Abstract
The identified mutations in the pfcrt, dhfr and dhps genes of Plasmodium falciparum show a very high correlation with resistance to chloroquine, pyrimethamine and sulfadoxine, the drugs that are still used as malaria chemoprophylaxis or treatment. We undertook a molecular screening of 82 Polish P. falciparum isolates, mainly imported from different countries of sub-Saharan Africa to assess their molecular drug-resistance profiles. Only 4 isolates showed no mutations in the three analyzed gene fragments. In the remaining isolates from one to six mutations in one or more examined genes were found. Different mutations in the pfcrt, dhfr and dhps genes were found in ca. 76%, 80% and 70% of P. falciparum isolates, respectively. About forty our patients used chloroquine or pyrimethamine + sulfadoxine as malaria chemoprophylaxis and/or antimalarial treatment, but without success. In all but 5 of the P. falciparum isolates obtained from these persons, mutations associated to resistance of the parasite to chloroquine and the antifolate drugs were found.
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Dorsey G., Kamya M.R., Singh A., Rosenthal P.J. 2001. Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda. Journal of Infectious Diseases, 183, 1417–1420. DOI: 0022-1899/2001/18309-0017S02.00.
Durand R., Jafari S., Bouchaud O., Ralaimazava., Keundjian A., Le Bras J. 2001. Plasmodium falciparum: pfcrt and dhfr mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers. Journal of Infectious Diseases, 184, 1633–1634. DOI: 0022-1899/2001/18412-00XX$02.00.
Dzbeński T.H., Kacprzak E., Kierznikowicz B., Knap J.P., Myjak P., Nahorski W.L., Pawłowski Z.S., Stefaniak J. 2004. (Eds. Z.S. Pawłowski and J.P. Knap) Profilaktyka, diagnostyka i leczenie malarii. Alpha-Medica Press, Warszawa.
Fidock D.A., Nomura T., Talley A.T., Cooper R.A., Dzekunov S.M., Ferdig M.T., Ursos L.M.B., Sidhu A.S., Naudé B., Deitsch H.W., Su X., Wootton J.C., Roepe P.D., Wellems T.E. 2000. Mutations in the Plasmodium falciparum digestive vacuole transmembrane protein pfcrt and evidence for their role in chloroquine resistance. Molecular Cell, 6, 861–871. DOI: 10.1016/S1097-2765(05)00077-8.
Gyang F.N., Peterson D.S., Wellems T.E. 1992. Plasmodium falciparum: Rapid detection of dihydrofolate reductase mutations that confer resistance to cycloguanil and pyrimethamine. Experimental Parasitology, 74, 470–472.
Jelinek T., Kilian A.H.D., Kabagambe G., von Sonnenburg F. 1999. Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in Uganda: correlation with polymorphism in the dihydrofolate reductase and dihydropteorate synthetase genes. American Journal of Tropical Medicine and Hygiene, 61, 463–466.
Jelinek T., Peyerl-Hoffmann G., Mühlberger N., Wichmann O., Wilhelm M., Schmider N., Grobusch M.P., von Sonneburg F., Gascon J., Laferl H., Hatz C., Alifrangis M., Burchard G., McWhinney P., Schulze M., Kollaritsch H., da Cunba S., Beřan J., Kern P., Gjørup I., Cuadros J. 2002. Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe. Malaria Journal, 1, 11. DOI: 10.1186/1475-2875-1-11.
Johnston S.P., Pieniazek N.J., Xayavong M.V., Slemenda S.B., Wilkins P.P., da Silva A.I. 2006. PCR as confirmatory technique for laboratory diagnosis of malaria. Journal of Clinical Microbiology, 44, 1087–1089. DOI: 10.1128/JCM.44.3.1087-1089.2006.
Mayor A.G., Gómez-Olivé X., Aponte J.J., Casimiro S., Mabunda S., Dgedge M., Barreto A., Alonso P.L. 2001. Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene and its relation to chloroquine resistance in Mozambique. Journal of Infectious Diseases, 183, 1413–1416. DOI: 0022-1899/2001/18309-.0016$02.00.
Myjak P., Nahorski W., Pieniazek N.J., Pietkiewicz H. 2002. Usefulness of PCR for diagnosis of imported malaria in Poland. European Journal of Clinical Microbiology and Infectious Diseases, 21, 215–218. DOI: 10.1007/S10096-001-0690-0.
Plowe C.V., Djimde A., Bouare M., Doumbo O., 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.
Severini C., Menegon M., Sannella A.R., Paglia M.G., Narciso P., Matteelli A., Gulletta M., Caramello P., Canta F., Xayavong M.V., Moura I.N.S., Pieniazek N.J., Taramelli D., Majori G. 2006. Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa. Infection, Genetics and Evolution, 6, 262–268. DOI: 10.1016/j.meegid.2005.07.002.
Wongsrichanalai C., Pickard A.L., Wernsdorfer W.H., Meshnick S.R. 2002. Epidemiology of drug-resistant malaria. Lancet Infectious Disease, 2, 209–218. DOI: 10.1016/S1473-3099(02)00239-6.
WHO 1999. Malaria, 1982–1997. Weekly Epidemiological Records, 743, 265–272.
Zindrou S., Dao L.D., Xuyen P.T., Dung N.P., Sy N.D., Skold O., Swedberg G. 1996. Rapid detection of pyrimethamine susceptibility of Plasmodium falciparum by restriction endonuclease digestion of the dihydrofolate reductase gene. American Journal of Tropical Medicine and Hygiene, 54, 185–188.
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An erratum to this article is available at http://dx.doi.org/10.2478/s11686-007-0059-3.
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Myjak, P., Nahorski, W., Szostakowska, B. et al. Detection of molecular markers for chloroquine and pyrimethamine/sulfadoxine resistance in imported cases of Plasmodium falciparum malaria in Poland. Acta Parasit. 52, 286–291 (2007). https://doi.org/10.2478/s11686-007-0031-2
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DOI: https://doi.org/10.2478/s11686-007-0031-2