Burden of respiratory syncytial virus infection in young children

Respiratory syncytial virus (RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants (below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-risk infants, lowers the burden of RSV infection in certain carefully selected patient groups.     

下呼吸道感染患儿外周血单个核细胞呼吸道合胞病毒感染的研究

为探讨呼吸道合胞病毒（ＲＳＶ）对外周血单个核细胞（ＰＢＭＣ）的感染情况及感染后细胞免疫的变化，采用免疫组化法对１８例ＲＳＶ性急性下呼吸道感染患儿ＰＢＭＣ内ＲＳＶ及其Ａ、Ｂ亚型抗原进行了检测；采用ＡＰＡＡＰ法、ＭＴＴ比色法和ＥＬＩＳＡ法对Ｔ细胞亚群及Ｔ细胞表面白细胞介素２受体表达、ＰＢＭＣ培养上清液白细胞介素２（ＩＬ－２）活性和可溶性ＩＬ－２受体水平进行了测定。结果显示：１８例ＲＳＶ感染患儿中７例ＰＢＭＣ内可检测到ＲＳＶ抗原；１１例ＲＳＶＡ亚型感染者５例ＰＢＭＣ内均为ＲＳＶＡ亚型阳性，７例ＲＳＶＢ型感染者２例Ｂ亚型阳性；７例恢复期和１０例对照组患儿均为阴性；发病３天以内ＰＢＭＣ中ＲＳＶ抗原阳性者多于３天以后（Ｐ＜０．０５）。ＲＳＶ感染组ＰＢＭＣ内ＲＳＶ抗原阳性者，ＣＤ４细胞比率和ＩＬ－２水平均低于阴性者（ｔ＝２．３８，２．４０，Ｐ值均＜０．０５）。提示：ＲＳＶ性急性下呼吸道感染患儿ＰＢＭＣ可被ＲＳＶ感染，可能由此加重免疫活性细胞损害，导致细胞免疫功能紊乱。     

A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants

Respiratory syncytial virus (RSV) infection is a major cause of bronchiolitis in infants while influenza A infection usually manifests as upper respiratory tract infection. We hypothesised that the immunological responses of infants to RSV infection and influenza A infection are different. This prospective study was undertaken to compare the cytokine responses during RSV and influenza A infection. Sera and nasopharyngeal aspirates (NPA) were collected from infants with a coryzal illness with or without wheeze who were admitted to the paediatric wards during 1998. Cytokines, adhesion molecules, RANTES, IgE and eosinophil cationic protein (ECP) were measured by enzyme linked immunosorbent assay or fluorescence enzyme immunoassay. The diagnosis of RSV and influenza infections was based on direct immunofluorescence and viral culture. Of the 39 infants studied, RSV infection was confirmed in 11 patients and Influenza A in 10 patients. All RSV patients and one influenza A patient had wheeze during the infection. The serum concentrations of interleukin (IL)-4 and IL-5, regulated upon activation normal T cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule 1 (sICAM-1) in infants with RSV infection were significantly higher than those with influenza A infection (all P < 0.02). The concentration of tumour necrosis factor-α (TNF-α) in NPA was significantly lower in infants with RSV infection (P < 0.01). Conclusion A predominant T helper cell type 2 cytokine and related immunological response was observed in infants with respiratory syncytial virus infection whereas a predominant pro-inflammatory cytokine response was observed in infants with influenza A infection. This may explain the different clinical manifestations of the two viral infections in infants. Received: 17 April 2000 / Accepted: 13 September 2000     

小儿呼吸道合胞病毒感染流行特点分析

目的探讨小儿呼吸道合胞感染病毒感染的流行特点及影响RSV流行的气候因素。方法对2001年1月至2006年12月因下呼吸道感染在浙江大学医学院附属儿童医院住院的39597例患儿取鼻咽分泌物标本进行呼吸道合胞病毒(RSV)抗原检测。结果39597例患儿中RSV检测阳性患儿共8657例(21.86%),<1岁者6804例(30.99%),1～3岁者1576例(14.84%),～13岁者277例(3.95%),各年龄组间检出率有统计学意义(P<0.01)。男性5783例(22.76%)高于女性2873例(20.24%),有统计学意义(P<0.01)。RSV检出率与气温之间存在直线负相关,气温每升高1℃,下呼吸道感染患儿中RSV的检出率下降1.8%。冬季是RSV流行高峰,其次是春季和秋季,夏季RSV感染率最低,全年都有RSV的散发流行。结论RSV是冬春季节引起小儿下呼吸道感染的主要病毒,年龄越小RSV感染率越高,男性较女性易感RSV。气温越低,RSV的检出率越高,低气温是杭州地区RSV流行的重要因素之一。     

The clinical features of respiratory syncytial virus: Lower respiratory tract infection after upper respiratory tract infection due to influenza virus

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are the primary pathogens of respiratory tract infection. However, epidemics of influenza virus infection have been observed to interrupt RSV epidemics (termed an epidemiological interference effect). METHODS: At a clinic in Tsuna county, Hyogo prefecture, Japan, a total of 1262 outpatients under 6 years of age with lower respiratory tract infection due to RSV (RSV-LRTI) and upper respiratory tract infection due to influenza virus (FLU-URTI) in three successive winter seasons (1999-2000, 2000-2001 and 2001-2002) were analyzed. RESULTS: The RSV-LRTI epidemic and FLU-URTI epidemic overlapped in each season, but the RSV-LRTI epidemic peak preceded that of the FLU-URTI epidemic. Epidemiological interference between RSV and influenza virus was observed in the second and third season; the number of patients with RSV-LRTI began to decrease after the start of the FLU-URTI epidemic and recovered to some extent after the FLU-URTI epidemic passed its peak. There were no differences in onset age, male-to-female ratio and severity of RSV-LRTI in outpatients before and after the start of the FLU-URTI epidemic in all the three seasons. CONCLUSION: An epidemiological interference between RSV and influenza virus was observed in Tsuna county in two of the three winter seasons. However, there was no difference between the clinical features of the patients with RSV-LRTI before and after the start of the influenza virus infection epidemic. The data suggest that the clinical severity of RSV infection is not changed by the epidemiological interference effect of influenza virus infection epidemics.     

Clinical predictors of respiratory syncytial virus infection in children

Aim: The aim of this study was to develop a clinical prediction model that identifies respiratory syncytial virus (RSV) infection in infants and young children.
Methods: Children ≤ 36 months of age with respiratory illness, who were suspected of having RSV infection, were enrolled in this prospective cohort study during the study period between January and February 2002. RSV testing was performed on all patients.
Results: Of the 197 patients enrolled in the study, 126 (64%) were positive for RSV and 71 (36%) patients were either negative for RSV or had a positive culture for viruses other than RSV. The mean age of patients was 5 months and 57% were male. Backwards stepwise logistic regression analysis identified cough (p = 0.000), wheezing (p = 0.002), and retractions (p = 0.008) as independent variables predictive of RSV infection. The prediction model had a sensitivity of 80% (95% CI, 71–87%), specificity of 68% (95% CI, 54–79%), positive predictive value 82% (95% CI, 74–89%), negative predictive value 66% (95% CI, 52–77), positive likelihood ratio 2.5 (95% CI, 1.8–3.7) and post-test probability of 82%.
Conclusion: The combination of cough, wheezing and retractions predicts RSV infection in infants and young children.     

急性呼吸道感染儿童两亚型呼吸道合胞病毒检测分析

目的 了解2006-2007年度重庆地区住院急性呼吸道感染(ARTIs)儿童两亚型呼吸道合胞病毒(RSV)的感染特点及流行规律.方法 收集2006年4月至2007年3月全年在重庆医科大学附属儿童医院呼吸科住院的部分ARTIs患儿的鼻咽深部吸取物390份,针对RSV G基因保守区序列设计分型引物,采用RT-PCR方法检测标本中RSV的基因组RNA.结果 390例标本中RSV阳性例数为133例(133/390,阳性率为34.10%).阳性标本中A亚型阳性129例,B亚型阳性4例.RSV阳性患儿中,84.9%为2岁以下小儿.2006年11月～2007年1月为RSV高发季节,RSV检测阳性率为55.6%～62.3%,2006年12月RSV检测阳性率最高.B亚型出现于本地区RSV感染低发季节(4、5、6月).RSV感染的临床表现主要为发热(56.4%)、咳嗽(98.5%)、喘息(63.9%)、气促(76.7%)、紫绀(84.9%).临床诊断依次为毛细支气管炎(33.1%),支气管肺炎(27.8%),间质性肺炎(18.1%),重症肺炎伴呼吸衰竭(10.5%),喘息性支气管炎(5.3%),支气管哮喘(4.5%).结论 本研究初步阐明了重庆地区两亚型RSV感染的流行病学特点,证实RSV是重庆地区冬春季婴幼儿ARI的重要病原,2006-2007年度以A亚型RSV流行为主.今后的研究将纳入门诊及社区惠儿并进行多年度连续监测以进一步阐明重庆地区两亚型RSV流行规律及病毒进化特点.     

呼吸道合胞病毒毛细支气管炎患儿血和痰中白三烯测定及临床意义

目的 探讨呼吸道合胞病毒(respiratory syncytial virus,RSV)毛细支气管炎(毛支炎)患儿血、痰中白三烯C4(leukotriene C4,LTC4)水平的变化及临床意义.方法轻-中度毛支炎组22例,重度毛支炎组11例,另选择无喘息非RSV感染性肺炎患儿12例作为对照(肺炎组).采用双抗体夹心酶联免疫吸附试验测定血清和痰中LTC4水平,并进行对比分析.结果急性期轻-中度毛支炎组、重度毛支炎组、肺炎组血清LTC4水平分别为(76.96±28.19)pg/ml、(103.53±16.85)pg/ml、(18.14±7.49)pg/ml;痰中LTC4水平分别为(31.83±19.14)pg/ml、(67.11±15.11)pg/ml、(6.81±2.90)pg/ml;恢复期血清LTC4水平分别为(36.04±16.38)pg/ml、(52.27±17.03)pg/ml、(18.14±7.49)pg/ml,3组间差异有统计学意义(F=48.09,P＜0.001;F=15.50,P＜0.001;F=44.43,P＜0.001).治疗后轻-中度和重度毛支炎组血清LTC4水平明显降低,但仍高于肺炎组,差异有统计学意义(P＜0.05).结论RSV毛支炎患儿血和痰中LTC4水平明显增高,并与病情的轻重相关.     

2000年冬-2006年春北京地区急性呼吸道感染患儿中呼吸道合胞病毒的监测

目的 对北京急性呼吸道感染患儿进行呼吸道合胞病毒（RSV）的监测并进行亚型分析,探讨其流行规律。方法 2000年11月-2006年3月,于首都儿科研究所附属儿童医院采集因急性呼吸道感染就诊的门诊及住院的患儿咽拭子或鼻咽分泌物标本10048份,接种于Hep-2细胞进行病毒分离,同时用免疫荧光法对鼻咽分泌物标本进行呼吸道病毒抗原的快速检测,对部分RSV阳性的标本用RT-PCR进行了亚型鉴定。结果 （1）在10048份标本中,有2286份为RSV阳性,阳性检出率为22．8％。其中病房标本7176份,RSV阳性2153份,阳性检出率为30．0％;门诊标本2872份,RSV阳性133份,阳性检出率为4．6％。（2）2000～2001年冬春、2002-2003年冬春、2004-2005年冬春RSV的阳性检出率分别为14．0％、18．2％和20．4％,而2001—2002年冬春、2003—2004年冬春和2005-2006年冬春RSV的阳性检出率分别为42．3％、41．0％和40．5％。（3）对938份RSV阳性标本的亚型监测结果：A亚型691份,占73．7％,B亚型247份,占26．3％,2000-2001、2004-2005年冬春季RSV感染以B亚型为主;而2001-2002、2002-2003、2003-2004年冬春季以A亚型为主;2005—2006年为A、B亚型同时流行。结论 RSV是冬春季婴幼儿下呼吸道感染的主要病毒病原,RSV呈现出隔年高峰的流行趋势,RSVA、B亚型是交替出现的,并且有时以相近的比例同时出现。     

Clinical course of hospitalised children infected with human metapneumovirus and respiratory syncytial virus

AIM: To describe the clinical presentation and outcomes of hospitalised patients infected with human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) in a tertiary hospital in Cape Town, South Africa. METHODS: hMPV was identified in 17 respiratory specimens submitted for viral studies during the period 2001-2003. These patients' medical folders were retrospectively reviewed for clinical, radiological and laboratory data, together with a convenience sample of 20 hRSV-infected patients. RESULTS: hMPV-infected patients were older than those infected with hRSV (P = 0.04) and required a longer hospital stay (P = 0.02). Presenting clinical signs and symptoms were similar between groups. Fourteen (87.5%) hMPV- and 16 (80%) hRSV-infected patients presented with co-morbid and/or immunosuppressive conditions (P > or = 0.5). The most common abnormalities on chest radiographs in both groups were bronchial wall thickening, focal consolidation and atelectasis. Six (37.5%) hMPV- and 11 (55%) hRSV-infected patients required admission to the paediatric intensive care unit (P > 0.1) with five (31.3%) hMPV- and eight (40%) hRSV-infected patients requiring intubation and ventilation (P > 0.5). Three (18.7%) hMPV-patients and three (15%) hRSV-infected patients died during this admission (P > 0.5). All hMPV-infected patients who died had significant co-morbid conditions. CONCLUSIONS: These data confirm that hMPV is a significant respiratory pathogen in this setting, with similar presentation and outcome to hRSV infection. This is the largest report of hMPV infection causing significant morbidity, prolonged hospital stay and death, associated with underlying risk factors.     

呼吸道合胞病毒毛细支气管炎42例白三烯致病作用研究

目的研究呼吸道合胞病毒(RSV)毛细支气管炎患儿在急性期和恢复期鼻咽分泌物中白三烯的水平,探讨白三烯在RSV毛细支气管炎发病中的作用。方法选取2003年11月至2004年3月在北京儿童医院呼吸病房住院的42例RSV毛细支气管炎患儿作为RSV毛细支气管炎组;选取同期不伴喘息的呼吸道感染患儿21例作为对照组,对照组患儿RSV抗原检测均为阴性。收集患儿的临床资料并进行临床评分,于入院第1～7天取患儿的鼻咽分泌物(nasopharyngeal secretion,NPS),用ELISA方法做白三烯C4(leukotriene C4,LTC4)的检测,同时测定NPS的蛋白质含量,用LTC4与蛋白的比值进行校正。应用SPSS11.5统计软件对数据进行统计分析。结果RSV毛细支气管炎组NPS中LTC4的质量质量浓度为14.89pg/μg,蛋白(0.21～149.18),而同期对照组为2.10pg/μg,蛋白(0.33～13.06),RSV毛细支气管炎组明显高于对照组,差异具有统计学意义(P=0.006);对毛细支气管炎组患儿入院第1天和第7天的白三烯质量浓度进行比较,NPS中的LTC4(P=0.561)稍有下降,但差异无统计学意义。根据临床评分,轻度组和中度组白三烯的质量浓度差异无统计学意义。结论RSV感染毛细支气管炎患儿NPS中LTC4的质量浓度明显高于对照组。入院第7天于临床症状明显好转时再次检测LTC4的质量浓度,无显著性改变,仍是增高的。根据临床评分轻度组和中度组白三烯的质量浓度差异无统计学意义。     

我国部分地区呼吸道合胞病毒分离株的亚型鉴定

为了解我国部分地区呼吸道合胞病毒（ＲＳＶ）的亚型分布情况，采用单克隆抗体和免疫荧光技术，对近年来从北京、广州、南京、长春、和ＲＳＶ感染爆发流行的津冀地区分离出的共１００株ＲＳＶ进行了亚型鉴定。结果：其中９７株为Ａ亚型，３株为Ｂ亚型。提示：近年来这些地区无论是南方还是北方流行的ＲＳＶ主要为Ａ亚型；津冀地区流行性喘憋性肺炎的爆发流行也与Ａ亚型有关。     

Use of permissive hypercapnia in the ventilation of infants with respiratory syncytial virus infection

We wished to retrospectively evaluate the effects of permissive hypercapnia (PHY) on barotrauma, mortality and length of stay when applied to ventilated infants with respiratory syncytial virus (RSV) bronchiolitis. Nineteen control infants with RSV induced respiratory failure were treated with conventional ventilation (April 1991–January 1994), after which time PHY was adopted as unit policy. A further 28 infants were then treated with PHY (January 1994–April 1996). Demographic and physiological data were collected from admission, and outcome variables including length of stay, barotrauma and mortality were recorded. The PHY group showed a significantly higher mean pCO₂ (7.6 vs 5.2 kPa), a lower mean pH (7.34 vs 7.40), and a reduction in maximal peak inspiratory pressures (25 vs 30 cmH₂O). Mortality, barotrauma, use of neuromuscular blockade and nosocomial infection did not differ between groups. There was a trend towards increased length of ventilation in the PHY group (median 7 vs 5 days). Conclusion Based on this retrospective data we can show no benefit for the use of permissive hypercapnia as a ventilatory strategy in this patient group. A prospective randomised controlled trial is warranted to accurately assess the outcome variables and cost implications of this strategy. Received: 22 June 1998 / Accepted in revised form: 25 August 1998     

Risk of concurrent bacterial infection in preterm infants hospitalized due to respiratory syncytial virus infection

OBJECTIVE: To evaluate the risk of concurrent bacterial infection in preterm infants hospitalized due to respiratory syncytial virus (RSV) disease. PATIENTS AND METHODS: Retrospective cohort analysis of all infants hospitalized due to RSV infection between January 1, 2001 and July 31, 2005. Patients were identified by ICD-10 diagnosis of RSV infection including codes J21.0, J21.9, J12.1, J20.5 and B97.4. Medical charts were reviewed and RSV infection had to be confirmed by positive antigen detection test on nasopharyngeal aspirates. RESULTS: A total of 464 infants had been hospitalized due to RSV infection and 42 (9.1%) were born<37 weeks of gestational age. Concurrent bacterial infections were diagnosed by either positive blood or urine cultures, stool culture, tracheal aspirates or smears in 4 of 42 preterm (9.5%) compared to 13 of 422 term (3.1%) infants (p=0.017, RR 3.092, CI 95% 1.251-7.641). Excluding the infants admitted to the intensive care unit (ICU) the total rate of bacterial co-infection was 1.9%. Ten of 42 preterm (23.8%) compared to 25 of 422 term (5.2%) infants were referred to ICU (p<0.001, RR 3.349, CI 95% 1.882-5.959). All preterm infants had pneumonia, and isolates were Streptococcus pneumoniae, Chlamydia pneumoniae and Streptococcus pneumoniae with Haemophilus influenzae. Mean length of stay in preterm infants with bacterial co-infection was 22.3 days compared to 10.3 days without bacterial co-infection (p<0.006). CONCLUSION: The overall low risk of concurrent bacterial infection was significantly increased in preterm infants associated with prolonged hospitalization and ICU admission.     

WU多瘤病毒与呼吸道合胞病毒感染患儿临床特征比较

目的探讨和比较WU多瘤病毒(WUPyV)以及呼吸道合胞病毒(RSV)所致呼吸道感染患儿的临床特征。方法应用多重PCR技术,检测呼吸道感染住院患儿WUPyV、RSV等病毒感染情况,并收集WUPyV和RSV感染患儿的临床资料。结果 2008年1月至2010年9月,在1 701例呼吸道感染住院患儿的咽拭子标本中检测出WUPyV阳性46例(2.7%),RSV阳性365例(21.5%);单纯WUPyV感染为22例(47.8%),单纯RSV感染为88例(24.1%)。RSV感染患儿的合并感染率高于WUPyV感染患儿,两者差异有统计学意义(χ2=11.723,P=0.001)。WUPyV阳性检测率在春季呈现高峰,RSV则在冬季。WUPyV感染患儿的中位年龄为26.2个月,RSV感染患儿为14.9个月,两者差异有统计学意义(U=669.5,P<0.05)。WUPyV感染患儿的临床表现和体征与RSV感染相似,咳嗽(χ2=13.34,P<0.001)和喘息(χ2=10.53,P<0.001)在RSV感染的患儿中更为多见。WUPyV感染后主要被诊断为支气管肺炎,而RSV感染后主要为毛细支气管炎。单纯RSV感染患儿更多需要激素治疗(χ2=9.321 P=0.002)。结论部分患儿呼吸道感染与WUPyV感染有关,WUPyV感染的临床特征与RSV感染类似。     

Risk factors for mechanical ventilation in respiratory syncytial virus infection

In a prospective study, risk factors for mechanical ventilation were identified in 102 patients with respiratory syncytial virus (RSV) infection admitted to the Sophia Children's Hospital, Rotterdam. Age, weight on admission and prematurity were associated with the need for mechanical ventilation. Using multivariate analysis, only low weight was an independent risk factor for mechanical ventilation. For infants weighing less than 5 kg the relative risk for mechanical ventilation was 4.4 (95% confidential interval 1.3–13.9).     

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS])

Aim

We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection.

Methods

This survey‐based, observational study was conducted during 2014–2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important).

Results

The five most important factors for parents were: healthcare professionals’ awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support.

Conclusion

The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.     

1978—1996年广州地区呼吸道合胞病毒感染分析

为了解广州地区儿童呼吸道合胞病毒（ＲＳＶ）感染的情况，采用病毒分离等方法，对广州地区１９７８～１９９６年连续１８年的儿童支气管炎和支气管肺炎进行了ＲＳＶ病原学检测。共检测患儿５２７３例，分离出ＲＳＶ的患儿５１３例。病毒分离总阳性率９．７％。１８年中以１９８５年、１９８６年和１９９２年ＲＳＶ分离率最高；一年中ＲＳＶ分离率从３月份开始增高，４月份达高峰，持续至５～８月，９月份开始下降。结论：１８年来广州地区有过３次ＲＳＶ感染流行高峰（１９８５年、１９８６年、１９９２年）；广州地区ＲＳＶ感染的流行季节主要发生在每年的春夏季。