Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


We measured antimalarial drug susceptibility of 84 field isolates from Blantyre, Southern Malawi, using the WHO microtest and the lactate dehydrogenase assay. We also genotyped these isolates to investigate whether variation in their absolute drug sensitivity is associated with specific sets of and mutations harbored by parasites. Our results show that nearly a decade after the withdrawal of chloroquine (CQ) as a first-line antimalarial in Malawi, most isolates are now sensitive to CQ and none is CQ-resistant as predicted by their drug sensitivity phenotype and genotype. We also found that these isolates are uniformly sensitive to a range of quinoline-based antimalarials and artemisinin derivatives. These findings reinforce previous reports about a reduction in the proportion of CQ-resistant parasites after the withdrawal of CQ in 1993 and pave the way for reassessing the clinical usefulness of CQ, artemisinins and other quinoline-based antimalarials in Malawi.


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  1. WHO, 1990. In vitro Micro-Test (Mark II) for the assessment of the response of Plasmodium falciparum to chloroquine, mefloquine, quinine, sulfadoxine/pyrimethamine and amodiaquine. Geneva: World Health Organization.
  2. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD, 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16 : 710–718.
  3. Le Bras J, Deloron P, 1983. In vitro study of drug sensitivity of Plasmodium falciparum: evaluation of a new semi-micro test. Am J Trop Med Hyg 32 : 447–451.
  4. Makler MT, Ries JM, Williams JA, Bancroft JE, Piper RC, Gibbons BL, Hinrichs DJ, 1993. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity. Am J Trop Med Hyg 48 : 739–741.
  5. Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193 : 673–675.
  6. Djimdé A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su X, Nomura T, Fidock DA, Wellems TE, Plowe CV, 2001. A molecular marker for chloroquine resistant falciparum malaria. N Engl J Med 344 : 257–263.
  7. Hatin I, Trape JF, Legros F, Bauchet J, Le Bras J, 1992. Susceptibility of Plasmodium falciparum strains to mefloquine in an urban area in Senegal. Bull World Health Organ 70 : 363–367.
  8. Cremer G, Basco LK, Le Bras J, Camus D, Slomianny C, 1995. Plasmodium falciparum: detection of P-glycoprotein in chloroquine-susceptible and chloroquine-resistant clones and isolates. Exp Parasitol 81 : 1–8.
  9. Ringwald P, Bickii J, Basco LK, 1996. In vitro activity of antimalarials against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon. Am J Trop Med Hyg 55 : 254–258.
  10. Pradines B, Tall A, Parzy D, Spiegel A, Fusai T, Hienne R, Trape JF, Doury JC, 1998. In vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents. J Antimicrob Chemother 42 : 333–339.
  11. Bloland PB, Lackritz EM, Kazembe PN, Were JB, Steketee R, Campbell CC, 1993. Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa. J Infect Dis 167 : 932–937.
  12. Kublin JG, Cortese JF, Njunju EM, Mukadam RAG, Wirima JJ, Kazembe PN, Djimdé AA, Kouriba B, Taylor TE, Plowe CV, 2003. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187 : 1870–1875.
  13. Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LMB, Sidhu A, Naude B, Deitsch KW, Su X, Wootton JC, Roepe PD, Wellems TE, 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6 : 861–871.
  14. Takechi M, Matsuo M, Ziba C, Macheso A, Butao D, Zungu I, Chakanika I, Bustos MDG, 2001. Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine-pyremethamine and other antimalarial drugs in Malawian children. Trop Med Int Health 6 : 429–434.
  15. Mita T, Kaneko A, Lum JK, Bwijo B, Takechi M, Zungu IL, Tsukahara T, Tanabe K, Kobayakawa T, Bjorkman A, 2003. Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi. Am J Trop Med Hyg 68 : 413–415.
  16. Mita T, Kaneko A, Lum JK, Zungu IL, Tsukahara T, Eto H, Kobayakawa T, Bjorkman A, Tanabe K, 2004. Expansion of wild type allele rather than back mutation explains the recent recovery of chloroquine sensitivity of Plasmodium falciparum in Malawi. Mol Biochem Parasitol 135 : 159–163.
  17. Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355 : 1959–1966.
  18. Basco LK, Bickii J, Ringwald P, 1998. In vitro activity of lumefantrine (benflumetol) against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon. Antimicrob Agents Chemother 42 : 2347–2351.
  19. Ringwald P, Bickii J, Basco LK, 1999. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon. Am J Trop Med Hyg 61 : 187– 192.
  20. Basco LK, Le Bras J, 1993. In vitro activity of monodesethylamodiaquine and amopyroquine against African isolates and clones of Plasmodium falciparum. Am J Trop Med Hyg 48 : 120–125.
  21. Bray PG, Hawley SR, Ward SA, 1996. 4-Aminoquinoline resistance of Plasmodium falciparum: insights from the study of amodiaquine uptake. Mol Pharmacol 50 : 1551–1558.
  22. Childs GE, Boudreau EF, Milhous WK, Wimonwattratee T, Pooyindee N, Pang L, Davidson DE Jr, 1989. A comparison of the in vitro activities of amodiaquine and desethylamodiaquine against isolates of Plasmodium falciparum. Am J Trop Med Hyg 40 : 7–11.
  23. Geary TG, Jensen JB, 1983. Lack of cross-resistance to 4-aminoquinolines in chloroquine-resistant Plasmodium falciparum in vitro. J Parasitol 69 : 97–105.
  24. Geary TG, Divo AA, Jensen JB, 1987. Activity of quinoline-containing antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 81 : 499–503.
  25. Bray PG, Hawley SR, Mungthin M, Ward SA, 1996. Physicochemical properties correlated with drug resistance and the reversal of drug resistance in Plasmodium falciparum. Mol Pharmacol 50 : 1559–1566.
  26. Hawley SR, Bray PG, O’Neill PM, Naisbitt DJ, Park BK, Ward SA, 1996. Manipulation of the N-alkyl substituent in amodiaquine to overcome the verapamil-sensitive chloroquine resistance component. Antimicrob Agents Chemother 40 : 23452349.
  27. Draper CC, Hills M, Kilimali VA, Brubaker G, 1988. Serial studies on the evolution of drug resistance in malaria in an area of East Africa: findings from 1979 up to 1986. J Trop Med Hyg 91 : 265–273.
  28. Van der Kaay HJ, Wernsdorfer WH, Froeling FM, 1985. In vitro response of Plasmodium falciparum to mefloquine: studies conducted in West and East-Africa. Ann Soc Belg Med Trop 65 : 147–153.
  29. Barnes DA, Foote SJ, Galatis D, Kemp DJ, Cowman AF, 1992. Selection for high-level chloroquine resistance results in deamplification of the pfmdr1 gene and increased sensitivity to mefloquine in Plasmodium falciparum. EMBO J 11 : 3067–3075.
  30. Sowunmi A, Oduola AM, Salako LA, Ogundahunsi OA, Laoye OJ, Walker O, 1992. The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro. Trans R Soc Trop Med Hyg 86 : 368–371.
  31. Nateghpour M, Ward SA, Howells RE, 1993. Development of halofantrine resistance and determination of cross-resistance patterns in Plasmodium falciparum. Antimicrob Agents Chemother 37 : 2337–2343.
  32. Wernsdorfer WH, Landgraf B, Wiedermann G, Kollaritsch H, 1994. Inverse correlation of sensitivity in vitro of Plasmodium falciparum to chloroquine and mefloquine in Ghana. Trans R Soc Trop Med Hyg 88 : 443–444.
  33. Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403 : 906–909.
  34. Thaithong S, Suebsaeng L, Rooney W, Beale GH, 1988. Evidence of increased chloroquine sensitivity in Thai isolates of Plasmodium falciparum. Trans R Soc Trop Med Hyg 82 : 37–38.
  35. Basco LK, Le Bras J, Rhoades Z, Wilson CM, 1995. Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from sub-Saharan Africa. Mol Biochem Parasitol 74 : 157–166.

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  • Received : 13 Dec 2006
  • Accepted : 28 Feb 2007

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