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      Incidence Rates for Tuberculosis Among HIV Infected Patients in Northern Tanzania

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          Abstract

          Background: HIV and tuberculosis (TB) are leading infectious diseases, with a high risk of co-infection. The risk of TB in people living with HIV (PLHIV) is high soon after sero-conversion and increases as the CD4 counts are depleted.

          Methodology: We used routinely collected data from Care and Treatment Clinics (CTCs) in three regions in northern Tanzania. All PLHIV attending CTCs between January 2012 to December 2017 were included in the analysis. TB incidence was defined as cases started on anti-TB medications divided by the person-years of follow-up. Poisson regression with frailty models were used to determine incidence rate ratios (IRR) and 95% confidence intervals (95% CI) for predictors of TB incidences among HIV positive patients.

          Results: Among 78,748 PLHIV, 405 patients developed TB over 195,296 person-years of follow-up, giving an overall TB incidence rate of 2.08 per 1,000 person-years. There was an increased risk of TB incidence, 3.35 per 1,000 person-years, in hospitals compared to lower level health facilities. Compared to CD4 counts of <350 cells/μl, a high CD4 count was associated with lower TB incidence, 81% lower for a CD4 count of 350–500 cells/μl (IRR 0.19, 95% CI 0.04–0.08) and 85% lower for those with a CD4 count above 500 cells/μl (IRR 0.15, 95% CI 0.04–0.64). Independently, those taking ART had 66% lower TB incidences (IRR 0.34, 95% CI 0.15–0.79) compared to those not taking ART. Poor nutritional status and CTC enrollment between 2008 and 2012 were associated with higher TB incidences IRR 9.27 (95% CI 2.15–39.95) and IRR 2.97 (95% CI 1.05–8.43), respectively.

          Discussion: There has been a decline in TB incidence since 2012, with exception of the year 2017 whereby there was higher TB incidence probably due to better diagnosis of TB following a national initiative. Among HIV positive patients attending CTCs, poor nutritional status, low CD4 counts and not taking ART treatment were associated with higher TB incidence, highlighting the need to get PLHIV on treatment early, and the need for close monitoring of CD4 counts. Data from routinely collected and available health services can be used to provide evidence of the epidemiological risk of TB.

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          Most cited references40

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          Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa.

          To determine the short-term and long-term risks of tuberculosis (TB) associated with CD4 cell recovery during antiretroviral therapy (ART). Observational community-based ART cohort in South Africa. TB incidence was determined among patients (n = 1480) receiving ART for up to 4.5 years in a South African community-based service. Updated CD4 cell counts were measured 4-monthly. Person-time accrued within a range of CD4 cell count strata (CD4 cell strata) was calculated and used to derive CD4 cell-stratified TB rates. Factors associated with incident TB were identified using Poisson regression models. Two hundred and three cases of TB were diagnosed during 2785 person-years of observation (overall incidence, 7.3 cases/100 person-years). During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500 and more than 500 cells/microl unadjusted TB incidence rates were 16.8, 9.3, 5.5, 4.6, 4.2 and 1.5 cases/100 person-years, respectively (P < 0.001). During early ART (first 4 months), adjusted TB rates among those with CD4 cell counts 0-200 cells/microl were 1.7-fold higher than during long-term ART (P = 0.026). Updated CD4 cell counts were the only patient characteristic independently associated with long-term TB risk. Updated CD4 cell counts were the dominant predictor of TB risk during ART in this low-resource setting. Among those with baseline CD4 cell counts less than 200 cells/microl, the excess adjusted risk of TB during early ART was consistent with 'unmasking' of disease missed at baseline screening. TB incidence rates at CD4 cell counts of 200-500 cells/microl remained high and adjunctive interventions are required. TB prevention would be improved by ART policies that minimized the time patients spend with CD4 cell counts below a threshold of 500 cells/microl.
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            The HIV-associated tuberculosis epidemic--when will we act?

            Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners.

              We hypothesized that rapid presentation may be a general feature of tuberculosis (TB) associated with human immunodeficiency virus (HIV) that limits the impact of HIV on the point prevalence of TB. To investigate this, we performed a cross-sectional HIV and TB disease survey with retrospective and prospective follow-up. HIV prevalence among 1,773 systematically recruited miners was 27%. TB incidence was much more strongly HIV associated (incidence rate ratio, 5.5; 95% confidence interval [CI], 3.5-8.6) than the point prevalence of undiagnosed TB disease (odds ratio, 1.7; 95% CI, 0.9-3.3). For smear-positive TB, 7 of 9 (78%) prevalent cases were HIV negative, and point prevalence was nonsignificantly lower in miners who were HIV positive (odds ratio, 0.8; 95% CI, 0.1-4.2). The calculated mean duration of smear positivity before diagnosis (point prevalence/incidence) was substantially shorter for HIV-positive than HIV-negative TB patients (0.17 and 1.15 years, respectively; ratio, 0.15; 95% CI, 0.00-0.73). HIV has considerably less impact on the point prevalence of TB disease than on TB incidence, probably because rapid disease progression increases presentation and case-finding rates. The difference in mean duration of smear positivity was particularly marked and, if generalizable, will have major implications for TB control prospects in high HIV prevalence areas.
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                Author and article information

                Contributors
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                24 October 2019
                2019
                : 7
                : 306
                Affiliations
                [1] 1Department of Epidemiology and Biostatistics, Institute of Public Health, Kilimanjaro Christian Medical University College , Moshi, Tanzania
                [2] 2Northern Zone Blood Transfusion Center , Moshi, Tanzania
                [3] 3National AIDS Control Program , Dar es Salaam, Tanzania
                [4] 4Department of Population Health, London School of Hygiene and Tropical Medicine , London, United Kingdom
                [5] 5Department of Community Health, Institute of Public Health, Kilimanjaro Christian Medical University College , Moshi, Tanzania
                [6] 6Department of Community Medicine, KCMC Hospital , Moshi, Tanzania
                Author notes

                Edited by: Vitali Sintchenko, University of Sydney, Australia

                Reviewed by: Pedro Xavier-Elsas, Federal University of Rio de Janeiro, Brazil; Carl-Magnus Svensson, Leibniz Institute for Natural Product Research and Infection Biology, Germany

                *Correspondence: Edson W. Mollel e.mollel@ 123456kcri.ac.tz

                This article was submitted to Infectious Diseases - Surveillance, Prevention and Treatment, a section of the journal Frontiers in Public Health

                Article
                10.3389/fpubh.2019.00306
                6821649
                31709218
                0106b112-97ca-4306-8b86-2fec22b2db24
                Copyright © 2019 Mollel, Maokola, Todd, Msuya and Mahande.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 July 2019
                : 07 October 2019
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 53, Pages: 9, Words: 7261
                Categories
                Public Health
                Original Research

                tuberculosis,hiv,tanzania,incidence rates,sub-saharan africa

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