Evidence of meeting #119 for Veterans Affairs in the 42nd Parliament, 1st session. (The original version is on Parliament’s site, as are the minutes.) The winning word was mefloquine.
A recording is available from Parliament.
Consultant Public Health Physician, As an Individual
Yes, and there were none in the chloroquine and proguanil arms, so that, to me, represents—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
I'm sorry to cut you off.
If you look at the incidence of psychotic disorders in the population, two out of 300 goes, if anything, a little lower than what you'd have in the general population.
Can you really extrapolate any sort of statistical significance from two instances of psychotic symptoms among 300 people?
Consultant Public Health Physician, As an Individual
If you're studying soldiers for six weeks, you don't get two soldiers out of 600 becoming psychotic—one of them committing suicide and one of them being confined to a mental home. By definition, soldiers are psychologically healthy, so there was something happening that was causing these terrible events in these soldiers.
I should add that the trial, towards the end, actually collapsed. I have to say, my superiors could see that it wasn't going the way they wanted, and I was taken off the control of that particular trial and sent to Bosnia. I never even found out about the guy who'd committed suicide until several years later when, by chance, I discovered that had occurred.
There was a coroner's inquest into that case, and the coroner asked, “Is it the case that this soldier was taking mefloquine?” I was in Bosnia at the time—I didn't even know that there was an inquest—and the coroner was told, “We don't know. He might have been taking mefloquine. We just can't find out. It's unfortunate that he died, committed suicide, but anyway, mefloquine doesn't cause anything particularly.... It doesn't affect soldiers any more than it does civilians”, which is a kind of fudgy answer. Therefore, the conclusion—
Liberal
Doug Eyolfson Liberal Charleswood—St. James—Assiniboia—Headingley, MB
Okay. I'm sorry to cut you off.
How much time do I have, Mr. Chair?
Consultant Public Health Physician, As an Individual
The conclusion was natural causes.
NDP
Rachel Blaney NDP North Island—Powell River, BC
Thank you both for being here.
Dr. Croft, as I listened to your testimony and some of the questions you were just answering, I couldn't help but think of the precautionary principle.
NDP
Rachel Blaney NDP North Island—Powell River, BC
When I think of 280 people taking medication and two of them having that kind of episode, I have to be honest. I'm not willing to risk any of the men and women in uniform in this country—
NDP
Rachel Blaney NDP North Island—Powell River, BC
—in that way.
One of the things you said in your testimony is that in the army, you do what you're told.
I would like you to just share a little about that and the impacts that could have on the people who have served our country. The Conservative member that you talked to earlier, Cathay Wagantall, talked about the actual stats that have come out. I don't have the numbers in front of me, but it's a tremendous number of people who have taken mefloquine.
One of the things that's a huge concern for me is that we don't actually have a program to contact any of those veterans to say to them, “Let's check to see if this might be....” That's the challenge. We've had other doctors say that sometimes these folks are being treated for post-traumatic stress disorder, which may or may not be part of their issue, but if they're not being treated appropriately for what's happened to them as a result of mefloquine, they're not getting the full treatment, which can be very hard on them and their loved ones.
I'm just wondering if you could speak to this. How can we do outreach? What is the reality when we have a system where you do what you're told? What do we need to ask the Canadian government to be responsible for?
Consultant Public Health Physician, As an Individual
Soldiers are a different population from the CATMAT population, who are travellers who are in a position where they can make informed choices as to whether to take drug A, drug B or drug C. Soldiers are generally told, “You're going to this location. Take this drug and have these vaccinations.” They're not given informed choices in the matter. In a sense, they shouldn't be because that can lead to an undermining of discipline.
On the other side of the equation, the standard of safety and tolerability must be of the highest level for soldiers. Therefore, giving a drug that's inherently going to be dangerous strikes me as being an affront to the vulnerability of soldiers. It's something that should never have happened.
By the same token, now that it has happened, every effort should be made to contact them by whatever means to see what can be done to mitigate their damaged circumstances. I can't really speak to the Canadian government and tell it what to do, but it seems to me that it's a matter of basic ethics to try to retrieve the damage now that it's occurred.
NDP
Rachel Blaney NDP North Island—Powell River, BC
Thank you for that.
You talked about the profile—and I hope I'm getting this right because I'm definitely not a physician—of the neuropsychiatric impact. I'm just wondering if you could explain what that means, compare it to the other medications that you can take for malaria and explain how their profiles are different.
Consultant Public Health Physician, As an Individual
I know this committee wants to look at the most recent research. My research is a bit historical now. The most recent research, which I think Dr. Libman will agree with, is the Cochrane review. I did the first Cochrane review of mefloquine, published in the British Medical Journal in 1997. It has now been updated four times. The most recent review, which looks at all the randomized controlled trials and tries to extract that type of data, came out in 2017.
To answer the question, that review looked at 20 different randomized controlled trials of mefloquine. It found that comparing it with, say, atovaquone-proguanil, three times more people taking mefloquine were likely to stop taking the drug because of side effects.
That really makes it not as effective. I know Dr. Libman is looking very doubtful, but the relative risk is 2.86, which I interpret as meaning you are three times more likely, if you're taking mefloquine, to stop your drug. If you stop your drug, you risk getting malaria.
Within that analysis, they are comparing mefloquine and atovaquone-proguanil. They find that 6% of mefloquine users discontinue the drug, 13% get insomnia, 14% get abnormal dreams, 6% get anxiety and 6% get depressed mood. That gives you a flavour of the types of figures one can expect, bearing in mind that these studies, these randomized controlled trials, tend to be done in perfectly healthy, unstressed populations. For soldiers, those figures are likely to be comparable or perhaps worse.
When you look at the comparison with doxycycline, the figures are even worse. Of mefloquine users, 31% get abnormal dreams, whereas only 3% of doxycycline users get abnormal dreams.
Consultant Public Health Physician, As an Individual
Of mefloquine users, 18% have anxiety and11% have depressed mood. There are much lower figures with doxycycline.
Right through that very rigorous analysis you're seeing neuropsychiatric events predominant in mefloquine users, so who would ever want to take mefloquine? Who would want to give it to soldiers, given that soldiers must be mentally, as well as physically, healthy?
NDP
Rachel Blaney NDP North Island—Powell River, BC
What we've heard from other witnesses is that this is the concern. Some of the results of taking the medication are the same as what you would experience potentially just from going overseas.
How is the soldier to be able to tell and disclose?
Consultant Public Health Physician, As an Individual
Exactly.
Of course, what one has to bear in mind is that if you're a soldier, you don't go to your sergeant major and say you're feeling a bit anxious or a bit depressed or you're having nightmares. You would be told to just carry on with it.
You wouldn't associate it with the medication you're taking, so you'd just carry on taking it. All the evidence is that if you carry on taking mefloquine, the adverse effects become more intense and the risk is that they become prolonged and perhaps permanent, as has happened in some cases.
Those types of risks don't apply to tourists and general travellers, who usually take it for only a couple of weeks. Here, we're talking about soldiers who may have to take this drug for typically six months, and in my view, that represents an unacceptable risk.
Liberal
Bob Bratina Liberal Hamilton East—Stoney Creek, ON
Thank you. I'll share my time with Mr. Eyolfson.
Mr. Libman, there was a study done in Australia fairly recently. It stated in the conclusions:
It is clear to the committee that in the view of the medical professionals, the weight of medical evidence does not support the claim that their current symptoms are caused by antimalarial use 18 years ago. More specifically, in summary, the committee was told that long term problems as a result of taking mefloquine are rare....
The committee heard there have been an estimated 40 million doses of mefloquine worldwide, with safety data on at least 1 million people.... The committee was provided with no evidence that the same symptoms reported by some veterans are manifesting in the Australian population or across the world in the civilian population. The committee heard that there is no evidence of an emerging global public health issue.
I don't know if you are familiar with that study, but how does that ring to you in terms of your observations?
Professor, Department of Medicine, McGill University Health Centre, As an Individual
What Dr. Croft mentioned in terms of the potential for neuropsychiatric effects, the Cochrane review that he mentioned, there's no argument with any of that.
The issue that I think you're bringing up is the question about long-term effects versus short-term effects. The end of my studies, and so on, all manifested the types of short-term effects he talked about. They can't demonstrate long-term effects, because the studies were simply not that long. It's the observational studies that were much longer and it's those studies that could not demonstrate that there was a long-term problem.
Everybody agrees that those effects happen in the short term. In the vast majority of cases, you stop the drug and the side effects go away. I don't generally treat soldiers, but I can certainly understand that if you have those neuropsychiatric effects, you would normally want to stop the drug and choose something else if need be.
However, in the question you're bringing up, I think what you're quoting from is the testimony to the Australian veterans committee.
Professor, Department of Medicine, McGill University Health Centre, As an Individual
That's a committee similar to this one, I believe.
What they're trying to bring out is the issue of long-term effects. Do we have any evidence from soldiers or others that the type of neuropsychiatric effects or other types continue after the drug is stopped? That's the critical point there.
The evidence that it continues for a long time after the drug is stopped.... What we have is what seem to be some very rare cases. All the attempts to show it in the studies have failed to show it. There are reports that it may have happened, but they're individual reports, so it's hard to see whether it's more common in the people who took mefloquine than it is in people who took any other drug.
We have a hypothesis that it might be a very rare event. The question then is whether, in that setting, it outweighs the benefits of the drug. The benefits are clear—preventing malaria is paramount.
