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PubMed2003

Effect of preexposure to ultrafine carbon black on respiratory syncytial virus infection in mice.

Epidemiological studies have indicated that exposure to elevated levels of particulate matter exacerbates several pulmonary diseases, including asthma, bronchitis, and viral infections. Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in infants and may lead to the development of asthma in childhood. To determine whether particle exposure modulates the immune response to RSV, eight-week-old female BALB/c mice received an intratracheal (i.t.) instillation of either 40 micro g ultrafine carbon black (CB) particles or vehicle. The following day, mice were i.t. instilled with either 106 pfu RSV or uninfected media. End points were examined 1, 2, 4, 7, and 10 days during RSV infection. Compared with RSV alone, tumor necrosis factor-alpha (TNF-alpha) protein was reduced in the bronchoalveolar lavage fluid (BALF) on days 1 and 2 of infection; there was also a reduction in BALF lymphocyte numbers on day 4, which correlated with reductions in both IFN-gamma-inducible protein (IP-10), lymphotactin, and IFN-gamma mRNAs in the lungs of RSV + CB mice. Multiprobe ribonuclease protection assays of RSV + CB lung tissue showed no changes in the RSV-associated chemokines regulated upon activation, normal T cell expressed and secreted (RANTES), eotaxin, monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP)-1 alpha or MIP-1 beta. Viral titers in RSV + CB mice were lower than RSV on days 2-4 of infection. By day 7 of infection, however, neutrophil numbers, proinflammatory cytokine mRNA expression, and protein levels of TNF-alpha and the Th2 cytokine interleukin (IL)-13 were increased in the lungs of RSV + CB mice, indicating an exacerbation of infection. These data indicate that preexposure to ultrafine particles induces an inflammatory milieu promoting allergic immune responses rather than IFNgamma production necessary for microbial defense.

Animals↗
PubMed2003

Ultrafine carbon black particles enhance respiratory syncytial virus-induced airway reactivity, pulmonary inflammation, and chemokine expression.

Exposure to particulate matter (PM) may exacerbate preexisting respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia. However, few experimental studies have addressed the effects of PM on lower respiratory tract (LRT) viral infection. Respiratory syncytial virus (RSV) is a major etiological agent for LRT infections in infants, the elderly, and the immunocompromised and may lead to chronic wheezing and the development of asthma in children. In this study, we examined the effects of carbon black (CB) on RSV-induced pulmonary inflammation, chemokine and cytokine expression, and airway hyperresponsiveness in a mouse model of RSV. Female BALB/c mice were instilled via the trachea (i.t.) with 1 x 106 plaque forming units (pfu) RSV or with uninfected culture media. On day 3 of infection, mice were i.t. instilled with either 40 micro g ultrafine CB particles or with saline. End points were examined on days 4, 5, 7, and 14 of RSV infection. Viral titer and clearance in the lung were unaffected by CB exposure. Neutrophil numbers were elevated on days 4 and 7, and lymphocyte numbers were higher on days 4 and 14 of infection in CB-exposed, RSV-infected mice. CB exposure also enhanced RSV-induced airway hyperresponsiveness to methacholine, bronchoalveolar lavage (BAL) total protein, and virus-associated chemokines monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1 alpha), and regulated upon activation, normal T cell expressed and secreted (RANTES). MIP-1 alpha mRNA expression was increased in the alveolar epithelium, where ultrafine particles deposit in the lung. These data demonstrate a synergistic effect of ultrafine CB particles on RSV infection, and suggest a potential mechanism for increased respiratory infections in human populations after PM exposure.

Animals↗
PubMed1993

Respiratory syncytial virus infection in young children hospitalized with respiratory illness in Riyadh.

The occurrence of respiratory syncytial virus (RSV) infection among young children hospitalized with lower respiratory tract illness, at King Khalid University Hospital in Riyadh, was examined during the autumn-winter season between September 1991 and February 1992. Sixty-nine cases were diagnosed by immunofluorescent antibody staining of viral antigen in nasopharyngeal aspirates from 127 children, constituting 54 per cent of these patients. Virus culture was attempted only in a few cases, yielding two isolates. Most children were < 1 year of age (median 2 months). Bronchiolitis and bronchopneumonia were the major diagnoses on admission. Hospitalization was for an average of 5 days (range 1-36 days). Treatment was supportive but most children received antibiotic therapy. There was no mortality. Few other bacterial or viral pathogens could be identified from RSV-positive or -negative patients. These results indicate that, during the season of infection, RSV may be the main pathogen of lower respiratory tract illness in hospitalized young children in this region.

Anti-Bacterial Agents↗
PubMed1998

Respiratory syncytial virus infection in infants hospitalized with respiratory illness in northern Jordan.

During the winter seasons of 1993 and 1994, a total of 256 nasopharyngeal aspirates (NPA) from infants aged less than 1 year old admitted to the pediatric ward of Princess Rahma Hospital, northern Jordan, with bronchiolitis and/or pneumonia, were tested for the presence of respiratory syncytial virus (RSV) using direct immunofluorescence assay (DFA) and cell culture (CC). Of the 256 specimens, 129 (50 per cent) were found positive by both DFA and CC, whereas 24 specimens (9 per cent) and 16 specimens (6 per cent) were found positive by DFA and CC, respectively. In an evaluation of the collected NPA specimens detected by DFA, a sensitivity of 89 per cent and a specificity of 78 per cent were demonstrated. These data suggest that virus isolation in CC is still important for the diagnosis of RSV, although DFA is a valuable, rapid diagnostic assay.

Cells, Cultured↗
PubMed2001

Clinical characteristics of respiratory syncytial virus infection in hospitalized healthy infants and young children in Qatar.

To evaluate seasonal trends, clinical profile, and outcome of disease in previously healthy infants and young children hospitalized for respiratory syncytial virus (RSV) infection at Hamad Medical Corporation in the state of Qatar, we reviewed the records of 257 children admitted between 1 January 1996 and 31 December 1998. RSV epidemics occurred yearly during the winter months with peak hospitalizations occuring between November and February. Of the 257 admissions, 160 (62.3 per cent) were male and 97 (37.7 per cent) female. The mean age of all children was 5.7 months (range, 10 days to 32 months). The most common admitting diagnoses were bronchiolitis (59.9 per cent), pneumonia (17.5 per cent), bronchiolitis with pneumonia (8.9 per cent), possible sepsis (7.8 per cent), asthma (4.7 per cent) and apnea (1.2 per cent). A family history of asthma was quite common (63.8 per cent), although no statistical significant difference was noted in complication or length of stay. Treatment was supportive, the majority of the patients received oxygen therapy in 77.8 per cent of cases, bronchodilators in 85.4 per cent, and antibiotics therapy in 49.4 per cent. The median duration of hospital stay was 6 days (range, 1 to 29 days). Of the 14 (5.4 per cent) patients requiring intensive care, four (1.6 per cent) needed mechanical ventilation. No deaths were reported, but subjects aged < or = 12 months had a significantly higher oxygen requirement, intensive care unit admission, bronchodilators and antibiotics therapy than those > 12 months old. Within 1-2 years after admission with RSV infection, 63 of the 257 patients attended for recurrent episodes of wheezy chest. These results indicate that, during the season of infection, RSV is an important pathogen in infants and young children in the state of Qatar, highlighting the need for development of effective vaccines to ameliorate the impact of annual RSV epidemics in infants and young children.

Age Distribution↗
PubMed2002

Respiratory syncytial virus may be a pathogen in allergic conjunctivitis.

PURPOSE: The host response to allergens appears to be regulated by T helper type 2 cell patterns of local cytokine production. We hypothesized that respiratory syncytial virus (RSV) infects the normal conjunctival epithelium and produces interleukin (IL)-4, causing a local allergic reaction. METHODS: Giemsa staining, immunocytochemical study, flow cytometric analysis, and reverse-transcriptase polymerase chain reaction (RT-PCR) were performed on tear and cytology samples from individuals with allergic and postoperative conjunctivitis. Histamine was assayed by radioimmunoassay, and IL-4 by enzyme-linked immunosorbent assay. RESULTS: The total number of cells collected by brush cytology did not differ between allergic and postoperative conjunctivitis. The levels of IL-4 and histamine in the specimens and mean IL-4 tear level were significantly increased in patients with allergic conjunctivitis. Cytocentrifuge preparations contained conjunctival epithelial cells with lymphocytes (a few CD3- and CD4-bearing cells), mast cells, eosinophils, and higher human leukocyte antigen (HLA)-DR expression in allergic patients. RT-PCR analysis showed that samples from allergic conjunctivitis expressed increased transcripts of IL-4 and IL-13. A higher percentage of RSV sequences were detected in allergic patient samples. Immunocytochemical study and RT-PCR showed that epithelial cells were infected with RSV. Average concentrations of IL-4 in culture supernatants were higher than levels in uninfected cells. CONCLUSIONS: These results suggest that the clinical features of human allergic conjunctivitis are associated with T helper type 2 cytokine expression. RSV in conjunctival epithelial cells may be an environmental pathogen in allergic conjunctivitis.

Adolescent↗
PubMed1997

Adenovirus and respiratory syncytial virus in chronic sinusitis using polymerase chain reaction.

The aim of this study is to investigate the role of adenovirus and respiratory syncytial virus (RSV) in chronic sinusitis using the polymerase chain reaction (PCR) to assay for the viruses. PCR has proved to be more sensitive and specific than viral cultures and immunoassays in the detection of viruses. Adenovirus and RSV are among the most common viruses to cause upper respiratory tract infections. Sinus mucosa biopsies from 20 patients undergoing endoscopic sinus surgery were sterilely collected. Four specimens (20%) tested positive for RSV by PCR and none tested positive for adenovirus. Only one specimen tested positive for RSV and one for adenovirus by viral culture and immunofluorescence. Bacterial cultures tested positive in 40% of the 20 specimens. PCR can be used to detect RSV in patients with chronic sinusitis and PCR is more sensitive than viral culture and immunofluorescence techniques on sinus polyps and mucosa.

Adenoviridae↗
PubMed1993

Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children.

Respiratory syncytial virus (RSV) lower respiratory tract and febrile upper respiratory tract illnesses were prospectively assessed in cohorts of 83 infants born to human immunodeficiency virus (HIV)- and of 48 infants born to non-HIV-infected mothers. Of the infants born to HIV-infected mothers, 18 were themselves infected with HIV, 26 were indeterminant and 39 were free from HIV. Ten RSV illnesses occurred in 8 HIV-infected, 2 illnesses in 2 indeterminant and 17 illnesses occurred in 17 non-HIV-infected children. RSV shedding was prolonged in HIV class P2- vs. non-HIV-infected children, at medians of 30 days (range, 1 to 199 days) and 6 days (range, 1 to 21 days), respectively (P = 0.02). Ribavirin and intravenous immunoglobulin failed to eradicate RSV from one child who shed virus for 199 days. Wheezing occurred in 1 of 4 vs. 9 of 10 episodes of lower respiratory tract illness in HIV-infected and non-HIV-infected children, respectively (P = 0.04). No differences were noted in duration of illness, temperature, respiratory rate or oxygen saturation between HIV- and non-HIV-infected children. Infection control and public health concerns regarding prolonged shedding of RSV in HIV-infected children must be recognized.

AIDS-Related Opportunistic Infections↗
PubMed1993

Clinical severity of respiratory syncytial virus group A and B infection in Sydney, Australia.

Respiratory syncytial virus (RSV) has two major antigenic groups, A and B. There is disagreement as to whether or not there is a difference in the clinical severity of disease caused by the two RSV groups. This 3-year prospective study of infants and children with RSV-positive bronchiolitis examines the relative virulence of RSV Groups A and B and assesses the role that breast-feeding may have in modifying the clinical severity of infection. Clinical severity was graded I (ventilated, severe), II (oxygen therapy, moderate), III (no ventilation or oxygen, mild). RSV serogrouping was performed. After exclusion of 60 subjects with known predisposing factors for severity, 444 infants and children were studied (Group A, 337; Group B, 107). The difference in proportion of subjects with severity grade I and II with Group A compared with Group B infection was 6% (95% confidence interval, 4.7 to 16.7). For infants 0 to 6 months of age this difference was 5.6% (95% CI, 7.3 to 18.4). Nineteen cases were nosocomially transmitted. There was a predominance of Group A RSV infection but no difference in severity between Group A and Group B infection.

Age Factors↗
PubMed1993

Detection of alpha-interferon in nasopharyngeal secretions and sera in children infected with respiratory syncytial virus.

We investigated the relationship between respiratory syncytial virus (RSV) antigen and interferon (IFN) in nasopharyngeal secretions (NPS) and sera obtained from 252 patients infected with RSV. A total of 146 (57.9%) of 252 patients had IFN in NPS with a mean titer of 28 units/ml and IFN was detected in 164 (71.6%) of 229 patients in the acute stage sera with a mean titer of 28 units/ml. IFN activities were neutralized with antiserum to IFN-alpha. RSV antigen in NPS decreased on Day 5 and later in parallel with the change of mean titer of IFN in NPS. IFN in NPS was detected in 40 to 60% of the samples with some fluctuation in the acute stage. Within 4 days IFN was detected in more than 70% of the sera whereas on Day 5 and later the IFN positivity rate decreased in sera. RSV antigen in NPS decreased in the older patient groups. No significant change of positive rate of IFN in NPS was observed in different age groups and the mean titer of IFN in NPS and sera did not vary with age, except in those younger than 3 months and older than 3 years of age.

Age Factors↗
PubMed1994

Passive protection against respiratory syncytial virus disease in infants: the role of maternal antibody.

Respiratory syncytial virus (RSV) is responsible for serious respiratory disease in young infants. More than 75% of the 678 children hospitalized for RSV at Baylor-affiliated hospitals in Houston, TX, between October, 1992, and March, 1993, were 5 months of age or younger. The importance of maternal antibody in the immunity against RSV disease has been debated. More recent epidemiologic studies have demonstrated protection against RSV in babies born to mothers with high levels of neutralizing RSV antibody. The contribution of IgG fusion or F protein antibody as a correlate with immunity from disease also has been described. With the availability of purified F protein vaccines such as the purified F protein vaccines manufactured by Lederle-Praxis-Biologicals (Pearl River, NY), immunization of pregnant women with RSV surface glycoproteins to arm the newborn with high neutralizing antibody can be considered. Advantages of maternal immunization to augment naturally occurring maternal RSV antibody are that babies most at risk for infection are least responsive to vaccines, that pregnant women respond well immunologically to vaccines in general and that placental transfer of maternal IgG antibody occurs naturally during the third trimester. The safety of maternally derived antibody would likely surpass that of exogenously administered immunoglobulin as well as would have a decreased cost. Disadvantages of maternal immunization to protect infants against RSV could include the potential inhibition of the infant's response to active immunization or subsequent disease, the lack of antibody transfer in premature infants, and liability issues. Evaluation of purified F protein vaccine in postpartum women is under way.

Antibodies, Viral↗
PubMed1994

Safety and immunogenicity of a subunit respiratory syncytial virus vaccine in children 24 to 48 months old.

A subunit vaccine for respiratory syncytial virus (RSV) consisting of purified fusion glycoprotein (designated PFP-1) was tested in children 24 to 48 months old. Two doses of 20 micrograms (n = 13) and 50 micrograms (n = 10) were compared with a saline (n = 24) placebo control group. Local and systemic reactions, reported within 96 hours postvaccination, were mild, transient, and did not differ significantly from the control cohort. Long term follow-up through at least one, and in some cases two, RSV seasons showed no serious RSV illness in vaccinees at any time. There was, therefore, no evidence of disease enhancement postvaccination. In the 20-micrograms cohort, 92% responded to vaccination by a 4-fold increase in enzyme-linked immunosorbent titer to the F glycoprotein and 42% had a 4-fold or greater rise in neutralizing titer to the A2 virus. In the 50-micrograms cohort 100% responded by enzyme-linked immunosorbent to the F glycoprotein and 70% responded by A2-neutralizing titers. The neutralizing titers in the vaccinated cohorts were similar to those seen previously in adults. These data show the ability of the subunit vaccine to boost existing immunity and to prime for a response to natural virus exposure in children who were seronegative at the time of vaccination.

Child, Preschool↗
PubMed1996

Purified fusion protein vaccine protects against lower respiratory tract illness during respiratory syncytial virus season in children with cystic fibrosis.

OBJECTIVE: To test in a double blind, placebo-controlled study a purified fusion protein (PFP-2) vaccine against respiratory syncytial virus (RSV) in RSV-seropositive children with cystic fibrosis (CF). METHODS: Seventeen CF children, mean age 4.5 years, received PFP-2 vaccine and 17 CF children, mean age 5.8 years, received a saline vaccine. At enrollment the Shwachman clinical score, Brasfield radiographic score, oxygen saturation (SpO2), anthropometric indices and other variables were recorded. After vaccination the reactions were assessed daily for 7 days. During the RSV season weekly telephone interviews were performed and children with an acute respiratory illness were evaluated and cultured for RSV. Serum was drawn before vaccination, 1 month after vaccination and at the end of the RSV season and tested for antibodies to RSV. RESULTS: Other than age the baseline measurements at enrollment were similar between groups. The PFP-2 vaccine produced mild local reactions and induced a significant neutralizing antibody response in two-thirds of the vaccinees and a significant enzyme-linked immunosorbent assay-fusion glycoprotein antibody response in nearly all the PFP-2 vaccinees. Vaccine-enhanced disease was not observed in PFP-2 vaccines infected with RSV. Protection against RSV infection was not observed; however, a significant reduction (t test, P < 0.01) in mean number of lower respiratory tract illnesses (0.8 vs. 2.1), antibiotic courses (2.2 vs 4.5) and days ill (30.5 vs. 67) occurred among RSV-infected PFP-2 vaccinees. CONCLUSIONS: Efficacy of the PFP-2 vaccine against lower respiratory tract illness during the RSV season was shown in RSV-seropositive children with CF.

Child↗
PubMed1996

Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants.

BACKGROUND: Recent studies in animals with experimental respiratory syncytial virus (RSV) infection indicate that passive immunization by intranasal or intratracheal application of gamma-globulins (immunoglobulins) may be beneficial for treatment of infants with lower respiratory tract infection caused by RSV. METHODS: We conducted a placebo-controlled, randomized multicenter study involving 68 infants with proven RSV infection admitted to 5 pediatric centers in Switzerland from November 1, 1992, through April 30, 1993. Treatment was carried out with aerosolized human IgG (Sandoglobulin) by assisted ventilation. On the day of hospital admission a single dose of 0.1 g of IgG per kg of body weight in a 5% solution or an identical amount of placebo, each delivered in 2 parts, was given. RESULTS: The two groups did not differ substantially in their response to the aerosol received. The rate of improvement for symptoms of respiratory tract infection, oxygen requirement and length of hospital stay were comparable for both groups. There was a significant reduction (P < 0.05) in the frequency of apneic spells observed in the treatment group by Day 3 posttreatment. Aerosol therapy was generally well-tolerated in nonintubated infants, but some severe side effects (increased oxygen requirements in two patients, pneumothorax in one patient) were observed in two of three intubated and ventilated infants treated with IgG. CONCLUSIONS: Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.

Aerosols↗
PubMed1998

Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia. DESIGN: Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial. PATIENT POPULATION: Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation. STUDY AGENTS: Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9% saline intravenously every 30 days for up to five doses. RESULTS: MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response. The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively). CONCLUSIONS: MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.

Antibodies, Monoclonal↗
PubMed1998

Sequential annual administration of purified fusion protein vaccine against respiratory syncytial virus in children with cystic fibrosis.

BACKGROUND: We recently showed the clinical benefit of the PFP-2 vaccine for respiratory syncytial virus (RSV) for children with cystic fibrosis (CF). OBJECTIVE: To determine the safety and immunogenicity of yearly sequential administration of the PFP-2 vaccine in CF children. STUDY DESIGN: Twenty-nine of the 34 CF children who participated in the previous study were enrolled in this open label vaccine study. All of the CF children ages 2.6 to 8.9 years received the PFP-2 vaccine, the PFP/PFP group received the PFP-2 vaccine in 1993 and 1994 and the saline/PFP group received the vaccine for the first time in 1994. At entry demographic data and measurements of lung function and nutrition were collected. Microneutralization test, enzyme-linked immunosorbent assay to F protein and Western blot assay were performed on plasma drawn before and 4 weeks after vaccination and at the end of the RSV season. During the study weekly telephone calls were made and acute respiratory illnesses were evaluated. RESULTS: Baseline measurements were similar between groups. Systemic and local vaccine reactions were mild and similar for both groups. A 4-fold or greater neutralizing antibody rise to RSV occurred in 4 of 14 (28.6%) and 9 of 14 (64.3%) in PFP/PFP and saline/PFP groups (P = 0.13), respectively. Four children in the PFP/PFP group and 7 in the saline/PFP group were infected with RSV. A reduction in lower respiratory illnesses (1.0 vs. 2.0), antibiotic courses (2.5 vs. 5.6) and days of illnesses (37.3 vs. 93.1) was observed in the PFP/PFP vaccinees infected with RSV compared with the saline/PFP group (t test; P < or = 0.05). One death occurred in the PFP/PFP group; the cause of death was consistent with septic shock and unrelated to vaccination or RSV infection. CONCLUSION: Sequential annual PFP-2 vaccination was safe and not associated with exaggerated respiratory disease.

Antibodies, Viral↗
PubMed1998

Costs and benefits of respiratory syncytial virus immunoglobulin to prevent hospitalization for lower respiratory tract illness in very low birth weight infants.

BACKGROUND: Respiratory syncytial virus immunoglobulin intravenous (RSV-IGIV) has been shown to reduce the risk of lower respiratory illness (LRI) hospitalization in preterm infants and infants with bronchopulmonary dysplasia (BPD). The purpose of this analysis was to estimate the economic costs and benefits of prophylaxis with RSV-IGIV in these groups. METHODS: The analysis was performed from a payer's perspective and therefore included only costs and cost savings that would be realized by an insurer. Estimates of the direct costs of prophylaxis and the risk and cost of LRI hospitalization were based on data about preterm very low birth weight infants cared for at our medical center. Estimates of the reduction in risk of LRI hospitalization associated with RSV-IGIV were based on data from a randomized trial (the PREVENT Study). RESULTS: The range of cost for a five-dose course of RSV-IGIV was estimated to be $3280 to $8800 for infants weighing 1.2 to 10.0 kg at the time of the initial dose. Risks of LRI hospitalization were estimated to be 12, 17 and 28%, respectively, for preterm infants without BPD, with mild BPD and with moderate to severe BPD. Estimates of duration and per diem cost of LRI hospitalizations were, respectively, 5 days and $971. The estimated net cost of prophylaxis per infant ranged between $5415 for a 6-kg infant without BPD to $1689 for an infant with BPD and age < or =3 months. CONCLUSIONS: The cost of RSV-IGIV typically exceeds the cost of hospitalizations prevented by several thousand dollars. Cost minus benefit is lower for infants with BPD and infants 3 months of age or younger.

Cost-Benefit Analysis↗
PubMed1998

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.

Antibodies, Monoclonal↗