TABLE 1.
Clinical profiles of VL patients from LR and HR regions and in vitro susceptibility of parasite isolates to SAG, AmB, and MIL, with expression indices of MIL transporters LdMT and LdRos3
| Strain | Sex/age (yr)a | Area in India/region category or source and/or description | Treatment (response)b | Susceptibility (ED50 [μg/ml])c
|
Fold decrease in expressiond
|
|||||
|---|---|---|---|---|---|---|---|---|---|---|
| SAG (Amas) | AmB
|
MIL
|
LdMT | LdRoS3 | ||||||
| Amas | Pro | Amas | Pro | |||||||
| LdAG83 | Standard Indian L. donovani strain | 2.06 ± 0.23 | 0.017 ± 0.01 | 0.023 ± 0.01 | 0.85 ± 0.03 | 1.05 ± 0.07 | 1 | 1 | ||
| K59 | F/21 | Vaishali/HR | SAG (NR) | 14.66 ± 3.29 | 0.180 ± 0.02 | 0.50 ± 0.006 | 1.86 ± 0.07 | 1.19 ± 0.07 | 2.84 ± 0.22 | 4.06 ± 0.21 |
| K131 | M/22 | Saharsha/HR | SAG (NR) | 19.38 ± 1.68 | 0.35 ± 0.08 | 0.43 ± 0.035 | 0.51 ± 0.06 | 0.63 ± 0.03 | 2.43 ± 0.25 | 11.1 ± 0.23 |
| K149 | M/20 | Saran/HR | AmB (R) | 15.70 ± 4.01 | 0.28 ± 0.10 | 1.46 ± 0.12 | 1.57 ± 0.16 | 1.56 ± 0.11 | 1.08 ± 0.56 | 7.69 ± 0.16 |
| K192 | M/24 | Saran/HR | AmB (R) | 20.30 ± 0.84 | 0.67 ± 0.10 | 0.78 ± 0.12 | 1.99 ± 0.17 | 1.91 ± 0.08 | 0.23e ± 0.04 | 1.9 ± 0.13 |
| K251 | M/11 | Saran/HR | NDf | 11.82 ± 1.28 | 0.55 ± 0.01 | 1.42 ± 0.09 | 1.59 ± 0.07 | 0.40 ± 0.05 | 7.68 ± 0.10 | 52.63 ± 0.06 |
| K417 | F/8 | Muzaffarpur/HR | AmB (R) | 14.65 ± 0.67 | 0.44 ± 0.01 | 0.69 ± 0.007 | 1.90 ± 0.04 | 1.72 ± 0.11 | 1.88 ± 0.23 | 5.02 ± 0.23 |
| K429 | M/26 | Saharsha/HR | AmB (R) | 13.76 ± 0.82 | 0.37 ± 0.10 | 1.34 ± 0.17 | 1.24 ± 0.18 | 1.26 ± 0.06 | 1.26 ± 0.52 | 8.85 ± 0.25 |
| K439 | M/16 | Muzaffarpur/HR | AmB (R) | 12.88 ± 0.12 | 0.77 ± 0.08 | 1.62 ± 0.134 | 1.07 ± 0.1 | 0.87 ± 0.04 | 4.76 ± 0.20 | 3.12 ± 0.20 |
| K481 | M/32 | Muzaffarpur/HR | AmB (R) | 17.53 ± 0.34 | 0.55 ± 0.07 | 0.69 ± 0.016 | 2.32 ± 0.14 | 1.90 ± 0.12 | ND | ND |
| K498 | F/55 | Madhubani/HR | AmB (R) | 15.82 ± 0.24 | 0.54 ± 0.01 | 1.16 ± 0.06 | 1.65 ± 0.05 | 1.32 ± 0.08 | 1.38 ± 0.24 | 7.63 ± 0.24 |
| K516 | F/60 | Motihari/HR | AmB (R) | 16.48 ± 0.61 | 0.62 ± 0.04 | 1.26 ± 0.029 | 2.02 ± 0.10 | 1.62 ± 0.16 | 8 ± 0.12 | 83.33 ± 0.17 |
| K509 | F/4 | Madhubani/HR | AmB (R) | 16.84 ± 0.26 | 0.65 ± 0.06 | ND | 2.16 ± 0.13 | 1.94 ± 0.11 | ND | ND |
| K80 | F/40 | Bhagalpur/LR | SAG (NR) pentamidine | 10.42 ± 2.17 | 0.18 ± 0.02 | 0.50 ± 0.006 | 1.32 ± 0.04 | 1.58 ± 0.16 | 1.24 ± 0.48 | 1.71 ± 0.48 |
| K111 | F/36 | Siwan/LR | SAG (R) | 5.63 ± 0.57 | 0.2 ± 0.01 | 1.02 ± 0.07 | 0.85 ± 0.19 | 0.47 ± 0.06 | 3.4 ± 0.12 | 5.26 ± 0.19 |
| K132 | F/24 | Munger/LR | ND | 3.95 ± 0.28 | 0.22 ± 0.01 | 1.22 ± 0.11 | 0.48 ± 0.05 | 0.53 ± 0.03 | 5.5 ± 0.16 | 55.55 ± 0.16 |
| K133 | M/20 | West Bengal/LR | SAG (R) | 3.45 ± 0.28 | 0.21 ± 0.01 | 0.65 ± 0.18 | 0.93 ± 0.10 | 0.83 ± 0.04 | 1.5 ± 0.26 | 4.52 ± 0.26 |
| K135 | F/45 | Gopalganj/LR | SAG (R) | 4.22 ± 0.38 | 0.25 ± 0.04 | 0.31 ± 0.014 | 0.72 ± 0.03 | 0.86 ± 0.03 | 2.86 ± 0.29 | 1.67 ± 0.29 |
| K216 | M/14 | West Bengal/LR | SAG (R) | 2.14 ± 0.28 | 0.25 ± 0.03 | 0.52 ± 0.018 | 0.91 ± 0.19 | 0.76 ± 0.02 | 1.4 ± 0.27 | 9.43 ± 0.26 |
| K435 | M/17 | Kushinagar/LR | AmB (R) | 11.82 ± 1.39 | 0.17 ± 0.01 | 0.57 ± 0.012 | 1.08 ± 0.25 | 1.16 ± 0.19 | 2.67 ± 0.19 | 4.76 ± 0.21 |
| K59M20 | Lab generated, MIL resistant | NAg | ND | ND | ND | >15 | >15 | 13.33 ± 0.2 | 100 ± 0.03 | |
| K417M20 | Lab generated, MIL resistant | NA | ND | ND | ND | >15 | >15 | 11.3 ± 0.17 | 100 ± 0.02 | |
M, male; F, female.
Responses were noted 30 days after treatment with SAG infusions (20 mg/kg of body weight) or with AmB infusions (1 mg/kg of body weight) on alternate days for 1 month. Patients with an absence of fever and with a reduction in spleen size were designated responders (R); patients who did not exhibit those outcomes were considered nonresponders (NR).
Mean ED50s ± standard deviations of the results from three separate assays. Amas, amastigotes; Pro, promastigotes.
Expression levels indicative of decreases relative to those seen with strain LdAG83.
4.28-fold increase relative to the results seen with strain LdAG83.
ND, not determined.
NA, not applicable.