Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media

During a 28-month period, 84 children with acute otitis media were studied by viral and bacterial cultures of middle ear fluid and viral cultures of nasal lavage fluid. Viruses were isolated from the middle ear fluid of 17 (20%) patients. Evidence of viral infection was demonstrated by positive viral cultures of middle ear fluid and/or nasal lavage fluid in 33 (39%) patients. Rhinovirus in one patient and influenza b virus in another were the only pathogens isolated. Influenza virus, enterovirus, and rhinovirus were the most common viruses found in middle ear fluids. Parainfluenza virus, adenovirus, and respiratory syncytial virus were found less often. In 82% of cases, the virus isolated from middle ear fluid was also isolated from nasal lavage fluid, but only 44% of viruses found in nasal lavage fluid were also found in middle ear fluid. Mixed bacterial and combined viral-bacterial infections were common. Only 15% of patients had no pathogen isolated from middle ear fluids. Using tissue culture techniques, we demonstrated that enterovirus and rhinovirus are also common middle ear pathogens. Our data reemphasize the significance of viruses as etiologic agents of acute otitis media and propose several questions regarding the viral-bacterial interactions and the types of viruses involved in the pathogenesis of the disease.     

Acute otitis media and respiratory virus infections

We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.     

Respiratory illness associated with influenza and respiratory syncytial virus infection

Aims: To estimate excess morbidity during periods of influenza and respiratory syncytial virus (RSV) activity. Methods: Retrospective analysis of a sentinel practice network database in active and non-active virus periods. Main outcome measures: clinical diagnoses of new episodes of influenza-like illness (ILI), acute bronchitis, asthma, and otitis media. Results: The clinical diagnosis of ILI was consistent with influenza virus activity and acute bronchitis with RSV. During periods of virus activity, estimates of excess morbidity in children aged 1–4 and 5–14 years diagnosed as having acute otitis media exceeded those diagnosed with each of the other three conditions; in children <1 year estimates for acute bronchitis were highest. Using a broad definition of virus activity and summarising the data for all children diagnosed with ILI, 60% was attributable to influenza (40% RSV) as were 37% of episodes diagnosed as acute bronchitis, 9% of those with asthma and 48% of those with otitis media. Using a narrow definition, corresponding proportions were: for ILI diagnoses 77% (23% RSV), acute bronchitis 32%, asthma zero, and otitis media 45%. Acute bronchitis was diagnosed twice as frequently in association with RSV as with influenza in all age groups: excess asthma episodes were only evident in RSV active periods. Conclusions: Except in relation to ILI, RSV caused more illness than the influenza virus in the respiratory diagnoses examined, emphasising the need for RSV prevention and treatment. Influenza was not associated with excess asthma episodes.     

Respiratory illness associated with influenza and respiratory syncytial virus infection.

AIMS: To estimate excess morbidity during periods of influenza and respiratory syncytial virus (RSV) activity. METHODS: Retrospective analysis of a sentinel practice network database in active and non-active virus periods. MAIN OUTCOME MEASURES: clinical diagnoses of new episodes of influenza-like illness (ILI), acute bronchitis, asthma, and otitis media. RESULTS: The clinical diagnosis of ILI was consistent with influenza virus activity and acute bronchitis with RSV. During periods of virus activity, estimates of excess morbidity in children aged 1-4 and 5-14 years diagnosed as having acute otitis media exceeded those diagnosed with each of the other three conditions; in children <1 year estimates for acute bronchitis were highest. Using a broad definition of virus activity and summarising the data for all children diagnosed with ILI, 60% was attributable to influenza (40% RSV) as were 37% of episodes diagnosed as acute bronchitis, 9% of those with asthma and 48% of those with otitis media. Using a narrow definition, corresponding proportions were: for ILI diagnoses 77% (23% RSV), acute bronchitis 32%, asthma zero, and otitis media 45%. Acute bronchitis was diagnosed twice as frequently in association with RSV as with influenza in all age groups: excess asthma episodes were only evident in RSV active periods. CONCLUSIONS: Except in relation to ILI, RSV caused more illness than the influenza virus in the respiratory diagnoses examined, emphasising the need for RSV prevention and treatment. Influenza was not associated with excess asthma episodes.     

苏州地区急性呼吸道感染住院患儿病毒病原学分析

目的：了解苏州地区急性呼吸道感染（ARI）住院患儿的病毒病原学情况。方法：采集1 668例7岁以下ARI住院患儿鼻咽分泌物,直接免疫荧光法检测呼吸道合胞病毒（RSV）,流感病毒A,B型（IV A,B）,副流感病毒1,2,3型（PIV 1,2,3）及腺病毒A(ADA)等7种常见呼吸道病毒,用RT-PCR法检测人类偏肺病毒（hMPV）N基因。结果：① 1 668例患儿中,病毒检测阳性597例（35.8%）。单项病毒感染561例（33.6%）,其中7种常见呼吸道病毒检出率为23.1%,以RSV为主（17.6%）,好发于冬春季,主要见于1岁以下婴幼儿;② hMPV阳性率为10.6%,3~5月份为检出高峰期。③ 36例混合感染中,22例为RSV合并hMPV感染,主要见于1岁以下婴幼儿。结论：RSV是该地区ARI的主要病毒病原,RSV感染好发于冬春季,多见于1岁以下婴幼儿,hMPV是3~5月份ARI患儿的主要病毒病原,混合感染多见于1岁以下婴幼儿。［中国当代儿科杂志,2009,11（7）：529-531］     

重庆地区婴幼儿重症肺炎呼吸道病毒病原分析

目的 了解重庆地区婴幼儿重症肺炎病毒病原的感染情况.方法 2006年12月至2008年3月,取ICU病房收集诊断为重症肺炎患儿的深部气道或机械通气气管导管内吸取物标本119例,采用RT-PCR或PCR方法 检测呼吸道合胞病毒(RSV)、人偏肺病毒(hMPV)、博卡病毒(HBoV)、腺病毒(ADV)、副流感病毒(PIV)1、2、3和流感病毒(IV)A、B等呼吸道病毒病原.结果 119例标本中病毒总检出例数为86例(72.3%),其中RSV检出率最高,为41.2%(49/119).有2种及以上病毒协同感染23例,占26.7%(23/86);RSV阳性中有19例存在协同感染,占38.8%(19/49).69例行细菌检测,其中53例为阳性,阳性率为76.8%.这69例标本中,病毒阳性率为76.8%;病毒细菌双阳性为41例,占59.4%.结论 (1)病毒感染仍是重庆地区婴幼儿重症肺炎的重要病因.(2)BSV是婴幼儿重症肺炎最常见病毒病原,其次为ADV和hMPV.(3)病毒的协同感染较在重症呼吸道患儿中可能较为普遍,但尚无证据说明病毒协同感染可加重病情.     

5150例急性下呼吸道感染儿童呼吸道病毒检测结果分析

目的 了解急性下呼吸道感染(ALRTI)住院患儿咽拭子呼吸道病毒的分布情况。方法 采用直接免疫荧光法,对该院2014 年3 月至2015 年2 月5 150 例ALRTI 住院患儿咽拭子标本进行流感病毒A 型(FA)、流感病毒B 型(FB)、腺病毒(ADV)、呼吸道合胞病毒(RSV)及副流感病毒1、2、3 型(PIV-1、2、3)检测,了解ALRTI 患儿中呼吸道病毒的分布情况。结果 5 150 例住院患儿的咽拭子样本中病毒检测阳性2 155 例(41.84%),其中RSV、 PIV-3 、FA 是检出率最高的前3 位病毒,分别为1 338 例(25.98%)、439 例(8.52%)、166 例(3.22%),并有29 例为2 种病毒混合感染。随年龄增加病毒检出率呈下降趋势(χ²=279.623,P<0.01)。RSV 检测阳性率自9 月开始呈增高趋势,11 月最高,达60.09%,6 月最低,仅为1.51%。PIV-3 检测阳性率5 月最高(21.38%),11 月最低(1.77%)。结论 ALRTI 患儿的病毒流行分布随年龄、季节而不同,秋冬季以RSV 流行为主,春夏季以PIV-3 流行为主。RSV 是ALRTI 住院儿童的最常见病毒。     

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.     

Presence of viral nucleic acids in the middle ear: acute otitis media pathogen or bystander?

Viruses play an important role in acute otitis media (AOM) pathogenesis, and live viruses may cause AOM in the absence of pathogenic bacteria. Detection of AOM pathogens generally relies on bacterial culture of middle ear fluid. When viral culture is used and live viruses are detected in the middle ear fluid of children with AOM, the viruses are generally accepted as AOM pathogens. Because viral culture is not sensitive and does not detect the comprehensive spectrum of respiratory viruses, polymerase chain reaction assays are commonly used to detect viral nucleic acids in the middle ear fluid. Although polymerase chain reaction assays have greatly increased the viral detection rate, new questions arise on the significance of viral nucleic acids detected in the middle ear because nucleic acids of multiple viruses are detected simultaneously, and nucleic acids of specific viruses are detected repeatedly and in a high proportion of asymptomatic children. This article first reviews the role of live viruses in AOM and presents the point-counterpoint arguments on whether viral nucleic acids in the middle ear represent an AOM pathogen or a bystander status. Although there is evidence to support both directions, helpful information for interpretation of the data and future research direction is outlined.     

Respiratory virus infection as a cause of prolonged symptoms in acute otitis media

We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.     

2007～2008年温州地区急性呼吸道感染病毒病原学研究

目的：分析2007~2008年温州地区急性呼吸道感染病毒病原学的检测结果,为临床提供病毒病原学诊断依据。方法：取5 097例急性呼吸道感染儿童鼻咽分泌物,采用直接免疫荧光法检测7种常见呼吸道病毒抗原。结果：①2 209份标本（43.3%）病毒病原检测阳性,其中呼吸道合胞病毒（RSV）1 725例（78.1%）,腺病毒（ADV） 61例（2.8%）,流感病毒A型（IVA）66例（3.0%）,流感病毒B型（IVB）12例（0.5%）,副流感病毒1型（PIV1）38例（1.7%）,副流感病毒2型（PIV2）7例（0.3%）,副流感病毒3型（PIV3）275例（12.4%）;②病毒检出率在小于3个月和小于6个月年龄组较高,分别为53.6% 和49.2%;③冬季病毒检出率最高。结论：2007～2008年温州地区急性呼吸道感染的病毒仍以RSV为主要病原体, ＜6个月的婴幼儿病毒感染率较高,好发于冬季。［中国当代儿科杂志,2010,12（1）：32-34］     

Correlation between serum interleukin 6 and C-reactive protein concentrations in patients with adenoviral respiratory infection

OBJECTIVE: To characterize adenoviral respiratory infection, we evaluated clinical features, laboratory findings and serum cytokine concentrations in patients with adenoviral infection and compared them with those in patients with influenza virus and respiratory syncytial virus (RSV) infections. METHODS: We enrolled 106 patients who had been diagnosed with acute viral respiratory infection caused by adeno-, influenza and respiratory syncytial viruses from January, 1995, through December, 1998. Forty-nine patients had adenovirus infection, 19 patients had influenza virus infection and 38 patients had RSV infection. Etiologic diagnosis was made based on the antigen detection by enzyme immunoassay (influenza virus, RSV), and viral isolation was done by tissue culture (adenovirus, influenza virus) from nasopharyngeal specimens. We evaluated clinical manifestations, laboratory findings (white blood cell count, C-reactive protein, erythrocyte sedimentation rate) and serum cytokine [interleukin (IL)-1-beta, IL-6, IL-8, interferon gamma and tumor necrosis factor alpha] concentrations. RESULTS: We observed prolonged fever, strong inflammatory response such as leukocytosis with neutrophilia and high C-reactive protein values in patients with adenoviral respiratory infection compared with those in patients with influenza virus and RSV infections. Serum IL-6 concentrations in patients with adenoviral respiratory infection were higher than those in patients with influenza virus and RSV infections. Other cytokine (IL-1-beta, IL-2, interferon gamma and tumor necrosis factor alpha) values did not differ among adenovirus, influenza virus and RSV infections. CONCLUSIONS: Patients with adenoviral respiratory infection have high grade and prolonged fever, strong inflammatory response and higher serum IL-6 than in influenza and RSV infection.     

2009—2010年苏州地区博卡病毒感染住院患儿临床特征分析

目的探讨苏州地区因急性呼吸道感染住院患儿中人类博卡病毒(human bocavirus,HBoV)感染的临床特征。方法收集2009年1月—2010年12月因急性呼吸道感染住院的3 826例患儿的痰标本,应用实时PCR检测HBoV DNA,直接免疫荧光法检测呼吸道合胞病毒、流感病毒(A、B)、副流感病毒(1～3)和腺病毒,同时采用逆转录PCR检测人偏肺病毒RNA,并进行细菌培养及荧光定量PCR检测支原体DNA,分析HBoV感染的临床特点及流行病学特征,并与呼吸道合胞病毒(RSV)进行比较。结果 3 816份标本共检测到HBoV 272例(7.13%),仅次于RSV;HBoV单独感染率为32.7%,与其他呼吸道病毒的合并感染率为18.38%,高于RSV和其他病毒的合并感染率(P<0.05)。HBoV感染全年均有发生,夏季最多;6～18月龄婴幼儿检出率最高,占48.17%。在住院患儿中,HBoV主要引起支气管肺炎(85.39%),临床症状主要表现为咳嗽(96.63%)、喘息(46.07%)、发热(56.18%)。与RSV相比,HBoV感染患儿的白细胞、中性粒细胞比例、CRP均高于RSV,差异有统计学意义(P<0.05)。结论 HBoV是苏州地区小儿呼吸道感染的重要病原体之一,有单独的致病性,与RSV相比,在年龄、季节分布、临床症状、实验室指标等方面有明显差异。     

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目的分析住院急性呼吸道感染(ARI)患儿病毒病原检测结果,为临床儿童急性呼吸道感染提供病毒病原学诊断依据。方法选择2003年4月至2005年3月重庆医科大学儿童医院呼吸内科住院治疗的急性呼吸道感染患儿,取其鼻咽分泌物做免疫荧光检测筛查7种常见呼吸道病毒抗原,包括呼吸道合胞病毒(RSV)、腺病毒、流感病毒A及B型、副流感病毒Ⅰ、Ⅱ、Ⅲ型,对检测标本阳性的病例进行统计分析。结果1052份标本中,阳性标本409份,占38.88%。其中RSV阳性标本360份,占总阳性标本例数的88.02%,副流感病毒Ⅲ37份占9.05%;RSV发病高峰时期在12月至次年2月和7、8月两个时期;RSV感染多见于3岁以下,发病高峰年龄为2～6个月,男女发病比例为2.24∶1。结论2003～2005年重庆地区急性呼吸道感染的病毒病原体仍以RSV为主。     

Bacterial coinfection in children hospitalized with respiratory syncytial virus infections

Clinical and bacterial findings were prospectively studied in 90 children hospitalized because of middle or lower respiratory tract infection caused by respiratory syncytial virus (RSV) during a surveillance period of 12 months. The results were compared with those of RSV-negative children hospitalized with identical indications during the 3 peak months of the RSV epidemic (N = 91) or for the 3 months after the outbreak (N = 99). A high frequency of pneumonia and acute otitis media were found in both RSV-positive and RSV-negative children during the epidemic, but not in control patients after the epidemic. Bacterial infection, based on a significant rise of antibody titer and/or on detection of pneumococcal antigen in serum or urine, was observed in 39% of the children with RSV infection. The respective figures were 24% in RSV-negative children hospitalized during the epidemic and 8% after the epidemic. Our observations stress the role of RSV as a predisposing agent for secondary bacterial infection in the airways of children. The most common bacteria involved in the mixed RSV-bacterial infections were Streptococcus pneumoniae and Haemophilus influenzae, the latter being found only in pneumonic patients. The presence or absence of pneumonia or acute otitis media was not significantly correlated with evidence of pneumococcal infection. We conclude that a bacterial pathogen should be actively sought when managing patients with lower respiratory tract syndromes, especially in those who have evidence of RSV infection.     

粤东地区住院小儿急性下呼吸道感染病毒病原学研究

目的：了解2007年粤东地区住院小儿下呼吸道感染患儿的病毒病原现状并比较各个年龄组、不同季节、不同病种的病毒检出情况。方法：选择因急性下呼吸道感染住院治疗的小儿345例,取其鼻咽抽吸物采用多重PCR方法以筛查呼吸道合胞病毒,腺病毒,流感病毒A型、B型,副流感病毒1型、3型,鼻病毒,博卡病毒及人类偏肺病毒。结果：①病毒总检出率为51.6%(178/345),其中呼吸道合胞病毒占首位,病毒检出率为19.3%（66/345）,而人类偏肺病毒为3.2%(11/345),博卡病毒为3.2%(11/345)。②1～3月份(阳性率为61.9%)、毛细支气管炎患儿(阳性率为72.6%)、1～6个月婴幼儿(阳性率为71.3%)病毒检出率较高,4～6月份(阳性率为40.2%)、3岁以上儿童(阳性率为19.0%)病毒检出率较低,呼吸道感染病毒病原的总阳性率与性别无关。结论：粤东地区小儿下呼吸道感染的主要病毒病原为呼吸道合胞病毒等常见病毒,此外博卡病毒及人类偏肺病毒等也是重要的病原体;年龄越小,阳性率越高,不同季节的呼吸道病毒检出率不同,毛细支气管炎患儿的病毒总检出率最高。［中国当代儿科杂志,2009,11（3）：203-206］