Publications by authors named "Paul MacPherson"

62 Publications

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers.

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Departments of Critical Care Medicine and Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ∼48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (∼50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.
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http://dx.doi.org/10.1016/j.jtct.2021.04.023DOI Listing
May 2021

Psychological changes in successful completers of an HIV-tailored smoking cessation program: mood, attachment and self-efficacy.

AIDS Care 2021 Apr 21:1-9. Epub 2021 Apr 21.

Ottawa Hospital Research Institute, Ottawa, Canada.

High rates of cigarette smoking is the leading contributor to the increasing risk of cardiovascular disease (CVD) among people living with HIV (PLH). Relapse rates among PLH who quit smoking are high among those receiving standard care, which may be due to several unique social and psychological challenges PLH face when they attempt to quit smoking. The purpose of the current study was to examine change in relevant psychological factors in a subgroup of participants (n = 14) who remained smoke-free at 6-months follow-up in an HIV-tailored smoking cessation counselling program (N = 50). We examined self-reported depressive symptoms, attachment style and self-efficacy across 5 time points (baseline, quite date, 4, 12 and 24 weeks). At study baseline, mean depression scores fell above the clinical cut off of 16 (M = 16.31; SD = 13.53) on the Centre for Epidemiological Studies - Depression (CES-D) scale and fell below the clinical cut off at 24 weeks post quit date (M = 13.36; SD = 10.62). Results of multi-level modeling indicated a significant linear reduction in depressive symptoms and a significant linear improvement in self-efficacy to refrain from smoking across study visits. These results suggest that positive change in mood and self-efficacy may be helpful for PLH who remain smoke-free during a quit attempt.
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http://dx.doi.org/10.1080/09540121.2021.1909697DOI Listing
April 2021

Infection with antiretroviral-susceptible HIV in an individual adherent to pre-exposure prophylaxis: strategies for treatment initiation.

Int J STD AIDS 2021 May 5;32(6):578-581. Epub 2021 Mar 5.

Department of Medicine, 12365University of Ottawa, Ottawa, Canada.

HIV pre-exposure prophylaxis (PrEP) is effective at preventing sexual acquisition of HIV, and failures in clinical trials are largely attributable to medication nonadherence. We report here a case of infection with a fully susceptible strain of HIV in an individual adherent to PrEP as demonstrated by pharmacy records and intracellular tenofovir diphosphate levels. At diagnosis, the viral load was 90 copies/mL precluding initial genotype testing due to low copy number. While PrEP failure is rare, this case underscores the importance of regular HIV testing for patient on PrEP and prompts discussion regarding the approach to treatment following failure where an initial genotype is not yet available or not possible due to low viral load. Few other case reports of PrEP failure exist in the literature and approaches to treatment varied widely. We suggest the initial viral copy number may guide next steps and discuss the risks and benefits of stopping PrEP, escalating therapy with integrase inhibitors or boosted protease inhibitors, or switching to non-nucleoside antiretroviral treatment regimens.
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http://dx.doi.org/10.1177/0956462420971125DOI Listing
May 2021

Discussing current syphilis case definitions: A proposal for a "probable infectious" case.

Public Health Nurs 2021 May 29;38(3):390-395. Epub 2020 Nov 29.

Department of Infectious Diseases, The Ottawa Hospital, Ottawa, ON, Canada.

Syphilis has increased in recent years, causing difficulties for clinicians and public health practitioners alike. While one issue with the current management of syphilis is that it has both a myriad of presentations and complicated laboratory results, another issue relates to the current case definitions used to define and track syphilis in public health surveillance. One item that is missing is a "probable" case definition, which could help capture the number of likely cases of syphilis that were appropriately treated clinically, but which failed to reach public health case definition based on serologic markers. This approach could produce a more accurate picture of the breadth of syphilis transmission in North America and help better appreciate the groups most affected by syphilis change. We put forward and argue this position herein.
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http://dx.doi.org/10.1111/phn.12850DOI Listing
May 2021

Low human papillomavirus (HPV) vaccine uptake among men living with human immunodeficiency virus (HIV): Cross-sectional findings from a clinical cohort.

Prev Med 2021 02 20;143:106329. Epub 2020 Nov 20.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Men living with human immunodeficiency virus (HIV) are internationally recognized as a priority population for human papillomavirus (HPV) vaccination. Our objective was to explore HPV vaccine uptake among men living with HIV in Ontario, Canada, and investigate differences between vaccinated and unvaccinated men. We used data from a cross-sectional questionnaire administered between 2016 and 2017 among men living with HIV and participating in the Ontario HIV Treatment Network Cohort Study. We calculated the proportion vaccinated against HPV, described vaccination experiences, and HPV vaccine knowledge, and calculated differences in characteristics between vaccinated and unvaccinated men. Among 1651 men (mean age = 51 years, 72% identified as gay), 7% were vaccinated (95% confidence interval[CI] 5.5-7.9%); 85% received their first dose at a primary care or HIV clinic. Among unvaccinated men, 40% were unaware of the HPV vaccine, 65% reported low perceived risk for HPV, and 8% discussed HPV vaccination with a physician. Compared to unvaccinated men, vaccinated men were younger, most identified as gay, had a higher education/income, reported a higher number of recent sex partners, and had a history of bacterial sexually transmitted infections (STIs), HPV, anogenital warts, and/or anal cancer. Our findings reveal that few men living with HIV were vaccinated against HPV. This may be influenced by low HPV awareness, prohibitive cost, and lack of physician recommendation. Several men reporting lower socio-economic status, older men, and heterosexual, bisexual, and other men who have sex with men were missed for vaccination. Primary care and HIV clinics may be ideal locations to increase uptake.
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http://dx.doi.org/10.1016/j.ypmed.2020.106329DOI Listing
February 2021

Barriers and enablers to source plasma donation by gay, bisexual and other men who have sex with men under revised eligibility criteria: protocol for a multiple stakeholder feasibility study.

Health Res Policy Syst 2020 Nov 2;18(1):131. Epub 2020 Nov 2.

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.

Background: Blood donation policy in Canada for gay, bisexual and other men who have had sex with men (gbMSM) has changed progressively in the last decade from indefinite deferral to 3-month deferral from last male-to-male sex. Driven by safety data and overseen by the national regulator, more inclusive policies continue to redress the disparity in donation for gbMSM. At the same time, the need for source plasma to prepare fractionated blood products is growing worldwide. The collection and processing of source plasma ensures greater safety compared to whole blood donation with respect to transfusion-transmitted infection. This greater safety offers an opportunity to evolve policies for gbMSM from time-based to behaviour-based deferral using revised eligibility criteria. However, changing policies does not in itself necessarily guarantee that gbMSM will donate or that staff in donor clinics are ready to support them to do so. In anticipation of a move to behaviour-based donation screening for gbMSM in Canada, we aim to assess the acceptability of and perceived barriers and enablers to source plasma donation using revised screening criteria for gbMSM among key stakeholders to inform policy implementation strategies.

Methods: This mixed-methods feasibility study will involve gbMSM and donor centre staff to understand modifiable barriers to implementing more inclusive eligibility criteria. Key informant interviews and surveys will be rooted in the Theoretical Domains Framework to identify modifiable factors associated with source plasma donation motives in gbMSM and training needs in donation centre staff. We will use an integrated knowledge translation approach involving a partnership between researchers, the national blood operator and gbMSM, situating knowledge users as key research team members to ensure their perspectives inform all aspects of the research.

Discussion: Our integrated knowledge translation approach will provide a more comprehensive and collaborative understanding of blood operator and gbMSM needs while accelerating the implementation of study findings. Given the historical backdrop of the decades of exclusion of sexually active gbMSM from blood donation, this study has the potential not only to inform a process and policy for gbMSM to donate source plasma, a blood product, but also offers opportunities for new relationships between these knowledge users.
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http://dx.doi.org/10.1186/s12961-020-00643-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605323PMC
November 2020

Vedolizumab treatment across antiretroviral treatment interruption in chronic HIV infection: the HAVARTI protocol for a pilot dose-ranging clinical trial to assess safety, tolerance, immunological and virological activity.

BMJ Open 2020 10 8;10(10):e041359. Epub 2020 Oct 8.

Medicine, Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario, Canada.

Introduction: Continuous antiretroviral therapy (ART) suppresses HIV plasma viral load (pVL) to very low levels, which allows for some immune recovery. Discontinuation of ART leads to pVL rebound from reservoirs of persistence and latency, and progressive immunodeficiency. One promising but controversial strategy targeting CD4 T lymphocytes with a monoclonal antibody (mAb) against α4β7 integrin has shown promise through sustained virological remission of pVL (SVR) in SIV-infected rhesus macaques. We propose to assess the safety and tolerability of vedolizumab, a licensed humanised mAb against human α4β7 integrin, in healthy HIV-infected adults on ART. This study will also assess, by analytical treatment interruption (ATI), whether vedolizumab treatment can induce SVR beyond ART and vedolizumab treatment.

Methods And Analysis: The HIV-ART-vedolizumab-ATI (HAVARTI) trial is a single-arm, dose-ranging pilot trial in healthy HIV-positive adult volunteers receiving ART. Twelve consenting persons will be enrolled in sequential groups of 4 to each serial dosing vedolizumab regimen (300 mg, 150 mg, 75 mg). The primary outcomes are: (1) to assess the safety and tolerability of seven serial infusions of vedolizumab at each of three doses; (2) to identify the immunovirological measures, including pVL and T-cell kinetics, that characterise HIV/ART cases before, during, after vedolizumab treatment and ATI; and (3) to seek SVR of pVL after ATI. Secondary outcomes will include immune reconstitution and pVL suppression as well as immune reconstitution and long-term safety following re-initiation of ART in the absence of SVR.

Ethics And Dissemination: The study protocol was approved by the Ottawa Health Science Network-REB and by the Health Canada Therapeutic Products Directorate. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open access journal within a year of study completion.

Trial Registration Number: ClinicalTrials.gov NCT03147859; https://clinicaltrials.gov/ct2/show/NCT03147859.
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http://dx.doi.org/10.1136/bmjopen-2020-041359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545629PMC
October 2020

Low human papillomavirus (HPV) knowledge related to low risk perception among men living with HIV: Implications for HPV-associated disease prevention.

Prev Med 2020 12 3;141:106274. Epub 2020 Oct 3.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Human papillomavirus (HPV)-associated anal cancer is orders of magnitude higher among men living with HIV than the general male population. Our objective was to examine factors associated with HPV awareness and self-perceived risk for HPV-associated anal cancer among men living with HIV, which may influence uptake of cancer prevention strategies. A cross-sectional questionnaire on HPV was administered from 2016 to 2017 to 1677 men in a multisite, HIV clinical cohort in Ontario, Canada. We used logistic regression and proportional odds models to identify factors associated with being familiar with HPV and increasing self-perceived risk for anal cancer, respectively. We used correspondence analysis to examine associations of specific HPV-related knowledge with self-perceived risk. Only 52% were familiar with HPV, and 72% felt they had no or low risk for anal cancer. Familiarity with HPV was more common among men who have sex with men than heterosexual men (58% vs. 21%). Older men were less likely to be familiar with HPV (adjusted odds ratio [aOR] per 10 years = 0.77; 95% confidence interval [CI]: 0.69, 0.85). Familiarity with HPV was associated with increasing self-perceived risk (aOR = 2.39; 95% CI: 1.87, 3.04). After accounting for differences in HPV awareness and sexual orientation, racialized men had lower self-perceived risk (aOR = 0.68; 95% CI: 0.52, 0.88). In the correspondence analysis, risk-focused HPV-related knowledge (e.g., knowing smoking increases risk) was associated with highest risk perception. Efforts are needed to improve HPV-related health literacy in this population. Our findings suggest specific HPV-related knowledge may differentially influence self-perceived risk for anal cancer.
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http://dx.doi.org/10.1016/j.ypmed.2020.106274DOI Listing
December 2020

Fostering Clinical Research in the Community Hospital: Opportunities and Best Practices.

Healthc Q 2020 Jul;23(2):30-36

An industry outreach associate at Clinical Trials Ontario, MaRS Centre in Toronto, ON. Linnea has over 15 years of clinical research and clinical marketing experience in the medical device industry and is the principal consultant at BESPOKE Business Solutions, Inc. Her role at Clinical Trials Ontario is to develop and manage the QuickSTART and Research Ready programs, aimed at reducing clinical trial start-up times and increasing research capacity at institutions across the province.

With potential to improve patient outcomes, quality of care and cost-effectiveness, clinical research activity in community hospitals has recently begun to increase. Recognizing that establishing or strengthening a clinical research program in this setting is an important, complex and challenging undertaking, this article introduces many of the resources, best practices and success stories that community hospitals can draw upon to develop and incentivize clinical researchers, operationalize the clinical research enterprise and make clinical research impactful.
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http://dx.doi.org/10.12927/hcq.2020.26277DOI Listing
July 2020

Knowledge and Attitudes of Canadian Cardiac Surgeons Regarding Patients With Human Immunodeficiency Virus.

Ann Thorac Surg 2021 03 23;111(3):945-950. Epub 2020 Jul 23.

Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, University of Ottawa, Ottawa, Ontario, Canada; Harry Perkins Institute of Medical Research and Fiona Stanley Hospital (Murdoch), University of Western Australia, Nedlands, Western Australia, Australia. Electronic address:

Background: Current data on cardiac surgical practices for people living with human immunodeficiency virus (HIV) are lacking. We hypothesized that cardiac surgeons would consider people living with HIV as candidates for the full scope of cardiac surgery, including heart transplant for these patients.

Methods: We conducted a prospective survey of 155 cardiac surgeons across Canada to evaluate their current clinical perceptions regarding cardiac surgery in people living with HIV. Specifically, we evaluated their assessment of eligibility toward a wide scope of cardiac surgeries by using representative clinical scenarios.

Results: A total of 63 surgeon responses (40.6%) were completed. The majority of surgeons agreed that a 50-year-old man with HIV and no other comorbidities, who had been receiving combination antiretroviral therapy for 5 years with an undetectable viral load since starting therapy and a CD4 count greater than 350 cells/μL, would be a candidate for valve replacement (73%), valve repair surgery (74.6%), or coronary artery bypass graft surgery (79.4%). Few surgeons believed that this patient would be eligible for cardiac transplantation (7.9%) or could be a cardiac transplant donor (1.6%). There was clinical equipoise over the eligibility for ventricular assist device surgery.

Conclusions: A majority of cardiac surgeons would perform coronary artery bypass graft surgery or valve surgery on patients with controlled HIV, but most consider HIV status as a prohibitive risk factor for cardiac transplantation. Although this may represent an opportunity for continuing medical education for cardiac surgeons, it also highlights the need for contemporary, high-quality evidence in this patient population.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.133DOI Listing
March 2021

Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals: Potential Role in Persistent Inflammation and Transcription From Stable HIV-1 Reservoirs.

J Acquir Immune Defic Syndr 2019 12;82(5):503-513

Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

Background: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory.

Setting And Methods: Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR.

Results: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals.

Conclusions: Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.
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http://dx.doi.org/10.1097/QAI.0000000000002185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857723PMC
December 2019

Evolving Toward Shared HIV Care Using the Champlain BASE eConsult Service.

MDM Policy Pract 2019 Jul-Dec;4(2):2381468319868216. Epub 2019 Aug 17.

C.T. Lamont Primary Health Care Research Centre, Bruyère Research Institute, Ottawa, Ontario, Canada.

Electronic consultation (eConsultation) is a potential strategy to improve access to specialist expertise and facilitate collaborative care models. The Champlain BASE eConsult service allows for asynchronous communication between primary care providers (PCP) and specialists on a secure, web-based system. HIV experts accessible include HIV physician specialists, HIV pharmacists, and social workers with expertise in HIV. This study aims to describe the use, value, and utility of this eConsultation service in the care of people living with HIV and to characterize the common question types and clinical topics asked by PCPs. We analyzed the data from eConsults sent to the HIV specialty group in Ontario's Champlain Local Health Integration Network between February 2015 and December 2017. Usage data and close-out survey responses were analyzed using descriptive statistics, eConsults were classified using a predefined list of validated taxonomy, and a thematic analysis was performed on the consultation logs to identify common clinical themes. Among the 46 eConsults, the most common question type related to drug treatment (58.7%, = 27) and management (19.6%, = 9). The main clinical themes involved the care of significant complexities in people living with HIV, such as comorbidities and drug interactions, and suggestions of coordinated patient care. As well, eConsult was used for advice regarding pre-exposure prophylaxis for HIV-negative patients at risk of HIV infection. PCPs highly valued the eConsult service (average rating 4.8/5). Overall, this study demonstrates that eConsult provides an efficient and valuable service to PCPs caring for patients living with or at risk for HIV by improving access to HIV specialists and facilitating the delivery of team-based comprehensive care.
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http://dx.doi.org/10.1177/2381468319868216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699006PMC
August 2019

Syphilis.

BMJ 2019 Jun 28;365:l4159. Epub 2019 Jun 28.

Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario.

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http://dx.doi.org/10.1136/bmj.l4159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598465PMC
June 2019

PrEP-RN: Clinical Considerations and Protocols for Nurse-Led PrEP.

J Assoc Nurses AIDS Care 2019 May-Jun;30(3):301-311

HIV pre-exposure prophylaxis (PrEP) is an increasingly important part of the HIV prevention armamentarium. Issues with PrEP, however, include access. We propose that one way to surmount this issue would be to have nurses provide PrEP. Although clinical guidelines exist for PrEP, they are overwhelmingly not targeted to nonprescriber clinicians. In this article, we overview current U.S. and Canadian PrEP guidelines and provide explicit guidance about how nurses can provide PrEP, including the clinical pathways and medical directives we use in our clinic. We call nurse-led provision of PrEP, PrEP-RN (Pre-Exposure Prophylaxis-Registered Nurse) and feel it may be an important step forward in HIV prevention.
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http://dx.doi.org/10.1097/JNC.0000000000000075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551248PMC
June 2020

Consideration of sexually transmitted infections in the differential diagnosis: Case studies.

J Am Assoc Nurse Pract 2019 Jan;31(1):65-71

Ottawa Public Health, Sexual Health Centre, Ottawa Ontario, Canada.

Background And Purpose: The rates of many sexually transmitted infections (STIs) have increased in recent years. Many health care professionals miss these potential diagnoses in clinical practice.

Methods: Two case studies are presented, one an adult female with dysuria; the other an adult male with a rash. Appropriate differential diagnoses and relevant history, examination, and investigation details are discussed.

Conclusions: Not all dysuria signifies a urinary tract infection. Although most rashes are not syphilis or HIV, it is important to rule out these etiologies for rashes in adults without a previous history of similar dermatologic conditions.

Implications For Practice: Due to increased rates of many STI and HIV, it is important for nurse practitioners who work in primary care to consider these infections in patients who present with dysuria and rashes. Similarly, nurse practitioners who work in STI clinic settings should consider non-STI diagnoses in their work. In both cases, a perspective that includes both STI and non-STI etiologies is essential.
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http://dx.doi.org/10.1097/JXX.0000000000000103DOI Listing
January 2019

Patient activation among people living with HIV: a cross-sectional comparative analysis with people living with diabetes mellitus.

AIDS Care 2018 11 24;30(11):1444-1451. Epub 2018 May 24.

a C.T. Lamont Primary Health Care Research Centre , Bruyère Research Institute , Ottawa , ON , Canada.

Standardized self-management supports are an integral part of care delivery for many chronic conditions. We used the validated Patient Activation Measure (PAM®) to assess level of engagement for self-management from a sample of 165 people living with HIV (PLWH) and 163 people with diabetes. We conducted multivariable logistic regression to assess associations between demographics and PAM® scores. PLWH had high levels of activation that were no different from those of people with diabetes (mean score = 67.2, SD = 14.2 versus 65.0, SD = 14.9, p = 0.183). After adjusting for patient characteristics, only being on disability compared to being employed or a student was associated with being less activated (AOR = 0.276, 95%CI = 0.103-0.742). Our findings highlight the potential for the implementation of existing standardized chronic disease self-management programs to enhance the care delivery for PLWH, with people on disability as potential target populations.
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http://dx.doi.org/10.1080/09540121.2018.1469723DOI Listing
November 2018

High prevalence of syndemic health problems in patients seeking post-exposure prophylaxis for sexual exposures to HIV.

PLoS One 2018 23;13(5):e0197998. Epub 2018 May 23.

Division of Infectious Diseases, St. Michael's Hospital, Toronto, Canada.

Introduction: The standard clinical approach to non-occupational HIV post-exposure prophylaxis (nPEP) focuses on biomedical aspects of the intervention, but may overlook co-occurring or 'syndemic' psychosocial problems that reinforce future vulnerability to HIV. We therefore sought to determine the prevalence of syndemic health problems in a cohort of Ontario nPEP patients, and explored the relationship between syndemic burden and HIV risk.

Methods: Between 07/2013-08/2016, we distributed a self-administered questionnaire to patients presenting to three clinics in Toronto and Ottawa seeking nPEP for sexual HIV exposures. We used validated screening tools to estimate the prevalence of depression (CES-D score ≥16), harmful alcohol use (AUDIT ≥8), problematic drug use (DUDIT ≥6 men/≥2 women), and sexual compulsivity (SCS ≥24) among men who have sex with men (MSM) respondents. In exploratory analyses, we examined the relationships between syndemic conditions using univariable logistic regression models, and the relationship between syndemic count (total number of syndemic conditions per participant) and HIV risk, as estimated by the HIRI-MSM score, using linear regression models.

Results: The 186 MSM included in the analysis had median age 31 (IQR = 26-36), including 87.6% having a college/undergraduate degree or higher. Overall, 53.8% screened positive for depression, 34.4% for harmful alcohol use, 30.1% for problematic drug use, and 16.1% for sexual compulsivity. Most participants (74.2%) had at least one syndemic condition and 46.8% had more than one. Exploratory analyses suggested positive associations between depression and harmful alcohol use (OR = 2.11, 95%CI = 1.13, 3.94) and between harmful alcohol use and problematic drug use (OR = 1.22, 95%CI = 0.65, 2.29). Syndemic count was associated with increased HIRI-MSM risk scores in univariable (2.2, 95%CI = 1.0, 3.3 per syndemic condition) and multivariable (2.1, 95%CI = 0.6, 3.6) linear regression models.

Conclusions: The prevalence of syndemic conditions in MSM seeking nPEP for sexual exposure is alarmingly high, and is associated with underlying HIV risk. Routine screening for these conditions may identify opportunities for intervention and could alleviate future vulnerability to HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965882PMC
November 2018

The patient rationale for seeking HIV PEP: Qualitative results from a nurse-led program.

Public Health Nurs 2018 09 6;35(5):386-395. Epub 2018 Apr 6.

Faculty of Law, University of Ottawa, Ottawa, ON, Canada.

Background: HIV PEP is an intervention to prevent HIV seroconversion among HIV-negative persons after they have come into contact with the virus. The literature suggests PEP is greater than 80% effective at reducing HIV seroconversion. To expand access to this prevention strategy, we established a nurse-led PEP program in two STI clinics.

Aims: We sought to explore why people seek PEP, and their experiences using it.

Materials & Methods: We invited participants who used our PEP program to engage in semi-structured qualitative interviews. These were audio-recorded, transcribed verbatim, and analyzed using the techniques of thematic analysis.

Results: Twelve men who initiated PEP through our program participated in an interview. Thematic analysis of the data identified three themes: (1) assessing risk, (2) euphoria and distress, and (3) reducing distress.

Discussion: Based on our findings, it appears as though instances of condomless sex were atypical and unplanned, they occurred due to contextual factors (e.g., consent, desire to explore, sexual chemistry/intensity), and they resulted in a state of temporary euphoria, which, afterward, transformed into distress (i.e., "feel[ing] stupid"). The participants used PEP not only for HIV prevention, but also (and perhaps more so) to address their emotional state. PEP used seemed to primarily occur to address situations of atypical sexual contact with partners they did not "know" or "trust".

Conclusion: We feel these results help contextualize how potential PEP users view HIV risk assessments, and how they determine their need for this intervention.
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http://dx.doi.org/10.1111/phn.12404DOI Listing
September 2018

Nurse-Led HIV PEP Program Used by Men at High Risk for HIV Seroconversion.

J Assoc Nurses AIDS Care 2018 Jul - Aug;29(4):550-559. Epub 2018 Feb 17.

We trialed a nurse-led HIV postexposure prophylaxis (PEP) program in two sexually transmitted infection clinics in Ottawa, Canada. From September 5, 2013 to September 4, 2015, 112 persons sought PEP: 103 were male, of whom 84 were men who have sex with men (MSM). Seventy-two patients (59 MSM) initiated PEP; 11 were diagnosed with HIV: 6 diagnoses occurred during initial assessment (all MSM; 1 also shared injection equipment); 5 MSM were diagnosed with HIV within 1 year of seeking PEP. This level of positivity indicated that, when access is facilitated, individuals at high risk of HIV seek PEP. However, the 8.5% of MSM who seroconverted within a year of taking PEP demonstrated that this group remained at risk and needed additional prevention services. Delivery of PEP should include provision of medication, as well as an opportunity to address individual-level HIV risk strategies and population-level syndemic conditions that contribute to ongoing HIV transmission among MSM.
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http://dx.doi.org/10.1016/j.jana.2018.02.004DOI Listing
August 2019

The Pre-Exposure Prophylaxis-Stigma Paradox: Learning from Canada's First Wave of PrEP Users.

AIDS Patient Care STDS 2018 01 29;32(1):24-30. Epub 2017 Nov 29.

5 St. Michael's Hospital , Toronto, Ontario, Canada .

With the emergence of daily oral tenofovir disoproxil fumarate and emtricitabine-based pre-exposure prophylaxis (PrEP) use in Canada, questions have emerged concerning the impacts of this HIV prevention tool on gay men's social and sexual lives. We conducted small focus groups and individual qualitative interviews with 16 gay men in Toronto who were part of the 'first wave' of Canadian PrEP users. Participants were on PrEP for at least one year as part of a demonstration project (November 2014-June 2016). These participants accessed PrEP before regulatory approval by Health Canada in February 2016. The mean age of participants was 37.6 years (SD 11.02); 94% completed secondary education, and 69% were white. Sex-stigma emerged as a complex theme in men's accounts of PrEP use across three overlapping domains: (1) PrEP-related stigma, including discussions of concealment and stigma from friends, family, and sexual partners, (2) PrEP as a perceived tool for combating HIV-related stigma, where some men said that they no longer discussed HIV status with sexual partners, and (3) PrEP as illuminating structural stigma, where it was attributed to unmasking stigma related to sex and sexuality. For some participants, PrEP has allowed for liberating sex and a self-described return to normalcy-normal, exciting, pleasurable sex that was no longer reliant on condom use. Paradoxically, some men said that PrEP use both led them to experience stigmatizing reactions within their social and sexual networks, while also helping to remove stigma, shame, and fear related to HIV, sexuality, and sex with gay men living with HIV.
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http://dx.doi.org/10.1089/apc.2017.0153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756933PMC
January 2018

Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis.

CMAJ 2017 11;189(47):E1448-E1458

Division of Infectious Diseases (Tan), St. Michael's Hospital, Toronto, Ont.; BC Centre for Excellence in HIV/AIDS (Hull, Harris), Vancouver, BC; Department of Pharmacy (Yoong), St. Michael's Hospital, Toronto, Ont.; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (Tremblay), Montréal, Que.; School of Nursing (O'Byrne), University of Ottawa, Ottawa, Ont.; Clinique L'Actuel (Thomas), Montréal, Que.; Canadian Association of Nurses in HIV/AIDS Care (Kille), Vancouver, BC; Clinique du Quartier Latin (Baril), Montréal, Que.; Direction régionale de santé publique (Cox), Centre intégré universitaire de santé et de services sociaux du Centre-Sud-de-l'Île-de-Montréal, Montréal, Que.; Department of Pharmacy (Giguere), The Ottawa Hospital, Ottawa, Ont.; Faculty of Pharmacy & Pharmaceutical Sciences (Hughes), University of Alberta, Edmonton, Alta.; Division of Infectious Diseases (MacPherson), The Ottawa Hospital, Ottawa, Ont.; Department of Emergency Medicine (O'Donnell), St. Paul's Hospital, Vancouver, BC; Winnipeg Regional Health Authority (Reimer), Winnipeg, Man.; Division of Infectious Diseases, Department of Medicine (Singh, Shafran), University of Alberta, Edmonton, Alta.; Dalhousie University (Barrett), Halifax, NS; Divisions of Internal Medicine and Infectious Diseases (Bogoch), Toronto General Hospital, Toronto, Ont.; Health Initiative for Men (Jollimore), Vancouver, BC; Institut national de santé publique du Québec (Lambert), Montréal, Que.; Research Institute of the McGill University Health Centre (Lebouche), Montréal, Que.; CATIE (Canadian AIDS Treatment Information Exchange) (Rogers), Toronto, Ont.

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http://dx.doi.org/10.1503/cmaj.170494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703677PMC
November 2017

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

BMC Infect Dis 2017 09 11;17(1):611. Epub 2017 Sep 11.

Centre de recherche du CHUM, Montreal, Canada.

Background: With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals.

Methods/design: The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile.

Discussion: The Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.
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http://dx.doi.org/10.1186/s12879-017-2692-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594495PMC
September 2017

Medical students' perception of lesbian, gay, bisexual, and transgender (LGBT) discrimination in their learning environment and their self-reported comfort level for caring for LGBT patients: a survey study.

Med Educ Online 2017 ;22(1):1368850

b Faculty of Medicine , University of Ottawa , Ottawa , Canada.

Background: Historically, medical students who are lesbian, gay, bisexual or transgendered (LGBT) report higher rates of social stress, depression, and anxiety, while LGBT patients have reported discrimination and poorer access to healthcare.

Objective: The objectives of this study were: (1) to assess if medical students have perceived discrimination in their learning environment and; (2) to determine self-reported comfort level for caring for LGBT patients.

Design: Medical students at the University of Ottawa (N = 671) were contacted via email and invited to complete a confidential web-based survey.

Results: Response rate was 15.4% (103/671). This included 66 cis-gender heterosexuals (64.1%) and 37 LGBT students (35.9%). Anti-LGBT discrimination had been witnessed by 14.6% and heterosexism by 31.1% of respondents. Anti-LGBT discrimination most often originated from fellow medical students. Respondents who self-identified as LGBT were more likely to have perceived heterosexism (favoring opposite-sex relationships) (OR = 8.2, p < 0.001) or anti-LGBT discrimination (OR = 6.6, p = 0.002). While half of LGBT students shared their status with all classmates (51.4%), they were more likely to conceal this from staff physicians (OR = 27.2, p = 0.002). Almost half of medical students (41.7%) reported anti-LGBT jokes, rumors, and/or bullying by fellow medical students and/or other members of the healthcare team. Still, most respondents indicated that they felt comfortable with and capable of providing medical care to LGBT patients (≥83.5%), and were interested in further education around LGBT health issues (84.5%).

Conclusion: Anti-LGBT discrimination and heterosexism are noted by medical students, indicating a suboptimal learning environment for LGBT students. Nonetheless, students report a high level of comfort and confidence providing health care to LGBT patients.
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http://dx.doi.org/10.1080/10872981.2017.1368850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653936PMC
April 2018

HIV-1 tat protein recruits CIS to the cytoplasmic tail of CD127 to induce receptor ubiquitination and proteasomal degradation.

Virology 2016 11 4;498:192-200. Epub 2016 Sep 4.

The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5; Division of Infectious Diseases, The Ottawa Hospital General Campus, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. Electronic address:

HIV-1 Tat protein down regulates expression of the IL-7 receptor alpha-chain (CD127) from the surface of CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. We have previously shown that soluble Tat protein is taken up by CD8 T cells and interacts with the cytoplasmic tail of CD127 to induce receptor degradation. The N-terminal domain of Tat interacts with CD127 while the basic domain directs CD127 to the proteasome. We have also shown that upon IL-7 binding to its receptor, CD127 is phosphorylated resulting in CIS-mediated proteasomal degradation. Here, we show that Tat mimics this process by recruiting CIS to CD127 in the absence of IL-7 and receptor phosphorylation, leading to CD127 ubiquitination and degradation. Tat therefore acts as an adapter to induce cellular responses under conditions where they may not otherwise occur. Thusly, Tat reduces IL-7 signaling and impairs CD8 T cell survival and function.
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http://dx.doi.org/10.1016/j.virol.2016.08.024DOI Listing
November 2016

Transcriptional regulation of the IL-7Rα gene by dexamethasone and IL-7 in primary human CD8 T cells.

Immunogenetics 2017 Jan 19;69(1):13-27. Epub 2016 Aug 19.

Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H8L6, Canada.

Interleukin-7 is essential for the development and maintenance of T cells, and the expression of the IL-7 receptor is tightly regulated at every stage of the T cell's lifespan. In mature CD8 T cells, IL-7 plays important roles in cell survival, peripheral homeostasis, and cytolytic function. The IL-7 receptor alpha-chain (CD127) is expressed at high levels on naïve and memory cells, but it is rapidly downregulated upon IL-7 stimulation. In this study, we illustrate the dynamicity of the CD127 promoter and show that it possesses positive as well as negative regulatory sites involved in upregulating and downregulating CD127 expression, respectively. We cloned the CD127 gene promoter and identified key cis-regulatory elements required for CD127 expression in mature resting primary CD8 T cells. The core promoter necessary for efficient basal transcription is contained within the first 262 bp upstream of the TATA box. Additional positive regulatory elements are located between -1200 and -2406 bp, conferring a further 2- to 4-fold enhancement in gene expression. While transcription of the CD127 gene is increased directly through a glucocorticoid response element located between -2255 and -2269 bp upstream of the TATA box, we identified a suppressive region that lies upstream of 1760 bp from the TATA box, which is likely involved in the IL-7-mediated suppression of CD127 transcription. Finally, we illustrated IL-7 does not bias alternative splicing of CD127 transcripts in primary human CD8 T cells.
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http://dx.doi.org/10.1007/s00251-016-0948-4DOI Listing
January 2017

An HIV-tailored quit-smoking counselling pilot intervention targeting depressive symptoms plus Nicotine Replacement Therapy.

AIDS Care 2017 01 19;29(1):24-31. Epub 2016 Jul 19.

e Division of Infectious Diseases , The Ottawa Hospital, Ottawa Hospital Research Institute, Faculty of Medicine, University of Ottawa , Ottawa , ON , Canada.

Cardiovascular disease (CVD) rates among people living with HIV/AIDS (PHAs) are high. Rates of cigarette smoking, a leading contributor to CVD among PHAs, are 40-70% (2-3 times higher than the general population). Furthermore, PHAs have high rates of depression (40-60%), a risk factor for smoking cessation relapse. The current pilot study examined the effectiveness of a specifically tailored 5-session smoking cessation counselling programme for PHAs, which addressed depression, in combination with Nicotine Replacement Therapy (NRT) in a cohort of PHA smokers (n = 50). At 6-month follow-up, 28% of participants demonstrated biochemically verified abstinence from smoking. This result compares favourably to other quit-smoking intervention studies, particularly given the high percentage of HIV+ smokers with depression. At study baseline, 52% of HIV+ smokers scored above the clinical cut-off for depression on the Centre for Epidemiological Studies - Depression (CES-D) scale. HIV+ smokers with depression at study baseline demonstrated quantitatively lower depression at 6-month follow-up with a large effect size (d = 1), though it did not reach statistical significance (p = .058). Furthermore, those with depression were no more likely to relapse than those without depression (p = .33), suggesting that our counselling programme adequately addressed this significant barrier to smoking cessation among PHAs. Our pilot study indicates the importance of tailored programmes to help PHAs quit smoking, the significance of addressing depressive symptoms, and the need for tailored counselling programmes to enhance quit rates among PHAs.
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http://dx.doi.org/10.1080/09540121.2016.1201195DOI Listing
January 2017

Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells.

Cell Immunol 2016 Aug-Sep;306-307:41-52. Epub 2016 Jul 5.

Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada; Division of Infectious Diseases, Ottawa Hospital General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. Electronic address:

Given the essential role interleukin (IL)-7 plays in T-cell survival, homeostasis and function, it is no surprise expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown IL-7 binding to its receptor on the surface of CD8 T cells leads to both suppression of CD127 gene transcription and loss of existing CD127 protein from the cell membrane. Indeed upon binding IL-7, CD127 is rapidly internalized into early endosomes where phosphorylation by JAK targets the receptor for degradation. We now show that IL-7 induces the expression of suppressor of cytokine signaling (SOCS) proteins CIS, SOCS1 and SOCS2 through the JAK/STAT-5 pathway and that CIS and SOCS2 specifically interact with CD127 in early endosomes and direct the receptor complex to the proteasome for degradation. These results illustrate how expression of the IL-7 receptor and thus IL-7 signaling is modulated in human CD8 T cells by a negative feedback mechanism dependent on members of the SOCS family of proteins.
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http://dx.doi.org/10.1016/j.cellimm.2016.07.002DOI Listing
June 2017

Approach to lymphogranuloma venereum.

Can Fam Physician 2016 Jul;62(7):554-8

Nurse practitioner at the Ottawa Public Health Sexual Health Centre.

Objective: To review the literature about lymphogranuloma venereum (LGV) and to provide an overview and discussion of practice guidelines.

Sources Of Information: The terms Chlamydia trachomatis and lymphogranuloma venereum were searched separately in PubMed. Empirical studies, practice reviews, and clinical guidelines were included. All reference lists were reviewed for additional articles.

Main Message: Since 2003, there has been a resurgence of LGV among men who have sex with men in many Western countries, including Canada. Although LGV is a serovar of Chlamydia trachomatis (serovar L), it can invade regional lymph nodes, and consequently presents with different symptoms than the other subtypes of chlamydia (serovars A through K). Specifically, LGV transitions through 3 phases: a painless papule or ulcer at the site of inoculation; invasion of the regional lymph nodes, which can present with an inguinal or rectal syndrome; and irreversible destruction of lymph tissue. In contrast, chlamydia serovars A to K exclusively produce superficial mucosal infections. Lymphogranuloma venereum also requires a different treatment regimen than other chlamydia serovars.

Conclusion: In light of the current resurgence of LGV, its unique symptoms and clinical course, and its requirement for a different treatment than other chlamydia serovars, it is important for primary care providers to recognize when LGV should be included as an appropriate differential diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955081PMC
July 2016