Jason Brophy

A national review of vertical HIV transmission

Objectives:Prevention of vertical HIV transmission has evolved significantly in Canada over the last two decades. The aim of this analysis is to describe the surveillance programme used, rate of vertical HIV transmission and changing epidemiology of HIV-affected pregnancies in Canada. Design:National perinatal HIV surveillance programme. Methods:From 1990, annual retrospective data was collected on demographic and clinical characteristics of HIV-infected mothers and their infants referred to 22 participating sites across Canada either before/during pregnancy or within 3 months after delivery. Factors impacting HIV transmission and demographic features were explored. Results:Two thousand, six hundred and ninety-two mother–infant pairs were identified. The overall rate of vertical HIV transmission was 5.2%, declining to 2.9% since 1997. The rate of transmission for mothers who received HAART was 1%, and 0.4% if more than 4 weeks of HAART was given. Forty percent of women delivered by caesarean section, with no difference in transmission rate compared with vaginal delivery for women treated with HAART (1.4 vs. 0.6%, P = 0.129) but significant risk reduction for those who did not receive HAART (3.8 vs. 10.3%, P = 0.016). Black women were the largest group; proportions of black and aboriginal women increased significantly over time (P < 0.001 for both). Heterosexual contact was the most common risk category for maternal infection (65%), followed by injection drug use (IDU) (25%). Conclusion:Vertical HIV transmission in Canada has decreased dramatically for women treated with HAART therapy. All pregnant women should be evaluated for HIV infection and programmes expanded to reach vulnerable populations including aboriginal, immigrant and IDU women.

Blastomycosis in Ontario, 1994–2003

Clinicians in Ontario should be aware of symptoms and areas where disease is endemic.

Early Initiation of Combination Antiretroviral Therapy in HIV-1–Infected Newborns Can Achieve Sustained Virologic Suppression With Low Frequency of CD4+ T Cells Carrying HIV in Peripheral Blood

BACKGROUND A human immunodeficiency virus type 1 (HIV-1)-infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1-infected children with sustained virologic suppression. METHODS Children born to HIV-1-infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1-infected children with sustained virologic suppression. RESULTS Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6 copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10(6) CD4(+) T cells). CONCLUSIONS In perinatally HIV-1-infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children.

Use of newer antiretroviral agents, darunavir and etravirine with or without raltegravir, in pregnancy: a report of two cases.

BACKGROUND Although antiretroviral therapy during pregnancy is associated with significant reductions in the risk of vertical transmission of HIV, attainment of this outcome in highly treatment-experienced pregnant women might be complicated by the lack of active drugs available to assemble a potent regimen. The recent licensing and availability of darunavir, etravirine and raltegravir has broadened management options available for highly treatment-experienced patients. However, data on their safety and efficacy in preventing vertical transmission are limited. METHODS A retrospective chart review of two cases describing obstetrical, infant and treatment outcomes associated with the use of regimens that include darunavir and etravirine with or without raltegravir during pregnancy was conducted. RESULTS We document two cases of pregnant HIV-positive women treated with antiretroviral therapy including darunavir, etravirine and raltegravir. Vertical transmission was averted and no congenital anomalies were observed. CONCLUSIONS In the absence of human development toxicity data for these agents, these cases provide preliminary anecdotal data on their safety during pregnancy. Although the outcomes of these cases are reassuring, additional studies and registries are required to establish the safety and efficacy of these agents during pregnancy.

Reducing the risk of pet-associated zoonotic infections.

Pet ownership can have health, emotional and social benefits; however, pets can serve as a source of zoonotic pathogens. One large, regional survey reported more than 75% of households having contact with a pet,[1][1] and close, intimate interactions with pets (e.g., sleeping in beds with owners,

The Epidemiology, Management, and Outcomes of Bacterial Meningitis in Infants

This study details patients diagnosed with bacterial meningitis in the first 90 days of life at 7 pediatric hospitals in Canada. OBJECTIVES: The pathogens that cause bacterial meningitis in infants and their antimicrobial susceptibilities may have changed in this era of increasing antimicrobial resistance, use of conjugated vaccines, and maternal antibiotic prophylaxis for group B Streptococcus (GBS). The objective was to determine the optimal empirical antibiotics for bacterial meningitis in early infancy. METHODS: This was a cohort study of infants <90 days of age with bacterial meningitis at 7 pediatric tertiary care hospitals across Canada in 2013 and 2014. RESULTS: There were 113 patients diagnosed with proven meningitis (n = 63) or suspected meningitis (n = 50) presented at median 19 days of age, with 63 patients (56%) presenting a diagnosis from home. Predominant pathogens were Escherichia coli (n = 37; 33%) and GBS (n = 35; 31%). Two of 15 patients presenting meningitis on day 0 to 6 had isolates resistant to both ampicillin and gentamicin (E coli and Haemophilus influenzae type B). Six of 60 infants presenting a diagnosis of meningitis from home from day 7 to 90 had isolates, for which cefotaxime would be a poor choice (Listeria monocytogenes [n = 3], Enterobacter cloacae, Cronobacter sakazakii, and Pseudomonas stutzeri). Sequelae were documented in 84 infants (74%), including 8 deaths (7%). CONCLUSIONS: E coli and GBS remain the most common causes of bacterial meningitis in the first 90 days of life. For empirical therapy of suspected bacterial meningitis, one should consider a third-generation cephalosporin (plus ampicillin for at least the first month), potentially substituting a carbapenem for the cephalosporin if there is evidence for Gram-negative meningitis.

An outbreak of vancomycin-resistant Enterococcus faecium in an acute care pediatric hospital: Lessons from environmental screening and a case-control study

BACKGROUND The present study describes a vancomycin-resistant enterococci (VRE) outbreak investigation and a case-control study to identify risk factors for VRE acquisition in a tertiary care pediatric hospital. OBJECTIVE To report an outbreak investigation and a case-control study to identify risk factors for VRE colonization or infection in hospitalized children. METHODS Screening for VRE cases was performed by culture or polymerase chain reaction. A case-control study of VRE-colonized patients was undertaken. Environmental screening was performed using standard culture and susceptibility methods, with pulsed-field gel electrophoresis to determine relationships between VRE isolates. Statistical analysis was performed using SAS version 9.0 (SAS Institute Inc, USA). RESULTS Thirty-four VRE-positive cases were identified on 10 wards between February 28, 2005, and May 27, 2005. Pulsed-field gel electrophoresis analysis confirmed a single outbreak strain that was also isolated from a video game found on one affected ward. Multivariate analysis identified cephalosporin use as the major risk factor for VRE colonization. CONCLUSIONS In the present study outbreak, VRE colonization was significantly associated with cephalosporin use. Because shared recreational items and environmental surfaces may be colonized by VRE, they warrant particular attention in housekeeping protocols, particularly in pediatric institutions.

HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine.

OBJECTIVE To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24months. DESIGN Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24months. Adverse events were recorded throughout. RESULTS Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38years (IQR 32-45, range 15-66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL<40c/ml) at baseline, with a median CD4 count of 510cells/mm(3) (376-695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74-3.05fold higher peak antibody response compared to those without (p from 0.006 to <0.0001). CONCLUSIONS This study is the first to examine the qHPV vaccine in HIV-positive women out to 24months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination. CLINICAL TRIAL REGISTRATION http://www.isrctn.com/ISRCTN33674451.

Trends in live birth rates and adverse neonatal outcomes among HIV-positive women in Ontario, Canada, 2002–2009: a descriptive population-based study

To characterise trends in live birth rates, adverse neonatal outcomes and socio-demographic characteristics of pregnant women with diagnosed HIV between the ages of 18 and 49 in Ontario, Canada from 1 April 2002 to 31 March 2010, we conducted a population-based study. Utilising linked administrative healthcare databases we used generalised estimating equations to characterise secular trends and examine the association between live births and socio-demographic characteristics, including age, region of birth and neighbourhood income quintile. Between 2002/2003 and 2009/2010, there were 551 live births during 15,610 person-years of follow-up. The proportion of HIV-positive mothers originally from Africa or the Caribbean increased from 26.7% to 51.6% over the study period. The risk of pre-term (risk ratio 2.13, 95% confidence interval 1.74 to 2.61) and small for gestational age births (risk ratio 1.53, 95% confidence interval 1.20 to 1.94) was higher in women with HIV compared with provincial estimates for these outcomes. Women with HIV have rates of pre-term and small for gestational age births that exceed provincial estimates for these outcomes. Further research is required to identify factors mediating these disparities that are amenable to pre-natal risk reduction initiatives.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada: A Nationwide Study

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.