Parainfluenza Viral Disease

Epidemiology

The human parainfluenza viruses are ubiquitous, with a worldwide geographic distribution. ^, Their transmission is principally by large-particle fomites via close person-to-person contact. Parainfluenza virus activity displays both endemic and epidemic patterns, with each serotype preferring different age groups and triggering distinct clinical syndromes but with enough overlap to preclude specific diagnosis based solely on clinical and epidemiologic grounds. In the United States, about 55% of confirmed cases are type 3, about 18% are type 1, about 14% are type 2, and about 13% are type 4.

Primary infection with human parainfluenza virus occurs early in childhood. Of the parainfluenza viruses, type 3 generally infects infants first, such that 50 to 67% of infants demonstrate serologic evidence of infection by 1 year of age. Parainfluenza virus types 1 and 2 most commonly infect children between 2 and 5 years of age. Parainfluenza virus type 4 less commonly causes symptomatic respiratory infections, but it may frequently be found as a viral coinfection with other pathogens.

Until the early 1960s, type 1 human parainfluenza virus caused endemic annual disease in the United States. For the past several decades, however, type 1 human parainfluenza virus has been associated with biennial outbreaks in the fall of odd-numbered years. Infections with type 2 human parainfluenza virus largely follow this same curious pattern but occur much less commonly than type 1 human parainfluenza virus infections. Infections with type 3 human parainfluenza virus have remained endemic throughout the year, with peaks in the late spring. Biennial outbreaks of type 1 human parainfluenza virus also occur in even-numbered years in Australia. During the 2020-2021 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the typical seasonal circulation patterns of human parainfluenza virus changed, but whether new seasonal patterns will emerge is not yet certain. ^, The incubation period for all serotypes of human parainfluenza virus is between 3 and 6 days in experimentally infected adults, but natural infections in children have incubation periods of 2 to 4 days.

The human parainfluenza viruses are second only to respiratory syncytial virus as the cause of acute upper and lower respiratory tract infections in young children in the United States. In a population-based study of children younger than 5 years hospitalized with fever or acute respiratory tract infection, 7% of children had laboratory-confirmed human parainfluenza virus infection (by cell culture and molecular amplification techniques), compared with 19% with respiratory syncytial virus and 6% with influenza A or B virus infections. The hospitalization rate for human parainfluenza virus infection in children younger than 5 years was 1.02 per 1000 children per year. Extrapolating to the entire U.S. population, these data suggest that approximately 23,000 human parainfluenza virus hospitalizations occur annually in children younger than 5 years. The rates of emergency department and outpatient health care visits attributable to human parainfluenza virus infections in young children are 10- to 50-fold greater than hospitalization rates. Further, immunity to human parainfluenza virus infection is neither complete nor durable, so older children and adults can be infected by young children and subsequently exhibit symptomatic infection, sometimes leading to office visits and hospitalization.

Pathobiology

The human parainfluenza virus genome encodes six structural proteins. The hemagglutinin-neuraminidase (HN) and fusion (F) proteins, which are exposed on the bilayered lipid envelope surrounding the helical nucleocapsid–RNA complex, mediate both attachment to host sialic acid–containing glycoproteins and penetration of the virus into susceptible mammalian cells. These proteins have retained their antigenic stability for many years, unlike the “drift and shift” of the hemagglutinin and neuraminidase of influenza viruses. The four serotypes of human parainfluenza virus are called types 1 to 4, including two subgroups (A and B) of type 4 virus.

The human parainfluenza viruses replicate in the ciliated epithelial cells that line the respiratory tract on its luminal surface. This selective tropism is consistent with the absence of invasive disease or viremia in the immunocompetent host, although rare cases of human parainfluenza virus 3 aseptic meningitis have been described. Syncytium formation, which is noted in viral cell cultures and in the lungs of immunocompromised patients with severe pneumonia, is not thought to be important in typical infections of previously healthy individuals.

Clinical Manifestations