Respiratory syncytial virus in a community population: circulation of subgroups A and B since 1965

Respiratory syncytial viruses were isolated from residents of Tecumseh, MI, with illnesses of all severities during the periods 1965-1971 and 1976-1981. These isolates were grouped using one monoclonal antibody specific for each subgroup. All were identified as either subgroup A or B. Subgroup A predominated in most years. No differences in age distribution or illness characteristics could be found between the subgroups. This study demonstrated that the currently recognized subgroups have been present in a single community since 1965, and their behavior in the past is similar to that currently described.     

Prevalence of respiratory syncytial virus subgroups over six consecutive outbreaks: 1981-1987

Indirect immunofluorescence with strain-specific monoclonal antibodies was used to determine the phenotype of respiratory syncytial virus (RSV) isolates obtained from infants hospitalized in greater Boston over six successive outbreaks from 1981 to 1987. Of 981 isolates, 591 (60%) were classified as subgroup A and 383 (39%) as subgroup B. The prevalence of subgroups varied both between and within yearly outbreaks. In 1983-84 and 1984-85, both subgroups circulated concurrently and in almost equal proportions; in 1981-82, 1982-83, and 1985-86 subgroup A was dominant, accounting for 93% of all RSV isolates; and in 1986-87 subgroup B accounted for 89% of all RSV isolates. In some outbreaks both geographic and temporal clustering of subgroups occurred. No major differences in age, gender, or frequency of nosocomially acquired RSV between infants infected with either subgroup were seen, either overall or between or within yearly outbreaks. An expanded panel of monoclonal antibodies revealed further heterogeneity among subgroup A isolates. Comparison of these results with similar studies from other geographic locations indicated that the pattern of RSV subgroup prevalence is a localized phenomenon.     

Respiratory syncytial virus infections in children and adults

Respiratory syncytial virus is the leading cause of hospital admission for lower respiratory tract infection in young children and appears to be responsible for a significant burden of disease in adults, particularly the elderly and the immunocompromised. In this review, we describe the epidemiology, diagnosis and clinical manifestations of infection attributed to this virus. We also consider current therapeutic and prophylactic options and appraise strategies for vaccination that are in clinical trials.     

Respiratory syncytial virus: Virology, diagnosis, and vaccination

Attempts to develop a respiratory syncytial virus vaccine have revealed the antigenic heterogeneity of the virus and have highlighted the difficulties of inducing protective responses in very young infants. Of the two subgroups of the virus, A and B, that cocirculate, A appears to be the most aggressive in infants, but protection against both will be required. Although a degree of protection is transferred from mother to the infant via the placenta and by breast feeding, the mechanisms of protection remain illunderstood and early hopes of exploiting this phenomenon have not been realized. The immune response to the virus in the very young is depressed but disease severity is not demonstrably linked to failure to control virus replication. Rather, immune mechanisms contribute directly to the development of bronchiolitis. The involvement of the immune response in the pathologic process increases the hazards of vaccination. Research is currently focused on the definition of viral epitopes necessary to induce only a protective immune response and their incorporation into a suitable vaccine vector.     

Respiratory syncytial virus, infants and intensive therapy

The aims of this study were to determine the presence of respiratory syncytial virus (RSV) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (PICU) of two university teaching hospitals in S?o Paulo State, Brazil. Nasopharyngeal secretions were tested for the RSV by the polymerase chain reaction. Positive and negative groups for the virus were compared in terms of evolution under intensive care (mechanical pulmonary ventilation, medications, invasive procedures, complications and case fatality). Statistical analysis was performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients were previously healthy while 85.7% required mechanical pulmonary ventilation, 20/21 patients presented with at least one complication, and the fatality rate was 14.3%. RSV positive and negative groups did not differ for the variables studied. Patients involved in this study were critically ill and needed multiple PICU resources, independently of the presence of RSV. Further studies involving larger cohorts are needed to assess the magnitude of the impact of RSV on the clinical evolution of infants admitted to the PICU in our settings.     

Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and virus genotype

In infants with respiratory syncytial virus (RSV) bronchiolitis, we investigated whether disease severity is associated with the genotype of the infecting virus, or with the infant's immunological response to the infection, as determined by measurement of interleukin-8 mRNA in the nasopharyngeal aspirate. This was a cross-sectional observational study, performed in the Accident and Emergency Department, wards, and Intensive Care Unit of a large pediatric hospital. Participants included 276 infants with respiratory syncytial virus infection. Outcome variables included: disease severity (infants requiring oxygen or ventilation were classified as having severe disease); RSV virus genotype (determined according to typing scheme based on the nucleoprotein and G glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal aspirate, as measured by a semiquantitative polymerase chain reaction assay. This was corrected for the amount of cellular material in the sample by expressing it relative to mRNA for a constitutively expressed gene, HGPRT. We found a highly significant association between the ratio of interleukin-8 mRNA/HGPRT mRNA in the nasopharyngeal aspirate and the occurrence of severe disease. Odds ratio per unit increase of interleukin-8 mRNA/HGPRT mRNA was 1.15 (95% CI, 1.06, 1.24), P = 0.0004. There was no association between virus genotype and either disease severity or amount of interleukin-8 mRNA/HGPRT mRNA. In conclusion, there is a strong, dose-related association between interleukin-8 mRNA produced locally in the airways and disease severity, and a lack of association with virus genotype. This suggests that clinical manifestations of respiratory syncytial virus bronchiolitis are determined by local immunological responses to infection, rather than by characteristics of the infecting virus.     

Respiratory syncytial virus infection: clinical features, management, and prophylaxis

Respiratory syncytial virus (RSV) infects almost all children by two years of age, resulting in a large number of hospital admissions in infants. Reactive airway disease is more common after RSV infection, even in previously healthy children. Management of the acute infection is supportive, but preliminary evidence suggests surfactant administration to ventilated infants may be of benefit. Whether ribavirin or corticosteroids reduce respiratory morbidity after RSV infection remains controversial. Immunoprophylaxis reduces RSV admissions, Palivizumab, a humanized monoclonal antibody, is a more cost-effective prophylaxis than RSV immune globulin. Nevertheless, the cost of prophylaxis, unless only given to very high-risk infants, exceeds savings made in reducing admissions.     

Respiratory syncytial virus: Update on infection, treatment, and prevention

Respiratory syncytial virus (RSV) infection, which primarily manifests as bronchiolitis or pneumonia, is the leading cause of lower respiratory tract infection in infants and young children. It is associated with more than 100,000 pediatric hospitalizations each year in the United States. Infants who were premature; have chronic lung disease, congenital heart disease, or immunodeficiency disorders; or have underlying metabolic or neuromuscular disorders are at increased risk for especially severe RSV disease. Treatment of children hospitalized with RSV disease is primarily supportive, with administration of supplemental oxygen and fluid replacement therapy. Bronchodilators may benefit at least a subset of such patients. Antiviral therapy with aerosolized ribavirin is available for high-risk, severely ill patients. Handwashing, cleaning of environmental surfaces, and cohorting in hospital settings may decrease RSV transmission. In children born premature and younger than 1 year of age, and in patients with bronchopulmonary dysplasia younger than 2 years of age, passive protection against severe RSV disease may be achieved through monthly injections of anti-RSV antibody (palivizumab) during winter months. No vaccine is available to provide active immunity against RSV, but live attenuated and subunit cloned surface protein vaccines are in development.     

Respiratory syncytial virus prevention and therapy: past, present, and future

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. More than 50 years after its discovery, and despite relentless attempts to identify pharmacological therapies to improve the clinical course and outcomes of this disease, the most effective therapy remains supportive care. Although the quest for a safe and effective vaccine remains unsuccessful, pediatricians practicing during the past decade have been able to protect at least the more vulnerable patients with safe and effective passive prophylaxis. This review summarizes the history, microbiology, epidemiology, pathophysiology, and clinical manifestations of this infection in order to provide the reader with the background information necessary to fully appreciate the many challenges presented by the clinical management of young children with bronchiolitis. The last part of this article attempts an evidence-based review of the pharmacologic strategies currently available and those being evaluated, intentionally omitting highly experimental approaches not yet tested in clinical trials and, therefore, not likely to become available in the foreseeable future.     

Respiratory syncytial virus immune globulin: decisions and costs.

A decision analysis was used to evaluate the economic effectiveness of respiratory syncytial virus immune globulin (RSVIG) prophylaxis on selected pediatric populations at risk for developing RSV bronchiolitis or all respiratory illness-related hospitalizations. We compared costs, outcomes, and cost-effectiveness of administering RSVIG to no treatment in different pediatric populations, including those at risk of developing RSV-bronchiolitis and those at risk of developing any respiratory illness-related hospitalization. We observed that if only infants at high risk of severe RSV infections received treatment with RSVIG, a calculated cost saving of about 27,000 dollars per hospitalization prevented were realized. If the Food and Drug Administration (FDA)-approved indications for RSVIG were followed, the cost to prevent one hospitalization due to RSV bronchiolitis would be over 53,000 dollars. If the aim, however, was to prevent all respiratory illness-related hospitalizations for this broader population, a much lower cost (4,000 dollars) to prevent one hospitalization would result. In this situation, cost neutrality was possible, with a therapy cost of 2,843 dollars compared to the actual average therapy cost of 4,444 dollars. Sensitivity analysis showed that the model was relatively insensitive to all variables, with the exceptions of costs related to RSVIG and intensive care unit (ICU) admissions. We conclude that RSVIG resulted in cost savings if therapy were reserved for the infants who are at highest risk for developing severe RSV infections. RSVIG is not cost-effective for preventing RSV bronchiolitis when used according to the FDA-approved indications. Education that emphasizes frequent hand-washing, avoidance of passive smoking, and lessening exposure to sick children remains the least expensive prevention tool.     

Genetic diversity and molecular epidemiology of the G protein of subgroups A and B of respiratory syncytial viruses isolated over 9 consecutive epidemics in Korea

To study genetic variation and molecular epidemiology of the G protein of respiratory syncytial virus (RSV), 253 strains from a children's hospital in Korea over 9 consecutive epidemics were analyzed. Restriction analysis of the entire G protein gene demonstrated 24 genotypes among 188 subgroup A and 6 among 65 subgroup B isolates. Two to 4 dominant genotypes of subgroup A cocirculated, and different genotypes predominated in each epidemic. Predominant genotypes were replaced with new genotypes during consecutive epidemics. One of 2 dominant genotypes among subgroup B predominated alternately or concurrently. Phylogenetic analysis revealed that there were multiple lineages, with clustering related to their location and time of isolation among strains from Korea and worldwide. Geographic and temporal distinction have been shown more clearly for subgroup B than subgroup A. These results suggest that the G protein of RSV is continuously evolving, with a distinct pattern presumably due to immune selection in a localized region over time.     

Viral infection and asthma: Respiratory syncytial virus and wheezing illness

A strong link between bronchiolitis and asthma has been indicated. Bronchiolitis that occurs in infants is manifested physiologically by a widespread narrowing of the air passages and, clinically, by asthma-like symptoms.The major cause of bronchiolitis is respiratory syncytial virus infection. While the precise pathophysiologic sequences of infection are incomplete, many observations have suggested that there is an infiltration of eosinophils in the airways. Current studies have shown that the respiratory syncytial virus penetrates the pulmonary defenses and initiates immunologic responses. The histamine and leukotriene mediators that are released produce an inflammatory reaction and the chemotactic factors bring eosinophils to the site of the reaction. Degranulation of eosinophils can release eosinophil cationic protein into the airways. Our finding that chemoattractants for eosinophils, interleukin-8 and RANTES (regulated upon activation, normal T cell expressed and presumably secreted) were detected in nasopharyngeal aspirates of infants with bronchiolitis suggests that such chemokines from epithelial cells may induce an eosinophil infiltration in the airway. Similar allergic inflammatory changes have been observed in asthma and in epithelial cells infected with respiratory viruses. Future investigation of the mechanism by which bronchiolitis can induce asthma will provide benefits in the treatment and prevention of asthma in sensitive individuals.     

Residential crowding and severe respiratory syncytial virus disease among infants and young children: A systematic literature review

Background

Varicella and herpes zoster are both caused by varicella zoster virus (VZV) infection or reactivation and may lead to complications associated with a (severe) societal burden. Because the epidemiology of VZV-related diseases in the Netherlands remains largely unknown or incomplete, the main objective of this study was to study the primary care incidence, associated complications and health care resource use.

Methods

We investigated the incidence of VZV complications in the Dutch general practitioner (GP) practices and pharmacies in a retrospective population-based cohort study (2004?C2008) based on longitudinal GP data including free text fields, hospital referral and discharge letters from approximately 165,000 patients.

Results

The average annual incidence of varicella GP-consultations was 51.5 per 10,000 (95% CI 44.4-58.7) overall; 465.5 per 10,000 for 0?C1?year-olds; 610.8 per 10,000 for 1?C4?year-olds; 153.5 per 10,000 for 5?C9?year-olds; 8,3 per 10,000 for >10?year olds. When only ICPC coded diagnoses were analyzed the incidence was 27% lower. The proportion of complications among varicella patients was 34.9%. Most frequently complications were upper respiratory tract infections. Almost half of the varicella patients received medication. The referral rate based on GP consultations was 1.7%. The average annual incidence of herpes zoster GP-consultations was 47.5 per 10,000 (95% CI 40.6-54.4). The incidence increased with age; 32.8 per 10,000 for <60?year-olds; 93.1 per 10,000 for 60?C64?year-olds and 113.2 per 10,000 for >65?year olds. When estimating herpes zoster incidence only on ICPC coded information, the incidence was 28% lower. The complication rate of herpes zoster was 32.9%. Post herpetic neuralgia was seen most often. Of patients diagnosed with herpes zoster 67.8% received medication. The referral rate based on GP consultations was 3.5%.

Conclusions

For varicella the highest incidence of GP-consultations was found in 1?C4?year-olds, for herpes zoster in the >65?years olds. The occurrence of complications was not age-dependent but varies per complication. When estimating incidence of VZV-related diseases in primary care, based on diagnostic codes only, one should be aware of a gross underestimation of the incidence. Our analysis may have important implications for the outcomes of upcoming cost-effectiveness analyses on VZV vaccination.     

Respiratory syncytial virus pneumonia: mechanisms of inflammation and prolonged airway hyperresponsiveness

PURPOSE OF REVIEW: Respiratory syncytial virus is the leading viral pathogen associated with lower respiratory tract infection in young children worldwide. The pathogenesis of acute bronchiolitis and the mechanisms by which the virus induces long-term airway disease remain to be elucidated. This review highlights new findings reported in the English-language medical literature from January 2004 to January 2005. RECENT FINDINGS: Several studies have confirmed a strong association between respiratory syncytial virus infection in infancy and an increased risk for recurrent wheezing. Evidence indicates that the exaggerated immune response and abnormal neurogenic mechanisms induced by the virus play a significant role in the pathogenesis of the disease. Different genetic and immune markers have been correlated with acute disease severity and with increased risk of long-term pulmonary abnormalities. Recently, the application of real time polymerase chain reaction has demonstrated the persistence of respiratory syncytial virus RNA in the lungs of infected mice for months after inoculation. This unexpected observation has stimulated discussions as to whether the long-term presence of the virus could contribute to the long-term airway disease observed in children after respiratory syncytial virus lower respiratory tract infection. SUMMARY: Despite almost half a century of active research into the pathogenesis of respiratory syncytial virus-induced acute and chronic airway disease, many questions remain unresolved. Studies in animal models demonstrate that interventions reducing viral replication resulted in improvement of acute disease severity and long-term pulmonary abnormalities. The stage is ready for clinical studies to determine whether preventing or delaying the primary infection could reduce the incidence of recurrent wheezing in children.