Clinical manifestations of human coronavirus NL63 infection in children in Taiwan

Human coronavirus NL63 (HCoV-NL63) is a global respiratory tract pathogen; however, the epidemiology of this virus in subtropical area is not well known. To evaluate the epidemics and disease spectrum of HCoV-NL63 infection in children in Taiwan, we prospectively screened children admitted to the hospital with respiratory tract infection from May 2004 to April 2005. Every enrolled child had a nasopharyngeal aspirate (NPA) sample taken. Quantitative RT-PCR was used to detect 1b gene of HCoV-NL63. A total of 539 NPAs were collected. Seven (1.3%) were positive for HCoV-NL63. All cases were boys younger than 3 years of age and most cases occurred in autumn. Co-infection with other pathogens was observed in three cases. The most common symptoms/signs of HCoV-NL63 infection were cough, fever, and inspiratory stridor. HCoV-NL63 was the most common pathogen (14.7%) in children with croup and was the cause of three cases of croup in October. The odds ratio of croup in children infected with HCoV-NL63 was 43.4 (95% CI 8.1∼233.1). In conclusion, HCoV-NL63 is an important respiratory tract pathogen as the main cause in children admitted to the hospital in Taiwan.     

The widening scope of coronaviruses

PURPOSE OF REVIEW: In the past 2 years, at least three distinct human coronaviruses have been discovered, including the etiological agent associated with severe acquired respiratory syndrome (SARS). These recently discovered viruses, with the exception of the SARS associated coronavirus (SARS-CoV), are likely to be common respiratory viruses and may be responsible for a substantial proportion of respiratory tract disease. RECENT FINDINGS: The SARS-CoV first appeared in 2002 and spread rapidly around the globe. Although the worldwide spread of SARS-CoV may have been halted, the emergence of this new virus demonstrates the potential threat represented by species-to-species transmission of coronaviruses. NL63, initially isolated from a young child with lower respiratory tract disease, represents a group of newly described group I coronaviruses that have been identified worldwide, which are associated with both upper and lower respiratory tract disease, particularly in young children. The distribution of HKU1, a newly identified group II coronavirus, is not yet established. NL63 and HKU1 are related to the common human coronaviruses 229E and OC43, respectively. SUMMARY: The discovery of at least three new human coronaviruses represents significant advances in the investigation of human respiratory tract disease. Further studies are required to fully define the impact of these new pathogens.     

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??Abstract??Objective??To establish a real-time fluorescent quantitative PCR assay to detect the human coronavirus NL63 from nasopharyngeal samples of children with acute respiratory tract infections in Fuzhou. Methods??The specific primers and Tap-man probes were designed targeting the 1a gene. The aimed fragment of 1a gene was amplified with PCR and ligated into a PMD18-T Easy vector for standards. A total of 151 clinical specimens were subsequently tested after determination of the sensitivity and specificity of the established real-time PCR. Amplify and preliminarily analyse the N gene. Results??The specificity of this assay was excellent. The linear amplification of the assay ranged from 101 copies/μL to 1010 copies/μL. Two of 151 clinical specimens??1.3%?? were tested positive for HCoV-NL63. Conclusion??The real-time fluorescent quantitative PCR assay is successfully established to detect HCoV- NL63 .     

新发现呼吸道病毒感染的流行病学及其临床特征

呼吸道感染是儿科的常见病、多发病,是引起世界范围内5岁以下儿童死亡的首位原因.其临床表现易被认识,但病因却很难明确.2001年以来许多新的人类病毒被发现,其中人类偏肺病毒、人类冠状病毒NL63和HKU1,以及人类博卡病毒,均已被证实可引起小儿呼吸道疾病,其流行病学及临床特征也得到较为深入的研究.     

Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study

BACKGROUND: Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). METHODS: We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. RESULTS: All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. CONCLUSIONS: Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.     

Etiology of acute lower respiratory tract infections in children in a rural community in The Gambia.

Approximately 500 children younger than 5 years old resident in 7 villages in a rural area of The Gambia were monitored closely for 1 year for episodes of acute lower respiratory tract infection (ALRI). Each episode was investigated with antigen detection techniques and antibody assays as well as culture for bacteria and viruses. A pathogen was identified in 76 (34.2%) of 222 cases with clinical signs of ALRI and in 34 (42%) of the 81 cases who, in addition, had radiologic evidence of ALRI. Evidence of infection with a bacterial pathogen, most commonly Streptococcus pneumoniae or Haemophilus influenzae, was obtained in 32 (14.4%) cases with clinical signs of ALRI (23.5% of those with radiologically proved pneumonia). Viral agents were cultured from 42 (19%) of 221 cases but also from 14 (14.6%) of 96 controls some of whom had minor symptoms of upper respiratory tract infection. In the absence of an outbreak of respiratory syncytial virus the viral agents recovered most often were influenza A and adenoviruses.     

Use of bacterial antigen detection in the diagnosis of pediatric lower respiratory tract infections

Two immunochemical methods were used to identify Haemophilus influenzae and Streptococcus pneumoniae capsular antigens in the urine and serum of 162 children with acute lower respiratory tract infection. These methods were compared with standard bacterial blood culture. Viral and mycoplasma cultures of respiratory secretions were obtained simultaneously to determine the frequency of antigenuria at the time of nonbacterial acute lower respiratory tract infection. Urine from groups of well children and children with acute otitis media was tested for capsular antigens to determine the incidence of antigenuria. Antigenuria was found in 24% of children 2 months to 18 years of age with acute lower respiratory tract infection compared with a 2% incidence of bacteremia. Antigenuria was found in 4% of asymptomatic children and 16% of children with acute otitis media. One third of children with symptoms of acute lower respiratory tract infection and viral isolates from the oropharynx had bacterial antigenuria. The sixfold increase in frequency of bacterial antigenuria in children at the time of lower respiratory symptoms suggests that bacterial acute lower respiratory tract infection may be more common than identified by traditional culture techniques. Because bacterial antigen may come from other sites such as the middle ear, further studies are needed to determine the role of antigen detection in the diagnosis of pediatric acute lower respiratory tract infection.     

Viral etiology of acute respiratory tract infections in children presenting to hospital: role of polymerase chain reaction and demonstration of multiple infections

BACKGROUND: Viral lower respiratory tract infections are a leading cause of hospitalization for young children. METHODS: We used polymerase chain reaction (PCR) and conventional methods of cell culture and antigen detection to establish the viral etiology of acute respiratory tract infections in 75 hospitalized children. RESULTS: One or more viral pathogens were detected in 65 (87%) children, with respiratory syncytial virus being the most commonly identified virus (36 children). Other viruses identified included influenza virus types A and B, parainfluenzavirus type 3, adenovirus, enterovirus, rhinovirus, coronavirus and human metapneumovirus. PCR increased the diagnostic yield significantly compared with antigen detection and culture, with 39 (21%) diagnoses identified by this method. Multiple infections were identified in 20 (27%) children. CONCLUSIONS: PCR-based methodologies offer increased sensitivity for the detection of most respiratory viruses in young children. The inclusion of PCR into diagnostic testing strategies is needed to broaden our understanding of the natural ecology of respiratory viruses and the significance of multiple infections.     

Viral infections in hospitalized children affected by acute lower respiratory tract disease

OBJECTIVE: To evaluate the frequency of the main respiratory viruses in hospitalized children affected by acute lower respiratory tract disease at a university hospital. METHODS: This is a prospective trial that included two cohorts of hospitalized children in the period from April to July 1996. The groups were selected according to the presence of lower respiratory tract disease on admission: Group A- with acute disease (history of less than 7 days) and B- without present or recent respiratory disease. The parameters for defining lower respiratory tract disease included physical and/or radiological pulmonary changes. Clinical and radiological criteria were established for the classification of lower respiratory tract diseases in group A. Nasopharyngeal swab was collected from all children on admission for viral detection by cellular cultures and direct immunofluorescence. RESULTS: 201 cases were selected, 126 in group A and 75 in group B. Viruses were identified in 71 children from groupA(56.4%) and only in 3 from group B (4.0%). The predominant agent in group A was respiratory syncytial virus, identified in 66 cases; adenovirus (4) and influenza (1) were detected in other patients. In group B two patients with respiratory syncytial virus and one with adenovirus were identified. The patients from group A affected by respiratory syncytial virus were younger (median age 3 months versus 13 months) and more wheezy on physical examination (78.7%) than the other patients of the group (33.3%). This virus was associated to most of the bronchiolitis cases (84%) and to half of the pneumonia cases (46.4%). CONCLUSION: The authors found a significant presence of viruses in the majority of children hospitalized with acute lower respiratory tract disease. The respiratory syncytial virus was the predominant agent identified. These results are similar to others previously reported both in developed and some developing countries. The authors emphasize that the present study evaluated only partially the possibility of simultaneous infection by other pathogens and that the present protocol was conducted during the season with the highest incidence of respiratory syncytial virus.     

90例儿童人博卡病毒感染临床分析

目的：探讨儿童人博卡病毒（HBoV）感染的临床特征。方法：采集843例下呼吸道感染患儿鼻、咽拭子标本,用多重RT-PCR方法检测HBoV和其他6种常见呼吸道病毒,分析HBoV阳性病例临床特征。结果：843例标本中检测出HBoV阳性90例（10.7%）,呼吸道合胞病毒（RSV）131例（15.5%）,流感病毒（IFV）117例（13.9%）,副流感病毒(PIV)84例（10.0%）,鼻病毒(RV)55例（6.5%）,冠状病毒(OC43)48例（5.7%）,人类偏肺病毒(HMPV)33例（3.7%）。HBoV合并其他呼吸道感染者45例（50%）,其中HBoV合并１种其他病毒感染者33例（37％）,合并2种其他病毒感染者11例（12％）,合并3种其他病毒感染者1例（1％）。伴喘息的患儿HBoV检出率高于不伴喘息的患儿（17.0% vs 9.2%,P<0.01）。HBoV阳性患儿常见的临床表现为频咳、喘息和发热。HBoV阳性组与RSV阳性组中喘息发生的构成比差异无统计学意义。结论：伴喘息发作的下呼吸道感染患儿中,HboV阳性检出率明显高于不伴喘息发作患儿,提示HBoV可能是除RSV外另一种引起儿童喘息的呼吸道病毒。HBoV与其他呼吸道病毒存在着混合感染。     

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目的了解北京地区门诊儿童急性呼吸道感染的病毒病原学特点。方法 2010年3月至2011年2月在北京儿童医院门诊就诊的急性呼吸道感染患儿540例,每例患儿采集咽拭子标本1份。采用多重PCR试剂检测常见呼吸道病毒核酸,包括呼吸道合胞病毒(RSV)A、B型,鼻病毒(RV),副流感病毒(PIV)1～4型,流感病毒(IFV)甲、乙型,腺病毒(ADV),人偏肺病毒(HMPV),人冠状病毒(HCoV),人博卡病毒(HBoV)及肠道病毒(EV)。结果 540例门诊采集的急性呼吸道感染患儿的咽拭子标本中,306例检出至少1种病毒,总阳性率56.7%。其中33例检出2种病毒,1例检出3种病毒,混合感染率为6.3%。各种病毒中,IFV检出率最高占16.7%,其次是ADV(12.8%),EV(7.8%),PIV(7.2%),。IFV中以甲型IFV为主(占95.6%),PIV中以PIV3型为主(占66.7%),RSV检出以RSVA型为主,占79.3%。结论病毒是引起儿童急性呼吸道感染的重要病原,北京儿童医院急性呼吸道感染的主要病毒病原是IFV、ADV、EV、PIV。     

Severe acute respiratory syndrome in children

BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS: We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS: We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS: Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.     

急性呼吸道感染住院儿童人偏肺病毒感染的流行情况及临床特征

目的了解急性呼吸道感染住院患儿人偏肺病毒(hMPV)呼吸道感染的流行情况及临床特征。方法收集2006年11月～2007年2月本院儿科中心的112例急性呼吸道感染住院患儿的鼻咽分泌物标本,对其中65例用直接免疫荧光法(DFA)检测常见7种呼吸道病毒特异性抗原阴性患儿鼻咽分泌物用间接免疫荧光法(IFA)检测hMPV抗原。结果1.IFA能检测到鼻咽分泌物中hMPV抗原;2.阳性8例,阳性率为12.31%,112例中单一hMPV感染率为7.14%;3.hMPV的检出高峰主要在11月份及次年1月份;4.在≤5岁年龄组阳性率为15%(6/40例),>5岁年龄组阳性率为8%(2/25例),二组hMPV感染阳性率差异无统计学意义(P>0.05);5.hMPV感染的临床表现无特征性。结论西安地区儿童急性呼吸道感染与hMPV感染有关;咳嗽、发热是hMPV感染后的主要临床症状。     

Clinical role of respiratory virus infection in acute otitis media

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.     

Esophagitis and findings of long-term esophageal pH recording in children with repeated lower respiratory tract symptoms

Esophagoscopy was performed on 116 children with recurrent lower respiratory tract symptoms; esophagitis of various degrees was detected in 45% of the cases. The presence of verified esophagitis correlated with endoscopic findings of bile-stained gastric contents, suggesting a role of bile reflux in the pathogenesis. Esophageal pH recordings covering an 18-24-h period were performed on 22 patients with esophagitis and 19 patients without esophagitis. Gastroesophageal reflux (GER) during the sleeping period was detected in 95% of children with esophagitis, as compared to 42% in children with no esophagitis (p less than 0.001). The percentage of time with esophageal pH below 4 of the total registration time was significantly greater (p less than 0.05) in children with esophagitis (9.5%) than in those with no esophagitis (4.0%)--the difference being due to a greater share of nocturnal GER of the recording time. These criteria could be applied to a search for clinically significant GER in children with recurrent lower respiratory tract symptoms and to select patients for esophagoscopy.     

Detection of respiratory viruses in asymptomatic children undergoing allogeneic hematopoietic cell transplantation

Detection of respiratory viruses by molecular methods, in children without respiratory symptoms undergoing hematopoietic cell transplantation (HCT), has not been well described. A prospective study of 33 asymptomatic children detected respiratory viruses in 8 of 33 (24%) patients before HCT. Human rhinovirus (HRV) was detected in five patients, and human adenovirus (hADV) in three patients. Two additional patients shed HRV, and one shed human coronavirus (hCoV), post‐HCT. Two patients had co‐infections. Of the 11 asymptomatic patients where respiratory virus was detected, 3 (27%) later developed an upper respiratory tract infection, from the same virus. Pediatr Blood Cancer 2013; 60: 149–151. © 2012 Wiley Periodicals, Inc.     

The cell biology of acute childhood respiratory disease: therapeutic implications

Respiratory syncytial virus (RSV), the recently identified human metapneumovirus (HMPV), and the human parainfluenza viruses (HPIVs), cause most cases of childhood croup, bronchiolitis, and pneumonia. Influenza virus also causes a significant burden of disease in young children, although its significance in children was not fully recognized until recently. This article discusses pathogens that have been studied for several decades, including RSV and HPIVs, and also explores the newly identified viral pathogens HMPV and human coronavirus NL63. The escalating rate of emergence of new infectious agents, fortunately meeting with equally rapid advancements in molecular methods of surveillance and pathogen discovery, means that new organisms will soon be added to the list. A section on therapies for bronchiolitis addresses the final common pathways that can result from infection with diverse pathogens, highlighting the mechanisms that may be amenable to therapeutic approaches. The article concludes with a discussion of the overarching impact of new diagnostic strategies.