title: Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya.
abstract: BACKGROUND
  Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity.
  
  
  METHODS
  Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001).
  
  
  RESULTS
  A total of 12 MSP-1(19kDa) haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32-37%), with an overall haplotype diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points.
  
  
  CONCLUSIONS
  High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains.
authors: Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya. SKariuki@kemricdc.org.
authors: Simon K
authors: SK
authors: Kariuki
authors: James
authors: J
authors: Njunge
authors: Ann
authors: A
authors: Muia
authors: Geofrey
authors: G
authors: Muluvi
authors: Wangeci
authors: W
authors: Gatei
authors: Feiko
authors: F
authors: Ter Kuile
authors: Dianne J
authors: DJ
authors: Terlouw
authors: William A
authors: WA
authors: Hawley
authors: Penelope A
authors: PA
authors: Phillips-Howard
authors: Bernard L
authors: BL
authors: Nahlen
authors: Kim A
authors: KA
authors: Lindblade
authors: Mary J
authors: MJ
authors: Hamel
authors: Laurence
authors: L
authors: Slutsker
authors: Ya Ping
authors: YP
authors: Shi
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D057148:Insecticide-Treated Bednets / Q000706:statistics & numerical data*; D007630:Kenya; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000517:prevention & control / Q000635:transmission*; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D009032:Mosquito Control / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan
references: N Engl J Med. 2012 Dec 13;367(24):2284-95
references: 23136909
references: J Clin Microbiol. 2006 Apr;44(4):1229-35
references: 16597843
references: Cochrane Database Syst Rev. 2004;(2):CD000363
references: 15106149
references: Infect Immun. 1992 Feb;60(2):675-82
references: 1730503
references: Mol Biol Evol. 1992 May;9(3):381-93
references: 1584009
references: Mol Biochem Parasitol. 2000 Mar 5;106(2):273-82
references: 10699256
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):108-14
references: 12749493
references: Science. 1995 Sep 22;269(5231):1709-11
references: 7569897
references: Trans R Soc Trop Med Hyg. 2002 Apr;96 Suppl 1:S131-6
references: 12055826
references: Med Vet Entomol. 1989 Jul;3(3):263-71
references: 2519671
references: J Immunol. 1988 Mar 15;140(6):1715-6
references: 3279122
references: Am J Trop Med Hyg. 1994 May;50(5):529-36
references: 7911282
references: Bioinformatics. 2009 Jun 1;25(11):1451-2
references: 19346325
references: Mol Biochem Parasitol. 2002 Nov-Dec;125(1-2):83-90
references: 12467976
references: PLoS One. 2009;4(3):e4708
references: 19262754
references: Gene. 2000 Jan 11;241(2):325-31
references: 10675045
references: Science. 1984 Aug 10;225(4662):628-30
references: 6204384
references: Clin Diagn Lab Immunol. 2001 Nov;8(6):1289-91
references: 11687480
references: Parasitology. 1994 Nov;109 ( Pt 4):413-21
references: 7800409
references: Am J Trop Med Hyg. 2007 Jun;76(6):1037-45
references: 17556608
references: Mol Biochem Parasitol. 1998 May 1;92(2):241-52
references: 9657329
references: J Eukaryot Microbiol. 2001 Jul-Aug;48(4):433-9
references: 11456319
references: PLoS Med. 2007 Mar;4(3):e93
references: 17355170
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):68-77
references: 12749488
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):100-7
references: 12749492
references: Exp Parasitol. 1990 Nov;71(4):386-92
references: 1699781
references: Trans R Soc Trop Med Hyg. 2006 May;100(5):395-400
references: 16288791
references: Bioinformatics. 2003 Dec 12;19(18):2496-7
references: 14668244
references: Malar J. 2008 May 27;7:93
references: 18505558
references: Malar J. 2010 Dec 06;9:353
references: 21134282
references: Philos Trans R Soc Lond B Biol Sci. 1997 Sep 29;352(1359):1385-94
references: 9355131
references: Am J Trop Med Hyg. 2007 Aug;77(2):250-5
references: 17690395
references: Mol Biol Evol. 2000 Oct;17(10):1467-82
references: 11018154
references: N Engl J Med. 2011 Nov 17;365(20):1863-75
references: 22007715
references: JAMA. 2004 Jun 2;291(21):2571-80
references: 15173148
references: Science. 1980 Jan 4;207(4426):71-3
references: 6985745
references: Mol Ecol Resour. 2010 May;10(3):564-7
references: 21565059
references: Nat Genet. 2007 Jan;39(1):126-30
references: 17159981
references: PLoS One. 2009 Dec 30;4(12):e8497
references: 20041125
references: Am J Trop Med Hyg. 1992 Dec;47(6):844-51
references: 1281968
references: Ann Trop Med Parasitol. 1989 Dec;83(6):559-68
references: 2694982
references: Nat Rev Immunol. 2001 Nov;1(2):117-25
references: 11905819
references: PLoS One. 2009 Nov 17;4(11):e7849
references: 19924281
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):137-41
references: 12749497
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):23-9
references: 12749482
references: J Exp Med. 1990 Jul 1;172(1):379-82
references: 1694225
references: Trans R Soc Trop Med Hyg. 2002 Nov-Dec;96(6):597-9
references: 12625130
references: Mol Biol Evol. 2007 Aug;24(8):1596-9
references: 17488738
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):16-22
references: 12749481
references: PLoS Clin Trials. 2006 May;1(1):e5
references: 16871327
references: Ann Trop Med Parasitol. 1994 Jun;88(3):263-70
references: 7944671
references: Am J Trop Med Hyg. 1996 Aug;55(2):144-9
references: 8780451
references: Gene. 2003 Jan 30;304:65-75
references: 12568716
references: Am J Trop Med Hyg. 2006 Jan;74(1):31-40
references: 16407343
references: Parasitol Today. 1993 Feb;9(2):50-4
references: 15463703