Two children with extra-nodal Mycobacterium avium complex infection.

Mycobacterium avium complex (MAC) is usually considered an opportunistic organism, which infects immunocompromised children or those with structural airway abnormalities. We present two cases of MAC infection affecting immune competent children, likely from hot tubs with primary involvement of pulmonary and urinary systems. These cases highlight the importance of asking about hot tub use in immune competent children with suspected or confirmed MAC infections.

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.

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.

Invasive candidiasis in low birth weight preterm infants: risk factors, clinical course and outcome in a prospective multicenter study of cases and their matched controls.

BACKGROUND: This multicenter prospective study of invasive candidiasis (IC) was carried out to determine the risk factors for, incidence of, clinical and laboratory features, treatment and outcome of IC in infants of birth weight <1250 g. METHODS: Neonates <1250 g with IC and their matched controls (2:1) were followed longitudinally and descriptive analysis was performed. Survivors underwent neurodevelopmental assessment at 18 to 24 months corrected age. Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant Development 2nd edition. Multivariable analyses were performed to determine risk factors for IC and predictors of mortality and NDI. RESULTS: Cumulative incidence rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750 g, <1000 g, <1500 g, respectively. Forty nine infants with IC and 90 controls were enrolled. Necrotizing enterocolitis (NEC) was the only independent risk factor for IC (p=0.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality rate (57%) and incidence of deafness (50%) than the overall cohort of infants with IC. NDI (56% vs. 33%; p=0.017) and death (45% vs. 7%; p=0.0001) were more likely in cases than in controls, respectively. IC survivors were more likely to be deaf (28% vs. 7%; p=0.01). IC independently predicted mortality (p=0.0004) and NDI (p=0.018). CONCLUSION: IC occurred in 1.5% of VLBW infants. Preceding NEC increased the risk of developing IC. CNS candidiasis is under-investigated and difficult to diagnose, but portends a very poor outcome. Mortality, deafness and NDI were independently significantly increased in infants with IC compared to matched controls.

Children hospitalized with respiratory syncytial virus infection in Saskatchewan pediatric tertiary care centers, 2002-2005.

OBJECTIVE: To describe the epidemiology and severity of illness of children hospitalized with respiratory syncytial virus (RSV) infection, including those who received palivizumab prophylaxis, at Royal University Hospital (RUH), Saskatoon and Regina General Hospital (RGH) from July 2002 to June 2005. METHODS: Children hospitalized for ≥ 24 hours with laboratory-confirmed RSV infection were enrolled, and their health records were retrospectively reviewed for patient demographics and referral patterns, use of palivizumab prophylaxis, severity of infection (length of hospitalization, need for and duration of pediatric intensive care and mechanical ventilation) and outcome of infection. RESULTS: A total of 590 children (324 males) were hospitalized over the three years. The median chronological age at admission was 5.3 months, and median hospital stay was 4.0 days. Gestational age at birth was ≥ 36 weeks in 82.4% of patients. RSV disease severity was mild to moderate in 478 patients (81.0%) and severe in 110 (18.6%). Thirty-nine patients (6.6%) required pediatric intensive care unit admission, for a median of 5.0 days. Twenty-two of these patients (56%) were mechanically ventilated for a median of 6.0 days. Two children died, not attributed to RSV infection. Twenty-two patients had received palivizumab prophylaxis before hospital admission, with 18 completing at least 2 of the monthly doses. Most of these children (17/22) had mild to moderate illness. CONCLUSIONS: RSV causes significant morbidity in Saskatchewan, affecting predominantly term infants. The majority of illness is mild to moderate. Some patients who have received palivizumab may still develop significant RSV disease.

Carriage of Haemophilus influenzae serotype A in children: Canadian Immunization Research Network (CIRN) study.

Background: Haemophilus influenzae serotype a (Hia) has recently emerged as an important cause of invasive disease, mainly affecting young Indigenous children. Carriage of H. influenzae is a pre-requisite for invasive disease and reservoir for transmission. To better understand the epidemiology of invasive Hia disease, we initiated a multicentre study of H. influenzae nasopharyngeal carriage among Canadian children. Methods: With prior parental consent, we collected nasotracheal tubes used during general anaesthesia in healthy children following routine dental surgery in a regional hospital of northwestern Ontario and a dental clinic in central Saskatchewan. In northwestern Ontario, all children were Indigenous (median age 48.0 months, 45.8% female); in Saskatchewan, children were from various ethnic groups (62% Indigenous, median age 56.3 months, 43.4% female). Detection of H. influenzae and serotyping were performed using molecular-genetic methods. Results: A total of 438 nasopharyngeal specimens, 286 in northwestern Ontario and 152 in Saskatchewan were analyzed. Hia was identified in 26 (9.1%) and 8 (5.3%) specimens, respectively. In Saskatchewan, seven out of eight children with Hia carriage were Indigenous. Conclusions: The carriage rates of Hia in healthy children in northwestern Ontario and Saskatchewan are comparable to H. influenzae serotype b (Hib) carriage among Alaska Indigenous children in the pre-Hib-vaccine era. To prevent invasive Hia disease, paediatric conjugate Hia vaccines under development have the potential to reduce carriage of Hia, and thus decrease the risk of transmission and disease among susceptible populations. Addressing the social determinants of health may further eliminate conditions favouring Hia transmission in Indigenous communities.

Historique: L'Haemophilus influenzae de sérotype a (Hia) a récemment émergé comme une cause importante de maladie invasive, particulièrement chez les jeunes enfants autochtones. Il faut être porteur de l'H. influenzae pour contracter une maladie invasive et devenir un réservoir de transmission. Pour mieux comprendre l'épidémiologie de l'infection invasive à Hia, les chercheurs ont lancé une étude multicentrique sur le portage nasopharyngé de l'H. influenzae chez les enfants canadiens. Méthodologie: Après avoir obtenu le consentement des parents, les chercheurs ont recueilli les sondes nasotrachéales utilisées pendant l'anesthésie générale chez des enfants en santé après une chirurgie dentaire courante dans un hôpital régional du nord-ouest de l'Ontario et une clinique dentaire du centre de la Saskatchewan. Dans le nord-ouest de l'Ontario, tous les enfants étaient autochtones (âge médian de 48,0 mois, 45,8 % de filles); en Saskatchewan, les enfants provenaient de divers groupes ethniques (62 % d'Autochtones, âge médian de 56,3 mois, 43,4 % de femmes). La détection de l'H. influenzae et le sérotypage ont été effectués au moyen de méthodes de génétique moléculaire. Résultats: Au total, les chercheurs ont analysé 438 échantillons nasopharyngés, soit 286 du nord-ouest de l'Ontario et 152 de la Saskatchewan. L'Hia a été décelé dans 26 (9,1 %) et huit (5,3 %) échantillons, respectivement. En Saskatchewan, sept des huit enfants porteurs de l'Hia étaient autochtones. Conclusions: Le taux de portage de l'Hia chez les enfants en santé du nord-ouest de l'Ontario et de la Saskatchewan était comparable à celui du portage de l'H. influenzae du sérotype b (Hib) chez les enfants autochtones de l'Alaska avant le déploiement des vaccins contre le Hib. Pour éviter l'infection invasive à Hia, les vaccins pédiatriques conjugués contre l'Hia en cours de développement peuvent réduire le portage de l'Hia, et donc le risque de transmission et de maladie dans les populations susceptibles. Le fait d'aborder les déterminants sociaux de la santé pourrait contribuer à éliminer les conditions favorables à la transmission à Hia dans les communautés autochtones.

Congenital rubella syndrome, a case series.

Rubella, or German measles, is a vaccine-preventable disease. Rubella infection is usually mild; however, infection in pregnancy is associated with severe outcomes for the baby, including pregnancy loss or a combination of developmental defects called congenital rubella syndrome. Within the last ten-year period, two cases of congenital rubella syndrome in Saskatchewan were reported to the provincial ministry and the Public Health Agency of Canada of the newborns of mothers who had recently arrived from Sub-Saharan Africa. Both infants had multiple health complications at birth consistent with congenital rubella and tested positive for the rubella virus. The article discusses the challenges encountered by the healthcare system in diagnosing, investigating, monitoring and managing cases of congenital rubella syndrome to prevent further sporadic transmission. The article emphasizes the need to provide additional support for cases and their households, especially new Canadians with less support to comply with public health advice and the importance of routine immunization to eliminate rubella globally.

Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.

Genetic deficiency of adenosine deaminase (ADA) can cause profound lymphopenia and result in the clinical presentation of severe combined immune deficiency (SCID). However, because of the ubiquitous expression of ADA, ADA-deficient patients often present also with nonimmunologic clinical problems, affecting the skeletal, central nervous, endocrine, and gastrointestinal systems. We now report that myeloid dysplasia features and bone marrow hypocellularity are often found in patients with ADA-SCID. As a clinical correlate to this finding, we have observed vulnerability to antibiotic-induced myelotoxicity and prolonged neutropenia after nonmyeloablative chemotherapy. We have also noted that, in the absence of enzyme replacement therapy, absolute neutrophil counts of patients with ADA deficiency vary inversely with the accumulation of deoxynucleotides. These data have significant implications for the application of standard and investigational therapies to patients with ADA-SCID and support further studies to investigate the possibility that ADA deficiency is associated with a stem cell defect. These trials were registered at www.clinicaltrials.gov as #NCT00018018 and #NCT00006319.

Respiratory infection and otitis media visits in relation to pneumococcal conjugate vaccine use in Saskatchewan.

BACKGROUND: In Saskatchewan, pneumococcal conjugate vaccination (PCV) was offered to high-risk children in 2002 and to all infants in 2005. OBJECTIVE: To describe trends in the frequency of medical visits for lower respiratory tract infection (LRI) and otitis media (OM) in relation to PCV use during the period 1990 to 2008. METHODS: Statistics regarding the number of children covered by the health insurance plan, PCV administration, and medical visits with a diagnostic code associated with LRI and OM were provided by Saskatchewan Health. Monthly rates were analyzed using dynamic state space models. RESULTS: In all series, there was a marked seasonal cycle and some higher-than-expected winter peak values, possibly associated with epidemics of specific respiratory viruses. Three abrupt decreases in baseline rate were observed for LRI and the final one, in February 2007, could be related to the increased proportion of children vaccinated with PCV. There was no statistical correlation between PCV use and OM visit frequency. CONCLUSION: Many environmental, biological and administrative factors may influence health services use, and an effect of low magnitude of a particular vaccine pertaining to nonspecific outcomes could be obscured in time-series analyses.

HISTORIQUE: En Saskatchewan, le vaccin conjugué contre le pneumocoque (VCP) est offert aux enfants très vulnérables depuis 2002, et à tous les nourrissons depuis 2005. OBJECTIF: Décrire les tendances en matière de fréquence de rendezvous chez le médecin pour des infections des voies respiratoires inférieures (IVRI) ou une otite moyenne (OM) par rapport à l'utilisation du VCP entre 1990 et 2008. MÉTHODOLOGIE: Santé Saskatchewan a fourni les statistiques relatives au nombre d'enfants couverts par le régime d'assurance-maladie, à l'administration du VCP et aux rendez-vous médicaux dont le code médical s'associait à une IVRI ou à une OM. Les chercheurs ont analysé les taux mensuels au moyen de modèles dynamiques à espace d'état. RÉSULTATS: Dans toutes les séries, les chercheurs ont constaté un cycle saisonnier marqué et certaines valeurs hivernales de pointe plus élevées que prévu, qui s'associaient peut-être à des épidémies de virus respiratoires particuliers. Ils ont observé trois diminutions abruptes des taux de départ pour ce qui est des IVRI. La dernière, en février 2007, pourrait être liée à l'augmentation de la proportion d'enfants ayant reçu le VCP. Ils n'ont remarqué aucune corrélation statistique entre l'utilisation du VCP et la fréquence des rendez-vous liés à l'OM. CONCLUSION: De nombreux facteurs environnementaux, biologiques et administratifs peuvent influer sur l'utilisation des services de santé, et l'effet marginal d'un certain vaccin sur des issues non spécifiques peut être masqué dans des analyses de séries chronologiques.

Prevention of respiratory syncytial viral infections in late preterm infants.

RSV prophylaxis is not routine in infant born 33 to 35 weeks gestation. Risk scoring tool can be utilized to identify infants that have significant chance for hospitalization. Premature birth is a leading cause of infant mortality and chronic pulmonary morbidity, therefore prevention of RSV hospitalization though immune prophylaxis in late preterm infants appears attractive.

International Olympic Committee (IOC) consensus paper on sports-related ophthalmology issues in elite sports.

Vision plays an important role in an athletes' success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity. The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions. The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue.

Spontaneous osteonecrosis of the jaw in a ß-Thalassemia intermedia patient.

The resultant anemia in hemoglobinopathies like thalassemia can lead to expansion of the bone marrow cavities due to compensatory hyperplasia. This article reports a case of spontaneous osteonecrosis of the left maxillary alveolus in a patient with ß-Thalassemia intermedia. The area affected presented as areas of osteosclerosis on the radiographic examination and sequestrectomy of the left maxillary alveolus was performed after consultation with his hematologist. The exact pathogenesis for the osteonecrosis is unclear. One possible postulation for the cause of osteonecrosis in our case could be that the alveolar bone suffered ischemic infarction secondary to occlusion of the microvasculature within the expanded cancellous bone.

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0-42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7-26 months). A median of 9.5 cases were reported per year (range 4-14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0-14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data.

Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes.

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy. METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated. RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C). CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes.

Comparative proteomic analysis of irinotecan-sensitive colorectal carcinoma cell line and its chemoresistant counterpart.

In this study, we used two-dimensional gel electrophoresis and MALDI-Q-TOF-MS/MS analysis to examine the global protein expression of a pair of colorectal carcinoma cell lines, SW620 and irinotecan-resistant SW620. Of the 30 spots identified as differentially expressed proteins (±over twofold, P<0.05) between the two cell lines, 26 spots (corresponding to 26 unique proteins) were positively identified by MALDI-Q-TOF-MS/MS analysis. These proteins could be grouped into main classes including metabolism (15.38%), cell SSproliferation/differentiation (11.53%), molecular chaperone (11.53%), mRNA splicing (11.53%), and so on. The proteins, which might be involved in the development of tumor drug resistance, such as α-enolase, cofilin, and thioredoxin-dependent peroxide 1, have been validated by western blot analysis and have been discussed. The proteins identified in this study may be useful in showing the mechanisms underlying irinotecan resistance.

Federated Transfer Learning for EEG Signal Classification.

The success of deep learning (DL) methods in the Brain-Computer Interfaces (BCI) field for classification of electroencephalographic (EEG) recordings has been restricted by the lack of large datasets. Privacy concerns associated with EEG signals limit the possibility of constructing a large EEG-BCI dataset by the conglomeration of multiple small ones for jointly training machine learning models. Hence, in this paper, we propose a novel privacy-preserving DL architecture named federated transfer learning (FTL) for EEG classification that is based on the federated learning framework. Working with the single-trial covariance matrix, the proposed architecture extracts common discriminative information from multi-subject EEG data with the help of domain adaptation techniques. We evaluate the performance of the proposed architecture on the PhysioNet dataset for 2-class motor imagery classification. While avoiding the actual data sharing, our FTL approach achieves 2% higher classification accuracy in a subject-adaptive analysis. Also, in the absence of multi-subject data, our architecture provides 6% better accuracy compared to other state-of-the-art DL architectures.

Dynamic dengue haemorrhagic fever calculators as clinical decision support tools in adult dengue.

BACKGROUND: The objective of this study was to develop multiple prediction tools that calculate the risk of developing dengue haemorrhagic fever. METHODS: Training data consisted of 1771 individuals from 2006-2008 admitted with dengue fever whereby 304 developed dengue haemorrhagic fever during hospitalisation. Least absolute shrinkage and selection operator regression was used to construct three types of calculators, static admission calculators and dynamic calculators that predict the risk of developing dengue haemorrhagic fever for a subsequent day (DAily Risk Tomorrow [DART]) or for any future point after a specific day since fever onset (DAily Risk Ever [DARE]). RESULTS: From 119 admission covariates, 35 were in at least one of the calculators, which reported area under the curve (AUC) values of at least 0.72. Addition of person-time data for DART improved AUC to 0.76. DARE calculators displayed a large increase in AUC to 0.79 past day 7 with the inclusion of a strong predictor, maximum temperature on day 6 since onset, indicative of a saddleback fever. CONCLUSIONS: All calculators performed well when validated with 2005 data. Addition of daily variables further improved the accuracy. These calculators can be used in tandem to assess the risk of dengue haemorrhagic fever upon admission and updated daily to obtain more precise risk estimates.

Review of pediatric encephalitis and encephalopathy cases following immunization reported to the Canadian Immunization Monitoring Program Active (IMPACT) from 1992 to 2012.

BACKGROUND: Neurological adverse events following immunization (AEFI) remain poorly characterized. Our objective was to describe pediatric acute and chronic encephalopathy and encephalitis cases following immunization reported via active sentinel surveillance from 1992 to 2012. METHODS: This case series provides a descriptive analysis of encephalopathy/encephalitis admissions reported to the Canadian Immunization Monitoring Program ACTive (IMPACT). Acute cases were reported if symptom onset (seizures, decreased level of consciousness, change in mental status) occurred 0-7 days after tetanus or pertussis-containing vaccines, 0-15 days after other inactivated vaccines, or 5-30 days after live vaccines. Chronic cases of subacute sclerosing panencephalitis or subacute progressive rubella encephalitis were reported at any interval after vaccination. Clinical data were examined to identify possible causes for encephalopathy/encephalitis other than vaccination. RESULTS: Sixty-one cases of encephalopathy/encephalitis following immunization were reported to IMPACT over 21 years; 57 (93.4%) were classified as acute and 4 (6.6%) were chronic cases of subacute sclerosing panencephalitis. Most patients (73.8%) were previously healthy and immunocompetent. The vaccines most frequently administered prior to presentation were diphtheria-tetanus-pertussis, measles-mumps-rubella, and influenza. At discharge, 38 patients (62.3%) had normal neurological status or were expected to recover. Forty patients (70.2%) with acute encephalopathy/encephalitis had a more likely alternate etiology besides vaccination based on neuroimaging, symptoms suggestive of infection, laboratory-confirmed non-vaccine-related infection, or clinical diagnosis. No cases of encephalitis were causally associated with pertussis or influenza vaccines. Two patients (50%) with subacute sclerosing panencephalitis had known wild-type measles infection prior to immunization. Three deaths were reported during hospitalization (4.9%); all were acute encephalitis/encephalopathy cases and none were confirmed to be vaccine-related. CONCLUSIONS: Encephalopathy/encephalitis following immunization remains a rare but serious adverse event. Most cases had another more likely etiology than vaccination. Continued monitoring and analysis of AEFI is paramount to ensure the safety of immunization programs.

Challenges to achieving and maintaining viral suppression among children living with HIV.

OBJECTIVES: The objective of this study was to determine the time to, and durability of, viral suppression, among Canadian children living with HIV after initiation of combination antiretroviral therapy (cART). DESIGN: Prospective, multicenter Canadian cohort study (Early Pediatric Initiation Canada Child Cure Cohort), using both prospective and retrospectively collected data. METHODS: Kaplan-Meir survival estimates with Cox regression were used to determine the time to and risk factors for viral suppression, defined as two consecutive undetectable viral loads (<50 copies/ml) at least 30 days apart after initiation of cART. RESULTS: A total of 228 children were enrolled between December 2014 and December 2018. The time to viral suppression was significantly shorter among children initiating cART after 5 ≤ 5 vs. years or less of age [adjusted hazard ratio (aHR) 1.57, 95% confidence interval (CI) 1.13-2.20], among those born after 2010 vs. prior (aHR 1.71, 95% CI 1.04-2.79), and among those without child protection services involvement (aHR 1.44, 95% CI 1.03-2.01). Overall, 27% of children had a viral rebound within 3 years of achieving viral suppression; the risk of viral rebound was significantly lower among children initiating cART after 5 vs. 5 years or less of age [adjusted odds ratio (aOR): 0.32, 95% CI 0.13-0.81], those whose families had not received social assistance (aOR 0.16, 95% CI 0.06-0.46), and females vs. males (aOR 0.51, 95% CI 0.26-0.99). CONCLUSION: Only 73% of the children in the Early Pediatric Initiation Canada Child Cure Cohort had maintained viral suppression 3 years after it was first achieved. Age at cART initiation, and socioeconomic factors were predictors of both time to viral suppression and risk of viral rebound in this cohort.

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: 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). METHODS: This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled. RESULTS: 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. CONCLUSION: 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.