EPIC

Mpox DNA can persist in the body for up to four weeks: Study

rahul.kalvapalle — Tue, 12 Mar 2024 20:04:03 +0000

Mpox DNA can persist in the body for up to four weeks: Study

rahul.kalvapalle Tue, 03/12/2024 - 16:04

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A sign containing information about monkeypox is seen in International Airport Treviso A. Canova, in Treviso, Italy, on Nov. 30, 2022 (photo by Manuel Romano/NurPhoto via Getty Images)

Betty Zou

Topic

Breaking Research

EPIC

Institutional Strategic Initiatives

Temerty Faculty of Medicine

Unity Health

Dalla Lana School of Public Health

ihpme

St. Michael's Hospital

Sunnybrook

Subheadline

The study is one of several projects supported by the mpox rapid research response launched by U of T's Emerging and Pandemic Infections Consortium (EPIC) and its hospital partners

DNA from the mpox virus can be found in different parts of the body for up to four weeks after symptom onset, according to a study led by researchers at Unity Health Toronto, the Sunnybrook Research Institute and the �ؿ�ζSM.

The researchers analyzed samples from 64 men who contracted mpox, including participants from the Mpox Prospective Observational Cohort Study led by Darrell Tan, an infectious disease physician at St. Michael’s Hospital, part of Unity Health Toronto – where some of Toronto’s first patients with mpox were identified and cared for – and associate professor in the department of medicine and the Institute of Medical Science at U of T's Temerty Faculty of Medicine and in the Institute of Health Policy, Management and Evaluation (IHPME) at the Dalla Lana School of Public Health.

They found that persistence of mpox virus DNA varied depending on where the samples were taken from. Among the key findings was that the DNA was detectable in nearly half of genital skin swabs and one in five skin swabs from other sites a week after symptoms had resolved.

The study, which was published in Open Forum Infectious Diseases, is one of several projects supported by the mpox rapid research response launched by the Emerging and Pandemic Infections Consortium (EPIC), an institutional strategic initiative, and its hospital partners during the global outbreak of mpox – previously known as monkeypox – in 2022.

According to the World Health Organization, nearly 94,000 confirmed cases of mpox, including 179 deaths, have been reported from 117 countries since January 2022. As of September 2023, 1,515 cases have been confirmed in Canada, mostly in Ontario and Quebec.

“Even though we’ve known about mpox for over 70 years, it was new to us because we hadn’t seen it outside the endemic regions,” said Robert Kozak, one of the study’s authors and a clinical microbiologist at Sunnybrook Research Institute and assistant professor in the department of laboratory medicine and pathobiology at Temerty Medicine. “There was still a lot about the virus and disease that we didn’t know,”

To answer key questions about viral shedding, Kozak teamed up with Tan and Sharmistha Mishra, an infectious disease physician at St. Michael’s Hospital and associate professor in the Temerty Faculty of Medicine’s department of medicine and Institute of Medical Science and IHPME.

(L-R) Robert Kozak, Sharmistha Mishra and Darrell Tan (supplied images)

The researchers used a technique called quantitative polymerase chain reaction (qPCR) to determine the persistence of mpox virus DNA. Samples were taken from six different sites on the body — genital region, nasal cavity, semen, skin, throat and urine — and over an extended period of time.

On average, mpox DNA was detected in skin swabs from the genital and perianal region and from other skin sites at 30 and 22 days after symptom onset, respectively. These findings are consistent with the sexually transmitted nature of mpox during the recent global epidemic, which primarily affected gay, bisexual and men who have sex with men.

The researchers were unable to detect viral DNA in a large proportion of semen samples and nasal cavity swabs taken when individuals first presented with symptoms, whereas in urine and throat swab samples, mpox DNA persisted for roughly two weeks after symptom onset.

Interestingly, the researchers did not observe a difference in the length of viral DNA persistence between people who received the antiviral drug tecovirimat and those who did not. Tan noted that while study participants were not randomly assigned to receive the drug, these results underscore the uncertainty around tecovirimat’s effectiveness in treating mpox infections.

He added the study provides several key learnings for his clinical colleagues. “First, we’ve documented the breadth of clinical samples in which mpox DNA can be identified and therefore can be used to confirm a diagnosis. Our findings also reinforce that it’s worthwhile for clinicians to collect such samples in individuals where an mpox diagnosis is being considered, even after symptoms of feeling unwell are gone," Tan said.

The researchers caution that just because mpox DNA can be detected up to four weeks after symptom onset, it doesn’t mean that individuals are infectious for that long.

“We don’t know for sure whether the presence of detectable viral DNA necessarily means that the virus is transmissible to other people, so more research definitely needs to be done to determine definitively the period of infectiousness,” Tan said.

To that end, Jacklyn Hurst, a postdoctoral fellow in Kozak’s lab, recently started work in the Toronto High Containment Facility to look for live virus in the same samples from which mpox DNA was detected. The researchers are also using the facility’s biobank of mpox patient samples to identify biomarkers that could predict whether a person will have a mild or severe infection.

“Without the Toronto High Containment Facility, we wouldn’t be able to do any of this. Having that facility will help us answer a lot of questions about this virus and how to stop it,” said Kozak.

He acknowledged the immense contributions of the patient community to this work. “A huge thank you to all the study participants. We wouldn’t be able to do this work without their sacrifice and commitment.”

Researchers partner with Moderna to develop new mRNA-based therapies for HIV and other diseases

siddiq22 — Wed, 26 Jul 2023 19:19:09 +0000

Researchers partner with Moderna to develop new mRNA-based therapies for HIV and other diseases

siddiq22 Wed, 07/26/2023 - 15:19

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(Photo by Amornrat Phuchom/iStock/Getty Images Plus)

Topic

Breaking Research

EPIC

Temerty Faculty of Medicine

Subheadline

Projects will develop mRNA vaccines to treat HIV infection and technologies to modulate the body's immune response

Two teams of researchers at the �ؿ�ζSM have partnered with Moderna Canada to advance new mRNA-based therapies for HIV and other diseases.

The projects – one led by Mario Ostrowski, an infectious disease physician at Unity Health Toronto and a professor of medicine, immunology and pathobiology and lab medicine at the Temerty Faculty of Medicine; and the other by Haissi Cui, assistant professor in the department of chemistry in the Faculty of Arts & Science, and Landon Edgar, assistant professor in the department of pharmacology and toxicology in the Temerty Faculty of Medicine and an investigator in the PRiME research group – are supported through the partnership framework agreement between U of T and Moderna.

Launched in April 2022, this partnership was the first between Moderna and a Canadian university and provides opportunities for U of T researchers to collaborate with a leading biotechnology firm to create new tools to prevent and treat diseases.

“The partnership between the �ؿ�ζSM and Moderna Canada is a testament to the power of industry and academic collaborations, and one that will advance the frontier of mRNA-based vaccines and therapies,” said Derek Newton, assistant vice-president, innovation, partnerships and entrepreneurship at U of T.

“Researchers from both organizations have a shared vision to create new health-care innovations to prevent and treat infectious diseases that will impact patients across Canada and globally.”

From left: Researchers Mario Ostrowski, Haissi Cui and Landon Edgar will be working on projects supported through the partnership framework agreement between U of T and Moderna (supplied photos)

Ostrowski’s project brings together his decades of research on the immune response to HIV with Moderna’s expertise in mRNA vaccines to develop personalized mRNA vaccines to treat HIV infection.

This strategy could address one of the biggest challenges in HIV management: the long-term persistence of viral reservoirs within immune cells in the body, which necessitates life-long antiretroviral therapy treatments for people with HIV. While these therapies help people with HIV live longer, they can also lead to side effects that negatively impact a person’s overall physical and mental health.

To tackle this challenge, the researchers will design mRNA vaccines that are tailored to the unique strain of HIV found in each person. Ostrowski believes that these highly targeted vaccines can activate powerful immune cells to seek out and eliminate hidden viral reservoirs. Similar approaches have been used successfully to create personalized therapeutic vaccines for people with cancer.

This work will also leverage the capabilities of the Toronto High Containment Facility (THCF), which is equipped to allow researchers to study high-risk pathogens, such as HIV and SARS-CoV-2, in a safe and secure way. The facility is a cornerstone of the Emerging and Pandemic Infections Consortium (EPIC) institutional strategic initiative, a partnership between U of T and five major Toronto hospitals to advance innovative infectious disease research and strengthen preparedness for future pandemics.

Containing the only containment level 3 (CL3) research lab in the Greater Toronto Area and the largest in the province, the THCF plays a critical role in supporting Ontario’s life sciences research ecosystem. Its unique infrastructure and capabilities enable cutting-edge research on vaccines and therapeutics and provide training opportunities needed to drive innovation and biomanufacturing in Ontario.

Modulating the body’s immune response is also at the core of the project led by Cui and Edgar.

Their work focuses on the sugars that coat the outside of all immune cells. These sugars, called glycans, have recently been shown to play an important role in fine-tuning the function of some immune system components. However, designing targeted and effective therapies to modulate the glycans themselves has remained elusive.

In collaboration with Moderna, Cui and Edgar will develop mRNA technologies that can be used to adjust glycan levels within specific tissues – or even on specific cell types. If successful, this approach could be used to alter how immune cells function in a myriad of diseases.

Through this cross-faculty and cross-sector collaboration, Cui and Edgar’s work would demonstrate the feasibility of using these cutting-edge technologies to manipulate the architecture of a cell’s surface and to improve immune responses through cell-surface engineering.

“At Moderna, we are focused on the creation of transformative mRNA medicines. For the past 13 years, we have been investing in research and innovation into different facets of mRNA science,” says Patricia Gauthier, Moderna Canada president and general manager.

“Our collaboration with the �ؿ�ζSM and its exceptional scientists further strengthens our resolve to push the boundaries of what can be achieved in this rapidly evolving field to improve the lives of patients through mRNA science.”

As part of the partnership, each team will be paired with a scientific expert at Moderna who can champion their research and provide support and feedback.

The selection of these two projects follows the announcement in October 2022 of a partnership between Moderna and a team of U of T researchers led by Omar F. Khan, an assistant professor in the Institute of Biomedical Engineering, to develop next-generation RNA platform technologies. The project recently received support from the Natural Sciences and Engineering Research Council of Canada Alliance Grant program, which aims to foster collaborations between university researchers and partner organizations in the private, public and not-for-profit sectors.

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Betty Zou & Mayuri Punithan

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Institute of Biomedical Engineering

Space doctor: U of T researcher co-chairs International Space University program in Brazil

mattimar — Wed, 26 Jul 2023 15:51:35 +0000

Space doctor: U of T researcher co-chairs International Space University program in Brazil

mattimar Wed, 07/26/2023 - 11:51

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From left: John Connolly, NASA lunar mission expert; Jonathan Clark, space medicine expert; Judith Hayes, NASA chief science officer; Safa Siddiqui, nuclear safety analysis engineer at Bruce Power; and Farhan Asrar, associate professor in U of T’s Temerty Faculty of Medicine (supplied photo)

Mariam Matti

Topic

Global Lens

Temerty Faculty of Medicine

Artificial Intelligence

Dalla Lana School of Public Health

machine learning

Medical Research

Space

Space exploration is often viewed as the realm of astronauts and engineers, but the �ؿ�ζSM’s Farhan Asrar is using his expertise in public health to chart an extraterrestrial path in medicine.

Asrar, an associate professor in the department of family and community medicine in the Temerty Faculty of Medicine with a cross-appointment with the Dalla Lana School of Public Health, researches the physical and psychological effects of space travel on the human body, the challenges astronauts face during prolonged space missions and the potential implications for human health back here on Earth.

As a member of the International Space University, he recently travelled to Brazil to co-chair the department of human performance in space of the Space Studies Program, an annual nine-week program hosted in different locations around the world that provides participants professional development experience covering all aspects of space. As a co-chair, Asrar played a key role in developing curriculum for the program, organizing talks with astronauts and educational opportunities – including a trip to Brazil’s Paralympic training site to explore similarities between astronauts and elite athletes – and providing mentorship to attendees.

“I really appreciate that space brings everyone together – regardless of your background, culture or country,” the Mississauga-based physician and researcher says.

U of T News caught up with Asrar before he left for South America to ask him about his journey into space medicine, the challenges astronauts face and his role with the International Space University.

What is space medicine?

We are looking at what happens to astronauts and their health in space – we know that the microgravity has impacts on the body including bone and heart health. The space medicine side would introduce countermeasures that can maintain health and bone health in space, especially for someone who is staying for longer periods.

It also involves the preventive side because it is looking at individuals who might have medical conditions that would put them in a high-risk situation, and it examines whether their bodies would be able to withstand the strains of this extreme space environment.

What are some of the challenges astronauts encounter in space?

The distance and extreme environment can be stressful for anyone. When you are in space, you are away from your loved ones. You are in this really confined space with a select number of individuals for the next six months or so. Even simple tasks like going to the bathroom become more complex.

In order to prevent issues related to bone and heart health, astronauts have to exercise for two hours on a daily basis. They also have their regular schedule like keeping their premises clean and research projects – and working to meet all those tasks and needs in an extreme environment can be quite challenging.

With further distances away from Earth, the time delay creates challenges in communication. If someone has a medical emergency or needs mental health support, it can be difficult to communicate in a timely manner. These are the sorts of things we’re examining in space medicine: how do we train people to be better prepared for these challenges?

As a member of the Temerty Centre for AI Research and Education in Medicine (T-CAIREM), I know that there are developments in machine learning and artificial intelligence that are being explored for use in every aspect of medicine. This also has a role in space medicine and improving the response time from Earth to astronauts.

Farhan Asrar leads an introductory lecture on space medicine for Space Studies Program participants (supplied photo)

What sort of work will you be doing with the International Space University’s Space Studies Program?

This year, the space studies program is being held in Brazil and I was invited to co-chair the department of human performance and space along with Judith Hayes, NASA's chief science officer under the human health and performance directorate.

We helped develop curriculum for the program along with other chairs, directors and academics. We’ve organized talks, educational activities and different sessions that are related to human performance and health and medicine in space. We’ll be there to support and mentor the participants when necessary.

We’ve invited CSA’s flight surgeon and NASA’s Space psychologist to share their expertise on the health of astronauts, the training they do to prepare for missions and the challenges they face. We’ve also invited NASA astronaut Jessica Meir and Canadian astronaut David Saint-Jacques to talk about his experience in space. He has worked as a family doctor in the Arctic, so it’ll be interesting to hear about his experiences with extreme environments and challenges he’s had here on Earth, too.

I’ve also been researching the link between sports and space medicine – so we organized a visit to Brazil’s Paralympic training site. There are a lot of similarities between athletes and astronauts: they both have to be physically fit, train every day, and their training and professions put a physical strain on their bodies. In this session, we’ll also educate participants about Paralympic training and then get into physical barriers in space.

What excites you most about space?

I really appreciate that space brings everyone together, regardless of your background, culture or country. It’s great to have so many individuals working together – even the crew missions are now more diverse.

There’s also a lot of technology like GPS and infrared thermometers that originated from space programs before they became part of our everyday lives. Infrared thermometers, for example, were invented to measure the temperature of distant celestial objects and become very popular during the pandemic to check a person’s temperature.

Similarly, the isolation and extreme environments that astronauts feel on their missions is something we felt during COVID-19. And we used telemedicine during the pandemic, which originated from space and taking care of astronauts at a distance. With the pandemic, we were put in many situations we weren’t used to – but you could often look to the space world and say, “Yes, we’ve been doing this for decades and we can share our expertise.”

There’s so much that space introduced to our lives that we don’t even realize.

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 — Thu, 11 May 2023 20:33:55 +0000

Research shows how boosting immune memory could help develop improved flu vaccine

siddiq22 Thu, 05/11/2023 - 16:33

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PhD student Karen Yeung is one of the recipients of the inaugural EPIC Doctoral Awards for her work on boosting immune memory to enhance protection against influenza (supplied photo)

Betty Zou

Topic

Breaking Research

Emerging and Pandemic Infections Consortium

EPIC

Temerty Faculty of Medicine

Karen Yeung is no stranger to outbreaks of respiratory infections. As a child growing up in Hong Kong, she lived through the first SARS outbreak in 2003 and witnessed the city dealing with repeated threats of bird flu in the years that followed.

Twenty years later, in the midst of a global pandemic caused by SARS-CoV-2, the fourth-year PhD student in the department of immunology at the �ؿ�ζSM's Temerty Faculty of Medicine is leading critical research to understand how our immune systems respond to influenza infection – and how we might be able to leverage that knowledge to create a long-lasting, universal flu vaccine.

Yeung is one of 31 recipients of the inaugural Emerging and Pandemic Infections Consortium (EPIC) Doctoral Awards, which supports outstanding students pursuing infectious disease research.

“Current flu vaccines work by inducing an antibody response against a specific component of the influenza virus, but this viral component mutates very quickly every year. This means that the antibodies that you make against this year’s flu vaccine likely won’t match the strain of flu that we’ll see next season,” says Yeung, who is supervised by Tania Watts, a professor of immunology at U of T who holds the Canada Research Chair in anti-viral immunity.

Immune cells called memory CD8+ T cells might hold the key to unlocking broad protection against multiple flu strains. These immune cells retain a memory of a pathogen long after the initial infection, which allows the body to quickly mount a powerful immune response the next time it encounters that pathogen. And unlike the antibodies generated from a flu vaccine, memory T cells recognize parts of the influenza virus that are more likely to remain unchanged between strains and from one year to another.

Previous work from Watts’ lab was the first to show that a protein receptor on CD8+ T cells called 4-1BB is an important player in the formation of memory T cells after a flu infection. 4-1BB is part of a communications cascade that relays cues to regulate the immune system. Yeung’s doctoral research aims to uncover how this pathway is turned on to produce memory CD8+ T cells.

“We’re really interested in how cells can communicate to each other through the language of receptors like 4-1BB and signaling,” Yeung says.

“When you have a lung infection due to flu, what kinds of signals are the CD8+ T cells receiving in the lungs that are helping them transition to memory T cells? How can we manipulate these mechanisms to form more of these memory cells?”

So far Yeung’s work points to monocytes – a type of immune cell that is recruited to the lungs early on during an infection – as providing the activating signal to allow more CD8+ T cells to become memory cells. Next, she’ll be looking at what happens during a secondary flu infection if 4-1BB signaling is disrupted and there are fewer protective memory T cells.

By deepening the understanding of how immune memory develops, Yeung’s research – which is funded by the Canadian Institutes for Health Research – is laying the groundwork for new approaches that could complement existing flu vaccine strategies to elicit a broader and longer-lasting immune response.

“It takes us closer towards a universal flu vaccine strategy, where one shot will be enough to protect against seasonal influenza and future influenza pandemics as well.”

'We should be preparing': Researcher Samira Mubareka on the risks posed by bird flu

Christopher.Sorensen — Thu, 06 Apr 2023 15:27:52 +0000

'We should be preparing': Researcher Samira Mubareka on the risks posed by bird flu

Christopher.Sorensen Thu, 04/06/2023 - 11:27

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(Photo by Kevin van Paassen/Sunnybrook Health Sciences Centre)

Betty Zou

Topic

Our Community

EPIC

Institutional Strategic Initiatives

Sunnybrook Health Sciences Centre

Temerty Faculty of Medicine

Laboratory Medicine and Pathobiology

From Brampton, Ont. to sites in nearby Halton and Niagara regions, there are a growing number of reports of birds that have tested positive for highly pathogenic avian influenza (HPAI) virus, or bird flu.

While HPAI typically infects birds – more than seven million across Canada, including nearly 750,000 in Ontario, according to the Canadian Food Inspection Agency – there have also been growing reports since 2022 of mammals getting infected and dying of bird flu, which is also known as H5N1, across a large geographic area. They include small land animals like raccoons and skunks to large carnivores like bears and mountain lions, as well as marine mammals like sea lions and dolphins.

Just this week a pet dog died in Oshawa, Ont. after testing positive.

To learn more about the bird flu outbreak and what we can do to prepare, writer Betty Zou spoke to Samira Mubareka, an infectious diseases physician, medical microbiologist and scientist at Sunnybrook Research Institute. She is also an associate professor in the department of laboratory medicine and pathobiology in the �ؿ�ζSM ’s Temerty Faculty of Medicine and a member of the U of T-based Emerging and Pandemic Infections Consortium (EPIC), an institutional strategic initiative.

Her research uses a collaborative One Health approach – looking at the interconnection between people, animals and their shared environment – to conduct surveillance in wildlife and look at the biology of emerging viruses and transmission between species, including humans.

How widespread is bird flu right now?

The level of avian influenza activity we’re seeing at the moment is unprecedented. To step back a bit, the first cases in North America were reported in late 2021 in birds in Newfoundland – and from there, it spread along the eastern seaboard into the United States along Atlantic flyways. Subsequently, there were cases reported in the west of Canada and the United States, followed by cases in Central and South America. Beyond affecting wild and farmed birds, we are seeing spillover of HPAI into mammals, many of whom die of severe neurological complications.

There has also been renewed focus on HPAI because a reported outbreak among farmed mink in Spain, with mammal-to-mammal transmission, and large die-offs of marine mammals, including sea lions. The virus also appears to be reassorting, or exchanging genetic material among H5N1 lineages. All of these represent red flags that reflect an amount of viral activity that we really haven’t seen before.

We’ve also never seen this level of bird depopulation – both from die-offs and as a control measure. This has potential to impact biodiversity, wildlife health and conservation, as well as food costs and security. There have been a significant number of outbreaks, including here in Ontario, and some of them have been fairly close to densely populated areas. Having said all this, it is important to underscore that the risk remains low for humans and that we have not had any human cases in Canada. Regardless, we need to prepare for that possibility.

H5N1 made the news in 2003 and 2014, but in both those instances the outbreaks were relatively contained. What’s changed this time that is causing it to be so widespread?

There could potentially be multiple factors. There may be some characteristics that are specific to this strain of H5N1 that are enabling this level of viral activity. One thing we do know is that bird populations are highly mobile and often exchange viruses when they’re migrating and co-mingling at migration sites, which provides an ecological context for viral reassortment and selection.

Having said that, these birds migrate every year, so why is this so different? I don’t know that we’ll get to the bottom of that without more research. People have started to look at how influenza virus pathogenesis is changing in these birds and how migration affects bird immunity, but what we don’t understand are some of the intersections between the virus and other potential exposures and ecological factors that the birds are encountering during migration or at their overwintering sites. I think there’s a lot to be learned and this is where a One Health approach could be instrumental.

How does H5N1 affect humans and what clinical interventions are available?

With people, unsurprisingly, there’s a range of clinical symptoms. Some people will experience little to no symptoms, but we don’t know exactly what proportion are asymptomatic, have mild symptoms or more severe symptoms with poor outcomes. Frequently, people have quoted mortality rates of between 40 per cent and 60 per cent for this virus, which is very high, but that could be due to biases from past events where only the most severe cases were identified.

Like with other influenza viruses, this virus could manifest as an upper respiratory tract infection or severe viral pneumonia with multi-system organ involvement and/or a severe neurological syndrome. As health-care providers, we need to be prepared for a range of symptoms. The good news is that I’m not aware of any widespread antiviral resistance. In terms of prevention, there is no vaccine specific to H5N1 available for Canadians at this moment, but we still recommend the seasonal influenza virus vaccine. Seasonal influenza vaccination reduces the burden of seasonal influenza, and it may also reduce the likelihood of H5N1 mixing with seasonal influenza viruses and potentially reassorting to become more transmissible or severe in humans.

What should individuals and health-care providers be thinking about in terms of risk factors for H5N1?

There are a few different risk factors and they’re generally related to animal exposure. One, obviously, is to have been in direct contact with animals that were known to have H5N1. People working in certain occupations like veterinary medicine and farming – particularly poultry farming – as well as anyone working directly with wild birds and other wildlife are considered at higher risk of being exposed.

You recently received funding support from EPIC to conduct risk assessment research on highly pathogenic avian influenza. Can you tell us about that work?

Absolutely. We know that in Canada, the virus is reassorting which means it is exchanging genetic materials with other viruses. Do these new pieces of genetic material cause the virus to behave differently? Scientists at the National Centre for Foreign Animal Disease and the Public Health Agency of Canada are leading the work to try and understand that and the risks posed by these new variants. We are collaborating with them and with EPIC member Theo Moraes, who has been central to that work. Theo’s team has developed a way to take cells from inside someone’s nose and grow them in the lab. These cells serve as a model to understand how well viruses replicate and, in turn, how much of a risk they could pose to people. This work also feeds into a grant we just received from the Canadian Institutes of Health Research on using a collaborative One Health approach to zoonotic virus detection and risk assessment at the wildlife-human interface.

How worried are you about the bird flu situation right now? How should we be preparing?

I’m more worried now than I was a few months ago because there are so many reports of spillover from birds to mammals. Hearing about human cases, even sporadic ones, is another red flag. We’re sufficiently concerned that we’ve started preparatory activities like getting our sequencing protocols ready. I’m also worried about the impact on wildlife health. When you have wildlife populations that are dying off, that in and of itself should have us concerned, regardless of whether humans are getting sick.

I think every one of these events is a reminder that we should be preparing. It’s important to note that right now the risk to individuals is still low, but that can change anytime. Let’s not to wait for it to change before we start preparing. We should be more proactive in surveillance and looking at things like vaccine and antiviral development – both for poultry and for humans. Vaccinating poultry is not as straightforward as you might think because there are trade implications.

The fact that we’re seeing new HPAI viruses in Canada underscores the importance of ongoing surveillance. We also need to do a better job of communicating to frontline health-care providers, especially those working in areas where the potential for a spillover from animals to humans is high. Enhanced efforts towards surveillance, medical countermeasures, communications and research are all steps in the right direction.

World Tuberculosis Day: How EPIC researchers at U of T are making an impact

lanthierj — Fri, 24 Mar 2023 17:23:33 +0000

World Tuberculosis Day: How EPIC researchers at U of T are making an impact

lanthierj Fri, 03/24/2023 - 13:23

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Jacqueline Watt (left) and Lauren Ramsay are PhD students at the �ؿ�ζSM working to tackle tuberculosis (supplied images)

Betty Zou

Topic

Breaking Research

EPIC

Institutional Strategic Initiatives

Temerty Faculty of Medicine

Tuberculosis (TB) is preventable and curable, yet it remains one of the world’s most deadly infectious threats and a significant global health challenge.

About 95 per cent of cases occur in low- and middle-income countries but the disease still poses a significant public health concern in Canada, where it disproportionately affects Indigenous communities and people born outside the country. According to Health Canada, the rate of TB among Inuit peoples is roughly 15 times higher than the rate among the general population.

On World TB Day, U of T News examines how members of EPIC, the �ؿ�ζSM’s Emerging and Pandemic Infections Consortium, are working to tackle the disease – from creating better vaccines to gaining a deeper understanding of TB’s financial toll on patients and families.

Better vaccines

“The BCG vaccine has been used worldwide since the early 1970s and while we’ve known that there are limitations with the vaccine, no one has been able to come out with something better,” said Jacqueline Watt, a PhD student in Professor Jun Liu’s lab in the department of molecular genetics in U of T’s Temerty Faculty of Medicine.

The vaccine is typically given to babies and is effective in protecting against rare forms of TB where the infection spreads to multiple sites in the body. However, childhood vaccination offers limited protection in adults against pulmonary TB, the most common type of disease that affects the lungs. This is because it generates a relatively weak, short-lived immune response and is based on a bacteria species that is related (but not identical) to the bacteria that causes TB, Mycobacterium tuberculosis.

Watt and her colleagues are addressing both these challenges by developing a new vaccine candidate using M. tuberculosis. To turn the disease-causing bacteria into a disease-protective one, the researchers deleted a single gene from the bacteria’s DNA, effectively removing its ability to cause illness.

Their early results are promising. In animal models of TB, their vaccine candidate offered greater and longer-lasting protection than the BCG vaccine and stimulated a much more robust immune response.

“The next thing I want to do is look into why it could be more protective to see if we can learn more about what parts of the immune response are important for protection versus disease progression,” Watt said.

Researchers in the Liu lab are also uncovering new insights into how M. tuberculosis uses molecules called small RNAs to regulate gene expression. They have identified a protein they’re calling SRB that serves as a chaperone to help small RNAs attach to their targets. While similar proteins have been found in other bacteria, this is the first time that such a protein has been described in TB-causing bacteria.

In a recent experiment, the researchers found that the SRB protein binds roughly 800 different small RNAs. Many of them have roles in key processes like bacterial metabolism and stress response and could be good targets for new drugs to treat TB, which are badly needed to combat the rise in drug-resistant strains of M. tuberculosis.

Financial toll

Researchers are concerned that the financial toll of TB will have a greater impact on the equity-deserving groups that are disproportionally affected by the disease.

“In Canada, we know quite a bit about the cost-effectiveness of various TB interventions like screening programs and diagnostic tests, but we don’t know a lot about direct patient costs and costs to their caregivers,” said Lauren Ramsay, a PhD student working in the Institute of Health Policy, Management and Evaluation (IHPME) at the Dalla Lana School of Public Health.

Working with IHPME Professor Beate Sander, a senior scientist at the Toronto General Hospital Research Institute and adjunct scientist at ICES and Public Health Ontario, Ramsay and her colleagues recently launched an online survey for adults with active TB living in urban centres.

The survey asks patients and caregivers about costs that they’ve incurred related to their diagnosis and care such as bus or taxi fare, parking, food and missed work. Researchers aim to recruit 50 patients at three TB clinics in Toronto and one in Ottawa. Because TB predominantly affects Indigenous peoples and people born outside of Canada, they are offering translation services to ensure that language is not a barrier in completing the survey.

“From the patient and caregiver perspective, we expect that the costs will be quite significant because there is a mandatory isolation period that most people with TB have to complete. Depending on the type of TB and how responsive it is to treatment, this could be as long as several months in rare cases,” said Ramsay. “During that time, you’re unable to go to work and you’re relying on your network to support you financially.”

Ramsay will combine the results of the patient survey with estimated health-care costs for a cohort of nearly 8,000 people with TB. The data, which spans 2002 to 2016, will also allow the researchers to look at whether people with TB incur higher health-care costs over their lifetime, even after they’ve been cured of the disease.

“I hope that this work can shine a light on where costs are highest for specific groups of people and spur discussions about services that can be provided to reduce the financial inequities that result from and are worsened by TB,” she said. “If we want to reduce financial and health-related inequities, TB is a critical area to focus on.”

This story has been edited and condensed; you can see the original here.

Lessons learned during Ebola crisis can help manage Marburg outbreak: U of T expert

Christopher.Sorensen — Thu, 23 Mar 2023 15:08:31 +0000

Lessons learned during Ebola crisis can help manage Marburg outbreak: U of T expert

Christopher.Sorensen Thu, 03/23/2023 - 11:08

Cutline

A colourized transmission electron micrograph of two Marburg Virus particles (image courtesy of NIAID)

Betty Zou

Topic

Our Community

Emerging and Pandemic Infections Consortium

EPIC

Temerty Faculty of Medicine

Public Health

World Health Organization

Earlier this year, Equatorial Guinea declared its first outbreak of Marburg virus disease, with 11 confirmed deaths so far.

The Marburg virus – a rare but severe hemorrhagic fever which affects both people and non-human primates – belongs to the same family of viruses as Ebola. The disease presents with similar symptoms, including high fever, diarrhea, abdominal pain and cramping, and occasionally severe bleeding.

Rob Fowler, a critical care physician at Sunnybrook Health Sciences Centre and a professor in the department of medicine at the Temerty Faculty of Medicine at the �ؿ�ζSM, volunteered with the World Health Organization (WHO) on the frontlines of the Ebola outbreak in West Africa in 2014 and in Congo in 2018. In 2021, he co-chaired the WHO guideline development group that published the first guidelines for Ebola virus disease therapeutics.

He recently spoke with writer Betty Zou at the U of T-based Emerging and Pandemic Infections Consortium (EPIC) about the recent Marburg outbreak and what lessons health professionals can learn from the prior Ebola crisis to help manage this infectious disease.

What do we know about Marburg virus and how it’s transmitted?

Marburg is typically spread from an animal reservoir to other animals or to humans. When it gets into humans, there can be human-to-human spread through direct contact. The direct contact is often through bodily secretions, such as someone vomiting, having diarrhea or bleeding.

Once the virus gets onto a person’s hands, it can enter the body through mucus membranes like your eyes or the inside of your nose and mouth. In rare instances, we’ve seen health-care workers get infected through a needle-stick or sharps injury in the skin that allows the virus to directly enter the blood. And very, very rarely, people have found residual virus in certain bodily fluids that evade the immune response after the acute infectious phase has passed.

How did you react when you first found out that the cluster of people who died of suspected hemorrhagic fever had tested positive for Marburg virus?

Any time there’s a Marburg outbreak, it’s worrisome. Historically, it’s a virus that spreads efficiently from person to person and the mortality has typically been very high.

Like Ebola, this virus often shows up in areas that have underdeveloped health-care systems and a lot of characteristics within society at large that enable person-to-person spread. Tight living quarters is one example. These areas oftentimes don’t have the ability to limit virus spread because of a lack of access to consistent running water. So Marburg or Ebola outbreaks are, of course, very tough for patients and health-care teams, but also very difficult for the health-care system and the population at large to manage.

I feel for the folks that are in the thick of it right now because it’s very, very hard.

What lessons can we take away from the Ebola outbreaks over the past decade to respond to the Marburg virus disease outbreak?

When you have a disease that has a high mortality rate – mortality for Marburg virus disease can range from 25 per cent to 90 per cent – and is very transmissible, we really need to focus on prevention and trying to stop the outbreak from getting larger.

If you’re not living in an area where clinicians are able to send samples for rapid testing, then you can get behind very quickly in an outbreak. Having reference testing laboratories that are geographically nearby is critical. It’s also really important to have a culture of infection prevention and control embedded in health-care settings. The same precautions we use to prevent norovirus transmission in Canada would work well to protect people from more serious viruses like Marburg and Ebola.

If we can provide health-care teams with basic precautionary tools – gloves, gowns, eye protection, medical masks, access to running water and soap – combined with well-practiced infection prevention and control hospital processes, then that will help to prevent spread within health-care facilities.

Another key element is clear and effective messaging to the public about how we can prevent spread in the community. In addition to excellent infection prevention and control practices in hospital, you also need equal engagement in the community where the virus can otherwise spread.

Rob Fowler, second from right, with WHO colleagues, clockwise from bottom left: Sharmistha Mishra, Benon Tumwebaze, Senyonga Muzafalu, Adrienne Chan, Peter Kiiza and Mekonnen Tadesse at the Ebola Clinical Training Centre in Freetown, Sierra Leone (photo courtesy of Rob Fowler)

Where are we with vaccines and treatments for Marburg virus disease?

There currently isn’t an approved vaccine for Marburg virus. However, there are a number of promising early-phase evaluations underway. Having an effective and accessible vaccine is key in terms of prevention of infection.

For treatments, there are nonspecific antiviral medications that may be effective – including repurposed medications such as remdesivir, which has been used to treat people with COVID-19 and tested previously in Ebola virus outbreaks.

Important products in development include monoclonal and polyclonal antibodies that are specific to the Marburg virus. In our experience with Ebola, those antibody treatments were incredibly effective in reducing mortality. For Marburg, that probably represents one of the brightest hopes. To develop these antibodies, there has to be a will – not just medical or societal will, but an economic will – to do it. For Ebola, that economic will existed during and after the 2014 outbreak in West Africa. For Marburg, there has been less of an economic imperative for companies to dive into this, but hopefully that changes.

One of the things that the WHO can do is bring people together from academia, industry and other sectors and set priorities that help to send a signal and direct funds. That has happened recently for Marburg and now there are more candidate drugs being tested. I think there’s lots of hope that, as with Ebola, Marburg will have effective therapies.

What’s your outlook on this current outbreak?

It’s hard to share predictions being so far away from what’s happening on the ground, but I think it’s fair to say that we’re never out of a danger zone when an outbreak is ongoing. Sometimes you have an initial surge of cases being diagnosed, followed by concern among the public and people not seeking care or not getting tested out of fear. That can create a lull between the first set cases and the next bump in cases. The incubation period is usually about a week, but can be up to about three weeks.

Theoretically, if you go three weeks without a new case, you might think that the outbreak is clearing. However, that assumes you know about all the new cases – which is almost never true. There’s a relatively large risk that there will be unknown cases. That’s why we generally go through at least two 21-day periods without a new case before we think an outbreak is over.

How can the EPIC community help respond to outbreaks like this one – now and in the future?

There’s so much expertise in the EPIC community – and in the Toronto and Canadian communities more broadly. I think we really have had an outsized influence on vaccine and therapeutic development, diagnostic testing and clinical care.

Canada has been a leader in developing vaccines and monoclonal antibody treatments that were very helpful during the 2014 Ebola outbreak in West Africa. Supporting lab-based diagnostic capacity in Africa was also incredibly helpful. The National Microbiology Lab in Winnipeg has been very good at supporting other countries and helping them build up their diagnostic capacity.

Canadians have helped to build the foundations of excellent acute and critical care for patients with Ebola – this goes such a long way to reduce mortality even when there isn’t a specific therapy available. Yet, all of this requires people to say that it’s not just someone else’s issue – it’s our collective issue that we can bring our expertise and resources to help with. It’s about individual people asking themselves the question, “Do I have something to offer?” The answer is almost always, “Yes.”

Emerging & Pandemic Infections Consortium (EPIC)

mark.teo — Thu, 16 Mar 2023 20:42:41 +0000

Emerging & Pandemic Infections Consortium (EPIC) mark.teo Thu, 03/16/2023 - 16:42

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