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.     

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.     

Effect of rHuEpo therapy in dialysis patients on endogenous erythropoietin synthesis after renal transplantation

BACKGROUND: Pertussis is a highly contagious respiratory disease and the most serious effects occur in young infants. Recently it has been shown that rapid and highly specific PCR can be a useful diagnostic tool for detection of pertussis infection. To our knowledge there are no previous studies concerning the disappearance of Bordetella pertussis DNA from the nasopharynx during antimicrobial treatment. METHODS: We studied prospectively how rapidly live B. pertussis organisms and DNA of these bacteria disappear from the nasopharynx during erythromycin therapy in unvaccinated infants. Eighty-five nasopharyngeal swabs obtained from nine erythromycin-treated infants with pertussis on consecutive days during hospitalization were tested by PCR and culture. The PCR products were further analyzed by Southern hybridization. RESULTS: On the fourth day of treatment 56% of the samples were positive by culture and 89% by PCR, whereas after 7 days the rates were 0 and 56%, respectively. In seven of nine patients PCR remained positive for 1 to 7 days longer than culture. The follow-up study also showed the semiquantitative nature of the PCR assay. The intensity of the PCR products in agarose gel usually weakened with time during erythromycin therapy. CONCLUSIONS: The results of this study show that PCR assay can achieve the specific diagnosis of pertussis infection in a large proportion of infants even when antimicrobial treatment has killed the organisms and culture is no longer positive.     

Polymerase chain reaction for the detection of Bordetella pertussis in clinical nasopharyngeal aspirates

A PCR procedure for the detection of Bordetella pertussis in nasopharyngeal aspirates (NPAs) was developed with primers derived from the pertussis toxin promoter region. The amplification resulted in a 191-bp PCR product specific for B. pertussis. A total of 681 NPAs collected from children with cough lasting >7 days was evaluated by PCR and culture; 104 aspirates were positive by PCR and 93 by culture. Sixteen cases were positive only by PCR and five culture positive aspirates were negative by PCR. An internal control was included in the assay to monitor the performance of the PCR and to identify possible inhibitory components in clinical samples. The PCR method was more efficient than culture in detecting B. pertussis in samples collected late in the disease, in antibiotic-treated children and in patients with mild disease.     

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.     

Whooping cough caused by Bordetella pertussis and Bordetella parapertussis in an immunized population

CONTEXT: The prevalence of Bordetella pertussis and Bordetella parapertussis infections among outpatients in an immunized population is not known. OBJECTIVE: To study the prevalence of these infections in outpatients with paroxysmal cough in Finland, where the pertussis vaccine coverage of 4 doses is 98%. DESIGN: Prospective cohort study. SETTING: Thirty-two health centers in southwestern Finland. PATIENTS: A total of 584 patients with paroxysmal cough seen at local health centers from October 1994 through March 1997 from whom nasopharyngeal swabs were collected. MAIN OUTCOME MEASURES: Prevalence of positive cultures for B pertussis or B parapertussis and/or positive polymerase chain reaction (PCR) results and frequency of symptoms in those with pertussis and parapertussis. RESULTS: A total of 153 subjects (26.2%) had Bordetella infection by culture or PCR: 93 (60.8%) had B pertussis infection, 49 (32.0%) had B parapertussis infection, and 1 1 (7.2%) had both. Of these cases, 39 (25.5%) had positive cultures and 95 (62.1%) had positive PCR results for B pertussis, and 19 (12.4%) had positive cultures and 55 (35.9%) had positive PCR results for B parapertussis. At the time of diagnosis, no difference was found in the frequency of symptoms between patients with B parapertussis infection and those with B pertussis infection. Bordetella parapertussis infection was as common as B pertussis infection in children before school entry, whereas in schoolchildren and adults, B pertussis infection was more common than B parapertussis infection (P<.001). CONCLUSION: Bordetella infections are common in an immunized population, and B parapertussis infections apparently are more prevalent than previously documented.     

ECLS in pertussis: does it have a role?

OBJECTIVES: To investigate the value of extracorporeal circulatory life support (ECLS) in paediatric patients with severe Bordetella pertussis infection. DESIGN: Single case report and a review of the ECLS database. SETTING: Tertiary referral hospital paediatric intensive care unit. PATIENTS AND PARTICIPANTS: A single case report of an infant with B. pertussis infection is described. Despite receiving ECLS, this infant died from overwhelming cardiac and cerebral insults. Outcome for children receiving ECLS registered on the Extracorporeal Life Support Organization database is reviewed. MEASUREMENTS AND RESULTS: The mortality of infants receiving ECLS for B. pertussis infection is high, with only 5 survivors reported among 22 registered cases. The majority of nonsurvivors had evidence of circulatory collapse in addition to severe respiratory failure, and these patients commonly died of hypoxic-ischaemic cerebral insult. These data suggest the existence of a subgroup of patients with respiratory failure only, who may benefit from ECLS, and a larger subgroup who suffer ischaemic cardiac and cerebral insults which are unlikely to be improved by ECLS. CONCLUSIONS: The value of ECLS in patients with B. pertussis infection who present with major cardiac dysfunction is questionable. Such patients almost invariably have a poor outcome despite maximal therapy.     

A histopathological comparison of the uvula between snorers and non-snorers

To study the specificity of serum antibodies against filamentous hemagglutinin (FHA) and pertactin for infection with Bordetella pertussis, we followed the acquisition of IgG serum antibodies against these 2 surface proteins of the organism in children who had been vaccinated with a monocomponent pertussis toxoid vaccine and who had experienced no symptoms of pertussis. Antibodies were estimated with enzyme-linked immunosorbent assay. In Part 1 of our study 5 consecutive samples obtained between 3 and 36 months of age from 71 children were available. Most had maternally derived antibodies to FHA (70 of 71) and pertactin (51 of 71) in the 3-month sera which declined in the subsequent sera. From about 1 year of age there were small but significant increases in antibodies against both antigens. At 3 years of age 71 of 71 had antibodies to FHA and 58 of 71 had antibodies to pertactin. In Part 2 of our study sera from 109 three-year old children were available. The 12 children with a history of family exposure to pertussis had significantly higher geometric mean titers of FHA antibodies than the 97 children with no history of family exposure. The geometric mean titers of pertactin antibodies did not differ. We suggest 3 explanations for the acquisition of FHA and pertactin antibodies in children with no history of pertussis: (1) asymptomatic B. pertussis infection in vaccinated children; (2) infection with Bordetella parapertussis; (3) infection with cross-reacting antigens from other organisms, e.g., nonencapsulated Haemophilus influenzae.     

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.     

The use of serodiagnosis in the retrospective investigation of a nursery outbreak associated with Escherichia coli O157:H7

AIMS: To use serology to investigate an outbreak of verocytotoxin (VT) producing Escherichia coli O157 in a hospital nursery, following the detection of faecal E coli O157 (phage type 49) producing VT type 2. METHODS: ELISA and immunoblotting techniques, based on lipopolysaccharide (LPS) purified from E coli O157; diagnostic bacteriology; serotyping and phage typing; DNA probes for VT. RESULTS: 29 of 126 sera contained antibodies to the LPS of E coli O157: 10 were from children, three were from staff, and 11 were from hospital kitchen staff. Five parents of children attending the nursery were antibody positive. Sixty four sera from other hospital staff and controls did not contain antibodies to the LPS of E coli O157. CONCLUSIONS: Serology detected evidence of infection with E coli O157 in 23% of sera examined. By bacteriology alone, only a single case of infection with E coli O157 would have been detected. Serology is valuable in providing evidence of infection with E coli O157.     

Regulation and tissue distribution of the human sodium iodide symporter gene

The inclusion of an appropriate internal control DNA in polymerase chain reaction (PCR) is a rapid and simple method for the detection of PCR failure. Two PCR coamplification internal control DNAs (ICD I and ICD II) with the same primer-binding sequences as the target DNA for the detection of Bordetella pertussis and Bordetella parapertussis were produced using an overlap extension technique and a PCR MIMIC construction kit, respectively. The ICD II was further evaluated in a prospective clinical study in 360 patients with a clinical diagnosis of pertussis. From 360 nasopharyngeal swabs the internal control was positive in 318 (88%) samples, but was negative in 42 (12%). After phenol-chloroform extraction an additional 10 internal controls became positive. For the detection of PCR failure, the use of internal control DNA is highly recommended for PCR-based identification of B. pertussis and B. parapertussis organisms from nasopharyngeal swabs and aspirates.     

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.     

Effect of rapid viral diagnosis on the management of children hospitalized with lower respiratory tract infection

BACKGROUND: Although rapid viral tests are commonly used in children with lower respiratory tract infection, their effect on patient management has not been studied. OBJECTIVES: To examine how physicians utilize an enzyme immunoassay for respiratory syncytial virus (RSV EIA) and a centrifugation-enhanced cellular immunofluorescence assay for multiple viral pathogens [viral respiratory panel (VRP)] in children hospitalized with respiratory illness; to determine the effect of testing on length of stay, antibiotic use and costs; and to determine physician attitudes toward RSV testing. DESIGN AND SETTING: Prospective study and survey at a large children's hospital. PATIENTS: Previously healthy children < 24 months of age consecutively admitted between January 1 and February 11, 1995, with symptoms of lower respiratory tract infection. RESULTS: Of 200 patients 160 were tested by RSV EIA; 92 were positive and 68 were negative. Tested children were younger, more tachypneic and more likely to require oxygen than those not tested. Overall the length of stay was similar in RSV-positive and -negative patients. Although equal proportions of each group were given antibiotic therapy, RSV-positive children received antibiotic therapy for fewer days than RSV-negative children (median 2 vs. 3 days; P = 0.0387). However, a crude cost analysis did not support a strategy of testing all bronchiolitis patients for RSV. Sixty-five of the 68 RSV-negative children were tested for RSV and other pathogens by VRP. In 55 cases the results were not available until after patient discharge and could not have influenced their management. One hundred three physicians caring for children in the study were surveyed. Of 75 respondents almost all thought that RSV EIA results influenced their management of patients and were important to parents. CONCLUSIONS: Most children hospitalized with symptoms of lower respiratory tract infection were tested for viral pathogens. The VRP provided little clinically useful information. In contrast RSV EIA results may have been used by clinicians to make antibiotic decisions. Physicians felt that rapid testing for RSV was important.     

Early tracheostomy tube change in children

OBJECTIVE: To review the safety of early tracheostomy tube change in children. DESIGN: Retrospective case series. SETTING: Pediatric tertiary care hospital. PATIENTS: Twenty-one consecutive pediatric patients undergoing routine tracheotomy. INTERVENTION: First tracheostomy tube change performed at patient's bedside at 3 (n = 15) or 4 (n = 5) days after surgery. OUTCOME MEASURE: The ability to safely change a tracheostomy tube at the patient's bedside 3 or 4 days after surgery. RESULTS: The first tracheostomy tube change was safely performed at 3 or 4 days after surgery in 20 patients. All changes were accomplished without complication or difficulty on the first attempt. The patients' ages ranged from 4 days to 16 years. The smallest child weighed 1.6 kg. Early tracheostomy tube change was not attempted in one obese 10-year-old girl whose pediatric tracheostomy tube became dislodged and formed a false tract 2 days after surgery. CONCLUSIONS: Most pediatric tracheostomy tubes can be safely changed at the patient's bedside approximately 3 days after surgery. Clinical applications of early tracheostomy tube change may include facilitating better hygiene, earlier completion of family caregiver tracheotomy education, and shorter hospital stays. It appears safe and advantageous for surgeons to consider early initial tracheostomy tube change for pediatric patients.     

A second primary malignancy in a cohort of patients with epithelial ovarian cancer--characteristics of diagnosis

OBJECTIVE: Our objective was to study the whooping cough cases diagnosed in a 15-year period in our hospital, referring to its clinical features, epidemiology and analytical findings. PATIENTS AND METHODS: A retrospective study based on 144 cases with a clinical diagnosis of whooping cough, from 1981 to 1995, was carried out. Special attention was paid to those cases with cultures positive for B. pertussis. RESULTS: Nasopharyngeal specimens for culture were taken in 119 cases. This was not carried-out in those with previous antibiotic therapy. Cultures were positive for B. pertussis in 46 patients (38.7%). The age varied between 20 days and 30 months. Twenty-one were female. The initial symptoms were: paroxysmal cough in 44 (95.7%), cyanosis in 34 (73.9%), inspiratory whoop in 27 (58.7%), respiratory distress in 12 (26.1%) and post-tussive vomiting in 10 (21.7%). Thirty-nine children (84.8%) of this group had not received any pertussis vaccine, the rest had received just the first dose. It had been contacted by persons having cough in 19 patients (41.3%). Leukocytosis (mean: 19,818/mm3), lymphocytosis (mean: 13,047/mm3) and high platelet count (mean 459,522/mm3) were common findings. CONCLUSIONS: Cultures were positive in 38.7% of the patients. There are similar findings by other authors. In this group, most of the children were unvaccinated, and less than 3 months of age. Typical symptoms of pertussis were observed in the majority of patients. In one forth of them respiratory distress was found, probably related to their young age. Vaccinated adults emerge as a contact group that should be studied.     

Workshop on chronic pain, pain control, and patient outcomes in rheumatoid arthritis and osteoarthritis

OBJECTIVE: Coincident with a change in the physician staff in our pediatric intensive care unit (PICU), the frequency and duration of invasive monitoring were decreased. We examined the impact of this change on outcomes, complications, and hospital charges in infants admitted to the PICU with respiratory syncytial virus (RSV) infection. STUDY DESIGN: We reviewed medical records of all children less than 1 year of age who were admitted to the PICU from January 1989 to July 1993 with confirmed RSV infection. Patient characteristics, therapeutic interventions, outcomes, and hospital charges were extracted and compared. RESULTS: Seventy-eight patients were identified, 38 admitted from January 1989 through July 1991 (group 1) and 40 from July 1991 through July 1993 (group 2). The groups were well matched in age, preexisting disease, and cardiorespiratory status on admission. Group 1 had significantly greater use of invasive monitoring, pharmacologic paralysis, inotropes, blood products, antibiotics, and parenteral nutrition. Outcomes were not different, but group 1 patients had significantly longer stays, more complications, and higher hospital charges. CONCLUSIONS: Routine use of invasive monitoring of PICU patients with RSV disease was associated with increased laboratory testing, overtreatment, and significant increases in costs and morbidity without improvement in outcome.