Army Malaria Institute -
Department of Drug Evaluation

Mission

To support new drug discovery programs and optimise drug regimens for the treatment and protection of Australian Defence Force personnel against malaria infections. In support of this mission the department assesses the antimalarial activity of promising candidate drugs using parasitological tools and animal models. Pharmacokinetic and pharmacological studies of antimalarial drugs are carried out to optimise dose regimes for treatment and prophylaxis against malaria infections.

Department Structure

Current Research Projects

• Drug discovery screening of synthetic and natural products for intrinsic antimalarial activity using in vitro testing against Plasmodium falciparum isolates of varying levels of drug resistance (collaboration with Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington DC, USA; Jacobus Pharmaceutical Company, Inc, New Jersey, USA; Human Protection & Performance Division, Defence Science & Technology Organisation, Melbourne, Victoria).
• Uptake and stage specificity of piperaquine in different P. falciparum isolates, in vitro.
• Generation of new in vitro models: transfected P. falciparum parasite lines for antimalarial drug evaluation.
• Molecular characterisation for resistant markers of clinical field isolates of P. falciparum.
• In vivo antimalarial activity screening of natural products using rodent-Plasmodium berghei models with Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane Queensland (collaboration with Medicines for Malaria Venture (MMV)
• Preclinical development of 3rd generation antifols (collaboration with Jacobus Pharmaceutical Company, Inc.) for treatment and prophylaxis against malaria infections.
• Therapeutic efficacy and tolerability of dihydroartemisinin-piperaquine (Artekin), artemisinin-piperaquine (Artequick) and artesunate-amodiaquine (Coarsucam) for the treatment of Plasmodium falciparum malaria in central Vietnam (collaboration with Military Institute of Hygiene and Epidemiology, Hanoi, Vietnam and the Institute of Malariology, Parasitology and Entomology, Qui Nhon, Binh Dinh, Vietnam).
• Therapeutic efficacy, tolerability and pharmacokinetics of artesunate-azithromycin for the treatment of Plasmodium falciparum malaria (collaboration with Department of Infectious Disease, Military Hospital 175, Ho Chi Minh City, Vietnam).
• Pharmacokinetics of dihydroartemisinin-piperaquine (Artekin) and artesunate-azithromycin for the treatment of Plasmodium falciparum malaria (collaboration with Department of Infectious Disease, Military Hospital 108, Hanoi, Vietnam).

Publications

2000

Kocisko DA, Walsh DS, Eamsila C, Edstein MD. Measurement of tafenoquine (WR 238605) in human plasma, and venous and capillary blood by High-Pressure Liquid Chromatography. Ther Drug Monitor, 2000, 22: 184-9.

Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother 2000; 44: 2100-8.

2001

Chen N, Russell B, Staley J, Kotecka B, Nasveld P, Cheng Q. Sequence polymorphisms in Pfcrt are strongly associated with chloroquine resistance in Plasmodium falciparum. J Infect Dis 2001; 183: 1543-5.

Edstein MD, Walsh DS, Eamsila C, Sasiprapha T, Nasveld PE, Kitchener S, Rieckmann KH. Malaria prophylaxis/radical cure: Recent experiences of the Australian Defence Force. Med Trop, 2001, 61: 56-8.

Edstein MD, Nasveld PE, Rieckmann KH. The challenge of effective chemoprophylaxis against malaria. ADF Health 2001, 2: 12-6.

Edstein MD, Kocisko DA, Brewer TG, Walsh DS, Eamsila C, Charles BG. Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers. Br J Clin Pharmac 2001, 52: 663-70.

Jensen NP, Ager AL, Bliss RA, Canfield CJ, Kotecka BM, Rieckmann KH, Terpinski J, Jacobus DP. Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. J Med Chem 2001; 44: 3925-31.

2002

Bragonier R, Reyburn H, Nasveld P, Edstein M, Auliffe A. Rainy-season prevalence of malaria in Bobonaro district, East Timor. Ann Trop Med Parasitol 2002; 96: 739-43.

Chen N, Baker J, Ezard N, Burns M, Edstein MD, Cheng Q. Molecular evaluation of the efficacy of chloroquine treatment of uncomplicated Plasmodium falciparum malaria in East Timor. Am J Trop Med Hyg 2002, 67: 64-6.

Maguire JD, Lacy MD, Sururi, Sismadi P, Krisin, Wiady I, Laksana B, Bangs MJ, Masbar S, Susanti I, Basuki W, Barcus MJ, Marwoto H, Edstein MD, Tjokrosonto S, Baird JK. Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated, Plasmodium falciparum malaria during an epidemic in Central Java, Indonesia. Ann Trop Med Parasitol 2002; 96: 655-8.

Nasveld PE, Kitchener S, Edstein MD, Rieckmann KH. Comparison of tafenoquine (WR238605) and primaquine in the post exposure (terminal) prophylaxis of vivax malaria in Australian Defence Force personnel. Trans Roy Soc Trop Med Hyg 2002; 96: 683-84.

2003

Edstein MD, Kocisko DA, Walsh DS, Eamsila C, Charles BG, Rieckmann KH. Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in Thai soldiers on monthly prophylaxis. Clin Infect Dis 2003; 37: 1654-58.

Ezard N, Burns M, Lynch C, Cheng Q, Edstein MD. Efficacy of chloroquine in the treatment of uncomplicated Plasmodium falciparum infection in East Timor, 2000. Acta Tropica 2003; 88: 87-90.

Frances SP, Cooper RD, Auliff AM, Edstein MD. Survey of Personal Protection Measures against Mosquitoes among Australian Defence Force personnel deployed to East Timor. Mil Med 2003; 168: 227-30.

Kotecka BM, Rieckmann KH, Davis TM, Batty KT, Ilett KF. Comparison of bioassay and high performance liquid chromatographic assay of artesunate and dihydroartemisinin in plasma. Acta Trop 2003; 87: 371-5.

McGready R, Stepniewska K, Edstein MD, Cho T, Gilveray G, Looareesuwan S, White NJ, Nosten F. The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. Eur J Clin Pharmacol 2003; 59: 545-52.

McGready R, Stepniewska K, Seaton E, Cho T, Cho D, Ginsberg A, Edstein MD, Ashley E, Looareesuwan S, White NJ, Nosten F. Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur J Clin Pharmacol 2003; 59: 553-57.

Russell BM, Udomsangpetch R, Rieckmann KH, Kotecka BM, Coleman RE, Sattabongkot J. Simple in vitro assay for determining the sensitivity of Plasmodium vivax isolates from fresh human blood to antimalarials in areas where P. vivax is endemic. Antimicrob Agents Chemother 2003; 47: 170-3

2004

Walsh SD, Eamsila C, Sasiprapha T, Sangkharomya S, Khaewsathien P, Supakalin P, Tang DB, Jarasrumgsichol P, Chuenchitra SC, Edstein MD, Rieckmann KH, Brewer TG. Randomized, double-blind, placebo controlled evaluation of monthly tafenoquine (WR 238605) for Plasmodium falciparum and P. vivax malaria in Royal Thai Army soldiers. J Inf Dis 2004; 190: 1456-1463.

Walsh SD, Eamsila C, Sasiprapha T, Sangkharomya S, Khaewsathien P, Supakalin P, Tang DB, Jarasrumgsichol P, Chuenchitra SC, Edstein MD, Rieckmann KH, Brewer TG. Prevention of vivax and falciparum malaria using monthly tafenoquine prophylaxis in Thailand. Contagion 2004; 2: 58-62.

Kitchener SJ, Nasveld NE, Gregory RM, Edstein MD. Tolerability of mefloquine prophylaxis in Australian soldiers on peacekeeping duties in East Timor. Med J Aust 2004; 182: 168-171.

2005

Dao NVH, Ngoa NP, Thuy LT, The ND, Bui Dai, Binh VQ, Anh LN, Rieckmann KH, Edstein MD. Fatty-food does not alter blood mefloquine concentrations in the treatment of falciparum malaria. Trans Roy Soc Trop Med Hyg 2005; 99: 927-931.

Shanks DG, Edstein MD. New Developments in the Chemoprophylaxis of Malaria. Drugs 2005; 65: 2091-2110.

Edstein MD, Kotecka BM, Anderson KL, Pombo DJ, Kyle DE, Rieckmann KH, Good MF. Lengthy antimalarial activity of atovaquone in human plasma following Malarone administration. Antimicrobial Agents Chemother 2005; 49: 4421-4422.

2006

Burns, M, Baker J, Auliff A, Gatton M, Edstein MD, Cheng Q. The efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in East Timor. Am J Trop Med Hyg 2006; 74: 361-366.

Bui Tri Cuong, Vu Quoc Binh, Bui Dai, Dinh Ngoc Duy, Claire M Lovell, Karl K Rieckmann, Michael D Edstein. Does food and gender affect the pharmacokinetics of primaquine in healthy Vietnamese subjects? Br J Clin Pharm 2006; 61: 682-689.

Elmes NJ, Bennett SM, Abdalla H, Carthew TL, Edstein MD. The pharmacokinetics of primaquine in healthy Australian male and female volunteers. Am J Trop Med Hyg 2006; 74: 951-952.

Haynes Fugmann B, Stetter J, Rieckmann K, Heilmann HD, Chan HW, Cheung MK, Lam WL, Wong HN, Croft SL, Vivas L, Rattray L, Stewart L, Peters W, Robinson BL, Edstein MD, Kotecka B, Kyle DE, Gerisch M, Radtke M, Schmuck G, Steinke W, Wollborn U, Schmeer K, Romer A. Artemisone – A highly active antimalarial drug of the artemisinin class. Angew Chem 2006; 45: 1-8.

2007

Edstein MD, Nasveld PE, Kocisko DA, Kitchener SJ, Gatton ML, Rieckmann KH. Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis. Trans Roy Soc Trop Med Hyg 2007; 101: 226-230.

Ratcliff A, Siswantoro H, Kenangalem E, Wuwung M, Brockman A, Edstein MD, Laihad F, Ebsworth EP, Anstey NM, Tjitra E and Price RN.  Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia. Trans Roy Soc Trop Med Hyg 2007; 101: 351-359.

Kitchener S, Nasveld P, Edstein MD.  Tafenoquine in the treatment of recurrent Plasmodium vivax malaria. Am J Trop Med Hyg 2007; 76: 494-496.

Charles BG, Blomgren A, Nasveld PE, Kitchener SJ, Jensen A, Gregory RM, Robertson B, Harris IE, Reid MP, Edstein MD.  Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment. Eur J Clin Pharmacol 2007; 63: 271-278.

Nguyen Van Hoang Dao, Bui Tri Cuong, Nguyen Dang Ngoa, Le Thi Thanh Thuy, Nguyen Duy The, Dinh Ngoc Duy, Bui Dai, Nguyen Xuan Thanh, Marina Chavchich, Karl H. Rieckmann, Michael D. Edstein. Vivax malaria: preliminary observations with a shorter course of treatment with artesunate plus primaquine. Trans Roy Soc Trop Med Hyg 2007; 101: 534-539.

Bruce G. Charles, Ann K. Miller,Peter E. Nasveld, Mark P. Reid, Ivor E. Harris, and Michael D. Edstein.  Population Pharmacokinetics of Tafenoquine during Malaria Prophylaxis in Healthy Subjects. Antimicrob Agents Chemother 2007; 51: 2709-2715.

Edstein MD, Kotecka BM, Ager AL, Smith KS, DiTusa CA, Diaz DS, Kyle, DE, Schiehser GA, Jacobus DP, Rieckmann KH, O’Neil MT.  Antimalarial pharmacodynamics and pharmacokinetics of a third-generation antifolate – JPC2056 – in cynomolgus monkeys using an in vivo-in vitro model. J Antimicrob Chemother 2007; 60: 811-818.

Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V, Prasetyorini B, Piera KA, Barends M, Brockman A, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN. Chloroquine resistant Plasmodium vivax: In vitro characterisation and association with molecular polymorphisms. PLoS ONE. 2007 Oct 31;2(10):e1089.

2008

Wes W Sharrock, Rossarin Suwanarusk, Usa Lek-Uthai, Michael D Edstein, Varakorn Kosiavasee, Thomas Travers, Anchalee Jaidee, François Nosten, Bruce Russell. Plasmodium vivax Trophozoites Insensitive to Chloroquine. Malaria J 2008; in press

N. J. Elmes, P. E. Nasveld, S. J. Kitchener, D. A. Kocisko, M. D. Edstein.  Comparison of three different dose regimens of tafenoquine versus primaquine for post exposure prophylaxis of vivax malaria in the South West Pacific. Trans Roy Soc Trop Med Hyg 2008; in press.

Johannes Nagelschmitz, Barbara Voith, Georg Wensing, Axel Roemer, Burkhard Fugmann, Richard K. Haynes, Barbara M. Kotecka,  Karl H. Rieckmann, Michael D. Edstein.  First-Time-In-Humans Safety, Tolerability, Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of the New Artemisinin Derivative, Artemisone. Antimicrob Agents Chemother 2008, in press.

Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E, Piera KA, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN.  Pvmdr1 amplification and polymorphisms associated with multidrug resistant P. vivax.  J Infect Dis 2008, in press.

Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Thomas Travers, Michael D. Edstein.  Short Report: Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects.  Am J Trop Med Hyg 2008, in press.

13 October, 2008