Human metapneumovirus infection in hospital referred South African children

Human metapneumovirus (hMPV) was first described in Dutch children with acute respiratory symptoms. A prospective analysis of the epidemiology, clinical manifestation, and seroprevalence of hMPV and other respiratory viruses in South African children referred to hospital for upper or lower respiratory tract infection were carried out during a single winter season, by using RT-PCR, viral culture, and enzyme-linked immunosorbent assays. In nasopharyngeal aspirates from 137 children, hMPV was detected by RT-PCR in 8 (5.8%) children (2-43 months of age) as a sole viral pathogen, respiratory syncytial virus (RSV) in 21 (15%), influenza A virus in 18 (13%) and influenza B virus in 20 (15%). Pneumonia was diagnosed in seven children and upper respiratory tract infection in one of the hMPV-infected children. One hMPV-infected child was admitted to the intensive care unit in need of mechanical ventilation and one child was infected with human immunodeficiency virus (HIV). No statistically significant differences were found between hMPV, RSV, and influenza virus infected groups with regard to clinical signs and symptoms and chest radiograph findings. The seropositive rate of hMPV specific IgG antibodies was 92% in children aged 24-36 months, the oldest seronegative child in our study was 7 years and 6 months of age. In conclusion, hMPV contributes to upper and lower respiratory tract morbidity in South African children.     

Evidence of human metapneumovirus in children in Argentina

Human metapneumovirus (hMPV) is a virus, which was first associated with acute lower respiratory infection in children but is detected currently in all age groups. Clinical symptoms are similar to those described for respiratory syncytial virus (RSV) infections, ranging from mild respiratory illness to severe bronchiolitis and pneumonia in children. To date, no cases of hMPV have been reported in Argentina. In this study, 440 respiratory samples obtained during the period 1998-2002 from children under 5 years old with acute respiratory infection were evaluated. Routine detection for RSV, adenovirus, influenza, and parainfluenza was undertaken by immunofluorescent assay. Of the samples negative for these viruses, only 100 were available. All these samples were tested for hMPV by RT-PCR using primers for the L gene. Eleven out of 100 (11%) respiratory samples were positive for hMPV by RT-PCR. A higher frequency of detection was observed in spring. hMPV was detected in all the years studied, except in 2001. Ten out of 11 children positive for hMPV were hospitalized. Median age was 5 months. Of seven patients, five (71%) required oxygen supplementation. The most frequent diagnosis was bronchiolitis (86%), sometimes accompanied by conjunctivitis and otitis media. The present study showed that hMPV was associated with acute lower respiratory infections in children in Buenos Aires, Argentina. This evidence strongly suggests that hMPV is a common pathogen with a wide geographical distribution, which should be included in the routine diagnosis of respiratory viruses in young children.     

Prospective study of human metapneumovirus infection in children less than 3 years of age

Most lower respiratory tract infections (LRTIs) in children under the age of 3 years are due to respiratory syncytial virus (RSV). Epidemiological, host, and viral factors eventually account for the severity of LRTIs, but they do not completely explain it. Human metapneumovirus (hMPV) was recently identified in children with LRTIs. In a population-based prospective multicenter study (the PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal secretions from children younger than 3 years of age with LRTIs for RSV A and B, influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the children requiring intensive care (n = 85), 18% had hMPV infections, and 60% of these children were infected with hMPV in combination with RSV. We did not detect hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (n = 120) from children not requiring intensive care support. hMPV was detected in <1% of virus-negative samples from patients without intensive care support (n = 620). Our data support the hypothesis that coinfections with RSV and hMPV are more severe than infections with either RSV or hMPV alone, at least in children younger than 3 years of age.     

Human metapneumovirus

The human metapneumovirus (hMPV) is a new Pneumovirinae related to the avian metapneumovirus type C. hMPV genome differs from human respiratory syncytial virus (RSV) genome by the gene order and the lack of nonstructural genes. Two genetic sub-groups and four sub-types of hMPV are identified. hMPV infections evolve as regular winter outbreaks which have roughly the same size and overlaping RSV epidemics. Among hospitalized children in Caen, hMPV is detected in 9.7% of the cases after RSV (37%), rhinovirus (18%), influenza virus (14.5%), adenovirus (9%), and parainfluenza virus (5%). Most of hMPV infections are observed in children suffering from bronchiolitis, but the localization to lower respiratory tract and the severity of the disease are less frequent in comparison with RSV infections. hMPV is very difficult to isolate using cell culture. Up to now, the only way for hMPV diagnosis was the TS-CRP assays. But the recent apparition of direct antigenic tests allows us to get a fair, rapid, and economic diagnostic tool.     

Human Coronavirus-NL63 infections in Korean children, 2004-2006.

BACKGROUND: Human coronavirus-NL63 (HCoV-NL63) has been isolated from children with respiratory tract infections and its prevalence in Korea has not been reported. OBJECTIVES: This study was designed to investigate the presence and the clinical features of HCoV-NL63 during two winter seasons. STUDY DESIGN: During April 2004-April 2006, nasopharyngeal specimens from children hospitalized with acute respiratory disease were tested for common respiratory viruses, including RSV, influenza A, influenza B, parainfluenza viruses, and adenovirus by IFA. hMPV infection was excluded by nested RT-PCR using primers for F-gene. To detect HCoV-NL63, previously described nested PCR assays for 1a and 1b were used. PCR products of the 1a gene for HCoV-NL63 were sequenced. RESULTS: Out of 872 nasopharyngeal aspirate from children aged under 16 years, 14 (1.7%) were positive for HCoV-NL63. Most of the patients had croup (64.2%) or bronchiolitis (21.4%). The peak prevalence was found in November (28.5%). Most were collected between November 2004 and February 2005. CONCLUSIONS: HCoV-NL63 may be one of the causative agents of acute respiratory tract infection, especially croup.     

Viral respiratory infections in hospitalized and community control children in Alaska

Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty‐two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two‐thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain. J. Med. Virol. 82:1282–1290, 2010. © 2010 Wiley‐Liss, Inc.     

Contribution of rhinoviruses to respiratory viral infections in childhood: a prospective study in a mainly hospitalized infant population

A prospective study was carried out to investigate the contribution of rhinoviruses to respiratory viral infections in children and to investigate the influence of age, passive smoking, and educational level of the head of the family on the clinical course of viral respiratory disease. Nasopharyngeal aspirates from 519 infants (90.8% inpatients, 9.2% outpatients) were screened for the presence of rhinoviruses, respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus types 1, 2, 3, influenza virus types A and B, and enteroviruses by tissue culture isolation procedure, enzyme-linked immunosorbent assay, and/or indirect immunofluorescence method. The total detection rate was 42.4%. The rate decreased with increasing age. Higher detection rates were observed in specimens from children suffering from a more severe respiratory disease, and the highest rate of virus-positive specimens was found in those aged 0-6 months. Second to RSV (23.1%), rhinoviruses were the most frequently recovered pathogens found in 11.8% of children with acute respiratory tract infections (RTI). In the age group 0-6 months the majority of severe respiratory illnesses was due to RSV. In infants aged 6 months to 1 year a decrease in the number of severe illnesses caused by RSV and an increase in the number of children suffering from a more severe RTI caused by rhinoviruses was found. With the possible exception of one group of children infected with rhinoviruses, a negative effect of passive smoking on the incidence and severity of viral RTI could not be established. A beneficial effect of breast feeding on the severity of viral RTI could not be definitely demonstrated.     

Human Metapneumovirus as a causative agent of acute bronchiolitis in infants.

BACKGROUND: Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family. OBJECTIVES: Since most bronchiolitis studies fail to detect any viral pathogen in part of the samples, we sought for the presence of hMPV in a well characterized bronchiolitis cohort. STUDY DESIGN: Nasal washes were obtained from 56 children admitted to the hospital for acute bronchiolitis. RNA extraction and subsequent RT-PCR were used to detect hMPV, and correlated the presence of the virus with clinical characteristics of the disease. RESULTS AND CONCLUSIONS: PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. hMPV was identified either as a unique viral pathogen or co-existed with RSV, with whom they shared a similar seasonal distribution. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. These findings suggest that hMPV is a common and important causative agent in infants with bronchiolitis, with clinical characteristics similar to that of RSV.     

Mixed respiratory virus infections

Mixed respiratory viral infections are double negative common and evidence that they are associated with severe disease is supported by some groups. This controversial observation can be explained by the lack of sensitivity of the assessed methods used for viral identification and by the small number of patients included in the randomized cohorts studied. Most studies showed that respiratory syncytial virus (RSV) is identified in about 70% of hospitalized infants with bronchiolitis during seasonal winter epidemics, followed by human metapneumovirus (hMPV, about 3-19%) or rhinoviruses (about 20%). Other respiratory viruses have also been reported, indicating significant causes of bronchiolitis and hospitalization during seasonal epidemics. The presence of more than one pathogen, and moreover, the association of RSV with rhinoviruses and also RSV with hMPV, may influence the natural course of bronchiolitis. A better understanding of these various interactions would help future decision-making, such as the extent to which searches for co-pathogens should be conducted in severe bronchiolitis patients already infected by RSV.     

Detection of human coronavirus NL63, human metapneumovirus and respiratory syncytial virus in children with respiratory tract infections in south-west Sweden

Two recently detected viruses, human metapneumovirus (hMPV) and coronavirus NL63 (HCoV-NL63), have been associated with acute respiratory tract infections, particularly in young children. This study investigated the frequency of hMPV and HCoV-NL63 infections in Swedish children by screening 221 nasopharyngeal aspirates, collected between November 2003 and May 2005, from 212 children attending the paediatric department of a county hospital in Sweden or submitted from local general practitioners. The samples were originally submitted to be tested for respiratory syncytial virus (RSV), and were examined retrospectively for hMPV and HCoV-NL63 by RT-PCR. Of the 212 patients, 101 were positive for RSV (48%), 22 (10%) were positive for hMPV, and 12 (6%) were positive for HCoV-NL63. The frequency of HCoV-NL63 infection increased from 1% in 2003-2004 to 10% in 2004-2005. Sequence analysis of parts of the coronavirus genomes showed considerable similarity to the HCoV-NL63 prototype sequence. The study demonstrated that HCoV-NL63 and hMPV occur in south-west Sweden with essentially the same frequency, seasonal distribution and clinical characteristics as have been reported in other countries.     

Human metapneumovirus in patients with respiratory tract infection in Kuwait

Human metapneumovirus (hMPV) has been recognized as an important cause of respiratory tract infections in all age groups and in all geographical area. The role of hMPV in causing respiratory tract infections in Kuwait was not yet investigated. The aim of this study was to determine the prevalence of hMPV infection in Kuwait among patients with respiratory tract infection with respect to other respiratory viruses. During January–December 2009, 460 respiratory samples from 388 patients with respiratory tract infection were collected from different hospitals. They were tested for hMPV RNA by real‐time PCR, and for other respiratory viruses by conventional PCR. Out of 388 patients, 110 (28%) were positive for viral respiratory infections; 21 (5.4%) were positive for hMPV, 29 (7.5%) were positive for rhinovirus, 13 (4%) were positive for respiratory syncytial virus, and 10 (3%) were positive for adenovirus. Most (n = 19, 90.5%) of hMPV‐positive patients were admitted to the intensive care unit, 76% of them were of age 2 years and below, and 24% of age 59 years and above. All hMPV‐positive elderly patients had pneumonia while 50% of hMPV‐positive infants had bronchopneumonia. Children with hMPV/rhinovirus co‐infection (n = 3, 1%) had recurrent chest infection and frequent intensive care unit admission. The hMPV infection was mostly detected between December and May, and genotype B was more prevalent than genotype A. This is the first study demonstrating the prevalence of hMPV infection in Kuwait, and suggests that hMPV infection is prevalent in infants and elderly patients with lower respiratory tract infection. J. Med. Virol. 83:1811–1817, 2011. © 2011 Wiley‐Liss, Inc.     

Characterization of human metapneumovirus infections in Israel

Respiratory tract infections are a leading cause of morbidity and mortality worldwide. Even with the advancement of diagnostic tools, the causative agent of 20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly identified human respiratory virus, human metapneumovirus (hMPV), was discovered in young children in The Netherlands. To study the prevalence of hMPV infections in Israeli children, respiratory specimens from 388 hospitalized children less than 5 years of age were evaluated for the presence of hMPV RNA, which was present in 42 (10.8%) of these samples. All hMPV-positive samples were negative for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B, adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV activity was between the months February and April. Sequence analysis of 20 positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have circulated in central Israel during the study period. Moreover, three of the four known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples. Seroprevalence of hMPV in 204 patients from the central part of Israel revealed that 100% of the children are hMPV seropositive by the age of 5 years old. We conclude that hMPV is a common respiratory pathogen in Israel, while mixed infections of hMPV with RSV or Flu in hospitalized children are apparently rare.     

Seasonality and clinical features of human metapneumovirus infection in children in Northern Alberta

Human metapneumovirus (hMPV) causes respiratory tract infections in all age groups. The characteristics of pediatric hMPV infection in Northern Alberta have not been studied. The objectives of this study were to determine the seasonality of pediatric hMPV infections over a 13-month period, the genetic relationship of hMPV isolates to hMPV detected in other parts of Canada, and the burden of illness and possible risk factors for pediatric hMPV hospitalization. Detection of hMPV by polymerase chain reaction was performed on nasopharyngeal specimens collected from outpatients and inpatients at the Stollery Children's Hospital in Edmonton, Alberta, November 12, 2002-December 31, 2003. Forty-two of 1,079 specimens were positive for hMPV (3.9%) from 41 patients (14 outpatients and 27 inpatients), with a peak incidence during January-April, but isolates were detected 10 months of the year. Co-infection was not detected in 39 specimens from which RSV had been detected. Two hMPV genetic clusters were detected, and the isolates were homologous to those of previous Canadian isolates. Four of the 14 outpatients had reactive airways disease. Possible risk factors in the 27 inpatients included prematurity (n = 8), congenital heart disease (n = 6), gastroesophageal reflux disease or aspiration (n = 6), global developmental delay (n = 5), and multiple congenital anomalies (n = 4). Risk factors for hospitalization appear to be similar to risk factors for respiratory syncytial virus hospitalization.     

Prospective study of Human Bocavirus (HBoV) infection in a pediatric university hospital in Germany 2005/2006.

BACKGROUND: Human Bocavirus (HBoV), a new species of the genus parvovirus newly detected in 2005, seems to be a worldwide distributed pathogen among children with respiratory tract infection (prevalence 2%-18%). Recently published retrospective studies and one prospective birth cohort study suggest that HBoV-primary infection occurs in infants. METHODS: Prospective single center study over one winter season (November 2005-May 2006) with hospitalized children without age restriction using PCR-based diagnostic methods. RESULTS: HBoV DNA was detected in 11 (2.8%) of 389 nasopharyngeal aspirates from symptomatic hospitalized children (median age 9.0 months; range: 3-17 months). RSV, HMPV, HCoV, and Influenza B were detected in 13.9% (n=54), 5.1% (n=20), 2.6% (n=10), and 1.8% (n=7), respectively. There was no influenza A DNA detected in any of the specimens. The clinical diagnoses were acute wheezing (bronchitis) in four patients, radiologically confirmed pneumonia in six patients (55%) and croup syndrome in one patient. In five to six patients with pneumonia, HBoV was the only pathogen detected. While no patient had to be mechanically ventilated, 73% needed oxygen supplementation. In four (36.4%) patients at least one other viral pathogen was found (plus RSV n=3; 27.3%; Norovirus n=1; 9.1%). CONCLUSION: HBoV causes severe respiratory tract infections in infants and young children. Its role as a copathogen and many other open questions has to be defined in further prospective studies.