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Original Research
13 December 2022

Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American OutbreakFREE

Publication: Annals of Internal Medicine
Volume 176, Number 1
Visual Abstract. Monkeypox in Montréal.
A global outbreak of monkeypox occurred beginning in mid-2022 outside endemic areas. The authors of this article use epidemiologic and laboratory surveillance data and a phylogenomic analysis to describe the monkeypox outbreak in Montréal—the first large outbreak in North America—and place it in a global context.

Abstract

Background:

Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas.

Objective:

To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America.

Design:

Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context.

Setting:

Montréal, Canada.

Patients:

Probable or confirmed cases of monkeypox.

Measurements:

Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described.

Results:

Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment.

Limitations:

Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions.

Conclusion:

A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons.

Primary Funding Source:

None.
Monkeypox is a viral zoonotic disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus, which also includes the variola virus, the now eradicated etiologic agent of smallpox (1). Monkeypox virus is endemic in west and central Africa. Transmission is believed to be by direct contact, fomites, and droplets, but MPXV is suspected to be substantially less transmissible than the smallpox virus (2–6). The incidence of monkeypox is increasing in endemic areas, which is hypothesized to be due to waning immunity to orthopoxviruses as a result of the eradication of smallpox and the cessation of smallpox vaccination as well as other factors, including increasing human-reservoir contact due to deforestation and encroachment on reservoir habitats (5, 7).
The natural history of MPXV infection is known to depend on the strain of virus and the route of inoculation (5, 6). Classically, monkeypox is described as an attenuated smallpox-like illness characterized by a 2- to 3-day febrile prodrome, prominent lymphadenopathy, followed by a centrifugally distributed rash beginning on the face that evolves from papules to vesicles or pustules that subsequently umbilicate, ulcerate, and crust (8).
In May 2022, the United Kingdom and other countries reported several cases of monkeypox, many presenting with genital lesions, without a clear epidemiologic link to endemic countries, indicating wider community transmission (9, 10). During the following weeks, monkeypox cases were confirmed in several countries, including Canada (10). Case series of the recent outbreak showed a preponderance of cases in the global men who have sex with men (MSM) community and a highly variable case presentation (9–13). Genomic analysis has placed most of the outbreak sequences in a lineage of clade IIb termed B.1, which is within what was previously termed the “West African” clade of MPXV (14, 15). The growing number of global cases prompted the World Health Organization to declare the outbreak a public health emergency of international concern on 23 July 2022. Montréal, in the province of Québec, Canada, has emerged as the site of the first large outbreak in North America.
In this article, we aim to present a comprehensive view of the monkeypox outbreak in Montréal. We present and synthesize information from several sources to share our experience with other jurisdictions and highlight the importance of a rapid and multifaceted community-focused public health response in containing this outbreak.

Methods

Case Definitions

Cases are defined by the Québec Ministry of Health and Social Services as suspected, probable, or confirmed (see Table 1 for definitions) (16).
Table 1. Monkeypox Case Definitions in Québec

Epidemiologic Data and Epidemic Curve

Data of probable or confirmed monkeypox cases from the Montréal outbreak collected between 1 May and 18 October 2022 were used by the Direction régionale de santé publique (DRSP) de Montréal (hereafter Montréal Public Health or DRSP) to summarize salient features of the outbreak. These data were collected as part of routine Public Health activities and were derived from case reporting to the DRSP based on results of Orthopoxvirus nucleic acid amplification testing (NAAT) done by the Laboratoire de Santé Publique du Québec ([LSPQ]; the Québec provincial public health laboratory) and reporting of cases to the DRSP by treating clinicians, followed by case investigation by DRSP with clinical data derived from telephone questionnaires. In Québec, the LSPQ offers pan-Orthopoxvirus NAAT, with positive results confirmed by the National Microbiology Laboratory (NML), Winnipeg, Canada, with MPXV-specific NAAT. The epidemic curve was generated on the basis of weekly aggregated data of positive Orthopoxvirus NAAT at the LSPQ using the date of specimen collection, including specimens collected until 18 October 2022.

Whole-Genome Sequencing and Phylogenetic Analysis

All clinical samples received by the Special Pathogens Section at the NML were first screened for MPXV by real-time polymerase chain reaction targeting B6R (MPX) for MPXV as well as 2 Orthopoxvirus genes, OPG083 and HA (hemagglutinin), on the LightCycler 96 (Roche Diagnostics). Samples were subjected to DNA extraction using a QIAGEN extraction protocol. Selected DNA samples were subjected to Nextera XT library (Illumina) preparation and subsequent shotgun metagenomics by paired-end sequencing (2 × 150 bp) on an Illumina NextSeq 2000 (or NextSeq 550) apparatus, with in excess of 40 million total reads targeted per sample. The bioinformatic pipeline used for the generation of consensus sequence is described at github.com/phac-nml/monkeypox-nf. All available sequences (1 sequence per patient) originating in Québec were retrieved up to 18 July 2022. This therefore represents a subset of positive cases reported in Figure 1, top, and may include cases outside of Montréal. We also retrieved a sample of global 2022 outbreak sequences (accession numbers and sources are shown in the Supplement Table). We used the bioinformatic processing workflow described at github.com/nextstrain/monkeypox to generate a phylogenetic tree using IQ-TREE after masking and alignment (17, 18).
Figure 1. Monkeypox cases, percent positivity, timeline of public health interventions, and first-dose vaccinations.
A. Epidemic curve of monkeypox cases based on laboratory surveillance of Orthopoxvirus NAAT testing in the province of Québec. Cases are shown per epidemiologic (Centers for Disease Control and Prevention) week and are grouped between cases where the sample is from a person who is a resident of Montréal and those from persons who reside outside Montréal. The percentage of samples submitted each week that was positive for Orthopoxvirus NAAT is indicated by the joined black squares, with scale on the right-sided axis. Cases initially increased to a first peak, declined, peaked again, and then declined toward near resolution of the outbreak. A timeline of major events in the public health response is included under the epidemic curve. B. First-dose monkeypox vaccinations administered in Montréal per epidemiologic week. Note the temporal association between the WHO PHEIC declaration and the AIDS 2022 Conference and first-dose vaccinations. NAAT = nucleic acid amplification testing; PEP = postexposure prophylaxis; PHEIC = public health emergency of international concern; PrEP = preexposure prophylaxis. WHO = World Health Organization.
Figure 1. Continued
Aggregate data provided by the DRSP and LSPQ were collected during usual activities; individual-level data from these sources was not available to authors outside of those organizations. Deidentified genomic data from sequences of isolates from Québec patients used in this study are available on National Center for Biotechnology Information GenBank.

Role of the Funding Source

No funding was received for this study.

Results

Epidemiology and Epidemic Curve

An outbreak of monkeypox was first detected in Montréal in May 2022 by an astute clinician working in a sexual health clinic (19). As of 18 October 2022, a total of 402 cases (346 confirmed, 56 probable) of monkeypox have been reported to Montréal Public Health (Figure 1, Montréal region highlighted). The epidemic curve is characterized by initial rapid growth between epidemiologic (Centers for Disease Control and Prevention) weeks 19 and 22 (8 May to 4 June), followed by 2 peaks around weeks 22 (29 May to 4 June) and 27 (3 to 9 July). Preexposure vaccination began 3 June during week 24 and was expanded on 14 June (indicated in Figure 1; see details in Public Health Response section). After the second peak, cases declined between weeks 28 and 31 (10 July to 6 August), followed by a further plateau around weeks 32 and 33 (7 to 20 August), and declined thereafter to near resolution, with only a single case reported in week 40 (2 to 8 October). The median age of patients was 37 years, and 97.5% were male (Table 2). Nearly all cases were among MSM, 5 of whom were experiencing homelessness. Nearly all patients likely acquired the infection through sexual contact (the remainder mostly undetermined); the proportion of patients who likely acquired the infection through a social venue with sex on premises (50% to 60% during weeks 19 to 21 [8 to 28 May]) has decreased by half from the start of the outbreak (<30% after week 21, ending 28 May). One patient likely acquired it through household (nonsexual) contact with a confirmed MSM case. There were 47 cases among health care workers, but there was no evidence to suggest that any acquired the infection through a work-related exposure or that health care workers who worked while infectious transmitted it to patients or institutional residents. To date, there is no evidence of transmission in homeless shelters in Montréal. About 80% of all contacts reported by patients (during their period of communicability), who may benefit from postexposure prophylaxis, have been nonidentifiable and nontraceable. This high proportion was stable over time, throughout the outbreak.
Table 2. Characteristics of Monkeypox Cases, as Self-reported to Public Health at the Time of Case Investigation

Clinical Features of Monkeypox in Montréal

Clinical characteristics self-reported by patients are summarized in Table 2. Most patients reported skin lesions, although a small number did not report any at the time of data collection (13 of 402, 3%). Lesions were located mostly on the genitals (46%), extremities (39%), and in the perianal region (36%). Palmar and plantar lesions were reported in 26% and 16% of cases, respectively. Symptoms other than cutaneous lesions were reported in 85% of cases, and lymphadenopathy was reported in 64% of cases. Of symptoms reported, the most common were fatigue (59%), fever (53%), and headache (51%). Sore throat and anorectal pain were reported in 35% and 30% of cases, respectively. To date, Montréal Public Health is aware of 10 hospitalizations for medical reasons: 5 linked to secondary bacterial infections (including 1 with ophthalmic involvement), 2 related to risk for upper airway obstruction, 1 for myocarditis, 1 for control of severe pain, and 1 involving a child aged less than 1 year. Six of 10 hospitalized patients received tecovirimat; no other MPXV-directed antiviral medications were given, and 7 patients received antibiotics. To our knowledge, only 1 hospitalized patient required admission to an intensive care unit. Median length of hospital stay was 7 days (range, 2 to 21 days).

Phylogenomic Analysis

Phylogenetic analysis of the Québec outbreak MPXV genomes places all sequences within the B.1 lineage of the clade IIb of MPXV (Figure 2). Québec sequences did not form a monophyletic group but rather are dispersed among other lineage B.1 sequences from the United States, Europe, Taiwan, and South Africa. There is limited divergence among B.1 sequences, consistent with related chains of transmission and the slower rate of evolution of this DNA virus.
Figure 2. Maximum likelihood phylogenetic tree of monkeypox virus clade IIb sequences visualized using Nextstrain.
An expanded view of lineage B.1 is provided; note the different scale and limited divergence among sequences in this expanded view compared with the rest of the phylogeny. Québec sequences are all estimated to be in lineage B.1. The distinct lineage A.2, including several 2022 sequences sampled from the United States, is also indicated and represents chains of transmission unrelated to those within lineage B.1.

Public Health Response

In response to the detection of a monkeypox outbreak in Montréal, public health authorities led several interventions with the objective of controlling transmission. These interventions included early and sustained engagement with the affected communities; alerting clinicians to promote rapid case detection and reporting; performing case investigation and contact tracing; and contributing to the development of interim guidance on diagnostic testing, case and contact management, and recommended infection and control prevention measures.
In late May, Montréal Public Health rapidly identified that preexposure immunization would be required to control this outbreak given that approximately 80% of all contacts could not be identified or traced. In fact, preexposure immunization quickly became the cornerstone of the regional response plan to the monkeypox epidemic. On the basis of data from the Canadian census and the ENGAGE study (20), it was estimated that the at-risk population in Montréal comprised approximately 32 000 MSM who had more than 1 sexual partner in the past 6 months (21). Efforts were aimed at securing sufficient vaccine supply and obtaining favorable recommendations from the Comité sur l’immunisation du Québec ([CIQ] Québec Immunization Committee).
In 2020, based on immunogenicity data, Health Canada authorized the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), a third-generation, nonreplicating, live attenuated vaccine against smallpox and monkeypox in adults (22). The vaccine, given as a primary series of 2 doses at least 28 days apart, offers a favorable risk profile compared with earlier generations of smallpox vaccines. The vaccine had been stockpiled in Canada, and limited supplies were released to Canadian jurisdictions responding to local outbreaks of monkeypox, including Montréal.
Vaccine indications were developed iteratively on the basis of the evolving epidemiologic situation (timeline in Figure 1). On 27 May, the vaccine became available for postexposure prophylaxis. The vaccine was (and continues to be) offered to close contacts as soon as possible, ideally within 4 days of exposure, to prevent disease but up to 14 days after the last exposure to reduce the severity of illness. On 3 June, the CIQ exceptionally permitted the administration of MVA-BN in preexposure prophylaxis under public health direction. That same day, vaccine indications in Montréal were expanded to include persons who reported at-risk behaviors in the past 14 days (that is, MSM who attended social venues with sex on premises, received or gave money or goods in exchange for sex, or MSM with 2 or more sex partners). Sufficient quantities of MVA-BN were obtained from the federal government to implement a 1-dose preexposure vaccination campaign starting on 14 June. Given overall limited availability and immunogenicity data suggesting a seroconversion rate in all groups of 67.5% to 94.6% 4 weeks after 1 dose of MVA-BN (23), it was decided to delay the administration of a second dose (except for immunocompromised persons), so as to vaccinate a larger segment of the population. On 14 June, Québec became the first jurisdiction to offer preexposure prophylaxis to all men and gay, bisexual, and transgender persons who have sexual contacts with at least 1 male partner in Montréal who is not a stable and exclusive sexual partner, as well as to workers and volunteers at social venues with sex on premises. Being a Montréal resident was not a requirement. Second doses were offered to immunocompromised persons initially and became widely available for the targeted population on 6 October 2022 after additional vaccine supply was obtained from the federal government. Given adequate vaccine supply, there was no need to use intradermal administration; all second doses were offered subcutaneously.
Vaccination was accessible at mass vaccination sites located near affected communities as well as sexual health clinics and a pop-up mobile clinic. Promotion of vaccination was done primarily by community partners and the local health and social services network, in collaboration with regional, provincial, and federal public health communications teams. Activities included distribution of posters and flyers to businesses in the community, including social venues with sex on premises; community workers doing outreach on a busy commercial street; and vaccine promotion through various social media outlets and an online dating app.
As of 18 October, more than 4 months into the preexposure vaccination campaign, 23 835 and 1333 persons have received first and second doses, respectively, of MVA-BN in Montréal (Figure 1, bottom). So far, 41 persons have been diagnosed with monkeypox more than 21 days after being vaccinated with MVA-BN (that is, the maximum incubation period), including 29 persons who were diagnosed with monkeypox more than 42 days after receiving 1 dose of MVA-BN.

Discussion

Montréal has emerged as the site of the first large outbreak of monkeypox in North America. The demographic characteristics reported here are concordant with published case series ([9–13], note some cases from Montréal were contributed to reference 10) and show that a large outbreak occurred among MSM and was nearly exclusively the result of sexual exposure. Similar symptoms and lesion distribution have been reported in clinical case series from the 2022 outbreak (9–13). There were few hospitalizations, and few severe cases were noted. In Montréal, 6 hospitalized patients received tecovirimat for either progressive or locally complicated disease. These patients were not prospectively followed here, so it is not possible to describe the response to tecovirimat. In Canada, indications for the use of tecovirimat are evolving; randomized controlled trials would help to better define the groups that would benefit most.
Phylogenomic analysis places all Québec outbreak sequences within the B.1 lineage of MPXV clade IIb, along with most global 2022 outbreak sequences (Figure 2). This phylogenetic tree is congruent in general topology to other recently estimated phylogenies (15, 24, 25). Our sequences are dispersed among recent European and American sequences and support the hypothesis that the outbreak is the result of linked chains of transmission globally in nonendemic areas. Limited divergence among sequences within the B.1 lineages prevented us from determining if Québec cases are the result of a single or multiple individual introduction events. This contrasts with at least six 2022 sequences from cases in the United States and Thailand that are more closely related to other, older clade IIb sequences and have been proposed as lineage A.2 (Figure 2); these are not nested within B.1 and therefore likely represent independent importation events from endemic countries and separate chains of human-to-human transmission (15, 25, 26).
The epidemic curve (Figure 1, top) is characterized by 2 peaks, followed by stabilization and decline in cases toward near resolution of the outbreak. The reason for an initial decline around epidemiologic weeks 24 to 25 (12 to 25 June) is unclear. Although anecdotally there were concerns in Montréal that there was a saturation of clinical capacity to collect specimens for testing and reliance on clinical diagnosis, the rate of test positivity did not increase during this time, suggesting this is a less likely explanation (Figure 1, top, connected points). The epidemiology of the outbreak also evolved during this time from early patients who were likely infected at social venues with sex on premises to more general sexual transmission among MSM communities. This may provide an alternative explanation for the transient decrease in cases as those potential superspreader events involving social venues with sex on premises occurred at the onset of the outbreak. A further possible hypothesis is that given that our epidemiologic curve is based on the date of specimen collection and not on symptom onset, a rapid increase in testing in early June due to increased vigilance and clinical recognition of monkeypox may have led to an apparent early peak. A final potential explanation for the initial decline is an early protective effect of first-dose vaccination (targeted initially to highest risk persons) (Figure 1, bottom). The steady decline of cases after week 27 (3 to 9 July) and control of the outbreak likely reflects the effect of the targeted 1-dose preexposure vaccination campaign as well as ongoing community efforts. Of note, the World Health Organization declaration of monkeypox as a public health emergency of international concern on 23 July 2022 and the AIDS 2022 Conference hosted in Montréal and associated media attention were associated with increased vaccine uptake (Figure 1, bottom), which in turn is temporally associated with further reduction in case numbers (Figure 1, top).
Given that a high and stable proportion (around 80%) of contacts were nonidentifiable and nontraceable, the effectiveness of contact tracing and postexposure prophylaxis interventions have been greatly limited. This was recognized in late May, early in the outbreak, and prompted a rapid pivot toward using scarce vaccine resources for preexposure prophylaxis (Figure 1). Some lessons learned from the response to the COVID-19 pandemic in Québec were also applied to the vaccination strategy. In Québec, in the context of scarce vaccine supply during the second wave of COVID-19 (December 2020 to April 2021), administration of the second dose of SARS-CoV-2 vaccine was delayed to maximize the population receiving a single dose, a strategy that was later supported by observational evidence in health care workers (27). Given this and data supporting good immunologic response to a single dose of MVA-BN, Montréal adopted this strategy to maximize monkeypox vaccine coverage. Ultimately, an assessment of the relative effectiveness of different public health interventions and the vaccination campaign will require careful observational studies.
The prompt recognition of the importance of preexposure vaccination in at-risk populations and the extended offer of MVA-BN to tourists coming to Montréal led to many being vaccinated (28). Other jurisdictions in Canada, the United States, and some European countries are now offering preexposure vaccination to high-risk persons (29–31). The U.S. Food and Drug Administration; the Canadian National Advisory Committee on Immunization; and its Québec counterpart, the CIQ, have issued guidance and exceptional authorization for MVA-BN to allow health care providers to use the vaccine by intradermal injection for persons aged 18 years or older at high risk for infection (32–34). This will increase the total number of doses available by up to 5-fold (34), but given the available vaccine supply, and the declining tempo of the outbreak and vaccination, this was never offered in Québec. Increasing and supporting equitable access to vaccines for at-risk populations worldwide should be a global priority for the prevention and control of monkeypox.
Conclusions about the effectiveness of interventions is limited by the descriptive and retrospective observational nature of these data. The clinical data reported here are reported by patients in telephone interviews and were not confirmed by clinical examination. Our analysis also excludes suspect cases, which may slightly underestimate the true number of monkeypox cases. Granular conclusions from our phylogenomic analysis are limited by the minimal divergence within Québec sequences and in the B.1 lineage in general.
Montréal experienced the first large outbreak of monkeypox in North America. This outbreak occurred primarily among Montréal's MSM population. Phylogenomic analysis places the Montréal outbreak squarely within other 2022 outbreak sequences in the newly defined B.1 lineage. The public health response to this outbreak was facilitated by the early recognition that preexposure immunization would be required to control transmission and by the prior approval of MVA-BN, the CIQ recommendation, and the vaccine's stockpiling and expeditious release by the Government of Canada. Controlling the monkeypox outbreak required a multifaceted approach: community engagement; public health investigation to understand transmission; pre- and postexposure vaccination; and supporting front-line clinicians to recognize, test, and diagnose cases rapidly.

Supplemental Material

Supplement. Supplementary Table

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 176Number 1January 2023
Pages: 67 - 76

History

Published online: 13 December 2022
Published in issue: January 2023

Keywords

Authors

Affiliations

Luke B. Harrison, MD, PhD https://orcid.org/0000-0003-3829-625X
Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada (L.B.H.)
Geneviève Bergeron, MD, MPH https://orcid.org/0000-0001-9001-979X
Direction régionale de santé publique de Montréal, Montréal, Québec, Canada (G.B.)
Geneviève Cadieux, MD, PhD
Direction régionale de santé publique de Montréal and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada (G.C.)
Hugues Charest, PhD
Laboratoire de santé publique du Québec, INSPQ, Sainte-Anne-de-Bellevue, and Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada (H.C., J.F.)
Laboratoire de santé publique du Québec, INSPQ, Sainte-Anne-de-Bellevue, and Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada (H.C., J.F.)
Inès Levade, PhD
Laboratoire de Santé publique du Québec, INSPQ, Sainte-Anne-de-Bellevue, Québec, Canada (I.L.)
Antoine Cloutier Blais, MD
Clinique l’Agora, Montréal, Québec, Canada (A.C.B., E.H.)
Emmanuelle Huchet, MD
Clinique l’Agora, Montréal, Québec, Canada (A.C.B., E.H.)
Clinique Médicale du Quartier Latin, Montréal, Québec, Canada (B.T., D.V.)
Clinique Médicale du Quartier Latin, Montréal, Québec, Canada (B.T., D.V.)
Jason Szabo, MD
Clinique Médicale l’Actuel, Montréal, Québec, Canada (J.S., R.T.)
Réjean Thomas, MD
Clinique Médicale l’Actuel, Montréal, Québec, Canada (J.S., R.T.)
Sébastien Poulin, MD
Clinique I.D., St-Jérôme, Québec, Canada (S.P.)
Christina Greenaway, MD, MSc
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Department of Medicine, Division of Infectious Diseases, Jewish General Hospital, and J.D. MacLean Centre for Tropical Diseases at McGill University, Montréal, Québec, Canada (C.G.)
Gerasimos J. Zaharatos, MD https://orcid.org/0000-0003-0656-0714
Department of Medicine, Division of Infectious Diseases, Jewish General Hospital, Montréal, Québec, Canada (G.J.Z., M.O.)
Department of Medicine, Division of Infectious Diseases, Jewish General Hospital, Montréal, Québec, Canada (G.J.Z., M.O.)
Arpita Chakravarti, MD, PhD
Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada (A.C.)
Robert Pilarski, MD
Clinique Médicale La Licorne, Montréal, Québec, Canada (R.P.)
Andrew Bui-Nguyen, MD
Clinique Quorum, Montréal, Québec, Canada (A.B., K.B.)
Khadija Benomar, MD
Clinique Quorum, Montréal, Québec, Canada (A.B., K.B.)
Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, J.D. MacLean Centre for Tropical Diseases at McGill University, and Research Institute of the McGill University Health Centre, Montréal, Québec, Canada (M.D.L., S.B.)
Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, and Research Institute of the McGill University Health Centre, Montréal, Québec, Canada (D.C.V.)
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada (A.T.D.)
Morag Graham, PhD
National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology & Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada (M.G.)
Marina B. Klein, MD, MSc
Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, and Research Institute of the McGill University Health Centre, Montréal, Québec, Canada (M.B.K.).
Sapha Barkati, MD, MSc, DTM&H https://orcid.org/0000-0002-9388-855X
Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, J.D. MacLean Centre for Tropical Diseases at McGill University, and Research Institute of the McGill University Health Centre, Montréal, Québec, Canada (M.D.L., S.B.)
Acknowledgment: The authors thank Annabelle Mouammine and Lyne Desautels at the LSPQ for providing technical support by collating the microbiological testing data for the province of Québec; Darian Hole, Chanchal Yadav, Natalie Knox, Emily Haidl, Madison Chapel, Geoff Peters, Alwyn Go, Vanessa Laminman, Brynn Kaplen, Kristina Dimitrova, and Levi Klassen at the NML for generating, processing, and analyzing the MPXV genome sequence data; and Mable Hagan and Anders Leung at the NML for providing sample coordination and organization of confirmatory testing. This project received logistic support from the McGill Interdisciplinary Initiative in Infection and Immunity–Clinical Research Platform.
Financial Support: Funding to acquire confirmatory test results and genomic data was provided by the Public Health Agency of Canada. This research received no specific grant from any funding agency.
Reproducible Research Statement: Study protocol, statistical code, and data set: Not available.
Corresponding Author: Sapha Barkati, MD, MSc, DTM&H, J.D. MacLean Centre for Tropical Diseases at McGill University, 1001 Boulevard Decarie, Montréal, QC H4A 3J1, Canada; e-mail, [email protected].
Author Contributions: Conception and design: S. Barkati, G. Bergeron, G. Cadieux, A. Chakravarti, L.B. Harrison, M.B. Klein, D.C. Vinh.
Analysis and interpretation of the data: S. Barkati, G. Bergeron, G. Cadieux, H. Charest, A.T. Duggan, M. Graham, C. Greenaway, L.B. Harrison, M.B. Klein, I. Levade, M. Libman, D.C. Vinh.
Drafting of the article: S. Barkati, G. Bergeron, G. Cadieux, A.T. Duggan, M. Graham, L.B. Harrison, M.B. Klein, I. Levade, M. Oughton, D.C. Vinh.
Critical revision of the article for important intellectual content: S. Barkati, G. Bergeron, A. Bui-Nguyen, G. Cadieux, J. Fafard, C. Greenaway, L.B. Harrison, M.B. Klein, M. Libman, D.C. Vinh, D. Vlad, G.J. Zaharatos.
Final approval of the article: S. Barkati, K. Benomar, G. Bergeron, A. Bui-Nguyen, G. Cadieux, A. Chakravarti, H. Charest, A. Cloutier-Blais, A.T. Duggan, J. Fafard, M. Graham, C. Greenaway, L.B. Harrison, E. Huchet, M.B. Klein, I. Levade, M. Libman, M. Oughton, R. Pilarski, S. Poulin, J. Szabo, R. Thomas, B. Trottier, D.C. Vinh, D. Vlad, G.J. Zaharatos.
Provision of study materials or patients: S. Barkati, A. Chakravarti, J. Fafard, C. Greenaway, E. Huchet, M. Libman, M. Oughton, R. Thomas, D. Vlad, G.J. Zaharatos.
Administrative, technical, or logistic support: S. Barkati, A.T. Duggan, M. Graham, M.B. Klein, J. Szabo, D.C. Vinh, G. J. Zaharatos.
Collection and assembly of data: K. Benomar, G. Bergeron, A. Bui-Nguyen, G. Cadieux, A. Chakravarti, H. Charest, A. Cloutier-Blais, A.T. Duggan, J. Fafard, M. Graham, L.B. Harrison, I. Levade, M. Libman, M. Oughton, R. Pilarski, S. Poulin, J. Szabo, B. Trottier, D.C. Vinh, G.J. Zaharatos.
This article was published at Annals.org on 13 December 2022.
* Drs. Harrison, Klein, and Barkati contributed equally to this work.

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Luke B. Harrison, Geneviève Bergeron, Geneviève Cadieux, et al. Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak. Ann Intern Med.2023;176:67-76. [Epub 13 December 2022]. doi:10.7326/M22-2699

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