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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)

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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.

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