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1.  Early-Onset Neonatal Sepsis 
Clinical Microbiology Reviews  2014;27(1):21-47.
Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.
PMCID: PMC3910904  PMID: 24396135
2.  Community-acquired pneumonia in children 
Paediatrics & Child Health  2003;8(10):616-619.
Community acquired pneumonia (CAP) is common in childhood. Viruses account for most cases of CAP during the first two years of life. After this period, bacteria such as Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae become more frequent. CAP symptoms are nonspecific in younger infants, but cough and tachypnea are usually present in older children. Chest x-ray is useful for confirming the diagnosis. Most children can be managed empirically with oral antibiotics as outpatients without specific laboratory investigations. Those with severe infections or with persistent or worsening symptoms need more intensive investigations and may need admission to hospital. The choice and dosage of antibiotics should be based on the age of the patient, severity of the pneumonia and knowledge of local antimicrobial resistance patterns. The Canadian Paediatric Society recommends the use of the heptavalent conjugate pneumococcal vaccine, which is efficacious in reducing chest x-ray positive pneumonia by up to 20%.
PMCID: PMC2795279  PMID: 20019854
Childhood; Community-acquired; Diagnosis; Pneumonia
5.  Environmental risks to Canadian children travelling overseas 
Paediatrics & Child Health  2000;5(7):387-389.
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.
PMCID: PMC2819937  PMID: 20177540
Bites; Climate; Environmental risks; Stings; Travel
7.  Differential yield of pathogens from stool testing of nosocomial versus community-acquired paediatric diarrhea 
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.
Retrospective cohort study and telephone survey.
Alberta Children’s Hospital (retrospective review) and Canadian tertiary care paediatric centres (telephone survey).
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.
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.
There is a need for the re-evaluation of routine ova and parasite screening, and bacterial culture in nonoutbreak episodes of NAD in children.
PMCID: PMC3250727  PMID: 22346400
Community-acquired infections; Diarrhea; Enteropathogens; Nosocomial infections
8.  The Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of neonatal group B streptococcal infections in Canada 
Paediatrics & Child Health  1999;4(4):257-263.
To determine the presentation and medical outcomes of neonatal group B streptococcus (GBS) disease in Canada, and describe maternal and obstetrical risk factors.
Retrospective review of health records and laboratory databases using standardized data collection forms.
All neonates diagnosed with GBS infections in 1992 at 13 Canadian paediatric centres.
A total of 105 infants meeting the criteria for neonatal GBS disease were identified. The majority of cases (78 or 74.3%) had early-onset disease (EOD); 78.9% (60 of 76) of these cases presented within 24 h of delivery. Rates of EOD (less than seven days) varied from 0.44/1000 live births to 2.1/1000 live births, with an overall rate of 1.2/1000 live births. Pneumonia was the most common clinical illness (43.8%), followed by bacteremia without focus (23.8%) and meningitis (16.2%). At least one maternal risk factor for neonatal GBS disease was noted in 46 of 78 (59%) infants with EOD. A median of one dose (range one to 23 doses) of intrapartum antibiotics was given in 18 of 75 (24%) of the pregnancies. Overall, the mean gestational age at birth was 36.2±4.7 weeks, with 38 of 96 (39.6%) infants having a gestational age at birth younger than 37 weeks (31 of 73 [42.5%] EOD cases were born with a gestational age younger than 37 weeks). The median birth weight was 3099 g (range 610 g to 4830 g). Thirty of 94 (31.9%) infants had a birth weight less than 2500 g. Seventeen (16.2%) infants died.
In 1992, neonatal GBS disease was a significant cause of morbidity and mortality in Canadian infants. More than half of the cases identified in this study could have been potentially preventable by the use of intrapartum antibiotics for women with known risk factors. There is a need for prospective studies to better define risk factors and preventative measures for neonatal GBS infections in Canada.
PMCID: PMC2827718  PMID: 20212931
Group B streptococcus; Neonatal; Outcome
9.  Pilus distribution among lineages of group b streptococcus: an evolutionary and clinical perspective 
BMC Microbiology  2014;14:159.
Group B Streptococcus (GBS) is an opportunistic pathogen in both humans and bovines. Epidemiological and phylogenetic analyses have found strains belonging to certain phylogenetic lineages to be more frequently associated with invasive newborn disease, asymptomatic maternal colonization, and subclinical bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of host tissues and play a role in biofilm formation, though few large-scale studies have estimated the frequency and diversity of the three pilus islands (PIs) across diverse genotypes. Here, we examined the distribution of pilus islands (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI-2b.
All 295 strains harbored one of the PI-2 variants and most human-derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1 and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present evidence for the frequent gain and loss of genes encoding certain pilus types.
These data suggest that pilus combinations impact host specificity and disease presentation and that diversification often involves the loss or acquisition of PIs. Such findings have implications for the development of GBS vaccines that target the three pilus islands.
PMCID: PMC4074840  PMID: 24943359
Streptococcus agalactiae; Pilus; MLST; Molecular epidemiology
10.  Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions 
Pediatrics  2013;131(2):e635-e646.
Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother’s previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.
PMCID: PMC3557411  PMID: 23359576
newborn; herpes simplex virus; acyclovir; pregnancy
11.  Whole-Genome Shotgun Sequencing of a Colonizing Multilocus Sequence Type 17 Streptococcus agalactiae Strain 
Journal of Bacteriology  2012;194(21):6005.
This report highlights the whole-genome shotgun draft sequence for a Streptococcus agalactiae strain representing multilocus sequence type (ST) 17, isolated from a colonized woman at 8 weeks postpartum. This sequence represents an important addition to the published genomes and will promote comparative genomic studies of S. agalactiae recovered from diverse sources.
PMCID: PMC3486095  PMID: 23045509
12.  Selection, Recombination, and Virulence Gene Diversity among Group B Streptococcal Genotypes▿ † 
Journal of Bacteriology  2009;191(17):5419-5427.
Transmission of group B Streptococcus (GBS) from mothers to neonates during childbirth is a leading cause of neonatal sepsis and meningitis. Although subtyping tools have identified specific GBS phylogenetic lineages that are important in neonatal disease, little is known about the genetic diversity of these lineages or the roles that recombination and selection play in the generation of emergent genotypes. Here, we examined genetic variation, selection, and recombination in seven multilocus sequence typing (MLST) loci from 94 invasive, colonizing, and bovine strains representing 38 GBS sequence types and performed DNA sequencing and PCR-based restriction fragment length polymorphism analysis of several putative virulence genes to identify gene content differences between genotypes. Despite the low level of diversity in the MLST loci, a neighbor net analysis revealed a variable range of genetic exchange among the seven clonal complexes (CCs) identified, suggesting that recombination is partly responsible for the diversity observed between genotypes. Recombination is also important for several virulence genes, as some gene alleles had evidence for lateral gene exchange across divergent genotypes. The CC-17 lineage, which is associated with neonatal disease, is relatively homogeneous and therefore appears to have diverged independently with an exclusive set of virulence characteristics. These data suggest that different GBS genetic backgrounds have distinct virulence gene profiles that may be important for disease pathogenesis. Such profiles could be used as markers for the rapid detection of strains with an increased propensity to cause neonatal disease and may be considered useful vaccine targets.
PMCID: PMC2725619  PMID: 19581371
13.  Association of Group B Streptococcus Colonization and Bovine Exposure: A Prospective Cross-Sectional Cohort Study 
PLoS ONE  2010;5(1):e8795.
While Group B Streptococcus (GBS) human colonization and infection has long been suspected as originating from cows, several investigators have suggested that ongoing interspecies GBS transmission is unlikely due to genotyping data demonstrating that human and bovine-derived GBS strains represent mostly distinct populations. The possibility of ongoing transmission between humans and their livestock has not been systematically examined.
Methodology/Principal Findings
To examine ongoing interspecies transmission, we conducted a prospective cross-sectional cohort study of 68 families and their livestock. Stool specimens were collected from 154 people and 115 livestock; GBS was detected in 19 (12.3%) humans and 2 (1.7%) animals (bovine and sheep). Application of multilocus sequence typing (MLST) identified 8 sequence types (STs or clones), with STs 1 and 23 predominating. There were 11 families in which two members submitted stools and at least one had GBS colonization. In 3 of these families, both members (consisting of couples) were colonized, yielding a co-colonization rate of 27% (95% CI: 7%–61%). Two of these couples had strains with identical MLST, capsule (cps) genotype, susceptibility, and RAPD profiles. One couple co-colonized with ST-1 (cps5) strains also had a bovine colonized with the identical strain type. On multivariate analysis of questionnaire data, cattle exposure was a predictor of GBS colonization, with each unit increase in days of cattle exposure increasing the odds of colonization by 20% (P = 0.02). These results support interspecies transmission with additional evidence for transmission provided by the epidemiological association with cattle exposure.
Although GBS uncommonly colonizes livestock stools, increased frequency of cattle exposure was significantly associated with human colonization and one couple shared the same GBS strains as their bovine suggesting intraspecies transmission. These results set the framework for GBS as a possible zoonotic infection, which has significant public health implications.
PMCID: PMC2808344  PMID: 20098699
14.  Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study 
There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).
This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.
Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.
Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.
PMCID: PMC2788568  PMID: 19930662
15.  Multilocus Sequence Types Associated with Neonatal Group B Streptococcal Sepsis and Meningitis in Canada▿  
Journal of Clinical Microbiology  2009;47(4):1143-1148.
Group B streptococci (GBS), a leading cause of neonatal sepsis and meningitis, are transferred to neonates from colonized mothers during childbirth. Prior studies using multilocus sequence typing (MLST) have found specific GBS clones (e.g., sequence type 17 [ST-17]) to be associated with neonatal disease in several geographic locations. Few population-based studies, however, have been conducted to determine the frequency of disease caused by specific GBS clones. MLST was used to assess the genetic diversity of 192 GBS strains from neonates and young children identified by population-based surveillance in Alberta, Canada, from 1993 to 2002. Comparisons were made to 232 GBS strains collected from colonized pregnant women, and all strains were characterized for one of nine capsule (cps) genotypes. A total of 47 STs were identified, and more than 80% of GBS strains were represented by 7 STs that have been shown to predominate in other populations. ST-17 and ST-19 were more prevalent in strains causing early onset disease (EOD) and late onset disease (LOD) than from pregnant women, whereas STs 1, 12, and 23 were more common in pregnant women. In addition, ST-17 strains and close relatives more frequently caused meningitis than sepsis and LOD versus EOD in this population of neonates. Further research is required to better understand why strains belonging to the ST-17 phylogenetic lineage are more likely to cause both LOD and meningitis and may provide clues into the pathogenesis of these conditions.
PMCID: PMC2668308  PMID: 19158264
16.  Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of aseptic meningitis 
The seasonality, clinical and radiographic features and outcome of aseptic meningitis have been described for regional outbreaks but data from a wider geographic area is necessary to delineate the epidemiology of this condition.
A retrospective chart review was completed of children presenting with aseptic meningitis to eight Canadian pediatric hospitals over a two-year period.
There were 233 cases of proven enteroviral (EV) meningitis, 495 cases of clinical aseptic meningitis and 74 cases of possible aseptic meningitis with most cases occurring July to October. Headache, vomiting, meningismus and photophobia were more common in children ≥ 5 years of age, while rash, diarrhea and cough were more common in children < 5 years of age. Pleocytosis was absent in 22.3% of children < 30 days of age with proven EV meningitis. Enterovirus was isolated in cerebrospinal fluid (CSF) from 154 of 389 patients (39.6%) who had viral culture performed, and a nucleic acid amplification test for enterovirus was positive in CSF from 81 of 149 patients (54.3%). Imaging of the head by computerized tomography or magnetic resonance imaging was completed in 96 cases (19.7%) and 24 had abnormal findings that were possibly related to meningitis while none had changes that were definitely related to meningitis. There was minimal morbidity and there were no deaths.
The clinical presentation of aseptic meningitis varies with the age of the child. Absence of CSF pleocytosis is common in infants < 30 days of age. Enterovirus is the predominant isolate, but no etiologic agent is identified in the majority of cases of aseptic meningitis in Canadian children.
PMCID: PMC1458346  PMID: 16603090
17.  DNA Polymorphism and Molecular Subtyping of the Capsular Gene Cluster of Group B Streptococcus†  
Journal of Clinical Microbiology  2005;43(12):6113-6116.
Serotyping and other phenotypic methods are often used to characterize the capsular polysaccharide of group B streptococci (GBS). We describe a capsular genotyping method that utilizes PCR of capsular polysaccharide synthesis genes (cps) and restriction enzyme digestion. This method facilitates the detection of DNA polymorphism in cps genes and correlates well with serotyping.
PMCID: PMC1317180  PMID: 16333106
18.  Respiratory syncytial virus bronchiolitis. 
Respiratory syncytial virus, the most common cause of bronchiolitis, is the leading cause of infant hospitalization in developed countries and accounts for substantial mortality and morbidity in developing countries. Children at increased risk of developing severe bronchiolitis are those <6 weeks of age, those born prematurely and those with an underlying cardiopulmonary disorder or immunodeficiency. Approximately 80% of cases occur in the first year of life. By two years of age, virtually all children have been infected by at least one strain of the virus. Classically, respiratory syncytial virus bronchiolitis manifests as cough, wheezing and respiratory distress. The mainstay of treatment is supportive care, consisting of adequate fluid intake, antipyretics to control fever and use of supplemental oxygen if necessary. Frequent and meticulous hand-washing is the best measure to prevent secondary spread. Treatment of respiratory syncytial virus bronchiolitis beyond supportive care should be individualized. Palivizumab has been shown to be effective in preventing severe respiratory syncytial virus bronchiolitis in high-risk children when given prophylactically. In the majority of cases, the disease is usually self-limited. The mortality rate is <1% and occurs predominantly in children at high risk for severe disease.
PMCID: PMC2640754  PMID: 16396064
19.  Risk factors for early-onset group B streptococcal disease in neonates: a population-based case–control study 
Infection with group B streptococcus (GBS) is a major cause of neonatal illness and death. We examined the antenatal and perinatal risk factors for early-onset GBS disease among neonates.
We identified cases by population-based surveillance in all microbiology laboratories serving Alberta. A case was defined as any instance of a positive sterile-site GBS culture in an infant born between 1993 and 1997 who was either less than 7 days old or stillborn after 20 weeks' gestation. We randomly selected controls from a computer-compiled list of all hospital births, including stillbirths after 20 weeks' gestation, in Alberta during the study period. To increase power, we chose 5 or 6 control infants born in the same year as each case infant. We reviewed hospital, prenatal clinic and physician health records and, between 1997 and 1999, conducted maternal interviews by telephone.
There were no differences between the 90 cases and 489 controls in sociodemographic variables or in many reproductive and behavioural variables. Case infants were more likely than control infants to be of low birth weight (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.68–7.65), to have been delivered preterm (OR 3.89, 95% CI 2.08–7.27), or to have a mother with amnionitis (OR 15.03, 95% CI 5.58–41.89), intrapartum fever (OR 4.65, 95% CI 2.48–8.69) or premature rupture of the membranes (OR 2.39, 95% CI 1.38–4.14). After adjustment for potential confounders, intrauterine fetal monitoring was associated with a more than 2-fold increase in the risk of neonatal GBS disease (OR 2.24, 95% CI 1.22–4.13).
Intrauterine fetal monitoring should be added to the list of risk factors in risk-based screening. Since many of the cases had no identifiable maternal risk factors, universal screening for GBS may be appropriate.
PMCID: PMC167120  PMID: 12900477
22.  Congenital cytomegalovirus infection. 
Cytomegalovirus (CMV) is the most common congenital infection in humans. Congenital CMV infection can follow either a primary or recurrent maternal infection, but the likelihood of fetal infection and the risk of associated damage is higher after a primary infection. Approximately 90% of congenitally infected infants are asymptomatic at birth. Jaundice, petechiae, and hepatosplenomegaly are the most frequently noted clinical triad in symptomatic infants. More frequent and more severe sequelae occur in symptomatic infants, notably psychomotor hearing loss and retardation. Congenital CMV infection can be diagnosed by isolation of the virus from the urine or saliva within the first three weeks of life. Rapid diagnosis can be accomplished by detection of CMV DNA by DNA amplification or hybridization techniques.
PMCID: PMC2594406  PMID: 12749681
23.  Evaluation of potential factors contributing to microbiological treatment failure in Streptococcus pyogenes pharyngitis 
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.
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.
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.
PMCID: PMC2094794  PMID: 18159315
Pharyngitis; Streptococcus pyogenes; Respitory viruses; Treatment failure

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