Tuberculosis Pathology and Diagnosis


Abbreviated as TB for Tubercule Bacillus is a common and deadly bacterial, infectious disease caused by some mycobacterium species such as Mycobacterium tuberculosis or Mycobacterium bovis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system, lymphatic system, circulatory system, genitourinary system, bones, joints, and even the skin.


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According to the World Health Organization (WHO), nearly 2 billion people—one–third of the world's population—is infected with M. tuberculosis (Latent TB Infection, LTBI), in addition to the millions living with active TB disease. In 2008, around 14.6 million people had active TB disease.[1] with an estimated 9.4 (range, 8.9-9.9 million) million incident cases (equivalent to 139 cases per 100 000 population) and 1.9 million people die from the disease worldwide[2].

Most of the estimated number of cases in 2008 occurred in Asia (55%) and Africa (30%), with small proportions of cases in Eastern Mediterranean Region (7%), the European Region (5%) and the Region of the Americas (3%) [3]. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS.

There are a number of known factors that make people more susceptible to TB infection:
Worldwide the most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high incidence of HIV in these countries.[4] Smoking more than 20 cigarettes a day also increases the risk of TB by two- to four-times.[5]

Also apparent are economic-social conditions that further put people at risk :
Living in a crowded environment, malnutrition, alcoholism, poor access to health service, diagnostic delays, prolonged infectiousness in poor communities are risk factors[2].

Accurate and early detection of TB remains a critical step in the management and control of TB (1).
Until now, the primary rapid tool remains the microscopic examination and disadvantage of this assay are well described in literature. Although the culture is considered the gold standard, it requires two to six weeks for results, since mycobacteria are slow-growing organisms.

Nucleic acid amplification test represents an important new tool for the early detection of mycobacterium in order to get faster treatment with improved patient outcome and cost effective solutions.

[1] "WHOReport 2008 Global Tuberculosis Control"
[2] “TB for Journalists”, March 2010, WHO
[3] "WHOReport 2009 Global Tuberculosis Control "
[4] World Health Organization (WHO). Global tuberculosis control - surveillance, planning, financing WHO Report 2006. Retrieved on 27 March 2006. 
[5] World Health Organization (WHO). Global Tuberculosis Control Report, 2006 - Annex 1 Profiles of high-burden countries. (PDF) Retrieved on 27 March 2006. 

Diagnosis of Tuberculosis

Accurate and early diagnosis of tuberculosis remains a critical step in the management and control of the disease. Doing so will interrupt TB transmission as well as cure the patient. To this day the primary tool in case detection remains the microscopic examination of Acid-Fast Bacilli (AFB). Worldwide it is the most commonly used test to detect Mycobacterrium tuberculosis and together with culture on solid and liquid media is considered as being the gold standard for diagnosis of active tuberculosis. Acid Fast Smear (AFS) microscopy has the advantage of being rapid and inexpensive with the ability of identifying the most contagious individuals.The lack of specificity and sensitivity of AFS(1) hampered this approach. Culture can detect M.TB bacilli in over 80% of TB cases with a specificity of over 98%. It is considered as being more sensitive than smear microscopy, requiring fewer bacilli for detection, allows species identification and is used for drug susceptibility testing. As Mycobacteria are slow growing organisms, this technique has the major disadvantage of requiring 2 to 6 weeks to obtain a result (2).

The development of Nucleic Acid Amplification Technology (NAAT) tests has been an important technical advance for the mycobacterial laboratory. Because NAAT allow for a faster and easier way to perform test with a high sensitivity and specificity.

Tosoh Corporation has developed a new gene amplification method: Transcription Reverse-transcription Concerted reaction (TRCR) that enables one step amplification and real-time detection of the MTB 16S rRNA target directly on respiratory and non-respiratory specimens.

Results can be gathered from decontaminated samples in less than 2,5 hours.

Overall sensitivity and specificity of TRCR for pulmonary specimens was 87 % and 98 % respectively with a detection limit of 50 CFU/ml(3).

High sensitivity and specificity and shortened turn around times, indicating a potential parallel use of this assay with smear microscopy, ensures faster treatment with improved patient outcome as well as offering a cost effective solution.

(1) Daniel,T.M. 1990. "The rapid diagnosis of tuberculosis: a selective review." J Lab. Med 116: 277-282
(2) Drobniewski, F. A.., M. Gibson, and D. Young. 2003. "Modern laboratory diagnosis of tuberculosis." Lancet Infect. Dis. 3: 141-147.
(3) V. Drouillon,G. Delogu,G. Dettori,P. H. Lagrange, M. Benecchi,F. Houriez K. Baroli,F. Ardito, R. Torelli, C. Chezzi, G. Fadda, and J.-L. Herrmann.
Multicenter Evaluation of a Transcription-Reverse Transcription Concerted Assay for Rapid Detection of Mycobacterium tuberculosis Complex in Clinical Specimens
Journal of Clinical Microbiology, November 2009, p. 3461-3465, Vol. 47, No. 11