RESUMEN
BACKGROUND: Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. METHODS: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. RESULTS: Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. CONCLUSIONS: AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. CLINICAL TRIALS REGISTRATION: India. CTRI/2009/091/000101.
Asunto(s)
Antimaláricos/administración & dosificación , Artemisininas/administración & dosificación , Etanolaminas/administración & dosificación , Fluorenos/administración & dosificación , Compuestos Heterocíclicos con 1 Anillo/administración & dosificación , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Peróxidos/administración & dosificación , Quinolinas/administración & dosificación , Compuestos de Espiro/administración & dosificación , Adolescente , Adulto , África/epidemiología , Anciano , Antimaláricos/uso terapéutico , Arteméter , Artemisininas/uso terapéutico , Asia/epidemiología , Niño , Método Doble Ciego , Quimioterapia Combinada , Etanolaminas/uso terapéutico , Femenino , Fluorenos/uso terapéutico , Semivida , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , India/epidemiología , Lumefantrina , Malaria Falciparum/epidemiología , Masculino , Persona de Mediana Edad , Peróxidos/uso terapéutico , Plasmodium falciparum/efectos de los fármacos , Quinolinas/uso terapéutico , Compuestos de Espiro/uso terapéutico , Adulto JovenRESUMEN
Liver function tests and liver biopsies were studied in 23 leprosy patients in reaction and 10 without reaction. The liver biopsies in leprosy patients with reaction showed exudative lesions, epithelioid and tuberculoid granulomas, and foam-cell granulomas. Portal vasculitis was encountered in a few cases. Neutrophilic infiltration into the foam-cell granulomas was seen in a few cases of lepromatous (LL) leprosy with reaction. In six cases of borderline (BL, BB and BT) leprosy with reaction, a spectrum of lesions bearing footprints of exudative lesions were seen evolving into epithelioid-cell granulomas. Foam-cell granulomas and tuberculoid and epithelioid granulomas along with exudative lesions were encountered in two cases on individual biopsy strips. An altered albumin-to-globulin ratio was the chief functional derangement observed in these cases. The spectrum of changes observed in borderline leprosy with reaction could be discrete steps in the evolution of upgrading reaction