1921
Volume 90, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first-line therapy for falciparum malaria; little is known about the prevalence of molecular markers of parasite drug resistance. Across the DRC, we genotyped 166 parasites in chloroquine resistance transporter () using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73 (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine-resistant CV, 35 (21.1%) parasites were mixed CVMNK and CV, and 3 parasites were other genotypes. Ninety-two infections (55.4%) harbored the K76 substitution that is highly correlated with chloroquine failure. The amodiaquine-resistant VMN haplotype was absent. Geographically, haplotypes were not clearly clustered. Chloroquine accounted for 19.4% of antimalarial use, and amodiaquine accounted for 15.3% of antimalarial use; there were no associations between drug use and mutant haplotype prevalence. In the DRC, our molecular survey indicates that resistance to chloroquine is substantial but that resistance to amodiaquine is absent. These contrasting findings highlight the need for molecular surveillance of drug resistance to inform malaria control policies.

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2014-06-04
2017-11-25
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References

  1. Sidhu AB, Verdier-Pinard D, Fidock DA, , 2002. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298: 210213.[Crossref]
  2. Picot S, Olliaro P, de Monbrison F, Bienvenu AL, Price RN, Ringwald P, , 2009. A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar J 8: 89.[Crossref]
  3. Yuan J, Cheng KC, Johnson RL, Huang R, Pattaradilokrat S, Liu A, Guha R, Fidock DA, Inglese J, Wellems TE, Austin CP, Su XZ, , 2011. Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science 333: 724729.[Crossref]
  4. 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: 19591966.[Crossref]
  5. Laufer MK, Takala-Harrison S, Dzinjalamala FK, Stine OC, Taylor TE, Plowe CV, , 2010. Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites. J Infect Dis 202: 801808.[Crossref]
  6. Ursing J, Kofoed PE, Rodrigues A, Blessborn D, Thoft-Nielsen R, Bjorkman A, Rombo L, , 2011. Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: a randomized trial. J Infect Dis 203: 109116.[Crossref]
  7. Espie E, Lima A, Atua B, Dhorda M, Flevaud L, Sompwe EM, Palma Urrutia PP, Guerin PJ, , 2012. Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial. Malar J 11: 174.[Crossref]
  8. Alifrangis M, Dalgaard MB, Lusingu JP, Vestergaard LS, Staalsoe T, Jensen AT, Enevold A, Ronn AM, Khalil IF, Warhurst DC, Lemnge MM, Theander TG, Bygbjerg IC, , 2006. Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania. J Infect Dis 193: 17381741.[Crossref]
  9. Gama BE, Pereira-Carvalho GA, Lutucuta Kosi FJ, Almeida de Oliveira NK, Fortes F, Rosenthal PJ, Daniel-Ribeiro CT, de Fatima Ferreira-da-Cruz M, , 2010. Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene. Malar J 9: 174.[Crossref]
  10. Beshir K, Sutherland CJ, Merinopoulos I, Durrani N, Leslie T, Rowland M, Hallett RL, , 2010. Amodiaquine resistance in Plasmodium falciparum malaria in Afghanistan is associated with the pfcrt SVMNT allele at codons 72 to 76. Antimicrob Agents Chemother 54: 37143716.[Crossref]
  11. Sa JM, Twu O, , 2010. Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type. Malar J 9: 374.[Crossref]
  12. Severini C, Menegon M, Sannella AR, Paglia MG, Narciso P, Matteelli A, Gulletta M, Caramello P, Canta F, Xayavong MV, Moura IN, Pieniazek NJ, Taramelli D, Majori G, , 2006. Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa. Infect Genet Evol 6: 262268.[Crossref]
  13. Taylor SM, Messina JP, Hand CC, Juliano JJ, Muwonga J, Tshefu AK, Atua B, Emch M, Meshnick SR, , 2011. Molecular malaria epidemiology: mapping and burden estimates for the Democratic Republic of the Congo, 2007. PLoS One 6: e16420.[Crossref]
  14. Juliano JJ, Kwiek JJ, Cappell K, Mwapasa V, Meshnick SR, , 2007. Minority-variant pfcrt K76T mutations and chloroquine resistance, Malawi. Emerg Infect Dis 13: 872877.[Crossref]
  15. Mobula L, Lilley B, Tshefu AK, Rosenthal PJ, , 2009. Resistance-mediating polymorphisms in Plasmodium falciparum infections in Kinshasa, Democratic Republic of the Congo. Am J Trop Med Hyg 80: 555558.
  16. Koukouikila-Koussounda F, Malonga V, Mayengue PI, Ndounga M, Vouvoungui CJ, Ntoumi F, , 2012. Genetic polymorphism of merozoite surface protein 2 and prevalence of K76T pfcrt mutation in Plasmodium falciparum field isolates from Congolese children with asymptomatic infections. Malar J 11: 105.[Crossref]
  17. Tsumori Y, Ndounga M, Sunahara T, Hayashida N, Inoue M, Nakazawa S, Casimiro P, Isozumi R, Uemura H, Tanabe K, Kaneko O, Culleton R, , 2011. Plasmodium falciparum: differential selection of drug resistance alleles in contiguous urban and peri-urban areas of Brazzaville, Republic of Congo. PLoS One 6: e23430.[Crossref]
  18. Laufer MK, Thesing PC, Dzinjalamala FK, Nyirenda OM, Masonga R, Laurens MB, Stokes-Riner A, Taylor TE, Plowe CV, , 2012. A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria. PLoS One 7: e42284.[Crossref]
  19. Frosch AE, Venkatesan M, Laufer MK, , 2011. Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data. Malar J 10: 116.[Crossref]
  20. Ecker A, Lakshmanan V, Sinnis P, Coppens I, Fidock DA, , 2011. Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes. J Infect Dis 203: 228236.[Crossref]
  21. Atemnkeng MA, Chimanuka B, Plaizier-Vercammen J, , 2007. Quality evaluation of chloroquine, quinine, sulfadoxine-pyrimethamine and proguanil formulations sold on the market in East Congo DR. J Clin Pharm Ther 32: 123132.[Crossref]
  22. Kazadi WM, Vong S, Makina BN, Mantshumba JC, Kabuya W, Kebela BI, Ngimbi NP, , 2003. Assessing the efficacy of chloroquine and sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in the Democratic Republic of Congo. Trop Med Int Health 8: 868875.[Crossref]
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  • Received : 25 Jun 2013
  • Accepted : 30 Nov 2013

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