Comparison of bacterial culture with BioFire® FilmArray® multiplex PCR screening of archived cerebrospinal fluid specimens from children with suspected bacterial meningitis in Nigeria.

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. RESULTS: A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. CONCLUSIONS: The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment.

Group B streptococcal colonization and transmission dynamics in pregnant women and their newborns in Nigeria: implications for prevention strategies.

OBJECTIVES: Because few studies have been conducted on group B Streptococcus (GBS) in Nigeria, we sought to estimate GBS colonization and transmission frequencies for 500 women and their newborns and identify risk factors for both outcomes. METHODS: GBS strains were characterized for antibiotic susceptibilities, capsule (cps) genotype, pilus island profile and multilocus sequence type (ST). RESULTS: In all, 171 (34.2%) mothers and 95 (19.0%) of their newborns were colonized with GBS; the vertical transmission rate was 48.5%. One newborn developed early-onset disease, yielding an incidence of 2.0 cases per 1000 live births (95% CI 0.50-7.30). Rectal maternal colonization (OR 26.6; 95% CI 13.69-51.58) and prolonged rupture of membranes (OR 4.2; 95% CI 1.03-17.17) were associated with neonatal colonization, whereas prolonged membrane rupture (OR 3.4; 95% CI 1.04-11.39) and young maternal age (OR 2.0; 95% CI 1.22-3.39) were associated with maternal colonization. Women reporting four or more intrapartum vaginal examinations (OR 6.1; 95% CI 3.41-10.93) and douching (OR 3.7; 95% CI 2.26-6.11) were also more likely to be colonized. Twelve STs were identified among 35 mother-baby pairs with evidence of transmission; strains of cpsV ST-19 (n = 9; 25.7%) and cpsIII ST-182 (n = 7; 20.0%) predominated. CONCLUSIONS: These data demonstrate high rates of colonization and transmission in a population that does not use antibiotics to prevent neonatal infections, a strategy that should be considered in the future.

The role of exposures to animals and other risk factors in sporadic, non-typhoidal Salmonella infections in Michigan children.

Salmonellosis is largely a major foodborne disease. However, contact with animals particularly reptiles, has been increasingly recognized as a risk factor for Salmonella infection among children. The major risk factors for salmonellosis in Michigan children have not been assessed. Therefore, we have evaluated the association between Salmonella infections and contact with animals among Michigan children aged ≤ 10 years by conducting a population-based case-control study. A total of 123 children with laboratory-confirmed Salmonella infections and 139 control children, who had not experienced symptoms of gastrointestinal illness during the month prior to the interviews, were enrolled. A multivariable analysis matched on age group revealed that children with Salmonella infections had reported more commonly than controls contact with reptiles [adjusted matched odds ratio (MOR) = 7.90, 95% confidence interval (CI): 1.52-41.01] and cats (MOR = 2.53, 95% CI: 1.14-5.88). Results of this study suggest an association between salmonellosis and contact with cats and reptiles in Michigan children. Additional efforts are needed to educate caretakers of young children about the risk of Salmonella transmission through animal contact.

Bloodstream infection-associated sepsis and septic shock in critically ill adults: a population-based study.

BACKGROUND: Few studies have investigated the epidemiology of sepsis and septic shock in a large population and none have been from Canada. The objective of this study was to define the epidemiology of bloodstream infection (BSI)-associated sepsis and septic shock among all critically ill patients in a large, fully integrated health region in Canada. PATIENTS AND METHODS: All critically ill adults admitted to multidisciplinary intensive care units (ICU) in the Calgary Health Region during May 1, 1999 to April 30, 2000 were included. Clinical, microbiologic and outcome information was obtained from regional databases. RESULTS: We surveyed 1981 patients having at least one ICU admission. Systemic inflammatory response syndrome (SIRS) was diagnosed in 92%, BSI-associated sepsis (BSI with SIRS) in 6% and BSI-associated septic shock (BSI with SIRS and hypotension) in 3%; respective hospital mortality rates were 36%, 40% and 49%. The most common BSI etiologies were Staphylococcus aureus, Escherichia coli and Streptococcus species; only one isolate (1%) was highly antibiotic resistant. Independent risk factors for death among patients with SIRS included age (>or= 65), hypothermia (< 35 degrees C), and higher APACHE II and TISS scores. A surgical diagnosis was associated with decreased mortality risk. Neither a positive blood culture nor hypotension at presentation independently predicted death. CONCLUSION: Knowledge of the epidemiology of these syndromes is important for assessing the burden of disease and providing background information for investigating new therapies.

The pathology of rotavirus-associated deaths, using new molecular diagnostics.

Rotavirus, the most common cause of severe, dehydrating gastroenteritis among children worldwide, annually causes approximately 500,000 deaths among children aged <5 years. The primary site of rotavirus infection is the small intestine. Pathologic investigations of patients who died of rotavirus infection are limited to data from a few reported autopsies, and dehydration with electrolyte imbalance is believed to be the major cause of death. Several recent reports suggest that children who died during a rotavirus illness were viremic before death, because rotavirus was detected at several extraintestinal sites. We report 3 rotavirus-associated deaths among children, 2 of whom had evidence of rotavirus genome in extraintestinal tissues detected by use of novel molecular diagnostic methods. The part played by rotavirus in fatal cases is unclear and requires additional investigation of diarrhea-associated deaths, because a better understanding might alter the approach to treatment and the need for antiviral therapy.

Clinical evaluation of Double Strength Isotrexin versus Benzamycin in the topical treatment of mild to moderate acne vulgaris.

BACKGROUND: Topical retinoid therapy has been shown to be an effective means of treating both the inflammatory and non-inflammatory lesions of acne vulgaris. AIM: To assess the efficacy and safety of the test product, a gel containing isotretinoin 0.1% w/w and erythromycin 4.0% w/w, with a currently used and effective treatment for mild to moderate acne vulgaris, a gel containing benzoyl peroxide 5.0% w/w and erythromycin 3.0% w/w. METHODS: This multi-centre, single-blind (investigator blind), parallel group study compared the efficacy and safety of isotretinoin/erythromycin gel (Double Strength Isotrexin) once daily against benzoyl peroxide/erythromycin gel (Benzamycin twice daily in the topical treatment of mild to moderate acne vulgaris. Patients (n = 188) with a history (mean duration 3.3 years) of facial acne vulgaris and with 15-100 inflammatory lesions and/or 15-100 non-inflammatory lesions, but not more than three nodulocystic lesions, were included. At baseline and weeks 2, 4, 8 and 12, the investigator assessed efficacy (total number and severity of inflammatory and non-inflammatory lesions and acne grade) while subjective global change assessments of facial acne from baseline and symptom-specific skin tolerance were assessed by the patient. The investigator recorded an overall global assessment of skin tolerability at week 12. Adverse events were recorded throughout. RESULTS: The treatments were comparable with regard to their effects on inflammatory and non-inflammatory lesions and acne grade. Few adverse events were considered to be treatment-related. Both the isotretinoin/erythromycin and benzoyl peroxide/erythromycin gels were generally well tolerated. Compliance was better with the isotretinoin/erythromycin gel, which had the advantages of not requiring mixing or storage in a refrigerator, and was applied once rather than twice daily. CONCLUSIONS: Isotretinoin/erythromycin gel given only once daily showed comparable efficacy with benzoyl peroxide/erythromycin given twice daily in the treatment of mild to moderate acne vulgaris of the face.

Population-based active surveillance for neonatal group B streptococcal infections in Alberta, Canada: implications for vaccine formulation.

BACKGROUND: Knowledge of circulating serotypes of group B Streptococcus (GBS) is important for formulation of vaccines. There are no Canadian data on the serotype distribution of neonatal GBS isolates. METHODS: Using a retrospective laboratory and health record survey between 1993 and 1994 (before introduction of Canadian prevention guidelines) and prospective active laboratory-based surveillance from 1995 to 1999 of all laboratories in Alberta, we identified 168 cases of invasive neonatal GBS infections including stillbirths among 262,398 total births; 118 of 123 (96%) isolates from 1995 to 1999 were serotyped, and the corresponding neonatal health records were reviewed. RESULTS: The average annual incidence was 0.64 of 1000 total births/year. Of these 95 (57%) had early onset disease (EOD), 15 (9%) were still births and 58 (34%) had late onset disease (LOD). Eighty-one percent of EOD cases were caused by serotypes Ia, Ia/c, Ia/c/R, III, III/R and V, V/R, whereas 81% of LOD cases were caused by serotypes III and III/R. GBS serotypes containing the C protein along with serotypes III and V as a group constituted 91% (107 of 118) of all GBS cases in our population. The most common clinical presentation was bacteremia without focus (74%) followed by meningitis (14%) and pneumonia (12%). During 1995 to 1999, in addition to 13 stillbirths, there were 6 of 64 (9%) neonatal deaths among EOD cases and 1 of 46 (2%) neonatal death among LOD cases. CONCLUSIONS: In this population-based study stillbirths account for a proportion of cases that are not routinely counted and represent a group for which intrapartum antibiotics would likely not be effective, but potentially preventable by vaccination. Inclusion of serotypes Ia, III and V in a conjugate vaccine or serotypes III and V conjugated with the C protein in a GBS vaccine could theoretically provide protection against the majority of GBS invasive disease in Alberta neonates.

Olecranon septic bursitis managed in an ambulatory setting. The Calgary Home Parenteral Therapy Program Study Group.

BACKGROUND: The epidemiology, outcome and management of olecranon septic bursitis (OSB) have not been described in a large cohort of ambulatory patients. METHODS: A retrospective study of all 118 cases of OSB presenting over 21 months to all regional Home Parenteral Therapy Program clinics in Calgary (referral base approximately 1 million). RESULTS: The minimum population annual incidence was 10/100,000. The mean (and standard deviation) age was 44 (13) years, and males predominated (88%). One-third of patients had at least one comorbid illness, with preceding injury in 53% of cases. The most common symptoms were pain (87%), redness (77%) and fever or chills (45%). Common signs included erythema (92%), swelling (85%), edema (75%), tenderness (59%), fluctuance (50%), heat (36%) and reduced range of motion (27%). Fever (body temperature of > or =37.8 degrees C) occurred in 20%. Staphylococcus aureus was identified in 88% of culture-proven cases of OBS. The most common antibiotic regimen was sequential intravenous administration of cefazolin (for a median of 4 d) followed by clindamycin orally (for a median of 8 d). Sixty (51%) patients required a drainage procedure and only 1 patient required admission to hospital. CONCLUSION: OSB is more common than reported and can be treated successfully in ambulatory settings with sequential intravenous therapy followed by oral therapy and drainage in selected cases.

Antibodies to capsular polysaccharides of group B Streptococcus in pregnant Canadian women: relationship to colonization status and infection in the neonate.

In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response.

Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions.

BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were conducted for a subset of respondents to confirm reported practices. Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease. RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 [82%] and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001). There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period. INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time. These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations. However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

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.

A CD-1 mouse model of infection with Staphylococcus aureus: influence of gender on infection with MRSA and MSSA isolates.

Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscessation, toxemia, and other infectious diseases. An animal model using CD-1 mice was developed to study the pathogenesis of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). When inoculated into the CD-1 mouse model, it was shown that both MSSA isolates, (HR 78 and CSA-1) and MRSA isolates (MRSA 456 and MRSA 457) led to chronic infection of the kidney. Female CD-1 mice inoculated with MRSA 456 proved to be more susceptible to infection and mortality than their male counterparts. Castrated mice became more susceptible to infection than intact male mice, suggesting a hormonal involvement in the infection process.

Disseminated bacille Calmette-Guérin infection in an infant with a novel deletion in the interferon-gamma receptor gene.

Six weeks after receiving BCG vaccination, a Canadian aboriginal infant presented with suspected sepsis, lymphadenopathy and hepatosplenomegaly. Lymph node biopsy revealed macrophages filled with acid-fast bacilli. Mycobacterium bovis was cultured from tissue specimens and there was evidence of concomitant cytomegalovirus disease. The infant died of disseminated BCG infection. A novel deletion at nucleotide 165 in the interferon-gamma receptor (IFN-gammaR1) was identified. The incidence of this mutation in the aboriginal population and the impact on the heterozygous state are unknown.

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhood respiratory infections.

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.

Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group.

OBJECTIVES: To describe the incidence and clinical features of invasive group A streptococcal (GAS) disease in children in Ontario and determine the risk of invasive GAS infection following chickenpox. METHODS: During 1992-1996, we conducted prospective, active, population-based surveillance for pediatric invasive GAS disease in Ontario, Canada (population: 11 million; 2.5 million children) and reviewed clinical and laboratory records. RESULTS: There were 1.9 cases of invasive GAS disease per 100,000 children per year. Streptococcal toxic shock syndrome (STSS) occurred in 7% of cases and necrotizing fasciitis (NF) in 4% for incidences of.08 and.13 per 100,000 per year, respectively. Case-fatality rates were 56% for STSS, 10% for NF, and 4% overall. The presence of chronic underlying illness other than asthma was associated with death (relative risk [RR]: 11; 95% confidence interval [CI]: 2.4-45). Fifteen percent of children identified had preceding chickenpox infection, which significantly increased the risk for acquisition of invasive GAS disease (RR: 58; 95% CI: 40-85). Children with invasive GAS and recent chickenpox were more likely to have NF (RR: 6.3; 95% CI: 1.8-22.3). CONCLUSIONS: Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality. Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.

Environmental risks to Canadian children travelling overseas.

Canadian children and youth travelling overseas face numerous environmental risks, including trauma, extreme temperatures, sun exposure, high altitudes, environmental pollution, and a variety of bites, stings and envenomations. Because skilled emergency response is limited or nonexistent in places where serious illness or injury is most likely to occur, avoiding or limiting these risks is imperative. Travel and paediatric health care providers must be able to identify environmental risks and to advise parents appropriately. Anticipating potential dangers and planning preventive strategies in advance can reduce both parental anxiety and the risk to children.