Phase II trial of recombinant interferon-alpha2b in patients with advanced intractable multidrug-resistant pulmonary tuberculosis: long-term follow-up.

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.

[Evaluation of an enzyme immunoassay for the rapid diagnosis of paucibacillary tuberculosis in adults]. / Evaluación del enzimoinmunoensayo para el diagnóstico rápido de la tuberculosis paucibacilar del adulto.

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)

[Human immunodeficiency virus infection associated with tuberculosis]. / Asociación de la infección por el virus de la inmunodeficiencia humana (HIV) y tuberculosis.

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.

[Multidrug-resistant tuberculosis associated with AIDS (kinetics of nosocomial epidemics of multidrug-resistant tuberculosis associated with AIDS. Possible transformation into endemic disease]. / Tuberculose multi-résistante associée au SIDA (cinétique d'une épidémie nosocomiale de tuberculose multi-résistante associée au SIDA. Transformation possible en endémie).

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.

The realistic possibilities of chemotherapy for pulmonary tuberculosis in South America.

The slow integration of antituberculosis programmes into general health service activities is the most important problem encountered. Short course regimes with high cost drugs require the supervision which, for the time being, is difficult to realize on a large scale except, perhaps, in big cities. Though pilot studies of short course regimes are welcomed, for the immediate use in both the capitals and the rural areas mainly self-administered low-cost systems may be considered for the chemotherapy of tuberculosis, with basic division of patients into groups of previously untreated and previously treated persons (which would affect the drug combination used), and smear (and culture?) positive or negative persons (which might affect the duration of therapy administered). For the latter, it is of considerable importance to continue improving the network of bacteriological laboratories.

Rifabutin for the treatment of newly-diagnosed pulmonary tuberculosis: a multinational, randomized, comparative study versus Rifampicin. Rifabutin Study Group.

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.

[South American blastomycosis. Apropos of new cases]. / Blastomycose sud-américaine. A propos de nouvelles observations.

Twenty-seven cases of South American blastomycosis are reported. Pulmonary lesions predominate and the diagnosis rests on the findings of Paracoccidioides brasiliensis in sputum and tissues. Serological examinations (complement fixation and immunodiffusion) are also useful. Treatment includes sulphonamides, imidazole derivatives and, in cases resistant to these drugs, Amphotericin B. Surgery is limited to abscesses, bone lesions and bronchial stenoses.

Adverse effects of antituberculosis drugs causing changes in treatment.

The adverse effects of drugs which caused changes in therapeutic regimens have been studied in 511 patients with pulmonary tuberculosis, at the Pavilion Koch of Buenos Aires University. In 384 patients who had not received any treatment before, the frequency of such modifications was 6.5%, and in 127 retreated patients it was 15.0%. The characteristics of the adverse effects and the measures aimed at reducing them were studied.

Evaluation of an enzyme-linked immunosorbent assay (ELISA) using an IgG antibody to Mycobacterium tuberculosis antigen 5 in the diagnosis of active tuberculosis in children.

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.