1921
Volume 98, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples ( = 64) compared with 22 in the post-ACT samples ( = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.17-0505
2018-03-26
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/14761645/98/5/tpmd170505.html?itemId=/content/journals/10.4269/ajtmh.17-0505&mimeType=html&fmt=ahah

References

  1. Ariey F, 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 5055. [Google Scholar]
  2. Straimer J, 2014. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428431. [Google Scholar]
  3. Dondorp AM, 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467. [Google Scholar]
  4. Amaratunga C, Witkowski B, Dek D, Try V, Khim N, Miotto O, Ménard D, Fairhurst RM, , 2014. Plasmodium falciparum founder populations in western Cambodia have reduced artemisinin sensitivity in vitro. 58: 49354937.
  5. Witkowski B, 2013. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 13: 10431049. [Google Scholar]
  6. Amaratunga C, Neal AT, Fairhurst RM, , 2014. Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in the ring-stage survival assay. Antimicrob Agents Chemother 58: 49384940. [Google Scholar]
  7. Ashley EA, 2014. Spread of artemisinin resistance in Plasmodium falciparum Malaria. N Engl J Med 371: 411423. [Google Scholar]
  8. Carrara VI, 2009. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS One 4: e4551. [Google Scholar]
  9. Amaratunga C, 2012. Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis 12: 851858. [Google Scholar]
  10. Liu H, 2015. In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China–Myanmar border of Yunnan Province, China from 2007 to 2013. Malar J 14: 47. [Google Scholar]
  11. Miotto O, 2013. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat Genet 45: 648655. [Google Scholar]
  12. Ménard D, 2016. A worldwide map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med 374: 24532464. [Google Scholar]
  13. WHO, 2016. Artemisinin and Artemisinin-Based Combination Therapy Resistance. Available at: http://apps.who.int/iris/bitstream/10665/208820/1/WHO_HTM_GMP_2016.5_eng.pdf?ua=1. Accessed June 27, 2017.
  14. Miotto O, 2015. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet 47: 226234. [Google Scholar]
  15. Takala-Harrison S, 2015. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis 211: 670679. [Google Scholar]
  16. MalariaGEN Plasmodium falciparum Community Project, 2016. Genomic epidemiology of artemisinin resistant malaria. eLife 5: 1724. [Google Scholar]
  17. Ouattara A, 2015. Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali. Am J Trop Med Hyg 92: 12021206. [Google Scholar]
  18. Taylor SM, 2015. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 211: 680688. [Google Scholar]
  19. Isozumi R, Uemura H, Kimata I, Ichinose Y, Logedi J, Omar AH, Kaneko A, , 2015. Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum. Emerg Infect Dis 21: 490492. [Google Scholar]
  20. Kamau E, 2015. K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis 211: 13521355. [Google Scholar]
  21. Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, Dorsey G, Rosenthal PJ, , 2014. Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One 9: e105690. [Google Scholar]
  22. Muwanguzi J, Henriques G, Sawa P, Bousema T, Sutherland CJ, Beshir KB, , 2016. Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children. Malar J 15: 36. [Google Scholar]
  23. Ocan M, Bwanga F, Okeng A, Katabazi F, Kigozi E, Kyobe S, Ogwal-Okeng J, Obua C, , 2016. Prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites isolated from adult symptomatic patients in northern Uganda. BMC Infect Dis 16: 428. [Google Scholar]
  24. Heuchert A, Abduselam N, Zeynudin A, Eshetu T, Löscher T, Wieser A, Pritsch M, Berens-Riha N, , 2015. Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013. Malar J 14: 208. [Google Scholar]
  25. Lu F, 2017. Emergence of indigenous artemisinin-resistant Plasmodium falciparum in Africa. N Engl J Med 376: 991993. [Google Scholar]
  26. National Malaria Control Programme (NMCP), Kenya National Bureau of Statistics (KNBS) and ICF International, 2016. Kenya Malaria Indicator Survey 2015. Nairobi, Kenya, and Rockville, Maryland NMCP, KNBS, and ICF International.
  27. 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: 72. [Google Scholar]
  28. Edgar RC, , 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 17921797. [Google Scholar]
  29. Alam MS, Mohon AN, Bayih A, Folefoc A, Pillai D, , 2014. Mutations in P. falciparum K13 propeller gene from Bangladesh: emerging resistance?Malar J 13 (Suppl 1): 71. [Google Scholar]
  30. Mohon AN, Alam MS, Bayih AG, Folefoc A, Shahinas D, Haque R, Pillai DR, , 2014. Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009–2013). Malar J 13: 431. [Google Scholar]
  31. Mishra N, 2015. Surveillance of artemisinin resistance in Plasmodium falciparum in India using the Kelch 13 molecular marker. Antimicrob Agents Chemother 59: 25482553. [Google Scholar]
  32. Ogutu BR, 2014. Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children aged less than five years: results of an open-label, randomized, single-centre study. Malar J. 13: 3343 [Google Scholar]
  33. Abuaku B, Duah N, Quaye L, Quashie N, Malm K, Bart-Plange C, Koram K, , 2016. Therapeutic efficacy of artesunate-amodiaquine and artemether–lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana. Malar J 15: 6. [Google Scholar]
  34. Espié E, Lima A, Atua B, Dhorda M, Flévaud L, Sompwe EM, Palma Urrutia PP, Guerin PJ, , 2012. Efficacy of fixed-dose combination artesunate–amodiaquine versus artemether–lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial. Malar J 11: 174. [Google Scholar]
  35. Ndounga M, Mayengue PI, Casimiro PN, Loumouamou D, Basco LK, Ntoumi F, Brasseur P, , 2013. Artesunate-amodiaquine efficacy in Congolese children with acute uncomplicated falciparum malaria in Brazzaville. Malar J 12: 53. [Google Scholar]
  36. Ogouyèmi-Hounto A, Azandossessi C, Lawani S, Damien G, de Tove YS, Remoue F, Kinde Gazard D, , 2016. Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J 15: 37. [Google Scholar]
  37. Schramm B, 2013. Efficacy of artesunate–amodiaquine and artemether–lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority. Malar J 12: 251. [Google Scholar]
  38. Sirima SB, 2016. Comparison of artesunate–mefloquine and artemether–lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial. Lancet Infect Dis 16: 11231133. [Google Scholar]
  39. Ashley EA, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411423. [Google Scholar]
  40. Cooper RA, Conrad MD, Watson QD, Huezo SJ, Ninsiima H, Tumwebaze P, Nsobya SL, Rosenthal PJ, , 2015. Lack of artemisinin resistance in Plasmodium falciparum in Uganda based on parasitological and molecular assays. Antimicrob Agents Chemother 59: 50615064. [Google Scholar]
  41. Huang B, 2015. Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy. Parasit Vectors 8: 634. [Google Scholar]
  42. Ouattara A, 2015. Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali. Am J Trop Med Hyg 92: 12021206. [Google Scholar]
  43. Torrentino-madamet M, 2014. Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J 13: 472. [Google Scholar]
  44. Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A, Lopez-Rubio J-J, , 2014. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol 32: 819821. [Google Scholar]
  45. Ingasia LA, Cheruiyot J, Okoth SA, Andagalu B, Kamau E, , 2016. Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya. Infect Genet Evol 39: 372380. [Google Scholar]
  46. Wang Z, Shrestha S, Li X, Miao J, Yuan L, Cabrera M, Grube C, Yang Z, Cui L, , 2015. Prevalence of K13-propeller polymorphisms in Plasmodium falciparum from China–Myanmar border in 2007–2012. Malar J 14: 168. [Google Scholar]
  47. Talundzic E, 2015. Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign. PLoS Pathog 11: e1004789. [Google Scholar]
  48. Joy DA, 2003. Early origin and recent expansion of Plasmodium falciparum. Science 300: 318321. [Google Scholar]
  49. Noor AM, 2009. The risks of malaria infection in Kenya in 2009. BMC Infect Dis 9: 180. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.17-0505
Loading
/content/journals/10.4269/ajtmh.17-0505
Loading

Data & Media loading...

  • Received : 23 Jun 2017
  • Accepted : 19 Oct 2017
  • Published online : 26 Mar 2018

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error