Date Published: January 17, 2017
Publisher: Public Library of Science
Author(s): Nina Moe, Sidsel Krokstad, Inger Heimdal Stenseng, Andreas Christensen, Lars Høsøien Skanke, Kari Ravndal Risnes, Svein Arne Nordbø, Henrik Døllner, Oliver Schildgen.
It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV).
We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.
Since the discovery of human metapneumovirus (HMPV) in 2001 , studies from all parts of the world have shown that HMPV causes respiratory tract infection (RTI) in children [2–7]. HMPV is usually detected in airway secretions from children with RTI by use of polymerase chain reaction (PCR) tests, and the virus seldom appears in healthy children . HMPV has been classified into the Pneumoviridae family. Two main genotypes (A and B) and at least four genetic subtypes (A1, A2, B1 and B2) exist [9–12]. Whether these genotypes cause similar or different infections is largely unclarified because some studies have shown quite similar manifestations [13–15], whereas others found that either genotypes A [16,17] or B  may cause more severe disease.
During nearly 9 years, we included 3,214 children out of 3,932 (81.7%) with acute RTI into our main study cohort (Fig 1). Among the 56.5% (1816/3214) of hospitalized children with LRTI, HMPV was detected in 9.4% (171/1816) and RSV in 47.3% (859/1816), while 0.6% (11/1816) had both HMPV and RSV (Fig 1). In total, 1,041 HMPV- and RSV-infected children were included in the present study (Fig 1). Their median age was 8.7 months (range 0.3–189.1 months) and the majority was younger than 5 years old (97.9%, 1019/1041). NPA were collected from 85.7% (892/1041) of these children within 24 hours after presentation, and within 48 hours in 96.0% (999/1041).
The present data from our large population-based study collected during a nearly 9-year-long period show that LRTI with HMPV clinically manifests itself independently of the co-detection of other viruses, and does not differ in relation to HMPV genotypes. Furthermore, clinical manifestations and final diagnoses in children with HMPV and RSV LRTI are quite similar. However, the clinical course varies in relation to age, and the age effect differed among single virus HMPV- and RSV-infected children. Lastly, our data confirm that hospitalized children born preterm and children with chronic diseases have an increased risk of developing severe LRTI among HMPV- and RSV-infected.