Substantial variability in community respiratory syncytial virus season timing

BACKGROUND: Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children. Prevention of RSV disease in children in certain high risk groups through use of immunoglobulin preparations has been recommended by the American Academy of Pediatrics since 1998. A more precise understanding of the timing of annual RSV epidemics should assist providers in maximizing the benefit of these preventive therapies. The objective of this study was to determine whether current national RSV surveillance data could be used to define the timing of seasonal outbreaks METHODS: Weekly RSV testing data from the National Respiratory and Enteric Viruses Surveillance System for the period July 1990 through June 2000 were analyzed. RSV season onset week, peak week and duration were calculated for the entire United States, Census regions and select local laboratories. Season variability was estimated by comparing calculations for individual RSV seasons to median measurements for the entire surveillance period RESULTS: RSV seasons in the South region began significantly earlier (P < 0.05) and lasted longer (P < 0.05) than seasons for the rest of the nation. RSV seasons in the Midwest region began significantly later (P < 0.01) and were shorter (P < 0.05) than those for the rest of the nation. Local RSV seasons varied substantially by year and by laboratory. The variability between laboratories generally increased with distance between laboratories CONCLUSIONS: Onset weeks and durations of RSV seasons vary substantially by year and location. Local RSV data are needed to accurately define the onset and offset of RSV seasons and to refine timing of passive immune prophylaxis therapy recommendations.     

Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection

Aim: To explore the relationship between cytokine responses and severity of respiratory syncytial virus (RSV) infection in infants. Methods: Intracellular interleukin-4 (IL-4) and interferon- γ (IFN- γ) expression in peripheral blood CD3 + and CD8 + lymphocytes was measured by four-colour flow cytometry. Serum IL-12, IL-4 and IFN- γ levels were also determined by enzyme-linked immunosorbent assay. Results: The frequency of IL-4 and IFN- γ expression in CD3 + CD8 - cells was the same in RSV-infected, non-RSV-infected and control infants and in those with RSV bronchiolitis or RSV pneumonia, indicating that no Th2 predominance exists in the acute phase of RSV infection and RSV bronchiolitis. Furthermore, RSV-infected infants had a more frequent IFN- γ expression in CD3 + CD8 + cells than controls, and they also showed a much lower serum IL-4/ IFN- γ ratio because of decreased IL-4 and elevated IFN- γ, the latter being most prominent in RSV bronchiolitis. The serum IL-12 level in RSV-infected infants was the same as in control infants, while those with non-RSV infections had a much higher level. Serum IL-12, IFN- γ and frequency of IFN- γ expression in CD3 + CD8 + cells in mild RSV infection were much higher than in controls, while no difference existed between severe cases and controls.

Conclusion: Type 2 cytokine predominance was not found in the acute phase of RSV infection and RSV bronchiolitis, but both were accompanied by enhanced production of IFN- γ and a much higher serum IFN- γ level than in healthy controls, especially in those with RSV bronchiolitis, suggesting a role in causing airway obstruction. IFN- γ and IL-12 may also play a protective role in RSV infections by diminishing viral replication, and high levels of IL-12 and IFN- γ may be associated with lessening of the severity of infection.     

IL-13基因多态性与RSV感染后婴幼儿喘息发病的关系

目的 探讨IL-13 Arg110Gln基因多态性与呼吸道合胞病毒(RSV)感染后喘息发作的关系.方法 根据临床表现,将RSV感染者分为无喘息组和喘息组,取其颊黏膜细胞,提取DNA,用实时PCR法对IL-13Arg110Gln基因检测,分析基因多态性与喘息发生和病情之间的关系.结果 在RSV感染患儿中存在IL-13Arg110Gln位点不同,在喘息组,A和G碱基的发生频率分别为58.92%、41.07%,而在无喘息组A和G碱基的发生频率则分别是44.39%、55.61%,两组比较差异有统计学意义.AA型较GG型患儿喘息发作病情重,住院天数多,差异有统计学意义.另外,AA型患儿IgE和嗜酸性细胞阳离子蛋白(ECP)水平明显高于GG型.结论 IL-13Arg110Gln多态性AA基因型与RSV感染后婴幼儿喘息的发病相关.     

Pathogenesis of respiratory syncytial virus disease in infancy

In a series of 54 children under 1 year old with respiratory syncytial virus infection, the highest proportion of severe illnesses (bronchiolitis and pneumonia), and the highest proportion of `slow'' antibody responses, were found in children under 6 months. Severe illness may therefore be related to immunological immaturity and to lack of protection by maternal antibody, rather than to an allergic response as has been suggested. A high male to female ratio (approximately 2: 1) was found both in the present series, and in two larger series of respiratory syncytial virus infection in infants.     

Relationship between clinical severity of respiratory syncytial virus infection and subtype

The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.     

Lower airway disease caused by respiratory syncytial virus

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and young children. Most infections due to RSV are mild and do not require hospitalization. RSV causes both upper respiratory tract infections as well as lower respiratory tract infections. Infants with underlying disease states like bronchopulmonary dyslasia, congenital heart disease and prematurity appear more prone to develop severe infection and have a higher incidence of hospitalization. The exact pathogenesis of RSV is not well understood. The mortality associated with primary RSV infection in healthy children is estimated to be between .005% to .02%. In hospitalized children the mortality rate is estimated to be from 1% to 3%. Several treatment modalities in the form of bronchodilators, corticosteroids, ribavirin, intravenous immune gammaglobulin and antibiotics are available. Studies have failed to show the true beneficial effect of any of the above treatment modalities. Supportive care is only needed. The best treatment is the supportive care in the form of oxygen and fluids and close monitoring of the vital signs including oxygen saturation.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.     

伴胼胝体发育不良的家族性痉挛性截瘫1例报告

家族性痉挛性截瘫 (ｆａｍｉｌｉａｌｓｐａｓｔｉｃｐａｒａｐｌｅｇｉａ ,ＦＳＰ)又称遗传性痉挛性截瘫或Ｓｔｒ櫣ｍｐｅｌｌ病 ,主要病理变化为脊髓的锥体束、后索、脊髓小脑束变性 ,临床以缓慢进行性双下肢痉挛性截瘫为特征。遗传方式可为常染色体显性或隐性遗传 ,也可为性链锁遗传。临床症状在各家系间或同一家系内均可能有所变异 ,因此 ,有人认为ＦＳＰ可能是由几个疾病单元组成的一个综合征[1] 。近代日本学者发现一组ＦＳＰ并发胼胝体菲薄的复合型ＦＳＰ患者[2～ 5] ,欧美亦有同样个案报道[6～ 7] 。但尚未见于国内文献 ,故报告如下…     

Respiratory syncytial virus: G gene genotype and disease severity

BACKGROUND: In a hospital-based study by Martinello (2002), specific G gene genotypes of respiratory syncytial virus subgroup A virus were associated with an increased severity of illness. AIM: We sought to confirm the association of G genotypes with disease severity in a population-based study. MATERIAL AND METHODS: Ninety-one type A respiratory syncytial viruses (identified in the 1999/2000 season by polymerase chain reaction and cell culture), collected in a German multicenter study (PRI.DE) were analyzed for G gene diversity (amino acids 1-165). Disease severity was classified according to World Health Organization criteria for pneumonia in outpatients and by a bronchiolitis score (Rodriguez, 1997) in inpatients. Multiple regression analysis was used to explain disease severity. RESULTS: Three clusters were identified (cluster 1, n = 35; cluster 2,n = 35; cluster 3, n = 21). Sixty-seven patients had severe disease. After controlling for other variables, illness severity was significantly greater for cluster 2 viruses (odds ratio, 7.0; 95% confidence interval, 1.6 49), compared with viruses in other clusters. Other known risk factors (male gender, age) were not associated with disease severity. Our cluster 2 is genetically distinct from the virulent genotype in Martinello's study. DISCUSSION: Previously reported associations between G genotypes and disease severity in hospitalized patients can be generalized across the spectrum of illnesses including outpatients. The association seems not to be linked to a specific G gene structure. Rather G gene diversity in combination with the susceptibility of the host cohort may form the basis of such associations. Because of the magnitude of the effect, the underlying mechanisms warrant further investigation.     

Current strategies in the prevention of respiratory syncytial virus disease

Infants infected with respiratory syncytial virus (RSV) develop both upper and lower respiratory tract infections resulting in laryngotracheobronchitis, bronchiolitis and pneumonia. Premature infants of less than 32 weeks' gestation and those with underlying chronic lung disease are particularly susceptible and incur significant morbidity and mortality following hospitalisation. Conservative RSV prevention strategies focus on the interruption of transmission by proper hand-washing techniques and reducing exposure to potential environmental risk factors. Major challenges have impeded the development of an RSV vaccine but a licensed product may be expected in the near future. Prophylaxis with a humanised mouse monoclonal antibody (palivizumab) has been effective in reducing the rate of RSV hospitalisation in high-risk premature infants in phase II-IV trials and is available for use within internationally approved guidelines. Experimental studies evaluating the use of palivizumab in patients with congenital heart disease, those with cystic fibrosis and immunosuppressed bone marrow transplant recipients are well underway, the results of which are eagerly awaited.     

Decreased innate immune cytokine responses correlate with disease severity in children with respiratory syncytial virus and human rhinovirus bronchiolitis

The immunopathogenesis of respiratory syncytial virus (RSV) and human rhinovirus lower respiratory tract infections in children remains to be defined. We measured nasal wash concentrations of 29 cytokines in infants with RSV or human rhinovirus lower respiratory tract infections. Concentrations of interferon-γ in RSV and innate immunity cytokines in both infections inversely correlated with disease severity.     

Features of respiratory syncytial virus

Respiratory syncytial virus infects almost all of us in early childhood and causes most cases of bronchiolitis – the most common reason to be admitted to hospital under 1 year of age in the developed world. Each winter, paediatric wards are tested by predictable epidemics of unpredictable intensity. Trials of vaccination in the 1960s were associated with catastrophic enhanced illness leading to intense research that has enriched immunology and virology as a whole. Treatment is still supportive but with modern facilities and training survival rates are high even in severe disease. Post bronchiolitis wheeze is common and hard to treat but new therapies are being proposed. Possible links between severe bronchiolitis atopy and asthma are still under investigation.     

Preventing respiratory syncytial virus infections

Respiratory syncytial virus infection is the leading cause of lower respiratory tract infections in young children. Palivizumab, a respiratory syncytial virus-specific monoclonal antibody, reduces the hospitalization rate of high-risk children but it is very costly. This statement replaces three previous position statements from the Canadian Paediatric Society about this topic, and was updated primarily to discuss recent changes in the American Academy of Pediatrics guidelines in the Canadian context. It reviews the published literature and provides recommendations regarding palivizumab use in high-risk children.     

The severity of respiratory syncytial virus bronchiolitis in young infants in the United Arab Emirates

Respiratory syncytial virus (RSV) respiratory infections are very common during infancy and account for the majority of hospitalizations during the fall and winter seasons. Patients vary in the severity of their illnesses, with most hospitalized patients needing oxygen and intravenous fluids. The objective of this study was to assess in hospitalized patients the severity of the disease in relation to age. We compared children who were <90 days old with children who were >90 days old for the duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. We conducted a retrospective case review of national children <2 years admitted to the pediatric ward at Sheikh Khalifa Medical City with RSV proven bronchiolitis/pneumonia over a 3-month period from 1 September to 30 November 2001. Morbidity for group 1 (birth-90 days) and group 2 (91 days-2 years) was compared by the Mann-Whitney U-test using duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. Multiple regression for duration of oxygen therapy was tested using the following risk factors as predictors: age group (1 or 2), previous ventilation, bronchopulmonary dysplasia (BPD) and prematurity. A total of 89 patients were admitted during this period. The mean age (SD) of group 1 (n = 28) and group 2 (n = 61) was 46.35 (25.57) days and 275.67 (156.79) days, respectively. The only statistically significant difference using the Mann-Whitney U-test was detected for duration of oxygen between the groups (p = 0.002). Using multiple regression, only age group acted as a predictor for duration of oxygen therapy (p < 0.001). This implies that the youngest children, group 1, are at a risk for prolonged oxygen therapy. Four patients from group 1 were admitted to the intensive care unit, of which two received ventilatory support. RSV respiratory infections affect infants <3 months old in a more severe form than older infants. Even though overall duration of stay was similar for both groups, young infants who in fact did require oxygen had a more protracted and severe illness compared with the older infants. This was evidenced by their longer duration of oxygen and more frequent need to be managed in the intensive care unit.