Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada.

BACKGROUND & AIMS: Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. METHODS: The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. RESULTS: HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening. CONCLUSIONS: Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. IMPACT AND IMPLICATIONS: HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions.

Case Series of Stillbirths Due to Syphilis in Edmonton, Alberta, Canada.

BACKGROUND: Data on the incidence and characteristics of stillbirths attributed to congenital syphilis were collected. METHODS: We extracted data on stillbirths in the Edmonton Zone on January 1, 2015, through June 30, 2021, born to persons diagnosed with infectious syphilis (primary, secondary, early latent, or early neurosyphilis) during pregnancy or at the time of delivery. RESULTS: Of 314 infants documented to be exposed to infectious syphilis during gestation, 16 (5.1%) were stillborn. Three of the 16 females with stillbirths were diagnosed with syphilis during pregnancy but not treated, 12 were diagnosed only at the time of stillbirth (1 of whom was treated early in pregnancy and presumably reinfected), and 1 had a stillbirth in the week after one dose of benzathine penicillin G. CONCLUSIONS: Stillbirths due to congenital syphilis were all due to failure to treat syphilis in pregnancy. Innovative strategies to prevent syphilis in the community and to reach those experiencing barriers to care are urgently required to not miss opportunities to diagnose and treat syphilis as early as possible during pregnancy.

Systematic Review of Antimicrobial Lock Solutions for Prevention of Bacteremia in Pediatric Patients With Intestinal Failure.

OBJECTIVES: The goal of this systematic review was to determine whether antimicrobial lock (AML) solutions prevent catheter-related bloodstream infections (CRBSI) in children with intestinal failure (IF). METHODS: Electronic databases were searched: Ovid MEDLINE (1946-), Ovid Embase (1974-), Wiley Cochrane Library (inception-), and Web of Science Core Collection via Clarivate Analytics (1900-). Randomized and nonrandomized trials, case or cohort studies that studied any AML solution, and used comparator groups were included if they studied children with IF. A meta-analysis compared the rates of CRBSI with AML solutions versus controls, and a Boucher analysis was used to indirectly compare AML solutions. RESULTS: Twenty-eight studies met eligibility criteria (1 open label and 27 observational studies). Quality was good (N = 13), fair (N = 9), and poor (N = 6). All but 4 studied ethanol and taurolidine. Of 15 ethanol studies, 11 reported a decrease and 3 reported a trend toward a decreased incidence of CRBSI compared to controls; 1 reported no difference. Of 9 taurolidine studies, 7 reported a decrease and 2 a trend toward decreased CRBSI rates. There was a decrease in CRBSI with ethanol versus control ( P = 0.008) and with taurolidine-citrate versus control ( P < 0.0005). Using Bucher indirect comparison of the pooled estimates from ethanol versus control to taurolidine versus control, the estimated difference was -0.99 (-4.125, 2.27; P = 0.55). CONCLUSIONS: There were no randomized trials and over half of the 28 included studies were fair or poor quality. All but 1 reported at least a trend toward reduction in CRBSI. AML solutions appear to prevent CRBSI.

Retrospective Cohort Study of the Incidence and Outcomes of Jarisch-Herxheimer Reactions After Treatment of Infectious Syphilis in Late Pregnancy.

ABSTRACT: Of 39 pregnant women at ≥20 weeks' gestation treated with benzathine penicillin G for infectious syphilis, we identified only 2 mild Jarisch-Herxheimer reactions. There were no immediate fetal sequelae. Data from our study do not support the recommendation for routine admission for the treatment of infectious syphilis in late pregnancy.

Listeriosis in infants: Prospective surveillance studies in Canada and Switzerland.

OBJECTIVES: International data on listeriosis during infancy from large populations are essential to guide evidence-based empiric antibiotic guidelines for sepsis in infancy. We aimed to determine the incidence, clinical manifestations, and outcome of listeriosis in infants <6 months of age in Canada and Switzerland. METHODS: Prospective, active surveillance of listeriosis in infants <6 months of age was conducted through the Canadian Paediatric Surveillance Program (May 2015 to April 2017) and the Swiss Paediatric Surveillance Unit (April 2017 to March 2018). Confirmed and probable cases were included. RESULTS: In Canada, eight sporadic listeriosis cases were reported (incidence, 1.1/100,000 live births/year). In Switzerland, four cases were reported (incidence, 4.5/100,000 live births/year) of which three were part of a confirmed outbreak with an unclear source. In the two countries, eight of the 12 cases (66.6%) presented as early-onset disease (within the first 7 days of life) and none presented after 28 days life. CONCLUSIONS: Neonatal listeriosis is rare. Infants presenting with sepsis, especially after 4 weeks of life, may not routinely require empiric antibiotic coverage for listeriosis. Outbreak-related cases still occur. Continued surveillance is important.

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators' Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. METHODS: In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants < 90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. RESULTS: Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23%) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p = 0.010), present with seizures (p = 0.031) and have extra-CNS disease (p < 0.001). Unfavorable outcome occurred in 12 cases (11% of all EV and HSV infections) but was more likely following HSV than EV infection (4 (57%) versus 8 (8%); p = 0.002). CONCLUSIONS: Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis. Neurodevelopmental follow-up should be considered in infants whose course of illness is complicated by seizures.

Live vaccines after pediatric solid organ transplant: Proceedings of a consensus meeting, 2018.

Growing evidence suggests receipt of live-attenuated viral vaccines after solid organ transplant (SOT) has occurred and is safe and needed due to lapses in herd immunity. A 2-day consortium of experts in infectious diseases, transplantation, vaccinology, and immunology was held with the objective to review evidence and create expert recommendations for clinicians when considering live viral vaccines post-SOT. For consideration of VV and MMR post-transplant, evidence exists only for kidney and liver transplant recipients. For MMR vaccine post-SOT, consider vaccination during outbreak or travel to endemic risk areas. Patients who have received antiproliferative agents (eg. mycophenolate mofetil), T cell-depleting agents, or rituximab; or have persistently elevated EBV viral loads, or are in a state of functional tolerance, should be vaccinated with caution and have a more in-depth evaluation to define benefit of vaccination and net state of immune suppression prior to considering vaccination. MMR and/or VV (not combined MMRV) is considered to be safe in patients who are clinically well, are greater than 1 year after liver or kidney transplant and 2 months after acute rejection episode, can be closely monitored, and meet specific criteria of "low-level" immune suppression as defined in the document.

Salmonella infections in Canadian children.

Nontyphoidal Salmonella (NTS) infections are primarily transmitted by contaminated food or water or contact with carrier animals (particularly reptiles), and present with diarrhea. Antibiotics do not decrease the severity or duration of diarrhea and may increase the incidence of NTS carriage, so they should only be used with suspected or proven bacteremia or invasive infection. Typhoid/paratyphoid fever manifests as bacteremia within 60 days of travel to resource-poor countries and presents with fever and variable abdominal complaints. Therefore, blood cultures are indicated for unexplained fever and a relevant travel history. When blood cultures are positive or when a child is unwell pending blood culture results, ceftriaxone is indicated. A switch to oral antibiotics (usually azithromycin) is often possible after blood cultures have cleared and the child is improved.

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+ T cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28-CD4+ T cells are not likely useful in CMV risk stratification in children.

Does Dientamoeba fragilis cause diarrhea? A systematic review.

It remains controversial whether Dientamoeba fragilis is a commensal parasite or a pathogen. The objective of this systematic review was to establish the strength of the evidence that Dientamoeba fragilis would cause diarrhea. A search was performed for studies that reported either the association between D. fragilis detection in stools and diarrhea or diarrhea outcomes with D. fragilis therapy or challenge. Data from seven studies of specific populations reported that 22% had D. fragilis in stools of which only 23% had diarrhea. Eleven studies of stool samples submitted to laboratories reported that 4.3% of individuals had D. fragilis of which 54% had diarrhea. Twelve studies reported that D. fragilis was detected from 1.6% of individuals with diarrhea and 9.6% of diarrheal stools. Five studies analyzed the prevalence of D. fragilis in individuals with and without diarrhea; the two with a statistically significant difference between groups had discordant results. The only cohort study with an appropriate control group reported diarrhea in a higher proportion of children with D. fragilis than in controls. No D. fragilis treatment studies included diarrhea as an outcome. There were only two challenge studies involving one person each. In conclusion, the evidence that D. fragilis would cause diarrhea or that treatment would hasten diarrhea resolution is inconclusive.

Potential strategies to improve childhood immunization rates in Canada.

Immunization rates in Canada are suboptimal. Strategies such as making immunization mandatory for child care or school entry and financial incentives are used in other countries. Additional strategies that could work in the Canadian context include requiring accurate immunization records at school entry, implementing immunization registries at the provincial/territorial level, educating parents and school-aged children about vaccine-preventable diseases and making it more convenient for parents to ensure their children are fully immunized.

Update on invasive meningococcal vaccination for Canadian children and youth.

Invasive meningococcal disease (IMD) is serious, often resulting in fulminant sepsis or meningitis. IMD in Canada is primarily attributable to serogroups B and C. There are routine programs for serogroup C vaccine at 12 months of age, with some jurisdictions routinely providing additional earlier doses. Adolescents routinely receive a booster dose of serogroup C vaccine or of a quadrivalent (serogroups A, C, W and Y) vaccine. Serogroup B vaccines are not recommended for routine use pending further data on the efficacy and duration of protection from the available vaccine. However, children at increased risk for IMD should start immunization for serogroups B and C as soon as possible, assuming that they are at least 2 months of age.

Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

BACKGROUND: Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). METHODS: All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. RESULTS: Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). CONCLUSIONS: ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body.

Letter to the Editor - Re: Canadian Pediatrics Society position statement on newborn circumcision: a risk-benefit analysis revisited.

EDITORIAL.

The Epidemiology of Childhood Salmonella Infections in Alberta, Canada.

OBJECTIVES: The objectives were to describe the incidence, demographics, laboratory findings, and suspected sources of childhood Salmonella infections in Alberta, Canada, with a focus on preventable cases. METHODS: Data from Notifiable Disease Reports for children with nontyphoidal salmonellosis (NTS) or typhoid/paratyphoid fever from 2007 through 2015 were analyzed. RESULTS: NTS was detected from 2285 children. Bacteremia was documented in 55 cases (2.4%), whereas a single infant had NTS meningitis. The suspected source was food (N = 577; 25.3%) followed by animal or animal manure contact (N = 426; 18.6%), of which a reptile was the suspected source in 264 cases (11.5%). There were 44 outbreaks with none sharing the same food source. Ninety-five children were diagnosed with typhoid/paratyphoid fever, of which 48 cases (51%) were typhoid cases in unimmunized children 2 years or older. CONCLUSIONS: There are still ∼275 pediatric cases of Salmonella infection in Alberta annually, the bulk of which are preventable. APPLICATION: Public education about reptile exposure, food safety, and pretravel immunizations could potentially prevent many cases of Salmonella infection.

Zika virus: What does a physician caring for children in Canada need to know?

Zika virus (ZIKV) was recently recognized to be teratogenic. The diagnosis of congenital ZIKV syndrome should be considered in children with unexplained microcephaly, intracranial calcifications, ventriculomegaly or major structural central nervous system abnormalities. Management is evolving but suggestions are provided for children with findings compatible with congenital infection and for those born to women with potential exposure during pregnancy.

Urine metabolomic profiling of children with respiratory tract infections in the emergency department: a pilot study.

BACKGROUND: Clinicians lack objective tests to help determine the severity of bronchiolitis or to distinguish a viral from bacterial causes of respiratory distress. We hypothesized that children with respiratory syncytial virus (RSV) infection would have a different metabolomic profile compared to those with bacterial infection or healthy controls, and this might also vary with bronchiolitis severity. METHODS: Clinical information and urine-based metabolomic data were collected from healthy age-matched children (n = 37) and those admitted to hospital with a proven infection (RSV n = 55; Non-RSV viral n = 16; bacterial n = 24). Nuclear magnetic resonance (NMR) measured 86 metabolites per urine sample. Partial least squares discriminant analysis (PLS-DA) was performed to create models of separation. RESULTS: Using a combination of metabolites, a strong PLS-DA model (R2 = 0.86, Q2 = 0.76) was created differentiating healthy children from those with RSV infection. This model had over 90 % accuracy in classifying blinded infants with similar illness severity. Two other models differentiated length of hospitalization and viral versus bacterial infection. CONCLUSION: While the sample sizes remain small, this is the first report suggesting that metabolomic analysis of urine samples has the potential to become a diagnostic aid. Future studies with larger sample sizes are required to validate the utility of metabolomics in pediatric patients with respiratory distress.

A risk-stratified approach to cytomegalovirus prevention in pediatric solid organ transplant recipients.

Optimal strategies to prevent cytomegalovirus (CMV) disease following pediatric solid organ transplantation remain controversial. The purpose of this study was to review the outcomes of a risk-stratified strategy that uses a hybrid or prophylactic strategy for donor (D)+ recipient (R)- patients, a preemptive strategy for D+R+/D-R+, and clinical follow-up alone for D-R+ patients. A retrospective chart review was undertaken at the Stollery Children's Hospital in Edmonton, Alberta for pediatric solid organ transplants 2004 through 2010. Transplants were risk-stratified according to D/R CMV serostatus, organ group, and type of induction or rejection immunosuppression. The incidence of DNAemia and CMV disease and adverse effects from prophylaxis were analyzed. The study included 197 recipients. CMV DNAemia was detected in 49 of 197 recipients (24.8%), and CMV disease occurred in eight of 197 (4%) of which all but one were D+R-. All recovered. Seventeen of 142 recipients who received prophylaxis (12%) had hematologic toxicity. No other toxicities were identified. In conclusion, A risk-stratified approach resulted in very low rates of CMV disease with minimal adverse effects. Lowering the dosage rather than stopping antivirals in the face of neutropenia has the potential to further lower the rate of CMV disease.

The genetic diversity of Epstein-Barr virus in the setting of transplantation relative to non-transplant settings: A feasibility study.

This study examines EBV strains from transplant patients and patients with IM by sequencing major EBV genes. We also used NGS to detect EBV DNA within total genomic DNA, and to evaluate its genetic variation. Sanger sequencing of major EBV genes was used to compare SNVs from samples taken from transplant patients vs. patients with IM. We sequenced EBV DNA from a healthy EBV-seropositive individual on a HiSeq 2000 instrument. Data were mapped to the EBV reference genomes (AG876 and B95-8). The number of EBNA2 SNVs was higher than for EBNA1 and the other genes sequenced within comparable reference coordinates. For EBNA2, there was a median of 15 SNV among transplant samples compared with 10 among IM samples (p = 0.036). EBNA1 showed little variation between samples. For NGS, we identified 640 and 892 variants at an unadjusted p value of 5 × 10(-8) for AG876 and B95-8 genomes, respectively. We used complementary sequence strategies to examine EBV genetic diversity and its application to transplantation. The results provide the framework for further characterization of EBV strains and related outcomes after organ transplantation.