Parainfluenza Viruses

Parainfluenza viruses are common human respiratory pathogens, in the main they produce relatively harmless upper respiratory tract infections (URTI), but they are also the commonest cause of a more serious condition in young children known as "croup" and occasionally cause pneumonia. Human parainfluenza virus types 1 and 3 belong to the genus Paramyxovirus, whereas types 2, 4a, and 4b are now classified with mumps virus in the genus Rubulavirus.

Clinical Features

Primary infection, typically in a young child, generally manifests itself as coryza and pharyngitis, often with some degree of bronchitis and low fever. However, there are two more serious presentations which are seen in 2-3% of infections (Table 28-4). In an infant, especially under Ihe age of 6 months, parainfluenzavirus type 3 may cause bronchiolitis and/or pneumonia clinically indistinguishable from that more commonly caused by the respiratory syncytia] virus (see below). In somewhat older children (6 months to 5 years) parainfluenzavirus type 1 and, to a lesser extent, type 2 are the major cause of croup (Jaryngotracheobronchitis). The child presents with fever, cough, stridor, and respiratory distress which may occasionally progress to laryngeal obstruction requiring intubation or tracheotomy.

Laboratory Diagnosis

Traditionally, parainfluenza viruses have been isolated in primary human or monkey kidney cells; since these cells have become no longer generally ob-

Table 28-4

Clmirol and Epidemiologic Features of Parainfluenza and Respiratory Syncytial Virus Infections

Table 28-4

Clmirol and Epidemiologic Features of Parainfluenza and Respiratory Syncytial Virus Infections

Virus

Major syndrome

Age

Epidemiology

Parainfluenza 1 and 2

Croup

First 5 years

Autumn epidemic

Parainfluenza 3

Bronchiolitis, pneumonia

First year

Endemic

Parainfluenza 4

Upper respiratory infection

Children

Endemic

Respiratory syncytial virus

Bronchiolitis, pneumonia

First year

Winter epidemic

tainable, they have been replaced by continuous cell lines such as H292 Trypsin is added to the maintenance medium to ensure cleavage of the viral F protein. Parainfluenza viruses multiply rather slowly and cause little cyto-pathic effect (CPE), except in the case of type 2 which induces syncytia. Viral growth is detected by hemadsorption of guinea pig red cells (see Fig. 5-2D). Differentiation lrom other hemadsorbing respiratory viruses may then be made by fluorescent antibody staining of the infected monolayer or by hemagglutination inhibition using virus from the cell culture supernatant.

Today, however, the pendulum has swung toward more rapid diagnostic techniques, notably immunofluorescence (IF) and EIA on nasopharyngeal aspirates. Immunofluorescence is used to demonstrate antigen in exfoliated cells, whereas EIA or RIA is sufficiently sensitive to detect free antigen in mucus suitably solubilized to liberate intracellular as well as extracellular protein.

Epidemiology

Like other respiratory agents, parainfluenza viruses are spread by droplets and by contact with respiratory secretions. The incubation period ranges from 2 to 6 days, and shedding continues for about a week. Parainfluenza viruses are highly transmissible, infecting most children by the age of 5 years. Indeed, type 3 infects the majority of infants within the first year or two of life and can spread within hospitals and babies' homes, causing cases of pneumonia and bronchiolitis. Types 1 and 2 tend lo cause croup, whereas type 4 produces only trivial illness. Reinfections with any given type of parainfluenza virus commonly occur, although clinical disease is generally mild and confined to the upper respiratory tract the second time round.

Control

Several types of experimental parainfluenza type 3 vaccines have shown some degree of protection in rodent or primate models. However, formidable problems militate against parainfluenza vaccines achieving wide acceptability. First, the immunity that follows natural infection with parainfluenza viruses is poor, and it is unrealistic to expect any vaccine to do more than limit the challenge virus to the upper respiratory tract. Second, in order to protect infants during the first months of life when parainfluenza 3 can be a threat, any vaccine would need to be administered shortly after birth, when immune responses are weakest and maternal antibodies are present. Third, in light of the worrying experience with earlier inactivated respiratory syncytia] virus and measles vaccines, which actually potentiated the disease occurring on subsequent challenge, subunit vaccines would also need to undergo very careful clinical trials before licensing.

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