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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2013-11-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00611-13 |
| _version_ | 1818838986813079552 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:47:07Z |
| format | Article |
| id | doaj.art-0acc5575c4354d92b00579755b729bc4 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T03:47:07Z |
| publishDate | 2013-11-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-0acc5575c4354d92b00579755b729bc42022-12-21T20:37:06ZengAmerican Society for MicrobiologymBio2150-75112013-11-014510.1128/mBio.00611-13Relapse 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> StrainKeshav Rai0Bart Cuypers1Narayan Raj Bhattarai2Surendra Uranw3Maya Berg4Bart Ostyn5Jean-Claude Dujardin6Suman Rijal7Manu Vanaerschot8Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumMolecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumDepartment of Microbiology, B. P. Koirala Institute of Health Sciences, Dharan, NepalDepartment of Microbiology, B. P. Koirala Institute of Health Sciences, Dharan, NepalMolecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumEpidemiology and Disease Control Unit, Department of Public Health, Institute of Tropical Medicine, Antwerp, BelgiumMolecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumDepartment of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, NepalMolecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.00611-13 |
| spellingShingle | 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 mBio |
| 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_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_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_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 |
| url | https://journals.asm.org/doi/10.1128/mBio.00611-13 |
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