It’s a warm and sunny summer day, but all that Dartmouth resident Sarah MacDonald wants to hear is that it’s miserable outside.
MacDonald, 21, is isolating in a hospital room for 16 to 21 days and being exposed to whooping cough — by choice — as part of the first controlled human infection model study in Canada that requires a full containment facility.
“When people try to talk to me about the weather, I’ll say, ‘Don’t tell me that it’s nice out. I only want to hear about the rain,’” MacDonald joked in a video call from her isolation room on Tuesday.
“It’s summer, so that part of being in here is kind of unfortunate. But it’s going to make a difference, so it’s worth it.”
The Canadian Center for Vaccinology’s (CCfV) first human challenge trial has officially kicked off in Halifax. Last week, the study’s first three participants were safely infected with mild cases of pertussis (whooping cough) at the center’s Challenge Unit located in the IWK Health Centre.
Building a better vaccine
The trial will help researchers better understand how the acute and highly contagious bacterial respiratory tract infection (caused by Bordetella pertussis bacteria) infects the body. It will also fill in gaps about pertussis vaccine infectivity, immune response to the infection, and pathogenesis (the disease’s development).
“Pertussis is probably one of the most infectious agents. Measles is number one of all the vaccine preventable diseases, and pertussis is probably number two. It’s a very infectious bacteria,” CCfV director Dr. Scott Halperin said in an interview.
“And while the vaccine is very good, it’s not good enough. So there is a real need for better vaccine. The whole reason behind the model is to understand the disease better so we can build a better vaccine.”
Halperin said whooping cough (so-named for the distinctive noise created when air is inhaled after a patient’s vigorous coughing brought on by the disease) has never been completely controlled despite decades of vaccination programs. Immunity provided by infection and vaccination don’t provide life-long protection.
A pertussis background sheet provided by the CCfV highlights why understanding the disease’s waning immunity is important.
Older people who are only partially immune due to a previous illness (or from fading pertussis vaccination immunity) are a “major” source of infection for infants. That group also happens to be “at particular risk” for pertussis-related complications and death.
400,000 deaths each year
Between 20 million and 40 million cases of pertussis are reported globally each year. About 400,000 of those cases result in death.
Whooping cough outbreaks tend to occur cycles of three to five years. While the illness is typically mild in adults, pertussis symptoms can be severe in unvaccinated and under-vaccinated infants.
It’s one of the leading causes of death among non-immunized children in developing countries and in areas where there’s low vaccine coverage.
“It was probably best controlled around the 1980s. In the 1980s, we started seeing a slow rise again in the number of cases,” Halperin said.
Health Canada and US agencies onboard
In addition to being in the CCfV’s highly specialized 10-bed hospital unit designed to fully contain respiratory infections, participants are continually surrounded and overseen by health care personnel. They’re also given the antibiotic azithromycin, considered an “extremely effective” pertussis treatment.
Halperin said while human challenge models have been conducted in Canada, none involved the use of pathogens that required full containment facilities.
“In Alberta several years ago, they were doing some rhinovirus, so the common cold, challenges,” he said.
“While it’s better to do them in a unit like ours, people have done them by reserving a wing of a hotel and just hoping nobody else walks by. I think a lot of people are discouraging of that, but you can get by with very mild pathogens.”
There are only two units in Canada with full containment facilities — the IWK’s 10-bed unit and an eight-bed unit at Montreal’s McGill University.
“You really need a unit that has full containment facilities so that the people who you infect don’t infect others in the community or outside,” Halperin said.
This human challenge trial also reaches beyond Canada’s borders. Researchers are collaborating with the Centers for Disease Control and Prevention (CDC) in the US and have approvals from not only Health Canada, but the US Food and Drug Administration (FDA).
“It has been a long time in the making. It’s a long term plan and it’s exciting to get the first participants in and get it going. It’s a platform, and I think that’s the important part. It’s not a study,” Halperin said.
“It’s building a platform that many studies will be built upon, and the ultimate goal is to improve pertussis vaccines and get to the point where we really control whooping cough. It’s a multi-faceted approach, and this is going to be an important component of it.”
‘Take pertussis research a long way’
CCfV’s lab director and clinical scientist Dr. May ElSherif said conducting a controlled human infection model is possible with pertussis because the disease is fairly mild in adults and doesn’t cause long-term or chronic issues.
In addition, successful antibiotic treatment is available and patients are no longer infectious after a five-day course.
Although pertussis has been widely studied in animal models, those models prove somewhat limiting because the pathogen only naturally spreads in humans. That’s why a controlled human infection model will prove invaluable.
“The platform will hopefully take pertussis research a long way. In addition to the platform being available for future applications, we are also collecting a repository of samples for other pertussis researchers to use,” ElSherif said.
“Nobody knows or does all the work. It has to be clinicians, immunologists, every speciality of research. That’s the great thing with the model, and then of course the future applications of the model.”
The pertussis human challenge trial requires two separate studies. The first will determine what dose results in mild, common cold symptoms among the 70% to 90% of participants who receive it. All will get antibiotic treatment to prevent severe illness.
The second study will confirm the dose derived from the first study. ElSherif said this will help researchers better describe the clinical course of the disease. They’ll repeat the dose determined by the first study with 10 participants. Another 10 will receive a higher dose, while 10 other volunteers will get a lower dose.
“There are so many advantages for the second study. First of all, now that we have monitored participants in study one, we’ll know what the incubation period will be, so that’s where we start focusing on how they feel when the symptoms start, how long symptoms last,” ElSherif explained.
“Also by then we would know when the optimum time is to collect samples, to study the disease for their own immune response. So (the first study) is going into not knowing much of what you’re going to get. With the second one, we really know what we’re getting so we can then focus and zoom in more on the fine points of interest and the events of interest for the disease.”
‘It sounds worse than it actually is’
Caitlin Ferry, 32, is one of the three participants currently in the Challenge Unit. From her isolation room, the Halifax resident said she was drawn to the study because the respiratory nature of pertussis makes it tricky to study without confinement.
As a research assistant working with a social psychologist, she also knows how important it is to find willing participants.
“I get super excited when participants are like, ‘Yeah, I’ll do the cockamamie thing that you’re thinking of doing in pursuing research,’ so I wanted to participate,” Ferry said.
A day on the unit involves waking up early, ordering breakfast or making coffee in her room, and prepping for the daily tests.
“I will go through saliva sample, urine sample, blood draws and nasal wash. And then I get a bit of a break to eat lunch,” Ferry said.
“I’ll work most of the day, I’ll get a couple more visits from staff to do the nasopharyngeal aspirate (nasal wash specimens), and then more vitals.”
Before enrolling in the trial, Ferry had a list of questions and concerns that were so thoroughly answered by the participant coordinator that she felt confident about participating. Because pertussis is typically mild in adults, there’s around the clock care, and a safe, effective antibiotic was provided, she also had no concerns about her own safety.
Beyond that, Ferry said her own enthusiasm has been buoyed by the obvious and ongoing excitement of the study’s researchers and staff.
“The excitement was palpable from day one. Folks have been clearly working on this for a very long time,” Ferry said. “From a researcher perspective it’s super, super exciting to get something actually going and to use this beautiful facility.”
While she works remotely during the day in between scheduled lab tests, her evenings are spent talking to and virtually watching shows with her partner. She also started a beading project she expects to finish before her isolation is over.
She described participating in the trial as “fulfilling,” and encourages eligible Nova Scotians to consider signing up.
“I think it sounds worse than it actually is. A lot of us are very familiar with quarantine, and it does come to an end. This is a short timeframe,” Ferry said. “Continuing to make use of the Internet and making use of video chat and phone calls can help a lot to stave off any sense of loneliness or isolation.”
‘They can’t do it without us’
Sarah MacDonald said although she’s missing out on two to three weeks of summer, good weather, and hanging out with her friends, participating in the trial is worth it not only because she’s helping with pertussis research.
The St. Francis Xavier University student said the financial compensation really sweetens the deal.
Challenge study participants receive $200 per day/night spent in the Challenge Unit and $50 for each follow up visit. Total reimbursement can amount to $4,630.
“I’m working remotely this summer, so I knew I’d be able to still work and be here for the study,” MacDonald said. “And it will be nice to have some extra money going back. I’m still a student so (it’s very helpful) to pay for classes and rent.”
In between remote work, lab tests, and keeping in touch with friends and family, MacDonald said she’s having fun. She has been painting while in isolation and expects to have a “nice little collection” by the time she leaves the facility.
“I was excited to have a couple of weeks with no responsibilities,” MacDonald said. “I don’t really have to do anything. I’m being well taken care of and I get three meals a day.”
While she describes the IWK Health Centre’s hospital food as “great,” MacDonald said challenge trial participants have also had take-out and can order food for delivery to the unit on their own dime. She hopes notions about hospital food don’t discourage potential participants from enrolling in the study — something she’s actively encouraging healthy and eligible Nova Scotians to do.
“It’s really worth it. They need people, and they can’t do it without us,” MacDonald said. “So you should come help. And it’s not as bad as it sounds. It’s actually pretty good.”
Researchers are actively recruiting for the pertussis trial. Volunteers must be between the ages of 18 and 40 years old and be healthy, informed, and consenting. More information can be found here.