Clinical epidemiology of newly discovered respiratory viruses

Abstract

Background: Lower respiratory tract infections (LRTI) are a leading cause of morbidity and mortality in young children. A number of new viruses associated with LRTI in young children have recently been discovered. These include Human Bocavirus (HBoV), Human Polyomavirus strains WU (WUPyV) and KI (KIPyV) and Human Coronavirus strains NL63 (HCoV-NL63) and HKU-1 (HCoV-HKU-1). There is, however, limited data on the epidemiology of these newly discovered respiratory viruses in industrializing country settings, including South Africa. Objective: To determine the clinical epidemiology of HBoV, HCoV-NL63, HCoVHKU1, HCoV-OC43, HCoV strain 229E (HCoV- 229E), WUPyV, KIPyV and human rhinovirus (HRV) in young children. Methods: Nasopharyngeal aspirates where taken from children who were hospitalized at Chris Hani Baragwanath Hospital between February 2000 and January 2002 with severe LRTI. These children had been enrolled in a double-blind, randomized, placebo-controlled trial of a 9-valent pneumococcal conjugate vaccine (PCV). Nucleic acid extraction was undertaken from archived nasopharyngeal aspirate samples and the respiratory viruses identified using real time duplex PCR. The study was limited to examining samples from HIV uninfected children with LRTI who were less than 24 months of age. Results: Overall, samples were available for 895 of 1565 nasopharyngeal aspirates, from children hospitalized with LRTI, collected from February 2000 to January 2002. A comparison between those LRTI episodes for which samples were unavailable compared to those for which samples were available indicated that children in whom samples were unavailable were younger than children with available samples (9.9±6.4 vs. 11.8±6.5 months; p<0.0001). In addition there was a higher frequency of wheezing episodes in children for whom samples were unavailable (60.4 vs. 54.6%; p=0.022). The overall prevalence of the viruses in children with any LRTI were 33.2% for HRV, 21.2% for HBoV, 16.1% for WUPyV, 10.1% for HCoV-OC43, 7.0% for KIPyV, 3.2% for HCoVNL63, 2.6% for HCoV-HKU-1, and 0.6% for HCoV-229E. There was a higher probability of detecting a selected virus in LRTI episodes among PCV-compared to placebo-recipients for HBoV (24.2% vs. 18.2%, respectively; p=0.028) and HRV (36.7% vs. 29.5%, respectively; p=0.023). Conversely, viruses identified more frequently in LRTI episodes among children who received placebo compared to PCV-recipients included WUPyV (20.2% vs. 12.1%, respectively; p=0.001), KIPyV (10% vs. 4.2%, respectively; p=0.001), HCoV-OC43 (14.1% vs. 6.2%, respectively; p≤0.0001) and HCoV-HKU1 (4.5% vs. 0.1%, respectively; p≤0.0001). Overall, the prevalence of the studied-viruses in the subgroup of children categorized as having bronchiolitis was 33.8% for HRV, 33.4% for WUPyV, 22.3% for HBoV, 11.1% for HCoVOC43, 5.3% for KIPyV, 2.3% for HCoV-NL63, 1.9% for HCoV-HKU1 and 0.4% for HCoV-229E. Viruses more commonly identified in placebocompared to PCV-recipients among children hospitalized with bronchiolitis included WUPyV (20.0% vs. 12.3%, respectively; p=0.029), HCoV-OC43 (15.9% vs. 7.2%, respectively; p=0.004) and HCoV-HKU1 (3.6% vs. 0.5%, respectively; p=0.015). The prevalence of the newly studied viruses in the subgroup of children categorized as having clinical pneumonia was 30.8% for HRV, 20.3% for HBoV, 16.4% for WUPyV, 9.1% for HCoVOC43, 8.6% for KIPyV, 4.1% for HCoV-NL63, 3.2% for HCoV-HKU1 and 0.6% for HCoV-229E. Viruses identified more frequently among placebo- compared to PCV-recipients, in those with clinical pneumonia, included WUPyV (20.4% vs. 11.9%, respectively; p=0.013),HCoV-HKU1 (5.3% vs. 0.9%, respectively; p=0.008). Conversely, HCoV-OC43 was identified more frequently in children with clinical pneumonia among PCV- (5.0%) compared to placebo-recipients (2.7%, p=0.004). There were seasonal peaks, during autumnwinter months (April to June), in the detection of HRV, WUPyV, HCoV-OC43, HCov-NL63 and HCoV-HKU1, whereas KIPyV, HBoV and HCoV- 229E were identified perennially. Conclusion: Prevalence of respiratory viruses is high in industrializing countries and the presence of these viruses is frequently associated with co-infections of more than one etiological agent. In industrializing countries such as in South Africa, the recently identified respiratory viruses play a role in development of pneumonia. KIPyV (12.7% vs. 4.1%, respectively; p=0.001),