Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations

Poisoning by spiders of Loxosceles genus

Fil: De Roodt, Adolfo R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Salomón, Oscar R. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Lloveras, Susana S. Hospital de Enfermedades Infecciosas Francisco J. Muñiz. Centro Municipal de Patología Regional Argentina y Medicina Tropical; Argentina.Fil: Orduna, Tomás A. Hospital de Enfermedades Infecciosas Francisco J. Muñiz. Centro Municipal de Patología Regional Argentina y Medicina Tropical; Argentina.Despite the great number of spiders in the world, only a small group of them is capable of producing death in humans. In Argentina, there are only three of the four genera of spiders considered of high risk to humans: Latrodectus is present in rural areas, Phoneutria is restricted to small regions while Loxosceles is distributed throughout the country. Accidents by Loxosceles represent around 4% of the total number produced by venomous animals in Argentina. The bite is accidental and may produce considerable local necrosis with scar formation and ulcers of slow and difficult healing that may require surgical repair. Some bitten people may suffer from intravascular hemolysis, disseminated coagulation and acute renal insufficiency leading to death. Despite the great number of studies performed on Loxosceles venoms, at present, the physiopathological course of poisoning is not clear and there is not common criteria for its treatment. In this review, biological and epidemiological data of this spider are described as well as the venom composition and the possible participation of its components in the poisoning. These data provide biological and biochemical tools to understand the course of poisoning and to have better criteria for the treatment and prevention of these accidents and their complications

Chagas disease in the central nervous system in patient infected with HIV : diagnostic and therapeutic difficulties

Fil: Simioli, Federico. Hospital de Enfermedades Infecciosas Francisco Javier Muñiz; Argentina.Fil: Sánchez-Cunto, Milagro. Hospital de Enfermedades Infecciosas Francisco Javier Muñiz; Argentina.Fil: Velázquez, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Lloveras, Susana. Hospital de Enfermedades Infecciosas Francisco Javier Muñiz; Argentina.Fil: Orduna, Tomás. Hospital de Enfermedades Infecciosas Francisco Javier Muñiz; Argentina.Chagas disease (ChD), caused by the protozoan Trypanosoma cruzi, is an endemic anthropozoonosis in Latin America, linked to deficients socio-economic and cultural aspects and is considered one of the neglected tropical diseases. We report a fatal case of Chagas disease reactivation with central nervous system involvement in a patient with HIV infection, whose diagnosis was confirmed by positive PCR (polymerase chain reaction) test of blood, with treatment response efficiency with benznidazol and management and etiologic treatment was difficult due to limited number of antitrypanosomal drugs and the occurrence of frequent and serious adverse effects

Poisoning by spiders of Loxosceles genus

Fil: De Roodt, Adolfo R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Salomón, Oscar R. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Lloveras, Susana S. Hospital de Enfermedades Infecciosas Francisco J. Muñiz. Centro Municipal de Patología Regional Argentina y Medicina Tropical; Argentina.Fil: Orduna, Tomás A. Hospital de Enfermedades Infecciosas Francisco J. Muñiz. Centro Municipal de Patología Regional Argentina y Medicina Tropical; Argentina.Despite the great number of spiders in the world, only a small group of them is capable of producing death in humans. In Argentina, there are only three of the four genera of spiders considered of high risk to humans: Latrodectus is present in rural areas, Phoneutria is restricted to small regions while Loxosceles is distributed throughout the country. Accidents by Loxosceles represent around 4% of the total number produced by venomous animals in Argentina. The bite is accidental and may produce considerable local necrosis with scar formation and ulcers of slow and difficult healing that may require surgical repair. Some bitten people may suffer from intravascular hemolysis, disseminated coagulation and acute renal insufficiency leading to death. Despite the great number of studies performed on Loxosceles venoms, at present, the physiopathological course of poisoning is not clear and there is not common criteria for its treatment. In this review, biological and epidemiological data of this spider are described as well as the venom composition and the possible participation of its components in the poisoning. These data provide biological and biochemical tools to understand the course of poisoning and to have better criteria for the treatment and prevention of these accidents and their complications