Oral treatment for Indian kala-azah: Pilot trial using atovaquone alone
In experimental visceral telshmanlasis, oral treatment with atovaquone (ATV) alone halts parasite replication in L donovant-irfeded mice and acts synergistteally with pentavalent antimony. To determine the safety, tolerance, and activity of ATV in kala-azar, 10 untreated patents (8 males) were given once-dairy ATV in suspension at 30 mg/kg/day with 25 g of fat. All patients received 20 days of treatment; respondent on day 20 were treated for 10 more days. Mean results for the 10 patients at study entry: age, 19.7 years (three <12 years old); 1.3 months of illness; weight, 32 kg; spleen size, 3.6 cm; WBC 5100; hemoglobin 10.2; platelets, 157000; and splenic aspirate parasite density score, 3.2 (log scale of 0 to 6+). ATV was safe and well-tolerated in all 10 patients. Four patients showed neither clinical or parasite-logic Improvement (nor deterioration) on day 20, and per the protocol, were switched to antimony therapy. Six patients qualified for 10 more days of ATV. On day 30,1 of 6 had improved clinically but not parasitotogteally; the remaining 5 showed either (a) apparent cure (n = 1) with no parasites seen on splenic aspirate (score = 0) or (b) partial responses with splenic aspirate scores decreasing from 4+ to 2+ (n = 2) or from 3+ to 1+ (scanty parasites, n = 2). Mean day 0 vs. day 30 changes in these 5 responders included: Kamofsky score, 78 to 90%; spleen size, 3.8 to 2.4 cm; WBC, 5300 to 6500; hemoglobin, 9.0 to 11.0; platelets, 128000 to 238000; and aspirate score 3.4 to 1.2. All 6 of these patients, including the 1 apparent cure who subsequently relapsed, were treated with and responded to antimony. ATV by itself induces measureabte activity in kala-azar, and represents a suitable and well-tolerated oral agent to test next in combination with conventional antimony to enhance the latter's declining efficacy.