Factors contributing to a coronavirus disease 2019 (COVID-19) outbreak on a mixed medical-surgical unit in a Canadian acute-care hospital.

Objective: To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities. Design: A case-control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit. Setting: This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021. Patients: Patients hospitalized on the unit for at least 12 hours and healthcare workers (HCW) working on the unit within 2 weeks of outbreak declaration were included. Methods: Risk factors for SARS-CoV-2 infection were analyzed using simple and multiple logistic regression. Whole-genome sequencing (WGS) was performed to identify SARS-CoV-2 strain relatedness. Network analysis was used to describe patient accommodation. Results: SARS-CoV-2 infections were identified in 21 patients (29.6%) and 11 HCWs (6.6%). WGS data revealed 4 distinct clades of related sequences. Several factors likely contributed to the outbreak, including failure to identify SARS-CoV-2, a largely incomplete or unvaccinated population, and patient wandering behaviors. The most significant risk factor for SARS-CoV-2 infection was room sharing with an infectious patient, which was the only factor that remained statistically significant following multivariate analysis (odds ratio [OR], 9.2l; 95% confidence interval [CI], 2.04-41.67; P = .004). Conclusions: This outbreak likely resulted from admission of 2 patients with COVID-19, with subsequent transmissions to 17 patients and 11 staff. WGS and bioinformatics analyses were critical to identifying previously unrecognized nosocomial transmissions of SARS-CoV-2. This study supports strategies to reduce nosocomial transmissions of SARS-CoV-2, such as single-patient rooms, promotion of COVID-19 vaccination, and infection prevention and control measures including management of wandering behaviors.

Mycobacterium fortuitum pacemaker infection: A case report.

BACKGROUND: Mycobacterium fortuitum is a rapidly growing mycobacterium, ubiquitous in soil and water, but it is an uncommon cause of infections in immunocompetent hosts. Cardiac device infections and bloodstream infections due to non-tuberculous mycobacteria are rare. CASE PRESENTATION: We present the case of an 85-year-old patient with infective endocarditis and pacemaker lead infection secondary to M. fortuitum.

HISTORIQUE: Le Mycobacterium fortuitum est une mycobactérie à la croissance rapide, omniprésente dans la terre et l'eau, mais est une cause d'infection peu courante chez les hôtes immunocompétents. Les infections des dispositifs cardiaques et du sang causées par des mycobactéries non tuberculeuses sont rares. PRÉSENTATION DE CAS: Les auteurs présentent le cas d'un patient de 85 ans atteint d'une endocardite infectieuse et d'une infection de la dérivation de son stimulateur cardiaque secondaire à un M. fortuitum.

Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease.

The modified 2-tier testing algorithm (MTTT) for Lyme disease (LD) has been approved by the US Food and Drug Administration. In this study, we show that the MTTT detected 28% more cases of early infection compared with the standard 2-tier algorithm while retaining high specificity in a region with a high incidence of LD.

Raisonnement clinique : Avortement septique à Neisseria meningitidis.

Le choc septique post-avortement est une cause mondiale importante de mortalité maternelle, mais on l'observe rarement dans les pays développés. Nous décrivons ici un cas d'avortement septique associé à un nouvel agent pathogène : Neisseria meningitidis. Une femme multipare de 30 ans s'est trouvée en choc septique après un avortement spontané incomplet. Elle a reçu un traitement empirique par antibiotiques et vasopresseurs, a subi une dilatation-aspiration d'urgence et a été admise à l'unité de soins intensifs. L'hémoculture et l'analyse de tissus endométriaux se sont révélées positives à la bactérie N. meningitidis. L'antibiothérapie a été ajustée en fonction de la culture et la patiente s'est rétablie. Il importe de reconnaître le choc septique, d'administrer l'antibiothérapie et de neutraliser la source d'infection dans les plus brefs délais. Ici, nous décrivons un cas d'avortement septique associé à un agent pathogène inhabituel. Nous soulignons aussi l'importance d'utiliser une antibiothérapie empirique à large spectre suivie d'une antibiothérapie spécifique aux résultats de culture pour obtenir la meilleure couverture possible.

Clinical Conundrum: Neisseria meningitidis Septic Abortion.

Septic shock after abortion is an important cause of global maternal mortality but is rarely encountered in developed countries. We describe a case of septic abortion with a novel associated pathogen: Neisseria meningitidis. A 30-year-old multiparous woman presented in septic shock after an incomplete spontaneous abortion. She received empiric antibiotics and vasopressors, underwent an urgent dilatation and curettage, and was admitted to the intensive care unit. Her blood cultures and endometrial tissue were positive for N. meningitidis. Antibiotics were adjusted based on culture, and the patient recovered. Septic shock requires prompt identification, antibiotic administration, and source control. Here, we identify an uncommon pathogen associated with septic abortion and highlight the importance of broad empiric and subsequent culture-guided antibiotic choice to ensure coverage.

Maternal CD8+ T-cell depletion alleviates intrauterine inflammation-induced perinatal brain injury.

We investigated the mechanisms by which CD8+ T-cell trafficking in placenta contributes to perinatal brain injury by studying effects of maternal CD8+ T-cell depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal CD8+ T cells were depleted with anti-CD8+ antibodies. IUI was induced with lipopolysaccharide (LPS). DEP was confirmed using flow cytometry. Preterm birth rate was evaluated. Offspring neurologic sequelae were assessed by Nissl staining, immune arrays, confirmatory individual TaqMan® gene assays, and neurobehavioral tests. DEP did not significantly prevent LPS-induced preterm birth but improved neurobehavioral performance (P < .001) and increased cortical neuronal density (P < .05) in LPS-exposed pups compared to controls. These changes were associated with decreased CCL3 and CXCL10 and increased CCL5 in DEP LPS-exposed mice. We demonstrate that DEP reduces perinatal brain injury following IUI. This supports a role for maternal CD8+ T-cell trafficking in placenta in mediating perinatal brain injury separate from preterm birth mechanisms.

P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a mouse model of intrauterine inflammation.

The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1ß secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we utilized embryo transfer experiments to delineate whether the P2X7 was the key mediator of IU inflammation-associated brain injury on maternal or fetal sides. In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth rate, improved offspring performance on neuromotor tests as well as the dendritic arborization and density of cortical neurons. Embryo transfer experiments demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects on offspring. Both genetic and pharmacologic blockade of IL-1ß signaling, by targeting maternal P2X7R, ameliorated perinatal brain injury following exposure to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically useful tool to prevent both preterm birth and prematurity-associated perinatal brain injury, and further studies are urgently needed.

Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury.

Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.

Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes.

Zika virus (ZIKV) crosses the placenta and causes congenital disease. Here we develop an animal model utilizing direct ZIKV inoculation into the uterine wall of pregnant, immunocompetent mice to evaluate transplacental transmission. Intrauterine inoculation at embryonic day (E) 10, but not E14, with African, Asian or American strains of ZIKV reduces fetal viability and increases infection of placental and fetal tissues. ZIKV inoculation at E10 causes placental inflammation, placental dysfunction and reduces neonatal brain cortical thickness, which is associated with increased activation of microglia. Viral antigen localizes in trophoblast and endothelial cells in the placenta, and endothelial, microglial and neural progenitor cells in the fetal brain. ZIKV infection of the placenta increases production of IFNß and expression of IFN-stimulated genes 48 h after infection. This mouse model provides a platform for identifying factors at the maternal-fetal interface that contribute to adverse perinatal outcomes in a host with an intact immune system.

Maternal Fructose Consumption Disrupts Brain Development of Offspring in a Murine Model of Autism Spectrum Disorder.

Objective The objective of this study was to localize by neuroimaging the altered structural brain development of these offspring using an autism model of transgenic mice lacking contactin-associated protein-like 2 (Cntnap2). Materials and Methods Pregnant dams were randomly allocated to fructose solution (10% W/V) as only drinking fluid or water. Cntnap2 heterozygous (+/-) offspring from each group were euthanized at 6 months of age and their whole brains evaluated by magnetic resonance imaging. T2-weighted images were acquired to evaluate the volumes of 29 regions of interest involved in autism spectrum disorder (ASD) pathogenesis. Whole brains were washed and processed for Nissl staining. Mann-Whitney U test and one-way analysis of variance were used for statistical analysis (significance: p < 0.05). Results The corpus callosum, anterior commissure, and caudate putamen were significantly smaller in Cntnap2 (+/-) male offspring exposed to fructose. No brain alterations were found in the female counterparts. Nissl staining of the caudate putamen revealed higher neuronal cell count in the male fructose offspring. Female group revealed an increase in caudate putamen neuronal cell count. Conclusion Metabolic dysregulation in pregnancy alters fetal brain development in genetically predisposed offspring. This is consistent with findings in human studies and supports the role of intrauterine factors in the etiology of autism.