Report of the Somalia Commission Inquiry

INQUIRY REPORT SUMMARY

Mefloquine is a relatively new anti-malarial drug, first made generally available to the Canadian public in 1993. It is used both to prevent malaria (that is, as a prophylactic) and to treat malaria. Mefloquine is used in areas where the local strains of malaria have developed a resistance to other anti-malarial drugs. Somalia is one such place.

Some suggestion has been made to this Inquiry that Mefloquine caused severe side effects, including abnormal and violent behaviour, among some Canadian Forces (CF) personnel in Somalia. We were not able to explore fully the possible impact of Mefloquine. This would have required additional hearings dedicated specifically to the issue, which time did not permit. However, we report here our general findings about Mefloquine and its possible impact on operations in Somalia.

It is clear that Mefloquine caused some minor problems in Somalia, as might be expected from a review of the medical literature. We learned of several incidents of gastro-intestinal upset, vivid dreams, nightmares referred to by soldiers as “meflomares,” and inability to sleep following the use of this drug. Side effects - or at least the minor side effects, and possibly also the major side effects - appeared to be most pronounced in the 24 to 48 hours after taking Mefloquine.

If Mefloquine did in fact cause or contribute to some of the misbehaviour that is the subject of this Inquiry, CF personnel who were influenced by the drug might be partly or totally excused for their behaviour. However, for reasons described more fully in Chapter 41, we are not able to reach a final conclusion on this issue. We can offer only general observations about the decision to prescribe Mefloquine for personnel deployed to Somalia:

The decision of the Department of National Defence (DND) in 1992 to prescribe Mefloquine for CF personnel deployed to Somalia appears to be consistent with the medical practice at the time. This view is based on medical literature from that time suggesting that Mefloquine was an appropriate anti-malarial drug for troops in Somalia and that severe neuropsychiatric symptoms were rare - in the order of one in 10,000 to one in 13,000. U.S. troops also used Mefloquine, although in a weaker form. We cannot say, however, whether DND took adequate precautions to ensure that persons susceptible to severe psychiatric disorders did not receive Mefloquine, since even in 1992 it was known that Mefloquine should not be prescribed to such individuals.

At the time of the deployment, there seems to have been no strong evidence that Mefloquine might interact with alcohol to produce or increase the risk of abnormal behaviour or to magnify such behaviour. The possible adverse effects of mixing alcohol with Mefloquine were analyzed in detail in the medical literature only after the Somalia deployment. DND, therefore, cannot be faulted for failing to relate the consumption of alcohol to the use of Mefloquine.

More recent medical information suggests that severe adverse effects from Mefloquine used as a prophylactic are not as rare as first thought, but views on this point conflict, and further investigation may be necessary.

Mefloquine use could have been a factor in the abnormal behaviour of some troops in Somalia. However, one cannot begin to determine whether Mefloquine contributed to the behaviour of the individuals in question without answers to the following questions:

1. Did the members in question use Mefloquine?

2. Did any of the members in question receive a more powerful 'treatment' dose of Mefloquine? This would happen only if they had contracted malaria. The more powerful treatment doses were known even at the time of the Somalia deployment to carry a greater risk of neuropsychiatric disorders than the weaker dose that most troops received to prevent malaria.

3. Did any of the members in question have a history of psychiatric disorders that could increase the risk of severe side effects from Mefloquine?

4. What day of the week did they take Mefloquine? What day or days of the week did their misbehaviour occur?

5. Did they complain at any point about any symptoms, mild or severe, that are now known to be associated with Mefloquine?

6. Did anyone notice abnormal behaviour by the members in question in the few days after the latter consumed Mefloquine? If so, what was the behaviour?

7. Is it reasonable to say that Mefloquine was or may have been a cause? Might some other factor instead have caused or contributed to the behaviour (alcohol consumption, racist attitudes, generally belligerent or aggressive nature of the individual, stressful environment, official tolerance of extreme behaviour)?

It is evident that further investigation is warranted before any firm conclusions about the role of Mefloquine can be drawn.

© Minister of Public Works and Government Services Canada 1997

Chemical Make-up of Mefloquine (Larium®)

Drug Category: Antimalarials

Indication: For the treatment of mild to moderate acute malaria caused by Mefloquineuine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. Also for the prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of Plasmodium falciparum.

Pharmacology: Mefloquine is an antimalarial agent which acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.

Mechanism of Action: Mefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.

Absorption: Well absorbed from the gastrointestinal tract. The presence of food significantly enhances the rate and extent of absorption.

Toxicity: Oral, rat: LD50 = 880 mg/kg. Symptoms of overdose include nausea, vomiting, and weight loss.

Protein Binding: 98%

Biotransformation: Hepatic. Two metabolites have been identified in humans. The main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, is inactive against Plasmodium falciparum. The second metabolite, an alcohol, is present in minute quantities.

Half Life: 2-4 weeks

Contraindication: Use of Lariam is contraindicated in patients with a known hypersensitivity to Mefloquineuine or related compounds (eg, quinine and quinidine) or to any of the excipients contained in the formulation. Lariam should not be prescribed for prophylaxis in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders, or with a history of convulsions.

Interaction: Drug-drug interactions with Mefloquine have not been explored in detail. There is one report of cardiopulmonary arrest, with full recovery, in a patient who was taking a beta blocker (propranolol). The effects of Mefloquineuine on the compromised cardiovascular system have not been evaluated. The benefits of Mefloquine therapy should be weighed against the possibility of adverse effects in patients with cardiac disease.

Because of the danger of a potentially fatal prolongation of the QTc interval, halofantrine must not be given simultaneously with or subsequent to Mefloquine.Concomitant administration of Mefloquine and other related compounds (eg, quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions. If these drugs are to be used in the initial treatment of severe malaria, Mefloquine administration should be delayed at least 12 hours after the last dose. There is evidence that the use of halofantrine after Mefloquineuine causes a significant lengthening of the QTc interval. Clinically significant QTc prolongation has not been found with Mefloquineuine alone.

This appears to be the only clinically relevant interaction of this kind with Mefloquine, although theoretically, coadministration of other drugs known to alter cardiac conduction (eg, anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H1-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. There are no data that conclusively establish whether the concomitant administration of Mefloquineuine and the above listed agents has an effect on cardiac function.

In patients taking an anticonvulsant (eg, valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of Mefloquine may reduce seizure control by lowering the plasma levels of the anticonvulsant. Therefore, patients concurrently taking antiseizure medication and Mefloquine should have the blood level of their antiseizure medication monitored and the dosage adjusted appropriately.When Mefloquine is taken concurrently with oral live typhoid vaccines, attenuation of immunization cannot be excluded. Vaccinations with attenuated live bacteria should therefore be completed at least 3 days before the first dose of Mefloquine.

No other drug interactions are known. Nevertheless, the effects of Mefloquine on travelers receiving comedication, particularly diabetics or patients using anticoagulants, should be checked before departure.In clinical trials, the concomitant administration of sulfadoxine and pyrimethamine did not alter the adverse reaction profile.

Drug Interaction
Acenocoumarol--Mefloquine can increase the anticoagulant effect
Anisindione--Mefloquine can increase the anticoagulant effect
Dicumarol--Mefloquine can increase the anticoagulant effect
Halofantrine--Increased risk of cardiac toxicity
Rifampin--Rifampin lowers mefloquine levels
Ritonavir--Mefloquine decreases the effect of ritonavir
Warfarin--Mefloquine can increase the anticoagulant effect
Ziprasidone--Increased risk of cardiotoxicity and arrhythmias

Food Interaction:
1. Avoid alcohol.
2. Take with a full glass of water.
3. Take with food.

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.
DrugBank Version: 2.5 —
Contact: Craig Knox or Genome Canada Help Desk

The Full Report on Meqfloquine

Mefloquine
From Wikipedia, the free encyclopedia

Mefloquine is an orally-administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam (manufactured by Roche Pharmaceuticals) and chemical name Mefloquine hydrochloride (formulated with HCl). Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the U.S. as a synthetic analogue of quinine.

Mefloquine
Systematic (IUPAC) name
2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol
Identifiers
CAS number
53230-10-7
ATC code
P01BC02
PubChem
4046
DrugBank
APRD00300
Chemical data
Formula
C17H16F6N2O
Mol. mass
378.312 g/mol
Pharmacokinetic data
Bioavailability
?
Metabolism
Extensively hepatic; main metabolite is inactive
Half life
2 to 4 weeks
Excretion
Primarily bile and feces; urine (9% as unchanged drug, 4% as primary metabolite
Therapeutic considerations
Pregnancy cat.
C (U.S.)
Legal status

Routes
oral

Contents
1 Uses
2 Side-effects
2.1 Neurological activity
3 Chirality and its implications
4 Recent peer-reviewed research findings from Walter Reed Army Institute of Research (WRAIR)
5 Proposed development of a commercially available safety test
6 Popular culture references
7 References
8 Further reading
9 External links

Uses
Mefloquine is used to prevent malaria (malaria prophylaxis) and also in the treatment of chloroquine-resistant falciparum malaria. As Mefloquine resistance spreads, Mefloquine has started to lose its efficacy.
Mefloquine is the drug of choice to treat malaria (though not necessarily to prevent malaria) caused by chloroquine-resistant Plasmodium vivax.[1]
Mefloquine has shown efficacy in an in vitro assay against Progressive Multifocal Encephalopathy (PML). Biogen Idec has recently announced that a trial of Mefloquine in HIV-related PML is beginning.[1]

Side Effects
Mefloquine may have severe and permanent adverse side effects. It is known to cause severe depression, anxiety, paranoia, aggression, nightmares, insomnia, seizures, birth defects, peripheral motor-sensory neuropathy,[2] vestibular (balance) damage and central nervous system problems. For a complete list of adverse physical and psychological effects — including suicidal ideation — see the most recent product information. Central nervous system events occur in up to 25% of people taking Lariam, such as dizziness, headache, insomnia, and vivid dreams. In 2002 the word “suicide” was added to the official product label, though proof of causation has not been established. Since 2003, the Food and Drug Administration (FDA) in the USA has required that patients be screened before Mefloquine is prescribed. The latest Consumer Medication Guide to Lariam has more complete information.

Attempting to obtain a diagnosis of Mefloquine toxicity is frustrated by the following reasons:
1. It may cause bad dreams.
2. In most cases, results from the primary tools used by neurologists - CAT scans, EMGs and MRIs - come up negative.
3. Thousands of travelers do take Mefloquine every year, however the adverse reaction data is spurious and under-reported because side-effects occur usually in a location away from the doctor that originally prescribed the drug.
4. Because the data is spurious and under-reported, reports of Mefloquine reactions are readily discounted as “anecdotal,” since Mefloquine toxicity is not as well-known and publicly acceptable as, for example, an allergic reaction to Penicillin.

In the 1990s, there were reports in the media[3] that the drug may have played a role in the Somalia Affair, which involved the torture and murder of a Somali citizen whilst in the custody of Canadian peacekeeping troops. There has been similar controversy, since three murder-suicides involving Special Forces soldiers at Fort Bragg, N.C., in the summer of 2002. To date, more than 19 cases of vestibular damage following the use of Mefloquine have been diagnosed by military physicians. The same damage has been diagnosed among business travelers and tourists.

Neurological Activity
In 2004, researchers found that Mefloquine in adult mice blocks connexins called Cx36 and Cx50.[4] Cx36 is found in the brain and Cx50 is located in the eye lens. Connexins in the brain are believed to play a role in movement, vision and memory, likely due to a role in the synchronization of neural activity.

Chirality and Its Implications
Mefloquine is a chiral molecule with two asymmetric carbon centers, which means it has four different diastereomers. The drug is currently manufactured and sold as a racemate of the (+/-) R*,S* enantiomers by Hoffman-LaRoche, a Swiss pharmaceutical company. According to some research,[5] the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects. It is not known whether Mefloquine goes through stereoisomeric switching in vivo.

The (+) enantiomer has a shorter half-life than the (-) enantiomer.
Recent peer-reviewed research findings from
Walter Reed Army Institute of Research (WRAIR)
Mefloquine was invented at WRAIR in the 1970s. WRAIR has published several papers outlining their efforts to make Mefloquine safer by producing a version of Mefloquine that is composed of only the (+) enantiomer (photo isomer).

“Adverse central nervous system (CNS) events have been associated with Mefloquine use. Severe CNS events requiring hospitalization (e.g., seizures and hallucinations) occur in 1:10,000 patients taking Mefloquinefor chemoprophylaxis. However, milder CNS events (e.g., dizziness, headache, insomnia, and vivid dreams) are more frequently observed, occurring in up to 25% of patients.”[6]

WRAIR defines the neurotoxicity of Mefloquine to be 25 µM from table 1 ref.[6] “We recently showed that Mefloquine severely disrupts calcium homeostasis in rat neurons in vitro at concentrations in excess of 20 µM, an effect closely related to the acute neurotoxicity of the drug in terms of dose effect and kinetics.”[6]

“However, the drug crosses the blood-brain barrier and accumulates as much as 30-fold in the central nervous system, and Mefloquine brain concentrations as high as 50 µM have been reported in human postmortem cases. Mefloquine brain concentrations as high as 90 µM have been reported in rats given a therapy-equivalent dose rate, with concentrations in subcompartments in the brain exceeding 100 µM. Since it has long been known that a prolonged disruption of neuronal calcium homeostasis may lead to neuronal cell death and injury, it is reasonable to suppose that such events may contribute to the clinical neuropathy of the drug.”[6]

In addition, WRAIR published the following in March 2006 regarding treatment-level brain-stem damage in rats:
It states:
1. “At the time this study was conceived, no formal FDA guidelines for neurotoxicity testing existed. In contrast, first-tier neurological screens, such as those recommended by the U.S. Environmental Protection Agency (EPA), are often employed to detect a broad range of possible neurological effects that may be induced by uncharacterized test compounds.”[7]
The FDA “approval” process in 1970 did not require safety testing for neurotoxicity, since no protocol existed at the time. Evidence suggests that it still does not exist, since the Walter Reed researchers had to use a test protocol from the EPA to write this paper.
2. “It is also important to point out that the Mefloquine-induced brain-stem injury revealed by silver staining is permanent in nature.”[7]
Proposed development of a commercially available safety test
WRAIR recently released a funding document STTR A06-T034 “Neurotoxicity Associated with Mefloquine, an Anti-Malarial Drug.”[8] This document calls for the development of a commercially-available “safety test” for Mefloquine users.

Popular Culture References
The fictional drug “Quinium,” which has significant similarities to Mefloquine, was featured in the episode “Goliath” of the television series Law and Order: SVU.[9]

References
^ Maguire JD, Krisin, Marwoto H, Richie TL, Fryauff DJ, Baird JK (2006). "Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia". Clin Infect Dis 42 (8): 1067–72. doi:10.1086/501357.
^ Jha S, Kumar R, Kumar R. (2006). "Mefloquine toxicity presenting with polyneuropathy—a report of two cases in India". Trans R Soc Trop Med Hyg 100 (6): 594–96. doi:10.1016/j.trstmh.2005.08.006.
^ Somalia and Mefloquine
^ Cruikshank, Scott J.; et al. (2004). "Potent block of Cx36 and Cx50 gap junction channels by Mefloquine". PNAS 101 (33): 12364–12369. doi:10.1073/pnas.0402044101.
^ Fletcher, A., and Shepherd, R. Use of (+)Mefloquine for the treatment of malaria. US patent 6664397.
^ a b c d Dow, Geoffrey S. (2004). "The Antimalarial Potential of 4-Quinolinecarbinolamines May Be Limited due to Neurotoxicity and Cross-Resistance in Mefloquine-Resistant Plasmodium falciparum Strains". Antimicrobial Agents and Chemotherapy 48 (7): 2624–2632. doi:10.1128/AAC.48.7.2624-2632.2004.
^ a b Dow, G.; et al. (2006). "Mefloquine Induces Dose-Related Neurological Effects in a Rat Model". Antimicrobial Agents and Chemotherapy 50 (3): 1045–1053. doi:10.1128/AAC.50.3.1045-1053.2006.
^ See http://www.acq.osd.mil/osbp/sbir/solicitations/sttr06/army06.htm
^ Benjamin, Mark (2005-05-25). "Ripped from my headlines!". salon.com.

Further Reading
Phillips-Howard, P. A., and F. O. ter Kuile. 1995. CNS adverse events associated with antimalarial agents: fact or fiction? Drug Saf. a370-383.

External Links
Manufacturer’s information page
Lariam Action USA, Clearinghouse for information on Mefloquine news, research, toxicity
2004 UPI story about military suicides
Senator Feinstein Urges Rumsfeld to Complete Lariam Study.
Discussion of Lariam side-effects at PeaceCorpsOnline.org

Beware Antimalarial Drug, Mefloquine--still being issued to troops

In 1994, the president of my publishing company assigned me to cover the humanitarian relief effort following the Rwandan genocide. My article became a tribute to the overlooked logistics industry for its part in making such efforts the success they are, but I also stepped into the mire of the antimalaria drug scandal.

Cpl. Scott Smith, a peacekeeper I interviewed, later committed suicide on Christmas Eve, 1994, in Rwanda—two months before his tour of duty was up. He was coming home to a fantastic job, and in my interviews and regular talks with him, I was impressed with his upbeat, resourceful attitude. I have dealt with despondent people and know their skill for covering depression. Scott showed none of the signs, but he did talk about the terrible nightmares and diarrhea he was having especially on the days the troops took their weekly Mefloquine pill. He had endured these side effects in deployments to the Gulf War and Somalia as well. (You start taking the pill one week in advance of visiting a tropical area and for four weeks following your return.)

For this assignment, the cameraman and I were also issued Mefloquine (Lariam®). When flying on the armed forces transports delivering supplies to the refugee camps in Goma, Zaire, the pilots joked about not being on Mefloquine because “you can’t have pilots hallucinating in the air.”

According to a report from the National Defence Department in Ottawa for the Somalia Enquiry, “some Canadian Forces pilots and divers received another anti-malarial drug, Doxycycline, because Mefloquine was thought to cause dizziness and loss of fine motor control in some users. The post-deployment report of the HMCS Preserver, for example, stated that all aircrew on active flying duties used Doxycycline. The report also noted that several CF members who suffered adverse effects from taking Mefloquine were switched to Doxycycline.”

The peacekeepers described the designated day their companies took Mefloquine as Manic Monday, Loco Tuesday, Wacky Wednesday, Psycho Thursday or Freaky Friday. On these days, military stats show the rate of vehicle accidents rose. There are now medical papers available describing the dangers of mixing alcohol with Mefloquine, and Scott was naturally drinking on that Christmas Eve in celebration of his going home soon. He loved being in Rwanda and helping the people who were so appreciative of the Canadians who stayed behind and risked their lives to bring world attention to the genocide being executed in Rwanda at a rate much higher and more efficiently than any organized genocide previously committed, even by the Nazis.

I was only on Mefloquine nine weeks, but just that short time created a state of insomnia that began in Rwanda and lasted six months until sleep deprivation weakened my immune system and I collapsed with pneumonia. Then I was heavily drugged so I could sleep. Fourteen years later, I am lucky if I get five hours solid sleep per night, and for seven years, my thyroid had to be monitored because it showed strange scar-like damage. I constantly fluctuated between hyper- and hypothyroidism, so doctors were never sure what treatment course to take. Instead of doing the wrong thing, they decided to monitor it every three months. Somehow, on my own, my thyroid finally corrected itself and is now working normally. Was it Mefloquine? Others who have taken this drug have suffered serious damage to their livers, hearts and/or thyroids and haven’t healed themselves.

The military in the U.S., Britain, Canada and Australia have minimized the dangers of Mefloquine since the U.S. Army asked Roche Labs to create a shot that would prevent soldiers from being infected with one form of malaria they could not treat, and as a result those infected with it often died. Today, the number of troops suffering from the devastating adverse effects from taking Mefloquine far outweighs the danger of any of them dying from this form of malaria.Yet, U.S. and Canadian forces—probably British and Australian and all coalition forces too, but I don’t have confirmation of that—have issued Mefloquine in Iraq (but have since stopped) and continue to issue it in Afghanistan, despite reported evidence from the Gulf War, Angola relief effort, Somalia and Haiti UN Missions and Rwandan mission, plus other tropical deployments, that a significant number of troops are suffering from debilitating side effects, including suicides and/or aggressive violent behavior that has ended up in murder, usually of family members and, for sure, of spouses.

SOLDIERS FOR THE TRUTH talk about it on their web site. The Canadian National Defence Department finally issued a paper discussing the adverse effects in 1995, but the public didn’t know about it. CTV broadcaster, Christine Neilsen, produced an investigative report on W5 in October 1997. She took the plea of the suicide soldier’s mother seriously to investigate his death because she too had suffered adverse effects from taking Mefloquine on an assignment to Angola. She proved that the Canadian peacekeepers were being used as unwitting guinea pigs for the drug and suggested the true culprit in the Somalia scandal was Mefloquine, which affected the soldiers’ behavior and emotional states. Her research assistant uncovered the signed documents between Health Canada, the Department of National Defence and the drug company. Did the Canadian people rise up in revolt as a result of this scandalous treatment of our armed forces? No, Parliament barely uttered a peep.

We say we support our armed forces, but no one puts the brakes on issuing a drug that decimates our forces faster and more viciously than armed conflict. A British Medical Report sites the number as high as 1 in 10 people suffer adverse effects. They have been observing the results because, of all Western nations, a high proportion of British travelers visit tropical countries where malaria occurs. Canada admits that 1 in 1,000 can be adversely affected. Israel estimates 1 in 100,000. Whatever the ratio really is, it is TOO HIGH. We charge our armed forces with the job of saving our butts, but we don’t raise a finger to protect them from a drug company that has expanded its production of Mefloquine from the States to Pakistan under a different name, and this subsidiary has yet to place adequate warnings on its label to prescription users. NOT ACCEPTABLE.

USER BEWARE:
DOCTOR MICHELLE BRILL-EDWARDS, Canadian drug safety expert from transcript of radio interview with CBC’s Jennifer Westaway, August 26, 2002, 9:45 a.m., Reference NO. 226387-7:

BRILL-EDWARDS: “Well firstly, I should mention that there's a spectrum of what you could... as lay people understand this affects on the brain, or neuro-psychiatric side effects. Some of these are very common, every day problems that are not so severe, things like disturbed sleep, terrible dreams and so forth. But the more severe end of that spectrum of effects on the brain are actual psychosis, what we call acute psychosis, which, in lay terms, would be going crazy, someone who is out of touch with reality and whose actions can be bizarre. In particular, a big concern had been unexplained feelings of suicide and homicide.”

BRILL-EDWARDS: “Usually, there's a very strict order to not use this drug with alcohol. And the U.S. military has a good track record of trying to keep their military men dry in the field of battle. But once they return home, of course, then that restriction is off and alcohol may become a question. And we know that the drug lasts for a very long time in the body and this mixture may be lethal.”

BRILL-EDWARDS: “There is one study done by the military that was a carefully-done study that watched military men taking the drug in the field and they were seen weekly. And it's a very interesting point that in that study, two men had to be withdrawn from the study because of suicidal ideation.”

WESTAWAY: “What military was this?”

BRILL-EDWARDS: “This was the American military. And interestingly, of the 203 - I think it was - men in the study who had Mefloquine doses use in prophylaxis, two developed suicidal ideation. That would suggest that we're dealing with a serious psychiatric side-effect rate that is in the order of one in 100, not one in 12,000. . . . It changes the whole balance of whether and when this drug should be used in comparison with other drugs.”

For more information, you can visit BOWDENS MEDIA MONITORING LTD. online.