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加纳部分地区恶性疟原虫对磺胺多辛-乙胺嘧啶耐药的分子标志物高流行率:对 ITPTp-SP 的威胁?

High Prevalence of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine in Parts of Ghana: A Threat to ITPTp-SP?

机构信息

Department of Biomedical Science, School of Allied Health Sciences, College of Health and Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana.

Centre for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, Accra, Ghana.

出版信息

J Trop Pediatr. 2021 Jan 29;67(1). doi: 10.1093/tropej/fmaa120.

DOI:10.1093/tropej/fmaa120
PMID:33404643
Abstract

Malaria in pregnancy is a huge public health problem as it is the cause of maternal anaemia, still birth, premature delivery, low birth weight among others. To tackle this problem, WHO recommended the administration, during pregnancy, of intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP). The introduction of this policy is likely to create SP drug pressure which may lead to the emergence of parasite strains resistant to the drug. This study investigated the prevalence of the molecular markers of SP resistance as pointers to potential failure of IPTp-SP among pregnant women attending antenatal clinic, women at the point of baby delivery and out patients department (OPD) attendees. The study was conducted in health facilities located in parts of Ghana. Prevalence of mutations in dhfr and dhps genes of Plasmodium falciparum was determined using the method described by Duraisingh et al. The outcome of the study indicated the presence of high prevalence of strains of P.falciparum with the resistant alleles of the dhfr or dhps genes in the three categories of participants. There was a high prevalence of triple mutations (IRN) in the dhfr gene of P.falciparum isolates: 71.4% in peripheral blood of antenatal attendees; 74.1% in placenta cord blood of delivering mothers and 71.1% in OPD attendees. Quintuple mutations were only found in 2 (0.5%) isolates from OPD attendees. This observation might have occurred due to the increased use of SP for IPTp among others. There is the need for an interventional measure in order to protect pregnant women and their unborn children. Lay summaryWhen pregnant women get infected with the malaria parasites they are exposed to all manner of dangers including pre-term delivery, still birth, maternal anaemia and low birth weight. Taking sulphadoxine-pyrimethamine (SP) at predetermined periods during pregnancy, referred to as 'intermittent preventive treatment with SP' (IPTp-SP)' helps to curtail these problems. However, the frequent taking of these drugs is likely to create SP drug pressure which may lead to the emergence of parasite strains that are not readily killed by the drugs. In order to ascertain this phenomenon and advice stakeholders, this study determined the prevalence of certain 'materials' certified as markers of parasite resistance to SP. Alarmingly, more than 5% of all the category of women recruited to participate in this study were found to harbour the parasites that causes malaria. The outcome, also suggest the existence of high levels of strains of the malaria parasite, carrying the materials that make them to become resistant to SP. Policy makers must pay attention to these observations and institute measures to avoid escalation of the situation.

摘要

疟疾是一种严重的公共卫生问题,它会导致孕妇贫血、死胎、早产、低体重儿等。为了解决这个问题,世界卫生组织(WHO)建议在怀孕期间使用磺胺多辛-乙胺嘧啶(SP)进行间歇性预防治疗(IPTp-SP)。该政策的实施可能会导致 SP 药物压力,从而导致寄生虫对药物产生耐药性。本研究调查了 SP 耐药性的分子标记物的流行情况,以作为孕妇、产妇和门诊(OPD)患者中 IPTp-SP 潜在失败的指标。该研究在加纳部分地区的医疗机构进行。采用 Duraisingh 等人描述的方法,确定了恶性疟原虫 dhfr 和 dhps 基因的突变情况。研究结果表明,在三个类别的参与者中,携带 dhfr 或 dhps 基因耐药等位基因的恶性疟原虫流行率很高。在接受产前检查的外周血中,恶性疟原虫分离株 dhfr 基因中的三重突变(IRN)的流行率为 71.4%;在分娩母亲的胎盘脐带血中为 74.1%;在 OPD 就诊者中为 71.1%。在 OPD 就诊者中,仅在 2 株(0.5%)分离株中发现了五重突变。这种观察结果可能是由于 SP 用于 IPTp 的使用增加等原因造成的。为了保护孕妇及其未出生的孩子,有必要采取干预措施。

当孕妇感染疟原虫时,她们会面临各种危险,包括早产、死胎、孕妇贫血和低体重儿。在怀孕期间,按照“间歇性预防治疗用磺胺多辛-乙胺嘧啶(IPTp-SP)”的规定,定期服用磺胺多辛-乙胺嘧啶(SP)有助于减少这些问题。然而,频繁服用这些药物可能会导致 SP 药物压力,从而导致寄生虫对药物产生耐药性。为了确定这种现象并为利益相关者提供建议,本研究确定了某些被确认为寄生虫对 SP 耐药性标志物的“材料”的流行率。令人震惊的是,在招募参与这项研究的所有女性中,超过 5%的人被发现携带引起疟疾的寄生虫。研究结果还表明,存在高水平的携带耐药性材料的恶性疟原虫。决策者必须关注这些观察结果,并采取措施避免情况恶化。

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