Veterans Affairs Committee on May 1st, 2019

[Dr. Elspeth Ritchie]

Yes, I'll add something quickly.

I think the whole concept of informed consent for a military member is problematic. In the past, people have been given a handful of pills on the plane. Even now, if you want to achieve rank, if you want to do well in your career and not be staying stateside, you're going to take the medication.

The other point that I'd like to make is that we don't know what brings somebody into more risk. One of the hypotheses I have is dehydration. I believe that, perhaps, part of the reason that the Somalia veterans suffered so much more, having been over there, is that we didn't have water, and the water we had was crappy; it smelled of salt. People didn't drink it. In a deployed environment, you can never guarantee a good supply of food and water, so the risks are too great and, in my opinion, if people can't take one of these other medications, they should not be deployed to a war zone.

[The Chair, Liberal, Neil Ellis]

Thank you.

Mr. Sheehan.

[Terry Sheehan, Liberal, Sault Ste. Marie, ON]

Thank you very much for both of your presentations. I'm a guest here today, and I find this very interesting and important, this discussion that we're having.

I'm from Sault Ste. Marie, and we have the 49th Field Artillery Regiment there and the 33 Service Battalion. Many of the members are my friends, and some go on to the regular forces and have seen service all over the world.

Dr. Elspeth Cameron Ritchie, in some of your testimony you said you can't go into the clinical because there's not enough data out there but you can hypothesize about some of this. Those friends that I'm talking to are both men and women. You said that you have some theories or you might be able to hypothesize what the different effects of this particular drug are on men and women.

[Dr. Elspeth Ritchie]

Women in the military, by and large, are of child-bearing age, so you're concerned about things like pregnancy and breastfeeding. We have a little bit of data that the use of mefloquine causes a higher rate of miscarriage in Somalia veterans. Women who are deployed are not supposed to be pregnant, but sometimes they're pregnant before they go and they don't pick it up in time, and sometimes they get pregnant when they're there. I think it's inherently very risky. Then there's the question about the expression of mefloquine through breast milk.

The other thing is that women tend to have a higher lipid concentration, so again, one would hypothesize that you might have more of it that goes through the blood-brain barrier. We know that in traumatic brain injury or others, women have different reproductive cycles. Obviously, you've got the estrogen and other hormones, so how could that influence it? There are a lot of questions about passing on mefloquine. There are a lot of medications we try not to use in pregnancy because there's the risk of fetal abnormalities. All of those I would be concerned about.

For better or worse, so far, we don't have that much data because not many women, to the best of my knowledge, have been deployed on mefloquine and have been pregnant.

[Terry Sheehan, Liberal, Sault Ste. Marie, ON]

That's very interesting.

In some of the data that I was reading before coming here, it mentioned that, in the Canadian Armed Forces, mefloquine accounts for less than about 5% of malaria prevention prescriptions.

This is going to go into some of the discussion that you were having earlier, so I want both of you to make some comments on this. Since June 2017, mefloquine has been recommended only when members requested it themselves or when the use of other drugs is contraindicated.

To both of you, are you satisfied with this decision? Then, of course, you may wish to expand on your opinion as to how the Canadian Armed Forces could adopt other measures than what has transpired since June 2017.

Perhaps Dr. Nevin will start.

[Dr. Remington Nevin]

I am surprised. That number seems a little high. Five per cent is much higher than the rate of use in other countries. For example, in the United States military—the United States developed mefloquine—we use mefloquine so rarely now that it accounts for, I believe, less than one half of one per cent of new anti-malarial prescriptions. That change is a result of a number of policy changes beginning in 2009, when the U.S. Army began to move away from mefloquine and, by 2013, the other services had agreed to that policy, and mefloquine was formally declared a drug of last resort. Funding became available to pay for the more expensive, generally better tolerated daily drug atovaquone proguanil.

As I mentioned, there are individuals who have previously tolerated mefloquine and who prefer it. I suppose, as long as the drug is available, indicated and licensed for prevention, if those individuals have an informed discussion with their physician and are aware of the risks, they can continue taking the drug. I would not recommend that, and I would not recommend that service members taking an anti-malarial for the first time take mefloquine, because of the inherent risks involved with using mefloquine and the unique risks of using mefloquine in an operational environment where one needs to identify the onset of any psychiatric or neurological symptom as being potentially prodromal to the development of permanent disability. That is a risk I just don't think can be justified in any setting.

[Dr. Elspeth Ritchie]

This is an area we disagree on, and we disagree on a few. I don't think service members should be deployed on mefloquine at all, not just because of the risk to themselves, but because of the risk to others. For a long time we have not had aviators fly on mefloquine. It's against the rules. Well, that makes sense to me. You don't want somebody who has hallucinations at the wheel or stick of an airplane, but I also don't want that person driving a tank. I don't want that person having a machine gun.

I think what you saw with Staff Sergeant Bales and his killing of 16 Afghan villagers, which we still don't know is related to mefloquine or not.... If you're deploying service members on mefloquine, you're leaving yourself and the Canadian military vulnerable to that kind of question.

In my opinion, they should not deploy on mefloquine. We know it's a hallucinogen. There's no question. The risk of deploying people on hallucinogens is too great for the military to tolerate. Or at least it is for our military, and I would make the assumption that it would be for the Canadian military as well.

[The Chair, Liberal, Neil Ellis]

Thank you.

Mr. Bratina.

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

Thanks, Mr. Chair.

I want to share a question with my colleague Mr. Robert-Falcon Ouellette.

[Robert-Falcon Ouellette, Liberal, Winnipeg Centre, MB]

Dr. Ritchie and Dr. Nevin, thank you very much.

I'm a former service member and served 23 years in operational units. Obviously, when you have personnel, and you want to manage personnel, often you have a large number of troops who you're trying to deploy very quickly sometimes, and you need to prescribe drugs.

I was very interested, Dr. Ritchie, that you say it shouldn't be prescribed at all. Could there be circumstances when this drug should be prescribed in operations? It doesn't have to be taken every day; it has to be taken on a periodic basis. If you are in operations, and you don't have access to the prescription medication that you might need in theatre, could there be occasions when it should be prescribed?

[Dr. Elspeth Ritchie]

The argument for a long time was that mefloquine is taken on a weekly basis rather than a daily basis, therefore compliance will be better, therefore you don't have to have as big a pill bottle. If you're going for 180 days you have a weekly dose instead of 180 pills. That's part of the reason the military kept using it. However, we found people fear mefloquine, therefore they don't take it; they're non-compliant, so they get malaria.

Again, if we are deploying people with weeks and months worth of MREs, rations, bullets, ammunition, I think we can deploy them with enough medication that they can take that bottle with 180 pills. You can make the argument that they may not be compliant with a daily dose, but we have seen that because there is such fear out there about mefloquine, often people won't take it.

Again, I'd like to emphasize one more time that this drug in the short term, not the long term, is a hallucinogen. You hear so many people talk about vivid, cartoonish dreams; you see some people abusing it for the recreational side effects. That's why I don't think it makes sense to use it in an operational environment where people have big weapons. The consequences of what they do, whether it's friendly fire or shooting other people, maybe not obeying the rules of engagement, the irritability—that's one thing we haven't talked about that I think is important—and the short fuse that you get, you hear over and over again when people are on mefloquine. Mefloquine rage is a very common term.

[Robert-Falcon Ouellette, Liberal, Winnipeg Centre, MB]

You mentioned there are people who don't take it in theatre. Do you have numbers on the number of personnel who do not take the prescription? Obviously if people get malaria you might not be able to accomplish the mission, and that poses a significant risk to accomplishing what was set out for you by the government and command.

[Dr. Elspeth Ritchie]

Usually the information on people not taking it is anecdotal because if you're ordered to take it you're not going to raise your hand and say you're not taking this.

However, I believe, Dr. Nevin, you have some data on malaria emergence. Can you speak a little more to that?

[Dr. Remington Nevin]

Let me turn the question around. Health Canada and the product manufacturer very clearly state you must discontinue this drug at the onset of any psychiatric or neurological symptoms. This means that Health Canada is telling us if you develop anxiety, depression, restlessness, confusion, insomnia, nightmares or abnormal dreams you must immediately stop taking the drug.

Let's look back and ask if the Department of National Defence has been seeing this happening in practice. We know from carefully designed and implemented randomized control studies that symptoms of anxiety or depression, for example, will occur in 4% of those taking mefloquine prophylactically. Abnormal dreams and nightmares will occur in over 10% of individuals taking mefloquine. We should be seeing a sizable minority of our deploying forces given mefloquine presenting to their doctors and stating they are having those symptoms and requesting that the drug be discontinued. For the last 25 or 30 years of this drug's use in operational settings in militaries around the world, we weren't seen anywhere near 10% or more of troops presenting, requesting that the drug be switched.

We've known all along, or we should have known all along, that this drug was not being used operationally in accordance with the manufacturer's guidance.

You said that if a soldier becomes ineffective due to malaria that's a bad thing. Granted it is, but if a soldier becomes ineffective due to permanent disability as a result of misuse of mefloquine, that's also bad. It would be nice if we had a safe and effective anti-malarial that we could dose weekly or monthly. That would be very good. We don't have that drug. We've never had that drug. Mefloquine is not that drug.

[Robert-Falcon Ouellette, Liberal, Winnipeg Centre, MB]

You've also mentioned the permanent brian damage. Has research been done trying to reverse any of that brain damage or toxicity in the system?

[Dr. Remington Nevin]

Some common manifestations of what we believe is the brain stem dysfunction caused by mefloquine neurotoxicity are such things as central vestibulopathy and central visual disorders: chronic dizziness, chronic vertigo, chronic disequilibrium, visual impairment caused by the neurotoxic effects of this drug. These disorders, these disabilities, are somewhat amenable to rehabilitation. Individuals who are examined by neuro-optometrists and neuro-otologists can sometimes receive therapy that improves their quality of life, reduces the incidents of complications from this disability, but it's never reversed completely; it's simply managed. Their quality of life is improved somewhat, but it's never back to what it was before the neurotoxic injury.

Neurotoxicity, brain damage, cannot be undone.

[The Chair, Liberal, Neil Ellis]

Thank you.

Mr. McColeman.

[Phil McColeman, Conservative, Brantford—Brant, ON]

Thank you, Chair.

Thanks to the witnesses for being here.

You mentioned, Dr. Nevin, that you had a response from the Minister of Veterans Affairs Canada, and you offered to share that with the committee.

Can I ask you to do that? As a housekeeping thing, can I ask that every member of this committee receive a copy of that response from the minister?

[Dr. Remington Nevin]

Yes, I'd be happy to submit that.

[The Chair, Liberal, Neil Ellis]

What you do is submit it to the clerk and the clerk will get it to us.

[Phil McColeman, Conservative, Brantford—Brant, ON]

I have five minutes and I have a lot I want to cover.

When I think of toxicity, I think of poison. You've used the word “poison”.

I relate to a very personal situation with my son, at two years of age, having very aggressive chemotherapy. Very toxic drugs were put into his body, and he has brain damage as a result.

Is quinism associated with any cancer treatments that you're aware of, toxic drugs used in cancer treatments? This would be 30 years ago.

[Dr. Remington Nevin]

The term “quinism” was coined to describe the disease caused by poisoning by quinoline drugs. These are mefloquine, chloroquine, tafenoquine, we believe, and primaquine, the synthetic drugs used in World War II. This disease is a consequence of what we believe is the inherent toxicity of this class of drug—the quinoline class of drug.

Quinolines make effective anti-malarials, and it just so happens that the quinolines are also toxic in a particular way to the brain.

[Phil McColeman, Conservative, Brantford—Brant, ON]

My question very clearly— I don't want to make a false connection—is whether there is anything you're aware of as a medical professional that is used with the basis of this drug in cancer treatments, or in the history of cancer treatments.

[Dr. Remington Nevin]

Interestingly, mefloquine and related quinoline anti-malarials have recently begun to be explored as treatments for certain types of central nervous system cancers. This makes sense, because these drugs readily penetrate the blood-brain barrier. They readily concentrate—sometimes at very high concentrations—in the brain, and they're neurotoxic; they kill brain cells. If brain cells are rapidly multiplying, as they do in cancer, drugs like mefloquine can have some theoretic benefit to treating those cancers.

The same property that renders these drugs inherently dangerous, in my opinion, when given to healthy service members, may make them very effective cancer agents.

[Phil McColeman, Conservative, Brantford—Brant, ON]

Based on the packaging requirements that you talked about, on the fact that the U.S. has it down to less than 0.5%, I think is what you said, we still have 5% of our serving members taking this drug.

There is the reluctance of any of the military to recognize it and acknowledge it, which was your testimony here today. Based on the fact that it is a poison because it is toxic, instead of making veterans go to court, which they're doing right now—the lawsuit has been filed—why does it make any sense for a government to deny veterans the acknowledgement that this is a poison that they've taken?