Volume 76, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Recent drug trials in Laos have shown high levels of resistance to chloroquine, but there are no published data on antimalarial drug susceptibility. We used the double-site enzyme-linked pLDH immunodetection (DELI) assay to estimate the antimalarial drug susceptibility of 108 fresh isolates from southern Laos. The geometric mean (95% confidence interval) 50% inhibitory concentration values (nmol/L) were 152.4 (123.8–187.6) for chloroquine, 679.8 (533.8–863.0) for quinine, 45.9 (37.9–55.7) for mefloquine, 5.0 (4.4–6.4) for artesunate, 6.3 (4.5–8.9) for dihydroartemisinin, and 59.1 (46.4–75.3) for lumefantrine. The proportion of isolates defined as resistant were 65%, 40%, and 8% for chloroquine, quinine, and mefloquine, respectively. Of 53 isolates genotyped for the T76K chloroquine-resistance mutation, 48 (91%) were mutants. in Laos is multi-drug resistant; antimalarial immunity resulting from the use of ineffective chloroquine before 2005 probably contributes significantly to the therapeutic responses in clinical trials.


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  1. White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113 : 1084–1092. [Google Scholar]
  2. Ebisawa I, Muto T, Kameko S, Mitsui G, 1970. Response of Laotian malaria strains to chemotherapy. J Exp Med 40 : 151–157. [Google Scholar]
  3. Al-Tawil N, 1977. Response of falciparum malaria to a standard regimen of chloroquine in Vientiane, Lao People’s Democratic Republic. J Trop Med Hyg 80 : 230–237. [Google Scholar]
  4. Al-Tawil N, 1978. Clearance of falciparum parasitemia with a single dose sulphadoxine-pyrimethamine in Vientiane, Laos. Southeast Asian J Trop Med Public Health 9 : 409–413. [Google Scholar]
  5. Watson L, 1999. Lao Malaria Review. Unpublished European Union Malaria Project Report. Vientiane, Lao PDR: European Union.
  6. Pillai DR, Labbe AC, Vanisaveth V, Hongvanthong B, Phompida S, Inthakon S, Zhong K, Kain KC, 2001. Plasmodium falciparum malaria in Laos: chloroquine treatment outcome and predictive value of molecular markers. J Infect Dis 183 : 789–795. [Google Scholar]
  7. Guthmann JP, Kasparian S, Phetsouvanh R, Nathan N, Garcia M, Phompida S, Brockman A, Gastellu M, Legros D, 2002. The efficacy of chloroquine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the Lao People’s Democratic Republic. Ann Trop Med Parasitol 96 : 553–557. [Google Scholar]
  8. Mayxay M, Newton PN, Khanthavong M, Pongvongsa T, Phetsouvanh R, Phompida S, Brockman A, White NJ, 2003. Chloroquine versus sulphadoxine-pyrimethamine for treatment of Plasmodium falciparum malaria in Savannakhet Province, Lao People’s Democratic Republic: An assessment of national antimalarial drug recommendations. Clin Infect Dis 37 : 1021–1028. [Google Scholar]
  9. Mayxay M, Phetsouvanh R, Phompida S, Newton PN, Khanthavong M, Vannachone B, Brockman A, White NJ, 2003. A randomized comparison of oral chloroquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in Laos. Trans R Soc Trop Med Hyg 97 : 343–344. [Google Scholar]
  10. Schwobel B, Jordan S, Vanisaveth V, Phetsouvanh R, Christophel EM, Phompida S, von Sonnenburg F, Jelinek T, 2003. Therapeutic efficacy of chloroquine plus sulphadoxine/pyrimethamine compared with monotherapy with either chloroquine or pyrimethamine/sulphadoxine in uncomplicated Plasmodium falciparum malaria in Laos. Trop Med Int Health 8 : 19–24. [Google Scholar]
  11. Mayxay M, Khanthavong M, Lindegårdh N, Keola S, Barends M, Pongvongsa T, Yapom R, Annerberg A, Phompida S, Phetsouvanh R, White NJ, Newton PN, 2004. Randomized comparison of chloroquine plus sulphadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao PDR (Laos). Clin Infect Dis 39 : 1139–1147. [Google Scholar]
  12. Stohrer JM, Dittrich S, Thongpaseuth V, Vanisaveth V, Phetsouvanh R, Phompida S, Monti F, Christophel EM, Lindegårdh N, Annerbergerg A, Jelinek T, 2004. Therapeutic efficacy of artemether-lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People’s Democratic Republic. Trop Med Int Health 9 : 1175–1183. [Google Scholar]
  13. Mayxay M, Thongpaseuth V, Khanthavong M, Lindegårdh N, Barend M, Keola S, Pongvongsa T, Phompida S, Phetsouvanh R, White NJ, Newton PN, 2006. An open, randomized comparison of artesunate plus mefloquine versus dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in the Lao People’s Democratic Republic (Laos). Trop Med Intl Hlth 11 : 1157–1165. [Google Scholar]
  14. Dittrich S, Alifrangis M, Stohrer JM, Thongpaseuth V, Vanisaveth V, Phetsouvanh R, Phompida S, Khalil IF, Jelinek T, 2005. Falciparum malaria in the north of Laos: the occurrence and implications of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene haplotype SVMNT. Trop Med Intl Hlth 10 : 1267–1270. [Google Scholar]
  15. Berens N, Schwoebel B, Jordan S, Vanisaveth V, Phetsouvanh R, Christophel EM, Phompida S, Jelinek T, 2003. Plasmodium falciparum: correlation of in vivo resistance to chloroquine and antifolates with genetic polymorphisms in isolates from the south of Lao PDR. Trop Med Int Health 8 : 775–782. [Google Scholar]
  16. Druilhe P, Moreno A, Blanc C, Brasseur PH, Jacquier P, 2001. A colorimetric in vitro drug sensitivity assay for Plasmodium falciparum based on a highly sensitive double-site lactate dehydrogenase antigen-capture enzyme-linked immunosorbent assay. Am J Trop Med Hyg 64 : 233–241. [Google Scholar]
  17. Moreno A, Brasseur P, Cuzin-Ouattara N, Blanc C, Druilhe P, 2001. Evaluation under field conditions of the colourimetric DELI-microtest for the assessment of Plasmodium falciparum drug resistance. Trans R Soc Trop Med Hyg 95 : 100–103. [Google Scholar]
  18. Brockman A, Singlam S, Phiaphun L, Looareesuwan S, White NJ, Nosten F, 2004. Field evaluation of a novel colorimetric method-double-site enzyme-linked lactate dehydrogenase immunodetection assay-to determine drug susceptibilities of Plasmodium falciparum clinical isolates from northwestern Thailand. Antimicrob Agents Chemother 48 : 1426–1429. [Google Scholar]
  19. Piper P, Lebras J, Wentworth L, Hunt-Cooke A, Houzé S, Chiodini P, Makler M, 1999. Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH). Am J Trop Med Hyg 60 : 109–118. [Google Scholar]
  20. Anderson TJC, Nair S, Jacobzone C, Zavai A, Balkan S, 2003. Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El Gazal Province, Sudan. Trop Med Intl Hlth 8 : 1068–1073. [Google Scholar]
  21. Anderson TJ, Nair S, Qin H, Singlam S, Brockman A, Paiphun L, Nosten F, 2005. Are transporter genes other than the chloroquine resistance locus (pfcrt) and multidrug resistance gene (pfmdr) associated with antimalarial drug resistance? Antimicrob Agents Chemother 49 : 2180–2188. [Google Scholar]
  22. Brasseur P, Druilhe P, Kouamouo J, Brandicourt O, Danis M, Moyou SR, 1986. High level of sensitivity to chloroquine of 72 Plasmodium falciparum isolates from southern Cameroon in January 1985. Am J Trop Med Hyg 35 : 711–716. [Google Scholar]
  23. Brasseur P, Kouamouo J, Brandicourt O, Moyou-Somo R, Druilhe P, 1988. Patterns of in vitro resistance to chloroquine, quinine, and mefloquine of Plasmodium falciparum in Cameroon, 1985–1986. Am J Trop Med Hyg 39 : 166–172. [Google Scholar]
  24. Basco LK, Le Bras J, 1994. In vitro susceptibility of Cambodian isolates of Plasmodium falciparum to halofantrine, pyronaridine and artemisinin derivatives. Ann Trop Med Parasitol 88 : 137–144. [Google Scholar]
  25. Ringwald P, Bickki J, Basco LK, 1996. In vitro activity of antimalarials against clinical isolates of Plasmodium falciparum in Yaounde. Am J Trop Med Hyg 55 : 254–258. [Google Scholar]
  26. Price RN, Cassar C, Brockman A, Duraisingh M, van Vugt M, White NJ, Nosten F, Krishna S, 1999. The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob Agents Chemother 43 : 2943–2949. [Google Scholar]
  27. Price RN, Uhlemann AC, Brockman A, McGready R, Ashley A, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S, 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364 : 438–447. [Google Scholar]
  28. Labbe AC, Bualombai P, Pillai DR, Zhong JY, Vanisaveth V, Hongvanthong B, Looareesuwan S, Kain KC, 2001. Molecular markers for chloroquine-resistant Plasmodium falciparum malaria in Thailand and Laos. Ann Trop Med Parasitol 95 : 781–788. [Google Scholar]
  29. Thomas SM, Ndir O, Dieng T, Mboup S, Wypij D, Maguire JH, Wirth DF, 2002. In vitro chloroquine susceptibility and PCR analysis of pfCRT and pfMDR1 polymorphisms in Plasmodium falciparum isolates from Senegal. Am J Trop Med Hyg 66 : 474–480. [Google Scholar]
  30. Brockman A, Price RN, van Vugt M, Heppner DG, Walsh D, Sookto P, Wimonwattrawatee T, Looareesuwan S, White NJ, Nosten F, 2000. Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. Trans R Soc Trop Med Hyg 94 : 537–544. [Google Scholar]
  31. Lim P, Chim P, Sem R, Nemh S, Poravuth Y, Lim C, Seila S, Tsuyuoka R, Denis MB, Socheat D, Fandeur T, 2005. In vitro monitoring of Plasmodium falciparum susceptibility to artesunate, mefloquine, quinine, and chloroquine in Cambodia: 2001–2002. Acta Trop 93 : 31–40. [Google Scholar]
  32. Huong NM, Hewitt S, Davis TME, Dao LD, Toan TQ, Kim TB, Hanh NT, Phuoung VN, Nhan DH, Cong LD, 2001. Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Vietnam: A study in vivo and in vitro. Trans R Soc Trop Med Hyg 95 : 325–329. [Google Scholar]
  33. Mayxay M, Chotivanich K, Pukrittayakamee S, Newton PN, Looareesuwan S, White NJ, 2001. The contribution of humoral immunity to the therapeutic response in falciparum malaria. Am J Trop Med Hyg 65 : 918–923. [Google Scholar]
  34. Vythilingam I, Phetsouvanh R, Keokenchanh K, Yengmala V, Vanisaveth V, Phompida S, Hakim SL, 2003. The prevalence of Anopheles (Diptera: Culicidae) mosquitoes in Sekong Province, Lao PDR in relation to malaria transmission. Trop Med Int Health 8 : 525–535. [Google Scholar]
  35. Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O, 2005. Resistance of Plasmodium falciparum field isolates to in vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366 : 1960–1963. [Google Scholar]

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  • Received : 08 Jun 2006
  • Accepted : 24 Oct 2006

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