Gutman Julie, Kalilani Linda, Taylor Steve, Zhou Zhiyong, Wiegand Ryan E, Thwai Kyaw L, Mwandama Dyson, Khairallah Carole, Madanitsa Mwayi, Chaluluka Ebbie, Dzinjalamala Fraction, Ali Doreen, Mathanga Don P, Skarbinski Jacek, Shi Ya Ping, Meshnick Steve, ter Kuile Feiko O
Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.
College of Medicine, University of Malawi Department of Community Health, College of Medicine, Blantyre.
J Infect Dis. 2015 Jun 15;211(12):1997-2005. doi: 10.1093/infdis/jiu836. Epub 2015 Jan 6.
The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy.
Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant.
Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: .
IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.
恶性疟原虫二氢蝶酸合酶（dhps）编码基因中的A581G突变，与涉及dhps和二氢叶酸还原酶（dhfr）编码基因的五重突变体（即所谓的六重突变体）相结合，已被证实与孕期接受磺胺多辛-乙胺嘧啶间歇性预防治疗（IPTp-SP）的女性胎盘炎症增加和婴儿出生体重降低有关。
2009年至2011年期间，未感染人类免疫缺陷病毒的分娩女性参与了一项在马拉维进行的IPTp-SP有效性观察研究。通过聚合酶链反应（PCR）检测寄生虫；对阳性样本进行测序以确定dhfr和dhps基因座的基因型。将dhps中K540E的存在用作五重突变体的标志物。
对1809名女性的样本进行了PCR分析；220例（12%）恶性疟原虫呈阳性。共对202个标本的dhps第581密码子进行了基因分型；17例（8.4%）携带六重突变体。六重突变体与外周血（调整患病率比[aPR]，2.76；95%置信区间[CI]，1.82 - 4.18）和胎盘血（aPR 3.28；95% CI，1.88 - 5.78）中专利感染风险较高以及寄生虫密度较高相关。近期使用SP与总体寄生虫密度增加或胎盘病理学改变无关，在携带dhps A581G突变的寄生虫女性中也是如此。
IPTp-SP未能抑制寄生虫生长，但并未加重感染六重突变体寄生虫女性的病理学改变。迫切需要新的孕期疟疾预防干预措施。
