Volume 95, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Chloroquine (CQ) remains the first-line treatment of malaria in Haiti. Given the challenges of conducting in vivo drug efficacy trials in low-endemic settings like Haiti, molecular surveillance for drug resistance markers is a reasonable approach for detecting resistant parasites. In this study, 349 blood spots were collected from suspected malaria cases in areas in and around Port-au-Prince from March to July 2010. Among them, 121 samples that were positive by polymerase chain reaction were genotyped for drug-resistant , , , and alleles. Among the 108 samples that were successfully sequenced for CQ resistant markers in , 107 were wild type (CVMNK), whereas one sample carried a CQ-resistant allele (CVIET). Neutral microsatellite genotyping revealed that the CQ-resistant isolate was distinct from all other samples in this study. Furthermore, the remaining parasite specimens appeared to be genetically distinct from other reported Central and South American populations.


Article metrics loading...

Loading full text...

Full text loading...



  1. Lindo JF, Bryce JH, Ducasse MB, Howitt C, Barrett DM, Morales JL, Ord R, Burke M, Chiodini PL, Sutherland CJ, , 2007. Plasmodium malariae in Haitian refugees, Jamaica. Emerg Infect Dis 13: 931933.[Crossref]
  2. Pan American Health Organization (PAHO), 2013. Situation of Malaria in the Region of the Americas, 2000–2012. Available at: http://www2.paho.org/HQ/index.php?option=com_content&view=article&id=9663:report-on-the-situation-of-malaria-in-the-americas-2012&catid=1617:malaria-statistics-maps&Itemid=2049&lang=fr. Accessed March 11, 2016.
  3. Sridaran S, Rodriguez B, Soto AM, De Oliveira AM, Udhayakumar V, , 2014. Molecular analysis of chloroquine and sulfadoxine-pyrimethamine resistance-associated alleles in Plasmodium falciparum isolates from Nicaragua. Am J Trop Med Hyg 90: 840845.[Crossref]
  4. Mejia Torres RE, Banegas EI, Mendoza M, Diaz C, Bucheli STM, Fontecha GA, Alam MT, Goldman I, Udhayakumar V, Zambrano JON, , 2013. Efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in Honduras. Am J Trop Med Hyg 88: 850854.[Crossref]
  5. Duverseau YT, Magloire R, Zevallos-Ipenza A, Rogers HM, Nguyen-Dinh P, , 1986. Monitoring of chloroquine sensitivity of Plasmodium falciparum in Haiti, 1981–1983. Am J Trop Med Hyg 35: 459464.
  6. Londono BL, Eisele TP, Keating J, Bennett A, Chattopadhyay C, Heyliger G, Mack B, Rawson I, Vely JF, Désinor O, Krogstad DJ, , 2009. Chloroquine-resistant haplotype Plasmodium falciparum parasites, Haiti. Emerg Infect Dis 15: 735740.[Crossref]
  7. Gharbi M, Pillai DR, Lau R, Hubert V, Khairnar K, Existe A, Kendjo E, Dahlström S, Guérin PJ, Le Bras J, , 2012. Chloroquine-resistant malaria in travelers returning from Haiti after 2010 earthquake. Emerg Infect Dis 18: 13461349.[Crossref]
  8. Neuberger A, Zhong K, Kain KC, Schwartz E, , 2012. Lack of evidence for chloroquine-resistant Plasmodium falciparum malaria, Leogane, Haiti. Emerg Infect Dis 18: 14871489.[Crossref]
  9. Elbadry MA, Existe A, Victor YS, Memnon G, Fukuda M, Dame JB, Yowell CA, Okech BA, , 2013. Survey of Plasmodium falciparum multidrug resistance-1 and chloroquine resistance transporter alleles in Haiti. Malar J 12: 426.[Crossref]
  10. Okech BA, Existe A, Romain JR, Memnon G, Saint Victor Y, Beau De Rochars MB, Fukuda M, , 2015. Therapeutic efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum in Haiti after many decades of its use. Am J Trop Med Hyg 92: 541545.[Crossref]
  11. Townes D, Existe A, Boncy J, Magloire R, Vely JF, Amsalu R, De Tavernier M, Muigai J, Hoibak S, Albert M, McMorrow M, Slutsker L, Kachur SP, Chang M, , 2012. Malaria survey in post-earthquake Haiti: 2010. Am J Trop Med Hyg 86: 2931.[Crossref]
  12. Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, , 1993. High sensitivity of detection of human malaria parasties by the use of nested polymerase chain reaction. Mol Biochem Parasitol 61: 315320.[Crossref]
  13. Anderson TJ, Haubold B, Williams JT, Estrada-Franco JG, Richardson L, Mollinedo R, Bockarie M, Mokili J, Mharakurwa S, French N, Whitworth J, Velez ID, Brockman AH, Nosten F, Ferreira MU, Day KP, , 2000. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum . Mol Biol Evol 17: 14671482.[Crossref]
  14. Anderson TJ, Su XZ, Bockarie M, Lagog M, Day KP, , 1999. Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology 119: 113125.[Crossref]
  15. McCollum AM, Mueller K, Villegas L, Udhayakumar V, Escalante AA, , 2007. Common origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother 51: 20852091.[Crossref]
  16. Dieringer D, Schlötterer C, , 2003. Microsatellite analyzer (MSA): a platform independent analysis tool for large microsatellite data sets. Mol Ecol Notes 3: 167169.[Crossref]
  17. Tateno Y, Nei M, Tajima F, , 1982. Accuracy of estimated phylogenetic trees from molecular data. I. Distantly related species. J Mol Evol 18: 387404.[Crossref]
  18. Felsenstein J, , 2005. PHYLIP (Phylogeny Inference Package) version 3.6. Available at: http://evolution.genetics.washington.edu/phylip/getme.html. Accessed March 11, 2016.
  19. Falush D, Stephens M, Pritchard JK, , 2003. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164: 15671587.
  20. Pritchard JK, Stephens M, Donnelly P, , 2000. Inference of population structure using multilocus genotype data. Genetics 155: 945959.
  21. Evanno G, Regnaut S, Goudet J, , 2005. Detecting the number of clusters of individuals using the software. Mol Ecol 14: 26112620.[Crossref]
  22. Larrañaga N, Mejía RE, Hormaza JI, Montoya A, Soto A, Fontecha GA, , 2013. Genetic structure of Plasmodium falciparum populations across the Honduras-Nicaragua border. Malar J 12: 354.[Crossref]
  23. Griffing S, Syphard L, Sridaran S, McCollum AM, Mixson-Hayden T, Vinayak S, Villegas L, Barnwell JW, Escalante AA, Udhayakumar V, , 2010. pfmdr1 amplification and fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum in Venezuela. Antimicrob Agents Chemother 54: 15721579.[Crossref]
  24. Griffing SM, Viana GMR, Mixson-Hayden T, Sridaran S, Alam MT, de Oliveira AM, Barnwell JW, Escalante AA, Povoa MM, Udhayakumar V, , 2013. Historical shifts in Brazilian P. falciparum population structure and drug resistance alleles. PLoS One 8: e58984.[Crossref]
  25. Excoffier L, Laval G, Schneider S, , 2005. Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online 1: 4750.
  26. Charles M, Das S, Daniels R, Kirkman L, Delva GG, Destine R, Escalante A, Villegas L, Daniels NM, Shigyo K, Volkman SK, Pape JW, Golightly LM, , 2016. Plasmodium falciparum K76T pfcrt gene mutations and parasite population structure, Haiti, 2006–2009. Emerg Infect Dis 22: 786793.[Crossref]
  27. Maïga-Ascofaré O, Le Bras J, Mazmouz R, Renard E, Falcão S, Broussier E, Bustos D, Randrianarivelojosia M, Omar SA, Aubouy A, Lepère J-F, Jean-François V, Djimdé AA, Clain J, , 2010. Adaptive differentiation of Plasmodium falciparum populations inferred from single-nucleotide polymorphisms (SNPs) conferring drug resistance and from neutral SNPs. J Infect Dis 202: 10951103.[Crossref]
  28. Carter TE, Warner M, Mulligan CJ, Existe A, Victor YS, Memnon G, Boncy J, Oscar R, Fukuda MM, Okech BA, , 2012. Evaluation of dihydrofolate reductase and dihydropteroate synthetase genotypes that confer resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum in Haiti. Malar J 11: 275.[Crossref]
  29. Plowe CV, Kublin JG, Doumbo OK, , 1998. P. falciparum dihydrofolate reductase and dihydropteroate synthase mutations: epidemiology and role in clinical resistance to antifolates. Drug Resist Updat 1: 389396.[Crossref]
  30. Cortese JF, Plowe CV, , 1998. Antifolate resistance due to new and known Plasmodium falciparum dihydrofolate reductase mutations expressed in yeast. Mol Biochem Parasitol 94: 205214.[Crossref]
  31. Peterson DS, Walliker D, Wellems TE, , 1988. Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA 85: 91149118.[Crossref]
  32. Rallón NI, Osorio LE, Giraldo LE, , 1999. Lack of an association between the ASN-108 mutation in the dihydrofolate reductase gene and in vivo resistance to sulfadoxine/pyrimethamine in Plasmodium falciparum . Am J Trop Med Hyg 61: 245248.
  33. Londono-Renteria B, Eisele TP, Keating J, Bennett A, Krogstad DJ, , 2012. Genetic diversity in the merozoite surface protein 1 and 2 genes of Plasmodium falciparum from the Artibonite Valley of Haiti. Acta Trop 121: 612.[Crossref]
  34. Jovel IT, Mejía RE, Banegas E, Piedade R, Alger J, Fontecha G, Ferreira PE, Veiga MI, Enamorado IG, Bjorkman A, Ursing J, , 2011. Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America. Malar J 10: 376.[Crossref]

Data & Media loading...

Supplementary Data

Supplementary PDF

  • Received : 16 Mar 2016
  • Accepted : 01 Jun 2016

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