A high tuberculosis case-fatality rate in a setting of effective tuberculosis control: implications for acceptable treatment success rates.

Worldwide, the case-fatality rate of smear-positive pulmonary tuberculosis among persons on treatment is 3.8%. We assessed the case-fatality rate among such patients in Baltimore between January 1993 and June 1998. Tuberculosis incidence was < 17/100 000 population, and 99% of patients received directly observed therapy. Of 174 patients, 42 (24%) died on treatment. Patients who died were older (mean age 62 vs. 47 years; P < 0.001) and were more likely to have underlying medical conditions. In multivariate analyses, older age, diabetes mellitus, and renal failure were independently associated with an increased risk of death. With effective control, tuberculosis may become concentrated in older persons with chronic diseases and be associated with high case-fatality rates. In such settings, acceptable treatment success rates may need to be revised.

Paradoxical worsening of tuberculosis in HIV-infected persons.

OBJECTIVE: To determine the incidence of paradoxical worsening of tuberculosis (TB) in HIV-infected persons. DESIGN: Observational cohort study. SETTING: Public, urban TB clinic. PATIENTS: HIV-infected persons treated for TB between January 1, 1996, and December 31, 1999, and followed through June 30, 2000. INTERVENTION: Patients received standard anti-TB therapy. Antiretroviral therapy was provided by primary medical providers. Patients receiving antiretroviral therapy were given nucleoside reverse transcriptase inhibitors alone or highly active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors in combination with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor). MAIN OUTCOME MEASURE: Paradoxical worsening of TB. RESULTS: There were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82 cases (7%; 95% confidence interval, 3 to 15%). Paradoxical worsening occurred in 3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by paradoxical worsening were more likely to have both pulmonary and extrapulmonary disease at initial diagnosis than cases without paradoxical worsening (83% vs 24%; p = 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical worsening (p = 0.06). CONCLUSIONS: Paradoxical worsening of TB occurred less frequently than in previous reports and was not associated with HAART. Paradoxical worsening also appeared to be associated with an increased risk of TB relapse. Further studies are warranted to better characterize the risk factors for paradoxical worsening and the appropriate duration of anti-TB therapy in patients in whom it occurs.

Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons.

OBJECTIVE: To determine the rate of tuberculosis relapse among HIV-seropositive and -seronegative persons treated for active tuberculosis with short-course (6-month) therapy. DESIGN: Consecutive cohort study. SETTING: City of Baltimore tuberculosis clinic. PATIENTS: Tuberculosis patients treated between 1 January 1993 and 31 December 1996. INTERVENTION: Patients received 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin. MAIN OUTCOME MEASURE: Passive follow-up for tuberculosis relapse was performed through September 30, 1998. RESULTS: There were 423 cases of tuberculosis during the study period; 280 patients completed a 6-month course of therapy. Therapy was directly-observed for 94% of patients. Of those who completed therapy, 47 (17%) were HIV-seropositive, 127 (45%) were HIV-seronegative, and 106 (38%) had unknown HIV status. HIV-infected patients required more time to complete therapy (median 225 versus 205 days; P = 0.04) but converted sputum culture to negative within the same time period (median 77 versus 72 days; P = 0.43) as HIV-seronegative or unknown patients. Relapse occurred in three out of 47 (6.4%) HIV-infected patients compared to seven out of 127 (5.5%) HIV-seronegative patients (P = 1.0). Relapse rates also did not differ when HIV-seropositive patients were compared with HIV-seronegative and patients with unknown HIV status (6.4% versus 3.0%; P = 0.38). Of the 10 patients with tuberculosis relapse, restriction fragment length polymorphism data were available for five; all five relapse isolates matched the initial isolate. CONCLUSIONS: These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.

Measurement of gamma-interferon in culture supernatants of antigen-stimulated lymphocytes from patients with Schistosoma mansoni infections by a reverse passive haemagglutination assay.

An assay for gamma-interferon (IFN gamma) in human lymphocyte culture supernatants, based on reverse passive haemagglutination (RPH) of red cells bearing a monoclonal anti-IFN gamma antibody, was developed and compared with a conventional virus inhibition assay. Test samples comprised supernatants of lymphocytes from patients with Schistosoma mansoni infections, cultured with or without a soluble worm antigen preparation. The two assays gave comparable results, the correlations for individual samples being good. The RPH assay was both specific and sensitive, allowing the detection of IFN gamma at 13 u/ml (1 ng/ml) or less. The advantages of the RPH assay were that it was quick, relatively inexpensive and suitable for testing large numbers of samples. In particular, between-experiment variation was very low, allowing the assay of different samples on different occasions.