Defence Health

Malaria research in the Australian Defence Force

The Australian Defence Force Malaria and Infectious Diseases Institute (ADFMIDI), formerly known as the Australian Army Malaria Institute (AMI), is a military medical research organisation that works to prevent mission failure during regional ADF deployments. ADFMIDI is located at Gallipoli Barracks, Enoggera, where it conducts laboratory and clinical medical research to decrease the risk of ADF members becoming ill from infections spread by insects such as mosquitoes.

ADFMIDI provides clinical advice to Defence health practitioners, diagnostic testing, training, regional capacity building, and is a WHO Collaborating Centre for Malaria. While its primary focus is on malaria, ADFMIDI is interested in any infectious diseases that might stop military operations. For instance, Japanese encephalitis virus and dengue virus vaccines have been tested in ADF volunteers, and insecticide impregnated uniforms and other military equipment have been field tested in Tin Can Bay and the Shoalwater Bay Training Areas to help limit the spread of Australian viruses like Ross River virus and Murray Valley encephalitis virus. Influenza killed more than 1000 Australian soldiers in the 20th Century and studies continue to examine the medical records of Australian soldiers during the 1918 influenza pandemic to ensure we are better prepared to deal with a similar threat today.

ADFMIDI is a mixed organisation of civilian and military scientific and medical staff that conducts scientific research independently and in collaboration with a number of other research organisations, including the University of Queensland and the Queensland Institute of Medical Research. ADFMIDI has had strong historical links to the regional US military medical laboratories in Bangkok and Singapore and has been collaborating with the Peoples Army of Vietnam for more than a decade. The Australian Government’s recently reaffirmed commitment to eliminate malaria in the Asia-Pacific region by 2030 involves ADFMIDI as the World Health Organization’s Regional Collaborating Centre for the Western Pacific.

Military personnel operating in conflict or disaster zones in the tropics are unable to completely avoid mosquito bites that may cause malaria, therefore the protection offered by medication is crucial to preventing the disease. To further complicate matters malaria parasites often develop resistance to drugs over time, meaning the ongoing discovery and testing of new anti-malarial medications is crucial, not only for deploying troops but also for vulnerable communities around the world who are at risk from the disease.

During the Second World War, ADFMIDI (then known as Land HQ Medical Research Unit) conducted critically important drug trials in Cairns to determine the cause of crippling malaria casualties in New Guinea and how best to use the limited medications available to protect soldiers during jungle warfare. This requirement continued into the Vietnam War when drug combinations were tested during actual combat operations and through more recent deployments in Timor-Leste.

Clinical Trials

Clinical trials are how new medications are evaluated to ensure they are effective and safe. These trials must be done before these treatments can be formally approved by regulators and become accessible to the general population.

Prior to any medication being used in humans it goes through a series of standardised tests in at least two different animal species. These tests are designed to identify short and longer term toxicity, demonstrate that the drug has the desired effect and to help establish the dosage to be used in subsequent human trials.

In Australia clinical trials of unapproved (unregistered) therapeutic goods (e.g. vaccines, medications) may be conducted under one of two schemes:

• The Clinical Trial Exemption (CTX) scheme – Under this scheme the researcher makes an application to conduct the clinical trial to the Therapeutic Goods Administration (TGA), which reviews the available relevant scientific data. For the trial to proceed the TGA must have notified the researcher that there is no objection to the conduct of the trial. The trial must also have been approved by a human research ethics committee and the organisation in which the trial is to be conducted.
• The Clinical Trial Notification (CTN) scheme – Under this scheme the researcher applies directly to a human research ethics committee, which reviews the trial protocol and provides ethical approval if it is satisfied that the proposed trial is scientifically and ethically sound. The ethics committee also assumes responsibility for monitoring the trial. The trial cannot start until the TGA has been notified.

Clinical trials are routinely described by “phase”. Phase I – III trials are conducted sequentially prior to a medication being registered by the TGA.  Phase IV (post marketing) trials are conducted with medications that are already registered and being used in the community.

Most clinical trials conducted by the Army Malaria Institute* have been Phase IV trials of TGA registered medications, although the trials involving the anti-malarial medication tafenoquine were Phase III trials.

Any clinical trials involving ADF members in the field or on operations are done after the Phase I and II trials have been conducted in a more controlled civilian environment.

The following describes clinical trials by phase:

• Phase I clinical trials are done to test a new medication for the first time in a small group of people (e.g. 20-80) to evaluate safety (e.g. to determine a safe dosage range and identify side effects).
• Phase II clinical trials are done to study a medication in a larger group of people (several hundred) to determine efficacy (that is, whether it works as intended) and to further evaluate its safety.
• Phase III studies are done to study the efficacy of a medication in large groups of trial participants (from several hundred to several thousand) by comparing the intervention to other standard or experimental medications (or to non-interventional standard care). Phase III studies are also used to monitor adverse effects and to collect information that will allow the medication to be used safely.
• Phase IV studies are done after a medication has been approved and registered by the TGA and is in routine use in the community. These studies are designed to monitor the effectiveness of the approved medication in the general population and to collect information about any adverse effects associated with widespread use over longer periods of time. They may also be used to investigate the potential use of the medication in a different condition, or in combination with other therapies.

More information about the regulation of clinical trials involving unapproved therapeutic goods is available from the TGA website.

General information about clinical trials in Australia is available from the Australian Clinical Trials website and from the National Health and Medical Research Council website.

Mefloquine trials

Tafenoquine trials

Other anti-malarial studies

* In 2017 the Army Malaria Institute was renamed the Australian Defence Force Malaria and Infectious Diseases Institute.