Volume 18, Number 4—April 2012
Letter
Leishmania Resistance to Miltefosine Associated with Genetic Marker
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.