Abstract
In a murine model of chronic disseminated paracoccidioidomycosis (strain 18; intravenous route), Ketoconazole (200 mg/kg in 0.2% agar) was given daily by gavage in three different schedules. Continuous treatment from an early stage of infection (day 3) up to week 20 was the most effective protocol, leading to remission of histopathological lesions and of both humoral and cellular anti-P. brasiliensis immune response, and clearance of the fungus in lungs; only 1 treated animal at week 20 showed pulmonary granulomas, although less extensive than control mice. Continuous treatment from early stage up to week 8, followed by a 16 week-period of drug discontinuity, caused remission of lesions in all but 3 treated mice which showed active pulmonary paracoccidioidomycosis similar to controls (14.2% of unresponsiveness to treatment). The continuous Ketoconazole protocol since a late stage of infection (week 4) up to week 20 produced a slower remission of lesions and immune response when compared with the first drug schedule. In this model of paracoccidioidomycosis, Ketoconazole showed no detectable side-effects and was a very effective drug especially in a prolonged administration protocol from an early stage of infection.
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References
Cucé LC, Wroclawski EL, Sampaio SAP: Treatment of paracoccidioidomycosis with ketoconazole. Rev Inst Med trop S Paulo 23:82–85, 1981.
Dixon WJ, Massey Jr FJ: Introduction to statistical analysis. Mc Graw-Hill, Tokyo, 1969, 3 ed.
Fava Netto C, Vegas VS, Scianname IM, Guarnieri DB: Antígeno polissacarídico do Paracoccidioides brasiliensis. Estudo do tempo de cultivo do P. brasiliensis, necessário ao preparo do antígeno. Rev Inst Med trop S Paulo 11:177–181, 1969.
Hay RJ, Chandler Jr FW: Experimental paracoccidioidomycosis: Cranial and nasal localization in mice. Br J exp Path 59:339–344, 1978.
Hoyos GL, McEwen JG, Brummer E, Castañeda E, Restrepo A, Stevens DA: Chronic murine paracoccidioidomycosis: Effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response. Sabouraudia 22:419–426, 1984.
Kong YM, Savage DC, Kong LNL: Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J Bact 91:876–883, 1966.
Lacaz CS, Iaria ST, Ferreira M, Martins AA, Vega VS: Blastomicose experimental (nota preliminar). Hospital, Rio de J. 36:341–349, 1949.
Linares LI, Friedman L: Experimental paracoccidioidomycosis in mice. Infect Immun 5:681–687, 1972a.
Linares LI, Friedman L: Pathogenesis of paracoccidioidomycosis in experimental animals. Scient Publ Pan Am Hlt Orgn (254):287–292, 1972b.
Mackinnon JE: Pathogenesis of South American blastomycosis. Trans R Soc trop Med Hyg 53:407–494, 1959.
Moscardi-Bacchi M, Franco MF: Experimental paracoccidioidomycosis in the intravenous infection in the presence or absence of previous immunization. Rev Soc bras Med trop 18:101–108, 1985.
Mota NGS, Viero RM, Reskallah-Iwasso MT, Peraçoli MTS, Soares AMVC, Montenegro MR: The effect of ketoconazole on experimental paracoccidioidomycosis in Syrian hamster: Immunological and histopathological study. Mycopathologia 88:141–148, 1984.
Negroni R, Robles AM, Arechavala A, Tuculet MA, Galimberti R: Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis. Rev Infect Dis 2:643–649, 1980.
Restrepo A, Bedout C, Cano LE, Arango MD, Bedoya V: Recovery of Paracoccidioides brasiliensis from a partially calcified lymph node lesion by microaerophilic incubation of liquid media. Sabouraudia 19:295–300, 1981.
Restrepo A, Gomez I, Cano LE, Arango MD, Gutierrez F, Sanin A, Robledo MA: Treatment of paracoccidioidomycosis with ketoconazole: A three-year experience. Am J Med 74(1B):48–52, 1983a.
Restrepo A, Gomez I, Cano LE, Arnago MD, Gutierrez F, Sanin A, Robledo MA: Post-therapy status of paracoccidioidomycosis treated with ketoconazole. Am J Med 74(1B):53–57, 1983b.
Restrepo A, Gomez I, Robledo MA: Eficacia del Ketoconazol en pacientes con paracoccidioidomicosis recidivante. Rev Inst Med trop S Paulo 24:173–179, 1982.
San Blas F, Cova LJ: Growth curves of the yeast-like form of Paracoccidioides brasiliensis. Sabouraudia 13:22–29, 1975.
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Ueda, A.K., Franco, M., Fabio, S.A. et al. Ketoconazole in the treatment of experimental murine paracoccidioidomycosis. Mycopathologia 98, 27–34 (1987). https://doi.org/10.1007/BF00431014
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DOI: https://doi.org/10.1007/BF00431014