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The increase in the incidence of AIDS-related tuberculosis over the last decades has fueled the dissemination of multiple drug resistance tuberculosis (including resistant strains to INH and rifampin). This has now been recognized in a variety of settings including hospitals, prisons and shelters. We have identified a nosocomial epidemic at the Muñiz Hospital in the city of Buenos Aires, Argentina. This has evolved as one of the largest institutional outbreaks yet to be recognized. The purpose of this paper is to characterize the evolution of this outbreak which at the end of 1997 had involved in excess of 500 cases. Among the 3,322 patients discharged at the Muñiz Hospital during the years 1996-1997 with the diagnosis of tuberculosis, 440 (13.24%) were discharged with the diagnosis of multiple drug resistance tuberculosis. The immediate mortality (during the ensuing four months following the bacteriological diagnosis) was of 91.3% of cases in 1995 and decreased progressively to 65.9% in 1996 and 55.9% in 1997. The bacteriological confirmation of the diagnosis was made after the patients death in a decreasing number of cases, going from 72.5% of the cases in 1995 to 28.3% of the cases in 1997. Despite the significant progress achieved with regard to the diagnosis and treatment of multiple drug resistance tuberculosis, the measures undertaken to decrease the spread of the cases have had limited success. This is chiefly attributable to the inability to isolate cases. This has continued to promote nosocomial spread of multiple drug resistance tuberculosis in our environment.

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SETTING: Multidrug-resistant tuberculosis patients without human immunodeficiency virus (HIV) infection, with Mycobacterium tuberculosis resistant to almost all of the available drugs. OBJECTIVE: Limited phase II trial with recombinant interferon-alpha2b in five chronic multidrug-resistant tuberculosis patients. METHODS: Three million units of r-IFN-alpha2b were administered subcutaneously every week for 12 weeks. Before and after treatment, and during a 30-month follow-up period, the patients underwent clinical and radiological examination, together with bacteriological, immunological and routine laboratory testing. RESULTS: Two of the five patients became long-term sputum smear and culture negative after r-IFN-alpha2b therapy; one of the patients showed clinical improvement and negative smear after therapy, but remained culture positive. The other two patients showed no response. CONCLUSION: The results of this trial suggest that r-IFN-alpha2b should be evaluated further in multidrug-resistant tuberculosis in prospective controlled trials.

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Se analizaron las historias clínicas de 12 pacientes de Tuberculosis con resistencia única a rifampicina asociada al Síndrome de Inmunodeficiencia Adquirida, cuyas muestras biológicas fueron estudiadas en el Laboratorio de Bacteriología "Dr. A. Cetrángolo" durante el período comprendido entre julio de 1991 y febrero de 1994. De los 12 pacientes, 11 eran hombres y 1 pertenecía al sexo femenino. La edad estuvo comprendida entre los 20 y 35 años. Los 10 pacientes con conducta de riesgo conocida eran adictos a drogas intravenosas. La tuberculosis fue pulmonar en 8 pacientes, extrapulmonar en 3 y localización combinada en 1 caso.

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Se analizaron las historias clínicas de 12 pacientes de Tuberculosis con resistencia única a rifampicina asociada al Síndrome de Inmunodeficiencia Adquirida, cuyas muestras biológicas fueron estudiadas en el Laboratorio de Bacteriología "Dr. A. Cetrángolo" durante el período comprendido entre julio de 1991 y febrero de 1994. De los 12 pacientes, 11 eran hombres y 1 pertenecía al sexo femenino. La edad estuvo comprendida entre los 20 y 35 años. Los 10 pacientes con conducta de riesgo conocida eran adictos a drogas intravenosas. La tuberculosis fue pulmonar en 8 pacientes, extrapulmonar en 3 y localización combinada en 1 caso. (AU)

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SETTING: Patients with newly-diagnosed drug-sensitive, radiographically active and bacteriologically confirmed pulmonary tuberculosis recruited at 6 centres in Argentina, Brazil and Thailand. OBJECTIVE: To assess the efficacy, tolerability and toxicity of two regimens containing different daily dosages of rifabutin in comparison with rifampicin. DESIGN: Multicentred, randomised, comparative study. In each group, study medications were administered daily for 6 months combined with isoniazid (6 months), and with pyrazinamide and ethambutol (both stopped after 2 months). Treatment success patients were followed-up for up to 2 years. RESULTS: A total of 520 patients were enrolled and randomly assigned to receive either rifampicin (n = 175), or rifabutin 150 mg (n = 174) or rifabutin 300 mg (n = 171). Considering all patients with positive baseline culture, the success rates at the last valid observation for each patient were 89%, 94% and 92% in the rifampicin, rifabutin 150 mg, and rifabutin 300 mg groups, respectively. The median time to culture conversion was comparable in the 3 groups and was 34 days for rifampicin and 37 days for each of the rifabutin groups. During the drug-free follow-up period, one relapse occurred in the rifampicin group, and two in each of the rifabutin groups. The 3 treatment schedules appeared well tolerated. No patients had to discontinue therapy because of an adverse event in the rifabutin 150 mg group, compared to one in the rifampicin and 5 in the rifabutin 300 mg group. CONCLUSION: All 3 regimens proved effective and well tolerated. Rifabutin at 150 mg/d showed the best risk-to-benefit ratio, in that this group had the highest proportion of patients completing treatment, the highest bacteriological conversion rates and the lowest incidence of adverse events.

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In order to detect an association between HIV infection and tuberculosis (TB), 130 TB inpatients were studied one of whom presented a pulmonary disease due to Mycobacterium avium intracellulare. All had advanced TB, 95.4%, with pulmonary localization. Serum anti-HIV antibodies were detected by ELISA and their presence confirmed by immunoblotting in 4 (3.1%) individuals, three males and one female, with different degrees of pulmonary TB. Of the males, 1 was bisexual, 2 were promiscuous, and the female was the sexual partner of a non symptomatic HIV-infected man. No immunological disturbances or other AIDS related alterations were observed. There was one case of miliary TB, but neither atypical X-ray abnormalities nor extrapulmonary involvement were found. Tuberculin reaction was positive in three of the four HIV infected patients. Clinical, radiological and bacteriological evolution were favorable. Adverse drug reaction occurred in two cases, one of them presenting serious toxidermia caused by isoniazid. Of the 130 individuals, 12 presented risk factors for HIV infection so that the prevalence of anti-HIV antibodies presented here, 4 cases out of 12, is consistent with data from previous reports for high risk populations.

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Se estudiaron 129 enfermos con tuberculosis grave y 1 con micobacteriosis debida a M. avium intracellulare internados en el Pabellón Koch del Hospital Francisco J. Miñiz durante el primer bimestre de 1988. Se hallaron anticuerpos contra HIV en 4 pacientes (3,1%), 3 hombres y una mujer. Todos ellos tenían algun factor de riesgo para infección con HIV: de los hombres, uno era bisexual y los otros dos declararon ser promiscuos; la mujer era pareja sexual de un individuo HIV positivo. En ninguno se detectaron trastornos inmunológicos, ni otras alteraciones atribuibles a la infección con HIV. Los 4 pacientes presentaron formas de tuberculosis pulmonar graves y en un caso diseminación miliar. No se hallaron formas atípiicas ni extrapulmonares. La prueba tuberculínica fue positiva en 3 de los 4 pacientes. La respuesta clínica, radiológica y bacteriológica fue favorable. Se produjeron reacciones adversas medicamentosas en dos pacientes, debiéndose suspender la administración de isoniacida en uno de ellos, debido a una toxidermia grave. La presentación y evolución de la tuberculosis fue similar en todos no habiéndose encontrado ninguna variable que permitera discriminar entre los HIV positivos o negativos. Enfatizamos la necesidad de realizar un estudio epidemiológico similar de mayor envergadura para detectar la tendencia ascendente que problablemente tendrá la asociación entre tuberculosis e infección con HIV (AU)

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In order to detect an association between HIV infection and tuberculosis (TB), 130 TB inpatients were studied one of whom presented a pulmonary disease due to Mycobacterium avium intracellulare. All had advanced TB, 95.4

, with pulmonary localization. Serum anti-HIV antibodies were detected by ELISA and their presence confirmed by immunoblotting in 4 (3.1

) individuals, three males and one female, with different degrees of pulmonary TB. Of the males, 1 was bisexual, 2 were promiscuous, and the female was the sexual partner of a non symptomatic HIV-infected man. No immunological disturbances or other AIDS related alterations were observed. There was one case of miliary TB, but neither atypical X-ray abnormalities nor extrapulmonary involvement were found. Tuberculin reaction was positive in three of the four HIV infected patients. Clinical, radiological and bacteriological evolution were favorable. Adverse drug reaction occurred in two cases, one of them presenting serious toxidermia caused by isoniazid. Of the 130 individuals, 12 presented risk factors for HIV infection so that the prevalence of anti-HIV antibodies presented here, 4 cases out of 12, is consistent with data from previous reports for high risk populations.

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Se estudiaron 129 enfermos con tuberculosis grave y 1 con micobacteriosis debida a M. avium intracellulare internados en el Pabellón Koch del Hospital Francisco J. Miñiz durante el primer bimestre de 1988. Se hallaron anticuerpos contra HIV en 4 pacientes (3,1%), 3 hombres y una mujer. Todos ellos tenían algun factor de riesgo para infección con HIV: de los hombres, uno era bisexual y los otros dos declararon ser promiscuos; la mujer era pareja sexual de un individuo HIV positivo. En ninguno se detectaron trastornos inmunológicos, ni otras alteraciones atribuibles a la infección con HIV. Los 4 pacientes presentaron formas de tuberculosis pulmonar graves y en un caso diseminación miliar. No se hallaron formas atípiicas ni extrapulmonares. La prueba tuberculínica fue positiva en 3 de los 4 pacientes. La respuesta clínica, radiológica y bacteriológica fue favorable. Se produjeron reacciones adversas medicamentosas en dos pacientes, debiéndose suspender la administración de isoniacida en uno de ellos, debido a una toxidermia grave. La presentación y evolución de la tuberculosis fue similar en todos no habiéndose encontrado ninguna variable que permitera discriminar entre los HIV positivos o negativos. Enfatizamos la necesidad de realizar un estudio epidemiológico similar de mayor envergadura para detectar la tendencia ascendente que problablemente tendrá la asociación entre tuberculosis e infección con HIV

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An enzyme-linked immunosorbent assay (ELISA) using Mycobacterium tuberculosis antigen 5 has been evaluated as a serodiagnostic test for active tuberculosis in children. Forty children of either sex, ages 1 to 14 yr, were studied, including 21 bacteriologically confirmed tuberculous patients and 19 control subjects who were evaluated for tuberculosis and found to be free of disease. At a 1:20 dilution, the test showed a sensitivity of 0.857 and a specificity of 1.000, with an accuracy value of 0.925, a positive predictive value of 1.000, and a negative predictive value of 0.864. The prevalence of disease calculated directly from the data of the study was found to be of 0.525. The geometric mean ELISA titer of the tuberculosis group was 1:58, and the difference in antibody titers between patient and control groups was found to be statistically significant (p less than 0.001). From our results, we conclude that ELISA using M. tuberculosis antigen 5 may be useful in those situations of high prevalence of disease when children suspected of tuberculosis are being evaluated.

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The ELISA has been extensively evaluated as a serodiagnostic method for tuberculosis. However, there is scarce information about its application to cases that cannot be diagnosed by microscopic examination: those with closed lesions or undergoing early stages of the disease. Since a reliable serological test might substantially contribute to their prompt detection, the objective of the present study was to determine the diagnostic value of an ELISA applied to adult smear-negative cases of tuberculosis. Sera from 235 patients with active tuberculosis--176 pulmonary and 59 extrapulmonary cases--and 181 control subjects were tested for IgG antibodies to PPD by ELISA. Eleven cases of non tuberculous mycobacterial (MOTT) disease and 33 cases of mycosis were also included in this group. With the adopted cut-off value, 73.9% (105/142) of smear positive and 52.7% (49/93) of smear negative tuberculosis cases, were correctly classified. Particularly in the latter, the test was positive in 55.2% (32/58) of patients with positive cultures for Mycobacterium tuberculosis and in 48.6% (17/35) of patients diagnosed by clinical, radiological and or histopathological findings. No antibody activity was demonstrated in 92.7% of sera from the control population which included 92 healthy volunteers, 32 non tuberculous diseased subjects and 13 household contacts of smear-positive cases. Among those control subjects who were skin tested, ELISA results were not related to the tuberculin reactivity: 93.7% (30/32) of tuberculin negative and 95.2% (40/42) of tuberculin positive healthy individuals had no detectable antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

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Se evaluó un enzimoinmunoensayo (EIE) para la detección de anticuerpos IgG circulantes anti-PPD en el diagnóstico de la tuberculosis paucibacilar del adulto. El 73,9% de 142 pacientes bacilíferos y el 52,7% de 93 casos con baciloscopia negativa resultaron seropositivos por EIE. Particularmente en este último grupo la prueba fue positiva en el 55,25 de 58 pacientes diagnosticados por cultivo y en el 48,6% de 35 pacientes con diagnóstico clínico-radiológico de tuberculosis. El 92,7% de 137 sueros de la población control carecia de anticuerpos detectables. En los sujetos sanos que fueron tuberculinizados los resultados del EIE no se realacionaron con la respuesta tuberculínica: el 93.7% (30/32) de los tuberuclino negativos y el 95,2% (40/42) de los reactores a la tuberculina fueron negativos por EIE. Trece de 33 casos de PPD. Ciertamente el EIE tuvo máxima sensibilidad en la detección de casos bacilíferos, no obstante permitió identificar también a más de la mitad de los pacientes con baciloscopia negativa. Por lo tanto, puede ser considerado um método útil para el diagnóstico presuntivo rápido de la tuberculosis paucibacilar, excepto en los casos en los que se plantee el diagnóstico diferencial con micosis o con otras micobacterosis (AU)

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The ELISA has been extensively evaluated as a serodiagnostic method for tuberculosis. However, there is scarce information about its application to cases that cannot be diagnosed by microscopic examination: those with closed lesions or undergoing early stages of the disease. Since a reliable serological test might substantially contribute to their prompt detection, the objective of the present study was to determine the diagnostic value of an ELISA applied to adult smear-negative cases of tuberculosis. Sera from 235 patients with active tuberculosis--176 pulmonary and 59 extrapulmonary cases--and 181 control subjects were tested for IgG antibodies to PPD by ELISA. Eleven cases of non tuberculous mycobacterial (MOTT) disease and 33 cases of mycosis were also included in this group. With the adopted cut-off value, 73.9

(105/142) of smear positive and 52.7

(49/93) of smear negative tuberculosis cases, were correctly classified. Particularly in the latter, the test was positive in 55.2

(32/58) of patients with positive cultures for Mycobacterium tuberculosis and in 48.6

(17/35) of patients diagnosed by clinical, radiological and or histopathological findings. No antibody activity was demonstrated in 92.7

of sera from the control population which included 92 healthy volunteers, 32 non tuberculous diseased subjects and 13 household contacts of smear-positive cases. Among those control subjects who were skin tested, ELISA results were not related to the tuberculin reactivity: 93.7

(30/32) of tuberculin negative and 95.2

(40/42) of tuberculin positive healthy individuals had no detectable antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

RESUMO

Se evaluó un enzimoinmunoensayo (EIE) para la detección de anticuerpos IgG circulantes anti-PPD en el diagnóstico de la tuberculosis paucibacilar del adulto. El 73,9% de 142 pacientes bacilíferos y el 52,7% de 93 casos con baciloscopia negativa resultaron seropositivos por EIE. Particularmente en este último grupo la prueba fue positiva en el 55,25 de 58 pacientes diagnosticados por cultivo y en el 48,6% de 35 pacientes con diagnóstico clínico-radiológico de tuberculosis. El 92,7% de 137 sueros de la población control carecia de anticuerpos detectables. En los sujetos sanos que fueron tuberculinizados los resultados del EIE no se realacionaron con la respuesta tuberculínica: el 93.7% (30/32) de los tuberuclino negativos y el 95,2% (40/42) de los reactores a la tuberculina fueron negativos por EIE. Trece de 33 casos de PPD. Ciertamente el EIE tuvo máxima sensibilidad en la detección de casos bacilíferos, no obstante permitió identificar también a más de la mitad de los pacientes con baciloscopia negativa. Por lo tanto, puede ser considerado um método útil para el diagnóstico presuntivo rápido de la tuberculosis paucibacilar, excepto en los casos en los que se plantee el diagnóstico diferencial con micosis o con otras micobacterosis

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