What is Human Parainfluenza Virus (HPIV)?

Human Parainfluenza Virus (HPIV)

Human parainfluenza virus (HPIV) is a common respiratory pathogen comprising four serotypes that cause a spectrum of respiratory illnesses ranging from mild upper respiratory tract infections to severe pneumonia, with significant morbidity and mortality in immunocompromised patients and young children. 1

Virology and Classification

HPIV belongs to the Paramyxoviridae family and consists of four major serotypes (HPIV-1, HPIV-2, HPIV-3, and HPIV-4). These are single-stranded, enveloped RNA viruses that are genetically and antigenically distinct 2. HPIV-4 is further divided into subtypes A and B, while HPIV-1 and HPIV-3 have distinct subgroups/genotypes 2.

Epidemiology

• HPIV circulates throughout the year but shows type-specific seasonal patterns:

  • HPIV-1 and HPIV-2: Primarily cause outbreaks during autumn and spring 1
  • HPIV-3: Most commonly detected type (80-90% of cases) in both children and immunocompromised patients 1
  • HPIV-4: Less common but still clinically significant

• Incubation period: Approximately 2.6 days (95% CI, 2.1-3.1) 1

• Transmission:

  • Primarily person-to-person through respiratory droplets
  • High rate (17.9%) of asymptomatic shedding, facilitating outpatient and nosocomial outbreaks 1
  • 90% of pediatric HPIV infections are community-acquired 1

Clinical Manifestations

HPIV causes a wide spectrum of respiratory illnesses:

• Upper respiratory tract infections (URTI):

  • Common cold symptoms
  • Pharyngitis
  • Otitis media
  • Conjunctivitis 3

• Lower respiratory tract infections (LRTI):

  • Croup (laryngotracheobronchitis) - particularly HPIV-1 and HPIV-2 1, 3
  • Bronchiolitis
  • Tracheobronchitis
  • Pneumonia 3

• Severity varies by population:

  • In healthy adults: Usually mild, self-limiting illness
  • In children: HPIV accounts for 40% of pediatric hospitalizations for LRTI and 75% of croup cases 3
  • In immunocompromised patients (especially HSCT recipients): Can cause severe pneumonia with high mortality 1

Risk Factors for Severe Disease

Risk factors for progression to lower respiratory tract disease include:

• Higher corticosteroid exposure
• Neutropenia
• Lymphopenia (<0.2 × 10^9/L)
• Infection early after allogeneic HSCT (<1 month)
• Higher APACHE II score
• Coinfections
• Older age (>65 years)
• Severe immunodeficiency 1

Diagnosis

HPIV diagnosis has evolved from traditional methods to more sensitive molecular techniques:

• Nucleic acid amplification testing (NAAT) - current gold standard:

  • Most sensitive method
  • Can identify all four HPIV serotypes
  • Often included in multiplex respiratory panels 1

• Specimen collection:

  • Respiratory secretions or nasopharyngeal swabs placed in viral transport medium
  • For lower respiratory involvement: Bronchoalveolar lavage (BAL) 1

• Traditional methods (less commonly used now):

  • Direct antigen detection (DAD)
  • Viral isolation by culture (VIC) - may take 4-7 days 1

Clinical Impact and Outcomes

• In immunocompetent adults: Generally mild disease with complete recovery

• In HSCT and leukemia patients:

  • Symptomatic HPIV infections occur in 2-7% of patients 1
  • At least one-third manifest as lower respiratory tract disease 1
  • Progression from upper to lower respiratory tract disease: 13-37% 1
  • Mortality in those with lower respiratory tract disease: 10-30% 1
  • HPIV pneumonia in HSCT recipients: 50% acute mortality and 75% mortality at 6 months 3

• Long-term complications:

  • Significant airflow decline in 40% of patients with upper respiratory tract infection 1
  • Bronchiolitis obliterans syndrome associated with HPIV infection within first 3 months after allogeneic HSCT 1

Treatment

Treatment options for HPIV infection are limited:

• For most immunocompetent patients:

  • Supportive care is the mainstay of treatment
  • No FDA-approved antiviral therapies specifically for HPIV 3

• For croup:

  • Corticosteroids have been found to be beneficial 3

• For immunocompromised patients with severe disease:

  • Some centers consider treating HPIV upper respiratory tract infection in patients with risk factors for lower respiratory tract disease, and those with established lower respiratory tract disease, with ribavirin and/or IVIG 1
  • However, evidence is limited by the lack of effective agents and randomized controlled trials 1
  • Novel therapies like DAS181 show promise for treating severe disease in immunocompromised patients 3
  • Monoclonal antibodies targeting HPIV F protein (such as PI3-E12) have shown potential in animal models 4

Prevention

• Infection control measures are crucial:

  • Good personal hygiene (frequent hand washing)
  • Covering mouth when coughing and sneezing
  • Safe disposal of oral and nasal secretions
  • Isolation of infected patients
  • Restricting visitors with respiratory symptoms 1

• Vaccines:

  • Currently no licensed vaccines available
  • Several candidates are in development 3

Conclusion

HPIV represents a significant respiratory pathogen with substantial clinical impact, particularly in vulnerable populations. While diagnostic capabilities have improved significantly with molecular testing, treatment options remain limited, highlighting the need for continued research into effective antiviral therapies and preventive vaccines.