Browsing by Author "Wallis, Robert S."

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    Drug Tolerance in Mycobacterium tuberculosis
    (Antimicrobial agents and chemotherapy, 1999) Wallis, Robert S.; Patil, Shripad; Cheon, Seon-Hee; Edmonds, Kay; Phillips, Manijeh; Perkins, Mark D.; Joloba, Moses; Namale, Alice; Johnson, John L.; Teixeira, Lucileia; Dietze, Reynaldo; Siddiqi, Salman; Mugerwa, Roy D.; Eisenach, Kathleen; Ellner, Jerrold J.
    Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between mycobacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human immunodeficiency virus-uninfected subjects with pulmonary tuberculosis in Brazil and Uganda. The rate of killing in vitro was determined by monitoring the growth index (GI) in BACTEC 12B medium after addition of drug to established cultures and was measured as the number of days required for 99% sterilization. Drugs differed significantly in bactericidal activity, in the following order from greatest to least, rifampin > isoniazid-ethambutol > ethambutol (P < 0.001). Isolates from subjects who had relapses (n 5 2) or in whom persistence was prolonged (n 5 1) were significantly more tolerant of isoniazidethambutol and rifampin than isolates from other subjects (P < 0.01).
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    Immunoadjuvant Prednisolone Therapy for HIV-Associated Tuberculosis: A Phase 2 Clinical Trial in Uganda
    (The Journal of infectious diseases, 2005) Mayanja-Kizza, Harriet; Jones-Lopez, Edward; Okwera, Alphonse; Wallis, Robert S.; Mugerwa, Roy D.; Uganda–Case Western Research Collaboration
    Human immunodeficiency virus (HIV)–infected patients with tuberculosis (TB) respond to effective antituberculous therapy, but their prognosis remains poor. Mounting evidence from clinical studies supports the concept of copathogenesis in which immune activation that is triggered by TB and mediated by cytokines stimulates viral replication and worsens HIV infection, especially when immune function is preserved. We performed a phase 2, randomized, double-blind, placebo-controlled clinical trial in Kampala, Uganda, to determine whether immunoadjuvant prednisolone therapy in HIV-infected patients with TB who have CD4+ T cell counts ⩾200 cells/μL is safe and effective at increasing CD4+ T cell countsShort-term prednisolone therapy reduced levels of immune activation and tended to produce higher CD4+ T cell counts. Although prednisolone therapy was associated with a more rapid clearance of Mycobacterium tuberculosis from the sputum, it was also associated with a transient increase in HIV RNA levels, which receded when prednisolone therapy was discontinued. The intervention worsened underlying hypertension and caused fluid retention and hyperglycemiaThe benefits of prednisolone therapy on immune activation and CD4+ T cell counts do not outweigh the risks of adverse events in HIV-infected patients with TB and preserved immune function
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    Induction of the Antigen 85 Complex of Mycobacterium tuberculosis in Sputum: A Determinant of Outcome in Pulmonary Tuberculosis Treatment
    (The Journal of infectious diseases, 1998) Wallis, Robert S.; Perkins, Mark; Phillips, Manijeh; Joloba, Moses; Demchuk, Barbara; Namale, Alice; Johnson, John L.; Williams, Donna; Wolski, Kathy; Dietze, Reynaldo; Mugerwa, Roy D.; Eisenach, Kathleen; Ellner, Jerrold J.
    Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90–180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values 60 pg/mL responded rapidly to treatment and were cured. Of those with values 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy