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      High Mortality in Adults Hospitalized for Active Tuberculosis in a Low HIV Prevalence Setting

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          Abstract

          Background

          This study aims to evaluate the outcomes of adults hospitalized for tuberculosis in a higher-income region with low HIV prevalence.

          Methods

          A retrospective cohort study was conducted on all adults hospitalized for pulmonary and/or extrapulmonary tuberculosis in an acute-care hospital in Hong Kong during a two-year period. Microscopy and solid-medium culture were routinely performed. The diagnosis of tuberculosis was made by: (1) positive culture of M. tuberculosis, (2) positive M. tuberculosis PCR result, (3) histology findings of tuberculosis infection, and/or (4) typical clinico-radiological manifestations of tuberculosis which resolved after anti-TB treatment, in the absence of alternative diagnoses. Time to treatment (‘early’, started during initial admission; ‘late’, subsequent periods), reasons for delay, and short- and long-term survival were analyzed.

          Results

          Altogether 349 patients were studied [median(IQR) age 62(48–77) years; non-HIV immunocompromised conditions 36.7%; HIV/AIDS 2.0%]. 57.9%, 16.3%, and 25.8% had pulmonary, extrapulmonary, and pulmonary-extrapulmonary tuberculosis respectively. 58.2% was smear-negative; 0.6% multidrug-resistant. 43.4% developed hypoxemia. Crude 90-day and 1-year all-cause mortality was 13.8% and 24.1% respectively. 57.6% and 35.8% received ‘early’ and ‘late’ treatment respectively, latter mostly culture-guided [median(IQR) intervals, 5(3–9) vs. 43(25–61) days]. Diagnosis was unknown before death in 6.6%. Smear-negativity, malignancy, chronic lung diseases, and prior exposure to fluoroquinolones (adjusted-OR 10.6, 95%CI 1.3–85.2) delayed diagnosis of tuberculosis. Failure to receive ‘early’ treatment independently predicted higher mortality (Cox-model, adjusted-HR 1.8, 95%CI 1.1–3.0).

          Conclusions

          Mortality of hospitalized tuberculosis patients is high. Newer approaches incorporating methods for rapid diagnosis and initiation of anti-tuberculous treatment are urgently required to improve outcomes.

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          Most cited references12

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          Tuberculosis

          Stephen D Lawn, Alimuddin I. Zumla, Gerardo Medina Basulto (2011)
          Tuberculosis results in an estimated 1·7 million deaths each year and the worldwide number of new cases (more than 9 million) is higher than at any other time in history. 22 low-income and middle-income countries account for more than 80% of the active cases in the world. Due to the devastating effect of HIV on susceptibility to tuberculosis, sub-Saharan Africa has been disproportionately affected and accounts for four of every five cases of HIV-associated tuberculosis. In many regions highly endemic for tuberculosis, diagnosis continues to rely on century-old sputum microscopy; there is no vaccine with adequate effectiveness and tuberculosis treatment regimens are protracted and have a risk of toxic effects. Increasing rates of drug-resistant tuberculosis in eastern Europe, Asia, and sub-Saharan Africa now threaten to undermine the gains made by worldwide tuberculosis control programmes. Moreover, our fundamental understanding of the pathogenesis of this disease is inadequate. However, increased investment has allowed basic science and translational and applied research to produce new data, leading to promising progress in the development of improved tuberculosis diagnostics, biomarkers of disease activity, drugs, and vaccines. The growing scientific momentum must be accompanied by much greater investment and political commitment to meet this huge persisting challenge to public health. Our Seminar presents current perspectives on the scale of the epidemic, the pathogen and the host response, present and emerging methods for disease control (including diagnostics, drugs, biomarkers, and vaccines), and the ongoing challenge of tuberculosis control in adults in the 21st century. Copyright © 2011 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 80 times – based on 0 reviews     Review now
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            Delay in diagnosis among hospitalized patients with active tuberculosis--predictors and outcomes.

            Christina Greenaway, J. FitzGerald, R Grewal … (2002)
            Delayed diagnosis of active pulmonary tuberculosis (TB) among hospitalized patients is common and believed to contribute significantly to nosocomial transmission. This study was conducted to define the occurrence, associated patient risk factors, and outcomes among patients and exposed workers of delayed diagnosis of active pulmonary TB. Among 429 patients newly diagnosed to have active pulmonary TB between June 1992 and June 1995 in 17 acute-care hospitals in four Canadian cities, initiation of appropriate treatment was delayed 1 week or more in 127 (30%). This was associated with atypical clinical and demographic patient characteristics, and after adjustment for these characteristics, with admission to hospitals with low TB admission rate of 0.2-3.3 per 10,000 admissions (odds ratio [OR]: 7.4; 95% confidence interval [CI]: 3.2,17.5) or intermediate TB admissions of 3.4-9.9/10,000 (OR: 2.3; CI: 1.6,3.2) as well as potentially preventable (late) intensive care unit admission (OR: 16.8; CI: 2.0,144) and death (OR: 3.3; CI: 1.7,6.5]). In hospitals with low TB admission rates, initially missed diagnosis, smear-positive patients undergoing bronchoscopy, late intensive care unit admission (OR: 2.3; CI: 0.1,56), and death (OR: 3.8; CI: 1.2,12.1) were more common than in hospitals with high TB admissions (> 10/ 10,000); a similar trend was seen in hospitals with intermediate TB admissions. Even after adjustment for workers' characteristics and ventilation in patients' rooms tuberculin conversions were disproportionately high in hospitals with low and intermediate TB admission rates and significantly higher in hospitals with overall TB mortality rate above 10% (OR: 2.5; CI: 1.6,3.7). In the hospitals studied, as the rate of TB admissions decreased, the likelihood of poor outcomes and risk of transmission of TB infection per hospitalized patient with TB increased. Institutional risk of TB transmission was poorly correlated with number of patients with TB and better correlated with indicators of patient care such as delayed diagnosis and treatment and overall TB-related patient mortality.
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              The impact of comorbidity on mortality following in-hospital diagnosis of tuberculosis.

              M Kollef, Gareth Fraser, E Iademarco … (1998)
              Despite the availability of curative chemotherapy, mortality remains high among patients hospitalized for tuberculosis. Although the elevated mortality rate is often attributed to the presence of multidrug resistant tuberculosis (MDRTB) or concomitant infection with the HIV, other factors must be contributory, especially among the HIV-negative population. Therefore, we performed a study to define the factors associated with mortality following the in-hospital diagnosis of tuberculosis in a region with low levels of MDRTB and coinfection with HIV. Retrospective cohort study. The eight hospitals in the Barnes-Jewish-Christian (BJC) Health System, which is a network of community and tertiary-care level facilities serving the St. Louis, MO, metropolitan area. All 203 patients hospitalized with culture-positive tuberculosis at one of the BJC system hospitals between 1988 and 1996. Follow-up information was obtained by telephone interview and review of medical and public health records. Death was verified through a search of the death certificate registry of Missouri and the records of the Social Security Administration. Mortality was defined as death from any cause during the 14 months following the initial date of hospitalization. The cumulative all-cause mortality rate for this cohort was 28.1%. The incidence of HIV positivity was 7.9% and of MDRTB was 1.5%. Multiple logistic regression analysis demonstrated that respiratory failure requiring mechanical ventilation (adjusted odds ratio [AOR] = 6.5; 95% confidence interval [CI] = 6.0 to 7.0; p 60 years (AOR = 3.5; 95% CI = 2.4 to 5.2; p 7-day delay in the suspicion of the diagnosis of tuberculosis and the institution of antituberculosis therapy following hospital admission. There was no association between the presence of these delays and mortality. Our data suggest that the 14-month mortality rate is high among patients diagnosed as having tuberculosis during hospitalization, despite low incidences of HIV infection and multidrug resistant disease. The factors that appear to contribute to this elevated mortality rate are markers of disease chronicity and severity of not only the tuberculosis, but also of the patient's underlying health status. Thus, while HIV positivity and multidrug resistance can be important determinants of mortality in some populations, other demographic factors and comorbid conditions may play a role as well. These data also suggest that tuberculosis is often superimposed on chronic illnesses that are important determinants of patient outcomes.
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                Author and article information

                Contributors
                Wenzhe Ho: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): 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: 2014
                Publication date (Electronic): 18 March 2014
                Volume: 9
                Issue: 3
                Electronic Location Identifier: e92077
                Affiliations
                [1 ]Department of Medicine and Therapeutics, Division of Infectious Diseases, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China
                [2 ]Faculty of Medicine, University of Sheffield, Sheffield, United Kingdom
                [3 ]Department of Microbiology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China
                [4 ]Stanley Ho Centre for Emerging Infectious Diseases, Chinese University of Hong Kong, Hong Kong SAR, China
                Temple University School of Medicine, United States Of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GL NL. Performed the experiments: GL RW FL TL. Analyzed the data: GL RW NL. Contributed reagents/materials/analysis tools: ML RL. Wrote the paper: GL JK NL.

                Article
                Publisher ID: PONE-D-13-48199
                DOI: 10.1371/journal.pone.0092077
                PMC ID: 3958438
                PubMed ID: 24642794
                SO-VID: 1d01d828-034d-4c62-9ab2-7d4c77d3cc7c
                Copyright statement: Copyright @ 2014
                License:

                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 : 18 November 2013
                Date accepted : 17 February 2014
                Page count
                Pages: 6
                Funding
                The authors have no support or funding to report.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Population Biology
                Subject: Population Metrics
                Subject: Death Rates
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Health Care
                Subject: Socioeconomic Aspects of Health
                Subject: Infectious Diseases
                Subject: Bacterial Diseases
                Subject: Tuberculosis
                Subject: Public and Occupational Health
                Subject: Tropical Diseases
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Clinical Research Design
                Subject: Cohort Studies
                Subject: Retrospective Studies
                Subject: Social Sciences
                Subject: Sociology
                Subject: Demography

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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