Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene and its relation to chloroquine resistance in Mozambique

被引:83
作者
Mayor, AG
Gómez-Olivé, X
Aponte, JJ
Casimiro, S
Mabunda, S
Dgedge, M
Barreto, A
Alonso, PL
机构
[1] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Unidad Epidemiol & Bioestadist, E-08036 Barcelona, Spain
[2] Minist Saude, Direcc Nacl Saude, Ctr Invest Saude Manhica, Maputo, Mozambique
[3] Minist Saude, Direcc Nacl Saude, Inst Nacl Saude, Maputo, Mozambique
[4] Minist Saude, Direcc Nacl Saude, Programa Nacl Control Malaria, Maputo, Mozambique
关键词
D O I
10.1086/319856
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
K76T, a mutation in the Plasmodium falciparum chloroquine (CQ) resistance transporter protein, has been implicated in resistance to CQ. A modified 14-day in vivo test to estimate the CQ resistance level was done in southern Mozambique: 21 (42%) of 50 subjects who completed the follow-up were CQ susceptible. Use of msa2-restriction fragment length polymorphism (RFLP) genotyping to differentiate new from recrudescent infections made little difference in the estimated prevalence of resistance. The K76T mutation prevalence was estimated by RFLP-polymerase chain reaction and sequencing, and its relation to parasitological CQ resistance was explored on day 0 samples: 51 of 56 pretreatment samples presented the T76 codon, and it was present in 100% of children with parasitological resistance. T76 also was present in 18 of 23 subjects in whom the infection resolved after CQ treatment. These findings show a high prevalence of the K76T mutation among wild isolates but also suggest additional factors responsible for CQ resistance.
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页码:1413 / 1416
页数:4
相关论文
共 10 条
[1]   RANDOMIZED TRIAL OF EFFICACY OF SPF66 VACCINE AGAINST PLASMODIUM-FALCIPARUM MALARIA IN CHILDREN IN SOUTHERN TANZANIA [J].
ALONSO, PL ;
SMITH, T ;
SCHELLENBERG, JRMA ;
MASANJA, H ;
MWANKUSYE, S ;
URASSA, H ;
DEAZEVEDO, IB ;
CHONGELA, J ;
KOBERO, S ;
MENENDEZ, C ;
HURT, N ;
THOMAS, MC ;
LYIMO, E ;
WEISS, NA ;
HAYES, R ;
KITUA, AY ;
LOPEZ, MC ;
KILAMA, WL ;
TEUSCHER, T ;
TANNER, M .
LANCET, 1994, 344 (8931) :1175-1181
[2]  
[Anonymous], 1996, WHOMAL961077
[3]   MALARIAL HAEMOZOIN BETA-HEMATIN SUPPORTS HEME POLYMERIZATION IN THE ABSENCE OF PROTEIN [J].
DORN, A ;
STOFFEL, R ;
MATILE, H ;
BUBENDORF, A ;
RIDLEY, RG .
NATURE, 1995, 374 (6519) :269-271
[4]   PLASMODIUM-FALCIPARUM - A RAPID TECHNIQUE FOR GENOTYPING THE MEROZOITE SURFACE PROTEIN-2 [J].
FELGER, I ;
TAVUL, L ;
BECK, HP .
EXPERIMENTAL PARASITOLOGY, 1993, 77 (03) :372-375
[5]  
Fidock DA, 2000, MOL CELL, V6, P861, DOI 10.1016/S1097-2765(05)00077-8
[6]   RAPID AND SIMPLE METHOD FOR ISOLATING MALARIA DNA FROM FINGERPRICK SAMPLES OF BLOOD [J].
FOLEY, M ;
RANFORDCARTWRIGHT, LC ;
BABIKER, HA .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1992, 53 (1-2) :241-244
[7]  
ROSARIO VE, 1978, LANCET, V1, P185
[8]   PRIMER-DIRECTED ENZYMATIC AMPLIFICATION OF DNA WITH A THERMOSTABLE DNA-POLYMERASE [J].
SAIKI, RK ;
GELFAND, DH ;
STOFFEL, S ;
SCHARF, SJ ;
HIGUCHI, R ;
HORN, GT ;
MULLIS, KB ;
ERLICH, HA .
SCIENCE, 1988, 239 (4839) :487-491
[9]   Complex polymorphisms in an similar to 330 kDa protein are linked to chloroquine-resistant P-falciparum in Southeast Asia and Africa [J].
Su, XZ ;
Kirkman, LA ;
Fujioka, H ;
Wellems, TE .
CELL, 1997, 91 (05) :593-603
[10]   Impact of chloroquine resistance on malaria mortality [J].
Trape, JF ;
Pison, G ;
Preziosi, MP ;
Enel, C ;
du Lou, AD ;
Delaunay, V ;
Samb, B ;
Lagarde, E ;
Molez, JF ;
Simondon, F .
COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES, 1998, 321 (08) :689-697