. Detection of 12 respiratory viruses with two-set multiplex reverse transcriptase-PCR assay using a dual priming oligonucleotide system. Korean J Lab Med. Dec 2007;27(6):420-7. [Medline].
5. Nolan SM, Surman SR, Amaro-Carambot E, et al. Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses. Vaccine. Sep 15 2005;23(39):4765-74. [Medline].
6. Arden KE, McErlean P, Nissen MD, et al. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol. Sep 2006;78(9):1232-40. [Medline].
7. Connolly SA, Lamb RA. Paramyxovirus fusion: real-time measurement of parainfluenza virus 5 virus-cell fusion. Virology. Nov 25 2006;355(2):203-12. [Medline].
8. Elizaga J, Olavarria E, Apperley J, et al. Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment. Clin Infect Dis. Feb 1 2001;32(3):413-8. [Medline].
9. Greer CE, Zhou F, Legg HS, et al. A chimeric alphavirus RNA replicon gene-based vaccine for human parainfluenza virus type 3 induces protective immunity against intranasal virus challenge. Vaccine. Jan 5 2007;25(3):481-9. [Medline].
10. Hohenthal U, Nikoskelainen J, Vainionpaa R, et al. Parainfluenza virus type 3 infections in a hematology unit. Bone Marrow Transplant. Feb 2001;27(3):295-300. [Medline].
11. Hu A, Colella M, Zhao P, et al. Development of a real-time RT-PCR assay for detection and quantitation of parainfluenza virus 3. J Virol Methods. Dec 2005;130(1-2):145-8. [Medline].
12. Iwata S. [Diagnostic tests: Parainfluenza virus 1, 2, 3, 4]. Nippon Rinsho. Jul 2005;63 Suppl 7:349-51. [Medline].
13. Laurichesse H, Dedman D, Watson JM, et al. Epidemiological features of parainfluenza virus infections: laboratory surveillance in England and Wales, 1975-1997. Eur J Epidemiol. May 1999;15(5):475-84. [Medline].
14. Maeda Y, Hatta M, Takada A, et al. Live bivalent vaccine for parainfluenza and influenza virus infections. J Virol. Jun 2005;79(11):6674-9. [Medline].
15. Matsuse H, Kondo Y, Saeki S, et al. Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes. Int Arch Allergy Immunol. Nov 2005;138(3):267-72. [Medline].
16. Nishio M, Tsurudome M, Ito M, et al. Identification of RNA-binding regions on the P and V proteins of human parainfluenza virus type 2. Med Microbiol Immunol. Mar 2006;195(1):29-36. [Medline].
17. Specter S, Hodinka R, Young S. Clinical Virology Manual. 3^rd ed. 2001:239-40.
18. Tanaka Y, Kato J, Kohara M, et al. Antiviral effects of glycosylation and glucose trimming inhibitors on human parainfluenza virus type 3. Antiviral Res. Oct 2006;72(1):1-9. [Medline].
19. Templeton KE, Bredius RG, Claas EC, et al. Parainfluenza virus 4 detection in infants. Eur J Pediatr. Aug 2005;164(8):528-9. [Medline].

Article Last Updated: Jul 24, 2008