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Parainfluenza Virus: Differential Diagnoses & Workup

Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Coauthor(s): Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Contributor Information and Disclosures

Updated: Jul 24, 2008

Differential Diagnoses

Adenoviruses
Chlamydial Pneumonias
Coxsackieviruses
Influenza
Mycoplasma Infections

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

Laboratory 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.

More on Parainfluenza Virus

Overview: Parainfluenza Virus
Differential Diagnoses & Workup: Parainfluenza Virus
Treatment & Medication: Parainfluenza Virus
Follow-up: Parainfluenza Virus
References
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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].

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  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].

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  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].

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  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].

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Further Reading

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Keywords

parainfluenza virus, human parainfluenza virus, HPIV, HPIV-1, HPIV-2, HPIV-3, HPIV-4, croup, laryngotracheobronchitis, PIV, paramyxoviruses, croup-associated virus, CA virus, Sendai virus, croup, bronchitis, bronchopneumonia, pharyngitis, tracheobronchitis, bronchiolitis, acute respiratory tract infections, pneumonia, respiratory syncytial virus, RSV

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Contributor Information and Disclosures

Author

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Subhash Chandra Parija, MBBS, MD, PhD, FRCPath is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences, India, and Royal College of Pathologists
Disclosure: Jawaharlal Institute of Postgraduate Medical education & Research , Pondicherry , India Salary Employment

Coauthor(s)

Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital Corporation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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