Volume 72, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The use of chloroquine treatment for malaria was abandoned in China in 1979 because of widespread drug resistance. Subsequent studies found decreases in the prevalence of chloroquine-resistant strains. To evaluate these decreases and assess the current status of chloroquine sensitivity in Hainan, China, we determined the prevalence of the chloroquine resistance transporter (PfCRT) 76T marker in the DNA of blood samples collected from 1978 to 2001. Results showed the presence of PfCRT 76T in 101 of 112 samples (90%) from 1978 to 1981, 30 of 43 samples (70%) from 1986, 22 of 34 samples (65%) from 1997 to 1998, and 37 of 68 samples (54%) from 2001. The prevalence of PfCRT 76T thus progressively decreased after chloroquine was discontinued as a treatment for malaria (χ = 5.2, < 0.022 [1978–1981 versus 1986]; χ = 7.4, < 0.006 [1978–1981 versus 1997–1998]; and χ = 28.8, < 0.0001 [1978–1981 versus 2001]). Reduced prevalence of the PfCRT 76T marker is consistent with greater rates of chloroquine sensitivity from drug assays of blood samples in 1997 and 2001. Monitoring for continued decreases will provide valuable information for future drug-use policies in China.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Chen L, Dai ZR, Cai XZ, Waki S, 1998. Epidemic history of drug-resistant falciparum malaria in Hainan province. J Guangzhou Univ Traditional Chin Med 15: 35–37. [Google Scholar]
  2. Liu DQ, Liu RJ, Ren DX, Gao DQ, Zhang CY, Qiu CP, Cai XZ, Ling CF, Liang AH, Tang Y, 1992. Alteration in resistance of Plasmodium falciparum to chloroquine after cessation of chloroquine medication for twelve years. Chin Parasitol Parasitic Dis 10 : 241–244. [Google Scholar]
  3. Liu DQ, Liu RJ, Ren DX, Gao DQ, Zhang CY, Qui CP, Cai XZ, Ling CF, Song AH, Tang X, 1995. Change in the resistance of Plasmodium falciparum to chloroquine in Hainan, China. Bull World Health Organ 73 : 483–486. [Google Scholar]
  4. Chen PQ, He KR, Peng NZ, Ou FZ, Fu LC, 2003. In vitro sensitivity of Plasmodium falciparum to chloroquine in Dongfang city in Hainan province. J Trop Med 3 : 167–168. [Google Scholar]
  5. Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, 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. [Google Scholar]
  6. Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 : 257–263. [Google Scholar]
  7. Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184 : 770–776. [Google Scholar]
  8. Rieckmann KH, Campbell GH, Sax LJ, Mreme JE, 1978. Drug sensitivity of Plasmodium falciparum: an in-vitro microtechnique. Lancet 1 : 22–23. [Google Scholar]
  9. Liu DQ, Liu RJ, Zhang CY, Cai XZ, Tang X, Yang HL, Yang PF, Dong Y, 1996. Present status of the sensitivity of Plasmodium falciparum to antimalarials in China. Chin Parasitol Parasitic Dis 14 : 37–41. [Google Scholar]
  10. Wootton JC, Feng X, Ferdig MT, Cooper RA, Mu J, Baruch DI, Magill AJ, Su XZ, 2002. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418 : 320–323. [Google Scholar]
  11. Chen N, Kyle DE, Pasay C, Fowler EV, Baker J, Peters JM, Cheng Q, 2003. pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines. Antimicrob Agents Chemother 47 : 3500–3505. [Google Scholar]
  12. Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15 : 867–877. [Google Scholar]
  13. Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF, 1990. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature 345 : 202–203. [Google Scholar]
  14. Wilson CM, Volkman SK, Thaithong S, Martin RK, Kyle DE, Milhous WK, Wirth DF, 1993. Amplification of pfmdr-1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol Biochem Parasitol 57 : 151–160. [Google Scholar]
  15. Haruki K, Bray PG, Ward SA, Hommel M, Ritchie GY, 1994. Chloroquine resistance of Plasmodium falciparum: further evidence for a lack of association with mutations of the pfmdr-1 gene. Trans R Soc Trop Med Hyg 88 : 694. [Google Scholar]
  16. Cox-Singh J, Singh B, Alias A, Abdullah MS, 1995. Assessment of the association between three pfmdr1 point mutations and chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg 89 : 436–437. [Google Scholar]
  17. Chaiyaroj SC, Buranakiti A, Angkasekwinai P, Looaressuwan S, Cowman AF, 1999. Analysis of mefloquine resistance and amplification of pfmdr1 in multidrug-resistant Plasmodium falciparum isolates from Thailand. Am J Trop Med Hyg 61 : 780–783. [Google Scholar]
  18. Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde 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. [Google Scholar]
  19. Expert Advisory Committee on Malaria, Ministry of Health, 2000. Malaria situation in the People’s Republic of China in 1999. Chin Parasitol Parasitic Dis 18 : 129–131. [Google Scholar]
  20. Bruce MC, Donnelly CA, Alpers MP, Galinski MR, Barnwell JW, Walliker D, Day KP, 2000. Cross-species interactions between malaria parasites in humans. Science 287 : 845–848. [Google Scholar]
  21. Chen L, Qu F, Zhou Y, 1982. Field observations on the antimalarial piperaquine. Chin Med J 95 : 281–286. [Google Scholar]
  22. Basco LK, Ringwald P, 2003. In vitro activities of piperaquine and other 4-aminoquinolines against clinical isolates of Plasmodium falciparum in Cameroon. Antimicrob Agents Chemother. 47 : 1391–1394. [Google Scholar]
  23. 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. [Google Scholar]
  24. Carlin JM, Vande Waa JA, Jensen JB, Akood MA, 1984. African serum interference in the determination of chloroquine sensitivity in Plasmodium falciparum. Z Parasitenkd 70 : 589–597. [Google Scholar]
  25. Denis MB, Davis TM, Hewitt S, Incardona S, Nimol K, Fandeur T, Poravuth Y, Lim C, Socheat D, 2002. Efficacy and safety of dihydroartemisinin-piperaquine (Artekin) in Cambodian children and adults with uncomplicated falciparum malaria. Clin Infect Dis 35 : 1469–1476. [Google Scholar]
  26. Karunajeewa H, Lim C, Hung TY, Ilett KF, Denis MB, Socheat D, Davis TM, 2004. Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria. Br J Clin Pharmacol 57 : 93–99. [Google Scholar]

Data & Media loading...

  • Received : 30 Jul 2004
  • Accepted : 16 Nov 2004

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error