Volume 88, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



The impact of malaria intervention measures (insecticide-treated net use and artemisinin combination therapy) on malaria genetics was investigated at two sites in western Kenya: an endemic lowland and an epidemic highland. The genetic structure of the parasite population was assessed by using microsatellites, and the prevalence of drug-resistant mutations was examined by using the polymerase chain reaction–restriction fragment length polymorphism method. Two years after intervention, genetic diversity remained high in both populations. A significant decrease in the prevalence of quintuple mutations conferring resistance to sulfadoxine-pyrimethamine was detected in both populations, but the mutation prevalence at codon 1246 of the multidrug resistance 1 gene had increased in the highland population. The decrease in sulfadoxine-pyrimethamine–resistant mutants is encouraging, but the increase in multidrug resistance 1 gene mutations is worrisome because these mutations are linked to resistance to other antimalarial drugs. In addition, the high level of genetic diversity observed after intervention suggests transmission is still high in each population.


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  1. World Health Organization, 2008. World Malaria Report. WHO Library Cataloguing-in-Publication Data 25. Geneva: World Health Organization. [Google Scholar]
  2. Global Fund to Fight AIDS, Tuberculosis and Malaria, 2011. Available at: http://www.theglobalfund.org/en/partnershipforum/2011/. [Google Scholar]
  3. Amin AA, Walley T, Kokwaro GO, Winstanley PA, Snow RW, , 2007. Commentary: reconciling national treatment policies and drug regulation in Kenya. Health Policy Plan 22: 111112.[Crossref] [Google Scholar]
  4. Amin A, Zurovac D, Kangwana B, Greenfield J, Otieno D, Akhwale W, Snow R, , 2007. The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya. Malar J 6: 72.[Crossref] [Google Scholar]
  5. Zhou G, Afrane YA, Vardo-Zalik A, Atieli H, Zhong D, Wamae P, Himeidan YE, Minakawa N, Githeko AK, Yan G, , 2011. Changing patterns of malaria epidemiology between 2002 and 2010 in western Kenya: the fall and rise of malaria. PLoS ONE 6: e20318.[Crossref] [Google Scholar]
  6. World Health Organization, 2007. Insecticide Treated Mosquito Nets: A Position Statement. Geneva: World Health Organization. [Google Scholar]
  7. Aregawi M, Cibulskis R, Otten M, Williams R, Dye C, , 2008. World Malaria Report, 2008. Geneva: World Health Organization. [Google Scholar]
  8. Roll Back Malaria, 2009. Malaria Elimination in Africa. Available at: http://www.rbm.who.int/globaladvocacy/eventsarchive.html. [Google Scholar]
  9. Nafo-Traore F, Judd EJ, Okwo-Bele J, , 2005. Protecting Vulnerable Groups in Malaria-Endemic Areas in Africa through Accelerated Deployment of Insecticide-Treated Nets: A Joint WHO-UNICEF Statement. Geneva: World Health Organization. WHO/HTM/RBM/2005.57: 2. [Google Scholar]
  10. Roll Back Malaria, 2005. Scaling Up Insecticide Treated Netting Programmes in Africa: A Strategic Framework for Coordinated National Action. Geneva: World Health Organization. [Google Scholar]
  11. Bhattarai A, Ali AS, Kachur SP, Martensson A, Abbas AK, Khatib R, Al-Mafazy AW, Ramsan M, Rotllant G, Gerstenmaier JF, Molteni F, Abdulla S, Montgomery SM, Kaneko A, Bjorkman A, , 2007. Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar. PLoS Med 4: e309.[Crossref] [Google Scholar]
  12. O'Meara WP, Bejon P, Mwangi TW, Okiro EA, Peshu N, Snow RW, Newton CR, Marsh K, , 2008. Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet 372: 15551562.[Crossref] [Google Scholar]
  13. Gatei W, Kariuki S, Hawley W, ter Kuile F, Terlouw D, Phillips-Howard P, Nahlen B, Gimnig J, Lindblade K, Walker E, Hamel M, Crawford S, Williamson J, Slutsker L, Shi Y, , 2010. Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya. Malar J 9: 353.[Crossref] [Google Scholar]
  14. Laufer MK, Plowe CV, , 2004. Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies. Drug Resist Updat 7: 279288.[Crossref] [Google Scholar]
  15. Bwijo B, Kaneko A, Takechi M, Zungu IL, Moriyama Y, Lum JK, Tsukahara T, Mita T, Takahashi N, Bergqvist Y, Bjorkman A, Kobayakawa T, , 2003. High prevalence of quintuple mutant dhfr/dhps genes in Plasmodium infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop 85: 363373.[Crossref] [Google Scholar]
  16. Wellems T, Plowe C, , 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770776.[Crossref] [Google Scholar]
  17. White NJ, , 2008. Qinghaosu (artemisinin): the price of success. Science 320: 330334.[Crossref] [Google Scholar]
  18. Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, , 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209218.[Crossref] [Google Scholar]
  19. Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE, , 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6: 861871.[Crossref] [Google Scholar]
  20. Hayton K, Su XZ, , 2004. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr Drug Targets Infect Disord 4: 110.[Crossref] [Google Scholar]
  21. Warhurst DC, , 1999. Drug resistance in Plasmodium falciparum malaria. Infection 27: S55S58.[Crossref] [Google Scholar]
  22. Ouellette M, , 2001. Biochemical and molecular mechanisms of drug resistance in parasites. Trop Med Int Health 6: 874876.[Crossref] [Google Scholar]
  23. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref] [Google Scholar]
  24. Dondorp AM, Yeung S, White L, Nguon C, Day NP, Socheat D, von Seidlein L, , 2010. Artemisinin resistance: current status and scenarios for containment. Nat Rev Microbiol 8: 272280.[Crossref] [Google Scholar]
  25. Bonizzoni M, Afrane Y, Baliraine FN, Amenya DA, Githeko AK, Yan G, , 2009. Genetic structure of Plasmodium falciparum populations between lowland and highland sites and antimalarial drug resistance in western Kenya. Infect Genet Evol 9: 806812.[Crossref] [Google Scholar]
  26. Ndenga B, Githeko A, Omukunda E, Munyekenye G, Atieli H, Wamai P, Mbogo C, Minakawa N, Zhou G, Yan G, , 2006. Population dynamics of malaria vectors in western Kenya highlands. J Med Entomol 43: 200206.[Crossref] [Google Scholar]
  27. Wooden J, Kyes S, Sibley CH, , 1993. PCR and strain identification in Plasmodium falciparum . Parasitol Today 9: 303305.[Crossref] [Google Scholar]
  28. Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA, , 1999. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg 60: 687692. [Google Scholar]
  29. Anderson TJ, Su XZ, Bockarie M, Lagog M, Day KP, , 1999. Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology 119: 113125.[Crossref] [Google Scholar]
  30. Oetting WS, Lee HK, Flanders DJ, Wiesner GL, Sellers TA, King RA, , 1995. Linkage analysis with multiplexed short tandem repeat polymorphisms using infrared fluorescence and M13 tailed primers. Genomics 30: 450458.[Crossref] [Google Scholar]
  31. Zhong D, Afrane Y, Githeko A, Yang Z, Cui L, Menge DM, Temu EA, Yan G, , 2007. Plasmodium falciparum genetic diversity in western Kenya highlands. Am J Trop Med Hyg 77: 10431050. [Google Scholar]
  32. Anderson TJ, Haubold B, Williams JT, Estrada-Franco J, Richardson L, Mollinedo R, Bockarie M, Mokili J, Mharakurwa S, French N, Whitworth J, Velez ID, Brockman AH, Nosten F, Ferreira MU, Day KP, , 2000. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum . Mol Biol Evol 17: 14671482.[Crossref] [Google Scholar]
  33. Vardo AM, Schall JJ, , 2007. Clonal diversity of a lizard malaria parasite, Plasmodium mexicanum, in its vertebrate host, the western fence lizard: role of variation in transmission intensity over time and space. Mol Ecol 16: 27122720.[Crossref] [Google Scholar]
  34. Ferreira MU, Nair S, Hyunh TV, Kawamoto F, Anderson TJ, , 2002. Microsatellite characterization of Plasmodium falciparum from cerebral and uncomplicated malaria patients in southern Vietnam. J Clin Microbiol 40: 18541857.[Crossref] [Google Scholar]
  35. Zhong D, Afrane Y, Githeko A, Cui L, Menge D, Yan G, , 2008. Molecular epidemiology of drug-resistant malaria in western Kenya highlands. BMC Infect Dis 8: 105.[Crossref] [Google Scholar]
  36. Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-Franco J, 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: 15901596.[Crossref] [Google Scholar]
  37. Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, , 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565568. [Google Scholar]
  38. Peakall R, Smouse PE, , 2006. Genalex 6: genetic analysis in Excel. Population genetic software for teaching and research. Mol Ecol Notes 6: 288295.[Crossref] [Google Scholar]
  39. Lewis PO, Zaykin D, , 2002. Genetic Data Analysis: Computer Program for the Analysis of Allelic Data. Version 1.1. Available at: http://hydrodictyon.eeb.uconn.edu/people/plewis/software.php. [Google Scholar]
  40. Piry S, Luikart G, Cornuet JM, , 1999. BOTTLENECK: a computer program for detecting recent reductions in the effective population size using allele frequency data. J Hered 90: 502503.[Crossref] [Google Scholar]
  41. Cornuet JM, Luikart G, , 1996. Description and power analysis of two tests for detecting recent population bottlenecks from allele frequency data. Genetics 144: 20012014. [Google Scholar]
  42. Haubold B, Hudson RR, , 2000. LIAN 3.0: detecting linkage disequilibrium in multilocus data linkage analysis. Bioinformatics 9: 847848.[Crossref] [Google Scholar]
  43. Durand P, Michalakis Y, Cestier S, Oury B, Leclerc MC, Tibayrenc M, Renaud F, , 2003. Significant linkage disequilibrium and high genetic diversity in a population of Plasmodium falciparum from an area (Republic of The Congo) highly endemic for malaria. Am J Trop Med Hyg 68: 345349. [Google Scholar]
  44. Abdel-Wahab A, Abdel-Muhsin AA, Ali E, Suleiman S, Ahmed S, Walliker D, Babiker HA, , 2002. Dynamics of gametocytes among Plasmodium falciparum clones in natural infections in an area of highly seasonal transmission. J Infect Dis 185: 18381842.[Crossref] [Google Scholar]
  45. Malisa A, Pearce R, Abdulla S, Mshinda H, Kachur P, Bloland P, Roper C, , 2010. Drug coverage in treatment of malaria and the consequences for resistance evolution: evidence from the use of sulphadoxine/pyrimethamine. Malar J 9: 190.[Crossref] [Google Scholar]
  46. Zalis MG, Pang L, Silveira MS, Milhous WK, Wirth DF, , 1998. Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance. Am J Trop Med Hyg 58: 630637. [Google Scholar]
  47. Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJ, Mutabingwa TK, Sutherland CJ, Hallett RL, , 2007. Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother 51: 991997.[Crossref] [Google Scholar]
  48. Sidhu AB, Valderramos SG, Fidock DA, , 2005. pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum . Mol Microbiol 57: 913926.[Crossref] [Google Scholar]
  49. Ogbonna A, Uneke CJ, , 2008. Artemisinin-based combination therapy for uncomplicated malaria in sub-Saharan Africa: the efficacy, safety, resistance and policy implementation since Abuja 2000. Trans R Soc Trop Med Hyg 102: 621627.[Crossref] [Google Scholar]
  50. Dokomajilar C, Nsobya SL, Greenhouse B, Rosenthal PJ, Dorsey G, , 2006. Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother 50: 18931895.[Crossref] [Google Scholar]
  51. Happi CT, Gbotosho GO, Folarin OA, Bolaji OM, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM, , 2006. Association between mutations in Plasmodium falciparum chloroquine resistance transporter and P. falciparum multidrug resistance 1 genes and in vivo amodiaquine resistance in P. falciparum malaria-infected children in Nigeria. Am J Trop Med Hyg 75: 155161. [Google Scholar]
  52. Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP, , 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191: 10141017.[Crossref] [Google Scholar]
  53. Kangwana BB, Njogu J, Wasunna B, Kedenge SV, Memusi DN, Goodman CA, Zurovac D, Snow RW, , 2009. Malaria drug shortages in Kenya: a major failure to provide access to effective treatment. Am J Trop Med Hyg 80: 737738. [Google Scholar]
  54. Mokuolu OA, Okoro EO, Ayetoro SO, Adewara AA, , 2007. Effect of artemisinin-based treatment policy on consumption pattern of antimalarials. Am J Trop Med Hyg 76: 711. [Google Scholar]
  55. Watsierah CA, Jura WG, Oyugi H, Abong'o B, Ouma C, , 2010. Factors determining anti-malarial drug use in a peri-urban population from malaria holoendemic region of western Kenya. Malar J 9: 295.[Crossref] [Google Scholar]

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  • Received : 15 May 2012
  • Accepted : 08 Oct 2012
  • Published online : 09 Jan 2013

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