ArticleEBioMedicine2018
A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 78 citations in OpenAlex.
- Natural Resistance ofThe American journal of tropical medicine and hygiene · 2019Trial
- Baseline of miltefosine resistance markers in zoonoticOne health (Amsterdam, Netherlands) · 2026Article
- Whole genome sequencing reveals genomic diversity and evidence of hybridization in MoroccanFrontiers in cellular and infection microbiology · 2026Article
- Next-generation molecular tools in veterinary parasitology: advances, challenges, and perspectives in the diagnosis of emerging parasites.Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria · 2026Review
- Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area.Parasites & vectors · 2025Article
- Immunotherapeutics Combining a Recombinant Chimeric Protein, Monophosphoryl Lipid A, and Miltefosine Against Visceral Leishmaniasis.Pathogens (Basel, Switzerland) · 2025Article
- Investigating the impact of HIS-1 and HSP-70 genes on drug response and pathology of Leishmania major using antisense oligonucleotides.Antonie van Leeuwenhoek · 2025Article
- Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B.Scientific reports · 2025Article
- Gene deletion as a possible strategy adopted by New World Leishmania infantum to maximize geographic dispersion.PLoS pathogens · 2025Article
- Spatial prediction of canine visceral leishmaniasis in an endemic urban area of Brazil.PloS one · 2025Article
- Understanding the genetic complexity of Leishmania infantum in the Americas: a focus on 3'NT/NU gene deletion.Memorias do Instituto Oswaldo Cruz · 2025Review
- Synthetic Peptides Selected by Immunoinformatics as Potential Tools for the Specific Diagnosis of Canine Visceral Leishmaniasis.Microorganisms · 2024Article
- Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.Genome research · 2024Article
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol.Tropical medicine and infectious disease · 2023Article
- Systematic Review of Treatment Failure and Clinical Relapses in Leishmaniasis from a Multifactorial Perspective: Clinical Aspects, Factors Associated with the Parasite and Host.Tropical medicine and infectious disease · 2023Review
- Article
- Fatty Acid Composition and Metabolism inInternational journal of molecular sciences · 2023Review
- A difficult to treatIDCases · 2023Article
- Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundMiltefosine has been used successfully to treat visceral leishmaniasis (VL) in India, but it was unsuccessful for VL in a clinical trial in Brazil.
methodsTo identify molecular markers that predict VL treatment failure whole genome sequencing of 26 L. infantum isolates, from cured and relapsed patients allowed a GWAS analysis of SNPs, gene and chromosome copy number variations.
findingsA strong association was identified (p = 0·0005) between the presence of a genetically stable L. infantumMiltefosine Sensitivity Locus (MSL), and a positive response to miltefosine treatment. The risk of treatment failure increased 9·4-fold (95% CI 2·11-53·54) when an isolate did not have the MSL. The complete absence of the MSL predicted miltefosine failure with 0·92 (95% CI 0·65-0·996) sensitivity and 0·78 (95% CI 0·52-0·92) specificity. A genotyping survey of L. infantum (n = 157) showed that the frequency of MSL varies in a cline from 95% in North East Brazil to <5% in the South East. The MSL was found in the genomes of all L. infantum and L. donovani sequenced isolates from the Old World (n = 671), where miltefosine can have a cure rate higher than 93%.
interpretationKnowledge on the presence or absence of the MSL in L. infantum will allow stratification of patients prior to treatment, helping to establish better therapeutic strategies for VL treatment. FUND: CNPq, FAPES, GCRF MRC and Wellcome Trust.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.