RESUMEN
Soil-transmitted-helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting preschool- and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to (i) evaluate the effect of type of diet (a heavy or light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and (ii) evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulfoxide (ALBSO) metabolite was enhanced more than 2-fold after food ingestion (a heavy or light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulfone (NHALBSO2) derivative and ALBSO for up to 96 h suggests that it may be feasible to develop a noninvasive tool to evaluate compliance/adherence to ALB treatment.
Asunto(s)
Antihelmínticos , Helmintiasis , Absorción Fisiológica , Adulto , Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Niño , Preescolar , Voluntarios Sanos , Helmintiasis/tratamiento farmacológico , Humanos , Administración Masiva de Medicamentos , SueloRESUMEN
Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.
Asunto(s)
Albendazol , Antihelmínticos , Humanos , Albendazol/uso terapéutico , Saliva/metabolismo , Administración Masiva de Medicamentos , Cooperación del PacienteRESUMEN
The rTSSA-II (recombinant Trypomastigote Small Surface II) antigen was evaluated by ELISA to detect anti-Trypanosoma cruzi antibodies in sera from naturally infected dogs and humans. For this evaluation ELISA-rTSSA-II was standardized and groups were classified according to the results obtained through xenodiagnosis, ELISA and PCR. Sensitivity (Se), Specificity (Sp), Kappa index (KI) and area under curve (AUC) were determined. The Se was determined by using 14 sera from dogs infected with T. cruzi VI (TcVI) whereas Sp was determined by using 95 non-chagasic sera by xenodiagnosis, ELISA-Homogenate and PCR. The performance of ELISA-rTSSA-II in dog sera was high (AUC=0·93 and KI=0·91). The Se was 92·85% (1 false negative) and Sp was 100%. Two sera from dogs infected with TcI and 1 with TcIII were negative. For patients infected with T. cruzi, reactivity was 87·8% (36/41), there was only 1 indeterminate, and Sp was 100%. Fifty-four sera from non-chagasic and 68 sera from patients with cutaneous leishmaniasis did not react with rTSS-II. ELISA-rTSSA-II showed a high performance when studying sera from naturally infected dogs and it also presented 100% Sp. This assay could be an important tool to carry out sero-epidemiological surveys on the prevalence of T. cruzi circulating lineages in the region.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos , Enfermedad de Chagas/diagnóstico , Enfermedades de los Perros/diagnóstico , Trypanosoma cruzi/inmunología , Animales , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/aislamiento & purificación , Antígenos de Superficie/inmunología , Antígenos de Superficie/aislamiento & purificación , Argentina/epidemiología , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Perros , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Humanos , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Sensibilidad y Especificidad , Estudios SeroepidemiológicosRESUMEN
SUMMARY: A 41-year-old pregnant woman with multiple virological failures started darunavir, enfuvirtide, zidovudine and lamivudine at week 28 of pregnancy. During week 38, the patient had a viral load <400 copies/mL and a CD4 count of 180 cells/mm(3) (13%). The child was found to be in good health, with negative HIV-polymerase chain reactions at birth, at two and at six months.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Proteína gp41 de Envoltorio del VIH/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Darunavir , Farmacorresistencia Viral Múltiple , Quimioterapia Combinada , Enfuvirtida , Femenino , Proteína gp41 de Envoltorio del VIH/administración & dosificación , Inhibidores de Fusión de VIH/administración & dosificación , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , VIH-1/efectos de los fármacos , Humanos , Recién Nacido , Fragmentos de Péptidos/administración & dosificación , Embarazo , Resultado del Embarazo , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Carga ViralRESUMEN
There are two new drugs approved and several in development for treatment of chronic HCV; among them nitazoxanide (NTZ). Twelve HIV/HCV genotype 1 co-infected patients were enrolled prospectively to receive a 30 days course of oral NTZ 500 mg bid. This therapy was well tolerated in this group of HIV patients co-infected with HCV genotype 1. Nevertheless no changes in HCV viral load were observed during treatment in none of the patients evaluated. This data suggests that despite the promising results reported for HCV genotype 4 mono-infected patients, NTZ exhibit poor activity as monotherapy in HIV/HCV co-infected patients with genotype 1.
Asunto(s)
Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Tiazoles/uso terapéutico , Carga Viral/efectos de los fármacos , Adulto , Antivirales/administración & dosificación , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Nitrocompuestos , Proyectos Piloto , Tiazoles/administración & dosificación , Insuficiencia del TratamientoAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Sarcoma de Kaposi/etiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Adulto , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Humanos , Persona de Mediana Edad , Sarcoma de Kaposi/prevención & control , Factores de TiempoRESUMEN
BACKGROUND: Chronic alcohol consumption has been associated with significant increases in the prevalence of infectious diseases, and it has been suggested that these increases are caused by a direct effect of ethanol on the immune response. The objective of this study was to determine whether chronic ethanol consumption would affect the development of protective immunity to Leishmania major, which is controlled by the T-helper 1 (Th1) subset of CD4 cells, and Strongyloides stercoralis, which is controlled by the Th2 subset. METHODS: Mice were fed ethanol-containing liquid diet (25% ethanol-derived calories), liquid isocaloric diet without ethanol, or solid chow and then exposed to either of the two parasites. The ability of the mice chronically consuming alcohol to eliminate the infections was determined, as were the levels of parasite-specific humoral and cellular immune responses. RESULTS: Mice chronically consuming alcohol were capable of eliminating both of these infections in a manner identical to the control mice. In addition, splenocytes from mice chronically consuming alcohol infected with L. major produced nitric oxide at the same levels as in control mice. Antibody responses were altered in a manner suggesting an increase in Th2 immunity and a decrease in Th1 immunity in the mice chronically consuming alcohol. In mice chronically consuming alcohol that were infected with S. stercoralis, eosinophils migrated to the parasite's microenvironment, and antibodies were produced at levels equivalent to those seen in control mice. CONCLUSIONS: Mice maintained on an ethanol-containing liquid diet had some alteration in their ability to produce Th1 and Th2 immune responses yet were capable of generating unimpaired protective Th1 and Th2 responses.
Asunto(s)
Consumo de Bebidas Alcohólicas/inmunología , Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Leishmania major/inmunología , Strongyloides stercoralis/inmunología , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacos , Animales , Femenino , Inmunoglobulina G/efectos de los fármacos , Inmunoglobulina G/inmunología , Leishmania major/efectos de los fármacos , Leishmaniasis Cutánea/inmunología , Ratones , Ratones Endogámicos C57BL , Strongyloides stercoralis/efectos de los fármacos , Estrongiloidiasis/inmunología , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
Se presenta un paciente de sexo masculino portador de una nocardiosis pulmonar asociada a SIDA. La radiografía de tórax mostró un infiltrado heterogéneo hilioapical izquierdo y se observaron signos de cavitación en la tomografía lineal. El recuento de linfocitos CD4 fue de 70/mm3. El diagnóstico se realizó por el hallazgo del agente etiológico en el esputo. Con el tratamiento con trimetropina-sulfametoxazol se logró la mejoría clínica y la negativización de los cultivos de esputo. En forma asociada presentó: sarcoma de Kaposi, candidiasis cutánea y esofagogástrica y bacteriemia por Salmonella O.S.A.
Asunto(s)
Humanos , Masculino , Adulto , Nocardiosis/epidemiología , Enfermedades Pulmonares Fúngicas/etiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Nocardiosis/fisiopatología , Nocardiosis/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Nocardia asteroides/patogenicidad , Sarcoma de Kaposi/complicacionesRESUMEN
Se presenta un paciente de sexo masculino portador de una nocardiosis pulmonar asociada a SIDA. La radiografía de tórax mostró un infiltrado heterogéneo hilioapical izquierdo y se observaron signos de cavitación en la tomografía lineal. El recuento de linfocitos CD4 fue de 70/mm3. El diagnóstico se realizó por el hallazgo del agente etiológico en el esputo. Con el tratamiento con trimetropina-sulfametoxazol se logró la mejoría clínica y la negativización de los cultivos de esputo. En forma asociada presentó: sarcoma de Kaposi, candidiasis cutánea y esofagogástrica y bacteriemia por Salmonella O.S.A.