Monitoring the Long-Term Effectiveness of Miltefosine in Indian Post-Kala-Azar Dermal Leishmaniasis
Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and nodules (polymorphic). Post-kala-azar dermal leishmaniasis plays a significant role in disease transmission, emphasizing the need for m...
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Published in | The American journal of tropical medicine and hygiene Vol. 110; no. 4; pp. 656 - 662 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
The American Society of Tropical Medicine and Hygiene
03.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and nodules (polymorphic). Post-kala-azar dermal leishmaniasis plays a significant role in disease transmission, emphasizing the need for monitoring chemotherapeutic effectiveness. Accordingly, this study aimed to quantify the parasite burden in PKDL patients after treatment with miltefosine by a quantitative polymerase chain reaction (qPCR). A Leishmania kinetoplastid gene-targeted qPCR was undertaken using DNA from skin biopsy specimens of patients with PKDL at three time points, i.e., at disease presentation (week 0, n = 157, group 1), upon completion of treatment (week 12, n = 39, group 2), and at any time point 6 months after completion of treatment (week ≥36, n = 54, group 3). A cycle threshold (Ct) <30 was considered the cutoff for positivity, and load was quantified as the number of parasites/µg genomic DNA (gDNA); cure was considered when samples had a Ct >30. The parasite load at disease presentation (group 1) was 10,769 (1,339-80,441)/µg gDNA (median [interquartile range]). In groups 2 and 3, qPCR results were negative in 35/39 cases (89.7%) and 48/54 cases (88.8%), respectively. In the 10/93 (10.8%) qPCR-positive cases, the parasite burdens in groups 2 and 3 were 2,420 (1,205-5,661)/µg gDNA and 22,195 (5,524-100,106)/µg gDNA, respectively. Serial monitoring was undertaken in 45 randomly selected cases that had completed treatment; all cases in groups 2 or 3 had a Ct >30, indicating cure. Overall, qPCR confirmed an 89.2% cure (as 83/93 cases showed parasite clearance), and the persistent qPCR positivity was attributed to nonadherence to treatment or unresponsiveness to miltefosine and remains to be investigated. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Financial support: Support was received from the WHO (registration number 2021/1141038-0); the Indian Council of Medical Research (number 6/9-7[151]2017-ECD II); the Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions (FIST) Program, Department of Science and Technology, Government of India (DST-FIST, SR/FST/LS1-663/2016); and the Department of Science and Technology, Government of West Bengal (969[Sanc.]ST/P/S&T/9G-22/2016). M. Chatterjee is a recipient of a JC Bose Fellowship (JCB/2019/000043), Science Engineering & Research Board, DST, Government of India. Authors’ addresses: Sutopa Roy, Srija Moulik, Madhurima Roy, and Mitali Chatterjee, Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India, E-mails: roy716sutopa@gmail.com, srijamoulik11@gmail.com, madsroy296@gmail.com, and ilatimc@gmail.com. Manab K. Ghosh, Department of Tropical Medicine, School of Tropical Medicine, Kolkata, India, E-mail: drmanabkumarghosh@gmail.com. Surya Jyati Chaudhuri, Department of Microbiology, Sarat Chandra Chattopadhyay Government Medical College and Hospital, Howrah, India, E-mail: drsurya85@rediffmail.com. Dhruv K. Pandey, Kala-Azar Elimination Programme, World Health Organization Country Office, New Delhi, India, E-mail: pandeyd@who.int. Saurabh Jain and Daniel Argaw Dagne, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland, E-mails: jainsau@who.int and daniel@who.int Disclosures: We certify that we have obtained all appropriate patient consent forms, where the patients have consented to the use of their images and all other clinical information reported in this journal. The patients understand that names or initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Ethical clearance was obtained from the Institutional Ethics Committee (IEC) of the Institute of Post-Graduate Medical Education and Research (Kolkata, India). Necessary permissions for the field study were obtained from the Central Directorate of the National Center for Vector Borne Disease Control, Ministry of Health & Family Welfare, and from the Department of Health & Family Welfare, Government of West Bengal. Informed written consent was taken from all patients enrolled, from either the patient or the legally accepted representative. Approval was obtained from the IEC for recruitment of new cases and repurposing of archived samples collected during field visits. |
ISSN: | 0002-9637 1476-1645 |
DOI: | 10.4269/ajtmh.23-0197 |