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.
Streptococcus agalactiae; Pilus; MLST; Molecular epidemiology
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%.
Childhood; Community-acquired; Diagnosis; Pneumonia
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.
newborn; herpes simplex virus; acyclovir; pregnancy
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pharyngitis; Streptococcus pyogenes; Respitory viruses; Treatment failure
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.
Bites; Climate; Environmental risks; Stings; Travel
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.
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.
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.
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.
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.
Community-acquired infections; Diarrhea; Enteropathogens; Nosocomial infections
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.
Group B streptococcus; Neonatal; Outcome
To compare the yield of two aerobic and an anaerobic BACTEC blood culture media in detecting bacteremia in ambulatory and hospitalized care settings at a children’s hospital, a prospective cohort study was completed. Over an 18-month period, equal blood volumes (minimum of 1 mL/bottle) were inoculated into a three-bottle culture set including aerobic BACTEC NR 6A, aerobic BACTEC PEDS Plus and anaerobic NR 7A broths. Chart reviews were completed on all children with bacteremia to determine whether the isolate was clinically significant based on predefined criteria. Among 5328 evaluable blood culture sets, 323 clinically significant organisms (110 from ambulatory and 213 from hospitalized children) were isolated. Most Streptococcus pneumoniae, Haemophilus species, and Neisseria or Moraxella species were recovered from children attending the emergency department or out-patient clinics. Important isolates in hospitalized children included most of the staphylococci and Enterobacteriaceae, and all group D enterococci, Gram-negative nonfermentative bacilli and all Candida species. Overall, significantly more isolates were detected only in the anaerobic bottle from ambulatory children (P<0.0001), including 13 of 54 (24%) patients with S pneumoniae bacteremias presenting to the emergency department. This study indicated that different BACTEC blood culture media combinations are needed in ambulatory and hospitalized pediatric care settings to ensure the optimal recovery of all types of isolates. Whereas aerobic blood culture bottles are adequate for detection of bacteremia in hospitalized children, the common occurrence of fastidious organisms mandates the need for a combined aerobic/anaerobic culture set in ambulatory pediatric care settings.
Ambulatory care; Bacteremia; Children; Hospitalization
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.
Retrospective case series.
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.
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).
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.
Childhood; Complications; Varicella zoster infections