Agomo Chimere Obiora, Oyibo Wellington Aghoghovwia, Sutherland Colin, Hallet Rachael, Oguike Mary
Malaria Research Laboratory, Nigerian Institute of Medical Research, Lagos, Nigeria.
ANDI Centre of Excellence for Malaria Diagnosis/WHO/TDR/FIND Malaria Specimen Bank Site, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
PLoS One. 2016 Jan 25;11(1):e0146908. doi: 10.1371/journal.pone.0146908. eCollection 2016.
The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine-pyrimethamine (SP) is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ) and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1) and type 1 antifolate antimalarial medicines (Pfdhfr).
Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene by real time polymerase chain reaction (PCR) using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1) gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene.
Two haplotypes of Pfcrt (n = 54) were observed: CVMNK 13(24.2%) and CVIET 41 (75.9%) of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28) haplotypes were NYSND 15(53.6%), YYSND 5(17.9%), NFSND 6(21.4%) and YFSND 2(7.1%). The Pfdhfr (n = 15) were ACNCSVI 4(26.7%), and ACICNSVI 1(6.7%) and ACIRNVI 10 (66.7%). The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/μl, P = 0.024) while Pfcrt 76T was associated with young maternal age (mean 24.1 ± 4.5 years; P = 0.006). The median parasitaemia were similar (P>0.05) in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt, Pfmdr1 or Pfdhfr genes (P>0.05).
Markers of resistance to chloroquine and pyrimethamine were high, whereas cycloguanil-resistance marker was not present in the studied population. The low level of mutations in the Pfmdr1gene indicates likely efficacy of amodiaquine against malaria in pregnancy.
使用抗疟药物进行预防和治疗是预防妊娠期疟疾的主要策略。尽管目前尼日利亚推荐使用周效磺胺 - 乙胺嘧啶（SP）对妊娠期疟疾进行间歇性预防治疗，但以前用于预防的药物如氯喹（CQ）和乙胺嘧啶仍可在柜台购买到。本研究描述了对喹啉（Pfcrt和Pfmdr 1）和1型抗叶酸抗疟药物（Pfdhfr）耐药或不耐药的标志物。
对当前妊娠期间首次到产前诊所就诊的孕妇的恶性疟原虫阳性干血斑，使用单倍型特异性探针通过实时聚合酶链反应（PCR）检测恶性疟原虫氯喹抗性转运蛋白（Pfcrt）基因第72 - 76密码子处的突变情况。采用PCR及序列分析来鉴定恶性疟原虫多药抗性1（Pfmdr1）基因第86、184、1034、1042和1246密码子以及Pfdhfr基因第16、50、51、59、108、140和164密码子处的突变。
观察到Pfcrt的两种单倍型（n = 54）：CVMNK 13例（24.2%）和CVIET 41例（75.9%）。该人群中未出现SVMNT单倍型。Pfmdr1（n = 28）的单倍型为NYSND 15例（53.6%）、YYSND 5例（17.9%）、NFSND 6例（21.4%）和YFSND 2例（7.1%）。Pfdhfr（n = 15）为ACNCSVI 4例（26.7%）、ACICNSVI 1例（6.7%）和ACIRNVI 10例（66.7%）。Pfcrt 76T、Pfdhfr108N、Pfmdr186Y和184F的发生率分别为75.9%、73.3%、25%和28.1%。Pfmdr1 86Y与低寄生虫血症相关（中位数 = 71个寄生虫/微升，P = 0.024），而Pfcrt 76T与产妇年龄小相关（平均24.1 ± 4.5岁；P = 0.006）。Pfcrt 76、Pfmdr1 184和Pfdhfr 108野生型和突变型菌株的寄生虫血症中位数相似（P>0.05）。孕妇的妊娠次数或孕周与Pfcrt、Pfmdr1或Pfdhfr基因中的突变存在与否无关联（P>0.05）。
对氯喹和乙胺嘧啶的耐药标志物水平较高，而在所研究人群中未发现对环氯胍的耐药标志物。Pfmdr1基因的低突变水平表明阿莫地喹对妊娠期疟疾可能有效。
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