Figueiredo Paula, Benchimol Carla, Lopes Dinora, Bernardino Luís, do Rosário Virgílio E, Varandas Luís, Nogueira Fátima
UEI Malária/Centro de Malária e Doenças Tropicais/IHMT/Universidade Nova de Lisboa, Lisbon, Portugal.
Malar J. 2008 Nov 17;7:236. doi: 10.1186/1475-2875-7-236.
Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.
Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in Plasmodium falciparum was investigated in the pfmdr1 (N86Y) and pfcrt (K76T) genes, associated with CQ resistance, as well as in pfdhfr (C59R) and pfdhps (K540E), conferring SP resistance.
The frequencies of pfmdr1 mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of pfcrt mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For pfdhfr the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning pfdhps, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).
The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.
疟疾是安哥拉发病率和死亡率最高的传染病。由于氯喹(CQ)广泛耐药,该国最近改变了非复杂性疟疾的一线治疗推荐方案,成人从CQ改为青蒿素联合疗法(ACT),孕妇则采用磺胺多辛/乙胺嘧啶(S/P)。然而,在非洲,S/P敏感性丧失的情况正在迅速发展,在本研究中,对一些与CQ和S/P相关的分子标记进行了研究。
从安哥拉大卫·贝纳迪诺博士儿童医院(HPDB)收治的245例非复杂性疟疾儿童中采集血样,调查恶性疟原虫中与CQ耐药相关的pfmdr1(N86Y)和pfcrt(K76T)基因以及赋予S/P耐药性的pfdhfr(C59R)和pfdhps(K540E)基因的突变情况。
密码子86处pfmdr1突变的频率为N占28.6%、Y占61.3%以及混合感染(NY)占10.1%。密码子76处pfcrt突变的频率为K占93.9%、T占5.7%以及混合感染(KT)占0.4%。对于pfdhfr,密码子59处的结果为C占60.6%、R占20.6%以及混合感染(CR)占18.8%。关于pfdhps,6.3%的分离株携带540E突变,5.4%为混合感染(K540E)。
这项流行病学研究的结果显示CQ耐药标记的存在率很高,而在所研究的标记中S/P的流行率要低得多。