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Mefloquine is a relatively new anti-malarial drug, first made
generally available to the Canadian public in 1993.1
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 area.
The suggestion was made to us 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. Readers will see readily that further investigation
is warranted before any firm conclusions about the role of mefloquine
can be drawn.
Anti-malarial medication was clearly necessary for Canadian troops
deployed to Somalia. There is a year-round risk of malaria in
Somalia.
A recent U.S. medical journal article reported 48 cases of malaria
among U.S. forces stationed in Somalia over the entire duration
of the U.S. deployment. 2 In addition, the malaria
produced by P. falciparum was considered more severe than
some other forms of malaria and therefore warranted strong precautions.3
A September 1992 memorandum from DND's Director, Health Protection
and Promotion, entitled "Preventive Medicine Recommendations
for Somalia", also discussed the malaria risk. The memorandum
recommended the weekly use of mefloquine:
All of Somalia is considered malarious with [P.] falciparum predominating and chloroquine resistance reported. Mogadishu is said to present a lower but still present risk.... Mefloquine weekly is recommended. DHPP 2 hereby provides blanket approval for mefloquine to be provided to personnel deploying on this mission.... Personnel for whom mefloquine is medically contraindicated as per Ref D, e.g., pilots, can be given doxycycline 100 milligrams per day.4
Most CF members stationed in Somalia in 1992 and 1993 were prescribed
mefloquine. However, some CF 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.5
The report also noted that several CF members who suffered adverse
effects from taking mefloquine were switched to doxycycline.
CF members began taking mefloquine one week before deployment
and continued to take it weekly during deployment and for four
weeks after deployment.6 They received a preventive
(prophylactic) dose of 250 milligrams once a week. A message of
December 25, 1992, confirmed that 3,000 mefloquine tablets were
issued on December 23, 1992, and that a further 24,000 tablets
were on order.7
Mefloquine was taken once a week, on Wednesdays. A standing operating
procedure dated November 11, 1992, stated:
Malaria prophylaxis will be provided by the use of once weekly dosing with Mefloquine. The UMS [Unit Medical Services] staff will supervise the distr of this med, and will likely occur at the same time and place each week; i.e. the Wed noon meal. A nom roll will be used to pos check distr. 8
However, a later standing operating procedure, dated January 2,
1993, stated that "All pers will take the anti-malaria pill
mefloquine every Friday."9 Still, it appears from
the limited information before us that mefloquine was normally
taken on Wednesdays. Later in this chapter we discuss the significance
of the day on which mefloquine was taken.
The first public suggestion that mefloquine might have caused,
or contributed to, abnormal behaviour in Somalia appears to have
been made by Maj Barry Armstrong, the officer commanding the surgical
section of the medical unit in Somalia. Speaking to the Canadian
Forces Medical Services Group Conference, Operational Medicine,
October 26,1993, Maj Armstrong argued as follows:
I believe that the UN's failures in Somalia are rather exceptional, considering previous peacekeeping successes. I believe that a simple reason may exist. Canadian and American troops may have been impaired by the use of mefloquine....
Mefloquine is well known to have neurologic side effects. The manufacturer's literature states that reactions are rare, but include convulsions, psychosis, nightmares, dizziness, headache, confusion, anxiety and depression. There are over 100 case reports of such serious reactions requiring hospitalization. From the medical literature, it seems that such reactions occur in 1 per 2,000 people when prophylactic doses are given, or up to 1 per 200 when stronger, treatment doses are given. [Treatment doses are given only to those who contract malaria; no suggestion has been made that any non-infected CF member in Somalia received the stronger treatment dose.]
Less severe reactions (not requiring hospitalization) are more common, but the incidence is not known. We had one psychiatric hospitalization in Belet [H]uen, which did not respond to the usual treatment of battle stress. The diagnosis made by psychiatrists at NDMC [National Defence Medical Centre], after he was evacuated, was an organic brain syndrome, probably due to mefloquine. The suicide attempt in theatre may also be mefloquine related.10
There are three of us presenting on Somalia today. Two of us had minor neuropsychiatric problems which occurred regularly in the 24 to 48 hours after our weekly mefloquine doses. If there are two of us, these reactions aren't so 'rare'. Burke in The Lancet, June 1993, writes, "As a demographer with a quarter of a century's experience, I know that if I encounter finite numbers of a supposedly rare occurrence, the true rate is higher." He goes on to recommend alternatives to mefloquine.
In 1992, mefloquine was the best choice as an anti-malarial. However, we realized some of the risks and did not prescribe this medication for pilots. The U.S. military has also rejected mefloquine use for their aircrew, because of the neuropsychiatric side effects.
The mechanism of mefloquine effects on the brain (like its effects on malaria) is unknown. However, it is structurally similar to quinine and quinidine. Mefloquine can cause additive effects with these drugs. Quinine and quinidine are known to be blockers of the fast sodium channel. This sodium channel is found on the cell membrane of nerve cells, and is activated early when nerve cells fire. Specifically, it is believed that agents similar to mefloquine block the sodium channel by locking closed the 'inactivation gate' in the channel. Some sodium channel blockers, such as Dilantin (diphenylhydantoin), have been clearly shown to have adverse effects on cognition. According to my literature review, these neuropsychiatric tests have not been done on any subjects taking mefloquine.
Further, it should be better known that the mefloquine malaria pills taken by the Canadian Forces are 10 per cent stronger than those given to the American Forces, despite both being labelled as 250 milligrams. (250 milligrams of mefloquine base in the Basel manufactured pills, versus 250 milligrams of mefloquine salt in the U.S. produced pills).
I believe that mefloquine causes sub-clinical adverse effects on cognition. The usual soldier taking the drug is not aware of any problems. Nevertheless, his thinking could be impaired. Like many people tipsy after 2 or 3 alcohol-based drinks, he would not recognize that his judgement was diminished. He would not recognize this because the adverse effect is on cognition, including impaired insight. Like the impaired driver who feels fine, our soldier would feel fine, despite his impairment....
Definitive proof regarding the effects of mefloquine on thinking would require a randomized, double-blind, placebo-controlled study. The measurements should be taken by neuropsychiatric testing (the same techniques used to prove the adverse neurologic effects of low-dose alcohol). Such a study would be much less expensive than the costs of flying MlAl tanks to Mogadishu. The real difficulty in Somalia might be drug side-effects. It would be wiser to conduct such a study of mefloquine, than to simply abandon the concept of international peace-making.
On October 6, 1994, John Cummins, a member of Parliament, issued
a press release relating to the death of Shidane Arone.11
The press release, although referring (apparently mistakenly)
to a drug to combat cholera, not malaria, raised the possibility
that the drug (presumably mefloquine) may have contributed to
the violent behaviour of MCpl Matchee:
Another element of this unfortunate affair which has not been addressed was that every Thursday troops in Somalia were given an experimental drug to combat cholera.12 The day the drug was administered in Somalia was known as "psycho Thursday". What effect this drug and the beer he consumed may have had on the behaviour of Corporal Matchee has never been discussed.
Mr. Cummins raised the same issue later that month in the House
of Commons:
[T]he minister and the military establishment ignored the well known effect of Mefloquine, a malaria drug administered to Canadian troops in Somalia. Side effects include violent dreams, hallucinations, confusion, anxiety and mental depression. Mefloquine could have precipitated the murder of the prisoner and Master Corporal Matchee's attempted suicide.13
In a letter dated October 26, 1994, to the Minister of National
Defence, Mr. Cummins restated his concern about mefloquine:
The Department should have known of the problems associated with the combination of mefloquine and alcohol prior to Somali[a], and certainly would have known afterwards but has so far failed to conduct either field or clinical research....
I would ask that you initiate the process for the release from military detention of Trooper Kyle Brown pending an investigation. 14
The Minister of National Defence replied to the letter from Mr.
Cummins on December 11, 1994.15 The Minister's letter
stated that mefloquine "was, at the time of deployment to
Somalia, and continues to be, the drug of choice for the prevention
of malaria in Africa." The Minister also noted that recent
CF use of mefloquine in Rwanda showed that side effects might
occur in 10 to 20 per cent of users. These side effects included
bad dreams and nausea. However, only three of 650 CF members in
Rwanda had to be switched to another drug because of significant
side effects from mefloquine.
The Minister's letter continued:
A close review of the relevant scientific literature does not indicate that mefloquine, when used to prevent malaria, impairs thinking or judgment.... On specific questioning, CF medical authorities in Rwanda have not expressed any particular concern about mefloquine-related effects on thinking or behaviour among the CF units deployed in Rwanda; further, their operational commanders have not expressed any such concerns. ...
In summary, after careful review, the Department of National Defence believes that mefloquine did not play any significant role in the tragic events in Somalia.
Before he had received this reply from the Minister, Mr. Cummins
made a formal Inquiry of the Ministry on November l4,1994.16
The inquiry asked what field studies were undertaken or funded
by the Department of National Defence into the possible adverse
effects of mefloquine, including the impairment of judgement of
CF personnel in Somalia and on their return to Canada. Mr. Cummins
asked a similar question about possible studies relating to Canadian
Forces in Rwanda. He also asked how much alcohol CF personnel
were allowed to have daily in Somalia and Rwanda, what adjustments
were made to the dosage of mefloquine as a result, and what advice
was given to persons required to take mefloquine who might be
expected to use alcohol during their tour of duty.
The response by the Minister indicated that no studies had been
undertaken into the possible adverse effects of mefloquine, and
none were considered necessary. The Minister replied that the
specific policy regarding the consumption of alcohol was left
to the field commander who determined the amount of alcohol permitted
per day during deployment. The reply stated that, in Somalia,
members were not permitted any alcohol during the first six weeks
of their deployment, following which each member was allowed two
beers per day, except on special occasions where no restrictions
were imposed - for example, a regimental birthday.
The Minister's reply also asserted that until quite recently,
there was no scientific evidence that personnel taking mefloquine
were at an enhanced risk of a serious adverse interaction when
drinking alcohol. Further, the prescribing information for mefloquine
did not at that time mention concern about such an interaction.
Thus, when CF members were deployed to Somalia and Rwanda, the
Minister believed that there was no evident need to warn those
taking mefloquine about an interaction with alcohol. However,
the Minister acknowledged that a 1995 Canadian medical journal
reported a single case of a likely interaction between mefloquine
and copious alcohol ingestion that resulted in a temporary psychotic
state in the patient.17 The Minister maintained that
this was the first reasonably documented reported case among the
millions of persons who have taken mefloquine worldwide in the
last decade, many of whom had likely consumed alcohol, even in
substantial amounts. For this reason, the Minister argued that
the risk of such an interaction would seem to be quite small.
The Minister did note that, in light of this medical journal report,
the Surgeon General felt it prudent to caution members taking
mefloquine specifically against the concurrent excessive use of
alcohol. A direction to that effect was being prepared at the
time.
Two main issues arise from the use of mefloquine by Canadian troops
in Somalia:
Even before the deployment of CF members to Somalia, DND believed
that mefloquine might not be suitable for certain individuals
- for example, pilots and divers - for whom some of the adverse
effects, such as dizziness and loss of fine motor control, could
be dangerous.
However, there was no indication from correspondence we have reviewed
that DND knew of any frequent major side effects of mefloquine.
In fact, DND medical advisers would have no reason to have such
knowledge. Almost all the medical literature at the time of deployment
claimed that serious neuropsychiatric effects from mefloquine
used as a prophylactic were rare. For example, one study published
in 1991 examined neuropsychiatric effects in subjects who had
used mefloquine and suggested that serious neuropsychiatric effects
occurred in only about one in 13,000 cases.18 The 1991
Canadian Recommendations for the Prevention and Treatment of Malaria
Among International Travellers stated the following:
Mild, non-specific reactions (nausea, heartburn, and mild dizziness) have been described in up to 20 per cent of users. Rarely, severe vertigo, seizures, and psychosis have been reported with weekly mefloquine prophylaxis, but these problems appear to be more frequently observed with higher doses as used for treatment....
Contraindications to the use of mefloquine include ... [s]eizure disorder or history of severe depression or psychosis.19
Only one of the studies we reviewed from the early 1990s suggested
that mefloquine might interact adversely with alcohol, and that
study simply stated that "[i]n four cases, the reporting
physician mentioned exertion, fatigue, sun exposure or alcohol
as potential co-factors.20 In fact, the first firmly
documented reference to the possible harm of combining mefloquine
and alcohol appeared in a 1995 Canadian Medical Association
Journal case study involving only one individual. 21
One weekly medical situation report from Somalia gave some indication
that some CF members were encountering possible side-effects relating
to mefloquine.22 The report, dating from mid -December
1992, noted "several" instances of gastrointestinal
upset, headache and thought disturbance, "temporally related
to mefloquine use".
The post-deployment report of HMCS Preserver discussed
the use of mefloquine and identified several side effects:23
Malaria Prophylaxis: The ship's company began taking Lariam (Mefloquin) 250mg weekly on 26 November 1992. Three members on B/P medication commenced Doxycycline 100mg daily. All aircrew on active flying duties started Doxycycline. Numerous reactions to mefloquin were reported. One patient contracted Falciparum malaria and denied missing medication. A large percentage of the reactions were GI related: with nausea, burning epigastric pain and diarrhoea. Several patients were switched to Doxycycline. Ten patients experienced nightmares, with one patient having feelings of unease and paranoia. One patient heard voices and talked to himself. All were switched to Doxycycline with no subsequent problems.
In-theatre experience with mefloquine was also touched on in a
few interviews conducted by Inquiry staff and in testimony. Several
of the CF members interviewed reported that mefloquine caused
or may have caused side effects, but they did not report the side
effects as serious. Among the symptoms they reported experiencing
themselves or that they heard about from others were queasiness,
euphoria, depression, inability to sleep, vivid dreams and nightmares.
Some of those interviewed about mefloquine were asked about the
possible effects of combining alcohol and mefloquine. None noticed
any additional change in behaviour associated with alcohol consumption.
Maj Mansfield testified about mefloquine :
I didn't have any adverse reactions to mefloquine, people might argue that I did, but there were others who clearly did and they would report things like really bad dreams. And ... you took the time to open the bottle and read the list of possible side effects and this was enormous ... [W]e used to joke at the time that ... if you get somebody angry he's just going to walk into the old church tower and waste 20 people, oh sorry, bad mefloquine trip.... But me, personally, I didn't have any problems with it. A couple of my troops did and it typically was bad ... dreams ... inability to sleep.24
CWO (ret) Jardine was also asked whether he had experienced any
particular reaction to mefloquine:25
No, other than it made you feel weird for the first day after you took it. You know, you sort of got that queasy feeling about it, your stomach unsettled and then it would go away.
CWO (ret) Jardine also testified that he never experienced any
unusual effects that seemed to be attributable to alcohol and
mefloquine.
As mentioned above, Maj Armstrong described one case of organic
brain syndrome in Belet Huen that NDMC concluded was "probably"
due to mefloquine. Maj Armstrong also argued that the suicide
attempt in theatre may have been mefloquine-related. As well,
he reported that two of the three presenters at the 1993 conference
had had recurrent minor neuropsychiatric problems in the 24 to
48 hours after their weekly mefloquine doses.
There was no indication from any of the reports we reviewed concerning
in-theatre medical problems that mefloquine may have interacted
adversely with alcohol. It is, of course, possible that such adverse
effects did occur but were not noticed or reported in the documents
we reviewed, in the interviews we conducted, or in the testimony
we heard.
Interaction with Alcohol
The first firmly documented mention in the English-language medical
literature of a possible adverse interaction between mefloquine
and alcohol appears to be a case note in a 1995 Canadian Medical
Association Journal. The case note reported one adult male's
acute psychosis and depression associated with the combination
of mefloquine and alcohol, "an association not previously
reported."26 The man was taking a weekly dose
of mefloquine and twice consumed about a half-litre of whisky.
He experienced paranoid delusions and auditory and visual hallucinations,
and felt depressed and suicidal. The authors concluded: "The
circumstances of this case strongly suggest that it was the combination
of [mefloquine] and ethanol that caused [the] two episodes of
severe psychiatric disturbance."
We located no other published studies identifying a possible adverse
interaction between mefloquine and alcohol, apart from the 1992
study, mentioned above, that briefly mentioned alcohol as a possible
risk factor.27
Adverse Effects of Mefloquine Alone
A U.S. study published in 1993 noted that in Somalia only rarely
would mefloquine be withdrawn from U.S. military populations during
operational use. "In Somalia, only 1 of 344 soldiers surveyed
changed anti-malarial medication due to an adverse event, a severe
headache".28 The study concluded that weekly mefloquine
(the prophylactic dose) was well tolerated. "Sleep disturbance
and increased dream activity were detected in two to three times
more individuals in the mefloquine groups. Depressive feelings
were noted in two to three times more individuals in the mefloquine
groups than in the chloroquine group early in the course of the
study, and resolved in the majority of subjects as tolerance developed."29
In late 1993 or early 1994, a draft letter was prepared for the
signature of the Surgeon General. The letter appeared to be a
response to Maj Armstrong's assertions that mefloquine caused
serious problems in Somalia. It concludes,
"[w]e are not aware of any data to support the suggestion
that [mefloquine] is perhaps causing previously unrecognized,
widespread, subclinical impairment of cognition". Dr. J.
S. Keystone, Director of the Tropical Disease Unit at The Toronto
Hospital, was asked by DND to review the letter. In his February
1994 reply, Dr. Keystone stated:
Based on my experience with hundreds of returned travellers who have used mefloquine and an examination of the medical literature on the subject, I fully concur with the conclusions reached by your staff concerning the potential adverse effect of mefloquine. I too am not aware of any data which support the suggestion that mefloquine causes "previously unrecognized, widespread impairment of cognition."30
Much of the reference literature since the time of the Somalia
deployment continues to identify mefloquine as an appropriate
anti-malarial drug for some regions of the world. A 1995 supplement
to the Canada Communicable Disease Report describes mefloquine
as the drug of choice of most travellers to chloroquine-resistant
regions.31 It calls mefloquine "an effective chemosuppressive
and therapeutic agent against drug resistant P. falciparum.
It is significantly more effective than the combination of chloroquine
and proguanil for malaria chemosuppression in sub-Saharan Africa."
The supplement reports that in chemosuppressive (prophylactic)
doses, mefloquine is well tolerated:
Adverse effects are similar in frequency and severity to those reported with weekly chloroquine use. Approximately 25 [per cent] of travellers will experience side effects from mefloquine, most of them mild and self-limited. The most frequent minor side effects from mefloquine use are nausea, strange dreams, dizziness, mood changes, insomnia, headache, and diarrhea.... Severe neuropsychiatric reactions (psychosis, convulsions) are infrequent with prophylactic doses and occur in approximately 1/10,000 to 1/13,000 individuals.... Excessive consumption of alcohol should be avoided due to a possible enhanced risk of neuropsychiatric reactions...32
The supplement identifies several situations when mefloquine should
not be used, among them, where individuals have a history
of severe psychiatric illness.
The 1995 Physician's Desk Reference notes that post-marketing
surveillance of Lariam (mefloquine) has identified several adverse
reactions, including central nervous system disturbances (psychotic
manifestations, hallucinations, confusion, anxiety and depression).33
The Desk Reference also issues the following general precautions:
Caution should be exercised with regard to driving, piloting airplanes and operating machines, as dizziness, a disturbed sense of balance, neurological or psychiatric reactions have been reported during and following the use of Lariam.... During prophylactic use, if signs of unexplained anxiety, depression, restlessness or confusion are noticed, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued. Lariam should be used with caution in patients with psychiatric disturbances because mefloquine use has been associated with emotional disturbances.
Therefore, even by 1995, although there was a continuing awareness
in medical literature of possible severe neuropsychiatric reactions
to mefloquine, there was also a continuing perception that these
reactions were rare.
The 1996 Compendium of Phannaceuticals and Specialties
carries several warnings about the use of mefloquine.34
Among them is one about the impact of mefloquine on behaviour:
"Patients with a past history of psychiatric disturbances
or convulsions should not be prescribed mefloquine prophylactically."
The Compendium identifies the following adverse effects of mefloquine:
Overall the most frequently reported adverse effects are nausea, vomiting, dizziness or vertigo, loss of balance, somnolence, sleep disorders, (insomnia, abnormal dreams), loose stools or diarrhea, and abdominal pain.
Less frequently reported symptoms include: Central and Peripheral Nervous System: sensory and motor neuropathies (including paresthesia), convulsions or seizures, visual disturbances, tinnitus and vestibular disorders, emotional problems (anxiety, restlessness, depressive moods, psychotic or paranoid reactions), forgetfulness, confusion, hallucinations.
Note: In the literature, the incidence of moderate to severe neuropsychiatric adverse drug reactions (e.g., seizures, psychotic reactions) with mefloquine has been reported at 1/215 following treatment and 1/13 000 following prophylactic use. [The latter figure would apply to CF members, since they were given mefloquine as a prophylactic.]
However, there is recent controversy about the frequency of severe
neuropsychiatric symptoms after taking prophylactic doses of mefloquine.
In June 1993 The Lancet printed a letter from a person
who reported severe nightmares, reduced sensation in his legs
and "occasionally wondering what it would be like to jump
the eight floors from my hotel room":
Later, when I consulted on another matter a British doctor who has been in Kampala some thirty years, he stated that he "never advises patients to take mefloquine. It is a very dangerous drug".35
A letter from Dr. G.C. Cook, a physician at the Hospital for Tropical
Diseases in London, England, was published in the British Medical
Journal in July 1995:
Advocates of widespread use of mefloquine have produced figures purporting to support a rarity of side effects (in particular neuropsychiatric ones), which are seemingly far less common when this agent is used in chemoprophylaxis than when it is used in chemotherapy. A great deal of clinical experience indicates, however, that these reports seriously underestimate the prevalence of side effects in travellers: only rarely does a week pass in which I am not informed (at the Hospital for Tropical Diseases) by at least one traveller of his or her personal experience of side effects of mefloquine (many of them severe) or of similar symptoms in a colleague or fellow traveller. Many travellers refuse to take mefloquine in the light of their experience of its neuropsychiatric side effects.
Mefloquine should be reserved for chemotherapy [treatment] of infection with P. falciparum that is resistant to quinine.36
As well, the British Medical Journal published a letter
in June 1995 expressing concern about the recommended wider use
of mefloquine for British travellers.37 The author
of the letter wrote that of 250 mining engineers and their families
based in West Africa, more than 162 developed problems, including
malaise, lethargy, headache and dizziness.
Another letter to the British Medical Journal indicated
that the U.K. Ministry of Defence had, since January 1995, been
conducting a double blind, randomized, controlled trial of chemoprophylaxis
with mefloquine versus chloroquine-proguanil. The letter noted:
The subjects of the trial are British troops exercising in Kenya. Of the total trial population of 624 soldiers, 317 were randomly assigned, by means of random numbers generated by a computer, to receive mefloquine and 307 to receive chloroquine-proguanil. A questionnaire on "unusual" symptoms or illnesses was administered at eight weeks of chemoprophylaxis and was returned by 145 (46%) soldiers in the mefloquine arm of the trial and 142 (46%) in the chloroquine-proguanil arm.
T'he preliminary results of the trial show that both mefloquine and chloroquine-proguanil have a much higher mild toxicity than has commonly been recognised. Altogether 131 (90%) respondents given mefloquine reported some toxicity as a result of their (unknown) chemoprophylaxis, as did 126 (89%) responders given chloroquine-proguanil.38
A table accompanying the letter showed reports of adverse reactions
of three to seven days' duration. Using these criteria, three
per cent of those using mefloquine reported paranoid feelings,
and two per cent had anxiety attacks.
We are not in a position to resolve the debate within the medical
community about the true frequency of severe side effects from
mefloquine use. DND or individual members of the CF may wish to
pursue this issue in another forum.
In fact, we learned that DND intends to conduct further study
on the effects of mefloquine. In April 1997, the Surgeon General,
MGen Clay, responded to recent media stories about the possible
effect of mefloquine on the behaviour of CF troops in Somalia.
MGen Clay explained:
Subjects for the study will be military personnel who are scheduled for deployment to a malarial region and are prescribed mefloquine as part of their usual pre-deployment preparation. Baseline psychometric testing will be conducted before and after personnel take the drug, to determine whether there are any objectively measurable neuropsychological effects associated with this drug.
Since receiving approval two years ago, the study has not been conducted simply because CF personnel have not been deployed in sufficient numbers to a region where the use of mefloquine is required. It was never planned to include soldiers deployed to non-malarial regions, nor was it planned to include a mefloquine-alcohol component in the study.
The study will be conducted under the direction of military medical personnel, using civilian experts as scientific advisers...
Mefloquine is the accepted prophylaxis when travelling in areas where chloroquine-resistant malaria is found. The Canadian Forces Medical Service will continue to monitor all developments concerning mefloquine, and will continue to use the expertise available in centres such as the Toronto Hospital's tropical disease unit.39
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 and inability to sleep following the use of
mefloquine. There were also a limited number of more serious events
that may have been linked to mefloquine. 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. It appears from the evidence before us
that most CF members took their mefloquine on Wednesdays. Thus,
if mefloquine were implicated in misbehaviour, one would expect
the misbehaviour to occur in the few days after the weekly mefloquine
pill was taken.
Among the violent incidents in 1993 that we investigated were
the following:
Wednesday, February 17 - two Somali nationals shot at riot
Thursday, March 4 - two Somali nationals shot at compound
Tuesday, March 16 - Shidane Arone killed
Wednesday, March 17 - one Somali national shot at International Committee of the Red Cross compound
Friday, March 19 - apparent attempted suicide by MCpl Matchee
We can, of course, draw no firm conclusions from this information.
We do not know whether those involved in these incidents had in
fact taken mefloquine. We do not know what day they took it if
they did. Most important, without extensive further investigation,
we cannot even hope to judge whether their behaviour may have
been influenced by mefloquine. That is for psychiatric and other
medical experts to determine.
As a case in point, the following additional investigation would
be necessary to determine whether mefloquine might have been a
factor in the behaviour of MCpl Matchee on the night of Mr. Arone's
death and when MCpl Matchee later apparently attempted suicide:
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 above, we
are not able to reach a conclusion on this issue. We can offer
only general observations about the decision to prescribe mefloquine
for personnel deployed to Somalia.
- Did the members in question use mefloquine?
- Did any of the CF 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.
- Did any of the CF members in question have a history of psychiatric disorders that could increase the risk of severe side effects from mefloquine?
- On what day of the week did they take mefloquine? On what day, or days, of the week did their misbehaviour occur?
- Did they complain at any point about any symptoms, mild or severe, that are now known to be associated with mefloquine?
- Did anyone notice abnormal behaviour on the part of the CF members in question in the few days after the latter consumed mefloquine? If so, what was the behaviour? Is it reasonable to say that mefloquine was, or might 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)?
1. Mefloquine hydrochloride. In Canada, mefloquine is sold under the trade name Lariam.
2. M.R. Wallace et al., "Malaria among United States troops in Somalia", American Journal of Medicine 100/1 (January 1996), pp. 49-55.
3. Briefing note, Gen A.J.G.D. de Chastelain, Chief of the Defence Staff (CDS), and Mr. R.R. Fowler, Deputy Minister (DM), to the Minister of National Defence (MND), November 10, 1994, Document book 124, tab 12A, P. 1/3. The briefing note was prepared by Capt (N) R.C.D. Climie, Director, Health Protection and Promotion (DHPP), NDHQ.
4. Memorandum, LCol M.L. Tepper, DHPP, and Capt (N) R.C.D. Climie, DHPP, "Preventive Medicine Recommendations for Somalia", file 6600-15 (DHPP 2), September 1992, DND 115004.
5. Letter, Capt (N) R.W Allen, Commanding Officer, HMCS Preserver, to Regional Surgeon, Maritime Forces Atlantic Headquarters (MARLANT HQ), "Post-Deployment Report Op Deliverance, 16 November 1992-7 April 1993", Document book 124, tab 5, p. 5.
6. Briefing note, CDS and DM to MND, November 10, 1994, Document book 124, tab A, p. 1/3.
7. Document book 23, tab 8.
8. Canadian Airborne Regiment, Standing Operating Procedures for United Nations Operations, 11/14/92, DND 178140, Control 000119.
9. CJFS Somalia and HQ and Signal Squadron Standing Operating Procedures, Foreword, January 2, 1993, p. 14/14, DND 385818, Control 004027.
10. This appears to be a reference to MCpl Matchee. Maj Barry Armstrong, Document book 124, tab 6, DND 129924.
11. Press release, "Delta MP Urges Defence Review of Military Sentences in 'Somali' Case", October 6, 1994.
12. Mr. Cummins may also have erred about the day on which the drug was taken. Other information before us suggests that mefloquine was normally taken on Wednesdays. However, Mr. Cummins may have had specific information about when MCpl Matchee took his medication and what medication he took.
13. House of Commons, Debates, October 18, 1994, p. 6847.
14. Letter, John Cummins, M.P., to the Honourable David Collenette, Minister of National Defence, regarding the case of Trooper Kyle Brown of the Airborne Regiment, October 26, 1994, DND 093991, Control 022469.
15. Letter, Honourable David Collenette to John Cummins, M.P., Investigation of Pre Brown, December 11, 1994, DND 093988, Control 022468.
16. Inquiry of Ministry, Mr. John Cummins (Delta), November 14, 1994, Q-105.
17. The Minister was almost certainly referring to a February 1995 article in the Canadian Medical Association Journal 152/4 (February 15, 1995), pp. 515-517.
18. T Weinke et al., "Neuropsychiatric Side Effects after the use of Mefloquine", American Journal of Tropical Medicine and Hygiene 45/1 (1991), pp. 86-91. The authors note, however, that the incidence of adverse effects could in fact be higher, since they were relying on information about the number of doses of mefloquine sold, which would almost certainly be higher than the number consumed. In other words, some individuals might have received a prescription for mefloquine but not used it.
19. Committee to Advise on Tropical Medicine and Travel, Canada Diseases Weekly Report (Health and Welfare Canada), vol. 17S2 (February 1991) "Canadian Recommendations for the Prevention and Treatment of Malaria among International Travellers", P. 5.
20. J.L. Bem, L. Kerr and D. Stuerchler, "Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions", Journal of Tropical Medicine and Hygiene 95 (1992), p. 169.
21. Canadian Medical Association Journal 15 2/4 (February 15, 1995), p. 515.
22. Weekly medical situation report, December 13-20, 1992, Document book 124, tab 3.
23. Letter, Capt (N) Allen to Regional Surgeon, MARLANT HQ, "Post Deployment Report Op Deliverance, 16 November 1992-7 April 1993", p. 5.
24. Testimony of Maj Mansfield, Transcripts vol. 103, pp. 20421-20422.
25. Testimony of CWO (ret) Jardine, Transcripts vol. 105, pp. 20972-20973.
26. Canadian Medical Association Journal 152/4 (February 15, 1995), p. 515.
27. Bem, Kerr and Stuerchler, "Mefloquine prophylaxis", pp. 167-179.
28. J. Sanchez et al., "Tolerability of prophylactic Lariam regimens", Tropical Medicine Parasitology 44 (1993), p. 257.
29. Sanchez et al., "Tolerability of prophylactic Lariam regimens", p. 257. However, Maj Armstrong noted in his address to the Canadian Forces Medical Services Group Conference in October 1993 that the mefloquine pills taken by the CF were 10 per cent stronger than those given to U.S. forces in Somalia (Document book 124, tab 6).
30. Letter, Dr. J.S. Keystone to Capt (N) R.C.D. Climie, DHPP, NDHQ, February 7, 1994, Document book 124, tab 8.
31. Committee to Advise on Tropical Medicine and Travel (CATMAT), Canada Communicable Disease Report (Health Canada), Supplement 1995, "Canadian Recommendations for the Prevention and Treatment of Malaria among International Travellers", October 1995, p. 6.
32. CATMAT, "Canadian Recommendations", p. 6.
33. The 1995 Physician's Desk Reference, vol. 85 (Medical Economics Co. Inc.).
34. "Larium", in Compendium of Pharmaceuticals and Specialties (1996), p. 752.
35. B. Meredith Burke, letter to the editor, The Lancet 341 (June 19, 1993), p. 1605.
36. Ashley Croft, Senior Registrar in public health medicine, Army Medical Directorate, Ministry of Defence, Aldershot, letter to the editor, British Medical Journal, July 15, 1995 (emphasis added).
37. I.C. Perry, Consultant in occupational medicine, letter to the editor, British Medical Journal, June 24, 1995.
38. Ashley Croft, letter to the editor, British Medical journal, July 15, 1995.
39. Letter to the editor, The Ottawa Citizen, April 22, 1997, p. A13.
40. Evidence at the court martial of Pre Brown gave
some information about the state of mind of MCpl Matchee on the
evening of Mr. Arone's death (March 16th). However, the descriptions
of MCpl Matchee's moods were not entirely consistent. In any event,
we are not in a position to state whether mefloquine contributed
to his particular state of mind without further, and likely extensive,
evidence.
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