Biomarkers for Clinical and Incipient Tuberculosis: Performance in a TB-Endemic Country
Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity o...
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| Published in | PloS one Vol. 3; no. 4; p. e2071 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
30.04.2008
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0002071 |
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| Abstract | Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.
Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.
These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB. |
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| AbstractList | Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.
Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.
These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB. Simple biomarkers are required to identify TB in both HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV.sup.+ subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4.sup.+ T cell-matched HIV.sup.+ TB.sup.- subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB. Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD.sup.+ or PPD.sup.- healthy subjects, healthy community members, and HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients from India. Results demonstrate high sensitivity (~80%) of detection of smear-positive HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients, and high specificity (>97%) with PPD.sup.+ subjects and endemic controls. While ~45% of the asymptomatic HIV.sup.+ TB.sup.- patients at high-risk for TB tested biomarker-positive, >97% of the HIV.sup.+ TB.sup.- subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV.sup.+ subjects. These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV.sup.+ TB.sup.+ patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV.sup.+ TB.sup.- subjects at high-risk for TB. Background Simple biomarkers are required to identify TB in both HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV.sup.+ subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4.sup.+ T cell-matched HIV.sup.+ TB.sup.- subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB. Methods and Results Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD.sup.+ or PPD.sup.- healthy subjects, healthy community members, and HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients from India. Results demonstrate high sensitivity (~80%) of detection of smear-positive HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients, and high specificity (>97%) with PPD.sup.+ subjects and endemic controls. While ~45% of the asymptomatic HIV.sup.+ TB.sup.- patients at high-risk for TB tested biomarker-positive, >97% of the HIV.sup.+ TB.sup.- subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV.sup.+ subjects. Conclusions These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV.sup.+ TB.sup.+ patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV.sup.+ TB.sup.- subjects at high-risk for TB. Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.BACKGROUNDSimple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.METHODS AND RESULTSAnti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB.CONCLUSIONSThese biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB. Background Simple biomarkers are required to identify TB in both HIV−TB+ and HIV+TB+ patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and –MPT51 antibodies as biomarkers for TB in HIV−TB+ and HIV+TB+ patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV+ subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4+ T cell-matched HIV+TB− subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB. Methods and Results Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD+ or PPD− healthy subjects, healthy community members, and HIV−TB+ and HIV+TB+ patients from India. Results demonstrate high sensitivity (∼80%) of detection of smear-positive HIV−TB+ and HIV+TB+ patients, and high specificity (>97%) with PPD+ subjects and endemic controls. While ∼45% of the asymptomatic HIV+TB− patients at high-risk for TB tested biomarker-positive, >97% of the HIV+TB− subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV+ subjects. Conclusions These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV+TB+ patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV+TB− subjects at high-risk for TB. Background Simple biomarkers are required to identify TB in both HIV−TB+ and HIV+TB+ patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and –MPT51 antibodies as biomarkers for TB in HIV−TB+ and HIV+TB+ patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV+ subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4+ T cell-matched HIV+TB− subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB. Methods and Results Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD+ or PPD− healthy subjects, healthy community members, and HIV−TB+ and HIV+TB+ patients from India. Results demonstrate high sensitivity (∼80%) of detection of smear-positive HIV−TB+ and HIV+TB+ patients, and high specificity (>97%) with PPD+ subjects and endemic controls. While ∼45% of the asymptomatic HIV+TB− patients at high-risk for TB tested biomarker-positive, >97% of the HIV+TB− subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV+ subjects. Conclusions These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV+TB+ patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV+TB− subjects at high-risk for TB. Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB. |
| Audience | Academic |
| Author | Sethi, Sunil Liu, Zhentong Wanchu, Ajay Dong, Yuxin Belisle, John Myneedu, V. P. Nadas, Arthur Laal, Suman |
| AuthorAffiliation | 7 Institute of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America 3 Department of Microbiology, Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases, New Delhi, India 5 Department of Pathology, New York University School of Medicine, New York, New York, United States of America 1 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India 2 Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India Oregon Health & Science University, United States of America 4 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America 8 Veterans Affairs Medical Center, New York, New York, United States of America 6 Department of Microbiology, New York University School of Medicine, New York, New York, United States of America |
| AuthorAffiliation_xml | – name: 5 Department of Pathology, New York University School of Medicine, New York, New York, United States of America – name: 6 Department of Microbiology, New York University School of Medicine, New York, New York, United States of America – name: Oregon Health & Science University, United States of America – name: 1 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India – name: 4 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America – name: 7 Institute of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America – name: 8 Veterans Affairs Medical Center, New York, New York, United States of America – name: 3 Department of Microbiology, Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases, New Delhi, India – name: 2 Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India |
| Author_xml | – sequence: 1 givenname: Ajay surname: Wanchu fullname: Wanchu, Ajay – sequence: 2 givenname: Yuxin surname: Dong fullname: Dong, Yuxin – sequence: 3 givenname: Sunil surname: Sethi fullname: Sethi, Sunil – sequence: 4 givenname: V. P. surname: Myneedu fullname: Myneedu, V. P. – sequence: 5 givenname: Arthur surname: Nadas fullname: Nadas, Arthur – sequence: 6 givenname: Zhentong surname: Liu fullname: Liu, Zhentong – sequence: 7 givenname: John surname: Belisle fullname: Belisle, John – sequence: 8 givenname: Suman surname: Laal fullname: Laal, Suman |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18446210$$D View this record in MEDLINE/PubMed |
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| Copyright_xml | – notice: COPYRIGHT 2008 Public Library of Science – notice: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2008 |
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| DOI | 10.1371/journal.pone.0002071 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: SL. Performed the experiments: YD SS. Analyzed the data: SL. Wrote the paper: SL. Other: Purifed the recombinant antigens: JB ZL. Performed the statistical analysis: AN. Recruited HIV−TB+ patients from LRS, performed bacteriological assessment of these patients: VM. Recruited and bled HIV−TB+ patients and community controls from PGIMER, performed the ELISA assays with the two antigens with their sera: SS. Recruited HIV+TB+ patients, HIV+TB- HR subjects, performed their clinical, radiological, CD4+ T cell status assessments: AW. |
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| Snippet | Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase... Background Simple biomarkers are required to identify TB in both HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients. Earlier studies have identified the M.... Simple biomarkers are required to identify TB in both HIV.sup.- TB.sup.+ and HIV.sup.+ TB.sup.+ patients. Earlier studies have identified the M. tuberculosis... Background Simple biomarkers are required to identify TB in both HIV−TB+ and HIV+TB+ patients. Earlier studies have identified the M. tuberculosis Malate... Background Simple biomarkers are required to identify TB in both HIV−TB+ and HIV+TB+ patients. Earlier studies have identified the M. tuberculosis Malate... |
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| SubjectTerms | Acquired immune deficiency syndrome AIDS Antibodies Antibodies, Bacterial - immunology Antigens Antigens, Bacterial - immunology Bacterial Proteins - immunology Biological markers Biomarkers Biomarkers - metabolism Case-Control Studies CD4 antigen Endemic Diseases Epidemics Health risks HIV HIV infections HIV Seropositivity - complications HIV Seropositivity - microbiology Human immunodeficiency virus Humans Immunology Immunology/Immune Response India - epidemiology Infectious Diseases/Respiratory Infections Lymphocytes T Malate synthase Malate Synthase - immunology Medical diagnosis Medical research Mycobacterium tuberculosis Mycobacterium tuberculosis - enzymology Mycobacterium tuberculosis - immunology Patients Risk Risk Factors Sensitivity Sensitivity analysis Smear T cells Tuberculin - immunology Tuberculosis Tuberculosis - complications Tuberculosis - diagnosis Tuberculosis - epidemiology |
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| Title | Biomarkers for Clinical and Incipient Tuberculosis: Performance in a TB-Endemic Country |
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