Biomarkers for clinical and incipient tuberculosis: Performance in a TB-endemic country

Ajay Wanchu, Yuxin Dong, Sunil Sethi, V. P. Myneedu, Arthur Nadas, Zhentong Liu, John Belisle, Suman Laal

Research output: Contribution to journalArticle

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Abstract

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 MPTS1 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.

Original languageEnglish (US)
Article numbere2071
JournalPLoS One
Volume3
Issue number4
DOIs
StatePublished - Apr 30 2008
Externally publishedYes

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Biomarkers
tuberculosis
biomarkers
Tuberculosis
HIV
Malate Synthase
malate synthase
Tuberculin
India
Immunodominant Epitopes
antibodies
T-cells
Antibodies
HIV infections
Sensitivity and Specificity
T-lymphocytes
lungs
HIV Infections
Healthy Volunteers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wanchu, A., Dong, Y., Sethi, S., Myneedu, V. P., Nadas, A., Liu, Z., ... Laal, S. (2008). Biomarkers for clinical and incipient tuberculosis: Performance in a TB-endemic country. PLoS One, 3(4), [e2071]. https://doi.org/10.1371/journal.pone.0002071

Biomarkers for clinical and incipient tuberculosis : Performance in a TB-endemic country. / Wanchu, Ajay; Dong, Yuxin; Sethi, Sunil; Myneedu, V. P.; Nadas, Arthur; Liu, Zhentong; Belisle, John; Laal, Suman.

In: PLoS One, Vol. 3, No. 4, e2071, 30.04.2008.

Research output: Contribution to journalArticle

Wanchu, A, Dong, Y, Sethi, S, Myneedu, VP, Nadas, A, Liu, Z, Belisle, J & Laal, S 2008, 'Biomarkers for clinical and incipient tuberculosis: Performance in a TB-endemic country', PLoS One, vol. 3, no. 4, e2071. https://doi.org/10.1371/journal.pone.0002071
Wanchu, Ajay ; Dong, Yuxin ; Sethi, Sunil ; Myneedu, V. P. ; Nadas, Arthur ; Liu, Zhentong ; Belisle, John ; Laal, Suman. / Biomarkers for clinical and incipient tuberculosis : Performance in a TB-endemic country. In: PLoS One. 2008 ; Vol. 3, No. 4.
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abstract = "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 MPTS1 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.",
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AU - Myneedu, V. P.

AU - Nadas, Arthur

AU - Liu, Zhentong

AU - Belisle, John

AU - Laal, Suman

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N2 - 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 MPTS1 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.

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