Increasing Failure of Miltefosine in the Treatment of Kala-azar in Nepal and the Potential Role of Parasite Drug Resistance, Reinfection, or Noncompliance
Suman Rijal,Bart Ostyn,Surendra Uranw,Surendra Uranw,Keshav Rai,Narayan Raj Bhattarai,Thomas P. C. Dorlo,Thomas P. C. Dorlo,Jos H. Beijnen,Manu Vanaerschot,Saskia Decuypere,S. S. Dhakal,Murari Lal Das,Prahlad Karki,Rupa Singh,Marleen Boelaert,Jean-Claude Dujardin,Jean-Claude Dujardin +17 more
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TLDR
Relapse in one-fifth of the MIL-treated patients observed in this study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.Abstract:
Background. Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. Methods. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. Results. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2−99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2−16.4) and 20.0% (95% CI, 12.8−27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Conclusions. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.read more
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Drug resistance and treatment failure in leishmaniasis: A 21st century challenge
Alicia Ponte-Sucre,Francisco Gamarro,Jean-Claude Dujardin,Michael P. Barrett,Rogelio López-Vélez,Raquel García-Hernández,Andrew W. Pountain,Roy Mwenechanya,Barbara Papadopoulou +8 more
TL;DR: The meaning of “resistance” related to leishmaniasis and its molecular epidemiology are discussed, particularly for Leishmania donovani that causes visceral leish maniasis, and how resistance can affect drug combination therapies are discussed.
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Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)
Naomi E. Aronson,Barbara L. Herwaldt,Michael Libman,Richard D. Pearson,Rogelio López-Vélez,Peter J. Weina,Edgar M. Carvalho,Moshe Ephros,Selma M. B. Jeronimo,Alan J. Magill +9 more
TL;DR: It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients, and that adherence to these guidelines to be voluntary.
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An Update on Pharmacotherapy for Leishmaniasis
Shyam Sundar,Jaya Chakravarty +1 more
TL;DR: There is an urgent need to implement a single-dose L-AmB or combination therapy in the Indian subcontinent for the treatment of post – kala-azar dermal leishmaniasis.
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Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)*
Naomi E. Aronson,Barbara L. Herwaldt,Michael Libman,Richard D. Pearson,Rogelio López-Vélez,Peter J. Weina,Edgar M. Carvalho,Moshe Ephros,Selma M. B. Jeronimo,Alan J. Magill +9 more
TL;DR: This research presents a novel and scalable approach called “informed consent” that allows for real-time decision-making in the management of infectious disease outbreaks in the rapidly changing environment.
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Chemotherapy of leishmaniasis: present challenges
TL;DR: It is clear that efforts for discovering new drugs applicable to leishmaniasis chemotherapy are essential, and the main aspects on the various steps of drug discovery in the field are discussed.
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Jorge Alvar,Iván D. Vélez,Iván D. Vélez,Caryn Bern,Mercè Herrero,Philippe Desjeux,Jorge Cano,Jean Jannin,Margriet den Boer +8 more
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TL;DR: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis and may also be helpful in regions where parasites are resistant to current agents.
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Failure of Pentavalent Antimony in Visceral Leishmaniasis in India: Report from the Center of the Indian Epidemic
Shyam Sundar,Deepak K. More,Manoj Kumar Singh,Vijay P. Singh,Sashi Sharma,Anand Makharia,Prasanna C. K. Kumar,Henry W. Murray +7 more
TL;DR: In India, 320 patients with visceral leishmaniasis received identical pentavalent antimony (Sb) treatment, and Sb induced long-term cure in 35% of those in Bihar versus 86% (95% CI, 79%-93%) of Those in Uttar Pradesh.
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Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance
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Single-Dose Liposomal Amphotericin B for Visceral Leishmaniasis in India
TL;DR: A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphoteric in B deoxycholate, and Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group.