An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region

摘要

Author summary Ninety percent of all cases of CL are concentrated in five countries, including Brazil. Brazil is among the most endemic countries in the Americas. According to the Brazilian Ministry of Health, 30,000 new cases are diagnosed every year and the prevalent species are L. braziliensis and L. guyanensis. In the region of Manaus (Western Amazon), L. guyanensis is responsible for 95% of the cases of CL. The recommended drugs for treatment of CL in Brazil are pentavalent antimonials, PI and amphotericin B (AmB). Pentavalent antimonial is the first-line treatment in Brazil, and AmB is recommended as second-line. The recommended dose for the treatment of CL is 10-20 mg/kg/day of meglumine antimoniate for a period of 20 days. Its efficacy varies from 26.3% to 81.6%. For treatment with AmB, the patient must come to the hospital and be monitored for renal function for several hours. We report a phase II pilot study comprising 159 patients with CL due to L. guyanensis treated with PI. The patients were randomly divided in three groups: 53 received a single intramuscular injection of 7mg/kg PI sa 53 received a regimen of two intramuscular injections of 7 mg/kg within a seven-day interval; and 53 were treated with three intramuscular injections of 7 mg/kg with a seven-day interval between each dose. All patients live in the region of Manaus and were monitored at Tropical Medicine Foundation of Amazonas. Patients underwent a dermatological and laboratorial examination at the start of the study and at weeks 1 and 4. PI was well tolerated and no severe adverse effects were detected. After a 6-month follow-up, we observed 81.% and 96.2% effectiveness for the cure rates in the groups receiving two and three intramuscular injections of 7 mg/kg PI in ACL patients at one-week intervals between doses, respectively. Only 45.3% of the patients treated with a single dose of the medication were considered to be cured. The use of PI in the aforementioned doses is the best option to treat ACL in this region given the long distance, the difficulty in accessing health centers, and the L. (V.) guyanensis predominance in the Brazilian Amazon. We recommend either two or three weekly doses of PI at 7 mg/kg for the treatment of ACL patients in the region.