Paradoxical Worsening of Tuberculosis in HIV-Infected Persons

Wendel, Karen A.; Alwood, Karla; Gachuhi, Regina; Chaisson, Richard E.; Bishai, William R.; Sterling, Timothy R.

doi:10.1378/chest.120.1.193

Cited by 138 publications

(80 citation statements)

References 25 publications

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“…of patients with HIV-TB coinfection develop IRD (11,13,15,71,77,102,104,128,129,149), beginning as early as 5 days after starting ART (116). Most patients develop symptoms within the first 2 to 6 weeks (71,77,104,128,129), though cases may occur after 1 to 4 years (58,62,129).…”

Section: Introductionmentioning

confidence: 99%

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

et al. 2009

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SUMMARY Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.

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Section: Introductionmentioning

confidence: 99%

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

et al. 2009

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“…This phenomenon has been described in patients who initially improve with anti-tuberculous chemotherapy, then have immune-mediated enlargement of existing lesions, but remain culture-negative 14,15 . It has also been described in acquired immunodeficiency syndrome (AIDS) patients with subclinical tuberculosis (normal chest radiographs) that were treated with highly active anti-retroviral therapy (HAART) in whom CD4+ T cells rebound and culture-positive tuberculosis is unmasked and progresses rapidly after treatment initiation [15][16][17] . With the introduction of HAART in areas where tuberculosis in endemic, reactivation of undiagnosed or latent tuberculosis may prove to be a problem, and would result in enhanced transmission of the disease.…”

Section: Discussionmentioning

confidence: 94%

The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome

et al. 2008

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The large reservoir of human latent tuberculosis (TB) contributes to the global success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary human latent TB. The lung burden of infection peaked at 5 weeks after aerosol infection followed by host containment of infection that was achieved in all rabbits. One-third of rabbits had at least one caseous granuloma with culturable bacilli at 36 weeks after infection suggesting persistent paucibacillary infection. Corticosteroid-induced immunosuppression initiated after disease containment resulted in reactivation of disease. Seventy-two percent of rabbits had culturable bacilli in the right upper lung lobe homogenates compared to none of the untreated controls. Discontinuation of dexamethasone led to predictable lymphoid recovery, with a proportion of rabbits developing multicentric large caseous granuloma. The development and severity of the immune reconstitution inflammatory syndrome (IRIS) was dependent on the antigen load at the time of immunosuppression and subsequent bacillary replication during corticosteroid-induced © 2007 Elsevier Ltd. All rights reserved. *Correspondence and requests for reprints should be addressed to: Yukari C. Manabe, MD Johns Hopkins University School of Medicine 1147B Rutland Street, Rm 1147B Baltimore, MD 21205 Phone: (410)614-6600 Fax: (410)614-9775 ymanabe@jhmi.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

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“…8 Studies to determine the incidence of TB-IRIS among HIV-infected patients demonstrated a wide range of 11% to 45% incidence over a duration of 1 year. 1,2,7,8,15,16 In a South African prospective study, only baseline CD4 count was an independent predictor of IRIS and a high CD 4 count was protective against IRIS. Ethiopian studies to determine the incidence of IRIS include one in an Addis Ababa, Ethiopia hospital to determine the incidence of IRIS and the pattern of opportunistic infections among 186 HIV/AIDS patients receiving ART.…”

Section: Discussionmentioning

confidence: 97%