Noni MacDonald

Respiratory Syncytial Viral Infection in Children with Compromised Immune Function

For 10 winters, 608 children five years old or younger who were hospitalized with respiratory syncytial virus (RSV) infection were prospectively studied to evaluate the relation between their immune status and the severity of their infection. Forty-seven had been immunocompromised by chemotherapy, steroid therapy, or a primary immunodeficiency disorder. Among the immunocompromised children, those receiving chemotherapy for cancer and those with immunodeficiency disease had more severe RSV disease, with pneumonia occurring at all ages, and a higher mortality rate. Children receiving long-term steroid therapy did not appear to have more severe clinical manifestations than normal children. Viral shedding, however, was significantly greater and more prolonged in the children receiving steroid therapy, and particularly in those receiving chemotherapy or with an immunodeficiency disease. Giant-cell pneumonia was documented in one child with leukemia. Over half the immunocompromised children acquired the RSV infection nosocomially. These findings indicate that children receiving chemotherapy for cancer and those with immunodeficiency disease are at risk for complicated or fatal infections from RSV and should be considered for antiviral and other therapies as they become available. Efforts should also be made to protect compromised children if hospitalization cannot be avoided.

Respiratory Syncytial Viral Infection in Infants with Congenital Heart Disease

Occasional reports have suggested that infants with congenital heart disease may have an increased risk of severe illness from respiratory syncytial virus (RSV) infection. We prospectively studied 699 infants hospitalized during the winters of 1976 through 1980, when RSV was prevalent in the community; 229 of these infants had proved RSV infections acquired either before admission or during hospitalization; 27 had both congenital heart disease and RSV infection, and 46 had congenital heart disease without RSV infection. Infected infants with congenital heart disease had significantly more severe illness than those without congenital heart disease, as judged by the requirement for intensive care and assisted ventilation and by the mortality rate (37 per cent vs. 1.5 per cent, P less than 0.01). The infection was acquired nosocomially by 21 per cent of infected infants; the mortality rate from nosocomial infection was also higher in infants with congenital heart disease (44 per cent vs. 5 per cent, P less than 0.01). Pulmonary hypertension was the one condition particularly associated with severe RSV illness. Eight of the 11 infants (73 per cent) with congenital heart disease and pulmonary hypertension died during their RSV illness. The courses in infants with congenital heart disease with and without RSV infection were also compared. Their ages, types of cardiac lesions, and incidence of pulmonary hypertension were similar, but the infants with RSV infection had a higher mortality rate (37 per cent vs. 6.5 per cent, P less than 0.1).

Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women

Background: Excess deaths have occurred among pregnant women during influenza pandemics, but the impact of influenza during nonpandemic years is unclear. We evaluated the impact of exposure during nonpandemic influenza seasons on the rates of hospital admissions and physician visits because of respiratory illness among pregnant women. Methods: We conducted a 13-year (1990–2002) population-based cohort study involving pregnant women in Nova Scotia. We compared rates of hospital admissions and physician office visits because of respiratory illness during the influenza season in each trimester of pregnancy with rates during the influenza season in the year before pregnancy and with rates in non-influenza seasons. Poisson regression analyses were performed to estimate rate ratios and 95% confidence intervals (CIs). Results: Of 134 188 pregnant women in the study cohort, 510 (0.4%) were admitted to hospital because of a respiratory illness during pregnancy and 33 775 (25.2%) visited their physician for the same reason during pregnancy. During the influenza seasons, the rate ratio of hospital admissions in the third trimester compared with admissions in the year before pregnancy was 7.9 (95% CI 5.0–12.5) among women with comorbidities and 5.1 (95% CI 3.6–7.3) among those without comorbidities. The rate of hospital admissions in the third trimester among women without comorbidities was 7.4 per 10 000 woman-months during the influenza season, compared with 5.4 and 3.1 per 10 000 woman-months during the peri-and non-influenza seasons respectively. Corresponding rates among women with comorbidities were 44.9, 9.3 and 18.9 per 10 000 woman-months. Only 6.7% of women with comorbidities had received influenza immunization. Interpretation: Our data support the recommendation that pregnant women with comorbidities should receive influenza vaccination regardless of their stage of pregnancy during the influenza season. Since hospital admissions because of respiratory illness during the influenza season were also increased among pregnant women without comorbidities, all pregnant women are likely to benefit from influenza vaccination.

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection

OBJECTIVE To describe differences in patients hospitalized with respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) at nine Canadian tertiary care hospitals. In addition, this study describes the variation in use of drug and other interventions. METHODS Data on patients hospitalized with RSV LRI and their outcomes were prospectively collected. Demographic data were obtained on enrollment by center study nurses. Data recorded daily included clinical assessment, oxygen saturation determination, and interventions (bronchodilators, steroids, ribavirin, antibiotics, intensive care, and mechanical ventilation) received during the day. Patients were divided into those with underlying diseases including congenital heart disease, chronic lung disease, immunodeficiency, or multiple congenital anomalies and those who were previously healthy. Mean RSV-associated length of stay and the proportion of patients receiving each intervention in each group were determined by hospital. RESULTS A total of 1516 patients were enrolled at nine hospitals during January 1 to June 30, 1993, and January 1 to April 30, 1994. Significant differences were observed among hospitals in the proportion of patients with underlying disease, postnatal age less than 6 weeks, hypoxia, and pulmonary infiltrate on chest radiograph. The mean length of stay varied among hospitals from 8.6 to 11.8 days and 4.6 to 6.7 days in compromised and previously healthy patients, respectively. Except for receipt of bronchodilators, compromised patients were significantly more likely to receive interventions than previously healthy patients. There was variation among hospitals in receipt of most interventions in compromised and previously healthy patients. This variation was statistically significant for previously healthy patients but not statistically significant in those with underlying disease, because the numbers of patients in the latter group were much smaller. The magnitude of the variation for each intervention, however, was not different between those with underlying disease compared with previously healthy patients. CONCLUSION Differences exist among tertiary pediatric hospitals in the nature of the patients admitted with RSV LRI. Variation occurred in the use of five interventions among the hospitals, regardless of whether the patient had underlying illness or was previously healthy. Given their current widespread use, high cost, and potential side effects, randomized clinical trials are needed to determine the efficacy of different drug treatments used to treat infants hospitalized with RSV.

Epidemiological Features of Pertussis in Hospitalized Patients in Canada, 1991- 1997: Report of the Immunization Monitoring Program—Active (IMPACT)

To assess the morbidity associated with the continued high levels of pertussis, we studied all children <2 years of age who were admitted to the 11 Immunization Monitoring Program--Active (IMPACT) centers, which constitute 85% of Canadas tertiary care pediatric beds. In the 7 years preceding implementation of acellular pertussis vaccine, a total of 1,082 pertussis cases were reported, of which 49.1% were culture-confirmed. The median age of the patients was 12.4 weeks; 78.9% of cases were in children <6 months of age. Complications of pertussis were common: pneumonia was reported in 9.4% of cases, new seizures in 2.3%, and encephalopathy in 0.5%. There were 10 deaths (0.9%), all in children < or =6 months of age. Duration of hospitalization was longer (9.3 days vs. 4.9 days; P = .001) and intensive care was required more frequently (19.2% vs. 4.9%; P = .001) in infants under <6 months of age than in those > or =6 months. Pertussis continues to cause significant morbidity and occasional mortality in Canada, particularly in young infants.

Influenza in children with cancer

We prospectively followed a group of unimmunized, immunosuppressed children with cancer to determine their relative risk of influenza and the severity of infection compared with those of siblings or matched community controls. The incidence of influenza infection was higher in children with cancer (23/73, 32%) than in control subjects (10/70, 14%, p =0.02). A preseason hemagglutination inhibition titer≥1:32, generally used as a marker of successful immunization in vaccine trials, was protective for all children in the control groups, but did not prevent influenza infection in 24% of the patients with cancer. Infection rates of patients and community controls with titers ≥1:32 differed significantly ( p =0.006). No significant differences were noted in duration of reported symptoms between groups, and clinical complications occurred too infrequently to analyze. However, 2 (11%) of 18 of the cancer patients with positive culture results were hospitalized during the illness and one patient developed a nosocomial infection. None of the control children was hospitalized. These findings suggest the need for further study of the immunologic response of immunosuppressed children to influenza infection and a clinical efficacy trial of the influenza vaccine in these patients.

The Sequelae of Haemophilus influenzae Meningitis in School-Age Children

BACKGROUND Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the childrens hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b.

Role of respiratory viruses in exacerbations of primary nephrotic syndrome

To determine whether respiratory virus infections (URI) are associated with exacerbation of nephrotic syndrome (NS) in childhood, a prospective two-winter study of 32 children with NS was done. We obtained pre- and post-season viral serologic studies, biweekly nose and throat viral cultures, daily urinalysis, biweekly telephone follow-up for URI and renal complaints, and clinical assessments as indicated. When a URI occurred, viral cultures were done weekly if the child was at home and twice weekly if hospitalized. Sixty-one URIs occurred; the agent was identified in 33 (51.6%) (respiratory syncytial virus 14, influenza virus five, parainfluenza virus five, varicella zoster virus four, adenovirus three, Mycoplasma pneumoniae one, and Chlamydia trachomatis one). Forty-one exacerbations occurred, 71% with URI; 29% had no URI during the preceding 10 days (P less than 0.01). Total relapse occurred in 29 of 41 exacerbations, 69% with URI and 31% without URI (P less than 0.01). Patients with unstable NS had more exacerbations than those with stable NS (15 of 19 (79%) vs four of 13 (31%), P less than 0.001) and more URI (2.32 vs 1.46 per child, P less than 0.05). Exacerbations in patients with minimal change, mesangioproliferative, and focal glomerulosclerosis occurred in 40%, 60%, and 64%, respectively. We conclude that exacerbations and relapses of childhood NS are temporally related to URI. Inasmuch as multiple viral agents were associated with exacerbations, nonspecific host response to infection, not viral antigen or antibody response, may be the link to NS.

Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children

OBJECTIVE To determine total and functional serogroup C antibody response after vaccination with a quadrivalent meningococcal polysaccharide vaccine. DESIGN Prospective, before and after intervention study. SUBJECTS Study subjects were between the ages of 0.5 and 19.9 years, and were eligible for a community-wide public health immunization campaign against Neisseria meningitidis serogroup C. METHODS Total and functional antibody response was measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS One month after vaccination, total capsular polysaccharide antibody significantly increased in all age groups; a significant rise in bactericidal antibody, that correlated with total capsular polysaccharide antibody, was seen in children 18 months of age and older. At 1 year bactericidal antibody titers were maintained but capsular polysaccharide antibody declined substantially in children younger than 5 years. CONCLUSION Total capsular polysaccharide antibody concentration appears to be a useful surrogate measure of bactericidal antibody in children 18 months and older. Children who originally received the vaccine at less than 18 months of age should be considered for revaccination if there is a new or continuing risk of disease. Because of the differences in the total and bactericidal antibodies formed, vaccine efficacy trials are required to define which serologic measures are associated with protection.

Transient Renal Failure Due to Simultaneous Ibuprofen and Aminoglycoside Therapy in Children with Cystic Fibrosis

To the Editor: Ibuprofen can retard the decline in pulmonary function in children with cystic fibrosis.1 Aminoglycosides are often given to treat pulmonary infections in children with cystic fibros...