Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola
Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola
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DOI：
10.1128/aac.00559-12
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发表时间：
2012-10-01
影响因子：
4.9
通讯作者：
Nery, Susana Vaz
中科院分区：
文献类型：
--
作者：
Fancony, Claudia;Gamboa, Dina;Nery, Susana Vaz
以青蒿素为基础的疟疾联合疗法已在整个非洲得到广泛应用。以前以氯喹(CQ)抗性基因为主的恶性疟原虫种群现在面临着不同的药物选择压力。恶性疟原虫、柯蒂斯卵形疟原虫和瓦氏卵形疟原虫与恶性疟原虫在整个非洲大陆共处，经常以混合感染的形式存在。在安哥拉北部的一次横断面调查中收集的血点DNA，通过聚合酶链式反应确定了人类疟原虫的流行情况。恶性疟原虫pfcrt和pfmdr1耐药相关基因座的基因分型采用实时定量聚合酶链式反应或直接测序的方法。在所采集的3316份标本中，有541份(16.3%)含有疟原虫感染，其中477份(88.2%)为单独感染恶性疟原虫，6.5%为恶性疟原虫和疟疾混合感染，1.1%为单独感染间日疟原虫。其余的大多数(3.7%)单独或与其他物种一起携带卵形弯曲线虫或瓦氏卵形线虫。在430株pfcrt基因分型的恶性疟原虫分离株中，61.6%携带野生型等位基因CVMNK，位于密码子72-76，或单独携带或与抗性等位基因CVIET联合携带。未发现其他pfcrt等位基因。Pfmdr1基因的86、184、1034、1042和1246位密码子上的野生型等位基因在测序菌株中占主导地位。与以前的研究相比，研究地区的恶性疟原虫包含与CQ敏感性和CQ耐药性相关的大致相同的基因组合，这表明要么是由于农村地区难以获得治疗而导致的药物压力较低，要么是政策变化的快速影响，而不是使用标准的单一疗法。
Artemisinin-based combination therapy for malaria has become widely available across Africa. Populations of Plasmodium falciparum that were previously dominated by chloroquine (CQ)-resistant genotypes are now under different drug selection pressures. P. malariae, P. ovale curtisi, and P. ovale wallikeri are sympatric with P. falciparum across the continent and are frequently present as coinfections. The prevalence of human Plasmodium species was determined by PCR using DNA from blood spots collected during a cross-sectional survey in northern Angola. P. falciparum was genotyped at resistance-associated loci in pfcrt and pfmdr1 by real-time PCR or by direct sequencing of amplicons. Of the 3,316 samples collected, 541 (16.3%) contained Plasmodium species infections; 477 (88.2%) of these were P. falciparum alone, 6.5% were P. falciparum and P. malariae together, and 1.1% were P. vivax alone. The majority of the remainder (3.7%) harbored P. ovale curtisi or P. ovale wallikeri alone or in combination with other species. Of 430 P. falciparum isolates genotyped for pfcrt, 61.6% carried the wild-type allele CVMNK at codons 72 to 76, either alone or in combination with the resistant allele CVIET. No other pfcrt allele was found. Wildtype alleles dominated at codons 86, 184, 1034, 1042, and 1246 of the pfmdr1 locus among the sequenced isolates. In contrast to previous studies, P. falciparum in the study area comprises an approximately equal mix of genotypes associated with CQ sensitivity and with CQ resistance, suggesting either lower drug pressure due to poor access to treatment in rural areas or a rapid impact of the policy change away from the use of standard monotherapies.