Ishani Nath

Why it's important to get your 2024 flu shot – and how to get it

Christopher.Sorensen — Thu, 07 Nov 2024 14:23:42 +0000

Why it's important to get your 2024 flu shot – and how to get it

Christopher.Sorensen Thu, 11/07/2024 - 09:23

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The flu vaccine is especially important for adults aged 65 years or older, pregnant people and individuals who have medical conditions that put them at higher risk of complications from influenza infection, ��TV experts say (photo by Canva)

Ishani Nath

Topic

Our Community

Centre for Vaccine Preventable Diseases

Dalla Lana School of Public Health

Leslie Dan Faculty of Pharmacy

Subheadline

��TV experts on the flu vaccine, where it's available and when's the best time to get it

None of Jeff Kwong’s patients has asked him about the influenza vaccine yet this fall – but the family physician wants to make sure that getting vaccinated is on people’s radar.

That’s because influenza causes an estimated 12,200 hospitalizations and 3,500 deaths in Canada each year.

Moreover, public health officials are doubly concerned this season because of a strain of influenza circulating in wild birds and some agricultural animals. While the risk of avian influenza to the general population remains low, A H5N1 has nevertheless infected some humans who have close contact with sick animals.

“While current influenza vaccines don’t protect against avian influenza, they may reduce the risk of infection with human influenza viruses and therefore the possibility of both human and avian influenza viruses infecting someone at the same time,” says Kwong, an associate scientist at Sunnybrook Research Institute and professor at the University of Toronto’s Dalla Lana School of Public Health.

“These co-infections could create a new ‘version’ of influenza that might spread easily among humans and cause very severe disease.”

What is influenza?

Influenza is a respiratory disease that typically causes fever, cough and body aches. While many people recover from influenza within a week to 10 days, for some, an infection can cause severe illness.

“It’s a good idea for everyone aged six months or older to get an influenza vaccine, but it’s especially important for adults aged 65 years or older, pregnant people and individuals who have medical conditions that put them at higher risk of complications from influenza infection,” says Kwong, who is the associate director of ��TV’s Centre for Vaccine Preventable Diseases (CVPD), adding that medical conditions of concern include heart diseases, diabetes and even obesity.

The most common reason Canadians give for not getting a flu shot is because they don’t think it’s necessary – a sentiment Natalie Crown, associate professor, teaching stream, in the Leslie Dan Faculty of Pharmacy, has heard before.

“Sometimes people will tell me they don’t get vaccinated because they think they don’t need it – for example, they’ll say they are healthy and rarely get sick themselves,” says Crown, who is also a CVPD member. “The reality is getting the flu vaccine is one of most effective ways of protecting ourselves from the flu and its complications, and we are doing our part to protect the more vulnerable people around us who are at higher risk of developing complications from the flu.”

��TV’s Discovery Pharmacy's new location in the atrium of the Leslie Dan Faculty of Pharmacy building is among the places ��TV community members can get their shot across the three campuses (photo by Dana Thompson)

When to get the influenza vaccine

The flu season doesn’t have a precise start and end date. According to the National Advisory Committee on Immunizations (NACI), influenza season typically starts in December but can start as early as October or as late as February.

Influenza vaccines were first made available for high-risk individuals and then for the public, beginning in late October and early November.

Since antibodies generated by influenza vaccines gradually decrease over time, Kwong takes a strategic approach to timing his influenza vaccine – but notes that may not be the best approach for everyone.

“I tend to wait until around mid-November to get my influenza vaccine, so I will be protected in December when influenza activity often starts, and I can be fairly confident that the vaccine will still offer some protection up to May,” says Kwong. “However, for those at high risk, getting the influenza vaccine in late October is not a bad idea because occasionally influenza activity can start earlier than December.”

Where to get the influenza vaccine

Influenza vaccines are typically available at local community pharmacies, through primary care providers or at dedicated community clinics offered by public health units across the country.

Members of the ��TV community can also visit UTogether for more information on where to get influenza, as well as COVID-19, vaccines across the university’s three campuses.

Learn more about vaccines at UTogether

Do you have questions about children's vaccines? A new phone line has the answers

Christopher.Sorensen — Mon, 05 Feb 2024 14:18:11 +0000

Do you have questions about children's vaccines? A new phone line has the answers

Christopher.Sorensen Mon, 02/05/2024 - 09:18

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(photo by SDI Productions/Getty Images)

Ishani Nath

Topic

Our Community

Centre for Vaccine Preventable Diseases

Temerty Faculty of Medicine

Pediatrics

Dalla Lana School of Public Health

Hospital for Sick Children

Vaccines

Subheadline

The SickKids Vaccine Consult Service (VCS) aims to answer caregivers’ questions about all pediatric vaccinations

Canada is in the midst of respiratory illness season, yet the number of individuals getting the updated COVID-19 and flu vaccines remains low. The number of children receiving routine vaccinations has also dropped since the pandemic.

For the past few years, questions about vaccines dominated headlines and internet searches. Is this vaccine safe? Will it work? Who needs to get vaccinated?

Shaun Morris, a clinician scientist at The Hospital for Sick Children (SickKids) and an associate professor of pediatrics in the University of Toronto’s Temerty Faculty of Medicine, and Pierre-Philippe Piché-Renaud, who is pursuing a clinical and research fellowship at SickKids and graduate studies at ��TV’s Dalla Lana School of Public Health, routinely field these types of questions from parents and caregivers.

Both are members of the Centre for Vaccine Preventable Diseases (CVPD) at the Dalla Lana School of Public Health.

Shaun Morris and Pierre-Philippe Piché-Renaud (supplied images)

To help boost confidence in vaccination through easy access to reliable, evidence-based information, Morris and Piché-Renaud have launched a new pilot project running until the end of March.

The SickKids Vaccine Consult Service (VCS), part of a larger project funded by the Public Health Agency of Canada (PHAC), is offering a phone service staffed by nurses to answer caregivers’ questions about all pediatric vaccinations. The intent is to make vaccine information more accessible and, ultimately, help parents make the best, most informed decision for their child, Piché-Renaud says.

Building on previous success

The pilot project builds off the success of a COVID-19-specific VCS phone line that ran from October 2021 to March 2023. The COVID-19 VCS received more than 2,700 calls from caregivers asking about COVID-19 vaccines for children. The phone line was staffed by health-care professionals who provided information tailored to each individual circumstance, including living situation or medical history – answers that could not typically be found on the internet.

The nurses fielding calls were trained to create an open and safe environment, explains Julia Orkin, the SickKids COVID-19 VCS medical lead and an associate professor in ��TV’s department of paediatrics in the Temerty Faculty of Medicine.

“It wasn’t, you know, ‘you must do this,’ it was really a shared supportive conversation,” she says. After calling in, 83 per cent of caregivers surveyed said their questions and concerns were addressed, and more than 60 per cent said they would proceed with vaccination.

The new phone service expands beyond the COVID-19 VCS by fielding questions not only about COVID-19 vaccines but all childhood immunizations. The service is open to anyone in Ontario, with a specific focus on patients with existing medical concerns and equity-deserving populations throughout the Greater Toronto Area.

Insurance coverage and internet access aren’t required to book a VCS consultation and translation services are available.

Piché-Renaud says that the conversations are about “taking it one step at a time, meeting parents where they are, and addressing their concerns.”

Research has shown that COVID-19 vaccine uptake was lower among certain groups – for instance, certain racialized and lower income populations. To reach these communities, Morris and Piché-Renaud are working with organizations like Black Creek Community Health Centre, Taibu Community Health Centre and the Paediatric Alliance of Ontario.

“The messaging is going to come through the people that [caregivers in these communities] already know and work with,” says Piché-Renaud.

Meeting an urgent need

Providing information on the importance of childhood vaccinations is particularly urgent.

“Immunization coverage for a variety of diseases is lagging behind, leaving kids susceptible to infections and outbreaks that are completely preventable. It’s essential to provide parents with clear, individually tailored messaging from a trusted source to enable them to make informed decisions for their children,” says Shelly Bolotin, director of the Centre for Vaccine Preventable Diseases and an associate professor at the Dalla Lana School of Public Health.

During the pandemic, routine childhood immunizations for preventable diseases like meningitis, measles and polio were set back to levels not seen since 2008. The proportion of Canadians who view vaccines as important for children also dropped from 91 to 82 per cent, according to UNICEF’s 2023 State of the World’s Children report. Canada has since seen cases of pertussis (whooping cough) and other vaccine preventable diseases.

“We’re still seeing kids who show up at SickKids and other paediatric hospitals with vaccine preventable illnesses, like certain types of meningitis,” says Piché-Renaud.

The physicians hope that through the VCS phone line and a related project working with SickKids pediatricians and patients, they will be able to better understand why some children are not getting vaccinated. With this information, they can then develop resources such as educational websites, or improve access to vaccination sites.

Making trusted vaccine information more accessible

Morris and Piché-Renaud encourage Ontario parents wondering about childhood vaccines to book a consultation appointment at SickKids VCS.

For Morris, empowering patients and families to make the best health decisions for themselves is one of the most important aspects of his job. Services like the VCS phone line help achieve that goal by “enabling people to connect to trusted sources of information and navigate through the quagmire of not good information, which is probably more common in the realm of immunization than in most areas.”

Infants are vulnerable to chickenpox earlier than previously thought: Study

Christopher.Sorensen — Fri, 24 Nov 2023 16:57:43 +0000

Infants are vulnerable to chickenpox earlier than previously thought: Study

Christopher.Sorensen Fri, 11/24/2023 - 11:57

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(photo by Mixmike/Getty Images)

Ishani Nath

Topic

Breaking Research

Temerty Faculty of Medicine

Dalla Lana School of Public Health

Hospital for Sick Children

Research & Innovation

Subheadline

The findings are in line with previous research indicating that the level of antibodies babies receive from their mothers at birth wear off quickly

Infants are not protected against the varicella-zoster virus, the virus that causes chickenpox, for several months before they are eligible for vaccination, a new study has found.

In some cases, infants may be at risk of infection as early as one month after they are born.

“Antibodies transferred through the placenta during pregnancy protect babies against many infectious diseases when they are born, including the varicella virus,” says Associate Professor Shelly Bolotin, director of the University of Toronto’s Centre for Vaccine Preventable Diseases (CVPD) at the Dalla Lana School of Public Health and the study’s first author.

“However, our research found that that protection fades quickly, leaving infants vulnerable to infection for many months before they are eligible for chickenpox vaccine, which in Ontario is given at age 15 months.”

Using samples collected at The Hospital for Sick Children (SickKids) in Toronto, researchers looked at the antibody levels in blood samples from 187 infants up to one year of age. They found that antibodies protecting against varicella wore off quickly, and that almost 80 per cent of infants were susceptible to infection by the time they were three months old. At six months, all the infants studied were susceptible to chickenpox infection.

The findings, published in the journal PLOS One, are in line with previous research indicating that the level of antibodies babies receive from their mothers at birth wear off quickly.

“Although many people think of chickenpox as a mild childhood infection, and it generally is, it can cause complications like skin infections, pneumonia or inflammation of the brain, particularly in young children,” says senior study author and CVPD member Michelle Science, an infectious disease consultant and medical adviser for infection prevention and control at SickKids.

Science, who is also an assistant professor in the Temerty Faculty of Medicine, notes that infants are at a higher risk of complications than older children, and are the most likely age group to be hospitalized. Prior to the vaccine’s availability, Canada saw approximately 350,000 varicella cases per year with 1,500 people hospitalized annually.

The chickenpox vaccine helps protect individuals from infection as well as the serious complications that can occur. Getting vaccinated also helps lower the number of cases of chickenpox in all age-groups in a community – even in those too young or too old to be vaccinated.

The chickenpox vaccine is already part of routine childhood vaccination in several countries, including Canada, Australia, Germany and the United States. In the U.K., the Joint Committee on Vaccination and Immunization recently recommended that a chickenpox vaccine program should be introduced into the routine childhood immunization schedule, and that a catch-up program for older children should also be implemented in the future.

“The results of our study confirm that everyone around an infant should be protected from chickenpox, either because they were previously infected or through vaccination,” says Science.

She adds that these results may be helpful for both parents and health-care providers, who should be thinking about varicella whenever they see a rash, even in a young baby, and in the assessment of an infant’s risk of infection if they are exposed to a case.

Bolotin and her co-authors noted that more research is needed on varying demographics and whether factors like breastfeeding or a mother’s age influence their baby’s antibody levels.

In the meantime, this study is a reminder of the importance of immunizations.

“Vaccination is not only about protecting yourself, it’s also about protecting your family, friends, and neighbours,” says Bolotin. “Our study further affirms how getting vaccinated can protect some of the most vulnerable – and in this case, the newest – members of our society.”

BlueDot is using AI to get ahead of the next pandemic

Christopher.Sorensen — Tue, 15 Aug 2023 18:11:56 +0000

BlueDot is using AI to get ahead of the next pandemic

Christopher.Sorensen Tue, 08/15/2023 - 14:11

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Kamran Khan, founder and CEO of BlueDot, is a scientist at Unity Health Toronto and a professor in the department of medicine in the University of Toronto’s Temerty Faculty of Medicine and the Dalla Lana School of Public Health (photo by JORGE UZON/AFP via Getty Images)

Ishani Nath

Centre for Vaccine Preventable Diseases

Temerty Faculty of Medicine

Artificial Intelligence

Dalla Lana School of Public Health

Global

Subheadline

Startup's data-driven forecasts extend as far as 10 years into the future

The Toronto offices for Kamran Khan’s BlueDot, which uses artificial intelligence to flag potential infectious disease outbreaks around the world, are located at the edge of Lake Ontario – appropriate for a company that, similar to a lighthouse, signals when there’s danger ahead.

“We use the internet as a medium for surveillance to detect early signals of outbreaks anywhere in the world before they’re officially reported by public health agencies,” explains Khan, a scientist at Unity Health Toronto and a professor in the department of medicine in the University of Toronto’s Temerty Faculty of Medicine and the Dalla Lana School of Public Health.

He breaks BlueDot’s work down into three key components: identifying threats early, rapidly assessing their risks and likely trajectories, and helping organizations to turn these insights into swift action.

“The whole purpose here is to compress time, because ultimately, time is the enemy when you’re dealing with an outbreak,” says Khan, a member of ��TV’s Centre for Vaccine Preventable Diseases.

BlueDot’s intelligence platform combines a computer’s ability to understand human language, known as natural language understanding (NLU), and machine learning, a form of AI that imitates humans’ ability to learn and gradually become more accurate. The platform sorts through massive volumes of online information – ranging from news reports, social media sites, government websites, and more – from around the globe, in more than 130 languages, every 15 minutes of every day.

“We’ve basically trained a machine to pick up early clues around the world and around the clock,” explains Khan.

The clues get cross-referenced with historic data to determine what is outside of the norm, and then triaged into high, medium and low risk threats. Global data – including commercial air travel data, climate conditions, mosquito observances and population demographics – are also added to the mix to determine whether a threat could spread.

This data analytic sequence is how BlueDot accurately predicted a Zika virus outbreak in Florida six months before it occurred, and sounded the alarm about COVID-19 nearly a week before it was officially reported by public health organizations like the CDC and WHO.

As COVID-19 restrictions have eased around the world, public health experts are now shifting focus to the next set of emerging global threats – what could spark the next pandemic, and will we be ready? Writer Ishani Nath sat down with Khan to learn how BlueDot uses artificial and human intelligence to help answer these questions and more.

How does BlueDot work – is it all done by machines or do humans play a role?

Our belief is that machines should play to their strengths, and humans should play to their own. There’s a whole process of using machine learning for gathering, organizing and ingesting unstructured data that’s multilingual and creating structure out of it 24 hours a day, 365 days a year. And then there’s a series of analytics and human intelligence that helps us differentiate what threats demand our immediate attention and anticipate where, when, and how they will impact the health of populations around the globe. Recent advances in generative AI are also creating opportunities for machines to produce “intelligence briefs” – but given the vital importance of these outputs, there will always be a need for human oversight.

For example, we first have to determine whether a threat appearing somewhere in the world is unusual. It’s important to remember that machine learning is only as good as the historic data that we train it on. But when we’re dealing with newly emerging diseases, we are often dealing with threats where there is little or no historic data. For instance, if we identify an outbreak of an influenza-like illness occurring in the Northern Hemisphere in July, we know that is unusual compared with observed historic trends. But for some newly emerging threats like COVID-19 – where we don’t have historic data – we have to tap into our in-house expertise in public health sciences, clinical medicine, pediatric infectious disease and veterinary sciences, while also collaborating with experts from academia and governments around the world to rapidly characterize and assess those novel threats.

Notable Event Alert screenshot from BlueDot (supplied image)

When it comes to vaccines, how can this information improve which threats get addressed?

Well, we’re not just considering what constitutes a vaccine-preventable disease today. By working with private sector organizations like pharmaceutical companies, we’re helping support decisions about what they should be investing in in terms of R&D to develop new vaccines for diseases where the landscape is going to significantly change in the future – for example, because of climate change.

And when vaccines are in market, are they manufacturing enough in relation to forthcoming demand? Are they producing it at the right time? Are they distributing it optimally and equitably? BlueDot’s public and private sector clients are using our intelligence to support key decisions – not just about what’s happening now, but also what’s coming next.

You mentioned climate change. Do you also consider climate and environmental data?

Yes. Going back to Zika for example – what we were able to determine and publish in the Lancet is where we would expect lots of infected travellers and no local outbreak versus lots of infected travellers, as well as environmental conditions suitable for a local outbreak. What happened six months later is entirely aligned with what we anticipated.

We’re now working on taking the latest climate change models and intersecting them with ecological models for mosquitoes and insects so we can anticipate where those insects will survive and thrive in new areas. If you don’t have the mosquito that can transmit a particular virus, then there’s no possibility of a local outbreak from that virus. But these ranges are changing. In some cases, it’s actually becoming too hot and they’re not able to effectively transmit. But in other cases, conditions are becoming more hospitable.

How far into the future do these forecasts extend?

We’re doing these forecasts looking 10 years into the future. The main reason we’re looking out that far, realizing there’s more uncertainty as you go further out, is that we are working with pharmaceutical and life sciences companies that develop and manufacture vaccines, therapeutics, diagnostics, PPE, disinfectants and more. Their interests are understanding and anticipating future demand. Do they invest in a chikungunya vaccine or a vaccine for a different infectious disease? A vaccine manufacturer has to consider: What am I investing in today, how many lives could it protect and is this a sound business decision recognizing that it might take a decade or more to actually bring that vaccine to market?

What’s next for BlueDot?

Building on top of large language models (LLMs) like GPT, we’ve developed some early capabilities where you can ask our platform questions in natural language. Like, “Every day, tell me how many cases of COVID there are in my location this week and if there’s an increase of 10 per cent or more above baseline, notify me.” Or, “Tell me how many travellers on flights are coming from London to Toronto in the next three months and the likelihood of an imported case of measles showing up.” We’re still actively in R&D mode but building on top of LLMs is showing a lot of promise.

How does working in this space shape how you personally feel about the future?

I’m excited by the fact that technology can help humans in powerful ways, but understand that humans have to help themselves. I often quote the Spanish-American philosopher George Santayana who said, “Those who cannot remember the past are condemned to repeat it.” My worry is we’re quick to forget and that we will repeat the cycle of panic followed by neglect until humanity realizes we have to be proactive – because we know it’s a certainty we will be dealing with more threats in the future. What I often ask myself is, what things can I do today that will have a tangible and positive impact on the lives of others?

This interview has been edited and condensed for clarity.

Research aims to help parents prepare for RSV immunizations for children

siddiq22 — Wed, 19 Jul 2023 18:50:09 +0000

Research aims to help parents prepare for RSV immunizations for children

siddiq22 Wed, 07/19/2023 - 14:50

Cutline

(photo by FatCamera/Getty Images)

Ishani Nath

Topic

Breaking Research

Centre for Vaccine Preventable Diseases

Pediatrics

Dalla Lana School of Public Health

Immunology

Vaccines

Two new ways to protect children from respiratory syncytial virus, better known as RSV, may soon be available in Canada – and a University of Toronto researcher aims to ensure parents can make an informed decision about vaccination.

Even though the majority of children will get infected by age 2, “most parents do not know about RSV,” says Tiffany Fitzpatrick, an assistant professor at the Dalla Lana School of Public Health and a member of the Centre for Vaccine-Preventable Diseases.

She’s heard from parents who only learned about the virus – which has a similar seasonal pattern to the flu and symptoms such as coughing, wheezing, and fever – after their child caught it. Although most cases are mild, RSV can lead to more severe illness like pneumonia, and is the leading cause of infant hospitalization in Canada and many other countries.

Tiffany Fitzpatrick (supplied image)

Health Canada is in the process of approving more immunization options to protect children against RSV – an antibody-based drug that may eventually be used to protect all newborns from severe RSV illness and a vaccine for pregnant people that would pass protection from parent to newborn. The potential impact of these new options, both for the health of Canadians and an already overburdened health-care system, is massive.

“This could be really revolutionary,” says Fitzpatrick, who is also a scientist at Public Health Ontario.

That is, as long as parents have the information necessary to make an informed decision about vaccination and understand the severity of RSV – a task that Fitzpatrick plans to address with her research, recently funded by the Canadian Immunization Research Network.

New RSV immunization options coming to Canada

The new RSV prevention drug and vaccine have been a long time coming. Despite more than 60 years of research, options for protecting vulnerable populations (such as newborns) against the virus remained limited – until now.

Currently, the only option for protecting newborns at the highest risk of hospitalization (those born very prematurely, born with heart or lung conditions, or those born in remote communities without quick access to medical care) is a monoclonal antibody therapy called palivizumab. The drug cannot treat RSV, but if injected every month during RSV season, it can help prevent severe illness.

However, palivizumab comes with a high price tag and needs to be administered every month – sometimes for up to six months – so it is typically reserved for high-risk infants. Health Canada recently approved a longer-acting antibody-based drug, nirsevimab, which would only require one injection per RSV season. Nirsevimab is expected to cost much less than palivizumab, and it may eventually be an option for all parents.

A vaccine for pregnant people to help protect newborns from infection is also in the pipeline and may be approved as soon as later this year. The vaccine, recently approved in the U.S. for older adults, offers the prospect of protection against RSV infection – not just disease – to all newborns for the first time.

This RSV vaccine, made by Pfizer and known as RSVpreF, would be given to individuals in their late second or third trimester of pregnancy. The vaccine prompts the pregnant person to makes antibodies that are transferred to their fetus, so their child is born with some protection against RSV. In a worldwide, double-blind clinical trial with pregnant women published in The New England Journal of Medicine, the RSVpreF vaccine was more than 81 per cent effective at protecting infants against serious health issues caused by RSV, like lower respiratory tract illness.

Health Canada is on the verge of approving a new drug and a vaccine to protect children from respiratory syncytial virus (RSV), shown here in an electron micrograph image (image by NIAID)

Speaking with parents about RSV and vaccination

In advance of the rollout of nirsevimab and Health Canada’s consideration of RSVpreF data, Fitzpatrick is listening to parents and learning about their understanding of RSV and potential concerns. Her research will involve conducting interviews with parents across Canada and using the information to create tailored educational materials that address questions and provide the information parents may need as they consider their future RSV immunization options.

“We need to start planning now to make sure that parents are anticipating this, and they have the information they need to be able to make that decision,” she says.

In addition to surveys and interviews, Fitzpatrick and her collaborators will be engaging with populations more vulnerable to RSV. For instance, research indicates that certain living conditions can play a role in a child’s risk for RSV.

“We know if a child is exposed to mould, or if they live in a crowded house, they’re much more likely to catch any respiratory virus and for it to become a much more severe disease,” Fitzpatrick says.

Specific regions and demographics are also disproportionately impacted by RSV. Collaborators on Fitzpatrick’s study will focus on parents in Nunavut – an area that has the highest rates of RSV hospitalization in the world.

“They’re going to be working with community partners there to understand the unique barriers and motivators for RSV immunization in Inuit communities,” she says.

Fitzpatrick is aiming to have the educational materials from her study available in time for next year’s RSV season, when nirsevimab and vaccines for pregnant people will hopefully both be available.

“I hope this research provides parents with the information that they need to make the decision that’s right for them,” she says, noting that as a public-health practitioner, she ultimately hopes people decide to get immunized “so we can prevent as much RSV disease as possible.”

Ishani Nath

Why it's important to get your 2024 flu shot – and how to get it

What is influenza?

When to get the influenza vaccine

Where to get the influenza vaccine

Learn more about vaccines at UTogether

Do you have questions about children's vaccines? A new phone line has the answers

Building on previous success

Meeting an urgent need

Making trusted vaccine information more accessible

Infants are vulnerable to chickenpox earlier than previously thought: Study

BlueDot is using AI to get ahead of the next pandemic

Read more about BlueDot at CTV News

Research aims to help parents prepare for RSV immunizations for children

New RSV immunization options coming to Canada

Speaking with parents about RSV and vaccination