The prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine among pregnant women at first antenatal clinic attendance and delivery in the forest-savannah area of Ghana.
The prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine among pregnant women at first antenatal clinic attendance and delivery in the forest-savannah area of Ghana.
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DOI：
10.1371/journal.pone.0271489
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
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在中度至高度疟疾传播地区，妊娠期间使用磺胺多辛-乙胺嘧啶 (IPTp-SP) 进行间歇性预防治疗可预防疟疾以及相关的妊娠期母婴不良结局。然而，IPTp-SP 的有效性受到恶性疟原虫二氢叶酸还原酶 (Pfdhfr) 和二氢蝶酸合酶 (Pfdhps) 基因突变的威胁，这两个基因分别对乙胺嘧啶和磺胺多辛产生耐药性。本研究确定了加纳森林-草原地区疟疾高传播区孕妇中 SP 抗性分子标记的流行情况。使用 Chelex 100 从 18 岁以上孕妇（255 个首次产前护理 (ANC) 诊所就诊的 255 个，31 个 2017 年至 2019 年分娩时的）中提取 286 个恶性疟原虫阳性干血点，提取基因组 DNA。使用分子倒置探针和下一代测序检测 Pfdhfr 和 Pfdhps 基因的突变。在 Pfdhfr 基因中，首次 ANC 就诊时收集的样本中，密码子 51、59 和 108 处的单核苷酸多态性 (SNP) 检出率分别为 83.1% (157/189)、92.0% (173/188) 和 91.0% (171/188)，而 SNP 的检出率为 96.6 (28/29)。分娩时收集的分离株为 96.6% (28/29) 和 96.8% (30/31)。在 ANC 访视和分娩时收集的分型分离株中，分别有 80.5% (128/159) 和 96.5% (28/29) 携带 Pfdhfr 三重突变体 N51I、C59R 和 S108N (IRN)。在 Pfdhps 基因中，密码子 431、436、437 处检测到的 SNP 比例为 0.6% (1/174)、76.2% (138/181)、33.2% (60/181)、1.2% (2/174)、0% (0/183) 和 16.6% (27/173)。在 ANC 采集的样本中分别为 540、581 和 613，在分娩时采集的样本中分别为 0% (0/25)、72% (18/25)、40% (10/25)、3.6% (1/25)、0% (0/29) 和 7.4% (2/27)。四重突变体 Pfdhfr N51I、C59R 和 S108N + Pfdhps A437G (IRN-GK) 在 ANC 和分娩时分别存在于 25.8% (33/128) 和 34.8% (8/23) 的分离株中。在 ANC 和分娩时收集的样本中分别检测到五重突变等位基因 Pfdhfr N51I、C59R 和 S108N + Pfdhps A437G 和 K540E (IRN-GE)。在 Pfdhfr 密码子 16 或 164 或 Pfdhps 581 处未发现突变。研究区域的孕妇中 Pfdhfr 三突变体恶性疟原虫感染的患病率很高。然而，在 IPTp-SP 开始之前，Pfdhfr/Pfdhps 四重和五重组合突变体 IRN-GK 和 IRN-GE 的患病率分别较低，并且没有检测到 Pfdhps A581G 突变体，表明 SP 仍然可能对加纳中部带森林草原地区的 IPTp-SP 有效。
Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of IPTp-SP is, however, threatened by mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to pyrimethamine and sulfadoxine, respectively. This study determined the prevalence of molecular markers of SP resistance among pregnant women in a high malaria transmission area in the forest-savannah area of Ghana. Genomic DNA was extracted from 286 P. falciparum-positive dried blood spots obtained from pregnant women aged ≥18 years (255 at first Antenatal Care (ANC) clinic visit and 31 at delivery from 2017 to 2019) using Chelex 100. Mutations in Pfdhfr and Pfdhps genes were detected using molecular inversion probes and next generation sequencing. In the Pfdhfr gene, single nucleotide polymorphisms (SNPs) were detected in 83.1% (157/189), 92.0% (173/188) and 91.0% (171/188) at codons 51, 59, and 108 respectively in samples collected at first ANC visit, while SNPs were detected in 96.6 (28/29), 96.6% (28/29) and 96.8% (30/31) in isolates collected at delivery. The Pfdhfr triple mutant N51I, C59R and S108N (IRN) was carried by 80.5% (128/159) and 96.5% (28/29) of the typed isolates collected at ANC visit and at delivery respectively. In the Pfdhps gene, SNPs were detected in 0.6% (1/174), 76.2% (138/181), 33.2% (60/181), 1.2% (2/174), 0% (0/183), and 16.6% (27/173) at codons 431, 436, 437, 540, 581 and 613 respectively in samples collected at ANC, and 0% (0/25), 72% (18/25), 40% (10/25), 3.6% (1/25), 0% (0/29) and 7.4% (2/27) in samples collected at delivery. Quadruple mutant Pfdhfr N51I, C59R, and S108N + Pfdhps A437G (IRN-GK) was present in 25.8% (33/128) and 34.8% (8/23) of isolates at ANC and at delivery respectively. Quintuple mutant alleles Pfdhfr N51I, C59R, and S108N + Pfdhps A437G and K540E (IRN-GE) were detected in 0.8% (1/128) and 4.4% (1/23) of samples collected at ANC and at delivery respectively. No mutations were identified at Pfdhfr codons 16 or 164 or Pfdhps 581. There is a high prevalence of Pfdhfr triple mutant P. falciparum infections among pregnant women in the study area. However, prevalence of the combined Pfdhfr/Pfdhps quadruple and quintuple mutants IRN-GK and IRN-GE respectively prior to commencement of IPTp-SP were low, and no Pfdhps A581G mutant was detected, indicating that SP is still likely to be efficacious for IPTp-SP in the forest-savannah area in the middle belt of Ghana.
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影响因子：
3
作者：
Dosoo DK;Chandramohan D;Atibilla D;Oppong FB;Ankrah L;Kayan K;Agyemang V;Adu-Gyasi D;Twumasi M;Amenga-Etego S;Bruce J;Asante KP;Greenwood B;Owusu-Agyei S
通讯作者：
Owusu-Agyei S
DOI：
10.1093/infdis/jiy223
发表时间：
2018-08-14
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Aydemir O;Janko M;Hathaway NJ;Verity R;Mwandagalirwa MK;Tshefu AK;Tessema SK;Marsh PW;Tran A;Reimonn T;Ghani AC;Ghansah A;Juliano JJ;Greenhouse BR;Emch M;Meshnick SR;Bailey JA
通讯作者：
Bailey JA
影响因子：
3
作者：
Chaponda EB;Mharakurwa S;Michelo C;Bruce J;Chandramoha D;Matthew Chico R
通讯作者：
Matthew Chico R
影响因子：
6.4
作者：
Lynch, Caroline;Pearce, Richard;Roper, Cally
通讯作者：
Roper, Cally
影响因子：
4
作者：
Berglez, J;Iliades, P;Macreadie, I
通讯作者：
Macreadie, I