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      Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India

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          Abstract

          Background

          India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India.

          Methods

          HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment.

          Results

          Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment.

          Conclusions

          Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.

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          Xpert MTB/RIF: a new pillar in diagnosis of extrapulmonary tuberculosis?

          Catharina Boehme, David Alland, Camilla Rodrigues … (2011)
          Approximately 10 to 15% of tuberculosis (TB) cases in India are estimated to have extrapulmonary disease, and due to a lack of diagnostic means, they often remain untreated. The early detection of Mycobacterium tuberculosis and multidrug resistance is a priority in TB diagnosis to improve the successful treatment rate of TB and reduce transmission. The Xpert MTB/RIF (Xpert) test, recently endorsed by the World Health Organization for the detection of pulmonary TB, was evaluated to test its utility in 547 patients with suspected extrapulmonary tuberculosis. Five hundred forty-seven extrapulmonary specimens were split and processed simultaneously for both culture (solid and liquid) and Xpert testing. For culture, the sensitivity was low, 53% (150/283 specimens). Xpert sensitivity and specificity results were assessed in comparison to a composite reference standard made up of smear and culture results and clinical, radiological, and histological findings. The sensitivity of the Xpert assay was 81% (228/283 specimens) (64% [89/138] for smear-negative cases and 96% [139/145] for smear-positive cases), with a specificity of 99.6%. The sensitivity was found to be high for the majority of specimen types (63 to 100%) except for cerebrospinal fluid, the sensitivity of which was 29% (2/7 specimens). The Xpert test correctly identified 98% of phenotypic rifampin (RIF)-resistant cases and 94% of phenotypic RIF-susceptible cases. Sequencing of the 6 discrepant samples resolved 3 of them, resulting in an increased specificity of 98%. In conclusion, the results of this study suggest that the Xpert test also shows good potential for the diagnosis of extrapulmonary TB and that its ease of use makes it applicable for countries where TB is endemic.
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            Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

            Flavio Alcantara, Dae-Hyun Kim, Jennifer Furin … (2003)
            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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              HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality.

              Jason R Andrews, Michelle Scott, Anthony P. Moll … (2010)
              The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected. To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates. We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records. Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001). Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2011
                Publication date (Electronic): 1 December 2011
                Volume: 6
                Issue: 12
                Electronic Location Identifier: e28066
                Affiliations
                [1 ]Médecins Sans Frontières, Mumbai, India
                [2 ]Médecins Sans Frontières, Cape Town, South Africa
                [3 ]Monash University, Melbourne, Australia
                [4 ]Hygiene and Preventive Medicine Institute, University of Sassari, Sassari, Italy
                [5 ]S. Maugeri Foundation, World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, Italy
                [6 ]Deptartment of Infectious Diseases, Galliera Hospital, Genoa, Italy
                [7 ]P.D. Hinduja National Hospital and Medical Research Centre (Hinduja), Mumbai, India
                [8 ]Médecins Sans Frontières, Operational Research Unit, Brussels, Belgium
                London School of Hygiene and Tropical Medicine, United Kingdom
                Author notes

                Conceived and designed the experiments: CM PI. Performed the experiments: BV HM CM CR. Analyzed the data: PI. Contributed reagents/materials/analysis tools: HSC BV EDS. Wrote the paper: PI CM TR HSC. Critically revised the manuscript: JL GS GBM EP PS.

                Article
                Publisher ID: PONE-D-11-17477
                DOI: 10.1371/journal.pone.0028066
                PMC ID: 3228724
                PubMed ID: 22145022
                SO-VID: fcdf82bb-84a3-4394-a943-d40ae4ba2318
                Copyright © Isaakidis 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
                Date received : 6 September 2011
                Date accepted : 31 October 2011
                Page count
                Pages: 9
                Categories
                Subject: Research Article
                Subject: Biology
                Subject: Microbiology
                Subject: Virology
                Subject: Viral Disease Diagnosis
                Subject: Population Biology
                Subject: Epidemiology
                Subject: Disease Informatics
                Subject: Infectious Disease Epidemiology
                Subject: Medicine
                Subject: Clinical Research Design
                Subject: Observational Studies
                Subject: Prospective Studies
                Subject: Infectious Diseases
                Subject: Bacterial Diseases
                Subject: Tuberculosis
                Subject: Multi-Drug-Resistant Tuberculosis
                Subject: Tropical Diseases (Non-Neglected)
                Subject: Tuberculosis
                Subject: Viral Diseases
                Subject: HIV
                Subject: Infectious Disease Control

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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