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Volume 18, Number 4—April 2012
Letter

Leishmania Resistance to Miltefosine Associated with Genetic Marker

Sandrine CojeanComments to Author , Sandrine Houzé, Djamel Haouchine, Françoise Huteau, Sylvie Lariven, Véronique Hubert, Florence Michard, Christian Bories, Francine Pratlong, Jacques Le Bras, Philippe Marie Loiseau, and Sophie Matheron
Author affiliations: University of Paris-Sud, Châtenay-Malabry, France (S. Cojean, F. Huteau, C. Bories, P.M. Loiseau); Paris Descartes University, Paris, France (S. Houzé, D. Haouchine, V. Hubert, J. Le Bras); Paris Diderot University, Paris (S. Lariven, F. Michard, S. Matheron); Montpellier University, Montpellier, France (F. Pratlong)

Main Article

Table

Comparions of IC50 for AmpB and miltefosine against promastigotes and axenic amastigotes and distribution of LdMT SNPs in Leishmania infantum isolates and reference strains*

Isolate Year AmpB Miltefosine IC50, µmol/L ± SEM
 Ldmt SNP
AmpB
Miltefosine
Promastigotes Axenic amastigotes Promastigotes Axenic amastigotes
– 1998 3 mg/kg/d × 5 d; then 1×/wk × 5 wk – – – – – –
S1 2000 3 mg/kg/d × 5 d; then 1×/wk × 5 wk – 0.09 ± 0.04† 0.10 ± 0.03 7.14 ± 0.56† 5.00± ± 0.7† L832
– 2001 4 mg/kg/d × 5 d; then 1×/wk × 5 wk 50 mg 2×/d – – – – –
S3 2005 4 mg/kg/d × 5 d; then 1×/wk × 5 wk‡ 0.13 ± 0.03 0.20 ± 0.03 25.93 ± 1.46† 21.00 ± 1.50† 832L/F
S4 0.24 ± 0.01† 0.15 ± 0.02 27.89 ± 1.76† 31.90 ± 1.60†
– 2007 4 mg/kg/d × 5 d; then 1×/wk × 5 wk – – – – –
S6 2008 4 mg/kg/d × 5 d; then 1×/wk × 5 wk – 0.16 ± 0.03 0.11 ± 0.03 44.30 ± 3.70† 50.10 ± 1.00† 832F
S7 2010 4 mg/kg/d × 5 d; then 1×/wk × 5 wk – – – – – L832
Reference strain
LV9 WT 0.03 ± 0.02 0.02 ± 0.05 4.46 ± 0.29† 6.20 ± 0.3 L832
LV9 Miltefosine-R 0.22 ± 0.04 0.70 ± 0.09 45.84 ± 2.40† 54.20 ± 2.20† 832F
DD8 WT 0.06 ± 0.02† 0.05 ± 0.03† 17.40 ± 1.70 12.40 ± 1.50 L832
DD8 AmpB-R 1.42 ± 0.06† 1.00 ± 0.07† 15.20 ± 1.00 10.30 ± 1.20 L832

*IC50, 50% inhibitory concentration; AmpB, amphotericin B; Ldmt, Leishmania donovani miltefosine transporter gene; SNP, single-nucleotide polymorphism; –, assay not performed because sample unavailable or not culturable; WT, wild type; R, resistant.
†Significance was analyzed by using the nonparametric Mann-Whitney U test to compare the IC50 of the isolates with the IC50 of reference strains; p<0.01 was considered significant. IC50 of AmpB and miltefosine was compared with IC50 of reference strains and S1/S3, S1/S4, and S1/S6. Miltefosine: S1/S3, S1/S4, S1/S6, S4/S6; p<0.01. AmpB: S1/S4 significant p<0.01; S1/S3, S1/S6 not significant.
‡For each relapse.

Main Article

Page created: March 16, 2012
Page updated: March 16, 2012
Page reviewed: March 16, 2012
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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