Human Metapneumovirus And Different Subtypes Of Respiratory Syncytial Virus Infections In Hospitalized Children With Pneumonia

PrefaceRespiratory tract infections are a leading cause of morbidity and mortality worldwide. Acute respiratory tract infections are the most common illness regardless of age or gender. Although the clinical manifestations of respiratory tract disease are easily recognized, the etiological agent responsible for disease is often not identified. For community-acquired pneumonia a microbiological diagnosis can be made in <50% of cases. This suggests that previously unknown pathogens may be circulating and may be responsible for a substantial proportion of respiratory tract disease.In the pediatric population, respiratory syncytial virus (RSV), parainfluenza viruses, and influenza virus are known as the major causes of respiratory tract infections. In 2001, von den Hoogen et al reported the discovery of a novel virus from children with respiratory tract illness in the Netherlands. Based on sequence data, this virus was shown to be an single-stranded negative sense RNA virus belonging to the family Paramyxoviridae, subfamily Pneumovirinae and genus Metapneumovirus, named as human metapneumovirus (HMPV). Serological studies revealed that HMPV is not an emerging virus, but had been circulating for at least 50 years. Its clinical manifestations resemble those of RSV, and thus it is difficult to distinguish one virus from another clinically.Evidence from many studies has demonstrated that HMPV is responsible for a substantial proportion of lower respiratory tract infections in infants and young children and is second only to RSV as a cause of pneumonia in early childhood. Additionally, there is no effective drug or vaccine treatment. HMPV can be detected in clinical specimens using reverse transcription-polymerase chain reaction (RT-PCR) as a general method because of its higher specificity and sensitivity relative to virus isolation using cultured cells.RSV, a pneumovirus , is the most closely related human pathogen to HMPV. RSV is the most important cause of viral respiratory tract infections in infants. About 70% of bronchiolitis are associated with RSV infection. Based on antigenic and genetic variation there are two major subgroups of RSV, A and B. The attachment glycoprotein (G) is the most variable between the two groups, it has therefore been used for molecular epidemiology studies.So far, there are limited researches on HMPV in the worldwide, especially in the Northeast of our country. In this study, our objective was to elucidate clinical characteristics of HMPV and RSV in hospitalized children with pneumonia.Materials and MethodsA total of 53 hospitalized children with pneumonia from Shengjing Hospital affiliated to China Medical University were observed from Dec 2006 to Nov 2007. Among them, 28 patients were male, and 25 patients were female. All the patients were between 35 days and 2 years old, except for one child of 6 years old. Throat swabs were collected from all patients within 48 hours after admission. The samples were kept at 4℃and transported within 24h to the laboratory. RNA were extracted from the throat swabs and were tested for HMPV and RSV A,B by two-steps reverse transcription-polymerase chain reaction.Results1. HMPV was identified in 6(11.3%) of the 53 specimens tested, among which one patient co-infected RSV A. HMPV was detected mostly in April. The mean age of HMPV-infected children was 7.52 months. 3 (50%) of the HMPV-infected children had acute asthma exacerbations. 2. RSV was identified in 24(45.3%) of the 53 specimens tested, among which RSV genotype A and RSV genotype B, accounted for 37.5% and 62.5%, respectively. RSV had a peak from November to January. The mean age of RSV-infected children was 3.50 months. 6(25%) of RSV-infected children had acute asthma exacerbations.3. Clinical manifestations are similar among HMPV, RSV A and RSV B.DiscussionViral infections are considered the most important cause of respiratory tract illness in children. Only 58.3% of the respiratory infections could be related to the presence of known viruses. These observations suggest that previously unknown pathogen may be circulating. In 2001, van den Hoogen et al reported the discovery of a novel virus from children with respiratory tract illness in the Netherlands. Epidemiological studies indicate that, like RSV, HMPV is a significant human respiratory pathogen with worldwide distribution. HMPV can be detected in clinical specimens using reverse transcription-polymerase chain reaction (RT-PCR) as a general method because of its higher specificity and sensitivity relative to virus isolation using cultured cells.Variability of HMPV genes may effect the sensitivity of study due to limited available sequence information. We have performed RT-PCR targeted F-gene, which is known to have highly conserved sequence and allow the differentiation of all four sublineages in several studies. In our study, HMPV was detected in 6(11.3%) children, RSV was detected in 24(45.3%) children. Clinical symptoms in HMPV-positive patients mirrored those in RSV-positive patients, similar to results reported in other HMPV studies.In our study, HMPV circulates predominately in April, and the peak of activity follows the peak of RSV activity. The result was consistent with several previous studies. The seasonality of HMPV could be the cause of an underestimation of the real impact of this virus in several studies, because these studies stopped before the end of HMPV transmission in the community.In our study, the relatively high median age of HMPV-infected children was similar to that reported by other authors. The median age for RSV-infected children was lower. Further research is needed to explain this difference.In our study, 3 (50%) of the HMPV-infected children and 6(25%) of RSV-infected children had acute asthma exacerbations. Several studies have reported both of RSV and HMPV have been associated with acute asthma exacerbations. Investigation of the inflammatory mediators and cytokines induced by HMPV or RSV during infection should shed light on the mechanisms of HMPV or RSV-induced wheezing.In our study, one of the HMPV-positive children co-infected with RSV A. The symptoms of the patient were clinically severe. Because little patient information and epidemiology data are available, it is unclear whether dual infection resulted in greater severity of illness.Conclusion1. HMPV as well as RSV plays an important pathogenic role in hospitalized children with pneumonia.2. Clinical symptoms in HMPV-positive patients mirrored those in RSV-positive patients. Both of the viruses may induce asthma...