No evidence for an association between infections with WU and KI polyomaviruses and respiratory disease

BACKGROUND: WU virus (WUV) and KI polyomavirus (KIPyV) are newly discovered related human polyomaviruses detected in respiratory samples. To investigate their potential role in respiratory disease, we determined their frequencies of detection, clinical presentations and epidemiological characteristics among samples referred for diagnostic respiratory virus testing. METHODS: Anonymised samples and accompanying study subject information were obtained from the Edinburgh respiratory specimen archive. Samples were screened by nested PCR using two sets of primers conserved between WUV and KIPyV, as well for other respiratory viruses (respiratory syncytial virus [RSV], adenoviruses [AdV], influenza A/B and parainfluenza viruses 1-3, human bocavirus, B19). RESULTS AND CONCLUSIONS: WUV and KIPyV were detected in 10 and 14 samples, respectively from 983 specimens (from 9 to 10 different individuals from 612 study subjects). Infections occurred in two types of study subject; those who were young (<2 years) with lower respiratory tract infections (n=8), and almost invariably co-infected with other respiratory viruses (RSV, AdV), and a second, generally older group either without respiratory disease (n=6) or with mild upper respiratory tract infections (n=5) but who were generally clinically severely immunosuppressed from leukaemia or transplant therapy. Findings from either group do not support an aetiological link between infection with WUV or KIPyV and respiratory disease.     

Molecular epidemiology of KI and WU polyomaviruses in infants with acute respiratory disease and in adult hematopoietic stem cell transplant recipients

Polyomaviruses KI (KIPyV) and WU (WUPyV) were described recently in children with acute respiratory disease. The pathogenic potential of these human viruses has not been determined completely, but a correlation between immunosuppression and virus reactivation has been suggested. In the present study, the association between KI/WUPyV infection and immunosuppression was investigated using sequential nasopharyngeal aspirates from asymptomatic adult hematopoietic stem cell transplant recipients. In parallel, an investigation on the WU/KIPyV prevalence in children with acute respiratory disease was also carried out. Two of the 126 samples obtained from the 31 hematopoietic transplant recipients were positive for KIPyV (1 sample, 0.79%) and WUPyV (1 sample, 0.79%). Both samples were obtained 15 days after allogeneic transplantation and virus persistence was not observed in subsequent samples. In symptomatic children, 7 of the 486 nasopharyngeal aspirates were positive for WUPyV (1.4%) and 1 for KIPyV (0.2%). Single polyomavirus infection was detected in four patients, whereas the remaining patients were co‐infected with respiratory syncityal virus (three patients) or adenovirus (one patient). The results suggest that WU/KIPyVs have a limited circulation in Italy and a low pathogenic potential in young children. Brief and asymptomatic infection can occur in hematopoietic transplant recipients. J. Med. Virol. 82:153–156, 2010. © 2009 Wiley‐Liss, Inc.     

Age-related pattern of KI and WU polyomavirus infection

BACKGROUND: The role of two recently identified polyomaviruses, KI and WU, in the causation of respiratory disease has not been established. OBJECTIVES: To determine the prevalence of KI and WU viruses (KIV and WUV) in 371 respiratory samples and evaluate their contribution to respiratory disease. STUDY DESIGN: Specimens were screened for KIV and WUV using single, multiplex or real time PCR; co-infection with other respiratory viruses was evaluated. RESULTS: Of the 371 samples analysed, 10 (2.70%) were positive for KIV and 4 (1.08%) were positive for WUV yielding an overall case prevalence of KIV and WUV infection of 3.77%. KIV and WUV were identified in patients aged <15 years (11 patients) with upper or lower respiratory tract infection and >45 years (3 patients) with upper respiratory tract infection. Co-infections were found in 5 (50%) and 3 (75%) of the KIV and WUV positive samples, respectively. CONCLUSIONS: This study supports previous conclusions that KIV and WUV detection in the respiratory tract may be coincidental and reflect reactivation of latent or persistent infection with these viruses. The age distribution of KIV and WUV infection in this study mirrors that found for the other human polyomaviruses, BK and JC.     

上海地区儿童下呼吸道人类偏肺病毒感染的初步研究

目的 了解人类偏肺病毒（hMPV）在上海地区儿童下呼吸道感染中的致病情况。方法 采集2004年8月-2005年1月秋冬季节我院479例因社区获得性急性下呼吸道感染（CALRTIs）住院儿童的呼吸道分泌物标本，对直接免疫荧光法常规检测病毒阴性的259份标本用逆转录．多聚酶链反应法（RT-PCR）检测hMPVM基因。对PCR阳性产物随机挑选23份直接作核苷酸序列测定，用DNAStar软件对基因序列分析。结果 259份标本中hMPV检测阳性例数为59例（22．8％），占总例数的12．3％。冬季检测阳性率明显高于秋季（31．3％vs7．5％，P〈0．01）。5岁及以下儿童53例（89．8％），5岁以上儿童6例（10．2％）。23份hMPV阳性标本目标基因部分核苷酸序列与GenBank中公布的hMPVM基因同源性达82．8％～100％，部分氨基酸序列同源性为93．0％～100％，对核苷酸序列作基因进化树分析显示存在2种不同的基因型，以Bj1816组为代表的基因型14株，以Bj1887组为代表的基因型9株。结论hMPV是上海地区儿童CALRTIs的重要致病原，上海地区儿童感染的hMPV同时存在2种不同的基因型。     

WU polyomavirus in children with acute lower respiratory tract infections, China.

BACKGROUND: WU polyomavirus (WUPyV), a new member of the genus of Polyomavirus in the family Polyomaviridae, has been found and associated with respiratory tract infections recently. However, its clinical role and pathogenicity has not been known. OBJECTIVES: To confirm that WU polyomavirus has been found in Chinese children. STUDY DESIGN: WU polyomavirus was detected and identified using PCR methods. A total of 278 specimens of nasopharyngeal aspirate were collected, and then PCR products were sequenced directly. RESULTS: One of 278 nasopharyngeal aspirates was positive for WUPyV in one child, and the positive rate was 0.4%. The results showed that the sequences of genome, LTAg and VP2 gene was identical to the reference sequences of WU polyomavirus prototype strains. CONCLUSIONS: We confirmed that WU polyomavirus had been found and identified in the respiratory secretions in China.     

Newly identified respiratory viruses associated with acute lower respiratory tract infections in children in Lanzou,China, from 2006 to 2009

Nasopharyngeal aspirates were collected from 813 children <14 years old with acute lower respiratory tract infections in Lanzhou, China, from December 2006 to November 2009. PCR or RT-PCR was used to screen for the presence of 10 respiratory viruses. Viral agents were identified in 73.92% (601/813) of specimens, including RSV in 40.71%, hMPV in 6.15%, IFVA in 7.13%, IFVB in 0.98%, PIV1-3 in 7.87%, HCoV-HKU1 in 2.21%, HCoV-NL63 in 3.81%, HRV in 19.93%, AdV in 7.50% and HBoV in 11.56%. Two or more viruses were detected in 34.44% (280/813) of cases. The newly identified respiratory viruses, HBoV, hMPV, HCoV-HKU1 and HCoV-NL63, accounted for 22.01% of the detected viral pathogens. RSV and HRV were frequently detected in patients with bronchiolitis, and hMPV was frequently associated with pneumonia. HCoV-NL63 was found to be one of the causative agents of acute respiratory wheezing in young children. No seasonal variation was found in the incidence of detection of HCoV-HKU1, HCoV-NL63 or HBoV. This 3-year study demonstrated that viral pathogens play an important role in children with ALRTIs, and more attention should be paid to these newly identified viral agents.     

Prevalence of WU and KI polyomaviruses in plasma, urine, and respiratory samples from renal transplant patients

WU and KI polyomaviruses (WUPyV, KIPyV) have been detected in respiratory, blood, stool, and lymphoid tissue, but not in urine samples. PCR based detection revealed higher frequency in immunocompromised individuals. In this study the prevalence of WUPyV and KIPyV was analyzed in respiratory, urine, and blood samples from renal transplant patients compared with healthy individuals. WUPyV and KIPyV were detected by nested PCR. The PCR products were sequenced and viral DNA loads were determined by quantitative real-time PCR. WUPyV and KIPyV were found in plasma (3.6%; 7/195), urine (14%; 7/50), and respiratory samples (10%; 9/90) of renal transplant patients, but not in plasma (0/200) and urine (0/36) specimens from healthy blood donors. WUPyV and KIPyV were detected mainly early after renal transplantation and the viral loads were low. A higher prevalence of WUPyV was found in plasma and urine samples, KIPyV was found more frequently in respiratory samples from renal transplant patients. It is hypothesized that immunosuppression due to the transplantation may result in reactivation of these viruses or may establish greater susceptibility to infection with KIPyV and WUPyV.     

我国急性呼吸道感染患儿中检测到KI和WU多瘤病毒

目的 了解多瘤病毒WU和KI在我国儿童急性呼吸道疾病中的感染情况.方法 采用PCR扩增的方法对2006年11月至2007年10月收集的急性呼吸道感染患儿的318份鼻咽抽吸物(NPA)标本进行了多瘤病毒WU和KI基因检测.结果 318份标本共检测出14份病毒核酸阳性标本,其中WUV 7份(2.2%),KIPyV 7份(2.2%).该14例基因检测阳性患儿临床均有上呼吸道感染或下呼吸道感染症状.结论 WUV和KIPyV可能也是儿童急性呼吸道感染中较为重要的一个病原,且与儿童上呼吸道感染和下呼吸道感染存在相关性.     

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.     

Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries

ObjectivesTo describe the role of bacteria (including bacterial resistance), viruses (including those recently described) and mixed bacterial–viral infections in adults presenting to primary care with lower respiratory tract infection (LRTI).MethodsIn all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%) had community-acquired pneumonia (CAP), and 2985 matched controls in a prospective study in 16 primary care networks in Europe, and followed patients up at 28–35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae and assessed susceptibility, atypical bacteria and viruses.ResultsA potential pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in 1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5% overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and 12.6% of H. influenzae were β-lactamase positive. The most common viral pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human respiratory syncytial virus as well as human rhinovirus, human coronavirus and human metapneumovirus were detected significantly more frequently in LRTI patients than in controls.ConclusionsA bacterial pathogen is identified in approximately one in five adult patients with LRTI in primary care, and a viral pathogen in just under half, with mixed infections in one in ten. Penicillin-resistant pneumococci and β-lactamase-producing H. influenzae are uncommon. These new findings support a restrictive approach to antibiotic prescribing for LRTI and the use of first-line, narrow-spectrum agents in primary care.     

儿童急性呼吸道博卡病毒感染的病毒载量与临床特征相关性研究

目的 研究急性呼吸道感染患儿人博卡病毒（ human bocavirus,H BoY）病毒载量与临床特征的相关性。方法 对2009年l1月至2010年12月间956例呼吸道感染的患儿及251例健康对照组儿童鼻咽部抽吸物、咽拭子采用PCR法进行HBoV检测,进而对阳性样本进行实时荧光定量PCR法测定博卡病毒DNA载量,并结合患儿的临床检查进行综合分析。结果 实验组与对照组HBoV阳性率存在显著差异,下呼吸道感染病例HBoV的病毒载量水平与上呼吸道感染病例及对照组儿童差异均有统计学意义,上呼吸道感染病例与对照组儿童病毒载量无统计学意义,重症下呼吸道感染患儿与普通下呼吸道感染患儿HBoV的病毒载量无统计学差异,HBoV混合感染与独立感染患儿病毒载量亦无统计学差异。结论 博卡病毒常年均可引起发病,是儿童呼吸道感染的重要病原体之一,但可能不是儿童急性呼吸道感染的唯一因素。HBoV病毒载量并不能独立反映临床疾病感染的严重程度。     

肺表面活性蛋白A基因多态性与呼吸道合胞病毒下呼吸道感染的相关性研究

目的探讨肺表面活性蛋白（SP）-A1-1101C/T和SP-A2-1649G/C位点基因多态性与呼吸道合胞病毒下呼吸道感染（RSV-LRTI）的相关性。方法应用聚合酶链反应-限制性酶切片段长度多态性（PCR-RFLP）分析法检测200例病例组和150例健康对照组2个位点的基因多态性,并进行基因型、等位基因型频率分析;采用DNA测序法进行测序分析。结果 1.病例组SP-A1-1101C/T位点TT、CT基因型频率分别为76.0%、24.0%,T、C等位基因频率分别为88.0%、12.0%;对照组TT、CT基因型频率分别为80.7%、19.3%,T、C等位基因频率分别为90.3%、9.7%,两组基因型及等位基因频率差异无统计学意义（χ2=1.088、0.953,P〉0.05）。2.病例组SP-A2-1649G/C位点CC、CG、GG基因型频率分别为41.5%、50.5%、8.0%,C、G等位基因频率分别为66.8%、33.2%;对照组CC、CG、GG基因型频率分别为43.3%、49.3%、7.4%,C、G等位基因频率分别为68.0%、32.0%,两组基因型及等位基因频率无统计学意义（χ2=0.141、0.122,P〉0.05）;但该位点基因型和等位基因在轻度和重度患儿间的差异有统计学意义（χ2=6.664、5.207,P〈0.05）,携带G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,（OR=1.656,95%CI：1.072～2.559,P=0.023〈0.05）。结论温州地区汉族儿童存在SP-A1-1101C/T、SP-A2-1649G/C基因多态性,未发现其与RSV-LRTI疾病易感性存在关联,但携带SP-A2-1649G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,表明G等位基因可能是影响RSV-LRTI疾病严重程度的一个候选基因。     

急性呼吸道感染住院患儿RSV和ADV与病情严重程度相关性研究

目的 通过对呼吸道合胞病毒(RSV)及腺病毒(ADV)临床检测阳性率来评价儿童急性呼吸道感染病情严重程度的相关性分析.方法 将82例患急性呼吸道感染的儿童(感染组)及30例健康儿童(健康组)作为观察对象,比较两组RSV和ADV阳性率;同时根据感染严重程度,将感染组患儿分为28例的非肺炎组、33例的普通肺炎组及21例的重症肺炎组,对比三组间RSV和ADV阳性率.此外,对感染组患儿中RSV和ADV阳性率与感染严重程度、血常规白细胞计数(WBC)、中性粒细胞百分比(N％)及淋巴细胞百分比(L％)的相关性.结果 感染组RSV和ADV阳性率明显高于健康组(P ＜0.05),而不同严重程度感染组中,以重症肺炎组RSV和ADV阳性率最高(P＜0.05),同时感染组中,RSV和ADV阳性率与患者的感染严重程度存在显著的直线相关性,但与WBC、N％及L％无直线相关性.结论 RSV和ADV阳性率可作为评价急性呼吸道感染患儿病情严重程度的指标.     

Identification of the novel KI polyomavirus in the respiratory tract of an Italian patient

Recently, a new human polyomavirus, KIV, was detected in respiratory specimens of patients with acute respiratory tract infection. Whether this reflects a causal role of the virus in the respiratory tract is still debated. To investigate the presence of KIV in respiratory samples of Italian patients and to determine the degree of similarity with other known polyomaviruses, 222 respiratory specimens collected by general practitioners between 2006 and 2007 were screened. The entire VP1 gene region was amplified and sequenced. Maximum Likelihood tree was generated by PAUP* software. One out of 222 samples tested was positive for KIV. Phylogenetic analysis indicated that this isolate clustered with other KIV isolates, while the WUV isolates seem to belong to a different lineage. The phylogenetic tree also showed that all other known polyomaviruses are quite distant from this isolate. This is the first report describing the presence of KIV in the respiratory tract of a 5-year-old Italian child with acute respiratory symptoms. Further investigations are needed to establish an etiological link of KIV with acute respiratory illness.     

重症慢性阻塞性肺疾病急性加重期下呼吸道感染病原菌及其耐药性分析

目的:了解重症慢性阻塞性肺疾病急性加重期(AECOPD)患者下呼吸道感染病原菌的特点及耐药情况,指导临床合理用药。方法:取我院2007年10月~2010年9月住院的189例重症AECOPD患者合格痰标本及防污染毛刷刷取的气管内分泌物标本进行细菌培养、鉴定及药敏试验。结果:共分离病原菌147株,其中以革兰阴性杆菌占首位,达64.6%,依次为铜绿假单胞菌、不动杆菌、大肠埃希菌和阴沟肠杆菌。其次是革兰阳性球菌,占21.8%。真菌占13.6%,以白念珠菌检出率最高。药敏结果显示革兰阴性杆菌对第三代头孢菌素耐药严重,对哌拉西林-他唑巴坦、碳青霉烯类抗生素较敏感;革兰阳性球菌对青霉素、克林霉素、红霉素耐药率高,未发现对万古霉素耐药。结论:重症AECOPD患者下呼吸道感染病原菌以革兰阴性杆菌为主,且耐药现象明显,二重感染逐年增加,且占有较大比重。临床AECOPD患者选用抗生素治疗时应重视细菌培养及药敏试验,减少不合理用药,减少耐药菌株与二重感染产生。     

鼻病毒在婴幼儿下呼吸道感染中作用的研究

目的探讨鼻病毒在婴幼儿下呼吸道感染中的作用。方法收集2008年5月到2009年4月北京儿童医院下呼吸道感染住院儿童鼻咽分泌物标本240份,使用Real-timeRT-PCR方法筛选鼻病毒阳性标本,并进行统计分析。结果在240例住院儿童中,入院诊断为肺炎的208例,占86．67％（208／240）,支气管炎21例（8．14％）,毛细支气管炎11例,无死亡病例,男女病例比例为1．93：1,且2009年2月采集标本数达到最多。采用Real-timeRT-PCR方法检测为鼻病毒阳性的标本71份,阳性率为29．58％（71／240）,且主要的临床诊断症状是肺炎。发病年龄以2岁以下婴幼儿为主,占81．69％（58／71）,其中以13～18月、324月年龄组发病率最高,发病率为33．33％。结论鼻病毒感染季节为春季和冬季,尤以2岁以下婴幼儿感染为主,主要症状表现为肺炎、支气管炎及毛细支气管炎等下呼吸道感染。鼻病毒流行具有季节性,且传染性强,传播速度快,应做好医院内防护措施,避免交叉感染。     

The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis

BackgroundBacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).ObjectivesTo systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.Data sourcesMEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.Study eligibility criteriaStudies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.ParticipantsChildren under 5 years with and without acute LRTI.MethodsThree reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel–Haenszel fixed- or random-effects models.ResultsMost eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23–2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17–3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04–1.90). High density colonization with S. pneumoniae (>6.9 log¹⁰ copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.ConclusionsDetection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.