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      Early Outcomes of MDR-TB Treatment in a High HIV-Prevalence Setting in Southern Africa

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          Abstract

          Background

          Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa.

          Methodology/Principal Findings

          We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/μl (range 5–824 cells/μl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12–451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12–374 days).

          Conclusions/Significance

          In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings.

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          Most cited references26

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          HIV infection and multidrug-resistant tuberculosis: the perfect storm.

          Multidrug-resistant (MDR) tuberculosis (TB) has emerged as a global epidemic, with ~425,000 new cases estimated to occur annually. The global human immunodeficiency virus (HIV) infection epidemic has caused explosive increases in TB incidence and may be contributing to increases in MDR-TB prevalence. We reviewed published studies and available surveillance data evaluating links between HIV infection and MDR-TB to quantify convergence of these 2 epidemics, evaluate the consequences, and determine essential steps to address these epidemics. Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness led to extraordinary attack rates and case-fatality rates among HIV-infected persons. Whether this sequence occurs in communities is less clear. MDR-TB appears not to cause infection or disease more readily than drug-susceptible TB in HIV-infected persons. HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin resistance. HIV-infected patients with MDR-TB have unacceptably high mortality; both antiretroviral and antimycobacterial treatment are necessary. Simultaneous treatment requires 6-10 different drugs. In HIV-prevalent countries, TB programs struggle with increased caseloads, which increase the risk of acquired MDR-TB. Surveillance data suggest that HIV infection and MDR-TB may converge in several countries. Institutional outbreaks, overwhelmed public health programs, and complex clinical management issues may contribute to the convergence of the MDR-TB and HIV infection epidemics. To forestall disastrous consequences, infection control, rapid case detection, effective treatment, and expanded program capacity are needed urgently.
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            Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

            Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes. Copyright 2003 Massachusetts Medical Society
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              Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

              Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                25 September 2009
                : 4
                : 9
                : e7186
                Affiliations
                [1 ]Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America
                [2 ]Partners In Health, Lesotho, Maseru, Lesotho
                McGill University, Canada
                Author notes

                Conceived and designed the experiments: KJS HS. Performed the experiments: KJS DBO HS. Analyzed the data: KJS HS. Wrote the paper: KJS SK JF PEF HS.

                Article
                09-PONE-RA-10948R1
                10.1371/journal.pone.0007186
                2746313
                19779624
                13371fcf-544f-416f-86eb-d8a5ce2dd3cd
                Seung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 10 June 2009
                : 25 August 2009
                Page count
                Pages: 7
                Categories
                Research Article
                Infectious Diseases/Antimicrobials and Drug Resistance
                Infectious Diseases/HIV Infection and AIDS
                Infectious Diseases/Respiratory Infections
                Respiratory Medicine/Respiratory Infections

                Uncategorized
                Uncategorized

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