Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum from three endemic malaria regions in Colombia
Keywords:
Plasmodium falciparum, sulfadoxine, pyrimethamine, mutation, dihydrofolate reductase, dihydropteroate synthase, Colombia
Abstract
Introduction. Plasmodium falciparum has the ability to counter the antiparasitic activity of sulphadoxine-pyrimethamine by progressively accumulating mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. These mutations gradually increase the resistance of the parasite to these drugs and lead to therapeutic failure.Objectives. To determine the frequency of mutations associated with resistance to sulphadoxine and pyrimethamine in the dhfr and dhps genes of P. falciparum in samples from patients in three endemic zones of Colombia -La Carpa, Guaviare; Casuarito, Vichada; and Tierralta and Puerto Libertador, Córdoba.
Materials and methods. Forty samples were selected from patients with uncomplicated P. falciparum malaria. The frequency profiles of the 108, 59 and 164 alleles of dhfr were obtained by application of an allele-specific polymerase chain reaction, whereas the other alleles (alleles 51 of the dhfr gene and 436, 437 and 540 of dhps) were obtained by polymerase chain reaction and restriction fragment length polymorphism.
Results. The 108N and 51I mutations in the dhfr gene were found in all of the 40 samples. No mutant alleles were found in the 59 and 164 codons of the dhfr gene, or in the 436 codon of the dhps gene. The 437G mutation was observed in 36 samples and the wild-type allele was present in 3 from Tierralta and one from La Carpa. The 540E mutation was only detected in two samples from Casuarito.
Conclusions. The 108N, 51I and 437G mutations prevail in the populations of P. falciparum, indicating a cumulative effect of mutations and the need to continue surveillance for other changes which can lead to the total loss of the efficacy of sulphadoxine-pyrimethamine.
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References
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23. Contreras CE, Cortese JF, Caraballo A, Plowe CV. Genetics of drug-resistant Plasmodium falciparum malaria in the Venezuelan state of Bolívar. Am J Trop Med Hyg. 2002;67:400-5.
24. Mendez F, Muñoz A, Carrasquilla G, Jurado D, Arévalo-Herrera M, Cortese J, et al. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol. 2002;156:230-8.
25. Zhou Z, Griffing SM, de Oliveira AM, McCollum AM, Quezada WM, Arrospide N, et al. Decline in sulfadoxine-pyrimethamine-resistant alleles after change in drug policy in the Amazon region of Peru. Antimicrob Agents Chemother. 2008;52:739-41.
26. Peek R, van Gool T, Panchoe D, Greve S, Bus E, Resida L. Drug resistance and genetic diversity of Plasmodium falciparum parasites from Suriname. Am J Trop Med Hyg. 2005;73:833-8.
27. Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, et al. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000;95:721-8.
28. Talisuna A, Langi P, Mutabingwa T, Watkins W, Van Marck E, Egwang T, et al. Population-based validation of dihydrofolate reductase gene mutations for the prediction of sulfadoxine-pyrimethamine resistance in Uganda. Trans R Soc Trop Med Hyg. 2003;97:338-42.
29. Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, et al. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis. 2002;185:380-8.
30. Pérez MA, Cortés LJ, Guerra AP, Knudson A, Usta C, Nicholls RS. Eficacia de la combinación amodiaquina más sulfadoxina/pirimetamina y de la cloroquina para el tratamiento del paludismo en Córdoba, Colombia, 2006. Biomédica. 2008;28:148-59.
2. Wyler DJ. Malaria-resurgence, resistance, and research (first of two parts). N Engl J Med. 1983;308:875-8.
3. Hyde JE. Mechanisms of resistance of Plasmodium falciparum to antimalarial drugs. Microbes Infect. 2002;4:165-74.
4. Sibley CH, Hyde JE, Sims PF, Plowe CV, Kublin JG, Mberu EK, et al. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol. 2001;17:582-8.
5. Noeld H, Wongsrichanalai C, Wernsdorfer WH. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol. 2003;19:175-81.
6. Gatton ML, Martin LB, Cheng Q. Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004;48:2116-23.
7. Yuthavong Y. Basis for antifolate action and resistance in malaria. Microbes Infect. 2002;4:175-82.
8. Sharma YD. Genetic alteration in drug resistance markers of Plasmodium falciparum. Indian J Med Res. 2005;121:13-22.
9. Cortese JF, Caraballo A, Contreras CE, Plowe CV. Origin and dissemination of Plasmodium falciparum drug-resistance mutations in South America. J Infect Dis. 2002;186:999-1006.
10. Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, et al. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis. 1997;176:1590-6.
11. Guerra AP, Knudson A, Nicholls RS, Galindo JA, Ravid Z, Rahirant S, et al. Genotipificación de los genes msp1 (bloque 2) y dhfr (codón108) de Plasmodium falciparum en muestras de campo recolectadas en cuatro localidades endémicas de Colombia. Biomédica. 2006;26:101-12.
12. Schmider N, Peyerl-Hoffmann G, Restrepo M, Jelinek T. Short communication: point mutations in the dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Colombia. Trop Med Int Health. 2003;8:129-32.
13. Gómez D, Chaparro J, Rubiano C, Rojas MO, Wasserman M. Genetic diversity of Plasmodium falciparum field samples from an isolated Colombian village. Am J Trop Med Hyg. 2002;67:611-6.
14. Rallón NI, Osorio LE, Giraldo LE. 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. 1999;61:245-8.
15. Giraldo LE, Acosta MC, Labrada LA, Praba A, Montenegro-James S, Saravia NG, et al. Frequency of the Asn-108 and Thr-108 point mutations in the dihydrofolate reductase gene in Plasmodium falciparum from southwest Colombia. Am J Trop Med Hyg. 1998;59:124-8.
16. Blair S, Carmona-Fonseca J, Piñeros JG, Ríos A, Álvarez T, Álvarez G, et al. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malar J. 2006;5:14.
17. Osorio L, Pérez LP, González IJ. Evaluación de la eficacia de los medicamentos antimaláricos en Tarapacá, Amazonas colombiano. Biomédica. 2007;27:133-40.
18. Pearce RJ, Drakeley C, Chandramohan D, Mosha F. Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of Northern Tanzania. Antimicrob Agents Chemother. 2003;47:1347-54.
19. Chaparro J, Wasserman M. Comparación de técnicas in vitro para detectar resistencia de Plasmodium falciparum a medicamentos. Biomédica. 1999;19:103-14.
20. Duraisingh MT, Curtis J, Warhurst DC. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol. 1998;89:1-8.
21. Urdaneta L, Plowe C, Goldman I, Lal A. Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Venezuela. Am J Trop Med Hyg. 1999;61:457-62.
22. McCollum AM, Mueller K, Villegas L, Udhayakumar V, Escalante AA. 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. 2007;51:2085-91.
23. Contreras CE, Cortese JF, Caraballo A, Plowe CV. Genetics of drug-resistant Plasmodium falciparum malaria in the Venezuelan state of Bolívar. Am J Trop Med Hyg. 2002;67:400-5.
24. Mendez F, Muñoz A, Carrasquilla G, Jurado D, Arévalo-Herrera M, Cortese J, et al. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol. 2002;156:230-8.
25. Zhou Z, Griffing SM, de Oliveira AM, McCollum AM, Quezada WM, Arrospide N, et al. Decline in sulfadoxine-pyrimethamine-resistant alleles after change in drug policy in the Amazon region of Peru. Antimicrob Agents Chemother. 2008;52:739-41.
26. Peek R, van Gool T, Panchoe D, Greve S, Bus E, Resida L. Drug resistance and genetic diversity of Plasmodium falciparum parasites from Suriname. Am J Trop Med Hyg. 2005;73:833-8.
27. Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, et al. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000;95:721-8.
28. Talisuna A, Langi P, Mutabingwa T, Watkins W, Van Marck E, Egwang T, et al. Population-based validation of dihydrofolate reductase gene mutations for the prediction of sulfadoxine-pyrimethamine resistance in Uganda. Trans R Soc Trop Med Hyg. 2003;97:338-42.
29. Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, et al. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis. 2002;185:380-8.
30. Pérez MA, Cortés LJ, Guerra AP, Knudson A, Usta C, Nicholls RS. Eficacia de la combinación amodiaquina más sulfadoxina/pirimetamina y de la cloroquina para el tratamiento del paludismo en Córdoba, Colombia, 2006. Biomédica. 2008;28:148-59.
How to Cite
1.
Galindo JA, Cristiano FA, Knudson A, Nicholls RS, Guerra Ángela P. Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum from three endemic malaria regions in Colombia. biomedica [Internet]. 2010 Mar. 1 [cited 2024 May 19];30(1):56-64. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/153
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