Respiratory syncytial virus

RSV is now understood to be the most significant viral respiratory pathogen of infants and is capable of causing both bronchiolitis and pneumonia. It is a particular risk to hospitalized infants as the virus is easily spread through close contact. The most vulnerable infants are those who suffer with either congenital heart disease or bronchopulmonary dysplasia who easily fall prey to pulmonary complications of infection. Strict environmental control and the use of protective clothing and eyewear should be implemented to decrease the nosocomial spread of RSV. Available diagnostic studies include viral isolation, fluorescent antibody stains, and enzyme immunoassays. Treatment of the disease is usually supportive but hospitalized patients frequently benefit from aerosolized ribavirin therapy. Hopefully, current vaccine trials will be successful and this pathogen will not only be treatable but will also be preventable.     

Role of respiratory syncytial virus in acute otitis media: implications for vaccine development

We summarize herein the results of various virologic studies of acute otitis media (AOM) conducted at our site over a 10-year period. Among 566 children with AOM, respiratory syncytial virus (RSV) was the most common virus identified in either middle ear fluid or nasal wash; it was found in 16% of all children and 38% of virus-positive children. Seventy-one percent of the children with RSV were 1 year of age or older, which was significantly older than all other viruses combined (P=0.045). RSV infection was associated with the common bacterial pathogens causing AOM. Past efforts to develop vaccines for RSV have emphasized prevention of lower respiratory tract infection in infants, which is a more serious problem but less common than AOM. Our results suggest that RSV vaccines that work only against infection in older children may have value in preventing AOM, the most common pediatric disease.     

Respiratory syncytial virus vaccine development

Development of an RSV vaccine for infants has been hindered by the lack of an ideal animal model that exhibits disease, and the challenge of effectively immunizing very young infants who are immunologically immature. Nevertheless, significant progress has been made recently in developing live attenuated viruses and protein subunit vaccine candidates. Numerous vaccine candidates are currently in early clinical trials. This paper reviews the significant obstacles to development of RSV vaccines, and the progress made to date.     

Respiratory syncytial virus suppression of the antiviral immune response: Implications for evaluation of candidate vaccines

Respiratory syncytial virus infections recur throughout life despite induction of immunity by the first natural infection. Results of an extensive series of studies indicate that the virus adversely affects the human antiviral recall response to challenge, although subsequent infections are less severe than the initial illness. The observations suggest that candidate vaccines for respiratory syncytial virus should not be expected to prevent clinical illness upon subsequent exposure. Candidate vaccines may be considered effective if they render a subsequent natural infection less severe. This is what would be expected from an initial and commonly more severe natural infection and sensitization.     

Respiratory syncytial virus infection in high-risk infants

The authors describes the frequency of respiratory syncytial virus (RSV) infections in high risk infants in ten hospitals, between 01.02.1999.-15.03.1999. RSV antigen test were performed from the nasopharyngeal or throat swabs of 58 infants with respiratory tract infections. Thirteen patients were positive. Among them 11 were prematures. Six infants were still receiving treatment in Neonatal Intensive Care Unit, while seven infants were readmitted to a Pediatric Intensive Care Unit. Distribution of risk factors (prematurity, bronchopulmonary dysplasia, ventilation in newborn period, smoking in the family, unseparated brothers or sisters) in patients were comparable with the data of literature. Eight infants needed head box O2-therapy. No deaths were detected. The results of this preliminary study in Hungary might emphasize the importance of RSV infection, as a frequent cause of rehospitalization and the possibility of prevention (immunoglobulin, palivizumab).     

Respiratory syncytial virus infections and preventive options

Respiratory syncytial virus (RSV) is the most prominent pathogen found in respiratory tract infections in children and the most important cause of bronchiolitis in the first two years of life. In the Netherlands approximately 2000 children are admitted each winter season. A serious course is mostly seen in children younger than 3 months, (ex-)prematures, children with bronchopulmonary dysplasia or congenital cardiac anomalies, children with cystic fibrosis younger then 2 years and children with impaired T cell immunity; such cases not rarely require intensive care. Treatment (fluid, nutrition, bronchodilator agents, corticosteroids, oxygen and ventilation) is usually symptomatic. Antiviral therapy is only indicated in immunodeficient patients. For prevention by passive immunization palivizumab was recently registered in the Netherlands, a monoclonal antibody against RSV that has to be administered intramuscularly from the start of the RSV season (15 mg per kg bodyweight once a month during five months). In a number of large-scale American multicenter studies both the number of hospital admissions related to RSV infection and the mean duration of hospital stay showed a statistically significant reduction in high-risk children who had been treated with palivizumab. Palivizumab appears to be indicated in children from the categories with an increased risk for serious RSV disease.     

Respiratory syncytial virus in infants and children

Respiratory syncytial virus (RSV) disease is a major cause of death and hospitalization in infancy and a frequent cause of morbidity throughout childhood. An epidemic occurred in the Washington, D. C. area in each of 16 respiratory disease seasons between 1957 and 1970. During the peak month of a “composite epidemic” 70% of bronchiolitis patients and 56% of all respiratory disease inpatients exhibited evidence of RSV infection. Approximately one-half of infants followed longitudinally were infected during their first RSV epidemic and almost all children were infected after living through two RSV epidemics. RSV infection does not produce solid resistance. First infection may have a 40% incidence of febrile pneumonitis; illness with reinfection is usually much less severe. Serum antibody does not protect as evident from the study of natural disease and the use of killed vaccine. Local antibody responses occur in natural illness. Possibly serum antibody in the absence of local antibody plays a part in illness.We have studied local and serum antibody response to potential attenuated vaccine: a 26°C-adapted RSV and a ts mutant RSV. Both produced the desired infection as evidenced by virus recovery, serum, and local antibody response. However, both appear to have had residual pathogenicity for young infants. This included mild bronchitis after the 26°C RSV and mild rhinitis, which might be acceptable, but also fever and otitis in one infant after the ts RSV. Also, some of the virus recovered in the ts studies had wild-type characteristics.An acceptable RSV vaccine strain will (a) infect without undergoing reversion or other genetic changes, (b) induce resistance to wild-type virus, (c) cause no or very mild inflammatory changes such as the rhinitis associated with the vaccines thus far tried.     

Respiratory syncytial virus seasonality in tropical Australia

Objective: Respiratory syncytial virus (RSV) is most common during the rainy season in a number of low‐ to middle‐income tropical settings, a pattern driven by seasonal changes in climate and nutrition. We investigated the seasonality of RSV in the high‐income tropical setting of North Queensland, Australia. Methods: We used RSV hospital admissions data from Cairns and Townsville to assess the seasonality of RSV. We examined the seasonal scale associations between selected meteorological exposures and RSV admissions using cross‐correlation of weekly data. Results: In both Cairns and Townsville, RSV admissions were highest in the latter half of the rainy season. In Cairns, RSV admissions were most strongly correlated with rainfall four weeks previously. In Townsville, RSV admissions were most strongly correlated with rainfall six weeks previously. Conclusions: The seasonality of RSV in the tropical setting of North Queensland appears to be driven by seasonal variations in rainfall. Further research is needed to assess the impact of climate on RSV incidence in the tropics.     

Respiratory syncytial virus infection and meningococcal disease.

Although viral respiratory tract infections may predispose to meningococcal disease, strong evidence that they do so exists only for influenza. Data on laboratory reported cases of respiratory syncytial virus (RSV) infections and meningococcal disease in England and Wales from mid-1989 to mid-1994 were analysed. Although the rise in RSV cases preceded the rise in meningococcal disease cases each winter, the interval between the rise and fall of the two diseases was inconsistent, no association was found between time series after removal of the seasonal component, and there was no evidence that more cases of meningococcal disease occurred in winters with more RSV disease. RSV may have less effect on the two most likely mechanisms whereby influenza predisposes to meningococcal disease, namely lowered immunity and impaired pharyngeal defences.     

Polysaccharide-based pneumococcal vaccines in the prevention of acute otitis media

New pneumococcal vaccines, consisting of 7-11 capsular polysaccharides coupled to protein carriers, are able to induce functionally active humoral and mucosal antibody responses. They also reduce mucosal carriage of pneumococci in the vaccinees. Preliminary results from efficacy trials suggest that about one-third of pneumococcal otitis could be prevented by using the seven-valent pneumococcal conjugate vaccine. If these efficacy estimates are true throughout childhood, up to 1.2 million episodes of acute otitis are preventable annually in the US. The true impact of the vaccine on otitis burden is dependent not only on the efficacy as demonstrated in the efficacy trials but also on the impact of the vaccine on the mucosal carriage of bacteria and on the herd immunity induced by vaccinations. Ongoing follow-up studies will reveal whether these factors increase or decrease the efficiency of the proposed vaccination programme.     

Pneumococcal otitis media and pneumococcal vaccines, a historical perspective

Although pneumococcal otitis media was recognized in the 19th century, the illness stimulated little interest in prophylaxis until recently. Whole cell vaccines of killed pneumococci, developed to prevent pneumonia, were replaced by vaccines of capsular polysaccharides following demonstration of their antigenicity in adults. Failure of the latter to stimulate antibodies in infants and young children and demonstration of the efficacy of capsular polysaccharide-protein conjugate vaccines in preventing infection with Hemophilus influenzae type b has led to the development of polyvalent pneumococcal polysaccharide-protein conjugate vaccines. Preliminary studies have shown them to be highly effective in preventing invasive pneumococcal disease in the first 2 years of life, and studies of their impact on otitis media are currently in progress.     

Respiratory syncytial virus activity--United States, 2003-2004

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) (i.e., bronchiolitis and pneumonia) among young children, resulting in an estimated 51,000-82,000 hospitalizations annually. RSV causes severe disease among older adults and persons of all ages with compromised respiratory, cardiac, or immune systems, and can exacerbate chronic cardiac and pulmonary conditions. In temperate climates, RSV infections occur primarily during annual winter season outbreaks. This report summarizes trends in RSV activity reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) during July 2003-June 2004 and presents preliminary data from the weeks ending July 3-December 4, 2004, indicating the onset of the 2004-05 RSV season. Health-care providers should consider RSV in the differential diagnosis for persons of all ages with LRTIs, implement appropriate isolation precautions to prevent nosocomial transmission, and provide appropriate immune prophylaxis to eligible children, including certain premature infants or children and infants with chronic lung and heart disease.     

基层医院呼吸道合胞病毒检测方法的筛选

目的筛选快速、可靠、易推广的适合基层医院的呼吸道合胞病毒（respiratory sycytial virus,RSV）的检测方法。方法双抗体夹心ELISA法、直接免疫荧光法、免疫层析金标法、桥联酶标法检测50例经临床确诊为RSV感染患儿的鼻咽分泌物。结果 RSV阳性检出率依次为40%、88%、84%、80%。结论直接免疫荧光法快速、可靠、易推广,是基层医院RSV感染早期诊断的优选方法。     

Influenza virus and rhinovirus-related otitis media: potential for antiviral intervention

Adults frequently develop eustachian tube dysfunction and middle ear pressure (MEP) abnormalities during natural and experimental influenza and human rhinovirus (HRV) infections. Oral rimantadine treatment did not reduce the otologic manifestations of experimental influenza in adults or natural influenza in children. However, intranasal zanamivir and oral oseltamivir significantly reduced MEP abnormalities during experimental influenza in adults, and oseltamivir treatment appears to reduce the likelihood of otitis media in children with acute influenza. Investigational anti-HRV agents, including intranasal tremacamra, intranasal AG7088, and oral pleconaril, warrant study in this regard. Depending on the virus, early antiviral therapy has the potential to impact the risk of otitis media following respiratory tract infections.