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      Pathomorphological peculiarities of tuberculous meningoencephalitis associated with HIV infection


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          Background and aims

          One of the most severe manifestation displays of tuberculosis (TB) generalization is meningitis/meningoencephalitis. The purpose of this work was to improve the diagnostic efficiency of TB central nervous system (CNS) affection in human immunodeficiency virus (HIV)-infected persons.

          Materials and methods

          Meninges and cerebral tissues, taken from died patients, who were HIV-infected and dead from TB of CNS affection, were investigated histologically.

          Results and discussion

          Our examination showed that clinical course of the pathologic process loses the peculiarity of TB-undulating character, and changes in tissues have monomorphism that appears in the presence of the same type of granulomas with a few Pirogov–Langhans cells. Alterative reactions with formation of the large fields of caseous necrosis, necrotic focuses, areas of infiltration with polymorphic cellular elements went out on the first plan in the disorder of cerebrum in patients with the terminal stage of HIV infection. The tendency to decrease in inflammatory–proliferative processes was observed, which is confirmed by the presence of the poorly expressed cellular reaction on the peripheries of focuses of caseous necrosis.


          Morphologic features of tuberculous meningoencephalitis in HIV-infected patients are the presence of edema, gliosis, trombovasculitis, small focal hemorrhage, tuberculous granuloma formation with a small number of Pirogov–Langhans cells, and the prevalence of alterative–exudative reactions.

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          Most cited references18

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          Site of extrapulmonary tuberculosis is associated with HIV infection.

          In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB. We retrospectively reviewed 320 cases of EPTB from 1995-2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease. Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18-89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4). Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.
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            Central nervous system tuberculosis.

            Central nervous system (CNS) involvement, one of the most devastating clinical manifestations of tuberculosis (TB) is noted in 5 to 10% of extrapulmonary TB cases, and accounts for approximately 1% of all TB cases. Definitive diagnosis of tuberculous meningitis (TBM) depends upon the detection of the tubercle bacilli in the CSF. Every patient with TBM should preferably be evaluated by imaging with contrast enhanced CT either before or within the first 48 hours of treatment. An extra-neural focus of tuberculosis should be sought clinically and radiologically in all patients with CNS TB as it may indicate safer and more accessible sites for diagnostic samplings. A minimum of 10 months treatment is warranted, prompted by the uncertain influences of disease severity, CNS drug penetration, undetected drug resistance and patient compliance. All patients with TB meningitis may receive adjunctive corticosteroids at presentation regardless of disease severity even for those with HIV infection. Drug resistance is strongly associated with previous treatment. The key principle of managing drug-resistant TB is never to add a single drug to a failing regimen. Early ventriculo-peritoneal shunting should be considered in those with hydrocephalus failing medical management. The single most important determinant of outcome is the stage of tuberculous meningitis at which treatment has been started.
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              High Mortality in Adults Hospitalized for Active Tuberculosis in a Low HIV Prevalence Setting

              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.

                Author and article information

                Interventional Medicine and Applied Science
                Interventional Medicine and Applied Science
                Akadémiai Kiadó (Budapest )
                14 September 2017
                September 2017
                : 9
                : 3
                : 144-149
                [ 1 ]Department of Infectious Diseases, Kharkiv National Medical University , Kharkiv, Ukraine
                Author notes
                [* ]Corresponding author: Vitalii V. Gargin; Department of Infectious Diseases, Kharkiv National Medical University, Avenue Nauki 4, Kharkiv 61022, Ukraine; Phone: +380 990498557; E-mail: vitgarg@ 123456ukr.net
                © 2017 The Author(s)

                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 for non-commercial purposes, provided the original author and source are credited.

                : 23 February 2017
                : 21 July 2017
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 19, Pages: 6
                Funding sources: No financial support was received for this study.
                ORIGINAL PAPER

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                HIV infection,brain,meningoencephalitis,tuberculosis,histology


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