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      High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening

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          Abstract

          Background

          The prevalence of asymptomatic tuberculosis (TB) in recently diagnosed HIV-1-infected persons attending pre-antiretroviral therapy (ART) clinics is not well described. In addition, it is unclear if the detection of Mycobacterium tuberculosis in these patients clearly represents an early asymptomatic phase leading to progressive disease or transient excretion of bacilli.

          Objective

          To describe the prevalence and outcome of subclinical TB disease in HIV-1-infected persons not eligible for ART.

          Methods

          The study was conducted in 274 asymptomatic ART-naïve HIV-1-infected persons in Khayelitsha Day Hospital, Cape Town, South Africa. All participants were screened for TB using a symptom screen and spoligotyping was performed to determine genotypes.

          Results

          The prevalence of subclinical TB disease was 8.5% (95% CI 5.1% to 13.0%) (n=18; median days to culture positivity 17 days), with 22% of patients being smear-positive. Spoligotyping showed a diverse variety of genotypes with all paired isolates being of the same spoligotype, effectively excluding cross-contamination. 56% of patients followed up developed symptoms 3 days to 2 months later. All were well and still in care 6–12 months after TB diagnosis; 60% were started on ART. A positive tuberculin skin test (OR 4.96, p=0.064), low CD4 count (OR 0.996, p=0.06) and number of years since HIV diagnosis (OR 1.006, p=0.056) showed trends towards predicting TB disease.

          Conclusion

          This study found a high prevalence but good outcome (retained in care) of subclinical TB disease in HIV-1-infected persons. The results suggest that, in high HIV/TB endemic settings, a positive HIV-1 test should prompt TB screening by sputum culture irrespective of symptoms, particularly in those with a positive tuberculin skin test, longer history of HIV infection and low CD4 count. Operational difficulties in resource-constrained settings with respect to screening with TB culture highlight the need for rapid and affordable point-of-care tests to identify persons with clinical and subclinical TB disease.

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          Most cited references10

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          Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.

          The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection. 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.
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            Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis

            Summary Intensified case finding is the regular screening for evidence of tuberculosis in people infected with HIV, at high risk of HIV, or living in congregate settings. We systematically reviewed studies of intensified case finding published between January, 1994, and April, 2009. In 78 eligible studies, the number of people with tuberculosis detected during intensified case finding varied substantially between countries and target groups of patients. Median prevalence of newly diagnosed tuberculosis was 0·7% in population-based surveys, 2·2% in contact-tracing studies, 2·3% in mines, 2·3% in programmes preventing mother-to-child transmission of HIV, 2·5% in prisons, 8·2% in medical and antiretroviral treatment clinics, and 8·5% in voluntary counselling and testing services. Metaregression analysis of studies that included only people with HIV showed that for each increment in national prevalence of tuberculosis of 100 cases per 100 000 population, intensified case finding identified an additional one case per 100 screened individuals (p=0·03). Microbiological sputum examination of all individuals without prior selection by symptom screening yielded an additional four cases per 100 individuals screened (p=0·05). Data on the use of serial screening, treatment outcomes in actively identified cases of tuberculosis, and cost-effectiveness, however, were lacking. Concerted action is needed to develop intensified case finding as an important method for control of tuberculosis.
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              HIV infection-related tuberculosis: clinical manifestations and treatment.

              Several aspects of human immunodeficiency virus (HIV) infection-related tuberculosis (TB) and its treatment differ from those of TB in HIV-uninfected persons. The risk of TB and the clinical and radiographic manifestations of disease are primary examples. Antiretroviral therapy has a profound effect on lowering the risk of TB in HIV-infected persons, but it can also be associated with immune reconstitution inflammatory disease and unmasking of previously subclinical disease. There are also differences in treatment of HIV infection-related TB because of overlapping drug toxicities and drug-drug interactions between antiretroviral therapy and anti-TB therapy.
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                Author and article information

                Journal
                Thorax
                thorax
                thoraxjnl
                Thorax
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0040-6376
                1468-3296
                31 May 2011
                August 2011
                31 May 2011
                : 66
                : 8
                : 669-673
                Affiliations
                [1 ]Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa
                [2 ]Division of Medicine, Imperial College London, London, UK
                [3 ]Department of Public Health, University of Oxford, Old Road Campus, Headington, Oxford, UK
                [4 ]Medical Research Council, National Institute for Medical Research, Mill Hill, London, UK
                [5 ]Leiden University Medical Center, Leiden, The Netherlands
                Author notes
                Correspondence to Tolu Oni, 3.03 Wolfson Pavillion, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa; tolullahoni@ 123456doctors.org.uk
                Article
                thoraxjnl160168
                10.1136/thx.2011.160168
                3142344
                21632522
                614148ed-9766-4c41-99c1-e06e34cf74b2
                © 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 24 January 2011
                : 28 April 2011
                Categories
                Respiratory Infection
                1506
                Original article

                Surgery
                sub-clinical tuberculosis,hiv-1,mycobacterium tuberculosis,tuberculosis,screening,diagnosis,immunodeficiency

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