Monkeypox Virus Infections in Humans.

Human monkeypox is a viral zoonosis endemic to West and Central Africa that has recently generated increased interest and concern on a global scale as an emerging infectious disease threat in the midst of the slowly relenting COVID-2019 disease pandemic. The hallmark of infection is the development of a flu-like prodrome followed by the appearance of a smallpox-like exanthem. Precipitous person-to-person transmission of the virus among residents of 100 countries where it is nonendemic has motivated the immediate and widespread implementation of public health countermeasures. In this review, we discuss the origins and virology of monkeypox virus, its link with smallpox eradication, its record of causing outbreaks of human disease in regions where it is endemic in wildlife, its association with outbreaks in areas where it is nonendemic, the clinical manifestations of disease, laboratory diagnostic methods, case management, public health interventions, and future directions.

New hepatitis C diagnoses in Ontario, Canada are associated with the local prescription patterns of a controlled-release opioid.

Increases in acute hepatitis C virus (HCV) incidence may be a result of the rising prevalence of injection drug use and the opioid epidemic. Among persons who inject drugs, sharing of needles/syringes is less common and leads to a smaller proportion of incident cases than does sharing of injection drug preparation equipment. In Canada and Europe, hydromorphone controlled release has been associated with frequent reuse and sharing of IDPE. Drug excipients within HCR have been shown to preserve virus survival within IDPE. We hypothesized that regional differences in HCV incidence would mirror regional differences in HCR prescribing. We reviewed HCV incidence data across Ontario, Canada for 2016. Opioid prescribing patterns in each Health Unit were reviewed. Multivariable Poisson regression analyses were performed to test the strength of hydromorphone controlled release dispensing patterns in explaining HCV incidence compared to all opioids. Less vehicle access, lack of education, lower income, less population density, higher white race/ethnicity and more opioid substitution therapy recipients remained significant positive predictors of hepatitis C incidence in the Ontario model. Higher hydromorphone controlled release dispensing rate was a stronger predictor of HCV incidence than all opioid prescriptions (standardized risk ratio = 1.17, P < .0001 vs sRR = 1.11, P = .02). When hydromorphone controlled release was excluded from the opioid prescription variable, dispensing patterns of all other opioids no longer remained a significant predictor (sRR = 1.042, P = .34). The observed relationship between HCV incidence and hydromorphone controlled release dispensing suggests that the type of opioid prescribed locally may contribute to variations in HCV incidence. These data add support to evidence that hydromorphone controlled release use is contributing to HCV spread in Ontario.

From client to co-worker: a case study of the transition to peer work within a multi-disciplinary hepatitis c treatment team in Toronto, Canada.

BACKGROUND: Despite the integration of peer workers into harm reduction services, there is little documentation regarding the experience of this integration or of models in which peers are fully integrated as members of health care teams. The purpose of this study was to gain an in-depth understanding of the transition from client to support worker from the perspective of two individuals who received treatment for hepatitis C at a multi-disciplinary, community-based program, grounded in a harm reduction approach to substance use. METHODS: A participatory case study design was selected. Interviews were conducted with two current peer workers who were also involved in the study design, analysis and writing. Data was coded and analyzed using an inductive approach to identify emergent themes. RESULTS: Five primary themes emerged during our analysis of the facilitators and challenges of the transition from client to support worker: (1) the role of prior experience, (2) changes in substance use practices, (3) shifts in relationships with community members and friends, (4) supportive organizational and structural factors, and (5) role transition as a journey. In some cases, themes overlapped and contained elements that were both facilitating and challenging. CONCLUSIONS: The transition from client to co-worker is a gradual process and one that is supported by, and in turn helps to support, a number of other personal transitions. The cases examined here suggest that a model of peer employment with broad qualification criteria, sufficient transition timelines, flexible job responsibilities, a solid investment in the inclusion of people with lived experience, and a harm reduction framework will support successful integration of current and/or former clients into health care teams.

Amniocentesis in the HIV-infected pregnant woman: Is there still cause for concern in the era of combination antiretroviral therapy?

The current standard of care in Canadian obstetrical practice is to offer pregnant women the opportunity for prenatal investigation to diagnose congenital abnormalities. Prenatal amniocentesis is Canada's most commonly practiced invasive procedure for the diagnosis of chromosomal and single gene disorders. The potential risk of intrapartum HIV transmission during amniocentesis raises several ethical concerns and limits the availability of prenatal genetic testing for HIV-positive pregnant women. Complete virological suppression with antiretroviral therapy may alleviate the risk of mother-to-child transmission during amniocentesis and increase accessibility of this important diagnostic tool in the HIV-positive population. The present report describes a case involving a 32-year-old HIV-positive pregnant woman whose plasma viral load was undetectable on antiretroviral therapy; she underwent successful prenatal amniocentesis without transmission of HIV to her infant.

La norme actuelle des soins dans la pratique obstétricale canadienne consiste à offrir aux femmes enceintes la possibilité d'une évaluation prénatale afin de diagnostiquer des anomalies congénitales. L'amniocentèse prénatale est l'intervention invasive la plus pratiquée au Canada pour diagnostiquer des troubles chromosomiques ou monogéniques. Le risque potentiel de transmission intrapartum du VIH pendant l'amniocentèse soulève plusieurs questions éthiques et limite la disponibilité des tests génétiques prénatals chez les femmes enceintes positives au VIH. La suppression virologique totale grâce à l'antirétrovirothérapie pourrait réduire le risque de transmission entre la mère et l'enfant pendant l'amniocentèse et accroître l'accessibilité à cet important outil diagnostique au sein de la population positive au VIH. Le présent rapport décrit le cas d'une femme enceinte de 32 ans positive au VIH sous antivirothérapie et dont la charge virale plasmatique n'était pas décelable. Elle a subi une amniocentèse prénatale sans transmettre le VIH à son nourrisson.

Different drugs, different sides: injection use of opioids alone, and not stimulants alone, predisposes to right-sided endocarditis.

OBJECTIVES: Many studies suggest that infective endocarditis (IE) in people who inject drugs is predominantly right sided, while other studies suggest left sided disease; few have differentiated by class of drug used. We hypothesised that based on differing physiological mechanisms, opioids but not stimulants would be associated with right sided IE. METHODS: A retrospective case series of 290 adult (age ≥18) patients with self-reported recent injection drug use, admitted for a first episode of IE to one of three hospitals in London Ontario between April 2007 and March 2018, stratified patients by drug class used (opioid, stimulant or both), and by site of endocarditis. Other outcomes captured included demographics, causative organisms, cardiac and non-cardiac complications, referral to addiction services, medical versus surgical management, and survival. RESULTS: Of those who injected only opioids, 47/71 (69%) developed right-sided IE, 17/71 (25%) developed left-sided IE and 4/71 (6%) had bilateral IE. Of those who injected only stimulants, 11/24 (46%) developed right-sided IE, 11/24 (46%) developed left-sided IE and 2/24 (8%) had bilateral IE. Relative to opioid-only users, stimulant-only users were 1.75 (95% CI 1.05 to 2.93; p=0.031) times more likely to have a left or bilateral IE versus right IE. CONCLUSIONS: While injection use of opioids is associated with a strong predisposition to right-sided IE, stimulants differ in producing a balanced ratio of right and left-sided disease. As the epidemic of crystal methamphetamine injection continues unabated, the rate of left-sided disease, with its attendant higher morbidity and mortality, may also grow.

Evaluating the safety and effectiveness of a nurse-led outpatient virtual IV vancomycin monitoring clinic: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) with vancomycin is a common treatment modality for certain Gram-positive infections. Data regarding the safety of various models of delivery are limited. OBJECTIVES: To review outcomes of a nurse-led OPAT vancomycin monitoring service. METHODS: This was a retrospective cohort study of consecutive patients referred to a nurse-led OPAT vancomycin clinic from December 2015 to March 2018. Patients were administered IV vancomycin in the home with active laboratory monitoring of vancomycin trough levels, renal function and complete blood count using an integrated electronic database linked with community laboratories (virtual vancomycin clinic, VVC). Monitoring was coordinated by nurses with physician approval of recommended dosing changes. Data were extracted from the electronic medical record. Demographics; clinical indication; microbial aetiology; culture source; antimicrobial regimen(s); serum creatinine and vancomycin trough values; initiation, discharge and completion dates; hospitalizations; adverse events; and outcomes were all evaluated. RESULTS: Two hundred and seventy-five patients underwent a total of 301 courses of OPAT with vancomycin; 285 courses were completed. The rate of treatment discontinuation due to adverse effects was 33/301 (11.0%), with 15/33 (45.5%) being due to renal adverse effects (15/301 [5.0%] of episodes). Two of 15 (18.2%) patients developed stage 2 acute kidney injury (AKI), and no patients had stage 3 AKI or required haemodialysis. Nine of 301 (3.0%) required readmission for treatment failure. Nursing costs associated with monitoring were $63.93 CAD/patient ($48.43 USD). CONCLUSIONS: A nurse-led VVC was a safe, effective and inexpensive modality for administering outpatient vancomycin.

Prevention of cytokine withdrawal-induced apoptosis by Mcl-1 requires interaction between Mcl-1 and Bim.

Growth factor withdrawal from hemopoietic cells results in activation of the mitochondrial pathway of apoptosis. Members of the Bcl-2 family regulate this pathway, with anti-apoptotic members counteracting the effects of pro-apoptotic members. We investigated the effect on Mcl-1 function of mutation at a conserved threonine 163 residue (T163) in its proline, glutamate, serine, and threonine rich (PEST) region. Under normal growth conditions, Mcl-1 half-life increased with alteration of T163 to glutamic acid, but decreased with mutation to alanine. However, both T163 mutants exhibited greater pro-survival effects compared with the wild type, which can be explained by an increased stability of the T163A mutant in cytokine-starved conditions. Both the mutant forms exhibited prolonged binding to pro-apoptotic Bim in cytokine-deprived cells. The extent to which Mcl-1 mutants were able to exert their anti-apoptotic effects correlated with their ability to associate with Bim. We further observed that primary bone marrow derived macrophages survived following cytokine withdrawal as long as Bim and Mcl-1 remained associated. In our study, we were unable to detect a role for GSK-3-mediated regulation of Mcl-1 expression. Based on these results we propose that upon cytokine withdrawal, survival of hemopoietic cells depends on association between Mcl-1 and Bim. Furthermore, alteration of T163 of Mcl-1 may change the protein such that its association with Bim is affected, resulting in prolonged association and increased survival.

Legionella co-infection in a patient with COVID-19.

We describe a case of an 80-year-old man with COVID-19 and Legionella bacterial co-infection who initially presented to hospital with fever, respiratory symptoms, and diarrhea with radiographic evidence of atypical infection. His initial nasopharyngeal swab was negative; however, a subsequent swab was positive. A Legionella urinary antigen test was positive for Legionella pneumophilia serogroup 1 antigen. Despite a low prevalence of bacterial co-infection in patients with COVID-19, a large number of patients receive antimicrobial therapy. Based on clinical context, a high index of suspicion is warranted for both bacterial and viral infectious processes during the COVID-19 pandemic; this will help to ensure that appropriate antimicrobial therapy is used.

Les auteurs décrivent le cas d'un homme de 80 ans co-infecté par la COVID-19 et la légionellose bactérienne qui a consulté à l'hôpital à cause de fièvre, de symptômes respiratoires et de diarrhée et dont la radiographie démontrait une infection atypique. Le premier écouvillon nasopharyngé a donné un résultat négatif, mais un écouvillon subséquent s'est révélé positif. Un test d'antigène urinaire des légionelles était positif à l'antigène Legionella pneumophilia du sérogroupe 1. Malgré une faible prévalence de co-infection bactérienne chez les patients atteints de la COVID-19, de nombreux patients reçoivent des antimicrobiens. D'après le contexte clinique, il faut faire preuve de vigilance à l'égard des processus bactériens et viraux pendant la pandémie de COVID-19 afin de s'assurer d'utiliser des antimicrobiens appropriés.

An unusual cervical mass.

Head and neck masses are usually indicative of infectious, neoplastic, or congenital entities. Most head and neck masses are related to local or regional disease, although systemic neoplastic disease can present in the cervical area. We present an interesting case report of a young woman with a neck mass caused by an organism most commonly associated with sexually transmitted infections, and not with the more common causes of cervical head and neck masses.

Les masses à la tête au cou sont souvent indicatrices de problèmes infectieux, néoplasiques ou congénitaux. La plupart de ces masses sont liées à une maladie locale ou régionale, même si elles peuvent être la manifestation de maladies néoplasiques systémiques. Les auteurs présentent le cas intéressant d'une jeune femme ayant une masse cervicale causée par un organisme généralement associé aux infections transmises sexuellement et non aux causes habituelles des masses au cou et à la tête.

Systematic review of HIV transmission between heterosexual serodiscordant couples where the HIV-positive partner is fully suppressed on antiretroviral therapy.

BACKGROUND: The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART. METHODS AND FINDINGS: We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0-0.05), with low heterogeneity (I(2) = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04-0.31) (I(2) = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0-0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use. CONCLUSIONS: Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.