Fluconazole as oral monotherapy for Indian kala-azar
To determine the safety and tolerance of once-daily oral fluconazote (FLU) in visceral teishmaniasrs, 2 adults (20 and 50 years old, 40 and 50 kg) and 4 children (9-12 years, 19-30 kg) were treated with (a) dose tevel-1,3 mg/kg for adults (>18 years) or 6 mg/kg for children (s 17 years) during days 1-15, and (b) double these doses (dose level-2) during days 15-30. There were no adverse reactions during 30 days of treatment. Day 30 splenic aspirate parasite density scores (log scale of 0 to 6+) indicated apparent cure (aspirate score = 0) in 1, partial response In 1 (4+ to 2+), and no response in 4 patients. The latter 5 patients then received antimony. Ten additional untreated patients (6 males) were then treated identically except that partial responders on day 30 received dose level-2 for 15 more days. Mean results (n = 10) at entry: age 30 years (five si 7 years); weight range 35-63 kg; III for 2.7 months; spleen size 4.3 cm; WBC 4840; hemoglobin 8.7; platelets 104400; and splenic aspirate score 3.4. Six patients were treated for 30 days resulting in 3 apparent cures, 1 partial response (score, 4+ to 1+, left AMA), and 2 failures. Four others were treated for 45 days resulting In 2 apparent cures and 2 failures. In the 5 total apparent cures, changes by day 30 included: all afebrite by day 6, spleen size 3.0 to 0.8 cm, WBC 5000 to 6800, hemoglobin 9.5 to 11.9, and mean aspirate score 3.0 to 0.4. Except for apparent cure patients, all others were next treated with antimony. However, each of the 5 apparent cures relapsed within 5.5 weeks (range, 1-10) after FLU and also required antimony. Therefore, while oral FLU alone at the doses used clearly has initial activity in kala-azar, future trials should test a higher dose or more likely test FLU in combination with conventional pentavalent antimony therapy.