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PubMed2005

The potential impact of prophylaxis against bronchiolitis due to the respiratory syncytial virus in children with congenital cardiac malformations.

AIMS: To determine the number of infants in the Mersey and North West regions with congenital cardiac disease for whom palivizumab may be appropriate, and to examine the potential impact of introducing prophylaxis with palivizumab on these patients and their economic management. METHODS: We identified those infants deemed to be at high risk, matching the population recently studied by the Cardiac Synagis Group, from the database of the cardiology department of the hospital. The number of patients under the care of the paediatric cardiologists admitted to Alder Hey Hospital with respiratory syncytial viral bronchiolitis over the last three seasons was identified from hospital coding records, and the database of the cardiology department. RESULTS: There are 131 patients at high risk each year. Of these, over the last three "bronchiolitis seasons", 39 infants have been admitted to the hospital with bronchiolitis due to the respiratory syncytial virus. This represents a hospitalisation rate of 10 per cent, as was seen in the study of the Cardiac Synagis Group. Using a monthly dose of 15 milligrams per kilogram for five doses, the cost per patient is 2,650 pounds sterling for the season. To treat the 131 patients seen at Alder Hey, therefore, would cost 346,800 pounds each year. Applying the reductions in hospitalisation identified in the study by the Cardiac Synagis Group to our population would produce an expected reduction in patients hospitalised from 13 to 7 per year, reducing the total length of stay in our hospital wards from 169 to 76 days, and in the paediatric intensive care unit from 93 to 21 days. This amounts to a potential saving of 190,800 pounds per year. Reducing transfers to more distant paediatric intensive care units for referrals refused because of lack of beds could save an additional 50,000 pounds. DISCUSSION: We estimate the net cost of introducing palivizumab for this population to be 106,000 pounds per year. There would, of course, be additional costs involved in setting up this service, as well as additional savings and benefits. This cost is comparable with other new biologic therapies now routinely used in the United Kingdom, such as etanercept for juvenile arthritis. There are, currently, no other obvious therapies that have the potential to reduce admissions to hospital and intensive care during the winter months, when beds are at their most scarce.

Antibodies, Monoclonal↗
PubMed1999

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Antibodies, Viral↗
PubMedDate not supplied

Detection of bovine respiratory syncytial virus in experimentally infected balb/c mice.

The present study used an RT-nested-PCR and an immunohistochemistry assay to detect bovine respiratory syncytial virus in tissues from experimentally infected balb/c mice. As a first step, Chicken Embryo Related (CER) cell monolayers infected with the BRSV-25-BR strain isolated in Brazil were used for antigen production. Then, the infected lung and tracheal tissues of female balb/c mice were collected on 3, 5, 7 and 10 days post-infection and submitted to both techniques. Primers specific to F and G genes that amplify fragments of 481 bp and 371 bp, respectively, were used. The BRSV detection was not successful in all of the animals tested. The genomic fragment of the G gene from the organs of some infected mice on all analyzed post-infection days was amplified. However, in the RT-nested-PCR corresponding to the F gene, it was not possible to observe any amplified fragment. This was probably due to the higher sensitivity of the developed technique to amplify the fragment corresponding to the G gene compared to the F gene. Moreover, only three of the lungs collected five days post-infection were positive by immunohistochemistry. To the author's knowledge, this is the first study reporting bovine respiratory syncytial virus detection in balb/c mice after experimental inoculation.

Animals↗
PubMed2006

Evaluation of respiratory syncytial virus detection by rapid antigen tests in childhood.

BACKGROUND: Rapid and reliable diagnosis is crucial for clinical management of respiratory syncytial virus infection in childhood. We assessed the performance characteristics of respiratory syncytial virus antigen immunoassays in children hospitalized for respiratory infection. METHOD: A total of 1600 children up to three years of age hospitalized for diseases potentially caused by RSV were included in the study. Nasopharyngeal secretions were obtained in a standardized manner in the first 24 hours after hospital admission and tested in parallel by PCR and rapid antigen tests for RSV. The following parameters were recorded: recruitment center, gender, age, presence of fever, rhinitis, stridor, barking cough, cough, wheezing, vomiting, disturbed eating or sleep, tachypnea, tachycardia, increased body temperature, decreased oxygen saturation, C-reactive protein, erythrocyte sedimentation rate and chest X-ray results. RESULTS: Considering PCR testing as gold standard, rapid antigen testing had a specificity of 89.9% and a sensitivity of 66.2% for all samples tested. Logistic regression analysis revealed age and recruitment center as the only parameters influencing sensitivity whereas no such influence on specificity was found. Positive likelihood ratios ranged from 4,9 to 6.9 in different age groups. Negative likelihood ratio was 0.24 (95% CI: 0.18-0.42) in children aged up to 3 months but 0.67 (95% CI: 0.53-0.84) for children older than 2 years. CONCLUSION: Rapid detection of RSV antigen in this study was useful in detection of RSV mediated disease in younger infants but shows decreasing sensitivity in children older than three months.

Antigens, Viral↗
PubMed1995

Bovine respiratory syncytial virus reinfections and decreased milk yield in dairy cattle.

The influence of Bovine Respiratory Syncytial Virus (BRSV) reinfections on the daily milk yield was studied by evaluating the milk production of 32 BRSV reinfected cows. For the estimation of milk production losses, four lactation curve models were used, including a gamma function, a second degree polynomial, and both of these models with a lag variable. Bovine respiratory syncytial virus reinfections seemed to have only a small effect on the daily milk production. Comparison of the true production with an estimated production according to the gamma function showed that the production for first lactation cows dropped 0.14 kg on average and for cows in their second or later lactation 0.56 kg on average, during 5 consecutive days in the infection period. For the second-degree polynomial model these values were respectively 0.42 kg and 0.80 kg. All calculated average production losses were relatively small and not significant (P > 0.15). The models without lag variable were more suitable than the models with the lag variable to estimate small production losses caused by BRSV reinfections. The power of this study was sufficient to detect a decrease in production of approximately 1-1.5 kg milk per cow per day. It was therefore concluded that BRSV reinfections were not associated with an important loss of milk production.

Animals↗
PubMed1998

Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia.

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193-205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193-203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.

Animals↗
PubMed1998

Passive protection of gnotobiotic calves using monoclonal antibodies directed at different epitopes on the fusion protein of bovine respiratory syncytial virus.

Two neutralizing, fusion-inhibiting bovine monoclonal antibodies (MAbs; B4 and B13) directed at different epitopes on the fusion protein of respiratory syncytial virus (RSV) protected the lungs of gnotobiotic calves from RSV infection. The MAbs were administered intratracheally 24 h before the calves were challenged with bovine RSV. A third, nonneutralizing, non-fusion-inhibiting but complement-fixing MAb, B1, provided no significant protection against infection, and the disease was not exacerbated. Pneumonic consolidation and mean virus titer in lung 7 days after challenge were significantly lower in calves given the fusion-inhibiting MAbs than in either control calves or those given MAb B1. The proliferative bronchiolitis with syncytial formation and widespread distribution of RSV antigen in the lower respiratory tract of the B1-treated and control calves were indistinguishable and typical of experimental bovine RSV infection. Syncytia were markedly absent, and little or no viral antigen was detected in either the B4- or B13-treated calves.

Animals↗
PubMed2000

Respiratory syncytial virus (RSV) immune globulin and palivizumab for prevention of RSV infection.

The efficacy, safety, administration, and advantages and disadvantages of respiratory syncytial virus (RSV) immune globulin and palivizumab for preventing RSV infection are discussed. Prevention of RSV infection has attracted considerable attention because of its dinical and economic impact. Studies have shown respiratory syncytial virus immune globulin intravenous (RSV-IGIV) and palivizumab to be effective in decreasing the number of hospitalizations and hospital days attributable to RSV. The number of intensive-care-unit admissions and the severity of RSV infection in high-risk children decreased with the use of these agents. Both agents have been well tolerated, with few adverse effects; however, their high cost necessitates strict guidelines on use. The patient populations at greatest risk are those with bronchopulmonary dysplasia, those with congenital heart disease, those with a history of apnea or respiratory arrest, immunocompromised patients, those with pulmonary consolidation on chest radiography, and those born prematurely. American Academy of Pediatrics guidelines do not preferentially recommend use of either agent; each has advantages and disadvantages. Prophylactic therapy with RSV-IGIV or palivizumab may reduce the likelihood of RSV infection in high-risk patients.

Antibodies, Monoclonal↗
PubMed1996

Protective Role of TNF-alpha in respiratory syncytial virus infection in vitro and in vivo.

Respiratory syncytial virus (RSV) infection causes substantial morbidity in young children and immunocompromised adults, yet its pathogenesis is poorly understood. Because the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) may be important in host response to viral infection, HEp-2 cells were treated with TNF-alpha and mice were given TNF-alpha antibody before RSV infection. Pretreatment of HEp-2 cells with TNF-alpha inhibited RSV replication as determined by cytopathic effect. Respiratory syncytial virus-infected BALB/c mice treated with antibody to TNF-alpha had greater maximal weight loss and slower recovery time than control mice. These results suggest a protective role for TNF-alpha in RSV infection.

Animals↗
PubMed2001

Management of respiratory syncytial virus infection.

Although bronchiolitis is the most common viral lower respiratory tract infection in infancy and childhood, and the virus responsible (respiratory syncytial virus) was discovered half a century ago, there is no effective treatment available. The antiviral agent ribavirin has not lived up to expectations and should be reserved for selected cases. Corticosteroids have not been shown to be effective in individual trials, although a recent meta-analysis suggested a mild beneficial short-term effect. Bronchodilators can be used on a trial-and-error basis. Prophylaxis with intravenous immunoglobulins enriched for anti-respiratory syncytial virus antibodies or humanized monoclonal antibodies can reduce the rates of related hospitalization by 50% when used in high-risk patients. However, logistical problems with the administration of intravenous immunoglobulins and the cost of both products preclude their widespread use.

Adrenal Cortex Hormones↗
PubMed1995

Hospitalizations for respiratory syncytial virus infection in Alaska Native children.

To characterize the epidemiology of Alaska Native children hospitalized for respiratory syncytial virus infections, we reviewed records of hospitalizations during the winter seasons of 1991 to 1992 and 1992 to 1993 at a hospital in Anchorage and a rural hospital in the Yukon Kuskokwim Delta (YKD) region of southwestern Alaska. The median age of hospitalization for respiratory syncytial virus infection was 2 months of age for YKD residents and 4.5 months for Anchorage residents. Sixteen percent of the hospitalized YKD children were less than 1 month of age, whereas the same was true for only 3% of the Anchorage children. Eight percent of the YKD patients required mechanical ventilation, whereas none of the Anchorage patients required ventilation. The median hospital stay was 4.8 days for YKD patients and 3.2 days for Anchorage patients. Hospitalization rates for infants less than 1 year of age were 33/1000 for Alaska Natives in Anchorage and 100/1000 for those in the YKD region. The extremely high hospitalization rate, especially among very young infants in the rural YKD region, points to a need for early preventive efforts.

Age Factors↗
PubMed2002

Respiratory syncytial virus prophylaxis: cost-effective analysis in Argentina.

INTRODUCTION: Respiratory syncytial virus is a major cause of bronchiolitis during the first year of life. Preterm infants and patients with bronchopulmonary dysplasia (BPD) have a higher risk of hospitalization. The objective of this study was to assess the risk of hospitalization and to evaluate the cost effectiveness of palivizumab use in our at risk population. METHODS: The study design was based on the hypothetical use of palivizumab in a cohort of patients. The cost effectiveness analysis included costs of palivizumab, the drug prescription and hospitalization. The effectiveness measure was the hospitalization rate decrease according to the result of the IMpact study: a 55% reduction in the need for hospitalization attributable to RSV. The years 1998 and 1999 were analyzed. Evaluable patients had follow-up at the High Risk Clinic and fulfilled the American Academy of Pediatrics criteria for palivizumab prophylaxis. RESULTS: Forty-two patients, 24 with BPD and 18 preterm infants without BPD, were evaluated. Ten patients required hospitalization because of respiratory syncytial virus; one of them died. Hospitalization cost was $184,777. The total palivizumab administration cost would have been $185,064. With a 55% decrease of hospitalization rate, the cost per hospitalization averted would have been $15,358, and the number needed to treat would have been 7.9. A sensitivity analysis showed that the cost per hospitalization averted could range between $2,171 and $48,630 according to the hospitalization rate. CONCLUSIONS: Because new effective but expensive treatments like palivizumab are available, this cost effective analysis can be an important tool in decisions about resource distribution.

Antibodies, Monoclonal↗
PubMed2004

Seasonal variation in respiratory syncytial virus epidemics in the Gambia, West Africa.

Respiratory syncytial virus outbreaks tend to occur seasonally and are a major cause of childhood morbidity. In The Gambia a regular pattern of outbreaks during six consecutive annual seasons was disrupted by 2 years of irregular outbreaks, followed by another 2 years of regular seasonal outbreaks. Improved understanding of the transmission dynamics of respiratory syncytial virus is essential to design and test effective interventions.

Developing Countries↗
PubMed2004

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.

Age Distribution↗
PubMed2006

Replication of bovine respiratory syncytial virus in murine cells depends on type I interferon-receptor functionality.

Bovine respiratory syncytial virus (BRSV) is able to counteract the alpha/beta interferon (IFN-alpha/beta)-mediated antiviral response for efficient replication in a host-specific manner. Mice models have been developed for experimental infection with human, but not bovine, respiratory syncytial virus strains. Here, it is shown that BRSV can replicate efficiently on primary cell cultures derived from type I IFN receptor-deficient, but not from wild-type IFN-competent, mice. However, BRSV infection was not enhanced in mice devoid of the type I IFN receptor. These results show that type I IFN is a major host-range determinant for infection at the cellular level, but that other factors control virus replication and pathology in vivo.

Animals↗
PubMed1995

Incidence of acute otitis media associated with group A and B respiratory syncytial virus infections.

The comparative association of respiratory syncytial virus group A and B infections with acute otitis media was determined by analysing the hospital records of children with community-acquired respiratory syncytial virus infection during three successive outbreaks from 1987 to 1992. Of 326 episodes analysed, 192 (59%) were caused by group A and 134 (41%) by group B infections. Acute otitis media was diagnosed in 101 (75%) children with group B infection, compared with 119 (62%) with group A infection (p = 0.01). Group A infections were more often associated with wheezing (71% versus 59% in group B; p = 0.02) and oxygen therapy in inpatients (48% versus 31%, respectively; p = 0.008). The higher incidence of acute otitis media associated with group B infections was observed both after adjustment for potential confounding variables and during each outbreak.

Acute Disease↗
PubMed1993

Reliable confirmation of antibodies to bovine respiratory syncytial virus (BRSV) by enzyme-linked immunosorbent assay using BRSV nucleocapsid protein expressed in insect cells.

The nucleocapsid (N) protein of bovine respiratory syncytial virus (BRSV) in the baculovirus expression system was evaluated as a source of antigen in an enzyme-linked immunosorbent assay (ELISA) for the detection of respiratory syncytial virus (RSV) antibodies. The recombinant N protein was purified from infected-cell extracts by sucrose gradient centrifugation and used in the ELISA for the detection of antibodies to various RSV strains. The ELISA was compared with the virus neutralization (VN) test for determining BRSV antibodies in 10 consecutive serum samples from four calves vaccinated with a live modified BRSV vaccine and from two nonvaccinated control calves. The ELISA compared favorably with the VN test for detecting serological responses. All serum samples which were positive in the VN test were also positive in the ELISA. None of the serum samples collected from the two nonvaccinated calves reacted in the ELISA. To determine the usefulness of the ELISA for epidemiological studies, 58 cattle serum samples were tested in the ELISA and the VN test. Approximately 94% (42 of 45) of field serum samples which were positive in the ELISA were also positive in the VN test. No case was found in which the ELISA result was negative and the VN test result was positive. Thirteen of the serum samples were negative in both methods. Our results indicate that the ELISA with the baculovirus-expressed N protein as an antigen is an efficient, sensitive, and specific method for detecting serum antibodies to RSV.

Animals↗
PubMed1994

Analysis of respiratory syncytial virus strain variation in successive epidemics in one city.

The variability of respiratory syncytial virus isolates from five successive epidemics in an urban population was determined. A total of 187 isolates of respiratory syncytial virus from the southern part of Birmingham, United Kingdom, were classified into subgroups A and B and were then further assigned to genetic lineages. Allocation of isolates into lineages was achieved by reverse transcription of infected cell RNA and then PCR amplification of selected regions of the genome; PCR products were examined by restriction mapping or nucleotide sequencing of parts of the nucleoprotein gene, the small hydrophobic protein gene, and the attachment protein gene. Previous work has shown that estimations of genetic diversity by analysis of genes coding for proteins likely (attachment protein) and unlikely (nucleoprotein and small hydrophobic protein) to be under immune pressure gave concordant results. Six genetic lineages of subgroup A isolates have been defined by this procedure; these isolates differ by up to 20% in the amino acid sequences of their attachment proteins; likewise, subgroup B isolates can be divided into two categories by restriction mapping of parts of their nucleoprotein and attachment protein genes. The same genetic lineages appeared to be present worldwide during the same period. The analysis of isolates from successive epidemics showed that different lineages predominated in each epidemic and that not all lineages were present in every epidemic. Some lineages appeared to increase in numbers over several years and then decline, possibly indicating a buildup of resistance in the community to a particular genotype.

Capsid↗