Veterans Affairs Committee on May 6th, 2019

[BGen Andrew Downes]

I don't think those questions really confirm anything. One of the problems is recall bias as well. We know that people often confound the different medications that they've been given, and sometimes that's one of the criticisms of surveys that are conducted after the fact. However, asking people questions gives you perhaps a sense of what the issue might be, but what we lack is a definitive test whereby we can confirm whether that is the case.

I should also point out that matters of the brain are very complicated. We understand very poorly the brain and brain functioning. Particularly in a combat environment, the exposures to multiple different traumas really confound matters a lot as well, so I think asking those questions has no real validity at all.

[Doug Eyolfson, Liberal, Charleswood—St. James—Assiniboia—Headingley, MB]

Thank you.

One thing that's been talked about in this discussion by certain proponents of this principle of this toxicity, and I've heard many references to it, is brain stem injury. What is the scientific evidence supporting the fact that there's any injury to the brain stem of people who've taken this drug?

[BGen Andrew Downes]

Perhaps I'll ask Dr. Jetly to answer that question.

[Col Rakesh Jetly]

There's actually very little. The only thing that I could find was one study on rats. It gave rats incremental dosages of mefloquine, which was, I think, eventually up to about 7 times the dose of treatment, so much higher than we would use for prophylaxis. They did some testing on the rats that showed some impairment in their functioning that could have to do with balance and things, which would sort of be brain stem. After they were euthanized and stained, they found some abnormalities in the brain stems. That's really it in terms of definitive studies.

[Doug Eyolfson, Liberal, Charleswood—St. James—Assiniboia—Headingley, MB]

Just to confirm, this is in rats that received seven times the dose that humans would for prophylaxis.

[Col Rakesh Jetly]

That's right. There were some old studies on monkeys from the 1940s and 1950s that were using precursors. They were using other quinolones. As the general was saying, there's really a bit of a leap scientifically from the biological studies. There really aren't definitive biological studies in humans that would suggest similar changes.

[The Chair, Liberal, Neil Ellis]

Ms. Blaney.

[Rachel Blaney, NDP, North Island—Powell River, BC]

Thank you, all, for being here today.

I'm going to come back to you, Colonel Jetly.

You just answered a question about the research. What research is needed? There seems to be a gap. That's what we've heard across the board. Do you have any recommendations on what type of research would be more helpful to you?

[Col Rakesh Jetly]

Yes, that's a great question.

The typical way we would study it is doing population-based research. We would do a careful analysis following people over time.

[Rachel Blaney, NDP, North Island—Powell River, BC]

Can you just make sure that's it's nuanced? I think one of the things that we've heard testimony on is that for people going overseas in this particular role, just the normal impacts are often very similar to what could be telling somebody that this is not the right medication for them to be on. They are the beginning symptoms.

Wouldn't the research have to be more closed in or focused on these particular type of folks?

[Col Rakesh Jetly]

The definitive research, if you want to go right down to it.... If you're saying to demonstrate brain changes, you would have to give half the people mefloquine and half the people not mefloquine, then send them to a war zone and expose them to mTBI, concussions and trauma and then scan them like crazy.

[Rachel Blaney, NDP, North Island—Powell River, BC]

Basically, is it worth the risk? I understand what you're saying. It's a very ethical point that you're bringing forward.

What has really stuck in my mind is that the symptoms that you receive at the very beginning of taking it, that any normal person who was not going into that kind of situation would start to feel, are the normal feelings and experiences when you first start taking it, like anxiety, nightmares....

[Col Rakesh Jetly]

You mean the normal adverse drug reactions, which some people would feel. Yes, absolutely.

[Rachel Blaney, NDP, North Island—Powell River, BC]

Yes, exactly.

I'm saying that if it's the same as what would actually most often happen to someone in that state of having to go overseas in that particular.... How do we know? To me, the biggest concern is that we're trying to ask our folks who are representing us in the military to take a huge risk and how do we know?

[Col Rakesh Jetly]

I'm a bit confused by the question, but the confounders are huge.

If you take young men and women into a war zone, deprive them of sleep and maybe dehydrate them, with the heightened stress and being away from their family.... We also have epidemiological data that shows a higher incidence of adverse childhood effects. When you take these people over and expose them to the horrors of war—Rwanda in my circumstance—or humanitarian crises, trying to tease out the difference between the trauma, the mefloquine and the doxycycline is a very difficult thing to do. That's why we have, as the general puts it, not great evidence on both sides.

I think the definitive study would be extremely difficult. I think ultimately as health care practitioners we need to listen to our patients and help them to deal with what they're struggling with.

There isn't a specific treatment that I know of for tinnitus caused by mefloquine, but I do know approaches to tinnitus that we would use, for example. I think what we need to do is have people come forward, compassionately listen to what they're feeling, and then try to address things almost with a symptom-based approach.

[Rachel Blaney, NDP, North Island—Powell River, BC]

I have some questions about the screening and diagnosing. It sounds, based on your answer, as if this is another challenge we're facing. I'm curious about whether there currently is a process the military is taking for screening and diagnosing folks who have some sort of reaction to mefloquine.

[Col Rakesh Jetly]

We have lots of screening in place; that's what militaries do. It's not specifically with regard to mefloquine, but after deployment, we have an enhanced post-employment screening. We're really looking for anybody who's having difficulties of any nature after deployment—physical, neuropsychiatric. If they do have concerns, we do a thorough assessment. We look for symptomology that fits certain syndromes, and then we address that.

[Rachel Blaney, NDP, North Island—Powell River, BC]

Thank you.

Brigadier-General Downes, thank you so much for your report today. I certainly appreciate what you had to say.

One of the things you mentioned in your report is that right now, military personnel and veterans are hearing about mefloquine and wondering if this is part of the symptomology they're experiencing with the multiple challenges they have.

Could you tell us a little about that and how it's rolling out within the work you do?

Also, we know that the surgeon general's report on mefloquine said that 12% of personnel had precautions, and 62% who had received a prescription were not assessed for those precautions.

I'm just wondering about that. I hope I got that correct.

[BGen Andrew Downes]

That report is from a number of years ago. It was ordered by my predecessor. Although I've read the report a number of times, I don't remember the specific numbers and what it said.

I do know that when we looked at it, we found there were a number of people who were prescribed mefloquine when there were existing contraindications to doing that. We have done a quality-of-care review on those particular files. We've also put in place a training program that all prescribers need to take, which reminds people of these issues. We also have screening forms, and everybody who's prescribed any of the anti-malarial medications has to go through all the contraindications, and sign it. There are black boxes on each one of those forms to highlight the specific contraindications.

We believe we've put in place a robust system. There is no other health system that I'm aware of in Canada that has gone to those lengths.

I should point out too that when Health Canada did their safety review on mefloquine, they found similar issues in the civilian prescribing population as well. This isn't unique to the military. I think this is something that happens in medical practice from time to time, and I do believe we've responded appropriately to it.

[The Chair, Liberal, Neil Ellis]

Thank you.

Mr. Bratina.

[Bob Bratina, Liberal, Hamilton East—Stoney Creek, ON]

Thank you.

I'm going to refer directly to the transcripted testimony from a previous meeting, because I want to be fair to the witness, Dr. Nevin, who was being questioned about mefloquine toxicity and quinism. He said the following:

Our group was formed largely to advocate for and to support and promote education and research on this medical condition, which we have termed “quinism”. We chose this language very deliberately. We believe that quinism is a disease, that chronic quinoline encephalopathy is a medical condition caused by the poisoning of the brain by these drugs.

The symptoms that I have been describing, the symptoms that are acknowledged as being potentially long term in individuals who take mefloquine, are not just side effects. These symptoms are not just adverse reactions to the drug. These symptoms and the signs that accompany them are manifestations of an underlying disease that has been caused by the poisoning of the central nervous system by these drugs.

There are many reasons why we believe that. The symptoms and signs clustered together, for example, are evidence of a disease. However, we have an increasing understanding with time of the pathophysiology, meaning the disorder in structure and function, of the central nervous system that underlies these signs and symptoms.

When you have a putative pathophysiology, when you think you understand how the body—or in this case, the brain—is being disordered and you have consistent signs and symptoms, you have a disease. It's not merely a syndrome. These aren't merely side effects. It's a disease.

The term “quinism”, the disease quinism, encompasses the entirety of the symptoms that are experienced by veterans suffering from mefloquine poisoning.

General Downes, could you respond to that?

[BGen Andrew Downes]

I'd like to respond to a number of different elements.

The first one is that quinism is not a recognized diagnosis. It doesn't exist in the manual of diagnoses that we use when we're coding things.

It is also a hypothesis, and Dr. Nevin refers to it himself as a hypothesis. A hypothesis is an idea that is not fully supported by research. He's put some evidence together to outline his case. In the future, evidence might demonstrate that he is correct, but at the moment, the evidence is weak.

Some of the research he is drawing on, for example, some of these rat studies and so on that Colonel Jetly was speaking about a moment ago, refer to brain stem injuries, but some of the symptoms that people are describing would not be consistent with brain stem injuries.

There are some inconsistencies in this idea, and I'm not an expert in the brain and in mefloquine, but I've been reading the work of experts who criticize Dr. Nevin's work. I'm trying to extract the truth from this discussion at the expert level.

I remain unconvinced that this is what's going on, but I think we should not be so arrogant as to dismiss it. I think we have to be open to the possibility and continue to monitor the work that's being done. One day, I hope to have a definitive answer.

[Bob Bratina, Liberal, Hamilton East—Stoney Creek, ON]

Would other factors be included in causing some of the extreme symptoms that we've seen and read about? For instance, use of other not prescribed drugs? We've heard of that happening. We're trying to draw conclusions from very serious incidents. Especially in the past, there have been references to the Canadian Airborne Regiment and so on. How can we say, for sure, that the behaviours were specifically the result of one thing when they could be the result of many things?

[BGen Andrew Downes]

That's a challenge. Trying to attribute an outcome to an incident or to a medication can be very difficult. When one looks at anecdotes, at single cases or groups of single cases, one might easily overlook other factors that might be at play.

When we were speaking a bit earlier—and there's no evidence for this—what role did heat have to play in this? Were people dehydrated? Was that a stressor? We don't know of other medications some of these people might have been taking. Were other substances being used? We don't know. That's why it's important to look at studies done at a population level where some of these things are controlled or where one can assume, based on the large numbers in the study, that they're being controlled.

[The Chair, Liberal, Neil Ellis]

Thank you.

Ms. Ludwig.