上海地区儿童急性呼吸道病毒感染的流行特征

目的 了解近年上海地区呼吸道合胞病毒(RSV)、甲型和乙型流感病毒(IV-A和IV-B)、副流感病毒1、2、3型(PIV-1、2、3)以及腺病毒(ADV)在急性呼吸道感染住院儿童中的流行特征.方法 回顾性分析2003-2006年连续4年复旦大学附属儿科医院收治入院的急性呼吸道感染儿童鼻咽吸取物7种常见呼吸道病毒的检出情况以及季节和年龄分布特点.直接免疫荧光法检测病毒.年龄分布比较作非参数检验.结果 4年期间共收集11214例患儿标本,其中98.7%取自急性下呼吸道感染,7种病毒总的阳性检出率为24.2%,其中RSV阳性率为17.7%,PIV-3为2.8%,ADV为2.2%,IV-A为0.7%,PIV-1为0.5%,PIV-2为0.3%,IV-B为0.1%,混合感染为0.2%.RSV通常在冬、春季流行,夏季很少检出,每2年RSV流行季节提前至秋季开始,持续流行较长时间.PIV-3、ADV和IV全年散发,某些月份时有流行.无固定的流行规律.病毒感染患儿年龄中位数RSV为4个月、PIV-3为8个月、PIV-1为9.5个月、PIV-2为10.5个月、ADV为12个月、IV为13个月,差异有统计学意义(X2154.319,P<0.01).RSV感染率随患儿年龄增长而降低,PIV-3在婴幼儿人群中感染率较高,ADV在1岁及以上儿童中感染率较高.结论 RSV是上海地区儿童呼吸道感染最常见的病毒病原,要幼儿易感,春、秋和冬季都有流行,PIV-3是第2位常见病原.感染儿童以婴幼儿常见,ADV是第3位常见病原,感染儿童年龄较大,IV检出率低,未出现ADV和IV在上海地区儿童中暴发流行.     

Epidemiology of acute viral respiratory tract infections in Korean children

OBJECTIVE: Viruses are the most common causes of respiratory tract infection in children. We investigated the aetiologies and the epidemiological features of acute viral respiratory tract infections in Korean children. METHODS: We tried to isolate respiratory syncytial virus (RSV) and parainfluenza virus from January 1994, influenza virus from February 1995, and adenovirus from April 1996 through August 1998, and identified the isolated viruses by indirect immunofluorescence (IF) staining in the children hospitalized with acute respiratory tract infections (ARTI). RESULTS: Virus was identified in 360 of 1389 (25.9%) nasopharyngeal aspirates cultured. Of a total of 392 viruses, 164 (41.8%) RSV, 90 (23%) parainfluenza virus, 66 (16.8%) influenza A virus, 54 (13.8%) adenovirus, and 18 (4.6%) influenza B virus were cultured, including cases in mixed viral infections. The male to female ratio of the culture-positive patients was 2:1, and the proportions of the patients aged >6 months, 6-11 months, 1, 2, 3, 4, 5, 6-7, 8-9, and >10 years were 22.5, 29.5, 25.7, 9.5, 3.8, 3.8, 1.7, 1.7, 1.2, and 0.6%, respectively. The major clinical diagnosis was bronchiolitis for RSV, croup for parainfluenza virus, and pneumonia for adenovirus and influenza virus. Infections by RSV, parainfluenza virus, and influenza virus occurred in annual epidemics, and infections by adenovirus occurred annually with or without epidemics. There were somewhat larger epidemics by adenovirus and influenza virus in May to July 1996 and March to June 1997, respectively. CONCLUSIONS: Viral agents are one of the main aetiologies and the main causes of admission in Korean children with ARTI.     

Longitudinal study of acute respiratory diseases in Rio de Janeiro: occurrence of respiratory viruses during four consecutive years.

The occurrence of different viruses in nasopharyngeal secretions from children less than 5 years old with acute respiratory infections (ARI) was investigated over a period of 4 years (1982-1985) in Rio de Janeiro. Of the viruses known to be associated with ARI, all but influenza C and parainfluenza types 1, 2 and 4 were found. Viruses were found more frequently in children attending emergency or pediatric wards than in outpatients. This was clearly related to the high incidence of respiratory syncytial virus (RSV) in the more severe cases of ARI. RSV positive specimens appeared mainly during the fall, over four consecutive years, showing a clear seasonal occurrence of this virus. Emergency wards provide the best source of data for RSV surveillance, showing sharp increase in the number of positive cases coinciding with increased incidence of ARI cases. Adenovirus were the second most frequent viruses isolated and among these serotypes 1, 2 and 7 were predominant. Influenza virus and parainfluenza virus type 3 were next in frequency. Influenza A virus were isolated with equal frequency in outpatient departments, emergency and pediatric wards. Influenza B was more frequent among outpatients. Parainfluenza type 3 caused outbreaks in the shanty-town population annually during the late winter or spring and were isolated mainly from outpatients. Herpesvirus, enterovirus and rhinovirus were found less frequently. Other viruses than RSV and parainfluenza type 3 did not show a clear seasonal incidence.     

Pulmonary infections with respiratory syncytial virus and the parainfluenza viruses

Respiratory syncytial virus (RSV) and the parainfluenza viruses (PIVs) are the most important causes of acute lower respiratory illness (LRI) in infants and children under 6 years of age. These enveloped viruses are members of the paramyxovirus family. They infect cells in the epithelium lining the trachea and intrapulmonary airways, and cause croup, bronchitis, bronchiolitis, and bronchopneumonia. RSV causes annual midwinter to early spring outbreaks of respiratory disease in temperate climates; epidemics are heralded by the appearance of increased numbers of cases of bronchiolitis, primarily in children under 2 years of age. PIV serotypes 1 and 2 cause epidemics of croup in the fall months. Infections with PIV serotype 3 can occur in an endemic pattern throughout the year, or may occur as outbreaks, usually in the fall or spring. Croup and bronchiolitis are the most common syndromes of PIV-3 LRI. Infection with these viruses induces short-lived partial resistance to reinfection, but the human host remains susceptible to reinfection with these agents throughout life. While antibody in respiratory secretions is related most directly to resistance to reinfection, cell-mediated immune responses are crucial for limitation and termination of established infection. Current research efforts are directed at more thorough characterization of the developing host immune response to individual viral antigens, and to development of methods for immunization using specific virion peptides. Recently, antiviral therapy has become available for serious RSV infection in young infants.     

Impact of respiratory syncytial virus infection as a cause of lower respiratory tract infection in children younger than 3 years of age in Japan

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral pathogen for lower respiratory tract infection (LRI) in infants and children. An RSV-specific monoclonal antibody has been developed to provide prophylaxis against RSV associated LRI (RSV-LRI). The objective of this study was to determine the impact of RSV as a cause of LRI in children younger than 3 years of age to provide data to aide in the implementation of forthcoming prophylaxis against RSV. METHODS: We analyzed the viral etiology of LRI in hospitalized Japanese children younger than 3 years of age admitted to Shizuoka Red Cross Hospital from July, 1997 to June, 2000. RESULTS: A total of 535 patients younger than 3 years of age were hospitalized with LRI at Shizuoka Red Cross Hospital from July 1, 1997 to June 30, 2000. Of these, a positive diagnosis of RSV infection was made in 168 patients (31.4%). Most of the patients with RSV infection had been well and had had no underlying disease that was defined as risk factor of RSV infection (94.0%). The peak incidence of LRI was observed in the winter each year and the number of LRI was strongly associated with the epidemic of RSV (r=0.700, P<0.0001). The number of patients with LRI younger than 6 months of age was 116 (21.7%). Of these 116 patients younger than 6 months with LRI, 55 patients (47.4%) were confirmed to have RSV infection. The proportions of RSV infection to total LRI was greatest in early infants younger than 6 months (P<0.0001). The number of patients with which RSV infection was detected in LRI patients younger than 3 years was highest during the first five months of life and there was a dramatic decrease in incidence of RSV infection with increasing age thereafter. CONCLUSIONS: The incidence of LRI hospitalization is highly affected by RSV infection epidemic. The proportion of RSV infections among early infants younger than 6 months is greater than that of older patients. The prophylaxis against RSV will be needed to be toward early infants.     

Progress in respiratory virus vaccine development

Viral respiratory infections cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. Although many viral pathogens are capable of causing respiratory disease, vaccine development has to focus on a limited number of pathogens, such as those that commonly cause serious lower respiratory illness (LRI). Whereas influenza virus vaccines have been available for some time (see the review by Clark and Lynch in this issue), vaccines against other medically important viruses such as respiratory syncytial virus (RSV), the parainfluenza viruses (PIVs), and metapneumovirus (MPVs) are not available. This review aims to provide a brief update on investigational vaccines against RSV, the PIVs, and MPV that have been evaluated in clinical trials or are currently in clinical development.     

Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy

Viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. However, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (LRI) are unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in infants to the induction of innate inflammatory responses. This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines. We prospectively examined previously naive infants in Buenos Aires, Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection with human metapneumovirus (hMPV) was second only to RSV in frequency. Both viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV elicited significantly lower levels of respiratory inflammatory cytokines than did RSV. Symptoms in infants infected with influenza virus were different from those in infants infected with RSV, but cytokine responses were similar. These findings suggest that hMPV and RSV either cause disease via different mechanisms or share a common mechanism that is distinct from innate immune activation.     

Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997

A 1985 estimate that 4500 respiratory syncytial virus (RSV)-associated deaths occur annually among US children has not been updated using nationally representative data. Thus, 1979-1997 multiple cause-of-death records for children <5 years old listing bronchiolitis, pneumonia, or any respiratory tract disease were examined. Deaths among children associated with any respiratory disease declined from 4631 in 1979 to 2502 in 1997. During the 19-year study period, 1806 bronchiolitis-associated deaths occurred (annual mean, 95 deaths; range, 66-127 deaths). Of these deaths, 1435 (79%) occurred among infants <1 year old. Congenital heart disease, lung disease, or prematurity was listed in death records of 179 (9.9%), 99 (5.5%), and 76 (4.2%) children dying with bronchiolitis, respectively. By applying published proportions of children hospitalized for bronchiolitis or pneumonia who were RSV-infected to bronchiolitis and pneumonia deaths, it was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.     

The impact of infection with human metapneumovirus and other respiratory viruses in young infants and children at high risk for severe pulmonary disease

We conducted a prospective, observational study to characterize the clinical manifestations of respiratory infections caused by human metapneumovirus (hMPV) and other viruses in 194 premature infants and young children with chronic lung disease or congenital heart disease in Buenos Aires. Children had 567 episodes of respiratory illness and were monitored until they were 2 years old or until the completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of moderate or greater severity. Human parainfluenza virus type 3 caused 24 infections (4%), and 5 (25%) of 20 lung infections led to hospitalization. Respiratory syncytial virus (RSV) caused 33 episodes--17% of infections and 32% of hospitalizations during the respiratory season. None of the 10 children infected with influenza virus had severe disease. The present study of at-risk children suggests that hMPV and influenza virus are infrequent agents of severe disease and highlights the need for preventive interventions against RSV in developing countries.     

Health care-acquired viral respiratory diseases

Health care-associated viral respiratory infections, common among hospitalized children, also occur among adults and institutionalized persons and result in increased patient morbidity, mortality, and health care costs. Approximately 20% of patients with healthcare-associated pneumonia have viral respiratory infections, with 70% of these infections caused by adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV). These infections typically reflect the level of viral activity within the community. This article focuses on the epidemiology, transmission, and control of health care-associated RSV and influenza virus.     

Patterns of shedding of myxoviruses and paramyxoviruses in children

In the Houston Family Study, young children were cultured for virus weekly or biweekly and during acute respiratory illnesses. The interval between the onset of illness and positive culture was examined for 179 infections during 1975-1979. In week 1 after onset, 73%, 73%, and 66% of cultures were positive for influenza A virus, respiratory syncytial virus (RSV), and parainfluenza virus type 3, respectively. Pooled data from influenza B virus infections in 1977 and 1980 showed that 73% of cultures were positive in week 1. Influenza A virus in week 2 or RSV in weeks 2 and 3 was isolated from very few children. However, 37% of cultures were positive for influenza B virus during week 2, and 17% of cultures were still positive for parainfluenza virus type 3 during week 3. Shedding of parainfluenza virus type 3 on days 29-38 was also observed. Parainfluenza virus type 3, RSV, and influenza A virus were isolated up to six days before the onset of illness.     

Viruses associated with acute lower respiratory tract infections in children from the eastern highlands of Papua New Guinea (1983-1985)

This study, conducted at Goroka Hospital from January 1983 to June 1985, examined the viruses identified in nasopharyngeal aspirates (NPA) and urines collected from 716 hospitalised children with moderate or severe pneumonia, in NPA from 170 children with mild pneumonia treated as outpatients and in NPA from a control group of 428 children attending the outpatient department of Goroka Hospital suffering from minor ailments other than upper or lower respiratory tract infections. One or more viruses were identified from 68%, 51% and 43% of children with moderate or severe pneumonia, mild pneumonia and the control group, respectively. One-third of viruses were identified in conjunction with another virus in both control and sick children. Viral identification rates were highest in children under 1 year of age. Cytomegalovirus, adenoviruses, respiratory syncytial virus (RSV), measles and rhinoviruses were the most frequently identified viruses. RSV was associated with mild as well as moderate and severe disease. No virus was associated with an increased risk of death. Annual epidemics of RSV occurred during the wet season. An epidemic of influenza A virus and also influenza B virus and 3 epidemics of parainfluenza 3 virus occurred during the study period. The high viral identification rates in this study suggest a high frequency of transmission associated with the social structure and environment of Papua New Guinean highland villages and high population mobility.     

Mortality caused by influenza and respiratory syncytial virus by age group in England and Wales 1999–2010

Please cite this paper as: Hardelid et al. (2012) Mortality caused by influenza and respiratory syncytial virus by age group in England and Wales 1999–2010. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00345.x. Background: The mortality burden caused by influenza cannot be quantified directly from death certificates because of under‐recording; therefore, the estimated number of influenza deaths has to be obtained through statistical modelling. Objective: To estimate the number of deaths caused by influenza and respiratory syncytial virus (RSV) in England and Wales between 1999 and 2010 using a multivariable regression model. Methods: Generalised linear models were used to estimate weekly deaths by age group (<15, 15–44, 45–74 and 75+ years) as a function of positive influenza and RSV isolates. Adjustment was made for temperature variation (using weekly means of daily Central England temperature time series), underlying seasonal variation and temporal trends. The parameters from the model were used to predict the number of deaths caused by influenza and RSV across winter seasons. Results: Between 7000 and 25 000 deaths across all ages were associated with influenza in the winter periods 1999–2009. The mortality burden was the highest among the over 75 age group, among whom 2·5–8·1% of deaths were caused by influenza. The lowest number of influenza deaths was estimated for the winter 2009/2010 when pandemic influenza A/H1N1 (2009) was the predominant circulating strain. RSV accounted for 5000–7500 deaths each winter season. Conclusions: The model presented provides a robust and reasonable approach to estimating the number of deaths caused by influenza and RSV by age group at the end of each winter.     

Correlation between respiratory syncytial virus genotype and severity of illness

Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract infections, but the viral factors associated with virulence remain unknown. To determine whether RSV genotype correlated with severity of illness, isolates were characterized by phylogenetic analysis of the RSV G gene, and a composite score was used to quantify severity of illness. During the 1998-1999 and 1999-2000 winter seasons, 137 subgroup A and 84 subgroup B isolates were identified. The severity of illness caused by subgroup A isolates did not differ from that caused by subgroup B isolates (P=.086). However, the GA3 clade was associated with significantly greater severity of illness, compared with clades GA2 (P=.004) and GA4 (P=.016). In a subpopulation of patients < or =24 months old who had no known risk factors for severe RSV disease, clade GA3 was again associated with greater severity of illness, compared with clade GA2 (P=.018). Severity of RSV infection is associated with RSV genotype.     

A single-season prospective study of respiratory viral infections in lung transplant recipients.

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.