Natural resistance of leishmania infantum to miltefosine contributes to the low efficacy in the treatment of visceral leishmaniasis in Brazil

Authors: Carnielli JBT, Monti-Rocha R, Costa DL, Molina Sesana A, Pansini LNN, Segatto M, Mottram JC, Costa CHN, Carvalho SFG, Dietze R
Publication Year: 2019
Journal: The American Journal of Tropical Medicine and Hygiene
Link: https://www.ncbi.nlm.nih.gov/pubmed/31436148

In India, visceral leishmaniasis (VL) caused by Leishmania donovani has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine against Brazilian VL, which is caused by Leishmania infantum, a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (aged 2-12 years) and adolescent-adults […]
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A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis

Authors: Carnielli JBT, Crouch K, Forrester S, Silva VC, Carvalho SFG, Damasceno JD, Brown E, Dickens NJ, Costa DL, Costa CHN, Dietze R, Jeffares DC, Mottram JC
Publication Year: 2018
Journal: EBioMedicine
Link: https://www.ncbi.nlm.nih.gov/pubmed/30268832

BACKGROUND: Miltefosine has been used successfully to treat visceral leishmaniasis (VL) in India, but it was unsuccessful for VL in a clinical trial in Brazil. METHODS: To 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 […]
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Identification and functional characterization of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

Authors: Benz C, Burchmore R, Costa CIA, Forkert A, Hamilton A, Hammarton TC, Monnerat S, Mottram JC, Novo C, Tetley L
Publication Year: 2013
Journal: PLoS One
Link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067327

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo.
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Natural resistance of leishmania infantum to miltefosine contributes to the low efficacy in the treatment of visceral leishmaniasis in Brazil

A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis

Identification and functional characterization of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

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