Galarah GolanbarChristopher Kwon

Vanessa Munoz

Case Study: Parainfluenza Virus

A 13-month-old child has a runny nose, mild cough and low grade fever for several days. The cough got worse and sounded like “barking.” The child made a wheezing sound when agitated. The child appeared well, except for the cough. A lateral X-ray examination of the neck showed a subglottic narrowing.

1. What are the specific and common names for these symptoms?

The symptoms of parainfluenza virus can vary widely, from cold-like symptoms to severe difficulty breathing in rare cases. Our case only describes a few of the multitude of symptoms that can be seen with infection by parainfluenza virus. Based on the description of the case above, we see that the child is suffering primarily from viral croup or laryngotracheobronchitis, which accounts for the majority of upper respiratory obstructions in children. [1,2] It is usually preceded by coryza, displaying features of the common head cold. Coryza is associated directly with rhinorrhea, or runny nose, although a low-grade fever is also a regular contributor. [3] The child is also described as having a mild cough, which can progress to the barking cough seen in patients with viral croup, and is the most common symptom seen in infection by parainfluenza virus. This occurs when the mucous membranes lining the nasopharyngeal cavities are inflamed. Additionally, when agitated, the child shows inspiratory stridor, or wheezing, characterized by a high-pitched sound, which accompanies and often exacerbates the persistent cough. [4] This may be a sign that the body is trying to clear the airways and recover from the illness by reflex. Parainfluenza virus, regardless of the type, is known to cause frequent episodes of infection throughout one’s life once it has been contracted.

2. What other agents could cause a similar clinical presentation (differential diagnosis)?

There are three common types of human parainfluenza virus (HPIV): Type 1, Type 2, and Type 3. Of these three, Types 1 and 2 have been found to be major contributors of viral croup, and have been known to cause biennial outbreaks in the fall. [5] Type 3 is known to be associated with bronchiolitis and pneumonia. [6] A fourth type of HPIV has been reported that is associated with respiratory infections. However, infection by this type is usually mild and infrequent. [7] Other causative microorganisms include influenza virus, respiratory syncitial virus (RSV), adenovirus, rhinovirus, enterovirus and the newly discovered metapneumovirus [6,7] When croup is caused by influenza virus, the symptoms are usually more severe. In a few rare cases, Mycoplasma pneumoniae had been isolated. [8] Other conditions that present similarly are spasmodic croup, and epiglottitis. In most cases of spasmodic croup, an upper respiratory tract infection is absent and there is no fever associated with it. Additionally, sudden onset of spasmodic croup is nocturnal and resolves by morning. Symptoms of epiglottitis are much more

severe, and include toxicity, high fever, dysphagia (fainting) and drooling. [6,7] The causative agents for epiglottitis are usually bacterial in nature, and can be confirmed by laryngoscopy, where the arytenoids and epiglottis can be seen as having an inflamed, cherry-red appearance. As a definitive test of the presence of epiglottitis, a lateral C-spine X-ray of the neck reveals the trademark thumbprint sign. [9] Additionally, HPIV Types 2 and 3 can induce expression of intercellular adhesion molecules-1 (ICAM-1) in some cells of the respiratory tract, providing receptors to which rhinoviruses can bind, causing superinfection. [10]

3. Were there readily available laboratory tests to confirm this diagnosis? If so, what were they?

Diagnosis follows a pattern, and immunological and radiological testing is done to confirm. Lateral posteroanterior (PA) X-rays of the soft tissues of the neck show the classic “steeple sign” of subglottic narrowing often caused by HPIV infection. However, only 50% of cases will show this pattern upon routine X-ray examinations. Naturally, the subglottic region of the neck shows a narrow passage for airflow; thus, in some cases where the classic steeple sign can be visualized, inflammation of this area significantly reduces airflow, and contributes to respiratory difficulties. [11]

Moreover, a presumptive diagnosis of HPIV can be made based on the trends in community viral surveillance, history, age, and findings from physical examination. Definitive diagnosis requires identification of the virus. There are 2 methods currently available for identification of HPIV: rapid identification techniques performed directly on respiratory secretions and viral culture of respiratory samples. The best clinical samples are nasal washes or nasal swabs that are immediately placed into sterile containers with viral media and are transported on ice to the virology laboratory. These principles of specimen collection are true for many of the respiratory viruses in clinical medicine, and are essential to the successful identification of viruses. [12]

Rapid identification of viral antigens by immunofluorescence or detection of viral RNA by amplification methods is possible, using respiratory tract secretions. [13,14,15] Direct antigen detection with commercially available fluorescent monoclonal antibody reagents, however, has low sensitivity and specificity. [15] New RNA amplification methods have been promising, with a reported sensitivity of 94% to 100% and a specificity of 95%, but they serve only as research tools at this time. [13,14]

Viral culture is the gold standard for detection. HPIVs may grow as early as 2 days or as long as 14 days after primary infection with the virus. HPIVs may produce a subtle cytopathic effect in cell culture that is detected by light microscopy. They may also demonstrate a hemadsorption phenomenon that is detected by adsorption of guinea pig red blood cells onto the surface of infected cells. Other hemadsorbing viruses include influenza, measles, and mumps. After demonstration of the cytopathic effects or hemadsorption, immunofluorescent monoclonal antibodies are used to differentiate PIV from other hemadsorbing viruses and to identify the specific PIV type.

4. Was there a possible treatment for this child?

There have been no clinically controlled trials proving effective antiviral treatment for PIV; however, ribavirin has demonstrated both in vivo and in vitro activity against PIV. [16,17,18,19,20] The use of inhaled ribavirin in immunocompromised patients or in those with severe disease could be helpful to these individuals. Symptomatic treatment of clinical syndromes is the only available treatment at this time. Symptomatic treatment of laryngotracheitis includes humidified cool air and inhalation of racemic epinephrine. Also, the use of high-dose systemic corticosteroids (i.e. dexamethasone) could be used in the treatment of moderate and severe disease, which shortens the course of clinical symptoms and reduces the incidence of endotracheal intubation. [21] Nebulized steroids (budesonide) have been recommended for use in children with moderate-to-severe laryngotracheitis. [22] For other clinical syndromes, the only available treatment consists of supportive therapy with oxygen, bronchodilators, and antibiotics used wisely in instances of bacterial superinfection.

References

1. Viral Croup: A Current Perspective. Leung, A.K.C., Kellner, J.D., Johnson, D.W. Journal of Pediatric Health Care November/December (2004): 297-301.

2. Infections: Croup. Dowshen, S., Homeier, B.P. Nemours Foundation. May, 2005. (http://www.kidshealth.org/parent/infections/bacterial_viral/croup.html)

3. Parainfluenza virus infections. Vega, R.M. eMedicine from WebMD. Sept. 24, 2007. (http://www.emedicine.com/ped/topic1730.htm)

4. Evaluation of Stridor and Wheezing. Holinger, L.D. Journal of Children’s Memorial Hospital, Chicago. Spring, 1998. (http://www.childsdoc.org/spring98/stridor/stridor.asp)

5. Definition of Human Parainfluenza Virus. (http://www.medterms.com/script/main/art.asp?articlekey=31631)

6. Viral Croup: A Current Perspective. Leung, A.K.C., Kellner, J.D., Johnson, D.W. Journal of Pediatric Health Care November/December (2004): 297-301.

7. Human Parainfluenza Virus Type 4 Infections: A report of 20 cases from 1998 to 2002. Billaud et al. Journal of Clinical Virology 34 (2005) 48–51.

8. Clinical courses of croup caused by influenza and parainfluenza virus. Peltola, V., Heikkinen, T., & Ruuskanen, O. The Pediatric Infectious Disease Journal 21 (2002)

9. Acute Epiglottitis. Jaffe, J.E. eMedicine.com by WebMD. (http://www.emedicine.com/Radio/topic263.htm)

10. Parainfluenza Virus. Parija, S.C., Marrie, T.J. eMedicine.com by WebMD. (http://www.emedicine.com/MED/topic1733.htm)

11. Concise Review for Primary-Care Physicians-Viral Croup: Current Diagnosis and Treatment by Julia Rosekranse, MD (http://www.mayoclinicproceedings.com/inside.asp?AID=3078&UID)

12. Quest Diagnosis Laboratories test guide (2006).

13. Fan J, Henrickson KJ: Rapid diagnosis of human parainfluenza virus type 1 infection by quantitative reverse transcription-pcr-enzyme hybridization assay. Journal of Clinical Microbiology 34:1914-1917, 1996.

14. Gilbert LL, Dakhama A, Bone BM, et al: Diagnosis of viral respiratory tract infections in children by using a reverse transcription-pcr panel. Journal of Clinical Microbiology 34:140-143, 1996.

15. Steele RW: Pneumonia in children: Current status of diagnosis and treatment. Journal of Respiratory Diseases 8:63-73, 1987.

16. Sidwell RW, Huffman JH, Khare GP, et al: Broad-spectrum antiviral activity of virazole 1-b-d-ribofuranosyl-1,2,4-triazole-3-carcoxamide. Science 177:705-706, 1972.

17. Steele RW: Antiviral agents for respiratory infections. Pediatric Infectious Diseases Journal 7:457-461, 1988.

18. Cobian L, Houston S, Greene J, et al: Parainfluenza virus respiratory infection after heart transplantation: Successful treatment with ribavirin. CID 21:1040-1041, 1995.

19. Gilbert B, Knight V: Biochemistry and clinical applications of ribavirin. Antimicrob Agents Chemother 30:201-205, 1986.

20. Gelfand E: Ribavirin treatment of viral pneumonia in severe combined immunodeficiency. Lancet 1:732-733, 1983.

21. Kairys SW, Olmstead EM, O'Connor GT: Steroid treatment of laryngotracheitis: A meta-analysis of the evidence from randomized trials. Pediatrics 83:683-693, 1989.

22. Klassen TP, Feldman ME, Watters LK, et al: Nebulized budesonide for children with mild-to-moderate croup. N Engl J Med 331:285-289, 1994.