Human parainfluenza virus 4 outbreak and the role of diagnostic tests

Abstract

Owing to the difficulties in isolating the virus and the lack of routine surveillance, the clinical significance of human parainfluenza virus 4 (HPIV-4) is less well defined than that of the other human parainfluenza viruses. We describe the first outbreak of HPIV-4 infection in a developmental disabilities unit, involving 38 institutionalized children and three staff members, during a 3-week period in autumn 2004. Most subjects had upper respiratory tract infections (URTI), while lower respiratory tract infections (LRTI) occurred in three children (7%), one complicated by respiratory failure requiring ventilation support. All patients recovered. Nasopharyngeal aspirates tested for HPIV-4 were positive by reverse transcriptase PCR (RT-PCR) in all 41 cases (100%), by direct immunofluorescence in 29 of 39 tested cases (74%), and by cell cultures in 6 of 37 cases (16%), and serum was positive for antibodies against HPIV-4 in all 35 cases (100%) with serum samples available. In addition, RT-PCR detected HPIV-4 in four children (three LRTI and one URTI) out of 115 patients with community-acquired respiratory tract infection. Molecular analysis of the 1,198-bp phosphoprotein sequences showed that HPIV-4 isolates among the cases were genetically similar, whereas the community controls were more genetically distant, supporting nosocomial transmission of a single HPIV-4 genotype during the outbreak. Moreover, the HPIV-4 causing the outbreak is more closely related to HPIV-4A than HPIV-4B. HPIV-4 may be an important cause of more severe respiratory illness in children. The present RT-PCR assay is a sensitive, specific, and rapid method for the diagnosing HPIV-4 infection. To better define the epidemiology and clinical spectrum of disease of HPIV-4 infections, HPIV-4 should be included in the routine panels of respiratory virus detection on respiratory specimens.

FIG. 1.

Epidemic curve summarizing the number of new cases versus day from outbreak. 3/F, cases from the third floor; 1/F, cases from the first floor.

FIG. 2.

Phylogenetic analysis of the deduced amino acid sequences of phosphoprotein genes of HPIV-4 from the index case (case 1) in relation to members of the family Paramyxoviridae. The tree was constructed by the neighbor-joining method using the Jukes-Cantor correction and bootstrap values calculated from 1,000 trees. The scale bar indicates the estimated number of substitutions per 100 amino acids.

FIG. 3.

Phylogenetic analysis of phosphoprotein genes of HPIV-4 from 36 cases and four community controls positive for HPIV-4 by RT-PCR. The tree was constructed by the neighbor-joining method using the Jukes-Cantor correction and bootstrap values calculated from 1,000 trees. The scale bar indicates the estimated number of substitutions per 1,000 nucleotides.