Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain

ABSTRACT Leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug...

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Autores principales:	Keshav Rai, Bart Cuypers, Narayan Raj Bhattarai, Surendra Uranw, Maya Berg, Bart Ostyn, Jean-Claude Dujardin, Suman Rijal, Manu Vanaerschot
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0acc5575c4354d92b00579755b729bc4
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spelling	oai:doaj.org-article:0acc5575c4354d92b00579755b729bc42021-11-15T15:42:48ZRelapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain10.1128/mBio.00611-132150-7511https://doaj.org/article/0acc5575c4354d92b00579755b729bc42013-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00611-13https://doaj.org/toc/2150-7511ABSTRACT Leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian subcontinent. This relapse rate of up to 20% within 12 months after treatment was shown not to be related to reinfection, drug quality, drug exposure, or drug-resistant parasites. We therefore aimed to assess other phenotypes of the parasite that may affect treatment outcome and found a significant association between the number of metacyclic parasites, parasite infectivity, and patient treatment outcome in the Indian subcontinent. Together with previous studies on resistance of L. donovani against pentavalent antimonials, these data suggest that the infectivity of the parasite, or related phenotypes, might be a more determinant factor for treatment failure in visceral leishmaniasis than drug susceptibility, warranting a reassessment of our current view on treatment failure and drug resistance in leishmaniasis and beyond. IMPORTANCE The high miltefosine relapse rate poses a major challenge for the current Kala-Azar Elimination Program in the Indian subcontinent and other leishmaniasis control programs worldwide. This relapse rate could not be related to reinfection, drug-resistant parasites, or reduced treatment quality. Here we report that an increased infectivity of the parasite is associated with miltefosine relapse of visceral leishmaniasis (VL) patients. These results supplement those obtained with antimonial-resistant L. donovani where an increased infectivity was also observed. This challenges the current view of Leishmania drug susceptibility being the biggest parasitic factor that contributes to treatment failure in leishmaniasis. These selected more infectious parasites may pose an additional burden to leishmaniasis control programs, highlighting the importance of multifaceted control measures to achieve leishmaniasis elimination in the Indian subcontinent and other regions where leishmaniasis is endemic.Keshav RaiBart CuypersNarayan Raj BhattaraiSurendra UranwMaya BergBart OstynJean-Claude DujardinSuman RijalManu VanaerschotAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 5 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Keshav Rai Bart Cuypers Narayan Raj Bhattarai Surendra Uranw Maya Berg Bart Ostyn Jean-Claude Dujardin Suman Rijal Manu Vanaerschot Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
description	ABSTRACT Leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian subcontinent. This relapse rate of up to 20% within 12 months after treatment was shown not to be related to reinfection, drug quality, drug exposure, or drug-resistant parasites. We therefore aimed to assess other phenotypes of the parasite that may affect treatment outcome and found a significant association between the number of metacyclic parasites, parasite infectivity, and patient treatment outcome in the Indian subcontinent. Together with previous studies on resistance of L. donovani against pentavalent antimonials, these data suggest that the infectivity of the parasite, or related phenotypes, might be a more determinant factor for treatment failure in visceral leishmaniasis than drug susceptibility, warranting a reassessment of our current view on treatment failure and drug resistance in leishmaniasis and beyond. IMPORTANCE The high miltefosine relapse rate poses a major challenge for the current Kala-Azar Elimination Program in the Indian subcontinent and other leishmaniasis control programs worldwide. This relapse rate could not be related to reinfection, drug-resistant parasites, or reduced treatment quality. Here we report that an increased infectivity of the parasite is associated with miltefosine relapse of visceral leishmaniasis (VL) patients. These results supplement those obtained with antimonial-resistant L. donovani where an increased infectivity was also observed. This challenges the current view of Leishmania drug susceptibility being the biggest parasitic factor that contributes to treatment failure in leishmaniasis. These selected more infectious parasites may pose an additional burden to leishmaniasis control programs, highlighting the importance of multifaceted control measures to achieve leishmaniasis elimination in the Indian subcontinent and other regions where leishmaniasis is endemic.
format	article
author	Keshav Rai Bart Cuypers Narayan Raj Bhattarai Surendra Uranw Maya Berg Bart Ostyn Jean-Claude Dujardin Suman Rijal Manu Vanaerschot
author_facet	Keshav Rai Bart Cuypers Narayan Raj Bhattarai Surendra Uranw Maya Berg Bart Ostyn Jean-Claude Dujardin Suman Rijal Manu Vanaerschot
author_sort	Keshav Rai
title	Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
title_short	Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
title_full	Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
title_fullStr	Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
title_full_unstemmed	Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain
title_sort	relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting <named-content content-type="genus-species">leishmania donovani</named-content> strain
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0acc5575c4354d92b00579755b729bc4
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Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting <named-content content-type="genus-species">Leishmania donovani</named-content> Strain

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