Article Figures & Data
Figures
- FIG. 1.
In vitro effects of three drugs against N. fowleri. (A) Growth curves of N. fowleri after treatment with each drug. N. fowleri trophozoites were cultured at a density of 104/ml in the absence (control) or presence of each drug. (B) The amoebicidal activity of three drugs against N. fowleri was evaluated by LDH release assay. Amoebae were treated with miltefosine and chlorpromazine at concentrations from 1.56 to 100 μg/ml and with amphotericin B at concentrations from 0.39 to 25 μg/ml. The optical density was measured on days 2, 4, and 6, respectively. Values are means ± the standard errors of three experiments performed in triplicate.
- FIG. 2.
Liver and kidney tissue of mice treated with chlorpromazine. (A and B) Liver tissue from a mouse administered 20 mg of chlorpromazine/kg had hepatocytes of normal size and shape (A, ×100; B, ×400). (C and D) Kidney from a mouse administered 20 mg of chlorpromazine/kg had renal cortical tubules of normal size and shape (C, ×100; D, ×400). The tissues were stained with hematoxylin and eosin.
- FIG. 3.
Survival curve of N. fowleri-infected mice treated with amphotericin B (A), miltefosine (B), or chlorpromazine (C). Mice were inoculated intranasally with 104N. fowleri trophozoites. At 3 days postinoculation, the groups were treated with 10 mg of amphotericin B/kg or 20 mg of miltefosine and chlorpromazine/kg, respectively. Each group (n = 20 mice) was treated with drugs once (day 3), twice (days 3 and 7), or three times (days 3, 7, and 11). The control group received 100 μl of saline.
- FIG. 4.
Brain tissue of mice infected with N. fowleri trophozoites. (A and B) The brain tissue of dead mouse after drug treatment shows N. fowleri trophozoites and inflammatory cells. In the boxed area in panel B, arrows indicate N. fowleri trophozoites surrounded by inflammatory cells (A, ×50; B, ×400). (C and D) The brain tissue of mice that survived during the experimental periods (1 month) after drug treatment had no N. fowleri trophozoites and showed no change (C, ×50; D, ×400). The tissues were stained by hematoxylin and eosin.
Tables
- TABLE 1.
MICs of the drugs tested for N. fowleri
Drug MIC100 (μg/ml)a Day 2 Day 4 Day 6 Amphotericin B 0.78 0.78 0.78 Miltefosine 25.00 25.00 25.00 Chlorpromazine 12.50 12.50 12.50 ↵ a MIC100, the lowest drug concentration that caused a 100% inhibition of growth. Complete inhibition of trophozoite growth in Nelson's medium was scored on days 2, 4, and 6.
- TABLE 3.
Survival and MTD of N. fowleri-infected mice treated with various drugs
Groupa No. of mice No. of surviving miceb (%) MTDc (days) Amphotericin B 20 8 (40) 17.3 Miltefosine 20 11 (55) 19.3 Chlorpromazine 20 15 (75) 17.2 Controld 20 0 (0) 11.2 ↵ a All groups were treated with drugs three times at days 3, 7, and 11, respectively. The control group received 100 μl of saline under the same conditions.
↵ b Mice were held for 28 days after inoculation, and the cumulative percentage was recorded on a daily basis.
↵ c The MTD was calculated based only on dead mice.
