Parainfluenza Virus Infection

Abstract

Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development.

Fig. 1

Structure of human parainfluenza virus serotypes 1 to 4. Parainfluenza viruses are single-stranded, enveloped RNA viruses and virions are pleomorphic, ranging in diameter from 150 to 200 µm. The RNA encodes six essential proteins in a conserved order: the nucleocapsid protein (NP), the phosphoprotien (P), the matrix protein (M), the fusion glycoprotein (F), the hemagglutinin neuraminidase glycoprotein (HN), and RNA polymerase (L). (Reproduced with permission from Moscona A. Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease. J Clin Invest 2005;115:1688–1698.13)

Fig. 2

Cycle of attachment, fusion, and replication for parainfluenza viruses. The HN glycoproteins attach to sialic acid residues on the surface of host epithelial cells and fusion glycoprotein mediate fusion of the viral envelope with the host cell membrane. After attachment, the genetic material is uncoated and replication occurs in the cytoplasm of host cells. The NP protein binds the viral RNA, creating a template for the RNA-dependent RNA polymerase, consisting of the P and L proteins. Once replication is completed, HN and F proteins are transferred to the host cell membrane which forms the envelope for new virons which is coated on the inner surface by the matrix protein. The HN protein then facilitates budding and release of new virions from the cell by cleaving the sialic acid residues. (Reproduced with permission from Moscona A. Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease. J Clin Invest 2005;115:1688–1698.13)

Fig. 3

Pathogenesis and disease progression of HPIV-associated croup. (Adapted from Bower J and McBride JT, Principles and Practices of Infectious Diseases. 8^th Edition 2015.27)

Fig. 4

The percentage of tests positive for human parainfluenza virus (HPIV) serotypes 1, 3, 2, and 4 reported to the National Respiratory and Enteric Viruses Surveillance System (NREVSS), by week, July 1990 to June 2004. (Reproduced from Fry AM, Curns AT, Harbour K, et al. Seasonal trends of human parainfluenza viral infections: United States, 1990–2004. Clin Infect Dis 2006;43:1016-1022.38)

Fig. 5

Age distribution of parainfluenza serotypes 1, 2, and 3 viral infections in outpatient children. The y-axis represents the percentage of children for whom infection with the three parainfluenza virus serotypes was detected per age group. Vertical lines identify serotype with the highest incidence of infection per age group. (Adapted from Knott, AM, Long, CE, et al. Parainfluenza viral infections in pediatric outpatients: seasonal patterns and clinical characteristics. J Pediatr Infect Dis 1994, 13:269–73.5)

Fig. 6

Comparison of influenza, parainfluenza, and RSV infections in hospitalized patients with chronic underlying conditions. Chronic pulmonary conditions included asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, sarcoidosis, and malignancy or asbestosis. Other chronic conditions included congestive heart failure, metabolic disease (i.e., diabetes), chronic anemia, chronic renal disease, and malignancies or immunocompromising conditions. The percent of viruses is shown distributed by age group. Black, respiratory syncytial virus (RSV); white, influenza; gray, human parainfluenza virus (HPIV). (Adapted from Glezen, WP et al. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 2000;283(4):499–505.67)

Fig. 7

Proportion of clinical syndromes associated with parainfluenza infection in children found in a survey of respiratory illnesses in children in an outpatient setting with a known viral etiology. Upper respiratory tract infection (URTI) indicates colds with or without fever. NOS indicates an undifferentiated febrile illness. (Adapted from Knott, AM, Long, CE, et al. Parainfluenza viral infections in pediatric outpatients: seasonal patterns and clinical characteristics. J Pediatr Infect Dis 1994, 13:269–273.5)

Fig. 8

Anterior/Posterior chest radiograph demonstrating tapering of the upper trachea or “steeple” sign seen in parainfluenza-associated croup infections. Arrows indicate area of obstruction resulting from inflammation of the subglottic region of the trachea. (Reproduced with permission from Huang,Chun-Chao and Shih, Shin-Lin. Steeple Sign of Croup. N Engl J Med 2012; 367:6.207)

Fig. 9

Chest radiograph and chest computed tomography (CT) of a 5-year-old child with HPIV3-associated necrotizing community-acquired pneumonia. Viral PCR of a nasopharyngeal sample was positive for HPIV3. Blood culture was positive for methicillin-resistant Staphylococcus aureus. Chest radiograph (A) reveals bilateral, multifocal infiltrates and a small left pleural effusion. (B) CT confirms dense consolidation in the left lower lobe, right upper, and right lower lobes; numerous satellite nodules in the left lower and upper lobe bronchiectasis; and multifocal cystic lesions bilaterally. (Reproduced with permission from Derek J. Williams, and Samir S. Shah J Pediatr Infect Dis 2012;1:1–5.94)

Fig. 10

Patterns found on high-resolution chest computed tomography (CT) in hematopoietic stem cell transplant recipients with HPIV3 pneumonia. (A) Peribronchial nodules. (B) Nodules and associated consolidation. (C) Very small peribronchial nodules in the left upper lobe. (D) Multiple small peribronchial nodules and ground-glass consolidation. (Reproduced with permission from Ferguson PE, et al. Clin Infect Dis 2009;48:905–909.116)