ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India.
Department of Dermatology and STD, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India.
Microbiol Spectr. 2024 Jun 4;12(6):e0402623. doi: 10.1128/spectrum.04026-23. Epub 2024 May 7.
UNLABELLED: Post-kala-azar dermal leishmaniasis (PKDL) patients are a key source of parasites, hindering the goal of eliminating visceral leishmaniasis (VL). Monitoring treatment response and parasite susceptibility is essential due to increasing drug resistance. We assessed the drug susceptibility of PKDL isolates ( = 18) from pre-miltefosine (MIL) era (1997-2004) with isolates ( = 16) from the post-miltefosine era (2010-2019) and post-miltefosine treatment relapse isolates ( = 5) towards miltefosine and amphotericin B (AmB) at promastigote stage and towards sodium antimony gluconate (SAG) at amastigote stage. PKDL isolates were examined for mutation in gene-encoding AQP1 transporter, C26882T mutation on chromosome 24, and miltefosine-transporter (MT). PKDL isolates from the post-miltefosine era were significantly more susceptible to SAG than SAG-resistant isolates from the pre-miltefosine era ( = 0.0002). There was no significant difference in the susceptibility of parasites to miltefosine between pre- and post-miltefosine era isolates. The susceptibility of PKDL isolates towards AmB remained unchanged between the pre- and post-miltefosine era. However, the post-miltefosine era isolates had a higher IC value towards AmB compared with PKDL relapse isolates. We did not find any association between AQP1 gene sequence variation and susceptibility to SAG, or between miltefosine susceptibility and single nucleotide polymorphisms (SNPs in the MT gene. This study demonstrates that recent isolates of have resumed susceptibility to antimonials . The study also offers significant insights into the intrinsic drug susceptibility of parasites over the past two decades, covering the period before the introduction of miltefosine and after its extensive use. IMPORTANCE: Post-kala-azar dermal leishmaniasis (PKDL) patients, a key source of parasites, hinder eliminating visceral-leishmaniasis. Assessment of the susceptibility of PKDL isolates to antimony, miltefosine (MIL), and amphotericin-B indicated that recent isolates remain susceptible to antimony, enabling its use with other drugs for treating PKDL.
未标注：痘后皮肤利什曼病（PKDL）患者是寄生虫的主要来源，阻碍了消除内脏利什曼病（VL）的目标。由于耐药性的增加，监测治疗反应和寄生虫敏感性至关重要。我们评估了米替福新（MIL）前时代（1997-2004 年）的 PKDL 分离株（= 18）和米替福新后时代（2010-2019 年）的分离株（= 16）以及米替福新治疗后复发分离株（= 5）对米替福新和两性霉素 B（AmB）在前鞭毛体阶段和对葡萄糖酸锑钠（SAG）在无鞭毛体阶段的药物敏感性。检测了 PKDL 分离株中编码 AQP1 转运蛋白的基因、24 号染色体上的 C26882T 突变以及米替福新转运蛋白（MT）的突变。米替福新后时代的 PKDL 分离株对 SAG 的敏感性明显高于米替福新前时代的 SAG 耐药分离株（= 0.0002）。米替福新前时代和后时代分离株对米替福新的敏感性无显著差异。PKDL 分离株对 AmB 的敏感性在前米替福新时代和后米替福新时代之间保持不变。然而，米替福新后时代的分离株对 AmB 的 IC 值高于 PKDL 复发分离株。我们没有发现 AQP1 基因序列变异与 SAG 敏感性之间或米替福新敏感性与 MT 基因中单核苷酸多态性（SNPs）之间的任何关联。这项研究表明，最近的 分离株恢复了对锑的敏感性。该研究还为过去二十年内在引入米替福新之前和之后期间 寄生虫固有药物敏感性提供了重要见解。
重要性：痘后皮肤利什曼病（PKDL）患者是寄生虫的主要来源，阻碍了消除内脏利什曼病（VL）。对 PKDL 分离株对抗锑、米替福新（MIL）和两性霉素 B 的敏感性评估表明，最近的分离株仍然对锑敏感，这使得它可以与其他药物一起用于治疗 PKDL。
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