Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome
Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)—infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement o...
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| Veröffentlicht in: | Clinical infectious diseases 2013-02, Vol.56 (3), p.450-460 |
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| creator | Marais, Suzaan Meintjes, Graeme Pepper, Dominique J. Dodd, Lori E. Schutz, Charlotte Ismail, Zahiera Wilkinson, Katalin A. Wilkinson, Robert J. |
| description | Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)—infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10 6 /L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4–62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53–.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART. |
| doi_str_mv | 10.1093/cid/cis899 |
| format | Article |
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Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)—infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10 6 /L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4–62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53–.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/cis899</identifier><identifier>PMID: 23097584</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; AIDS ; Anti-Retroviral Agents - therapeutic use ; Antiretroviral drugs ; Antitubercular Agents - therapeutic use ; Arts ; Bacterial diseases ; Bacterial diseases of the nervous system. Bacterial myositis ; Biological and medical sciences ; Central nervous system tuberculosis ; Cerebrospinal fluid ; Cerebrospinal Fluid - microbiology ; Drug therapy ; Female ; General aspects ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV/AIDS ; Human bacterial diseases ; Human immunodeficiency virus ; Humans ; Immune Reconstitution Inflammatory Syndrome - cerebrospinal fluid ; Immune Reconstitution Inflammatory Syndrome - drug therapy ; Immune Reconstitution Inflammatory Syndrome - etiology ; Immunopathology ; Infectious diseases ; Logistic Models ; Male ; Medical sciences ; Meningeal tuberculosis ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - isolation & purification ; Neutrophils ; Prospective Studies ; Risk Factors ; Severity of Illness Index ; South Africa ; TNF inhibitors ; Tuberculosis ; Tuberculosis and atypical mycobacterial infections ; Tuberculosis, Meningeal - cerebrospinal fluid ; Tuberculosis, Meningeal - drug therapy ; Tuberculosis, Meningeal - etiology ; Viral meningitis</subject><ispartof>Clinical infectious diseases, 2013-02, Vol.56 (3), p.450-460</ispartof><rights>Copyright © 2013 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>2014 INIST-CNRS</rights><rights>Copyright Oxford University Press, UK Feb 1, 2013</rights><rights>The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-a42792d4d713f7a11a34de240999693b2fc696ed91ea30f225779d623901b7293</citedby><cites>FETCH-LOGICAL-c491t-a42792d4d713f7a11a34de240999693b2fc696ed91ea30f225779d623901b7293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23482834$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23482834$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27204311$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23097584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marais, Suzaan</creatorcontrib><creatorcontrib>Meintjes, Graeme</creatorcontrib><creatorcontrib>Pepper, Dominique J.</creatorcontrib><creatorcontrib>Dodd, Lori E.</creatorcontrib><creatorcontrib>Schutz, Charlotte</creatorcontrib><creatorcontrib>Ismail, Zahiera</creatorcontrib><creatorcontrib>Wilkinson, Katalin A.</creatorcontrib><creatorcontrib>Wilkinson, Robert J.</creatorcontrib><title>Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)—infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10 6 /L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4–62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53–.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.</description><subject>Adult</subject><subject>AIDS</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antiretroviral drugs</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>Arts</subject><subject>Bacterial diseases</subject><subject>Bacterial diseases of the nervous system. Bacterial myositis</subject><subject>Biological and medical sciences</subject><subject>Central nervous system tuberculosis</subject><subject>Cerebrospinal fluid</subject><subject>Cerebrospinal Fluid - microbiology</subject><subject>Drug therapy</subject><subject>Female</subject><subject>General aspects</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV/AIDS</subject><subject>Human bacterial diseases</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune Reconstitution Inflammatory Syndrome - cerebrospinal fluid</subject><subject>Immune Reconstitution Inflammatory Syndrome - drug therapy</subject><subject>Immune Reconstitution Inflammatory Syndrome - etiology</subject><subject>Immunopathology</subject><subject>Infectious diseases</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meningeal tuberculosis</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - isolation & purification</subject><subject>Neutrophils</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><subject>South Africa</subject><subject>TNF inhibitors</subject><subject>Tuberculosis</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Tuberculosis, Meningeal - cerebrospinal fluid</subject><subject>Tuberculosis, Meningeal - drug therapy</subject><subject>Tuberculosis, Meningeal - etiology</subject><subject>Viral meningitis</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV1rFDEUhoMo9kNvvFcGpCDiaD4nyY0gxepCRbH1OmSTMzXLTFKTTGH_vdFda_Ui5MB58nJOHoSeEPyaYM3euODbKUrre-iQCCb7QWhyv9VYqJ4rpg7QUSkbjAlRWDxEB5RhLYXihyicZfixQHTbV90F3EAOtVU2-u5LBh9cDSl2aewulzVkt0xpKd0niCFehRpKt5rnJUL3FVyKpYa6_OZXcZzsPNua8ra72Eaf0wyP0IPRTgUe7-9j9O3s_eXpx_7884fV6bvz3nFNam85lZp67iVho7SEWMY9UI611oNmazq6QQ_gNQHL8EipkFL7gTKNyVpSzY7R213u9bKewTuINdvJXOcw27w1yQbzbyeG7-Yq3RgmOMYct4AX-4Cc2teUauZQHEyTjdDWN0RKpugwCNHQ5_-hm7Tk2NYzhA5KCqEFa9TLHeVyKiXDeDsMweaXQdMMmp3BBj-7O_4t-kdZA072gC3OTmO2sT39y0mKOSOkcU933KY0D3dyuKKKcfYTmDavjA</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Marais, Suzaan</creator><creator>Meintjes, Graeme</creator><creator>Pepper, Dominique J.</creator><creator>Dodd, Lori E.</creator><creator>Schutz, Charlotte</creator><creator>Ismail, Zahiera</creator><creator>Wilkinson, Katalin A.</creator><creator>Wilkinson, Robert J.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20130201</creationdate><title>Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome</title><author>Marais, Suzaan ; Meintjes, Graeme ; Pepper, Dominique J. ; Dodd, Lori E. ; Schutz, Charlotte ; Ismail, Zahiera ; Wilkinson, Katalin A. ; Wilkinson, Robert J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-a42792d4d713f7a11a34de240999693b2fc696ed91ea30f225779d623901b7293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>AIDS</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antiretroviral drugs</topic><topic>Antitubercular Agents - therapeutic use</topic><topic>Arts</topic><topic>Bacterial diseases</topic><topic>Bacterial diseases of the nervous system. Bacterial myositis</topic><topic>Biological and medical sciences</topic><topic>Central nervous system tuberculosis</topic><topic>Cerebrospinal fluid</topic><topic>Cerebrospinal Fluid - microbiology</topic><topic>Drug therapy</topic><topic>Female</topic><topic>General aspects</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>HIV/AIDS</topic><topic>Human bacterial diseases</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune Reconstitution Inflammatory Syndrome - cerebrospinal fluid</topic><topic>Immune Reconstitution Inflammatory Syndrome - drug therapy</topic><topic>Immune Reconstitution Inflammatory Syndrome - etiology</topic><topic>Immunopathology</topic><topic>Infectious diseases</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meningeal tuberculosis</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - isolation & purification</topic><topic>Neutrophils</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><topic>South Africa</topic><topic>TNF inhibitors</topic><topic>Tuberculosis</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Tuberculosis, Meningeal - cerebrospinal fluid</topic><topic>Tuberculosis, Meningeal - drug therapy</topic><topic>Tuberculosis, Meningeal - etiology</topic><topic>Viral meningitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marais, Suzaan</creatorcontrib><creatorcontrib>Meintjes, Graeme</creatorcontrib><creatorcontrib>Pepper, Dominique J.</creatorcontrib><creatorcontrib>Dodd, Lori E.</creatorcontrib><creatorcontrib>Schutz, Charlotte</creatorcontrib><creatorcontrib>Ismail, Zahiera</creatorcontrib><creatorcontrib>Wilkinson, Katalin A.</creatorcontrib><creatorcontrib>Wilkinson, Robert J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marais, Suzaan</au><au>Meintjes, Graeme</au><au>Pepper, Dominique J.</au><au>Dodd, Lori E.</au><au>Schutz, Charlotte</au><au>Ismail, Zahiera</au><au>Wilkinson, Katalin A.</au><au>Wilkinson, Robert J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>56</volume><issue>3</issue><spage>450</spage><epage>460</epage><pages>450-460</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><abstract>Background. Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)—infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. Methods. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Results. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10 6 /L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4–62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53–.99]). Conclusions. TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>23097584</pmid><doi>10.1093/cid/cis899</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult AIDS Anti-Retroviral Agents - therapeutic use Antiretroviral drugs Antitubercular Agents - therapeutic use Arts Bacterial diseases Bacterial diseases of the nervous system. Bacterial myositis Biological and medical sciences Central nervous system tuberculosis Cerebrospinal fluid Cerebrospinal Fluid - microbiology Drug therapy Female General aspects HIV HIV Infections - complications HIV Infections - drug therapy HIV/AIDS Human bacterial diseases Human immunodeficiency virus Humans Immune Reconstitution Inflammatory Syndrome - cerebrospinal fluid Immune Reconstitution Inflammatory Syndrome - drug therapy Immune Reconstitution Inflammatory Syndrome - etiology Immunopathology Infectious diseases Logistic Models Male Medical sciences Meningeal tuberculosis Mycobacterium tuberculosis Mycobacterium tuberculosis - isolation & purification Neutrophils Prospective Studies Risk Factors Severity of Illness Index South Africa TNF inhibitors Tuberculosis Tuberculosis and atypical mycobacterial infections Tuberculosis, Meningeal - cerebrospinal fluid Tuberculosis, Meningeal - drug therapy Tuberculosis, Meningeal - etiology Viral meningitis |
| title | Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome |
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