Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Evaluation of potential factors contributing to microbiological treatment failure in Streptococcus pyogenes pharyngitis.

BACKGROUND: A cohort study of children with pharyngitis aged two to 16 years was conducted to assess the role of microbial and host factors in group A beta-hemolytic streptococcus (GABHS) microbiological treatment failure. METHODS: GABHS-infected children had pharyngeal swabs repeated two to five days after completing a 10-day course of penicillin V. M and T typing, and pulsed field gel electrophoresis were performed on the isolates, and the isolates were evaluated for tolerance. Patient characteristics and clinical features were noted and nasopharyngeal swabs for respiratory viruses were taken at enrolment. RESULTS AND CONCLUSIONS: Of 286 patients enrolled, 248 (87%) could be evaluated. GABHS was cultured from 104 patients (41.9%), of whom 33 (33.7%) had microbiological treatment failures on follow-up. Although there was a trend toward failure for younger children (mean 6.5+/-2.4 years versus 7.3+/-2.4 years, P=0.07) and M type 12 (24% versus 10%, P=0.08), no factors were associated with treatment failure.

Reduced susceptibility to penicillin among pneumococci causing invasive infection in children - Canada, 1991 to 1998.

OBJECTIVE: To determine, over time, the rate and serotypes of pneumococci with reduced penicillin susceptibility obtained from children with invasive infection. DESIGN: Active, hospital-based, multicentre surveillance spanning from 1991 to 1998. SETTING: Eleven Canadian tertiary care paediatric facilities located from coast to coast. POPULATION STUDIED: 1847 children with invasive pneumococcal infection whose isolates (from a normally sterile site) were available for serotyping and standardized testing for penicillin susceptibility at the National Centre for Streptococcus. MAIN RESULTS: The prevalence of reduced penicillin susceptibility increased from 2.5% of 197 cases in 1991 to 13.0% of 276 cases in 1998. In the latter year, 8.7% of isolates had intermediate level resistance, and 4.3% had high level resistance. Since they were first detected in 1992, strains with high level resistance have been encountered only sporadically at most centres, but by 1998, all centres but two had encountered examples. Of 40 isolates with high level resistance and 101 isolates with intermediate level resistance, serotypes matched those included in new seven-valent conjugate vaccines for children in 97.5% and 79.2% of cases, respectively. CONCLUSIONS: Pneumococci with reduced susceptibility to penicillin are increasing in frequency across Canada among children with invasive infection. The Immunization Monitoring Program, Active data indicate that new conjugate vaccines could help to curb infections due to pneumococci with reduced susceptibility to penicillin but are unlikely to control completely the problem of antibiotic resistance.

The Immunization Monitoring Program Active (IMPACT) prospective five year study of Canadian children hospitalized for chickenpox or an associated complication.

BACKGROUND: Varicella vaccine was approved for use in Canada in 1998. A major goal of universal varicella vaccine programs is to reduce severe infection and associated complications. Baseline data are essential against which to judge the effectiveness of routine childhood immunization. OBJECTIVE: To describe morbidity and mortality among children hospitalized for chickenpox. Methods. From January 1, 1991, to March 31, 1996, chickenpox admissions to 11 pediatric referral centers were actively identified. Patient and illness characteristics were compared for 3 subgroups defined by prior health: healthy; unhealthy but immunocompetent; immunocompromised. RESULTS: Of 861 cases 488 (56.7%) were healthy, 75(8.7%) were unhealthy and 298 (34.6%) were immunocompromised. The immunocompromised children differed from healthy/unhealthy cases in mean age (6.4 vs. 4.0/4.6 years, respectively, P < 0.0001); median interval from rash onset to admission (2 vs. 5/5 days, P < 0.0001); complication rate (20% vs. 90%/79%; P = 0.001); and rate of acyclovir therapy (98% vs. 24%/39%; P = 0.001). Unhealthy vs. healthy cases had a higher frequency (P < 0.01) of intensive care (13.3% vs. 4.7%), ventilation (9.3% vs. 2.0%) and death (4% vs. 0.2%). CONCLUSION: These data provide a baseline for morbidity/mortality resulting from chickenpox before varicella vaccine use in Canada.

Severe Kawasaki disease in infants: two fatal cases.

Kawasaki disease is a systemic vasculitis that manifests itself in many ways. Infants may present as atypical cases and commonly experience severe inflammatory changes. The two cases that are presented here highlight unusual severity and pathology. Patient 1 was a three-month-old infant with atypical Kawasaki disease who developed gangrenous lesions, and coronary and extracoronary artery aneurysms. Multiorgan failure ensued with diffuse cardiac and extracardiac aneurysms and thromboses at autopsy. Patient 2 was a five-month-old infant with Kawasaki disease, cholangitis and peripheral gangrene. Severe coronary artery aneurysms developed and he died following a myocardial infarction, despite multiple doses of intravenous immunoglobulin, acetylsalicylic acid (ASA) and corticosteroids. There is a higher occurrence of atypical disease and more severe vasculitis in infants with Kawasaki disease. Pathological changes are described, including coronary and extracardiac lesions. Patient 1 shows extensive peripheral gangrene and widespread aneurysms, and patient 2 illustrates severe cardiac complications with diffuse organ inflammation. Therapies including intravenous immunoglobulin, ASA, corticosteroids and antithrombotics are reviewed.

Population-based surveillance of Hib invasive infections in children in British Columbia Alberta and Ontario - 1995 to 1997.

OBJECTIVE: To assess vaccine effectiveness through enhanced disease surveillance following the change in childhood immunization programs in 1995, when all provinces and territories chose to use polyribosyl ribitol phosphate-tetanus protein (PRP-T) Haemophilus influenzae type b (Hib) conjugate vaccine, generally in combination with diphtheria-pertussis-tetanus inactivated polio vaccine (DPT-IPV) (as PENTA vaccine) because the protective efficacy of this regimen had not been directly measured. DESIGN: Prospective, active, laboratory-based Hib case surveillance was implemented in British Columbia and Alberta, and enhanced, stimulated laboratory surveillance in Ontario during 1995 to 1997, centred on invasive infections in children. Case details and immunization histories were uniformly collected and centrally collated. MAIN RESULTS: Thirty-eight Hib cases were detected, but only 12 cases arose among PENTA-eligible children, an attack rate of 0.85 cases/100,000 child-years of observation. Annual case totals declined from 20 in 1995 to seven in 1997, when only one to three cases were encountered in each province and the incidence rate in children under age five years was 0.6/100,000. Only four cases occurred after primary immunization with PENTA, a failure rate of 0.28 cases/100,000 child-years of observation. Three cases among PENTA-eligible children reflected parental refusal of infant vaccinations, accounting for 25% of cases in eligible children. CONCLUSIONS: PRP-T conjugate vaccine was highly effective when given in combination with DPT-IPV vaccine. Provincial programs that used this regimen resulted in the near elimination of invasive Hib disease in children, but unimmunized children remain at risk.

Evaluation of the Strep A OIA assay versus culture methods: ability to detect different quantities of group A Streptococcus.

The Strep A OIA assay by Biostar (Boulder, Co., USA) is a unique optical immunoassay system for the rapid detection of Group A streptococcal carbohydrate. As part of a community-based pediatric cohort study of Group A Streptococcus (GAS) persistence following antibiotic therapy of pharyngitis, the performance of the Strep A OIA assay was compared with the amount of growth from standard throat swab culture methods. A total of 363 throat swabs taken over the course of the study was evaluated from 248 children between 2 and 18 years of age. Two culture methods were performed: an agar plate with the throat swab using Columbia agar base with 5% sheep blood incubated under an anaerobic environment for 48 h and Todd-Hewitt broth (THB) enhancement. The Strep A OIA was then performed. A total of 144 of 363 (39.7%) samples was positive for GAS by one or more of the laboratory tests across study visits: agar culture detected 132 of 144 (91.7%), THB culture detected 128 of 144 (88.9%), and the Strep A OIA assay detected 129 of 144 (89.6%). Complete agreement among all three laboratory tests was found for 333 of 363 (91.7%) of the samples. Agar culture results were comparable to THB cultures with a sensitivity of 96.9%, specificity of 96.6%, a positive predictive value of 93.9%, and a negative predictive value of 98.3%. Although the performance of the Strep A OIA assay had similar specificity (96.5%) and positive predictive value (93.8%) compared with the combined results of the two culture methods, the sensitivity (89.0%) and negative predictive value (93.6%) were lower. A significant difference (p < 0.001) was found in the ability of the Strep A OIA assay to detect agar culture-positive swabs that had a light growth (1+ or 2+) (63.0%) versus a moderate (3+) or heavy (4+) growth (98.1%) of GAS. Although the Strep A OIA assay allows GAS throat swab results to be reported an average of 24 h sooner than either of the cultures, the rapid assay was not as sensitive in detecting light growth GAS-positive cultures.

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 Canada's 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.

Differential yield of pathogens from stool testing of nosocomial versus community-acquired paediatric diarrhea.

OBJECTIVES: To evaluate the role of routine stool examination for all pathogens in paediatric nosocomial diarrhea (NAD) and community-acquired diarrhea (CAD) over a two-year period at Alberta Children's Hospital and current practices in other Canadian hospitals. A secondary objective was to characterize features that may predict NAD or CAD etiology. STUDY DESIGN: Retrospective cohort study and telephone survey. SETTING: Alberta Children's Hospital (retrospective review) and Canadian tertiary care paediatric centres (telephone survey). METHODS: The health and microbiological records of all children with an admission or discharge diagnosis of diarrhea were reviewed using a standardized data collection form. In addition, a telephone survey of laboratories serving all paediatric hospitals in Canada was conducted using a standard questionnaire to obtain information about practices for screening for pathogens related to NAD. RESULTS: Four hundred and thirty-four CAD episodes and 89 NAD episodes were identified. Overall, rotavirus and Clostridium difficile were the most commonly identified pathogens. Bacterial culture was positive in 10.6% CAD episodes tested, with Escherichia coli O157:H7 identified as the most common non-C difficile organism. In NAD, no bacteria were identified other than C difficile (toxin). Screening for ova and parasites had negligible yield. Viruses were more frequent in the winter months, while bacterial pathogens were more common in the summer and fall months. Over 50% of Canadian paediatric hospitals still routinely process NAD specimens similarly to CAD specimens. CONCLUSIONS: There is a need for the re-evaluation of routine ova and parasite screening, and bacterial culture in nonoutbreak episodes of NAD in children.

Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral therapy.

BACKGROUND: There has been little recent information on the epidemiology and outcome of childhood osteomyelitis since the era of sequential intravenous-oral antibiotic therapy. METHODS: Retrospective chart review. OBJECTIVE: To review the recent experience and outcome of osteomyelitis in children. RESULTS: Between 1984 and 1996 we identified 146 patients with osteomyelitis. Decreased limb use and fever were the most common presenting symptoms, and tenderness was the most common sign. Staphylococcus aureus was the most common causative organism, and Haemophilus influenzae was not identified after 1990. Bone biopsies or aspirates were superior (83%) to blood cultures (32%) in yielding organisms. 99mTc bone scan was the most sensitive imaging test (94%). Lack of use of anti-teichoic acid titers and serum bactericidal titers did not adversely affect outcome. The median duration of intravenous antibiotic therapy was 11 days, with a median duration of total antibiotics of 38 days. Complications occurred in 6.6% of patients. CONCLUSION: S. aureus remains the most important cause of osteomyelitis. Despite inconsistent use of tests for diagnosis and management and use of sequential intravenous-oral therapy, the overall outcome remains excellent.

Predictors and outcome of admission for invasive Streptococcus pneumoniae infections at a Canadian children's hospital.

Rates of admission for invasive Streptococcus pneumoniae infection in children vary considerably between institutions. We performed a retrospective study to investigate factors used in the decision to admit patients with invasive S. pneumoniae infection to Alberta Children's Hospital. Of 254 patients who were initially assessed in the emergency department, 38.2% were admitted to the hospital. Significant risk factors for admission as determined by a logistic regression model included murmur (odds ratio [OR], 18.98; 95% confidence interval [CI], 4.08-88.23), focal infection (OR, 11.41; 95% CI, 5.07-25.67), and older age (OR, 2.72; 95% CI, 1.03-7.17). Higher hemoglobin level (OR, 0.96; 95% CI, 0.93-0.99) and temperature of > 38.5 degrees C (OR, 0.39; 95% CI, 0.18-0.85) were associated with a lower risk of admission. Two patients died (case-fatality rate, 0.7%). Despite the low rate of admission for invasive S. pneumoniae infections at our hospital, the mortality rate was comparable with those at institutions with higher rates of admission, thus suggesting that the factors we identified may be useful in deciding whether to admit patients with (or who are at high risk for) invasive S. pneumoniae infections.

A practical guide for the diagnosis and treatment of pediatric pneumonia.

OBJECTIVE: To develop guidelines for the diagnosis and management of community-acquired pediatric pneumonia. OPTIONS: Clinical assessment, radiography, laboratory testing, and empirical antimicrobial therapy. OUTCOMES: Increased awareness of age-related causes, improved accuracy of clinical diagnosis, better utilization of diagnostic testing and the rational use of empirical antimicrobial therapy resulting in more rapid diagnosis, initiation of appropriate therapy and decreased morbidity and mortality. EVIDENCE: A MEDLINE search for relevant articles published from 1996 to September 1996 using the MeSH terms "pediatric," "pneumonia," "respiratory tract infection," "pneumonitis," "etiology," "diagnosis," "therapy," "antibiotics," "resistance," "radiology," "microbiology" and "biochemistry." VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. When application of the hierarchy was not feasible or appropriate, different evaluation criteria were used. BENEFITS, HARMS AND COSTS: Increased awareness of the causes of pneumonia, accurate diagnosis and prompt treatment should reduce costs associated with unnecessary investigations and complications due to inappropriate treatment. RECOMMENDATIONS: Age is the best predictor of the cause of pediatric pneumonia, viral pneumonia being most common during the first 2 years of life. The absence of a symptom cluster of respiratory distress, tachypnea, crackles and decreased breath sounds accurately excludes the presence of pneumonia (level II evidence). Bacterial cultures of samples from the nasopharynx and throat have no predictive value; however, Gram staining and culture of sputum from older children and adolescents are useful (level III evidence). Oral antimicrobial therapy will provide adequate coverage for most mild to moderate forms of pneumonia in children (level III evidence). Parenteral therapy is typically reserved for neonates and patients with severe pneumonia admitted to hospital (level III evidence). VALIDATION: These recommendations are based on consensus of Canadian experts in infectious diseases and microbiology. They are the only guidelines to address antimicrobial treatment from an age-related, etiologic perspective. SPONSOR: The development of these guidelines and the technical support and assistance of Core Health Inc. in preparing this manuscript were funded through an unrestricted educational grant from Abbott Laboratories Canada. The sponsoring company was not involved in determining the membership of the consensus group or the content of the guidelines.

Varicella zoster virus infections in Canadian children in the prevaccine era: A hospital-based study.

OBJECTIVE: To describe the clinical course of children admitted for varicella zoster virus (VZV) infections to a pediatric hospital before the release of VZV vaccine in Canada. DESIGN: Retrospective case series. SETTING: Tertiary pediatric hospital. Population studied was children aged 18 years or younger admitted to hospital between 1983 and 1992 who were discharged with a diagnosis of varicella or zoster. Of the 201 children who were identified, 36 were excluded, leaving 165 for analysis. RESULTS: There was a male:female ratio of 1.5:1 and a median age of 5.3 years (range two weeks to 18 years). The group included those who were previously healthy (70, 42.4%), immunocompromised (60, 36.4%), and those with nonimmunocompromising conditions (35, 21.2%). Comparison of immunocompetent and immunocompromised children revealed that complication of VZV infection was a more common reason for admission among the former (86 of 105, 81.9%, P<0.001), whereas treatment with acyclovir to limit dissemination was the most common reason in the latter (53 of 60, 88.3%, P<0.001). Skin and soft tissue infections were the most common complications in immunocompetent children (36 of 98) and those younger than five years (26 of 53), whereas pulmonary complications predominated among immunocompromised patients (eight of 98) and neurological complications in five- to 10-year-olds (16 of 36). Only one death (0.6%) occurred in an immunocompetent patient. Group A beta-hemolytic streptococci and Staphylococcus aureus caused equal numbers of secondary infections (92% of all isolates). CONCLUSIONS: Complications of VZV infections and secondary prophylactic antiviral treatment of immunocompromised children explain the majority of hospitalizations in this institution, and can be monitored after VZV vaccine introduction. Complications vary significantly with underlying healthy status and age.

Practice guidelines for ordering stool ova and parasite testing in a pediatric population. The Alberta Children's Hospital.

A comprehensive utilization review was done of all stool ova parasite examinations performed at a pediatric hospital during a 3-year period from June 1, 1989 to July 1, 1992. A total of 2,652 stool specimens were surveyed from 1,532 children. Forty-one percent (1,081) of the workload was from inpatients, 37% (976) was from emergency room (ER) visits/other outpatients, and 22% (233) was from patients attending the gastroenterology (GI) clinic. The prevalence of enteric parasites in hospitalized children was 4% (35 of 829) compared to rates of 10% (47 of 470) and 13% (30 of 233) for children attending the ER/other outpatient clinics and GI clinic, respectively. Giardia lamblia was found most often (31%[45 of 146]), followed by Dientamoeba fragilis (23%[33 of 146]), Entamoeba coli (16%[24 of 146]), Blastocystis hominis (13% [19 of 146]), Cryptosporidium (8% [12 of 146]), Endolimax nana (4% [6 of 146]), Enterobius vermicularis (2% [3 of 146]), Hymenolepis nana (2% [3 of 146]), and Iodamoeba buetschlii (1% [1 of 146]). Most children were colonized/infected with a single parasite (85%) with a much smaller number having two or more parasites. Only nine children (6%) who were immunocompetent and hospitalized for more than 4 days were found to have enteric parasites. Over the past 18 months, significant sustainable cost savings have resulted from the implementation of practice guidelines for ordering pediatric stool ova and parasite examinations.