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Studies on antimalarial drug susceptibility in Colombia, in relation to Pfmdr1 and Pfcrt

Published online by Cambridge University Press:  21 April 2008

E. RESTREPO-PINEDA ,
E. ARANGO ,
A. MAESTRE ,
V. E. DO ROSÁRIO  and
P. CRAVO
E. RESTREPO-PINEDA
Affiliation:
Grupo Malaria, Universidad de Antioquia, Sede de Investigación Universitaria, Calle 62 # 52-59, Medellín, Colombia
E. ARANGO
Affiliation:
Grupo Malaria, Universidad de Antioquia, Sede de Investigación Universitaria, Calle 62 # 52-59, Medellín, Colombia
A. MAESTRE
Affiliation:
Grupo Malaria, Universidad de Antioquia, Sede de Investigación Universitaria, Calle 62 # 52-59, Medellín, Colombia
V. E. DO ROSÁRIO
Affiliation:
Centro de Malária e Outras Doenças Tropicais/IHMT/UEI Biologia Molecular/UEI Malária, Lisbon, Portugal, Rua da Junqueira 96, Código postal: 1349-008
P. CRAVO
Affiliation:
Centro de Malária e Outras Doenças Tropicais/IHMT/UEI Biologia Molecular/UEI Malária, Lisbon, Portugal, Rua da Junqueira 96, Código postal: 1349-008
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Summary

In Colombia, Plasmodium resistance to antimalarials such as chloroquine and antifolates is a serious problem. As a result, the national Colombian health authorities are monitoring the efficacy of alternative drugs and schemes. The study of genetic polymorphisms related with drug resistance is required in the region. In vitro responses to chloroquine, quinine, mefloquine, amodiaquine, desethylamodiaquine, artesunate and dihydroartesunate were carried out by HRP ELISA. SNP analysis in Pfcrt and Pfmdr1 genes was performed by PCR-RFLP in 77 samples from the North West region of Colombia. In vitro resistance to chloroquine was high (74%), followed by mefloquine (30%) and desethylamodiaquine (30%). A positive correlation between the IC50 of paired drugs was also detected. The allele Pfmdr1 N86 (wild) was present in 100% of the samples and 1246Y (mutant) in 92%. However, their presence did not correlate with in vitro drug resistance. Presence of the mutations K76T and N75E in Pfcrt was confirmed in all samples. Analysis of 4 codons (72, 74, 75 and 76) in pfcrt confirmed the presence of the haplotypes CMET in 91% and SMET in 9% of the samples.

Keywords

malariaPlasmodium falciparumpfcrtpfmdrColombia
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 5 , May 2008 , pp. 547 - 553
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

Afonso, A., Hunt, P., Cheesman, S. A., Alves, C., Cunha, C. V., Rosário, V. and Cravo, P. (2006). Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10. Antimicrobial Agents and Chemotherapy 50, 480–489.CrossRefGoogle ScholarPubMed
Babiker, H. A., Pringle, S. J., Abdel-Muhsin, A., Mackinnon, M., Hunt, P. and Walliker, D. (2001). High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1. Journal of Infectious Diseases 183, 1535–1538.CrossRefGoogle ScholarPubMed
Basco, L. K. and Ringwald, P. (2002). Molecular epidemiology of malaria in Cameroon. X. Evaluation of PFMDR1 mutations as genetic markers for resistance to amino alcohols and artemisinin derivatives. American Journal of Tropical Medicine and Hygiene 66, 667–671.CrossRefGoogle ScholarPubMed
Bjorkman, A. and Bhattarai, A. (2005). Public health impact of drug resistant Plasmodium falciparum malaria. Acta Tropica 94, 163–169.CrossRefGoogle ScholarPubMed
Blair, S., Carmona-Fonseca, J., Piñeros, J. G., Ríos, A., Alvarez, T., Alvarez, G. and Tobón, A. (2006). Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malaria Journal 5, 14.CrossRefGoogle ScholarPubMed
Blair, S., Lopez, M. L., Piñeros, J. G., Alvarez, T., Tobon, A. and Carmona, J. (2003). Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium falciparum malaria, Antioquia, Colombia, 2002. Biomedica 23, 318–327.CrossRefGoogle ScholarPubMed
Cortese, J. F., Caraballo, A., Contreras, C. E. and Plowe, C. (2002). Origin and dissemination of Plasmodium falciparum drug-resistance mutations in South America. Journal of Infectious Diseases 186, 999–1006.CrossRefGoogle ScholarPubMed
Djimde, A., Doumbo, O. K., Cortese, J. F., Kayentao, K., Doumbo, S., Diourte, Y., Dicko, A., Su, X. Z., Nomura, T., Fidock, D. A., Wellems, T. E., Plowe, C. V. and Coulibaly, D. (2001 a). A molecular marker for chloroquine-resistant falciparum malaria. New England Journal of Medicine 344, 257–263.CrossRefGoogle ScholarPubMed
Djimde, A., Doumbo, O. K., Steketee, R. W. and Plowe, C. V. (2001 b). Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 358, 890–891.CrossRefGoogle ScholarPubMed
Duraisingh, M. T., Jones, P., Sambou, I., Von Seidlein, L., Pinder, M. and Warhurst, D. C. (2000). The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Molecular and Biochemical Parasitology 108, 13–23.CrossRefGoogle Scholar
Duraisingh, M. and Refour, P. (2005). Multiple drug resistance genes in malaria–from epistasis to epidemiology. Molecular Microbiology, 57, 874–877.CrossRefGoogle Scholar
Ferreira, I. D., Lopes, D., Martinelli, A., Ferreira, C., do Rosário, V. E. and Cravo, P. (2007). In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from Sao Tome and Principe. Tropical Medicine and International Health 12, 353–362.CrossRefGoogle ScholarPubMed
Fidock, D. A., Nomura, T., Talley, A. K., Cooper, R. A., Dzekunov, S. M., Ferdig, M. T., Ursos, L. M. B., Singh Sidhu, A. B., Naude, B., Deitsch, K. W., Su, X. Z., Wootton, J. C., Roepe, P. D. and Wellems, T. E. (2000). Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Molecular Cell 6, 861–871.CrossRefGoogle Scholar
Foote, S. J., Kyle, D. E., Martin, R. K., Oduola, A. M., Forsyth, K., Kemp, D. J. and Cowman, A. F. (1990). Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature, London 345, 255–258.CrossRefGoogle ScholarPubMed
Howard, E. M., Zhang, H. and Roepe, P. D. (2002). A novel transporter, Pfcrt, confers antimalarial drug resistance. Journal of Membrane Biology 190, 1–8.CrossRefGoogle ScholarPubMed
Lopes, D., Nogueira, F., Ferreira, C., Gil, J. P., do Rosário, V. E. and Cravo, P. (2002). pfcrt and pfmdr1 mutations and chloroquine resistance in Plasmodium falciparum from Sao Tome and Principe, West Africa. Annals of Tropical Medicine and Parasitology 96, 831–834.CrossRefGoogle ScholarPubMed
Menard, D., Djalle, D., Manirakiza, A., Yapou, F., Siadoua, V., Sana, S., Matsika-Claquin, M. D., Nestor, M. and Talarmin, A. (2005). Drug-resistant malaria in Bangui, Central African Republic: an in vitro assessment. American Journal of Tropical Medicine and Hygiene 73, 239–243.CrossRefGoogle ScholarPubMed
Mita, T., Kaneko, A., Lum, J. K., Bwijo, B., Takechi, M., Zungu, I. L., Tsukahara, T., Tanabe, K., Kobayakawa, T. and 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. American Journal of Tropical Medicine and Hygiene 68, 413–415.CrossRefGoogle ScholarPubMed
Montoya, P., Tobón, A., Blair, S., Carmona, J. and Maestre, A. (2007). Polimorfismos del gen pfmdr1 en muestras clínicas de Plasmodium falciparum y su relación con la respuesta terapéutica a antipalúdicos y paludismo grave en Colombia. Biomedica 27, 204–215.CrossRefGoogle Scholar
Moore, D.V and Lanier, J. E. (1961). Observations on two Plasmodium falciparum infections with an abnormal response to chloroquine. American Journal of Tropical Medicine and Hygiene 10, 5–9.CrossRefGoogle ScholarPubMed
Noedl, H., Attlmayr, B., Wernsdorfer, W. H., Kollaritsch, H. and Miller, R. S. (2004). A histidine-rich protein 2-based malaria drug sensitivity assay for field use. American Journal of Tropical Medicine and Hygiene 71, 711–714.CrossRefGoogle ScholarPubMed
Noedl, H., Bronnert, J., Yingyuen, K., Attlmayr, B., Kollaritsch, H. and Fukuda, M. (2005). Simple histidine-rich protein 2 double-site sandwich enzyme-linked immunosorbent assay for use in malaria drug sensitivity testing. Antimicrobial Agents and Chemotherapy 49, 3575–3577.CrossRefGoogle ScholarPubMed
Noedl, H., Wernsdorfer, WH., Miller, R. S. and Wongsrichanalai, C. (2002). Histidine-rich protein II: a novel approach to malaria drug sensitivity testing. Antimicrobial Agents and Chemotherapy 46, 1658–1664.CrossRefGoogle Scholar
Nsimba, B., Jafari-Guemouri, S., Malonga, D. A., Mouata, A. M., Kiori, J., Louya, F., Yocka, D., Malanda, M., Durand, R. and Le Bras, J. (2005). Epidemiology of drug-resistant malaria in Republic of Congo: using molecular evidence for monitoring antimalarial drug resistance combined with assessment of antimalarial drug use. Tropical Medicine and International Health 10, 1030–1037.CrossRefGoogle ScholarPubMed
Plowe, C. V., Djimde, A., Bouare, M., Doumbo, O. and Wellems, T. E. (1995). Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. American Journal of Tropical Medicine and Hygiene 52, 565–568.CrossRefGoogle ScholarPubMed
Pradines, B., Mabika Mamfoumbi, M., Parzy, D., Owono Medang, M., Lebeau, C., Mourou Mbina, J. R., Doury, J. C. and Kombila, M. (1998). In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine. Parasitology 117, 541–545.CrossRefGoogle ScholarPubMed
Price, N. R., Uhlemann, A. C., Brockman, A., McGready, R., Ashley, E., Phaipun, L., Patel, R., Laing, K., Looareesuwan, S., White, N. J., Nosten, F. and Krishna, S. (2004). Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364, 438–447.CrossRefGoogle ScholarPubMed
Reed, M. B., Saliba, K. J., Caruana, S. R., Kirk, K. and Cowman, A. F. (2000). Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature, London 403, 906–909.CrossRefGoogle ScholarPubMed
Rodriguez, D. C. (1961). Cases of malaria caused by Plasmodium falciparum resistant to treatment with chloroquine. Arquivos da Higiene e Saude Publica 26, 231–235.Google Scholar
Sanchez, C. P., McLean, J. E., Rohrbach, P., Fidock, D. A., Stein, W. D. and Lanzer, M. (2005). Evidence for a pfcrt-associated chloroquine efflux system in the human malarial parasite Plasmodium falciparum. Biochemistry 44, 9862–9870.CrossRefGoogle ScholarPubMed
Sidhu, A. B., Uhlemann, A. B., Valderramos, S. G., Valderramos, J. C., Krishna, S. and Fidock, D. A. (2006). Decreasing pfmdr1 copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. Journal of Infectious Diseases 194, 528–535.CrossRefGoogle ScholarPubMed
Tinto, H., Rwagacondo, C., Karema, C., Mupfasoni, D., Vandoren, W., Rusanganwa, E., Erhart, A., Van Overmeir, C., Van Marck, E. and D'Alessandro, U. (2006). In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda. Transactions of the Royal Society of Tropical Medicine and Hygiene 100, 509–514.CrossRefGoogle Scholar
Vinayak, S., Biswas, S., Dev, V., Kumar, A., Ansari, M. A. and Sharma, Y. D. (2003). Prevalence of the K76T mutation in the pfcrt gene of Plasmodium falciparum among chloroquine responders in India. Acta Tropica 87, 287–293.CrossRefGoogle ScholarPubMed
Walliker, D. (2005). The hitchhiker's guide to malaria parasite genes. Trends in Parasitology 21, 489–493.CrossRefGoogle ScholarPubMed
Warhurst, D. C. (2003). Polymorphism in the Plasmodium falciparum chloroquine resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. Malaria Journal 19, 31.CrossRefGoogle Scholar
Wellems, T. E., Panton, L. J., Gluzman, I. Y., Rosário, V. E., Gwadz, R. W., Walker-Jonah, A. and Krogstad, D. J. (1990). Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature, London 345, 253–255.CrossRefGoogle ScholarPubMed
Wellems, T. E. and Plowe, C. V. (2001). Chloroquine-resistant malaria. Journal of Infectious Diseases 184, 770–776.CrossRefGoogle ScholarPubMed
Wernsdorfer, W. H. and Noedl, H. (2003). Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology. Current Opinion in Infectious Diseases 16, 553–558.CrossRefGoogle Scholar
Wootton, J. C., Feng, X., Ferdig, M. T., Cooper, R. A., Mu, J., Baruch, D. I., Magill, A. J. and Su, X. Z. (2002). Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature, London 418, 320–323.CrossRefGoogle ScholarPubMed
Zalis, M. G., Pang, L., Silveira, M. S., Milhous, W. K. and Wirth, D. F. (1998). Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance. American Journal of Tropical Medicine and Hygiene 58, 630–637.CrossRefGoogle ScholarPubMed