From U of T News, by Aideen Teeling
Darrell Tan remembers diagnosing the first-ever case of mpox in Ontario in May 2022. Based on reports of growing mpox epidemics in Europe and the United States, his mind went straight to an outbreak scenario in Canada.
“My head was spinning with questions: how is it going to manifest?” he says.
Tan is an infectious disease physician and clinician-scientist at Unity Health Toronto and co-led the Emerging and Pandemic Infections Consortium’s mpox rapid research response along with Sharmistha Mishra, a fellow infectious disease physician and mathematical modeler at Unity Health Toronto.
Launched in July 2022, the funding program provided over $1.13 million to 5 research projects involving 15 scientists — from the University of Toronto and hospital partners Sunnybrook Research Institute, Unity Health Toronto and the University Health Network — to support the rapid establishment of an interdisciplinary research platform grounded in a clinical cohort and community engagement. The outcomes of these projects shaped our understanding of mpox and steered the clinical and public health response in Ontario and beyond. Collectively, this work has uncovered new insights into how the viral infection and transmission, including via environmental surfaces, vaccine effectiveness and distribution strategies.
Mpox (previously known as monkeypox) is a viral infection that spreads through close contact and is characterized by flu-like illness and painful rashes typically found on the hands, feet, face and anogenital region. As of March 2026, 2,345 cases of mpox have been recorded in Canada, with over half of cases found in Ontario. Earlier this month, two cases of a different strain of the mpox virus were reported in Toronto.
When mpox first emerged in Canada in 2022, there were many questions about how it would impact a population that had little to no pre-existing immunity against the virus.
To answer these questions, Tan established the Mpox Observational Cohort Study (MPOCS), which has since enrolled over 100 participants. By following the participants over time, the researchers generated a more complete picture of the symptoms, duration and treatment strategies for mpox, and provided a wealth of information to guide physicians in diagnosing and treating a suspected case of mpox. The participants also shared information about the timing and types of exposures, their concerns about isolation, and helped researchers understand environmental transmission of the virus.
The day after diagnosing his first mpox case, Tan reached out to the Gay Men Sexual Health Alliance (GMSH) discuss with its leaders about how to engage with gay, bisexual and other men who have sex with men (gbMSM), which reports indicated were the communities most affected by mpox.
“How are we going to mobilize the community around [mpox]?” says Tan, who is also an associate professor of medicine at U of T’s Temerty Faculty of Medicine.
A concern raised by a community member led to the creation of an online image atlas showing how lesions can vary in their appearance across different skin tones and parts of the body. Created using photos from the cohort study, the image atlas is an important tool to help physicians diagnose mpox and to reduce stigma around its portrayal in media.
Beyond diagnosing mpox, Tan says one of the benefits of having a large longitudinal cohort is the ability to ask other important questions. For example, the researchers noticed that people could have lesions for weeks, even after they felt better. This led them to investigate where the virus replicates in the body and how long it remains infectious.
Tan and Mishra teamed up with Rob Kozak, a clinical microbiologist at Sunnybrook Health Sciences Centre, to study biological samples donated by MPOCS participants, which are stored in the MPOCS Biobank housed at the Toronto High Containment Facility.
The researchers showed that mpox skin lesions can shed infectious virus particles for up to three weeks and that virus can be found for up to four weeks in the anogenital region.
Tan says these results not only informed diagnostic strategies in asymptomatic cases but also framed his conversations with patients about how long the virus remains present and what precautions should be taken to limit viral spread.
Building on this work, Kozak and Tan published another study showing that the only antiviral available to treat mpox, tecovirimat, failed to reduce the number of infectious viral particles shed by mpox patients. These findings, which were replicated by other studies, have been used to advocate for the development of more effective antiviral drugs against mpox.
“As we’re figuring out the virus, the virus is figuring us out as well,” says Kozak, who is also an assistant professor in the department of laboratory medicine and pathobiology.
As a virologist, Kozak was interested in discovering how the virus causes disease and why some people got sicker than others.
Following reports that mpox tends to cause particularly severe illness in people living with human immunodeficiency virus (HIV), Kozak and postdoctoral researcher Jacklyn Hurst used dual RNA-sequencing to investigate which viral genes were turned on and induced expression of immune response genes in cells from mpox patients also living with HIV. In people with HIV and mpox, they observed decreased expression of immune response genes and an increase in harmful viral genes, which sheds light on the arms race taking place inside cells that may lead to worse illness.
Kozak says EPIC funding was critical in enabling his early research that led to larger funding from external agencies. He is now collaborating with the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan to understand mpox infections in animals, which may reveal new treatment strategies in human cases.
Mpox shares remarkable genetic similarities with the smallpox virus, which was eradicated in 1980. Canada has maintained a stockpile of smallpox vaccines for emergency use which public health teams were able to access during the mpox outbreak, but supplies were limited.
For Mishra, one of her early priorities was developing mechanistic and explanatory mathematical models of transmission to help inform an effective and equitable vaccine campaign. The question of early vaccine allocation was posed to Mishra by public health decision makers right at the start of the outbreak.
Mishra, who holds a Tier 2 Canada Research Chair in Mathematical Modeling and Program Science, says that mathematical models can help researchers to see beyond what is being reported clinically.
“What might be the potential trajectories we might see in the short term, in the medium term, and in the potential long term?” she asks.
Empowered by EPIC’s mpox rapid response funding, Mishra and then PhD student Jesse Knight published a study in the Canadian Medical Association Journal projecting that distributing vaccines to cities based on the size of gbMSM sexual networks and the characteristics and configuration of networks could prevent a significant number of mpox infections — findings that were used to inform public health vaccination strategies in Ontario.
Mishra built on her EPIC-funded modelling studies to further investigate the effectiveness of the smallpox vaccine against mpox. In a landmark study published in the British Medical Journal, Mishra, Jeff Kwong, Christine Navarro and colleagues at Public Health Ontario demonstrated that a single dose of vaccine had an estimated effectiveness of 58%.
As an associate professor of medicine at Temerty Medicine and at the Dalla Lana School of Public Health, Mishra says robust estimates of vaccine effectiveness not only make modelling data more reliable, but also provide critical thresholds for public health interventions by informing policymakers about how much of the population would need to receive vaccination to prevent ongoing outbreaks.
Tan, Kozak, and Mishra, alongside the entire rapid response team, have also leveraged their experience from Ontario’s 2022 mpox outbreak to build national and international research partnerships with countries continuing to face growing mpox outbreaks.
“You don’t do infectious disease research locally,” says Mishra.
She says connecting with colleagues in Nigeria and Sierra Leone through the Canada-Africa Mpox Partnership (CAMP) network, has allowed her to share the mpox modeling approaches developed through the EPIC rapid response to foster mutual capacity building and will enhance future surveillance for mpox and other emerging pathogens in these regions.
Almost four years after Canada’s first case of mpox was reported — with a new strain of the virus threatening to cause a resurgence in cases — all three researchers remain vigilant about the possibility of a new outbreak and focused on the questions that remain unanswered.
“Surveillance is key as well as encouraging vaccination,” says Kozak. “We can’t let our guard down when it comes to mpox.”