title: Effect of transmission reduction by insecticide-treated bednets (ITNs) on antimalarial drug resistance in western Kenya.
abstract: Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance.
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Shah
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
authors.forename: Jodi
authors.initials: J
authors.lastname: Vanden Eng
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Blackstock
authors.forename: Kimberly
authors.initials: K
authors.lastname: Garner
authors.forename: Wangeci
authors.initials: W
authors.lastname: Gatei
authors.forename: John E
authors.initials: JE
authors.lastname: Gimnig
authors.forename: Kim
authors.initials: K
authors.lastname: Lindblade
authors.forename: Dianne
authors.initials: D
authors.lastname: Terlouw
authors.forename: Feiko
authors.initials: F
authors.lastname: ter Kuile
authors.forename: William A
authors.initials: WA
authors.lastname: Hawley
authors.forename: Penelope
authors.initials: P
authors.lastname: Phillips-Howard
authors.forename: Bernard
authors.initials: B
authors.lastname: Nahlen
authors.forename: Edward
authors.initials: E
authors.lastname: Walker
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002738:Chloroquine / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D057148:Insecticide-Treated Bednets; D007630:Kenya; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000635:transmission*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D015999:Multivariate Analysis; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):44-9
references.pmid: 12749485
references.citation: Int J Parasitol. 2003 Sep 15;33(10):1051-8
references.pmid: 13129527
references.citation: Parasitol Today. 2000 Aug;16(8):340-7
references.pmid: 10900482
references.citation: Malar J. 2004 May 07;3:9
references.pmid: 15132750
references.citation: Am J Trop Med Hyg. 2003 Sep;69(3):236-7
references.pmid: 14628936
references.citation: Lancet. 2001 Sep 29;358(9287):1066-7
references.pmid: 11589941
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):68-77
references.pmid: 12749488
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):100-7
references.pmid: 12749492
references.citation: Malar J. 2010 Dec 06;9:353
references.pmid: 21134282
references.citation: Am J Trop Med Hyg. 2007 Feb;76(2):237-44
references.pmid: 17297030
references.citation: Am J Trop Med Hyg. 2008 Sep;79(3):320-30
references.pmid: 18784222
references.citation: Lancet Infect Dis. 2002 Apr;2(4):209-18
references.pmid: 11937421
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):161-7
references.pmid: 12749500
references.citation: Am J Trop Med Hyg. 2010 Sep;83(3):489-95
references.pmid: 20810808
references.citation: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003755
references.pmid: 16625591
references.citation: Am J Trop Med Hyg. 2010 Aug;83(2):250-7
references.pmid: 20682863
references.citation: Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):170-80
references.pmid: 18165490
references.citation: Adv Parasitol. 2006;61:77-128
references.pmid: 16735163
references.citation: Acta Trop. 2005 Jan;93(1):97-106
references.pmid: 15589802
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):10-5
references.pmid: 12749480
references.citation: Am J Trop Med Hyg. 2003 Sep;69(3):238-43
references.pmid: 14628937
references.citation: JAMA. 2004 Jun 2;291(21):2571-80
references.pmid: 15173148
references.citation: Malar J. 2010 Nov 24;9:338
references.pmid: 21106088
references.citation: J Infect Dis. 2002 Feb 1;185(3):380-8
references.pmid: 11807721
references.citation: J Infect Dis. 2003 Jun 15;187(12):1870-5
references.pmid: 12792863
references.citation: Infect Genet Evol. 2007 Jan;7(1):52-9
references.pmid: 16690361
references.citation: Acta Trop. 2005 Jun;94(3):218-29
references.pmid: 15847846
references.citation: Antimicrob Agents Chemother. 2004 Aug;48(8):2924-9
references.pmid: 15273102
references.citation: N Engl J Med. 2006 Nov 9;355(19):1959-66
references.pmid: 17093247
references.citation: Malar J. 2010 Jul 05;9:190
references.pmid: 20602754
references.citation: J Infect Dis. 2003 Jun 1;187(11):1756-64
references.pmid: 12751033
references.citation: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):16-22
references.pmid: 12749481
references.citation: Bull World Health Organ. 2004 Feb;82(2):84
references.pmid: 15042228
references.citation: Malar J. 2008 Nov 17;7:236
references.pmid: 19014684
references.citation: Infect Genet Evol. 2006 May;6(3):241-8
references.pmid: 16112915
references.citation: Antimicrob Agents Chemother. 2003 Sep;47(9):2929-32
references.pmid: 12936996
references.citation: Malar J. 2004 Oct 18;3:35
references.pmid: 15491495