History of Tafenoquine

Tafenoquine is a quinoline antimalarial drug developed by the Walter Reed Army Institute of Research (WRAIR), as part of the same drug discovery program as mefloquine, which is now widely regarded as a suicide pill.

I thought I’d try and end it again a few weeks ago. That was an attempted hanging. I heard my neck crack, and the doctor said to me, ‘You’re lucky that you didn’t die then.’

2018 testimony of an Australian soldier subjected to the AMI drug trials in East Timor

This page provides an overview of the clinical use of tafenoquine and is currently a work in progress as more details come to light. Further detail on the clinical trials of tafenoquine will be posted here and some of the key research papers will be posted here. For the time being, this page focuses largely on the clinical trials of tafenoquine by the Australian Army Malaria Institute (AMI) in Bougainville (Papua New Guinea) and East Timor from 1999 to 2001. These studies were sponsored by GlaxoSmithKline (GSK), WRAIR and USAMMDA.

Tafenoquine is an 8-aminoquinoline, a particular class of drug well known for its neurotoxic properties since the late 1940s.[1] During WWII and the years that followed, having accepted the clinical evidence of neurotoxicity in several of the 8-aminoquinolines which had been widely used by allied troops, the U.S. government conducted a dedicated neurotoxicity screening program using primate models, in order to find a safe alternative treatment and prevention drug for P. vivax malaria.[2] This program found extensive, direct physical evidence of permanent brain damage in primates administered 8-aminoquinolines, in parts of the brain linked to the chronic neuropsychiatric symptoms also exhibited by humans who are adversely affected by these drugs.[1]

This screening program led to the eventual adoption of primaquine as the standard P. vivax antimalarial drug, which it remains to this day. Due to its short elimination half-life, primaquine is used at relatively low doses of 15-30 mg per day for 14 consecutive days when used for post exposure prophylaxis (PEP) to “eradicate” the dormant liver stage of the P. vivax parasite.[3]

ADFIMI has advised that no neurotoxicity testing has been performed on primates by the (then) Australian Army Malaria Institute (AMI), now ADFIMI.

Australian Department of Defense, 2018

Prior to the AMI clinical trials of tafenoquine in Bougainville and East Timor at the turn of the century, tafenoquine did not undergo screening for neurotoxicity in primate models. The Australian Department of Defense has since confirmed that it has never undertaken tafenoquine neurotoxicity testing in primates as a matter of policy.[4]

I was put in the locked psychiatric ward at Townsville under close surveillance and remember being isolated with some other very mentally sick people. What I went through there in hospital can’t really be explained to someone who hasn’t crossed the line to insanity.

2016 Personal account of an Australian soldier subjected to the AMI tafenoquine Study 033 in East Timor

In 1998, an AMI clinical trial in Bougainville found that Malarone (from another drug class) was as effective against malaria (less P. vivax eradication) and better tolerated than the existing Australian Defense Force (ADF) first line drug doxycycline. AMI recommended against the adoption of Malarone due to cost, less than the cost of a cup of coffee per day.[5] Regardless, Malarone replaced mefloquine as the ADF’s second line antimalarial in 2006, when the latter drug was relegated to “drug of last resort” due to the risk of neuropsychiatric side effects.[6] Malarone is now regarded as so safe that it is sold over the counter (without prescription) in many countries.

Throughout the history of the use of primaquine, a significant proportion of individuals have contracted P. vivax malaria despite compliance with the recommended dose regimen. Drug failures have typically been mis-attributed to “poor compliance” or assumed “drug resistance” in the malaria parasite. However there has never been any direct scientific evidence of P. vivax resistance to primaquine. This has only ever been an assumption.

By late 1998 the ADF had two safe and effective drugs available for malaria prevention, and a PEP drug which had been the standard P. vivax prevention drug for 50 years.

Contradicting the ADF’s recent claims that an outbreak of malaria during the early stages of the INTERFET deployment necessitated the use of the experimental drug tafenoquine, WRAIR officials have stated that the U.S. military was looking for large numbers of allied troops able to participate in clinical trials as part of its commercial arrangements with GSK.

We were very mission driven, very altruistic, really babes in the woods when it came to business and such, and it showed, right? We routinely got taken advantage of, and didn’t understand the operating environment.”

Former WRAIR Director, 2018

Commencing in Bougainville in late 1998, AMI embarked on a series of tafenoquine clinical trials which then continued in East Timor until mid-2001, involving a total of 1,540 tafenoquine subjects. The first of these trials was a PEP study which administered subjects in Bougainville (from the Peace Monitoring Group) then East Timor (from the 3rd Battalion [3 RAR] then 5th/7th Battalion [5/7 RAR] of the Royal Australian Regiment) with up to 1,200 mg of tafenoquine over three days. The next study (Study 033) involving the 1st Battalion of the Royal Australian Regiment (1 RAR) in East Timor, compared tafenoquine with mefloquine for weekly 200 mg prophylaxis, commencing with a 600 mg “loading dose”. A third tafenoquine study administered the drug to a small number of individuals with relapsing P. vivax malaria, initially at 200 mg per day for three days then 200 mg weekly.

Since the conclusion of the AMI tafenoquine studies, there have been no follow up health studies on the original 1,540 tafenoquine study subjects to determine the chronic adverse health effects of this drug. In 2009, laboratory studies by WRAIR scientists found that tafenoquine is “the only antimalarial drug more neurotoxic than mefloquine”.[7] Despite clear evidence of widespread, chronic neuropsychiatric illness among the ADF tafenoquine clinical trial subjects, and despite repeated requests, no longitudinal follow up studies have been undertaken.

More recently, leading scientists have discovered that the 8-aminoquinolines (including primaquine and tafenoquine) are largely ineffective because they need to be metabolised by an enzyme known as CYP2D6. Up to one quarter of the population carry a genetic deficiency which means they remain at risk of contracting malaria even if they are fully compliant with the prescribed drug regimen.[8,9]

Despite this, last year tafenoquine was approved by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) for both the treatment of relapsing P. vivax malaria (the GSK drug is known as Krintafel® [US]/Kozenis® [Australia]) or the prevention of malaria in adults (the 60 Degrees Pharmaceuticals drug is known as Arakoda® [US]/Kodatef® [Australia]). The regulatory approval of Krintafel® by the FDA entitled GSK to the award of a “priority review voucher”, a saleable product valued at up to USD$350 million, even if a single tablet of this drug is never sold. Several years earlier the CEO of 60 Degrees Pharmaceuticals, who founded his company while working as a contractor for USAMMDA, was awarded the license for tafenoquine by the U.S. Army in a contract worth more than USD$18 million for registering the drug with the FDA and the TGA. The 60 Degrees Pharmaceuticals application to the FDA was based primarily on the results of the AMI Study 033 tafenoquine prophylaxis trial involving 654 troops from 1 RAR serving on peacekeeping operations in East Timor 2000-2001. The results of this study are believed to be fraudulent.

The Australian veterans whose lives were destroyed by tafenoquine during the notorious drug trials in Bougainville and East Timor have been lobbying their government for a “Royal Commission of Inquiry” into the controversy.


  1. R. L. Nevin, “Idiosyncratic quinoline central nervous system toxicity: historical insights into the chronic neurological sequelae of mefloquine,” International Journal for Parasitology: Drugs and Drug Resistance, vol. 4, no. 2, pp. 118–125, 2014.
  2. J. A. Shannon, “Vivax malaria and the 8-aminoquinolines,” American Journal of Medicine, vol. 1, no. 5, pp. 581-82,1946. https://doi.org/10.1016/0002-9343(46)90080-0
  3. J. Recht, E. Ashley, N. White, World Health Organization & Mahidol Oxford Research Unit, Safety of 8-aminoquinoline antimalarial medicines, 2014. https://apps.who.int/iris/handle/10665/112735
  4. Australian Department of Defense, FOI 329/17/18 Statement of reasons under the Freedom of Information Act, 28 March 2018. https://www.righttoknow.org.au/request/documents_relating_to_tafenoquin#incoming-12000
  5. N.J. Elmes et al., “Malaria in the Australian Defence Force: the Bougainville experience,” ADF Health, vol. 5, no. 2, pp. 69-72, 2004. https://researchonline.jcu.edu.au/29759/
  6. Surgeon General Australian Defence Force, Health Directive No 215: Malaria, Department of Defense, Canberra, Australia, 2013.
  7. R. Agboruche et al, In-vitro toxicity assessment of antimalarial drugs on cultured embryonic rat neurons,
    macrophage (RAW 264.7), and kidney cells (VERO- CCl-81)
    , 2009. https://muckrock.s3.amazonaws.com/foia_files/Research_Day_Poster.ppt
  8. G. Camera, P. Jirawatcharadech, R. Priestley et al., “Antimalarial activity of primaquine operates via a two-step biochemical relay,” Nature Communications, vol. 10, Article 3226, 2019. https://doi.org/10.1038/s41467-019-11239-0
  9. J. Quinn, S. McCarthy, “Correspondence: Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria,” New England Journal of Medicine, vol. 380, pp. 1875-76, 2019. https://www.nejm.org/doi/full/10.1056/NEJMc1902327