Parainfluenza Viruses

Etiology

HPIVs are members of the Paramyxoviridae family. Four HPIVs cause illness in humans, classified as types 1-4, with diverse manifestations of infection. Type 4 is divided into two antigenic subtypes, 4a and 4b. HPIVs have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope derived from budding through the host cell membrane. The major antigenic moieties are the hemagglutinin neuraminidase (HN) and fusion (F) surface glycoproteins.

Epidemiology

By 5 yr of age, most children have experienced primary infection with HPIV types 1, 2, and 3. HPIV-3 infections generally occur earliest, with half of infants infected by age 1 yr, and over 90% by age 5 yr. HPIV-1 and HPIV-2 are more common after infancy, with approximately 75% infected by age 5 yr. Although HPIV-4 is not recognized as often, about half of children have antibody by the age of 5 yr. In the United States and temperate climates, HPIV-1 has typically been reported to have biennial epidemics in the fall in odd-numbered years ( Fig. 286.1 ). HPIV-2 has been reported to cause yearly outbreaks in the fall, but is less common than HPIV-1 or HPIV-3. HPIV-3 can be endemic throughout the year but typically peaks in late spring. In years with less HPIV-1 activity, the HPIV-3 season has been observed to extend longer or to have a second peak in the fall (see Fig. 286.1 ). The epidemiology of HPIV-4 is less well defined, because it is difficult to grow in tissue culture and was often excluded from previous studies, but a recent study suggests it may circulate throughout the year and peak in fall of odd-numbered years. National HPIV trends are created from weekly laboratory test result data that are reported on a voluntary basis, and are available at the Centers for Disease Control and Prevention (CDC) National Respiratory and Enteric Virus Surveillance System (NREVSS) website ( https://www.cdc.gov/surveillance/nrevss ).

HPIVs are spread primarily from the respiratory tract by inhalation of large respiratory droplets or contact with infected nasopharyngeal secretions. HPIVs are notable for causing outbreaks of respiratory illness in hospital wards, clinics, neonatal nurseries, and other institutional settings. The incubation period from exposure to symptom onset may range from 2 to 6 days. Children are likely to excrete virus from the oropharynx for 2-3 wk, but shedding can be more prolonged, especially in immunocompromised children, and may persist for months. Primary infection does not confer permanent immunity, and reinfections are common throughout life. Reinfections are usually mild and self-limited, but can cause serious lower respiratory tract illness, particularly in children with compromised immune systems.

Pathogenesis

HPIVs replicate in the respiratory epithelium. The propensity to cause illness in the upper large airways is presumably related to preferential replication in the larynx, trachea, and bronchi in comparison with other viruses. Some HPIVs induce cell-to-cell fusion. During the budding process, cell membrane integrity is lost, and viruses can induce cell death through the process of apoptosis. In children, the most severe illness generally coincides with the time of maximal viral shedding. However, disease severity is likely related to the host immune response to infection as much as to direct cytopathic effects of the virus. Virus-specific immunoglobulin A antibody levels and serum antibodies to the surface HN and F glycoproteins are able to neutralize HPIV, and both likely contribute to host immunity. Cell-mediated cytotoxicity is also important for controlling and terminating HPIV infection.