To improve our knowledge in the development, survival and spread of drug resistance in malaria parasites and to monitor the extent of drug resistance and efficacy of standard and new antimalaral drugs in areas of interest to ADF. The department explores and evaluates novel malaria detection/diagnosis methods including molecular and various rapid diagnostic kits. The department is engaged in studies investigating P. vivax genetics that determine or correlate with relapses of infections.
Despite the use of radical cure regimens, post operational relapses of P. vivax infections in ADF personnel have become a major health problem. Studies in parasite genetics are under way to investigate factors that associated with increased risk of relapses.
Many rapid diagnostic tests (RDTs) for P. falciparum have been developed and are commercially available. Most of these RDTs are based on detecting parasite antigens in patient's blood. The detection sensitivity of these kits is highly variable. In collaboration with WPRO/WHO and FIND we are investigating the possible causes of the sensitivity variation. Our research focus on defining genetic diversity in parasite antigens, difference in the level of antigens produced by parasites and the variation in epitopes recognised by monoclonal antibodies. The study outcome will help the selection and quality control of RDTs, as well as help to improve the detection sensitivity of malaria RDTs .
For assisting microscopic confirmation of malaria infections, we have established PCR-based detection for 4 human malaria species. We will continue to improve out capacity to perform multiplex PCR and develop field adaptable PCR methods. Currently, the department is actively involved in the AusAID Pacific Malaria Initiatives. We are investigating the prevalence of the malaria infections and the transmission parameters in Vanuatu and Solomon Islands using molecular tools.
(Current and past staff names in bold)
Joanne Baker, Michelle L Gatton, Jennifer Peters, Mei-Fong Ho, James McCarthy and Qin Cheng. Transcription and Expression of Plasmodium falciparum Histidine-Rich Proteins in Different Stages and Strains: Implications for the Performance of Rapid Diagnostic Tests. PLoS One, 2011: manuscript in review.
Codd A, Teuscher F, Kyle D, Cheng Q, Gatton M. Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure. Malar J. 2011; 10:56.
Alyson M Auliff, Bharath Balu, Michael T O’Neil, Qin Cheng, John H Adams. Stable integration of Plasmodium vivax dihydrofolate reductase-thymidylate synthase Gene using the piggyBac transposon. 2011: manuscript in preparation.
Fukuda MM, Klein TA, Kochel T, Quandelacy TM, Smith BL, Villinski J, Bethell D, Tyner S, Se Y, Lon C, Saunders D, Johnson J, Wagar E, Walsh D, Kasper M, Sanchez1 JL, Witt CJ, Cheng Q, Waters N, Shrestha SK, Pavlin JA, Lescano AG, Graf PCF, Richardson JH, Durand S, Rogers WO, Blazes DL, Russell KL, the AFHSC-GEIS Malaria and Vector Borne Infections Writing Group. Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments. BMC Public Health, 2011; 11(Suppl 2):S9.
Teuscher F, Gatton M, Chen N, Peters J, Kyle D, Cheng Q. Artemisinin induced dormancy in Plasmodium falciparum: Duration, recovery rates and implications in treatment failure. J Inf Dis, 2010; 202: 1362-1368.
Baker J, Ho MF, Pelecanos A, Gatton M, Chen N, Abdullah S, Albertini A, Ariey F, Barnwell J, Bell D, Cunningham J, Djalle D, Echeverry DF, Gamboa D, Hii J, Kyaw MP, Luchavez J, Membi C, Menard D, Murillo C, Nhem S, Ogutu B, Onyor P, Oyibo W, Wang SQ, McCarthy J, Cheng Q. Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of rapid diagnostic tests. Malar J, 2010; 9:129.
Alyson M Auliff, John H Adams, Michael T O’Neil, Qin Cheng. Defining the role of mutations in Plasmodium vivax dihydrofolate reductase-thymidylate synthase Gene using an episomal Plasmodium falciparum transfection system. Antimicrob. Agents Chemother. 2010; 54(9):3927-32.
Nasveld PE, Edstein MD, Reid M, Brennan L, Harris IE, Kitchener SJ, Leggat PA, Pickford P, Kerr C, Orht C, Prescott W, Tafenoquine Study Team. Randomised, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother. 2010; 54(2):792-8.
Chavchich M, Gerena L, Peters J, Chen N, Cheng Q, Kyle DE. Induction of resistance to artemisinin derivatives in Plasmodium falciparum: role of pfmdr1 amplification and expression. Antimicrob Agent Chemother, 2010; 54:2455-2464.
Chen N, Chavchich M, Peters JM, Kyle DE, Gatton ML, Cheng, Q. De-amplification of pfmdr1-containing amplicon on chromosome 5 in Plasmodium falciparum is associated with reduced resistance to artelinic acid in vitro. Antimicrob Agent Chemother, 2010; 54:3395-3401.
Gamboa D, Ho MF, Bendezu J, Torres K, Chiodini PL, Barnwell JW, Incardona S, Perkins M, Bell D, McCarthy J, Cheng, Q. A large proportion of Plasmodium falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test (RDT) performance in the region. PLoS One, 2010; 5(1):e8091.
Figtree M, Lee R, Bain L, Kennedy B, Mackertich S, Urban M, Cheng Q, Hudson BJ, Plasmodium knowlesi acquired in Indonesian Borneo. Emerg Infect Dis, 2010; 16(4):672-674.
Taleo GA, Bobogare A, A Auliff, L Bain, L Boaz, Q Cheng, A Clements, A Ebringer, MD Edstein, N Elmes, S Forsyth, K Gray, I Harris, H Iata, Jennifer Iavro, K Lilley, H Reid, WW Sharrock, A Vallely, NC Waters, S Yama, GD Shanks. Pacific Malaria Initiative Survey Group (PMISG) on behalf of the Ministries of Health of Vanuatu and Solomon Islands. Malaria on Isolated Melanesian Islands Prior to the Initiation of Malaria Elimination Activities. Malar J, 2010; 9:218.
Harris I, Sharrock W, Bain L, Gray K, Bobogare A, Boaz L, Lilley K, Krause D, Vallely A, Gatton M, Cheng Q. A large proportion of asymptomatic malaria infections with low and sub-microscopic parasite densities in Temotu province, Solomon Islands: challenges for malaria diagnostics in an elimination setting. Malar J, 2010; 9:254.Gatton ML, Cheng Q. Interrupting Malaria Transmission: Quantifying the Impact of Interventions in Regions of Low to Moderate Transmission. PLoS One, 2010; 5(12):e15149.
McGowan S, Porter C, Lowther J, Stack C, Golding S, Skinner-Adams T, Trenholme K, Teuscher F, Donnelly S, Grembecka J, Mucha A, Kafarski P, DeGori R, Buckle A, Gardiner D, Whisstock J, Dalton J. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase: a new route for antimalarial compounds. PNA , 2009; 106 (8): 2537-2542.
Alyson M Auliff, John H Adams, Michael T O’Neil, Qin Cheng. Investigation of genetic mutations in Plasmodium vivax dihdrofolate reductase and susceptibility to conventional and new antifolates antimalarials using a Plasmodium falciparum expression system. Am J Trop Med Hyg, 2009; 81 (5): supp 1.Upcroft JA, Kraue, KG, Burgess AG, Dunn LA, Chen N, Upcroft P. Sequence map of the 3-Mb Giardia duodenalis assemblage A chromosome. Chromosome Res, 2009; 17:1001-1014.
Chen N, Gao Q, Wang SQ, Wang GZ, Gatton M and Cheng Q. (2008) No genetic bottle-neck in Plasmodium falciparum wild type pfcrt alleles re-emerging in Hainan Island, China following high-level Chloroquine resistance. Antimicrob. Agent. Chemother 52(1): 345-347.
Gatton, ML. and Cheng Q. (2008) Therapeutic efficacy of anti-malarials: parasite diversity, PCR-genotyping and statistics. Trends Parasitol. 24(2):68-73.
Russell B, Chalfien F, Prasetyorini B, Kenangalem E, Piera K, Suwanarusk R, Brockman A, Prayoga, Sugiarto P, Cheng Q, Tjitra E, Anstey NM, Price RN (2008) Determinates of in vitro drug susceptibility testing of Plasmodium vivax. Antimicrob. Agent. Chemother 52(3): 1040-1045.
Appleyard B, Tuni M, Cheng Q, Chen N, Bryan J, McCarthy JS. Malaria in pregnancy in the Solomon islands: barriers to prevention and control. Am J Trop Med Hyg. 2008 Mar;78(3):449-54.
Hawkins VN, Auliff A, Prajapati SK, Rungsihirunrat K, Hapuarachchi HC, Maestre A, O'Neil MT, Cheng Q, Joshi H, Na-Bangchang K, Sibley CH. Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase. Malar J. 2008 Apr 28;7:72.
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. Amplification of pvmdr1 associated with multidrug resistant P. vivax. J Infect Dis, 2008; 198 (10): 1558-64.
Carlton JM, Adams JH, Silva JC, Bidwell SL, Lorenzi H, Caler E, Crabtree J, Angiuoli SV, Merino EF, Amedeo P, Cheng Q, Coulson RM, Crabb BS, Del Portillo HA, Essien K, Feldblyum TV, Fernandez-Becerra C, Gilson PR, Gueye AH, Guo X, Kang'a S, Kooij TW, Korsinczky M, Meyer EV, Nene V, Paulsen I, White O, Ralph SA, Ren Q, Sargeant TJ, Salzberg SL, Stoeckert CJ, Sullivan SA, Yamamoto MM, Hoffman SL, Wortman JR, Gardner MJ, Galinski MR, Barnwell JW, Fraser-Liggett CM. Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature. 2008 Oct 9;455(7214):757-63.
Jennifer M. Peters, Elizabeth V. Fowler, Darren Krause, Qin Cheng, Michelle L. Gatton (2007) Differential changes in Plasmodium falciparum var transcription during adaptation to culture. J. Infect. Dis. 195:748-755.
Chen, N., Auliff, A., Rieckmann, K., Gatton, L.M. and Cheng, Q. (2007) Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J. Infect. Dis. 195(7):934-941.
O’Neil, M.T., Korsinczky, M.L.J, Gresty, K., Auliff, A. and Cheng Q. (2007) A P. falciparum heterologous expression system for the assessment of antifolate resistance caused by mutant P. vivax dihydrofolate reductase-thymidylate synthase. J. Infect. Dis. 196:467-474.
Baker J, McCarthy J, Gatton M, Lee N, Bell D, Peters J, Cheng Q. Rapid Diagnostic Tests for malaria: are they sufficiently reliable? Journal of the Australian Defence Health Service, 2007; 8: 12-17.
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.
Krause, D., Gatton, M.L., Frankland, S., Eisen, D.P., Good, M.F. Lilley, L. and Cheng, Q. (2007) Characterisation of the antibody response against Plasmodium falciparum erythrocyte membrane protein-1 in human volunteers. Infect. Immun. 75(12): 5967-5973.
Gatton, M.L., Peters, J.M, Gresty, K., Fowler, E.V., Chen, N. & Cheng Q. (2006) Detection sensitivity and quantitation of Plasmodium falciparum var gene transcripts by real-time RT-PCR in comparison with conventional RT-PCR. Am. J. Trop. Med. Hyg. 75(2):212-218.
Fowler, E.V., Chavchich, M., Chen, N., Peters, J.M., Kyle, D., Gatton, M.L and Cheng, Q. (2006) Physical linkage to drug resistance genes results in conservation of var genes among West Pacific Plasmodium falciparum isolates. J. Infect. Dis. 194:939-948.
Gatton, M.L and Cheng, Q. (2006) Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine. J. Antimicrob. Agent. Chemother. 58(1):47-51.
Lee, N., Baker, J., Andrews, K., Gatton, M., Bell, D., Cheng, Q. and McCarthy, J. (2006) The effect of sequence variation in Plasmodium falciparum Histidine-Rich Protein 2 on the binding of specific monoclonal antibodies: implications for Rapid Diagnostic Tests for malaria. J. Clin. Microb 44(8):2773-2778.
Auliff, A., Wilson, D., Russell, B., Gao, Q., Chen, N., Anh, L.N., Maguire, J., O'Neil, M. and Cheng, Q. (2006) Amno acid mutations in Plasmodium vivax DHFR and DHPS from several geographical rerions and susceptibility to antifolate drugs. Am. J. Trop. Med. Hyg 75(4): 617-621.
Lee, N., Baker, J., Bell, D., McCarthy, J. and Cheng, Q. (2006) Assessing the genetic diversity of Plasmodium falciparum and Plasmodium vivax aldolases and its potential effect on the performance of Aldolase-based Rapid Diagnostic Tests (RDTs). J Clin Microb 44(12):4547-4549.
21 September, 2011