Respiratory syncytial virus infections in hospitalized Canadian children: regional differences in patient populations and management practices. The Pediatric Investigators Collaborative Network on Infections in Canada

Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for respiratory tract infection during the first 2 years of life. The optimal approach to management remains controversial. During the 1991 to 1992 RSV season RSV-infected children admitted to eight Canadian tertiary care pediatric centers were followed to: (1) assess the morbidity and mortality attributable to RSV infection among hospitalized patients with and without known risk factors for severe disease; and (2) assess regional variation in the management of RSV infection. Of 529 RSV-infected patients 69% (363) had one or more of the risk factors for severe disease and the remaining 31% (166) had none. There were significant differences (P < or = 0.01) between the high and low risk groups, respectively, for: intensive care unit admission (27%, 2%), assisted ventilation (14%, 0.6%), ribavirin therapy (20%, 2%), supplemental oxygen (75%, 34%), antibiotic therapy (69%, 58%) and length of hospital stay > or = 7 days (39%, 6%). Among low risk patients, centers varied significantly (P < or = 0.01) in the use of systemic corticosteroids (from 3 to 69% of patients), supplemental oxygen (13 to 74%), bronchodilators (68 to 93%) and ribavirin (0 to 10%). The observed regional variation in management of hospitalized children with RSV infection has implications for both the costs of hospital care and the conduct of multicenter trials of ribavirin and other therapies for RSV infection.     

Gender differences in N-alkyl protoporphyrin IX production in rats after the administration of porphyrinogenic xenobiotics

OBJECTIVE: To study the effect of an educational intervention on the management of hospitalized infants with bronchiolitis. DESIGN: Sequential, prospective cohort study. SETTING: A 235-bed children's hospital with nearly all private rooms. PATIENTS: Consecutively admitted, previously healthy children younger than 24 months with symptoms of bronchiolitis. The first cohort was enrolled between January 1 and January 21, 1996; the second cohort between January 29 and February 18, 1996, following a 1-week intervention period; the third (follow-up) cohort between December 1996 and February 1997. INTERVENTION: Educational program and practice guidelines aimed at appropriate utilization of diagnostic tests, decreased antibiotic and bronchodilator use, increased compliance with isolation, decreased length of stay, and maintenance of quality care. MAIN OUTCOME MEASURES: Utilization of respiratory syncytial virus (RSV) enzyme immunoassay, initiation and duration of parenteral antibiotic therapy, number of nebulized bronchodilator treatments, isolation orders, length of stay, and readmission rate. RESULTS: A total of 90 patients were studied preintervention, 63 postintervention, and 90 during the follow-up period. The groups were comparable in demographic and clinical features. No patient had a documented serious bacterial infection; however, almost half in each group received parenteral antibiotics, despite recommendations against this. Immediately postintervention, children with positive RSV test results received antibiotics on fewer days than other children (median 0.6 vs 2.4 days; P=.004), suggesting that physicians stopped treatment with antibiotics once a viral diagnosis was confirmed. This effect did not persist into the follow-up period. Viral testing was reduced and isolation orders increased. Use of bronchodilators was reduced from 91% preintervention to 80% during the follow-up period (P=.046), and the median number of treatments was reduced from 15.0 to 10.0 (P=.005). There was no change in length of stay, which was 2 to 3 days, or in readmission rate, which was 1% to 4%. CONCLUSION: Educational efforts centered around practice guidelines can improve some aspects of the treatment of patients hospitalized with bronchiolitis.     

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.     

Approaching the RSV season with a nursing plan of action

As the statistics show with year-in, year-out regularity, during November through March in the United States, approximately 90,000 infants and young children will be hospitalized with a severe lower respiratory infection attributable to the respiratory syncytial virus (RSV). This virus, discovered only as recently as 1956, appears to be ubiquitous, infecting virtually 100% of children by age 4. For most of them the resulting illness will be mild and easily vanquished by an intact immune system. For some, however, RSV infection confers considerable morbidity, and these infants and children are the concern of the symposium held in conjunction with Pediatric Nursing's 11th annual conference. The symposium addressed several aspects of RSV infection: Who is at risk and should be hospitalized? How can nurses contribute to the care of hospitalized patients? Are there environmental risks to health-care personnel from ribavirin aerosol, the antiviral treatment approved for RSV infection? Are there special considerations for mechanically ventilated patients? Speakers generally concluded that symptomatic treatment and antiviral therapy with ribavirin aerosol can reduce severe morbidity in severely infected patients with minimal occupation risk to health-care personnel.     

Immunological properties of plaque purified strains of live attenuated respiratory syncytial virus (RSV) for human vaccine

Respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in infants, young children, and the elderly. Efforts to develop satisfactory live or inactivated vaccines have not yet been proven successful. Our research focuses on the development of four purified live attenuated RSV sub-type A human vaccine clones. Temperature sensitive (ts) and attenuated purified clones of either cold-adapted (ca) RSV or high-passage (hp) RSV were administered intra-nasally (i.n.) to BALB/c mice and tested for immunogenicity. All four clones produced significant anti-RSV F IgG2a and IgG1 titres in the sera of mice, RSV-specific neutralizing titres higher than those produced by their wild-type progenitor viruses, cytotoxic T-lymphocyte (CTL) activity, and total protection against wild-type (wt) viral challenge. These purified vaccine candidates await testing in humans to determine which contain the required balance between immunogenicity and attenuation.     

High resolution EEG

Rhinovirus is an important cause of respiratory infection among all age groups, but it is primarily thought of as being responsible for upper respiratory tract infection. Rhinovirus was isolated from the respiratory tract of 48 pediatric patients who were hospitalized (40) or seen in a pediatric emergency room (8) during the period of July, 1985, through December, 1988. Twenty-eight (58%) of the patients presented during the spring and early summer. Forty-one (86%) of the 48 patients were less than 12 months of age. All except four of the patients had viral cultures performed because of respiratory symptoms. Bronchiolitis was the single most frequent clinical diagnosis and was noted in equal proportion among children less than 3 months and 3 to 12 months of age. Nine patients were assigned a diagnosis of suspected sepsis. Rhinovirus infection was a complication of underlying illness for 17 (44%) of the 40 hospitalized patients, and those patients tended to be older than the otherwise healthy hospitalized infants with rhinovirus. Twenty-six patients (54%) were treated with antibacterial agents, although only one patient was documented to have a concomitant bacterial infection (Chlamydia trachomatis). Overall rhinovirus isolation during the study period represented 0.7% of all specimens submitted for viral isolation compared with 8.2% for respiratory syncytial virus. Rhinovirus infection leads to hospitalization less frequently than does respiratory syncytial virus infection, but the severity of illness and clinical presentation in young infants are similar.     

Preparation of respiratory syncytial virus subgroup A and B antigens for enzyme immunoassay antibody detection

A simplified method was described for purification of respiratory syncytial virus (RSV) subgroup A and B aimed to be used as antigens in enzyme immunoassay (EIA). The titer of each RSV subgroup and the amount of protein was determined from the visible band in 45% sucrose gradient. The quality of prepared RSV subgroup antigens for EIA was described in terms of the achievable final titer, the amount of protein, and EIA criss-cross titration. The RSV subgroup A and B antigens, diluted as 1:100 (low opalescent band in 45% sucrose layer) or 1:800 (high opalescent band in 45% sucrose layer) produced a positive reaction in EIA criss-cross titration with IgG antibodies from the patient's serum (convalescent phase) diluted as 1:25,600 (for RSV A) and 1:6,400 (for RSV B). This method offers shorter and more simplified steps of viral antigen purification, and provides acceptable quantity and quality of viral antigens appropriate for use in EIA.     

Respiratory syncytial virus infection in tropical and developing countries

Little is known about the epidemiology of respiratory syncytial virus (RSV) infection in tropical and developing countries; the data currently available have been reviewed. In most studies, RSV was found to be the predominant viral cause of acute lower respiratory tract infections (ALRI) in childhood, being responsible for 27-96% of hospitalised cases (mean 65%) in which a virus was found. RSV infection is seasonal in most countries; outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates and in the wet season in tropical countries with seasonal rainfall. The situation on islands and in areas of the inner tropics with perennial high rainfall is less clear-cut. The age group mainly affected by RSV in developing countries is children under 6 months of age (mean 39% of hospital patients with RSV). RSV-ALRI is slightly more common in boys than in girls. Very little information is available about the mortality of children infected with RSV, the frequency of bacterial co-infection, or the incidence of further wheezing after RSV. Further studies on RSV should address these questions in more detail. RSV is an important pathogen ill young children in tropical and developing countries and a frequent cause of hospital admission. Prevention of RSV infection by vaccination would have a significant impact on the incidence of ALRI in children in developing countries.     

Detection of Bordetella pertussis and respiratory synctial virus in air samples from hospital rooms

OBJECTIVE: To evaluate the distribution of Bordetella pertussis and respiratory syncytial virus (RSV) in the hospital setting. DESIGN: Air samples were collected using filters in the hospital rooms of 12 children with pertussis and 27 children with RSV infection. Material eluted from these filters was subjected to RSV- and B pertussis-specific polymerase chain reaction (PCR) amplification. SETTING: Patients were hospitalized in private rooms in one of two referral centers, a university teaching hospital and a university-affiliated private children's hospital. PATIENTS: 12 children (16 days-3 years of age) with documented pertussis infection and 27 patients (10 days-7 years of age) with documented RSV infection. RESULTS: B pertussis DNA was detected in 7 (58%) of 12 rooms housing pertussis patients and in 16 (25%) of 63 total samples. B pertussis DNA was detected as far as 4 m away from the patient's bedside. The detection of B pertussis DNA in air samples did not change over the short duration of hospitalization. RSV RNA was detected in 17 (63%) of 27 rooms housing RSV-infected patients and in 32 (22%) of 143 total samples. RSV RNA was detected at distances as far as 7 m from the patient's bedside and for up to 7 days of hospitalization. CONCLUSIONS: Using PCR-based detection methods, B pertussis DNA and RSV RNA both can be detected in air samples from the hospital rooms of infected patients. Both can be detected at large distances from a patient's bedside in a minority of cases. These detection methods are suitable for further studies of control measures used to contain nosocomial infections caused by both B pertussis and RSV.     

Phospholipase A2 activity in salivary glands and saliva of the lone star tick (Acari: Ixodidae) during tick feeding

The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors. In the present study, the possibility of an infectious etiology was prospectively studied in 27 consecutive patients with SAT. Special emphasis was put on the role of enteroviruses. Coupled sera (interval one month) were taken from all patients and single sera from 29 control subjects for virus antibody determinations. Stool samples were collected for virus isolation and fine-needle aspiration samples from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken from SAT patients. Enteroviral antibodies were tested using three different methods: indirect EIA, heavy chain capture RIA, and standard complement fixation (CF) test. Antibodies against other common viral pathogens, including enteroviruses, were screened using the CF test and those against Mycoplasma pneumoniae and Chlamydia pneumoniae using EIA and microimmunofluorescence techniques, respectively. Common respiratory viruses were also screened from nasopharyngeal suction samples by antigen detection EIA. Based on serological findings, one patient had acute Cytomegalovirus infection. All other patients were negative in antibody tests, virus isolation, RT-PCR, and antigen detection. Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine-needle aspiration samples. There was no evidence of recent enteroviral infections in SAT patients. The results suggest that SAT is not usually associated with acute infections. No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.     

Antigenic and nucleic acid analysis of nosocomial isolates of respiratory syncytial virus

Monoclonal antibodies and ribonuclease protection were used to analyze antigenic and genomic diversity among 42 isolates of group A respiratory syncytial virus (RSV) from studies of nosocomial RSV carried out at the University of Rochester during the 1974-1975 and 1975-1976 RSV seasons. Three distinct subgroups or lineages and a total of 12 viral variants were present. Against this background of diversity, an outbreak was recognized that included 13 indistinguishable isolates occurring during a 2-week period. This outbreak accounted for 6 of the 8 infants with nosocomial infection. In contrast to the limited diversity of the nosocomial isolates, isolates from the 10 infants with community-acquired infection included 8 variants. Like those from community outbreaks of RSV, isolates of RSV from hospitalized patients are virologically heterogeneous. However, discrete outbreaks associated with transmission of a single strain can occur.     

Effects of viral respiratory disease education and surveillance on antibiotic prescribing

BACKGROUND AND OBJECTIVES: We describe a partnership between family practice residency clinics and a state public health virology laboratory that has produced comprehensive viral respiratory disease education and surveillance. Family practice residents have been provided with education on respiratory viruses and the results of ongoing viral surveillance. The preliminary effects of this program on antibiotic prescribing by senior residents are evaluated in this paper. METHODS: We used a questionnaire to assess the acceptance by family practice residents of the educational component and the utility of ongoing viral surveillance. We used chart review to evaluate rates of antibiotic prescribing and the number of patients diagnosed per year with acute upper respiratory infection and acute bronchitis by senior residents in 1992 (preexposure) and 1996 (postexposure). RESULTS: By the third year of training, most residents (79%) reported receiving adequate training regarding common viral respiratory diseases. Moreover, residents reported that they were less likely to prescribe antibiotics to patients presenting with respiratory infections when provided with specific information on circulating viral pathogens. Antibiotic prescribing in the postexposure group was 68% lower for upper respiratory infection (URI) and 45% lower for a composite of URI and bronchitis. CONCLUSIONS: Education and monitoring of circulating respiratory viruses can result in familiarity with common disorders in primary care and reduce unnecessary antibiotic use.     

Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia

BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia. OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia. PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia. Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group). The 2 patient groups were comparable in their clinical and laboratory profiles. RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001). The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04). The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04). The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001). Doxycycline was as efficacious as the other regimens chosen for the treatment of community-acquired pneumonia. CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia.     

Chromosomal response of insect and mammalian cells to streptonigrin: a comparative study

Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO2, pCO2 and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO2 and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8-6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3-12.9) in children with recurrent episodes of apnoea. CONCLUSIONS: Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea.     

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.     

Etiology of pneumonia and other common childhood infections requiring hospitalization and parenteral antimicrobial therapy. SE-TU Study Group

The etiology of acute lower respiratory tract infections (mostly pneumonia) in children is well characterized, but these are only some of the community-acquired infections warranting parenteral antimicrobial therapy. We prospectively evaluated all such infections among children aged 3 months to 15 years by use of blood cultures, examination of nasopharyngeal aspirates, and serologies for 15 viral, 7 bacterial, and 1 protozoal agent. Immunocompromised patients and those with urinary tract infection, meningitis, or osteoarticular infection were excluded. In all, 170 children were included. The pathogenic agent was identified in 62% of the cases. Bacteria were detected in 54%, and a pneumococcus was found in 59% of the cases identified. Viruses were found in 15% overall. Sole bacterial or viral infections were detected in 47.1% and 8.1%, respectively. Since thorough screening established the etiology in less than two-thirds of patients ill enough to be hospitalized and treated parenterally, better diagnostics are needed, especially to identify those who would truly benefit from antimicrobial therapy.     

Repeatability of treadmill exercise ejection fraction and wall motion using technetium 99m-labeled sestamibi first-pass radionuclide ventriculography

Bacterial antibodies were studied in acute, intermediate and convalescent phase sera (mean duration from first to last sample 36 days) of 121 children hospitalized for acute lower respiratory tract infection. Antibody responses were observed in 45% of all cases and in 29% of the 21 children < 1 year old. A total of 15 responses to Streptococcus pneumoniae (pneumolysin), 20 to Haemophilus influenzae, 9 to Moraxella catarrhalis, 3 to chlamydiae and 8 to Mycoplasma pneumoniae were found. In 79 patients with 4 consecutive samples available, 52% of the 31 responses were measurable within 5 days from admission. Overall the responses were not associated with upper respiratory tract bacterial findings or acute otitis media. Significantly more responses were found in the 121 children with acute lower respiratory tract infection than in healthy controls (P < 0.007). We conclude that bacterial antibody assays provide a useful tool in the study of the etiology of acute lower respiratory tract infection in young children, even if the interval between paired serum samples is short.     

Long-term follow-up of a randomized trial on adjuvant chemotherapy and hormonal therapy in locally advanced breast cancer

Epidemiological research on respiratory syncytial virus (RSV) infections in children was carried out at the Virology Laboratory, University Teaching Hospital (UTH), in Lusaka, Zambia, from January-December 1996. Specimens including 736 nasal washings and 2424 throat swabs were collected from children with acute respiratory infections (ARI) and tested for RSV by enzyme immunoassay and by virus isolation. RSV was isolated in 62 (4.1%) of 1496 throat swabs collected from March to September and was detected in 99 (16.3%) of 609 nasal washings from March to November. The average RSV isolation rate was 2.6% and the average RSV detection rate was 13.5%. The highest RSV isolation (8.1%) and detection (30.5%) rates were in June 1996. RSV antibody in the 278 serum specimens collected from Zambian children, who were hospitalized in the paediatric ward, UTH, was detected using a standard neutralization test. The antibody positive rate was 60-80% in children > 4 years. It is evident that RSV is one of the main causal agents of ARI in children in Zambia.     

Patient compliance in the treatment of respiratory tract infections

The survey on outpatients compliance in the treatment of respiratory tract infections was performed in Croatia during April 1996. A total of 213 physicians, 201 adult patients, and 178 parents of sick children were polled by the appropriate questionnaires. The results have shown that in the treatment of respiratory tract infections physicians commonly prescribe thrice-daily antibiotic regimens for 8-10 days. Concerning patients' knowledge, 85% of patients deem that regularity, and 64% that duration of antibiotic administration influences treatment outcome. Over 80% of patients are compliant with once-or twice-daily regimens, but only 50% take regularly and timely drugs that are dosed every 6 or 8 hours. Common reasons for irregular taking of antibiotics are forgetfulness and dosing during sleeping. In terms of appropriate duration of antibiotic therapy, about 20% of patients usually take antibiotic for 8-10 days, 60% for 5-7 days, and 20% for < or = 4 days. It may be concluded that the patients are poorly compliant with oral antibiotics treatment.