Clinical and Genomic Investigation of an International Ceftriaxone- and Azithromycin-Resistant Shigella sonnei Cluster among Men Who Have Sex with Men, Montréal, Canada 2017-2019.

Multidrug-resistant (MDR) Shigella sonnei have become prevalent among men who have sex with men and have become a global public health concern. From June 2017 to April 2019, 32 men were infected with MDR S. sonnei acquired locally, in Montréal, which was suggestive of an outbreak. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), phylogenetic analysis, antimicrobial resistance and virulence characterization, and association to international clusters were performed. The outbreak strain was ceftriaxone- and azithromycin-resistant due to the acquisition of blaCTX-M-27, and mphA and ermB genes, respectively, with reduced susceptibility to ciprofloxacin due to a single point mutation (gyrA S83L). One out of 27 patients treated with a fluoroquinolone experienced microbiological failure. Epidemiological evidence first supported by a rare unique MDR Shigella sonnei documented only in men in 2017 followed by similar pulsed-field gel electrophoresis profiles was confirmed by WGS. A core genome high-quality single-nucleotide variant (hqSNV)-based phylogeny found a median of 6 hqSNV differences among isolates. Virulence gene content was investigated, but no Shiga toxins were detected. An international cluster of highly related isolates was identified (PDS000019750.208) and belonged to the 3.7.29.1.4.1 S. sonnei genotype (Global III VN2.KH1.Aus). Genomic analysis revealed that this Montréal cluster was connected to other documented outbreaks in Australia, the United States, and the United Kingdom. This study highlights the urgent need for public health measures to focus on the prevention and the early detection of S. sonnei, since global transmission patterns of MDR strains is concerning and few antimicrobial treatment options are available. IMPORTANCE Shigella sonnei, an important foodborne pathogen, recently became a frequent sexually transmitted agent involved in large and persistent outbreaks globally among men who have sex with men. Most strains also harbor several multidrug-resistant (MDR) determinants of particular concern. This study characterizes an outbreak strain at the source of an important MDR cluster identified in Montréal in 2017. Associations were made to many high-profile international outbreaks, and the causative S. sonnei lineage of these clusters was identified, which was not evident in past reports. The worldwide occurrence of this strain is of concern since treatment with antimicrobials like ceftriaxone and azithromycin may not be effective, and rare microbiological failures have been documented in patients treated with ciprofloxacin. Our investigation highlights the threats of Shigella spp. infection and the necessity for antimicrobial susceptibility monitoring in order to mitigate S. sonnei's impact on public health and to avoid transmission to other at-risk communities.

An Unsupervised Smart App-Optimized HIV Self-Testing Program in Montreal, Canada: Cross-Sectional Study.

BACKGROUND: Although HIV self-testing strategies have been recommended by the World Health Organization, HIV self-tests are not yet approved in Canada. Currently approved HIV self-tests offer toll-free lines that are insufficient for initiating expedited linkages to counseling and care, accurate interpretation, and support during HIV self-testing. We developed an innovative, multilingual software app called HIVSmart! to plug these gaps. OBJECTIVE: This study aimed to test our app-optimized oral HIV self-testing strategy for feasibility in men who have sex with men (MSM) who presented to test at a large sexual health clinic (Clinique Médicale L'Actuel) in Montreal. METHODS: Between July 2016 and February 2017, we offered a strategy consisting of the OraQuick In-Home HIV Test (an investigational device) and a tablet installed with the HIVSmart! app to study participants, who presented at a private office in the clinic, mimicking an unsupervised home environment. We evaluated the strategy for its feasibility, acceptability, and preference. Using the HIVSmart! app, participants were guided through the self-testing process. We determined feasibility with a metric defined as the completion rate, which consisted of the following 3 steps: (1) self-test conduct; (2) self-test interpretation; and (3) linkages to care. Participants independently performed, interpreted, recorded their self-test and result, engaged in pre- and posttest counseling, and sought linkages to care. Laboratory tests (p24, Western Blot, and RNA), as per country algorithms, were expedited, and linkages based on the rapid test status were arranged. RESULTS: Mean age of the 451 participants enrolled was 34 (range, 18-73) years. Of all participants, 97.1% (438/451) completed and submitted the survey through the HIVSmart! app. In total, 84.7% (371/438) of the participants were well educated (beyond high school) and 52.5% (230/438) had been tested within the past 6 months. Of the 451, 11.5% (52/451) were on pre-exposure prophylaxis. Feasibility (completion rate), an average proportion of the 3 steps, was computed to be 96.6% (419/451). The acceptability of the strategy was high at 98.5% (451/458). A majority of the participants (448/451, 99.3%) were found to be self-tested and lab-confirmed negative and were counseled after self- and rapid tests. In total, 0.7% (3/451) of the participants who self-tested positive and were lab-confirmed positive were linked to a physician within the same day. Furthermore, 98.8% (417/422) of the participants found the app to be useful and 94.0% (424/451) were willing to recommend it to a friend or partner. CONCLUSIONS: The HIVSmart! app-optimized strategy was feasible, accepted, and preferred by an educated, urban MSM population of Montreal. With the app, participants were able to perform, interpret, store results, and get rapidly linked to care. The HIVSmart!-optimized, self-testing strategy could be adapted and contextualized to many at-risk populations within Canada and worldwide, thereby maximizing its public health impact.

Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV.

OBJECTIVE: Use of preexposure prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence because of decreased condom use among MSM. This study examines whether PrEP is associated with STIs in the 12 months following PrEP prescription relative to the 12 months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving postexposure prophylaxis (PEP). DESIGN: Retrospective cohort study including PrEP users with more than 12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010 to 2015 at Clinique l'Actuel (Montréal, Canada). METHODS: Incidence of chlamydia, gonorrhoea, syphilis and hepatitis C virus over 12 months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI-screening visits. Models comparing PrEP and PEP users were further adjusted for age and education. RESULTS: One hundred and nine PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12 months after PrEP relative to the 12 months prior (IRR: 1.72, CI: 1.22-2.41; aIRR: 1.39, CI 0.98-1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46-3.24; aIRR: 1.76, CI: 1.14-2.71). CONCLUSION: Increased rates of STIs among individuals after initiation of PrEP may suggest greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.