This document discusses the role of serology and rapid tests in tuberculosis diagnosis. It provides background on tuberculosis as a global health problem, with 22 high burden countries including Indonesia as the third highest. Current TB diagnosis relies on outdated methods like smear microscopy and culture that are slow and inaccurate. New tests are needed that are sensitive, specific, rapid, easy to use, and cost-effective. While serology tests have been proposed, WHO recommends against inaccurate tuberculosis tests as they could worsen the epidemic. The document explores developing a comprehensive antibody profile to define an active TB diagnostic using high-throughput proteome screening methods. It also notes the Xpert MTB/RIF test as a promising molecular point-of-care assay.

1. ROLE OF SEROLOGY & RAPID TEST
IN DIAGNOSIS OF TUBERCULOSIS
Jusak Nugraha
Dep.Clinical Pathology Faculty of
Medicine, Airlangga University

2. Indonesia Ketiga
22 High Burden Countries 1.
2.
India
China
3. Indonesia
4. South Africa
5. Nigeria
6. Bangladesh
7. Ethiopia
8. Pakistan
9. Philippines
10. DR Congo
11. Russia
12. Viet Nam
13. Kenya
14. UR Tanzania
15. Uganda
China 16. Brazil
14.3% 17. Mozambique
Indonesia 5.8%
18. Thailand
South Africa 4.9%
19. Myanmar
Nigeria 4.9% India 20. Zimbabwe
21.1% 21. Cambodia
Bangladesh 3.8%
22. Afghanistan
Ethiopia 3.3%
Pakistan 3.2%
Other
Philippines 2.7%
15.9%

3. Conventional laboratory diagnosis of
tuberculosis
TB
Diagnostics
Latent TB Smear Culture Rapid tests
IGRA DST Serology
Reverse
Serology

4. Current TB diagnosis
• Global problem of poor case detection
• Diagnosis relies on “old technology”
– Clinical symptoms - can often be confused with
other pathologies
– Smear microscopy – variable and poor sensitivity
– Culture - slow
– X-ray – not specific
4

5. How to improve TB case detection
• WHO has recognised the need for development
of new TB diagnostic tools
• New tests should have the following features:
– Sensitive
– Specific
– Rapid
– Easy to operate
– Cost-effective
5

6. Flow diagram for the diagnosis of tuberculosis in clinical practice (WHO 2003) .

7. WHO recommends against inaccurate
tuberculosis tests. (The Lancet, Vol 377, Issue 9760, p: 113 -
114, 8 January 2011)
• Misleading serology tests for tuberculosis could
be worsening the epidemic in some high-burden
countries.
• “If they worked, the problem of a gap in the
pipeline for a point-of-care assay would have
been solved decades ago”, comments Madhukar
Pai, co-chair of the STOP-TB Partnership's new
diagnostics working group. “The pity is that they
don't work. In fact, they're inaccurate and
useless.”

18. Morpheus tells Neo (The Matrix):
“there’s a difference between knowing
the path and walking the path.”

19. Postgenomic
Era Post-genomic

20. Perkembangan diagnostik TB

21. 2005
Nugraha: Epitope mapping of ESAT-6 antigen
2 important epitopes were found
1. The protective epitope of ESAT-6 antigen
found in healthy pulmonary disease ward
nurses.
2. The heavy infection epitope of ESAT-6
antigen found in pulmonary TB patients.

23. Two kind of epitopes found
I MTEQQWNFAGIEAAASAIQGNVTSIHSLLDEGKQS
1 heavy infection epitope 35
!! MTEQQWNFAGIEAAASAIQGNVTSIHSLLDEGKQS
1 protective epitope 35

24. Sample pad
Absorbance pad
Conjugate pad Control line
1 2
Capture line contain Ag
1  heavy infection epitope
2  protective epitope
Line-1 filled with heavy infection epitope dan line-2 filled with
protective epitope

25. Interpretation
• Protection negative, heavy infection positive  ill/sick patient
line 1 2 control
• Protection positive, heavy infection positive  inactive TB/Latent
line 1 2 control
• Protection negative, infection negative, control pos  not exposed to M.
tb.
1 2 control

26. Probed microarrays
Naive Immunized

28. Conclusions
A comprehensive antibody profiling of M.
tuberculosis infection needs to be developed
to define a diagnostic for active TB
High-throughput methods for whole
proteome screens are available.
Pai M : Xpert® MTB/RIF test is first molecular
assay for TB that can potentially be used at the
point-of-treatment.

29. THANK YOU
29