Trends in drug resistance codons in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Kenyan parasites from 2008 to 2012

详细信息    查看全文

• 作者：Dennis W Juma (1)
  Angela A Omondi (1)
  Luiser Ingasia (1)
  Benjamin Opot (1)
  Agnes Cheruiyot (1)
  Redemptah Yeda (1)
  Charles Okudo (1)
  Jelagat Cheruiyot (1)
  Peninnah Muiruri (1)
  Bidii Ngalah (1)
  Lorna J Chebon (1)
  Fredrick Eyase (1)
  Jacob Johnson (1)
  Wallace D Bulimo (1)
  Hoseah M Akala (1)
  Ben Andagalu (1)
  Edwin Kamau (1)
  
  1. Global Emerging Infections Surveillance (GEIS) Program ; United States Army Medical Research Unit-Kenya (USAMRU-K) ; Kenya Medical Research Institute (KEMRI) - Walter Reed Project ; Kisumu and Nairobi ; Kenya
  
• 关键词：Malaria ; Plasmodium falciparum dihydrofolate reductase ; Plasmodium falciparum dihydropteroate synthase
• 刊名：Malaria Journal
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：439 KB
• 参考文献：1. Bousema, JT, Gouagna, LC, Meutstege, AM, Okech, BE, Akim, NI, Githure, JI, Beier, JC, Sauerwein, RW (2003) Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in western Kenya. Trop Med Int Health 8: pp. 427-430 g/10.1046/j.1365-3156.2003.01047.x" target="_blank" title="It opens in new window">CrossRef
  2. Mberu, EK, Mosobo, MK, Nzila, AM, Kokwaro, GO, Sibley, CH, Watkins, WM (2000) The changing in vitro susceptibility pattern to pyrimethamine/sulfadoxine in Plasmodium falciparum field isolates from Kilifi, Kenya. Am J Trop Med Hyg 62: pp. 396-401
  3. Amin, AA, Zurovac, D, Kangwana, BB, Greenfield, J, Otieno, DN, Akhwale, WS, Snow, RW (2007) The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya. Malar J 6: pp. 72 g/10.1186/1475-2875-6-72" target="_blank" title="It opens in new window">CrossRef
  4. Peters, PJ, Thigpen, MC, Parise, ME, Newman, RD (2007) Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria prevention in pregnancy using intermittent preventive treatment. Drug Saf 30: pp. 481-501 g/10.2165/00002018-200730060-00003" target="_blank" title="It opens in new window">CrossRef
  Report of the Technical Consultation on Intermittent Preventive Treatment in Infants (IPTi), Technical Expert Group on Preventive Chemotherapy. World Health Organization, Geneva
  5. Sridaran, S, McClintock, SK, Syphard, LM, Herman, KM, Barnwell, JW, Udhayakumar, V (2010) Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations. Malar J 9: pp. 247 g/10.1186/1475-2875-9-247" target="_blank" title="It opens in new window">CrossRef
  6. McCollum, AM, Poe, AC, Hamel, M, Huber, C, Zhou, Z, Shi, YP, Ouma, P, Vulule, J, Bloland, P, Slutsker, L, Barnwell, JW, Udhayakumar, V, Escalante, AA (2006) Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. J Infect Dis 194: pp. 189-197 g/10.1086/504687" target="_blank" title="It opens in new window">CrossRef
  7. Peterson, DS, Wallikier, 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 U S A 85: pp. 9114-9118 g/10.1073/pnas.85.23.9114" target="_blank" title="It opens in new window">CrossRef
  8. Triglia, T, Menting, JG, Wilson, C, Cowman, AF (1997) Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proc Natl Acad Sci U S A 94: pp. 13944-13949 g/10.1073/pnas.94.25.13944" target="_blank" title="It opens in new window">CrossRef
  9. Nzila-Mounda, A, Mberu, EK, Sibley, CH, Plowe, CV, Winstanley, PA, Watkins, WM (1998) Kenyan Plasmodium falciparum field isolates: correlation between pyrimethamine and chlorcycloguanil activity in vitro and point mutations in the dihydrofolate reductase domain. Antimicrob Agents Chemother 42: pp. 164-169
  10. Kublin, JG, Dzinjalamala, FK, Kamwendo, DD, Malkin, EM, Cortese, JF, Martino, LM, Mukadam, RA, Rogerson, SJ, Lescano, AG, Molyneux, ME, Winstanley, PA, Chimpeni, P, Taylor, TE, Plowe, CV (2002) Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185: pp. 380-388 g/10.1086/338566" target="_blank" title="It opens in new window">CrossRef
  11. Foote, SJ, Galatis, D, Cowman, AF (1990) Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. Proc Natl Acad Sci U S A 87: pp. 3014-3017 g/10.1073/pnas.87.8.3014" target="_blank" title="It opens in new window">CrossRef
  12. Plowe, CV, Cortese, JF, Djimde, A, Nwanyanwu, OC, Watkins, WM, Winstanley, PA, Estrada-Franco, JG, Mollinedo, RE, Avila, JC, Cespedes, JL, Carter, D, Doumbo, OK (1997) Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176: pp. 1590-1596 g/10.1086/514159" target="_blank" title="It opens in new window">CrossRef
  13. Oesterholt, MJ, Alifrangis, M, Sutherland, CJ, Omar, SA, Sawa, P, Howitt, C, Gouagna, LC, Sauerwein, RW, Bousema, T (2009) Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya. PLoS One 4: pp. e4364 g/10.1371/journal.pone.0004364" target="_blank" title="It opens in new window">CrossRef
  14. Triglia, T, Wang, P, Sims, PF, Hyde, JE, Cowman, AF (1998) Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihydropteroate synthase in sulfadoxine-resistant malaria. EMBO J 17: pp. 3807-3815 g/10.1093/emboj/17.14.3807" target="_blank" title="It opens in new window">CrossRef
  15. Khalil, I, Ronn, AM, Alifrangis, M, Gabar, HA, Satti, GM, Bygbjerg, IC (2003) Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. Am J Trop Med Hyg 68: pp. 586-589
  16. Mbaisi, A, Liyala, P, Eyase, F, Achilla, R, Akala, H, Wangui, J, Mwangi, J, Osuna, F, Alam, U, Smoak, BL, Davis, JM, Kyle, DE, Coldren, RL, Mason, C, Waters, NC (2004) Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother 48: pp. 3598-3601 g/10.1128/AAC.48.9.3598-3601.2004" target="_blank" title="It opens in new window">CrossRef
  17. Spalding, MD, Eyase, FL, Akala, HM, Bedno, SA, Prigge, ST, Coldren, RL, Moss, WJ, Waters, NC (2010) Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya. Malar J 9: pp. 338 g/10.1186/1475-2875-9-338" target="_blank" title="It opens in new window">CrossRef
  18. Iriemenam, NC, Shah, M, Gatei, W, van Eijk, AM, Ayisi, J, Kariuki, S, Vanden Eng, J, Owino, SO, Lal, AA, Omosun, YO, Otieno, K, Desai, M, ter Kuile, FO, Nahlen, B, Moore, J, Hamel, MJ, Ouma, P, Slutsker, L, Shi, YP (2012) Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malar J 11: pp. 134 g/10.1186/1475-2875-11-134" target="_blank" title="It opens in new window">CrossRef
  19. Malakooti, MA, Biomndo, K, Shanks, GD (1998) Reemergence of epidemic malaria in the highlands of western Kenya. Emerg Infect Dis 4: pp. 671-676 g/10.3201/eid0404.980422" target="_blank" title="It opens in new window">CrossRef
  20. Emelda, AO, Victor, AA, Abdisalan, MN, Robert, WS (2010) Changing malaria intervention coverage, transmission and hospitalization in Kenya. Malar J 9: pp. 285 g/10.1186/1475-2875-9-285" target="_blank" title="It opens in new window">CrossRef
  21. Alam, MT, de Souza, DK, Vinayak, S, Griffing, SM, Poe, AC, Duah, NO, Ghansah, A, Asamoa, K, Slutsker, L, Wilson, MD, Barnwell, JW, Udhayakumar, V, Koram, KA (2011) Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana. J Infect Dis 203: pp. 220-227 g/10.1093/infdis/jiq038" target="_blank" title="It opens in new window">CrossRef
  22. Vinayak, S, Alam, MT, Mixson-Hayden, T, McCollum, AM, Sem, R, Shah, NK, Lim, P, Muth, S, Rogers, WO, Fandeur, T, Barnwell, JW, Escalante, AA, Wongsrichanalai, C, Ariey, F, Meshnick, SR, Udhayakumar, V (2010) Origin and evolution of sulfadoxine resistant Plasmodium falciparum. PLoS Pathog 6: pp. e1000830 g/10.1371/journal.ppat.1000830" target="_blank" title="It opens in new window">CrossRef
  23. Zhou, Z, Griffing, SM, de Oliveira, AM, McCollum, AM, Quezada, WM, Arrospide, N, Escalante, AA, Udhayakumar, V (2008) Decline in sulfadoxine-pyrimethamine-resistant alleles after change in drug policy in the Amazon region of Peru. Antimicrob Agents Chemother 52: pp. 739-741 g/10.1128/AAC.00975-07" target="_blank" title="It opens in new window">CrossRef
  24. Alam, MT, Vinayak, S, Congpuong, K, Wongsrichanalai, C, Satimai, W, Slutsker, L, Escalante, AA, Barnwell, JW, Udhayakumar, V (2011) Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand. Antimicrob Agents Chemother 55: pp. 155-164 g/10.1128/AAC.00691-10" target="_blank" title="It opens in new window">CrossRef
  25. Garner, P, Gulmezoglu, AM, Garner, P, Gulmezoglu, AM (2006) Drugs for preventing malaria in pregnant women. Cochrane Database Syst.
  26. Gasaira, AF, Kamya, MR, Ochong, EO, Vora, N, Achan, J, Charlebois, E, Ruel, T, Kateera, F, Meya, DN, Havlir, D, Rosenthal, PJ, Dorsey, G, Gasaira, AF, Kamya, MR, Ochong, EO, Vora, N, Achan, J, Charlebois, E, Ruel, T, Kateera, F, Meya, DN, Havlir, D, Rosenthal, PJ, Dorsey, G (2010) Effect of trimethroprim-sulfamethazole on the risk of malaria in HIV infected Ugandan children living in an area of widespread antifolate resistance. Malar J 9: pp. 177 g/10.1186/1475-2875-9-177" target="_blank" title="It opens in new window">CrossRef
  27. Le Bras, J, Durand, R (2003) The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam Clin Pharmacol 17: pp. 147-153 g/10.1046/j.1472-8206.2003.00164.x" target="_blank" title="It opens in new window">CrossRef
  28. Gesase, S, Gosling, RD, Hashim, R, Ord, R, Naidoo, I, Madebe, R, Mosha, JF, Joho, A, Mandia, V, Mrema, H, Mapunda, E, Savael, Z, Lemnge, M, Mosha, FW, Greenwood, B, Roper, C, Chandramohan, D (2009) High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581. PLoS One 4: pp. e4569 g/10.1371/journal.pone.0004569" target="_blank" title="It opens in new window">CrossRef
  29. Wang, P, Lee, CS, Bayoumi, R, Djimde, A, Doumbo, O, Swedberg, G, Dao, LD, Mshinda, H, Tanner, M, Watkins, WM, Sims, PF, Hyde, JE (1997) Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Mol Biochem Parasitol 89: pp. 161-177 g/10.1016/S0166-6851(97)00114-X" target="_blank" title="It opens in new window">CrossRef
  30. Ishraga, A-E, Michael, A, Insaf, K, Ib, B, Emad, M, Mustafa, E, Hayder, G (2007) The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics. Malar J 6: pp. 108 g/10.1186/1475-2875-6-108" target="_blank" title="It opens in new window">CrossRef
  31. 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: pp. 523-527
  32. McCollum, AM, Schneider, KA, Griffing, SM, Zhou, Z, Kariuki, S, Ter-Kuile, F, Shi, YP, Slutsker, L, Lal, AA, Udhayakumar, V, Escalante, AA (2012) Differences in selective pressure on dhps and dhfr drug resistant mutations in western Kenya. Malar J 11: pp. 77 g/10.1186/1475-2875-11-77" target="_blank" title="It opens in new window">CrossRef
  33. Mwangangi, JM, Mbogo, CM, Orindi, BO, Muturi, EJ, Midega, JT, Nzovu, J, Gatakaa, H, Githure, J, Borgemeister, C, Keating, J, Beier, JC (2013) Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20聽years. Malar J 12: pp. 13 g/10.1186/1475-2875-12-13" target="_blank" title="It opens in new window">CrossRef
  
• 刊物主题：Parasitology; Infectious Diseases; Tropical Medicine;
• 出版者：BioMed Central
• ISSN：1475-2875

文摘

Background Sulphadoxine-pyrimethamine (SP), an antifolate, was replaced by artemether-lumefantrine as the first-line malaria drug treatment in Kenya in 2004 due to the wide spread of resistance. However, SP still remains the recommended drug for intermittent preventive treatment in pregnant women and infants (IPTP/I) owing to its safety profile. This study assessed the prevalence of mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes associated with SP resistance in samples collected in Kenya between 2008 and 2012. Methods Field isolates collected from Kisumu, Kisii, Kericho and Malindi district hospitals were assessed for genetic polymorphism at various loci within Pfdhfr and Pfdhps genes by sequencing. Results Among the Pfdhfr mutations, codons N51I, C59R, S108N showed highest prevalence in all the field sites at 95.5%, 84.1% and 98.6% respectively. Pfdhfr S108N prevalence was highest in Kisii at 100%. A temporal trend analysis showed steady prevalence of mutations over time except for codon Pfdhps 581 which showed an increase in mixed genotypes. Triple Pfdhfr N51I/C59R/S108N and double Pfdhps A437G/ K540E had high prevalence rates of 86.6% and 87.9% respectively. The Pfdhfr/Pfdhps quintuple, N51I/C59R/S108N/A437G/K540E mutant which has been shown to be the most clinically relevant marker for SP resistance was observed in 75.7% of the samples. Conclusion SP resistance is still persistently high in western Kenya, which is likely due to fixation of key mutations in the Pfdhfr and Pfdhps genes as well as drug pressure from other antifolate drugs being used for the treatment of malaria and other infections. In addition, there is emergence and increasing prevalence of new mutations in Kenyan parasite population. Since SP is used for IPTP/I, molecular surveillance and in vitro susceptibility assays must be sustained to provide information on the emergence and spread of SP resistance.