- Introduction
- Materials and Methods
- Results
- Sample collection.
- Frequency and prevalence of codon 72–76 haplotypes of the Pfcrt gene in study sites of Mozambique in 2009–2010.
- Prevalence and frequency of SNPs at codons 86, 184, and 1246 of the Pfmdr-1 gene.
- Frequency of constructed haplotypes at codon 86, 184, and 1246 of the Pfmdr-1 gene.
- Frequency of combined Pfcrt-Pfmdr-1 haplotypes.
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2011. World Malaria Report. Available at: http://www.who.int/malaria/world_malaria_report_2011/9789241564403_eng.pdf. Accessed November 18, 2012.
-
2.
World Health Organization, 2010. World Malaria Report. Available at: http://whqlibdoc.who.int/publications/2010/9789241564106_eng.pdf. Accessed November 17, 2012.
-
3.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619–2620.
-
4.
Noedl H, Se Y, Sriwichai S, Schaecher K, Teja-Isavadharm P, Smith B, Rutvisuttinunt W, Bethell D, Surasri S, Fukuda MM, Socheat D, Chan TL, 2010. Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in southeast Asia. Clin Infect Dis 51: e82–e89.
-
5.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ, 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.
-
6.
Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NP, White NJ, Anderson TJ, Nosten F, 2012. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 379: 1960–1966.
-
7.
Roper C, Pearce R, Nair S, Sharp B, Nosten F, Anderson T, 2004. Intercontinental spread of pyrimethamine-resistant malaria. Science 305: 1124.
-
8.
Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B, 2003. Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet 361: 1174–1181.
-
9.
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.
-
10.
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.
-
11.
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.
-
12.
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257–263.
-
13.
Warhurst DC, 2003. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. Malar J 2: 31.
-
14.
Ariey F, Fandeur T, Durand R, Randrianarivelojosia M, Jambou R, Legrand E, Ekala MT, Bouchier C, Cojean S, Duchemin JB, Robert V, Le Bras J, Mercereau-Puijalon O, 2006. Invasion of Africa by a single pfcrt allele of south east Asian type. Malar J 5: 34.
-
15.
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.
-
16.
Alifrangis M, Lusingu JP, Mmbando B, Dalgaard MB, Vestergaard LS, Ishengoma D, Khalil IF, Theander TG, Lemnge MM, Bygbjerg IC, 2009. Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the P. falciparum dihydropteroate synthase gene. Am J Trop Med Hyg 80: 523–527.
-
17.
Mang’era CM, Mbai F, Omedo IA, Mireji PO, Omar SA, 2012. Changes in genotypes of Plasmodium falciparum human malaria parasite following withdrawal of chloroquine in Tiwi, Kenya. Acta Trop 123: 202–207.
-
18.
Ndiaye M, Faye B, Tine R, Ndiaye JL, Lo A, Abiola A, Dieng Y, Ndiaye D, Hallett R, Alifrangis M, Gaye O, 2012. Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal. Am J Trop Med Hyg 87: 640–645.
-
19.
Raman J, Mauff K, Muianga P, Mussa A, Maharaj R, Barnes KI, 2011. Five years of antimalarial resistance marker surveillance in Gaza Province, Mozambique, following artemisinin-based combination therapy roll out. PLoS ONE 6: e25992.
-
20.
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.
-
21.
Lekana-Douki JB, Dinzouna Boutamba SD, Zatra R, Zang Edou SE, Ekomy H, Bisvigou U, Toure-Ndouo FS, 2011. Increased prevalence of the Plasmodium falciparum Pfmdr1 86N genotype among field isolates from Franceville, Gabon after replacement of chloroquine by artemether-lumefantrine and artesunate-mefloquine. Infect Genet Evol 11: 512–517.
-
22.
Zeile I, Gahutu JB, Shyirambere C, Steininger C, Musemakweri A, Sebahungu F, Karema C, Harms G, Eggelte TA, Mockenhaupt FP, 2012. Molecular markers of Plasmodium falciparum drug resistance in southern highland Rwanda. Acta Trop 121: 50–54.
-
23.
Thomsen TT, Ishengoma DS, Mmbando BP, Lusingu JP, Vestergaard LS, Theander TG, Lemnge MM, Bygbjerg IC, Alifrangis M, 2011. Prevalence of single nucleotide polymorphisms in the Plasmodium falciparum multidrug resistance gene (Pfmdr-1) in Korogwe District in Tanzania before and after introduction of artemisinin-based combination therapy. Am J Trop Med Hyg 85: 979–983.
-
24.
Enosse S, Magnussen P, Abacassamo F, Gomez-Olive X, Ronn AM, Thompson R, Alifrangis M, 2008. Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique. Malar J 7: 115.
-
25.
Schwalbach J, Schapira A, Suleimanov G, 1985. Chloroquine-resistant malaria in Mozambique. Lancet 2: 897–898.
-
26.
Abacassamo F, Enosse S, Aponte JJ, Gomez-Olive FX, Quinto L, Mabunda S, Barreto A, Magnussen P, Ronn AM, Thompson R, Alonso PL, 2004. Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria. Trop Med Int Health 9: 200–208.
-
27.
Mayor AG, Gomez-Olive X, Aponte JJ, Casimiro S, Mabunda S, Dgedge M, Barreto A, Alonso PL, 2001. Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene and its relation to chloroquine resistance in Mozambique. J Infect Dis 183: 1413–1416.
-
28.
Kampango A, Cuamba N, Charlwood JD, 2011. Does moonlight influence the biting behaviour of Anopheles funestus? Med Vet Entomol 25: 240–246.
-
29.
Charlwood JD, 2011. Studies on the bionomics of male Anopheles gambiae Giles and male Anopheles funestus Giles from southern Mozambique. J Vector Ecol 36: 382–394.
-
30.
Charlwood JD, Thompson R, Madsen H, 2003. Observations on the swarming and mating behaviour of Anopheles funestus from southern Mozambique. Malar J 2: 2.
-
31.
Alifrangis M, Enosse S, Pearce R, Drakeley C, Roper C, Khalil IF, Nkya WM, Ronn AM, Theander TG, Bygbjerg IC, 2005. A simple high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum cloroquine resistance transporter genes using ploymerase chain reaction and enzyme linked immunosorbent assay-based technology. Am J Trop Med Hyg 72: 155–162.
-
32.
Duraisingh MT, Roper C, Walliker D, Warhurst DC, 2000. Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr1 gene of Plasmodium falciparum. Mol Microbiol 36: 955–961.
-
33.
Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJ, Mutabingwa TK, Sutherland CJ, Hallett RL, 2007. Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother 51: 991–997.
-
34.
Walliker D, Hunt P, Babiker H, 2005. Fitness of drug-resistant malaria parasites. Acta Trop 94: 251–259.
-
35.
Mwai L, Ochong E, Abdirahman A, Kiara SM, Ward S, Kokwaro G, Sasi P, Marsh K, Borrmann S, Mackinnon M, Nzila A, 2009. Chloroquine resistance before and after its withdrawal in Kenya. Malar J 8: 106.
-
36.
Kamugisha E, Bujila I, Lahdo M, Pello-Esso S, Minde M, Kongola G, Naiwumbwe H, Kiwuwa S, Kaddumukasa M, Kironde F, Swedberg G, 2012. Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine? Acta Trop 121: 148–151.
-
37.
Sisowath C, Petersen I, Veiga MI, Martensson A, Premji Z, Bjorkman A, Fidock DA, Gil JP, 2009. In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis 199: 750–757.
-
38.
Baliraine FN, Rosenthal PJ, 2011. Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda. J Infect Dis 204: 1120–1124.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 0 | 0 | 0 |
| Full Text Views | 335 | 126 | 0 |
| PDF Downloads | 80 | 30 | 0 |
Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique
Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.
Author Notes
Authors' addresses: Thomas T. Thomsen, Section for Functional Genomics, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark, E-mail: thomas.thomsen@bio.ku.dk. Laura B. Madsen, Helle H. Hansson, Ib C. Bygbjerg, and Michael Alifrangis, Centre for Medical Parasitology, Institute for International Health, Immunology and Microbiology, CSS, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark, E-mails: lmadsen@sund.ku.dk, hellehan@sund.ku.dk, iby@sund.ku.dk, and micali@sund.ku.dk. Elsa V. E. Tomás, Mozambican-Danish Rural Malaria Project, Morrumbene, Inhambane Province, Mozambique, E-mail: erzeliatomas@yahoo.com.br. Derek Charlwood, Centre for Health Research and Development, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark, and Instituto Nacional de Saudé, Avenida Eduardo Mondalane, Maputo, Mozambique, E-mail: jdcharlwood@gmail.com.