Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case ...definitions, standardized diagnostic approaches, and priorities for research. Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.
Objective
Dolutegravir is recommended worldwide as a first‐line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants ...of dolutegravir‐treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada.
Design
The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies.
Setting
Paediatric HIV clinics.
Population
Live‐born infants born in Canada to WLWH between 2007 and 2017.
Methods
Data on mother–infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites.
Main outcome measures
Congenital anomalies.
Results
Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85–4.36%) had non‐chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7–7.6%) or later in the pregnancy (3.9%, 95% CI 2.6–5.6%). Four of the 80 (5.0%, 95% CI 1.4–12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00–3.10%).
Conclusion
Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies.
Tweetable
Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.
Tweetable
Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.
Background
Premature development of cardiovascular disease in children living with HIV‐1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, ...systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH.
Methods
This was a cross‐sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation‐Canadian Child Cure Cohort (EPIC4) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury intestinal fatty acid binding protein‐1 (IFABP), systemic inflammation tumour necrosis factor (TNF) and interleukin‐6 (IL‐6) and endothelial activation angiopoietin‐2 (Ang2), soluble vascular endothelial growth factor‐1 (sVEGFR1) and soluble endoglin (sEng) were quantified by enzyme‐linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways.
Results
Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL‐6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein‐1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir‐boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7–17, P = 0.0020).
Conclusions
Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.
The reduction in human immunodeficiency virus (HIV) transmission through breastmilk with maternal combination antiretroviral therapy (cART) has led many pregnant women living with HIV and healthcare ...providers to question exclusive formula feeding in resource-rich settings. Here, we describe cART prophylaxis in 3 breastfed infants whose mothers had sustained virologic suppression; all 3 of these infants remained uninfected.
Objectives. A number of studies have looked at the role of infectious diseases in triggering juvenile dermatomyositis (JDM). Previous studies have found a moderately high frequency of infectious ...symptoms prior to disease onset; however, no specific pathogens could be identified. We sought to correlate preceding infectious symptoms with onset and outcomes of JDM. Methods. We studied an inception cohort of all JDM cases diagnosed at The Hospital for Sick Children (SickKids) between 1988 and 2006. Data pertaining to symptoms at onset, diagnosis and disease outcomes were abstracted. Two independent paediatric infectious disease specialists reviewed all records of patients with symptoms or tests suggestive of infection. Results. A total of 110 patients were reviewed; of these, 78 had sufficient information about disease onset for inclusion. Potential indications of an infectious process prior to JDM onset were found in 55/78 (71%) patients and were further evaluated for evidence of infection temporally associated with symptom onset. Features suggestive of infection prior to JDM symptom onset were found in 40/55 probable (30/40) or possible (10/40). Most children with probable infections had respiratory illnesses 24/30 (80%). Fewer patients than expected had disease onset during summer months. The presence of an infection at onset was not found to be associated with differences in characteristics at diagnosis or disease outcomes. Conclusions. A substantial number of JDM patients have a clinical history consistent with an infection prior to onset. Newly diagnosed patients should undergo a full infectious disease assessment as part of their initial work-up; specific attention should be given to respiratory infections.
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.
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.
National perinatal HIV surveillance programme.
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.
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%).
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.
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