Affiliation:
1. ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India
2. Department of Dermatology and STD, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India
Abstract
ABSTRACT
Post-kala-azar dermal leishmaniasis (PKDL) patients are a key source of
Leishmania donovani
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 (
n
= 18) from pre-miltefosine (MIL) era (1997–2004) with isolates (
n
= 16) from the post-miltefosine era (2010–2019) and post-miltefosine treatment relapse isolates (
n
= 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 (
P
= 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
50
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
Leishmania
have resumed susceptibility to antimonials
in vitro
. The study also offers significant insights into the intrinsic drug susceptibility of
Leishmania
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
Leishmania donovani
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.
Funder
Indian Council of Medical Research
Publisher
American Society for Microbiology