Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

Viral respiratory tract infections in lung transplant recipients may be severe. During three consecutive winter-spring seasons, 49 symptomatic lung transplant recipients with suspected respiratory viral infection, and 26 asymptomatic patients were investigated for presence of respiratory viruses either in 56 nasopharyngeal aspirate or 72 bronchoalveolar lavage samples taken at different times after transplantation. On the whole, 1 asymptomatic (3.4%) and 28 symptomatic (57.1%) patients were positive for human metapneumovirus (hMPV, 4 patients), influenza virus A (3 patients), and B (2 patients), respiratory syncytial virus (2 patients), human coronavirus (2 patients), human parainfluenza virus (2 patients), rhinovirus (5 patients), while 4 patients were coinfected by 2 respiratory viruses, and 5 were infected sequentially by 2 or more respiratory viruses. In bronchoalveolar lavage samples, hMPV predominated by far over the other viruses, being responsible for 60% of positive specimens, whereas other viruses were present in nasopharyngeal aspirates at a comparable rate. RT-PCR (detecting 43 positive samples/128 examined) was largely superior to monoclonal antibodies (detecting 17 positive samples only). In addition, HCMV was detected in association with a respiratory virus in 4/18 HCMV-positive patients, and was found at a high concentration (>10(5) DNA copies/ml) in 3/16 (18.7%) patients with HCMV-positive bronchoalveolar lavage samples and pneumonia. Coinfections and sequential infections by HCMV and respiratory viruses were significantly more frequent in patients with acute rejection and steroid treatment. In conclusion: (i) about 50% of respiratory tract infections of lung transplant recipients were associated with one or more respiratory viruses; (ii) hMPV largely predominates in bronchoalveolar lavage of symptomatic lung transplant recipients, thus suggesting a causative role in lower respiratory tract infections; (iii) RT-PCR appears to be the method of choice for detection of respiratory viruses in lung transplant recipients, (iv) a high HCMV load in bronchoalveolar lavage is a risk factor for viral pneumonia, suggesting some measure of intervention for the control of viral infection.     

Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy

The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0-12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV-RNA and hBoV-DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified.     

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.     

南京地区儿童人偏肺病毒感染的流行病学及临床特征分析

目的了解南京地区儿童人偏肺病毒（hMPV）感染的流行病学特点及临床特征。方法收集2009年8月至2010年7月南京医科大学附属南京儿童医院住院及门诊呼吸道感染患儿的鼻咽抽吸物（NPA）及咽拭子（NPS）共642例,采用逆转录聚合酶链反应法（RT—PCR）检测hMPVM基因,将阳性PCR扩增产物进行测序、同源性和进化分析。结果642例标本中共检出hMPV阳性扩增产物35份,检出率为5．5％。系统进化分析显示南京地区hMPVB1型占51．4％,A2b型占31．4％。hMPV的发病高峰在4月份。其致呼吸道感染以1岁以内多见（71．4％）。35例hMPV感染患儿中有15例（42．8％）存在混合感染,其中与HRV的混合感染检出率最高。临床诊断以肺炎（17例,48．6％）最为常见。结论人偏肺病毒是南京地区儿童急性呼吸道感染的重要病原之一,该年度其优势流行型别为B1型,南京地区A、B两型hMPV感染患儿临床特征无明显差异。     

人偏肺病毒感染住院儿童的临床特征及病毒基因特性分析

目的 了解急性呼吸道感染住院儿童中人偏肺病毒(hMPV)的感染情况、临床特征及人偏肺病毒基因特性.方法 对2006年2月至5月、2008年3月至4月及2008年9月至2009年2月收集的天津市儿童医院急性呼吸道感染住院儿童的310份鼻咽吸取物标本进行巢式PCR检测hMPV N基因片段,并对其中17株N基因片段进行序列测定,分析序列特征并绘制种系发生树.收集所有阳性患者的临床资料.同时采用多重PCR对N基因阳性标本进行其他常见呼吸道病毒的检测.结果 310份标本中共检出20份(6.5%)hMPV.hMPV阳性患儿的年龄中位数为15.0个月(16天～9岁),其中≤2岁患儿占90.0%(18/20).男性占60.0%(12/20).17株N基因种系发生树分析显示,11株为A2b亚型.20例hMPV阳性患儿的临床诊断均为支气管肺炎,占所有采集的肺炎患儿标本的7.1%(20/282),其临床症状以咳嗽、喘息、呼吸急促、发烧等常见.35%(7/20)需要重症监护,15%(3/20)需要吸氧治疗.平均住院时间为(11.9±4.8)d.A、B型间临床特征未见明显差别.hMPV无明显流行高峰.2例hMPV阳性患儿分别与腺病毒和鼻病毒混合感染.结论 hMPV可引起婴幼儿肺炎等严重疾病.天津地区流行的hMPV以A2b为优势流行型.     

Contribution of common and recently described respiratory viruses to annual hospitalizations in children in South Africa

The contribution of viruses to lower respiratory tract disease in sub-Saharan Africa where human immunodeficiency virus may exacerbate respiratory infections is not well defined. No data exist on some of these viruses for Southern Africa. Comprehensive molecular screening may define the role of these viruses as single and co-infections in a population with a high HIV-AIDS burden. To address this, children less than 5 years of age with respiratory infections from 3 public sector hospitals, Pretoria South Africa were screened for 14 respiratory viruses, by PCR over 2 years. Healthy control children from the same region were included. Rhinovirus was identified in 33% of patients, RSV (30.1%), PIV-3 (7.8%), hBoV (6.1%), adenovirus (5.7%), hMPV (4.8%), influenza A (3.4%), coronavirus NL63 (2.1%), and OC43 (1.8%). PIV-1, PIV-2, CoV-229E, -HKU1, and influenza B occurred in <1.5% of patients. Most cases with adenovirus, influenza A, hMPV, hBoV, coronaviruses, and WU virus occurred as co-infections while RSV, PIV-3, and rhinovirus were identified most frequently as the only respiratory pathogen. Rhinovirus but not RSV or PIV-3 was also frequently identified in healthy controls. A higher HIV sero-prevalence was noticed in patients with co-infections although co-infections were not associated with more severe disease. RSV, hPMV, PIV-3, and influenza viruses had defined seasons while rhinovirus, adenovirus, and coronavirus infections occurred year round in this temporal region of sub-Saharan Africa.     

Epidemiological and clinical features of hMPV, RSV and RVs infections in young children.

BACKGROUND: Human metapneumovirus (hMPV) has recently been isolated from children with acute respiratory tract infections (RTIs). The epidemiological and clinical characteristics of hMPV infection need further investigation. OBJECTIVES: The purpose of this study was to compare the clinical features of hMPV, respiratory syncytial virus (RSV) and rhinoviruses (RV) infections in children less than 3 years of age presenting to an emergency department with acute respiratory illness. STUDY DESIGN: From December 2002 to April 2004, all children under age three (n=931) admitted for acute respiratory illness to Dijon Hospital, France, were investigated for respiratory viruses in nasal washes. RESULTS: hMPV was detected in 6% of children (in 10.1% (n=38) the first winter and in 3.3% (n=17) the second winter); RSV was detected in 28.5% of the children, while rhinoviruses were found in 18.3%. Five hMPV-infected children had evidence of dual infection, two with RSV and three others with RV. The median age of the patients with hMPV infection was 6 months, and the main clinical symptoms were rhinorrhea (74.5%) and cough (67%). A lower tract disease occurred in 66% of hMPV-positive patients. Gene sequencing of hMPV isolates revealed co-circulation of the two major groups of hMPV during the study period; no difference in pathogenicity was found. There was no difference in the prevalence of bronchiolitis where hMPV, RSV or rhinoviruses were present. Asthma was found more often in hospitalized children with hMPV and rhinoviruses than among those with RSV (p<0.001). CONCLUSIONS: These results provide further evidence of the importance of hMPV as a pathogen associated with respiratory tract infection in children.     

Epidemiological and clinical study of viral respiratory tract infections in children from Italy

Impact of recently discovered viruses on epidemiology of acute respiratory tract infections (ARTI) is still unclear. We studied the impact of recently discovered human metapneumovirus (hMPV), human bocavirus (HBoV), and new coronaviruses (HCoV‐NL63 and HKU1) on the global epidemiology of ARTI. From October 2006 to April 2007, 237 pediatric patients affected by ARTI were enrolled in our study. Specimens were tested for respiratory viruses by polymerase chain reaction. One hundred twenty‐four out of 237 samples (52.3%) were positive for one or more viruses. Picornaviruses were the most prevalent viruses (n = 61, 43.6%), followed by respiratory syncytial virus (n = 34, 24.3%) and Adenovirus (n = 25, 17.9%); hMPV (n = 9, 6.4%) was the fourth most common virus detected. HBoV and HCoV showed a low prevalence (respectively 2.9% and 2.1%). RSV was the prevalent agent of LRTI (38%). Viruses were identified in more than 50% of the studied ARTI, providing useful information on clinical features and epidemiology of specific agents affecting children in cold months. Although routine surveillance of respiratory viruses does not seem cost‐effective, continuous monitoring of ARTI etiology could be a useful tool for planning resources for the development of new vaccines and antiviral agents. J. Med. Virol. 81:750–756, 2009 © 2009 Wiley‐Liss, Inc.     

WU polyomavirus infection among children in South China

This study aimed at investigating the prevalence and clinical characteristics of children with respiratory infection by WU polyomavirus (WUPyV) in Southern China. Nasopharyngeal aspirate samples were collected from 771 children with acute respiratory tract infection admitted to hospital and 82 samples from healthy subjects for routine examination at the outpatient service at the Second Affiliated Hospital of Shantou University, Medical College from July 2008 to June 2009. WUPyV was detected by the polymerase chain reaction (PCR) and DNA sequencing. All WUPyV‐positive specimens were characterized further for nine viruses causing common respiratory infections, including in?uenza A and B, respiratory syncytial virus (RSV), parainfluenza virus (PIV) 1 and 3, human metapneumovirus, human bocavirus, adenovirus, and rhinovirus by PCR or real time (RT)‐PCR. Fifteen out of 771 specimens from patients with acute respiratory tract infection, but none from healthy subjects, were positive for WUPyV and the positivity rate was 2%. Patients with WUPyV infection were between 2 and 48 months of age, and nine of the patients were male while six female. Four out of 15 patients were co‐infected with RSV, one with adenovirus or rhinovirus, respectively. Patients with WUPyV infection displayed predominantly cough, moderate fever, and wheezing, and were diagnosed with pneumonia (n = 8), bronchiolitis (n = 4), upper respiratory tract infections (n = 2) and bronchitis (n = 1). One patient developed encephalitis. Therefore, WUPyV infection can cause acute respiratory tract infection with atypical symptoms, including severe complications, in children. J. Med. Virol. 83:1440–1445, 2011. © 2011 Wiley‐Liss, Inc.     

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.     

Human metapneumovirus associated with respiratory tract infections in a 3-year study of nasal swabs from infants in Italy

The newly described human metapneumovirus (hMPV) is reported here to be more commonly associated with lower respiratory tract disease. The present study examined nasal swab specimens from 90 infants with acute respiratory tract infections in Pisa, Italy, over a period of three respiratory virus seasons. The incidence of infection varied in each of the 3 years, with the rates of positivity for hMPV being 7% in 2001 but 37 and 43% in 2000 and 2002, respectively. hMPV was noted to occur seasonally in a pattern typical of the frequency of occurrence of respiratory syncytial virus. More than one-half (14 of 23) of the infants infected with hMPV had bronchopneumonia. One-third (9 of 23) of the hMPV-infected patients were also infected with another respiratory virus, a relationship that has not previously been reported. Mixed infections did not account for a higher percentage of cases of bronchopneumonia than hMPV infection alone did. Furthermore, 7 of 17 infants whose plasma was also tested for hMPV RNA were demonstrated to have virus in both nasal swab and blood specimens. The study indicates that hMPV is seen as commonly as other respiratory viruses, may be associated with severe respiratory disease in infants, can establish mixed infections with other respiratory viruses, and has a seasonal occurrence.     

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.     

Respiratory syncytial virus and human rhinoviruses are the major causes of severe lower respiratory tract infections in Kuwait

Respiratory infections are very common in Kuwait, yet little is known about the cause of severe lower respiratory tract infections. This study was designed to investigate the viral cause of lower respiratory tract infections using sensitive molecular methods. PCR was applied to investigate 10 respiratory viruses in respiratory samples from 1,014 patients aged between 3 days to 76 years with acute lower respiratory tract infections. Of the 1,014 patients with lower respiratory tract infections, 288 (28.4%) had a viral infection. One hundred fifty‐five (53.8%) presented with bronchiolitis, 100 (43.7%) with pneumonia, and 33 (11.5%) with croup. One hundred six (36.8%) and 99 (34.4%) patients had evidence of respiratory syncytial virus and human rhinoviruses infections, respectively. Adenoviruses were detected in 44 (15.2%) patients, while influenza A virus in 21 (7.3%) patients. The majority of respiratory syncytial virus infections (84%) were among patients aged <1 year. Similarly, of the 99 patients infected by human rhinoviruses, 50 (50.5%) were also among this age group. In contrast, most of influenza A virus infections, 12 of 21 (57.1%), were among patients aged over 16 years. Parainfluenza virus‐2 and human coronaviruses were not detected in any of the patients' samples. Over the 3‐year period, most of the hospitalized patients were seen during the autumn and winter months from October through March. These data show that respiratory syncytial virus and human rhinoviruses may be the major causes of lower respiratory tract infections in children admitted to hospital in Kuwait. J. Med. Virol. 82:1462–1467, 2010. © 2010 Wiley‐Liss, Inc.     

The highest prevalence of human metapneumovirus in Ahwaz children accompanied by acute respiratory infections

PURPOSE: The newly described human metapneumovirus (hMPV) has been recently discovered as an etiological agent of acute respiratory infections (ARTI) in infants and children. The aim of this study was to determine the prevalence of hMPV and its potential role as causative agent of ARTI in Ahwaz children. METHODS: In the present study, we examined 124 nasal swabs from infants affected by ARTI for the presence of hMPV by RT-PCR technique. RESULTS: Sixty-eight out of 124 (54.4%) cases were positive for hMPV which is the highest incidence of hMPV ever reported in the world, 94.1% of positive cases belonged to genotype A; whereas no B genotype was detected. Our positive hMPV children were affected by upper (URTI) as well as lower respiratory tract infection (LRTI); however, LARTIs had higher prevalence. CONCLUSIONS: We suggest a probable role of F protein alteration as the causative agent for the highest prevalence of hMPV infection among Ahvaz children.