Table 1.
Identification | Promastigotes | Amastigotes | MSL | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Miltefosine (mM) |
Amphotericin B (nM) |
Miltefosine (mM) |
Infectivity g | ||||||||
Species a | International Code b | IOCL# c | State d | EC50 ± SEM e | AI f | EC50 ± SEM e | AI f | EC50 ± SEM e | AI f | % | Presence/ Absense h |
L. donovani | LD-15/MHOM/SD/00 | NA | NA | 9.00 ± 0.82 | 0.82 | 35.0 ± 0.5 | NA | NA | |||
L. infantum | MHOM/BR/2005/NLC | IOCL3241 | MG | 10.98 ± 1.95 | 1.00 | 51.0 ± 5.0 | NA | 1.79 ± 0.42 | NP | 50% | NA |
L. infantum | MHOM/BR/2009/BLVD | IOCL 3118 | AM | 7.07 ± 1.63 | 0.64 | 58.0 ± 1.0 | 1.14 | MSL- | |||
L. infantum | MHOM/BR/2006/NMT-HUB402982MO | IOCL 2898 | DF | 15.61 ± 0.74 | 1.42 | 53.0 ± 6.0 | 1.04 | MSL- | |||
L. infantum | MHOM/BR/2005/DRD | IOCL 2788 | ES | 10.95 ± 1.12 | 1.0 | 66.0 ± 4.0 | 1.29 | MSL- | |||
L. infantum | MHOM/BR/2005/HRNS-1 | IOCL 2789 | ES | 8.17 ± 1.04 | 0.74 | 62.0 ± 3.0 | 1.22 | 4.23 ± 0.53 | 2.36 | 66% | MSL- |
L. infantum | MCAN/BR/2008/CP-18 | IOCL 3068 | ES | 17.41 ± 1.77 | 1.59 | 70.0 ± 0.0 | 1.37 | 3.68 ± 0.05 | 2.06 | 39% | MSL- |
L. infantum | MHOM/BR/2005/804-NMV | IOCL 2943 | MA | 9.30 ± 0.40 | 0.85 | 48.0 ± 7.0 | 0.94 | NA | |||
L. infantum | MHOM/BR/2006/890 | IOCL 3694 | MA | 5.89 ± 0.11 | 0.54 | 50.0 ± 2.0 | 0.98 | MSL+ | |||
L. infantum | MHOM/BR/2006/6889 | IOCL 3696 | MA | 11.24 ± 1.08 | 1.02 | 35.0 ± 4.0 | 0.69 | MSL+ | |||
L. infantum | MHOM/BR/2006/6905 | IOCL 3699 | MA | 23.65 ± 1.21 | 2.15 | 27.0 ± 6.0 | 0.53 | 3.05 ± 0.39 | 1.70 | 51% | MSL+ |
L. infantum | MHOM/BR/2006/MA07A 4P TMS | IOCL 3706 | MA | 9.85 ± 1.19 | 0.9 | 25.0 ± 3.0 | 0.49 | NA | |||
L. infantum | MHOM/BR/2005/841RVSS | IOCL 2977 | MA | 13.71 ± 1.43 | 1.25 | 31.0 ± 0.1 | 0.61 | NA | |||
L. infantum | MHOM/BR/2007/1724FRS | IOCL 2978 | MA | 16.95 ± 1.14 | 1.54 | 34.0 ± 9.0 | 0.67 | 3.54 ± 1.03 | 1.98 | 64% | NA |
L. infantum | MHOM/BR/2007/1728JLM | IOCL 2979 | MA | 13.29 ± 0.88 | 1.21 | 30.0 ± 8.0 | 0.59 | NA | |||
L. infantum | MHOM/BR/2007/1735TAS | IOCL 2981 | MA | 12.89 ± 1.46 | 1.17 | 27.0 ± 5.0 | 0.53 | NA | |||
L. infantum | MHOM/BR/2006/P112A 4P NMV | IOCL 3682 | MA | 19.68 ± 1.39 | 1.79 | 20.0 ± 2.0 | 0.39 | MSL+ | |||
L. infantum | MHOM/BR/2006/MA03-A 4P (GMS) | IOCL 3685 | MA | 23.70 ± 0.78 | 2.16 | 30.0 ± 1.0 | 0.59 | 3.77 ± 0.01 | 2.10 | 50% | MSL+ |
L. infantum | MHOM/BR/2002/LPC-RPV | IOCL 2906 | MG | 8.15 ± 1.29 | 0.74 | 43.0 ± 16.0 | 0.84 | MSL- | |||
L. infantum | MHOM/BR/2011/AD1 | IOCL 3368 | MG | 11.07 ± 1.50 | 1.01 | 28.0 ± 2.0 | 0.55 | MSL- | |||
L. infantum | MHOM/BR/2011/CR1 | IOCL 3370 | MG | 7.30 ± 1.40 | 0.66 | 63.0 ± 1.0 | 1.24 | MSL- | |||
L. infantum | MHOM/BR/2012/AD5 | IOCL 3383 | MG | 14.29 ± 0.91 | 1.3 | 53.0 ± 5.0 | 1.04 | NA | |||
L. infantum | MHOM/BR/2012/AD7 | IOCL 3385 | MG | 7.51 ± 0.91 | 0.68 | 39.0 ± 14.0 | 0.76 | NA | |||
L. infantum | MHOM/BR/2012/CR2 | IOCL 3386 | MG | 9.45 ± 0.97 | 0.86 | 64.0 ± 8.0 | 1.25 | NA | |||
L. infantum | MCAN/BR/2010/CA1 | IOCL 3378 | MG | 20.72 ± 1.90 | 1.89 | 41.0 ± 11.0 | 0.8 | MSL- | |||
L. infantum | MCAN/BR/2010/CA2 | IOCL 3379 | MG | 12.64 ± 1.30 | 1.15 | 30.0 ± 2.0 | 0.59 | 4.57 ± 1.09 | 2.55 | 52% | MSL- |
L. infantum | MCAN/BR/2002/LVV-137 | IOCL 2666 | MS | 9.82 ± 0.34 | 0.89 | 51.0 ± 3.0 | 1.00 | MSL+ | |||
L. infantum | MCAN/BR/2010/MEG | IOCL 3214 | MS | 7.10 ± 0.54 | 0.65 | 62.0 ± 7.0 | 1.22 | MSL- | |||
L. infantum | MCAN/BR/2002/LVV-136 | IOCL 2665 | MS | 16.26 ± 1.36 | 1.48 | 26.0 ± 3.0 | 0.51 | MSL+ | |||
L. infantum | MHOM/BR/2009/202 | IOCL 3140 | MT | 7.73 ± 1.32 | 0.7 | 51.0 ± 13.0 | 1.00 | NA | |||
L. infantum | MCAN/BR/2009/GRANDÃO I | IOCL 3134 | MT | 9.31 ± 0.09 | 0.85 | 56.0 ± 8.0 | 1.10 | NA | |||
L. infantum | MCAN/BR/2009/GRANDÃO II | IOCL 3135 | MT | 11.46 ± 0.98 | 1.04 | 46.0 ± 4.0 | 0.90 | NA | |||
L. infantum | MCAN/BR/2009/SOL | IOCL 3137 | MT | 9.79 ± 0.43 | 0.89 | 47.0 ± 3.0 | 0.92 | NA | |||
L. infantum | MHOM/BR/2006/791 | IOCL 3698 | PA | 12.37 ± 1.70 | 1.13 | 35.0 ± 6.0 | 0.69 | MSL- | |||
L. infantum | MHOM/BR/2008/RJS | IOCL 3053 | PE | 14.35 ± 0.39 | 1.31 | 60.0 ± 6.0 | 1.18 | MSL- | |||
L. infantum | MHOM/BR/2005/742EMS | IOCL 2972 | PI | 23.45 ± 1.06 | 2.14 | 41.0 ± 5.0 | 0.80 | MSL+ | |||
L. infantum | MHOM/BR/2006/1406MBS | IOCL 2976 | PI | 7.73 ± 1.16 | 0.7 | 49.0 ± 1.0 | 0.96 | 3.27 ± 0.01 | 1.83 | 46% | MSL- |
L. infantum | MHOM/BR/2005/867-JNS | IOCL 2944 | PI | 7.59 ± 0.84 | 0.69 | 53.0 ± 6.0 | 1.04 | NA | |||
L. infantum | MHOM/BR/2005/792FFS | IOCL 2973 | PI | 14.47 ± 1.36 | 1.32 | 68.0 ± 11.0 | 1.33 | NA | |||
L. infantum | MHOM/BR/2006/891 | IOCL 3692 | PI | 6.73 ± 1.42 | 0.61 | 36.0 ± 5.0 | 0.71 | MSL+ | |||
L. infantum | MHOM/BR/2006/930 | IOCL 3693 | PI | 12.03 ± 1.08 | 1.1 | 62.0 ± 21.0 | 1.22 | MSL+ | |||
L. infantum | MHOM/BR/2006/P109A 4P JAS | IOCL 3688 | PI | 8.03 ± 0.42 | 0.73 | 35.0 ± 6.0 | 0.69 | MSL+ | |||
L. infantum | MHOM/BR/2006/867 | IOCL 3695 | PI | 8.45 ± 0.84 | 0.77 | 34.0 ± 8.0 | 0.67 | MSL- | |||
L. infantum | MHOM/BR/2006/6893 | IOCL 3697 | PI | 8.41 ± 1.21 | 0.77 | 37.0 ± 7.0 | 0.73 | 3.41 ± 0.75 | 1.91 | 69% | MSL+ |
L. infantum | MHOM/BR/2006/6914 | IOCL 3700 | PI | 9.76 ± 1.58 | 0.89 | 38.0 ± 3.0 | 0.75 | MSL+ | |||
L. infantum | MHOM/BR/2006/AAS 3P | IOCL 3703 | PI | 22.06 ± 1.58 | 2.01 | 32.0 ± 8.0 | 0.63 | 4.04 ± 0.76 | 2.26 | 79% | MSL- |
L. infantum | MHOM/BR/2006/AAS 4P | IOCL 3704 | PI | 9.49 ± 1.88 | 0.86 | 33.0 ± 9.0 | 0.65 | MSL+ | |||
L. infantum | MHOM/BR/2006/Pi 11A 4P MBS | IOCL 3705 | PI | 10.51 ± 0.52 | 0.96 | 34.0 ± 12.0 | 0.67 | MSL- | |||
L. infantum | MHOM/BR/2007/1732EPG | IOCL 2980 | PI | 15.22 ± 0.68 | 1.39 | 32.0 ± 3.0 | 0.63 | NA | |||
L. infantum | MHOM/BR/2007/1739MSS | IOCL 2982 | PI | 13.37 ± 1.70 | 1.22 | 27.0 ± 0.0 | 0.53 | NA | |||
L. infantum | MHOM/BR/2006/6909 | IOCL 3680 | PI | 15.41 ± 0.80 | 1.4 | 29.0 ± 0.5 | 0.57 | 1.69 ± 0.56 | 0.94 | 36% | MSL+ |
L. infantum | MHOM/BR/2006/6912 | IOCL 3681 | PI | 13.34 ± 1.13 | 1.21 | 26.0 ± 4.0 | 0.51 | MSL+ | |||
L. infantum | MHOM/BR/2006/JSMG 3P | IOCL 3683 | PI | 11.26 ± 2.07 | 1.03 | 30.0 ± 1.0 | 0.59 | MSL+ | |||
L. infantum | MHOM/BR/2006/ARS 3P | IOCL 3684 | PI | 12.20 ± 1.37 | 1.11 | 27.0 ± 5.0 | 0.53 | MSL- | |||
L. infantum | MHOM/BR/2006/FFS 3P PI-05 | IOCL 3687 | PI | 20.45 ± 1.09 | 1.86 | 23.0 ± 1.0 | 0.45 | 3.09 ± 0.97 | 1.73 | 61% | MSL+ |
L. infantum | MHOM/BR/2006/RUSS-3P | IOCL 3701 | PI* | 16.04 ± 2.02 | 1.46 | 31.0 ± 4.0 | 0.61 | NA | |||
L. infantum | MHOM/BR/2006/Pi 04A 4P DHRi | IOCL 3702 | PI* | 8.25 ± 1.38 | 0.75 | 27.0 ± 5.0 | 0.53 | MSL+ | |||
L. infantum | MHOM/BR/2006/MA01-A 4P | IOCL 3707 | PI* | 9.46 ± 1.40 | 0.86 | 32.0 ± 6.0 | 0.63 | MSL+ | |||
L. infantum | MHOM/BR/2006/MA04A 4P JNN | IOCL 3686 | PI* | 16.20 ± 0.78 | 1.48 | 31.0 ± 2.0 | 0.61 | MSL- | |||
L. infantum | MCAN/BR/2015/TUBO9 | IOCL 3598 | RJ | 11.63 ± 0.48 | 1.06 | 34.0 ± 3.0 | 0.67 | MSL- | |||
L. infantum | MHOM/BR/2011/Diag 1367 | IOCL 3330 | RN | 8.24 ± 1.13 | 0.75 | 36.0 ± 2.0 | 0.71 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 03 | IOCL 3336 | RN | 6.56 ± 0.66 | 0.6 | 29.0 ± 0.0 | 0.57 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 18 | IOCL 3339 | RN | 6.37 ±0.29 | 0.58 | 38.0 ± 2.0 | 0.75 | 1.41 ± 0.50 | 0.79 | 70% | MSL- |
L. infantum | MHOM/BR/2011/TC 28 | IOCL 3340 | RN | 8.07 ± 1.24 | 0.73 | 56.0 ± 16.0 | 1.10 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 50 | IOCL 3341 | RN | 9.06 ±0.60 | 0.83 | 55.0 ± 4.0 | 1.08 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 65 | IOCL 3342 | RN | 9.75 ± 0.60 | 0.89 | 41.0 ± 1.0 | 0.8 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 95 | IOCL 3343 | RN | 9.86 ± 0.50 | 0.9 | 45.0 ± 6.0 | 0.88 | MSL- | |||
L. infantum | MHOM/BR/2011/TC 96 | IOCL 3344 | RN | 7.45 ± 0.62 | 0.68 | 56.0 ± 9.0 | 1.10 | NA | |||
L. infantum | MHOM/BR/2011/TC 98 | IOCL 3345 | RN | 8.53 ± 0.81 | 0.78 | 66.0 ± 6.0 | 1.29 | NA | |||
L. infantum | MHOM/BR/2011/TC 105 | IOCL 3346 | RN | 9.91 ± 0.76 | 0.9 | 43.0 ± 15.0 | 0.84 | NA | |||
L. infantum | MHOM/BR/2011/TC 115 | IOCL 3347 | RN | 7.35 ± 0.69 | 0.67 | 40.0 ± 3.0 | 0.78 | NA | |||
L. infantum | MHOM/BR/2011/TC 86 | IOCL 3388 | RN | 8.69 ± 0.21 | 0.79 | 69.0 ± 9.0 | 1.35 | NA | |||
L. infantum | MCAN/BR/2010/LUNA II | IOCL 3196 | RS | 10.88 ± 0.88 | 0.99 | 48.0 ± 2.0 | 0.94 | MSL- | |||
L. infantum | MCAN/BR/2011/IMTS-14 | IOCL 3257 | SP | 20.11 ± 1.52 | 1.83 | 40.0 ± 5.0 | 0.78 | MSL- | |||
L. infantum | MCAN/BR/2008/Lchagasi-UFRJ | IOCL 3324 | SP | 20.79 ± 0.82 | 1.89 | 46.0 ± 4.0 | 0.90 | 2.04 ± 0.46 | 1.14 | 89% | NA |
a Two Leishmania species, L. donovani and L. infantum were used in this study. b International Code for each isolate/strain used in this work. MHOM are isolates obtained from humans, MCAN are isolates from dogs. The strains from patients who participated in the Miltefosine clinical trial (IOCL 2943, IOCL 2944, IOCL 2973, IOCL 3692, IOCL 3693, IOCL 3694) are identified in bold. c Codes for Leishmania strains deposited in the Leishmania Collection at Fundação Oswaldo Cruz (CLIOC). d Brazilian State of origin of the isolates. AM = Amazonas; DF = Distrito Federal; ES = Espírito Santo; MA = Maranhão; MG = Minas Gerais; MS = Mato Grosso do Sul; MT = Mato Grosso; PA = Pará; PE = Pernambuco; PI = Piauí; RJ = Rio de Janeiro; RN = Rio Grande do Norte; RS = Rio Grande do Sul; SP = São Paulo. PI* Brazilian State of the institution that sent the isolates (State of origin of sample not confirmed). e EC50 ± SEM of miltefosine determined for promastigotes (in three independent experiments) and amastigotes (in two independent experiments) and of amphotericin B for promastigotes (also in two independent experiments). f Activity index was calculated by dividing the EC50 of each clinical isolate by the EC50 of the L. infantum reference strain NLC. NP = not applicable. g Mean percentage of infection obtained for each isolate/strain after 72 h of infection and in the absence of drug. h MSL = miltefosine sensitivity locus. MSL+ indicates the presence of the locus in homozygosis; MSL- absence of the referred locus in homozygosis; NA = not available. Data reported in Schwabl, et al. [24].