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


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 (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.


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.
Wanchu
Ajay
A
Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Dong
Yuxin
Y
Sethi
Sunil
S
Myneedu
V P
VP
Nadas
Arthur
A
Liu
Zhentong
Z
Belisle
John
J
Laal
Suman
S
D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D019353:Endemic Diseases; D006679:HIV Seropositivity / Q000150:complications / Q000382:microbiology; D006801:Humans; D007194:India / Q000453:epidemiology; D008292:Malate Synthase / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000276:immunology; D012307:Risk Factors; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C082911:MPT51 protein, Mycobacterium; D014373:Tuberculin; D008292:Malate Synthase