On 19 June 2018, the Senate referred the following matter to the Senate
Foreign Affairs, Defence and Trade References Committee for inquiry and report
by 17 September 2018:
the current and past policies and practices for:
prescribing Quinoline anti-malarial drugs to ADF personnel, and
identifying and reporting adverse drug reactions from Quinoline
anti-malarial drugs among ADF personnel;
the nature and extent of any adverse health effects of those who have
taken Mefloquine/Tafenoquine on serving and former ADF personnel;
the support available for partners, carers and families of personnel who
experience any adverse health effects of Quinoline anti-malarial drugs;
a comparison of international evidence/literature available on the
impact of Quinoline anti-malarials;
how other governments have responded to claims regarding Quinoline
any other related matters.
On 20 August 2018, the Senate agreed a reporting extension until
29 November 2018.
On 29 November 2018 the Senate agreed to a further extension until
6 December 2018.
The committee decided to table on 4 December 2018.
Conduct of the inquiry
Details of the inquiry were placed on the committee's website at http://www.aph.gov.au/senate_fadt.
The committee also contacted a number of relevant individuals and organisations
to notify them of the inquiry and invite submissions by 31 July 2018. The
committee continued to receive submissions after the closing date. Submissions
received are listed at Appendix 1.
The committee held six public hearings: Brisbane on 30 August;
Townsville on 31 August; Melbourne on 5 November and Canberra on 11 October, 15
October and 8 November 2018. A list of witnesses who gave evidence is available
at Appendix 3. Following the hearing on 30 August in Brisbane, the committee
conducted a site visit to the Australian Defence Force Malaria and Infectious
Disease Institute (ADFMIDI) at Enoggera Barracks.
The committee thanks the organisations and individuals who made
submissions and those who participated in the public hearings for the inquiry.
The committee recognises the difficulties faced by individuals who are
unwell in participating in the inquiry processes and thanks those who were able
to make submissions and provide evidence. The committee appreciates that many individuals
made submissions with their mates and families in mind and that they told their
story also for those who, for whatever reason, are unable to at this time. The
committee sincerely appreciates their efforts.
The committee wishes to particularly acknowledge the partners and
families of veterans who also provided evidence to the committee.
Realising the challenges for potential submittors, the committee
provided assistance to those who wished to make submissions and thanks the
Department of Veterans' Affairs (DVA) who also made assistance available. DVA
also made staff available at hearings to facilitate access to support and services
Structure of the report
Chapter 1 includes key terminology, concepts and medications and
summarises some other relevant inquiries (ToR e);
Chapter 2 details the disagreement evident during the inquiry between
individuals and advocates and the medical community over the cause of their
symptoms (ToR a(ii), b and d);
Chapter 3 covers Australian Defence Force (ADF) antimalarial
polices and details about the trials, including the issue of informed consent
(ToR a, a(i), a(ii) and b);
Chapter 4 covers the actions taken by the Department of Defence (Defence)
and DVA to date, assistance available, witnesses' experience of seeking
assistance and what assistance needs to be provided moving forward; (ToR c) and
Chapter 5 details the committee's conclusions and
Key terminology, concepts and medications
|Atovaquone and proguanil hydrochloride (brand name
||Listed on the Australian Register of Therapeutic Goods for
malaria treatment since 1998 and prevention since late 2001.
It is a combination of two drugs: atovaquone and proguanil.
It has been the second line preventative antimalarial for the ADF since 2006,
used when doxycycline is not suitable. It needs to be taken daily.
||An antibiotic. There are a number of brands listed on the
Australian Register of Therapeutic Goods. It is listed on the World Health
Organization (WHO) Model List of Essential Medicines for treating bacterial
infections as well as for malaria treatment and prevention.
|Malaria chemoprophylaxis or malaria prophylaxis
||Taking one or more dugs to prevent malaria.
|Mefloquine (brand name Lariam)
||An antimalarial for prevention and treatment which was put
on the Australian Register of Therapeutic Goods on 27 January 1993.
Roche Products Pty Ltd advised that mefloquine emerged from 'An extensive
research program undertaken independently by the United States Army [the
Walter Reed Army Institute of Research] in 1963, in which over 100,000
separate compounds were evaluated prior to mefloquine being selected'.
As at 19 February 2018, mefloquine was approved in 27 countries and more
than 40 million patients have been treated since it was first made
It is listed on the WHO Model List of Essential Medicines for both malaria prevention
It is also listed by the US Centers for Disease Control and Prevention for
malaria prevention and treatment.
It is still a recommended preventative antimalarial for travellers to
||An antimalarial used to prevent and treat relapses of
malaria. It is given to people as they leave a malarious area as eradication,
to kill any malaria parasites that may still be present in the body. It is
taken twice daily for 14 days.
||Medication given to prevent disease.
||Prevention of relapse.
||Recently approved by the US FDA for prevention
and radical cure of malaria.
In September 2018 it was approved by the Australian Therapeutic Goods
Administration (TGA) for prevention
and radical cure
of malaria. At the time of the trials it was not yet approved in Australia
for use as an anti-malarial medication. It is chemically related to
and is structurally different to mefloquine.
Like primquine, tafenoquine shares a key safety concern which is the
potential to cause hemolysis (destruction of red blood cells) in individuals
with a hereditary disorder, deficiency of Glucose‐6‐Phosphate‐Dehydrogenase (G6PD)
enzyme. Hence individuals must be tested for G6PD deficiency before receiving
either of these drugs.
More than 4,000 people, both military and civilian, have taken tafenoquine in
clinical studies around the world.
The difference between mefloquine
The differences between mefloquine and tafenoquine were discussed with
GlaxoSmithKline Australia Pty Ltd. Dr Alison Webster, Head, Global Health
Clinical Research and Development, GSK advised:
They're members broadly of a class of drugs that are called
quinolines, but within that class there are very different chemicals, or
medicines. Tafenoquine is an analogue of primaquine. Primaquine and tafenoquine
are 8-aminoquinolines. They uniquely have an activity against the dormant liver
stage of vivax malaria and so uniquely have the ability to prevent relapse of
vivax malaria. They also share a particular safety issue, which is that they
can cause anaemia in patients who lack a certain enzyme called G6PD. All
patients who take either primaquine or tafenoquine must be tested for G6PD
deficiency before they receive the drug. Mefloquine is a different kind of
quinoline, but there are many others. Chloroquine is a member of that group, as
well...All of these are unique chemicals with their own specific safety profile
and their own specific activity against malaria.
Mr Svend Peterson, Managing Director, Roche Products Pty Ltd explained
to the committee it is important that there are a range of malaria prevention
and treatment options available to reduce the risk of infection and death from
malaria as not all patients can tolerate the medications and certain parasites
have become resistant to some antimalarials.
Malaria is a life threatening disease caused by parasites which are transmitted
to people by mosquitoes. There are five parasite species that cause malaria in
humans with P. falciparum
and P. vivax causing most of the disease burden.
According to the latest WHO World Malaria Report released in November
2018 there were an estimated 219 million cases of malaria in 2017, up from
216 million cases in 2016. In 2017 there were an estimated 435,000 malaria-related
deaths, compared to 451,000 in 2016 and 607,000 in 2010.
The WHO has noted that resistance to antimalarial medicines is a recurring
The UN Secretary-General's 2018 progress report on the UN Sustainable
Development Goals states:
The world is not on a trajectory towards ending malaria by
2030 — in fact, the trends are worrisome. In 2016, there were 216 million cases
of malaria, compared with 210 million cases in 2013.
Australian travellers to malaria endemic areas are at risk of
contracting malaria and approximately 400 cases of imported malaria occur each
The Medicines for Malaria Venture (MMV) reported that P.vivax malaria is
responsible for a significant burden of illness.
The WHO estimated that 3.4 per cent of all malaria cases were caused by P.
vivax, with 56 per cent of the vivax cases in the South-East Asia Region.
In 2016 WHO estimated 8.5 million cases of P.vivax malaria of which around
5 million were in South-East Asia with 27,000 deaths.
Malaria and the ADF
South East Asia is an area of operations for the military which puts ADF
members at risk of malaria. In the ADF, 64 ADF members became infected with
malaria during the INTERFET deployment and over 200 more developed malaria on
return to Australia. These numbers were the catalyst for the approved clinical
studies which were 'deemed necessary to help determine if Defence should review
its policy of prescribing doxycycline as the preferred antimalarial...'.
Details about the trials are provided in Chapter 3.
In the ADF, between 1998 to 2007, 637 cases of malaria were recorded in
ADF members; between 2012 and 2017 there were 30 cases recorded, at an average
of five per year; and to date in 2018, four cases have been recorded.
Over these years the Australian Defence Force Malaria and Infectious Disease
Institute (ADFMIDI) formerly known as the Australian Army Malaria Institute
'a world-renowned, industry leader of malarial studies' has been responsible
for developing solutions to the problem of malaria on operations.
Other relevant Australian committee inquiries
On 17 March 2016, the Senate Foreign Affairs, Defence and Trade
References Committee tabled a report on the mental health of ADF serving
personnel. The report included two recommendations in relation to mefloquine.
Dated 15 September 2016, the government response sets out its response to the
Other relevant inquiries
The use of mefloquine by defence forces overseas has been the subject of
parliamentary and other inquiries or reviews in other jurisdictions.
In June 2017, the House of Commons Standing Committee on Veterans
Affairs undertook a study on 'mental health focused on improving the
transitional support between Canadian Armed Forces and Veterans Affairs' which
included the claims around the effect of mefloquine. There were two
recommendations regarding mefloquine: that Veterans Affairs Canada reach out to
members of the Canadian Armed Forced who served in Somalia, Rwanda or other
deployment in that time period to ensure each is receiving the mental and
physical health services, support, benefits and programs to which they are
entitled; and that Veterans Affairs Canada cooperate with any institution
concerned in any research program that would study the effects of mefloquine.
In June 2017 Canada released a report from a military taskforce on
mefloquine. Health Canada simultaneously made public its own findings about the
safety of the drug. Both concluded there is no evidence that the drug causes
long-lasting and permanent neurological and psychiatric problems. The military
report recommended that mefloquine be considered as a drug of last resort. The
findings of the reports have angered some Canadian veterans who claim they are
experiencing symptoms as a result of 'mefloquine toxicity'.
In 2017 the Canadian Surgeon General noted in the Canadian Standing
Committee on Veterans Affairs Review, Mental Health of Canadian Veterans: A
Family Purpose that:
More than 17,000 Canadian Armed Forces personnel and tens of
millions of people wordwide have received Mefloquine since it was first
licensed to prevent and treat malarial infection. We are aware of the potential
short-term side effects of Mefloquine; however, even given this extensive use
of Mefloquine, severe neuropsychiatric adverse effects have very rarely been
associated with its use.
In May 2016 the House of Commons Defence Committee published its report:
An acceptable risk? The use of Lariam for military personnel. The
committee concluded that the Ministry of Defence should designate Lariam (Mefloquine)
as a drug of last resort and that prescribing it should be restricted: only to
those who are unable to tolerate the available alternatives; only after a face
to face individual risk assessment has been conducted; and only after the
patient has been made aware of the alternatives and have been given the choice
between Lariam and another suitable antimalarial drug.
Following this inquiry on 12 September 2016, the Ministry of Defence
introduced a new policy on prescribing antimalarial drugs.
The revised policy directs that all antimalarial drugs are only supplied after
a face to face travel health risk assessment performed by an appropriately
trained and regulated health care professional. A hotline was also set up for
anyone who had concerns. However, the new policy did not designate Lariam as a
drug of last resort.
In relation to the UK inquiry the then Vice Chief of the Defence Force, VADM
Ray Griggs noted in 2016 that:
The point I would make about the key difference between the
UK and Australia is that, as I said at the outset, we have a tiered approach to
the prescription of antimalarials, that mefloquine is our third in line and
that it is being used quite rarely. In the UK, there is no tiering and
mefloquine has been used much more extensively. The UK inquiry centred on
whether people were given the appropriate amount of information and the
counselling part prior to being prescribed the drug. So it was a slightly
On 25 July 2018 the House of Commons Defence Committee presented a
report on Mental Health and the Armed forces, Part One: The Scale of mental
health issues. The report notes there is a lack of research into the mental
health effects of physical exposure to factors such as neurotoxcity or mild
traumatic brain injury:
An example is the antimalarial drug Lariam, or Mefloquine,
where our predecessor Committee found that a minority of those who used it
suffered serious mental health issues. Such side effects were known to occur,
yet the Ministry of Defence did not take the appropriate steps to minimise the
risks to those whom it prescribed the drug. A number of witnesses have
suggested that other drugs being prescribed by the Armed Forces may be having
similar effects but that the current lack of research and data over neurotoxicity
and its potential mental health effects may be resulting in cases being missed
or being misdiagnosed, for example as PTSD.
Other governments and organisations
Although there have been no specific inquiries, current US policy is
that mefloquine 'should be reserved for individuals with intolerance or
contraindications to both first-line medications [doxycycline and atovaquone-proguanil]'.
The Office of Secretary of Defence published a 2009 policy
advising that doxycycline was the antimalarial of first choice, followed by
atovaquone/proguanil, and that mefloquine use was restricted to only those
personnel with contraindications to the other antimalarials, which is
consistent with ADF policy. It further warned that it should be used cautiously
in persons with a history of Traumatic Brain Injury or Post Traumatic Stress
Disorder (PTSD) and other psychiatric diagnoses, such as depression,
schizophrenia, and anxiety disorders.
It was reported in the media that mefloquine was investigated as a
contributing factor in a series of murder-suicides at Fort Bragg, North
Carolina in 2002 but the military panel concluded it was an unlikely factor.
More recently, the media has reported calls by individuals and
organisations for Congressional hearings into the use of mefloquine in the US
In December 2016 the German defence ministry took mefloquine off the
list of medications prescribed for soldiers.
Defence advised that similar to Ireland, in late 2017 Roche withdrew Lariam from
the German market which became the catalyst for the German Ministry of Defence
to order the cessation of use of mefloquine. Prior to that mefloquine had become
a third-line antimalarial in 2013 when a new manufacturer's 'black box'
warning was added.
Defence advised that mefloquine remains the first line antimalarial of
the Irish Defence Force. Local advocates have campaigned for it to be a drug of
last resort. Lariam was, however, withdrawn from sale in Ireland in July 2016
which the company said followed a review of the products and was not related to
legal actions as it was still on the market in 16 other European countries. A
number of current and serving members of the Irish Defence Force have submitted
claims against the Defence Force and as at 27 June 2017 55 claims
had been received. One claim was settled on 30 November 2017 without admission
of liability and the other cases are still pending.
Defence advised that in response to concerns raised in countries about
the use of mefloquine, the Force Health Protection Working Group of the
Committee of the Chiefs of Military Medical Services in NATO was asked to
review the matter. The working group has recommended that:
...the use of mefloquine is still justified when prescribed in
line with national prescribing guidelines and the standard product information.
The recommendation will enter the ratification process by COMEDS within the
next few weeks to months.
Further detail is available in the submission from Defence.
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