RESUMO
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.
Assuntos
Albendazol , Anti-Helmínticos , Humanos , Albendazol/uso terapêutico , Saliva/metabolismo , Administração Massiva de Medicamentos , Cooperação do PacienteRESUMO
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.
Assuntos
Anti-Helmínticos , Helmintíase , Absorção Fisiológica , Adulto , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Criança , Pré-Escolar , Voluntários Saudáveis , Helmintíase/tratamento farmacológico , Humanos , Administração Massiva de Medicamentos , SoloRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Tiazóis/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Antivirais/administração & dosagem , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Nitrocompostos , Projetos Piloto , Tiazóis/administração & dosagem , Falha de TratamentoRESUMO
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.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários , Doença de Chagas/diagnóstico , Doenças do Cão/diagnóstico , Trypanosoma cruzi/imunologia , Animais , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/isolamento & purificação , Antígenos de Superfície/imunologia , Antígenos de Superfície/isolamento & purificação , Argentina/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Humanos , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Sensibilidade e Especificidade , Estudos SoroepidemiológicosRESUMO
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.
Assuntos
Terapia Antirretroviral de Alta Atividade , Proteína gp41 do Envelope de HIV/uso terapêutico , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Darunavir , Farmacorresistência Viral Múltipla , Quimioterapia Combinada , Enfuvirtida , Feminino , Proteína gp41 do Envelope de HIV/administração & dosagem , Inibidores da Fusão de HIV/administração & dosagem , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Humanos , Recém-Nascido , Fragmentos de Peptídeos/administração & dosagem , Gravidez , Resultado da Gravidez , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Carga ViralRESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Leishmania major/imunologia , Strongyloides stercoralis/imunologia , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Feminino , Imunoglobulina G/efeitos dos fármacos , Imunoglobulina G/imunologia , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Strongyloides stercoralis/efeitos dos fármacos , Estrongiloidíase/imunologia , Células Th1/imunologia , Células Th2/imunologiaAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/etiologia , Infecções Oportunistas Relacionadas com a AIDS/complicações , Adulto , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Humanos , Pessoa de Meia-Idade , Sarcoma de Kaposi/prevenção & controle , Fatores de TempoRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Nocardiose/epidemiologia , Pneumopatias Fúngicas/etiologia , Síndrome da Imunodeficiência Adquirida/complicações , Nocardiose/fisiopatologia , Nocardiose/diagnóstico por imagem , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Nocardia asteroides/patogenicidade , Sarcoma de Kaposi/complicaçõesRESUMO
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.