Protection of military personnel against vector-borne diseases: a review of collaborative work of the Australian and US military over the last 30 years.
Collaboration between the United States and Australia was important during World War II in the Pacific. The work conducted between 1941 and 1945 by the Australian Land Headquarters Medical Research Unit is described in detail by LTC A. W. Sweeney in his book, Malaria Frontline. (8)
During the Vietnam War, many cases of vector-borne disease were observed in Australian, United States, and other Allied defense personnel. The medical resources and personnel of both countries collaborated to optimize and evaluate measures against diseases. The high number of malaria cases in Australian soldiers in Vietnam in 1965 resulted in the establishment in 1966 of the 1 Malaria Research Unit, under the direction of Professor Robert H. Black at the University of Sydney. This unit was moved to Ingleburn, 35 km southwest of Sydney, New South Wales, in 1974. (1)
In 1985, LTC Sweeney visited medical research units in the United States and fostered a formal collaboration between AMRU and US military scientists. One of the first collaborations involved field testing of new mosquito repellents and permethrin treated military uniforms at Cowley Beach, northern Queensland, Australia. This field trial was conducted by 4 scientists from the Letterman Army Institute of Research, Presidio of San Francisco, and AMRU. The study showed that a combination of wearing permethrin treated battle dress uniforms and repellents containing deet provided the best protection against mosquitoes. (9) A subsequent field trial at the same site in 1990 conducted by AMRU and the US Department of Agriculture compared methods of protection against trombiculid larvae (chiggers). This study showed that permethrin treated uniforms provided protection against mites that cause scrub itch. (10)
Medical Officers in Malaysia
Australian medical officers first worked in Malaysia at the US section of the Institute of Medical Research (IMR) in Kuala Lumpur in the early 1980s. They collaborated with US Army and Malaysian medical officers on protection against scrub typhus and snake envenomation. The joint studies conducted showed that doxycycline was an effective prophylaxis for scrub typhus, (11) and field surveillance showed that disease in Malaysia was underreported. (12,13)
Exchange Scientists in Thailand and Australia
In 1988, the US section of IMR Malaysia closed and an exchange was established with the Armed Forces Research Institute for Medical Sciences (AFRIMS) in Bangkok, Thailand, and the Australian AMRU. Between 1989 and 1992, mAj M. D. Edstein from AMRU worked at AFRIMS primarily on preclinical drug development and clinical evaluation of standard and new antimalarial drugs. During this 3-year period, MAJ Edstein and US Army and Thai Army collaborators researched new antimalarial compounds using nonhuman primates for causal prophylactic and radical curative activity. Of these studies, WR182393, a non-8-aminoquinoline guanylhydrazone, exhibited both causal prophylactic and radical curative properties in the rhesus monkey (Macaca mulatto)/ Plasmodium cynomolgi test model, a vivax malaria-like model. (14) However, using the same model, the prophylactic combination of proguanil plus sulfamethoxazole was found not to be causally prophylactic. (15) Additionally, the proguanil analog WR250417 (also known as PS-15) was shown to extend the prepatent period of P cynomolgi from 8.5 days to 18.3 days in drug-treated monkeys, but did not prevent a primary infection. (16)
For clinical studies, new high performance liquid chromatographic (HPLC) methods were developed for the analysis of antimalarial drugs such as quinine, (17) halofantrine, (18) mefloquine-sulfadoxine-pyrimethamine, (19) and ciprofloxacin. (20) These HPLC methods were used to characterize the pharmacokinetic-pharmacodynamic interaction of mefloquine in resistant P falciparum malaria on the Thai-Burma/Myanmar ** border, (21) assess the efficacy of halofantrine in treating Thai patients who failed mefloquine chemoprophylaxis, (22) evaluate the potential of ciprofloxacin in treating drug-resistant falciparum malaria, (23) assess the effect of food on the disposition of halofantrine in treating falciparum malaria (24) and determine the effectiveness of high-dose mefloquine in treating multidrugresistant falciparum malaria. (25)
At the time of those studies, mefloquine was the treatment of choice for uncomplicated multiresistant falciparum malaria. A standard dose of 15 mg/kg of mefloquine became ineffective in treating acute falciparum malaria in an area with deteriorating multidrug resistance on the Thai-Myanmar border. By increasing the mefloquine dose to 25 mg/kg, the clinical and parasitologic responses were significantly more rapid with high dose mefloquine compared with the standard dose. (26) The failure rate by day 28 of follow-up was 40% and 9% with 15 mg/kg and 25 mg/kg of mefloquine respectively. Adverse events were dose-related and included dizziness, anorexia, nausea, vomiting, and fatigue.
Mefloquine in combination with sulfadoxine and pyrimethamine (MSP) at a single dose of 15/30/1.5 mg/kg, respectively, also became ineffective. In 1985-1986, MSP cured over 98% of 5,192 patients with falciparum malaria on the Thai-Myanmar border. Four years later, the efficacy of MSP in 395 patients at the same location had declined to 71%. In these patients, the mean serum mefloquine concentration at the time of first recrudescence was 638 (546-730) ng/mL, a value previously associated with successful treatment. These findings suggested that P falciparum had rapidly developed resistance to mefloquine, despite the addition of sulfadoxine and pyrimethamine. The recommendation was to abandon the MSP combination. (21) The development of resistance to mefloquine highlighted the urgent need to evaluate new antimalarial drugs such as halofantrine. The recommended regimen of halofantrine was 3 doses of 500 mg (1,500 mg total or 24 mg/kg) at 6-hour intervals given with food to enhance drug absorption. However, this halofantrine regimen was found to be ineffective in treating 30% (7/23) of Thai soldiers who showed slide-positive results for malaria while receiving mefloquine chemoprophylaxis. (22) The serum halofantrine concentrations were higher in patients cured by halofantrine compared with those who failed treatment. These observations suggested that the 24 mg/ kg regimen of halofantrine was not optimal for the treatment of multiple drug-resistant falciparum malaria in Thailand. A higher dose of halofantrine (72 mg/kg) was more effective in treating uncomplicated falciparum malaria with a failure rate of 15%, but evidence of possible cardiotoxicity was observed and required investigation. (26) Studies by other investigators led to the demise of halofantrine due to cardiotoxicity.
In 1992, MAJ Edstein was replaced at AFRIMS by MAJ S. P. Frances, an entomologist, who worked on personal protection measures against malaria vectors, and biology of the vectors of scrub typhus. While at AFRIMS, Frances conducted laboratory and field evaluations of repellents and toxicants against mosquito vectors of malaria and mite vectors of Orientia tsutsugamushi. (27-33) He also worked on vectors of scrub typhus, resulting in the establishment of colonies of Leptotrombidiun deliense (mites) naturally infected with O tsutsugamushi, and improved understanding of the ecology of mites, rodent hosts, and the pathogen that causes scrub typhus in Thailand. (34-44)
During the same time (1992-1995), LTC G. D. Shanks worked at AMRU in Australia. He worked closely with MAJ Edstein, who had returned to Australia, on development of anti-malarial drugs. A number of valuable findings during this time included several clinical trials in Papua New Guinea. (45-48)
Collaboration between AMI and US military scientists has continued. In the 1990s, evaluation of repellent active ingredients deet, AI3-37220, and CIC4, ** along with personal protection measures against mosquitoes was undertaken. In 2001, an evaluation of Australian and US repellents was conducted in Australia at Cowley Beach by the AMI with US Army MAJ M. Debboun from WRAIR. The study compared the protection provided by commercial and military repellent on human volunteers. (49) This collaboration continued with evaluation of additional active ingredients in the laboratory and field, (50) as well as field evaluation of a low profile US bednet in Papua New Guinea. (51) The prototype bednet that was tested has been in use by US military personnel for more than a decade. (52) More recently, 3 books on repellents and personal protection measures used by civilian and military personnel were edited by US Army and Australian Defence Forces entomologists. (53-55)
Financial support from the Defence Warfighters Program of the Armed Forces Pest Management Board to AMI in 2008, allowed evaluation of Australian military shirt fabrics treated with permethrin to be tested to determine protection against mosquito bites of malaria and dengue vectors. (56,57)
The development of mefloquine as an anti-malarial drug was reviewed by Shanks. (58) The constraints of shrinking military and civilian budgets for development of antimalarial drugs highlighted the need to continue to conduct collaborative development of drugs. Despite this, collaborative research to develop new anti-malarial drugs between the two nations has continued.
From 1998-2011, exchange scientists from WRAIR undertook collaborative evaluation of the new anti-malarial drug tafenoquine (formerly known as WR238605 or etaquine) for malaria prevention and in vitro studies into artemisinin induced dormant ring-stages of P falciparum as a plausible explanation for recrudescence. In 1998, a field study of tafenoquine was conducted in Ubon Ratchatani province, Thailand, with Thai soldiers and collaborators from Australia, United States, and Thai military. (59) The major focus of the study was to determine the safety, tolerability, efficacy, and pharmacokinetics of tafenoquine following an oral loading dose of 400 mg daily for 3 days and monthly administration of 400 mg for 5 consecutive months. (59) In participants completing the follow-up period (96 tafenoquine and 91 placebo recipients), there were 22 P vivax, 8 P falciparum, and one mixed infection. With the exception of one P vivax infection in the tafenoquine group, all infections occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria, 96% for P vivax malaria, and 100% for P falciparum malaria. The soldier in the tafenoquine group who developed malaria during the study had a lower plasma tafenoquine concentration of 40 ng/mL at the time of diagnosis, which was approximately 3-fold lower than the trough concentrations of the other soldiers who were protected from infection by tafenoquine. (60) The phase II study revealed that monthly tafenoquine was safe, well tolerated, and highly effective in preventing P vivax and multidrug-resistant P falciparum malaria in Thai soldiers during 6 months of prophylaxis. This study was the first investigation of tafenoquine in Southeast Asia and in protecting volunteers from both P vivax and P falciparum malaria.
To assist in the development and evaluation of tafenoquine, a rapid and sensitive HPLC method for tafenoquine was developed by CPT D. A. Koscisko, US Army, during his assignment to AMI from 1999-2001. With this method, the population pharmacokinetics of tafenoquine was characterized in Thai soldiers who participated in the phase II study. (61,62) A one-compartment model was found best to describe the pharmacokinetics of tafenoquine after oral administration. The drug is widely distributed to body tissues with a high apparent volume of distribution and a lengthy elimination half-life of 16.4 days, suitable for weekly prophylaxis.
LTC D. E. Kyle, US Army, established the WRAIR laboratory at AMI in 2001. He collaborated in studies of the drug Artimisone, which showed it was more effective than artemisinin drugs in curing P falciparum in Aotus monkeys. (6,63,64) He has continued collaboration with AMI in his role as a professor at South Florida University with studies of the role of gene amplification and expression that induces resistance in P falciparum. (65-68)
In February 2004, LTC Kyle returned to the United States and was replaced at AMI by MAJ Mike O'Neil. From 2004 to 2006, he participated in the assessment of the pharmacodynamics and pharmacokinetics of the novel dihydrofolate reductase inhibitor, JPC2056, and its principal active metabolite JPC2067 in cynomolgus monkeys using an in vivo-in vitro (ex vivo) model. (69) In a 2-phase crossover design, cynomolgus monkeys were administered multiple doses (20 mg/kg daily for 3 days) of JPC2056. Plasma samples collected from treated monkeys were assessed for ex vivo antimalarial activity against P falciparum lines having wild-type (D6), double-mutant (K1) and quadruple-mutant (TM90-C2A) DHFR-thymidylate synthase (TS) and a P falciparum line transformed with a P vivax dhfr-ts quadruple-mutant allele (D6-PvDHFR). Plasma JPC2056 and JPC2067 concentrations were measured by LC-mass spectrometry. The mean inhibitory dilution (ID90) of monkey plasma at 3 hours after the last dose against D6, K1, and TM90-C2A was 1613, 1120, and 1396, respectively. Less activity was observed with the same monkey plasma samples against the D6-PvDHFR line, with a mean [ID.sub.90] of 53. Geometric mean plasma concentrations of JPC2056 and JPC2067 at 3 hours after the last dose were 150 and 17 ng/mL, respectively. The elimination half-life of JPC2056 was shorter than its metabolite after both regimens (6.6 versus 11.1 hours). The high ex vivo potency of JPC2056 against P falciparum DHFRTS quadruple-mutant lines provides optimism for the future development of JPC2056 as a therapeutic agent.
In 2006, LTC N. Waters (US Army) was assigned to the WRAIR laboratory at AMI. He participated in a major AMI activity and Australian Government Pacific Malaria Initiative assisting in malaria eradication efforts in the Solomon Islands and Vanuatu. (70) The Drug Resistance and Diagnostics department of AMI collaborated with LTC Waters on studies of the molecular assessment of parasite drug resistance. (71) They found that Pfalciparum from both Solomon Islands and Vanuatu had high levels of resistance to Chloroquine (72) and Fansidar. (73) LTC Waters was next assigned to the US Military Academy, West Point, NY, in 2011, and has brought cadets to Australia each year from 2011-2015 to work in the AMI laboratories.
After more than 20 years of having US Army officers working in Australia at AMI, the exchange program has lapsed due to nonavailability of those officers. However, the collaboration between the 2 countries continues, especially in the fields of entomological research, drug development, and pharmacology. With the continued meager funding of some fields of medical research and different priorities within the US and Australian Defence Forces, continued collaboration is important to continue to conduct valuable research on a variety of vector-borne diseases. The effect of malaria, dengue, and scrub typhus have remained focal for both countries, and collaborative research will continue to minimize the impact of these diseases on military personnel and civilians alike.
We thank Mrs Oranuch, AFRIMS, Bangkok, Thailand, for allowing us to use archival photos from AFRIMS collection. Studies reviewed in this paper were supported by a number of funding agencies, and we thank them for their support of both the Australian Defence Force and the US Department of Defense. The opinions expressed herein are those of the authors and do not reflect those of the Joint Health Command (Australia) or any Defence policy.
(1.) Rieckmann KH, Sweeney AW. Army Malaria Institute-its evolution and achievements. First decade: 1965-1975. J Mil Vet Hlth. 2012; 20:17-24.
(2.) Rieckmann KH, Edstein MD, Cooper RD, Sweeney AW. Army Malaria Institute-its evolution and achievements. Second decade: 1975-1985. J Mil Vet Hlth. 2012; 20:9-20.
(3.) Rieckmann KH, Sweeney AW, Edstein MD, et al. Army Malaria Institute-its evolution and achievements. Third decade (1st half): 1985-1990. J Mil Vet Hlth. 2012; 20:59-70.
(4.) Rieckmann KH, Frances SP, Kotecka BM, et al. Army Malaria Institute-its evolution and achievements. Third decade (2nd half): 1990-1995. J Mil Vet Hlth. 201321:36-56.
(5.) Rieckmann KH, Q Cheng, R Cooper, et al. Army Malaria Institute-its evolution and achievements. Fourth decade (1st half): 1995-2000. J Mil Vet Hlth. 2014; 22:30-49.
(6.) Rieckmann, KH, Q Cheng, SP Frances, et al. Army Malaria Institute-its evolution and achievements. Fourth decade (2nd half): 2000-2005. J Mil Vet Hlth. 2015; 23:10-41.
(7.) Gambel JM, RG Hibbs. U.S. military overseas medical research laboratories. Mil Med. 1996; 161:638-646.
(8.) Sweeney AW. Malaria Frontline, Australian Army Research during World War II. Melbourne, Victoria, Australia: Melbourne University Press; 2003.
(9.) Gupta RK, Sweeney AW, Rutledge LC, et al. Effectiveness of controlled-release personal-use arthropod repellents and permethrin-impregnated clothing in the field. J Am Mosq Control Assoc. 1987; 3:556-560.
(10.) Frances SP, Yeo AET, Brooke EW, Sweeney AW. Clothing impregnations of dibutylphthalate and permethrin as protectants against a chigger mite, Eutrombicula hirsti (Acari: Trombiculidae). J Med Ent. 1992; 29:907-910.
(11.) Twartz JC, Shirai A, Selvaraju G, et al. Doxycycline prophylaxis for human scrub typhus. J Infect Dis. 1982; 146:811-818.
(12.) Brown GW, Shirai A, Jegathesan A, et al. Febrile illnesses in Malaysia-an analysis of 1,629 hospitalized patients. Am J Trop Med Hyg. 1984; 33:311-315.
(13.) Taylor A, Kelly DJ. Scrub typhus in Malaysia. Fam Pract. 1984; 7:26-28.
(14.) Corcoran KD, Hansukjariya P, Sattabongkot J, et al. WR182393 (a guanylhydrazone) has causal prophylactic and radical curative activity in the Macaca mulatta-Plasmodium cynomolgi model. Am J Trop Med Hyg. 1993; 49; 473-477.
(15.) Shanks GD, Edstein MD, Chedester AL, et al. Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta-Plasmodium cynomolgi model. Am J Trop Med Hyg. 1994; 50:641-645.
(16.) Edstein MD, Corcoran KD, Shanks GD, et al. Evaluation of WR250417 (a proguanil analogue) for causal prophylactic activity in the Plasmodium cynomolgi--Macaca mulatta model. Am J Trop Med Hyg 1994; 50: 181-186.
(17.) Edstein MD, Prasitthipayong A, Sabchareon A, et al. Simultaneous measurement of quinine and quinidine in human plasma, whole blood and erythrocytes by high-performance liquid chromatography with fluorescence detection. Ther Drug Monit. 1990; 12:493-500.
(18.) Keeratithakul D, Teja-Isavadharm P, Shanks GD, et al. An improved high-performance liquid chromatographic method for the simultaneous measurement of halofantrine and desbutylhalofantrine in human serum. Ther Drug Monit. 1991; 13:64-68.
(19.) Edstein MD, Lika ID, Chongsuphajaisiddhi T, et al. Quantitation of Fansimef components (mefloquine + sulfadoxine + pyrimethamine) in human plasma by two high-performance liquid chromatographic methods. Ther Drug Monit. 1991; 13:146-151.
(20.) Teja-Isavadharm P, Keeratithakul D, Watt G, et al. Measurement of ciprofloxacin in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography. Ther Drug Monit. 1991; 13:263-267.
(21.) Nosten F, Ter Kuile F, Chongsuphajaisiddhi T, et al. Mefloquine-resistant falciparum malaria on the Thai-Myanmar border. Lancet. 1991; 337:1140-1143.
(22.) Shanks GD, Watt G, Edstein MD, et al. Halofantrine for the treatment of mefloquine chemoprophylaxis failures. Am J Trop Med Hyg. 1991; 45:488-491.
(23.) Watt G, Shanks GD, Edstein MD, et al. Ciprofloxacin treatment of drug-resistant falciparum malaria. J Inf Dis. 1991; 164:602-604.
(24.) Shanks GD, Watt G, Edstein MD, et al. Halofantrine given with food for falciparum malaria. Trans Roy Soc Trop Med Hyg. 1992; 86:233-234.
(25.) Ter Kuile F, Nosten F, Thieren M, et al. High-dose mefloquine in the treatment of multidrug-resistant falciparum malaria. J Inf Dis. 1992; 166; 1393-1400.
(26.) Ter Kuile F, Dolan G, Nosten F, et al. Halofantrine versus mefloquine in treatment of multidrug resistant falciparum malaria. Lancet. 1993; 341:1044-1049.
(27.) Frances SP, Eikarat N, Sripongsai B, Eamsila C. Response of Anopheles dirus and Aedes albopictus to repellents in the laboratory. J Am Mosq Control Assoc. 1993; 9:474-476.
(28.) Eamsila C, Frances SP, Strickman D. Evaluation of permethrin-treated military uniforms for personal protection against malaria in northeastern Thailand. J Am Mosq Control Assoc. 1994; 10:515-521.
(29.) Frances SP, Klein TA, Hildebrandt DW, et al. Laboratory and field evaluation of the repellents, deet, CIC-4 and AI3-37220, against Anopheles dirus (Diptera: Culicidae) in Thailand. J Med Entomol. 1996; 33:511-515.
(30.) Frances SP, Eamsila C, Pilakasiri C, Linthicum KJ. Effectiveness of repellent formulations containing deet against mosquitoes in northeastern Thailand. J Am Mosq Control Assoc. 1996; 12:331-333.
(31.) Frances SP, Klein TA, Wirtz RA, et al. Plasmodium falciparum and Plasmodium vivax circumsoprozoite proteins in anophelines collected in eastern Thailand. J Med Entomol. 1996; 33:990-991.
(32.) Frances SP, Khlaimanee N. Laboratory tests of arthropod repellents against Leptotrombidium deliense--noninfected and infected with Rickettsia tsutsugamushi--and noninfected L. fletcheri (Acari: Trombiculidae). J Med Entomol. 1996; 33:232-235.
(33.) Frances SP, Sithiprasana R, Linthicum KJ. Response of Aedes aegypti and Aedes albopictus uninfected and infected with dengue virus to deet in the laboratory. J Med Entomol. 2011; 48:334-336.
(34.) Frances SP. Rickettsial diseases of military importance: an Australian perspective. J Mil Vet Hlth. 2011; 19(4):25-30.
(35.) Frances SP, Eamsila C, Strickman D. Antibodies to Orientia tsutsugamushi in soldiers in northeastern Thailand. Southeast Asian J Trop Med Publ Hlth. 1997; 28:666-668.
(36.) Frances SP, Watcharapichat P, Phulsuksombati D, Tanskul P. Occurrence of Orientia tsusugamushi in rodents and chiggers (Acari: Trombiculidae) in an orchard near Bangkok, Thailand. J Med Entomol. 1999; 36:449-453.
(37.) Frances SP, Watcharapichat P, Phulsuksombati D, Tanskul P. Transmission of Orientia tsutsugamushi, the aetiologic agent for scrub typhus, to co-feeding mites. Parasitol. 2000; 120:601-607.
(38.) Frances SP, Watcharapichat P, Phulsuksombati D. Development and persistence of antibodies to Orientia tsutsugamushi in the roof rat, Rattus rattus and laboratory mice following attachment of naturally infected Leptotrombidium deliense. Acta Tropica 2000; 77:279-285.
(39.) Frances SP, Watcharapichat P, Phulsuksombati D. Vertical transmission of Orientia tsutsugamushi in two lines of naturally infected Leptotrombidium deliense (Acari: Trombiculidae). J Med Entomol. 2001; 38:17-21.
(40.) Frances SP, Watcharapichat P, Phulsuksombati D, Tanskul P Investigation of the role of Blankaartia acuscutellaris (Acari: Trombiculidae) as a vector of scrub typhus in central Thailand. Southeast Asian J Trop MedPubl Hlth. 2001; 32:863-866.
(41.) Coleman RE, Monkanna T, Linthicum KJ, et al. Occurrence of Orientia tsutsugamushi in small mammals from Thailand. Am J Trop Med Hyg. 2003; 69:519-524.
(42.) Lerdthusnee K, Khlaimanee N, Monkanna T, et al. Efficiency of Leptotrombidium chiggers (Acari: Trombiculidae) at transmitting Orientia tsutsugamushi to laboratory mice. J Med Entomol. 2002; 39:521-525.
(43.) Phasomkusolsil S, Tanskul P, Ratanatham S, et al. Transstadial and transovarial transmission of Orientia tsutsugamushi in Leptotrombidium imphalum and Leptotrombidium chiangraiensis (Acari: Trombiculidae). J Med Entomol. 2009; 46:1442-1445.
(44.) Phasomkusolsil S, Tanskul P, Ratanatham S, et al. Influence of Orientia tsutsugamushi infection on the developmental biology of Leptotrombidium imphalum and Leptotrombidium chiangraiensis (Acari: Trombiculidae). J Med Entomol. 201248:1270-1275.
(45.) Shanks GD, Edstein MD, Suriyamongol V, et al. Malaria chemoprophylaxis using proguanil/dapsone combinations on the Thai-Cambodian border. Am J Trop Med Hyg. 1992; 46:643-648.
(46.) Shanks GD, Edstein MD, Kereu RK, et al. Post exposure administration of halofantrine for the prevention of malaria. Clin Infect Dis. 1993; 17:628-631.
(47.) Shanks GD, Barnett A, Edstein MD, Rieckmann KH. Effectiveness of doxycycline combined with primaquine for malaria prophylaxis. Med J Aust. 1995; 162:306-307,9-10.
(48.) Shanks GD, Roessler P, Edstein MD Rieckmann KH. Doxycycline for malaria prophylaxis in Australian soldiers deployed to United Nations missions in Somalia and Cambodia. Mil Med. 1995; 160:443-445.
(49.) Frances SP, Dung NV, Beebe NW, Debboun M. Field evaluation of repellent formulations against day and night-time biting mosquitoes in a tropical rainforest in northern Australia. J Med Entomol. 2002; 39:541-544.
(50.) Frances SP, MacKenzie DO, Klun JA, Debboun M. Laboratory and field evaluation of SS220 and deet against mosquitoes in Queensland, Australia. J Am Mosq Control Assoc. 2009; 25:174-178.
(51.) Frances SP, Cooper RD, Gupta RK, Debboun M. Efficacy of a new self supporting low profile bednet for personal protection against Anopheles farauti (Diptera: Culicidae) in a village in Papua New Guinea. J Med Entomol. 2003; 40:68-72.
(52.) Kitchen LW, Lawrence KL, Coleman RE. The role of the United States military in the development of vector control products, including insect repellents, insecticides, and bed nets. J Vector Ecol. 2009; 34:50-61.
(53.) Debboun M, Frances SP, Strickman D, eds. Insect Repellents: Principles, Methods & Uses. Boca Raton, FL: CRC Press; 2007.
(54.) Strickman D, Frances SP, Debboun M. Prevention of Bug Bites, Stings, and Disease. New York, NY: Oxford University Press; 2009.
(55.) Debboun M, Frances SP, Strickman D, eds. Insect Repellents Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2015.
(56.) Frances SP, Sferopoulos R, Lee B. Protection from mosquito bites provided by permethrin-treated military fabrics. J Med Entomol. 2014; 51:1220-1226.
(57.) Frances SP, MacKenzie DO, Sferopoulos R, Lee B. The landing of field mosquitoes on permethrin treated military uniforms in Queensland, Australia. J Am Mos Control Assoc. 2014; 30:312-314.
(58.) Shanks GD. The rise and fall of mefloquine as an antimalarial drug in southeast Asia. Mil Med. 1994; 159:275-281.
(59.) Walsh DS, Eamsila C, Sasiprapha T, et al. Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multi-drug resistant P falciparum malaria. J Infect Dis. 2004; 190:1456-1463.
(60.) Edstein MD, Kocisko DA, Walsh DS, et al. Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in Thai soldiers on monthly prophylaxis. Clin Infect Dis. 2003; 37:1654-1658.
(61.) 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; 22:184-189.
(62.) Edstein MD, Koscisko DA, Brewer TG, et al. Population pharmacokinetics of the new antimalaria agent tafenoquine in Thai soldiers. Br J Clin Pharmacol. 2001; 52:663-660.
(63.) Haynes RK, Fugmann B, Stetter J, et al. Artemisone-a highly active antimalarial drug of the artemisinin class. Angew Chem Int Ed Engl. 2006; 45(13):2082-2088.
(64.) Obaldia N 3rd, Kotecka BM, Edstein MD, et al. Evaluation of artemisone combinations in Aotus monkeys infected with Plasmodium falciparum. Antimicrob Agents Chemother. 2009; 53(8):3592-3594.
(65.) Chen N, Chavchich M, Peters JM, et al. Deamplification of pfmdr1-containing amplicon on chromosome 5 in Plasmodium falciparum is associated with reduced resistance to artelinic acid in vitro. An timicrob Agents Chemother. 2010; 54(8):3395-3401.
(66.) Chavchich M, Gerena L, Peters J, et al. Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Agents Chemother. 2010; 54(6):2455-2464.
(67.) Teuscher F, Gatton ML, Chen N, et al. Artemisinin-induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure. J Infect Dis. 2010; 202(9):1362-1368.
(68.) Teuscher F, Chen N, Kyle DE, Gatton ML, Cheng Q. Phenotypic changes in artemisinin-resistant Plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition. Antimicrob Agents Chemother. 2011; 56(1):428-431.
(69.) Edstein MD, Kotecka BM, Ager AL, et al. 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(4):811-818.
(70.) Harris I, Sharrock WW, Bain LM, et al. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malar J. 2010; 9:254. doi: 10.1186/1475-2875-9-254.
(71.) Shanks GD, MD Edstein, Q Cheng, et al. Army Malaria Institute-its evolution and achievements fifth decade: 2006-2015. J Mil Vet Hlth. 2016 24(1). Available at: http://jmvh.org/article/army-malaria-institute-its-evolution-and-achievements-fifth-de cade-2006-2015/. Accessed May 24, 2016.
(72.) Gresty K, Gray KA, Bobogare A, et al. Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihyrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy. Malaria J. 2014:13:402.
(73.) Gresty K, Gray KA, Bobogare A, et al. Genetic mutations in pfcrt and pfmdrl at a time of the artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands. Malaria J. 2014:13:406.
Stephen P. Frances, PhD
Michael D. Edstein, PhD
Mustapha Debboun, PhD, BCE
G. Dennis Shanks, MD
Mention of a commercial product does not constitute an endorsement of the product by the Australian Defence Force or US Department of Defense.
* The country of Burma was renamed Myanmar in 1989.
** deet (diethylmethyl benzamide); AI3-37220 (1-(3-cyclohexen1-cabonyl)-2-m ethyl piperidine); CIC-4 (2-hydroxomethylcyclohexl) acetic acid)
Dr Frances is with the Australian Army Malaria Institute, Enoggera, Queensland.
Dr Edstein is with the Australian Army Malaria Institute, Enoggera, Queensland.
Dr Debboun is the Director of the Mosquito Control Division, Harris County Public Health, Houston, Texas.
Dr Shanks is with the Australian Army Malaria Institute, Enoggera, Queensland. He is also a Professor at the University of Queensland School of Public Health, Brisbane, Australia.
|Printer friendly Cite/link Email Feedback|
|Author:||Frances, Stephen P.; Edstein, Michael D.; Debboun, Mustapha; Shanks, G. Dennis|
|Publication:||U.S. Army Medical Department Journal|
|Date:||Oct 1, 2016|
|Previous Article:||A multiagency approach to reducing West Nile virus risk in Richmond County, Georgia, in 2015.|
|Next Article:||Emerging tick-borne Rickettsia and Ehrlichia at joint base Langley-Eustis, fort Eustis, Virginia.|