Tuberculosis Diagnosis


Abdollah Karimi 1 , Roxana Mansour Ghanaie 1 , * , Farideh Shiva 1

1 Pediatric Infections Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran

How to Cite: Karimi A, Mansour Ghanaie R, Shiva F. Tuberculosis Diagnosis, Arch Pediatr Infect Dis. 2015 3(1 TB): e20597. doi: 10.5812/pedinfect.20597.


Archives of Pediatric Infectious Diseases: 3 (1 TB); e20597
Published Online: January 13, 2015
Article Type: Editorial
Received: May 23, 2014
Accepted: June 8, 2014

1.1. Description of Some New Diagnostic Methods

Recently, in vitro T-cell-based methods, the Tuberculin Skin Test alternative, have been made available to diagnose TB infection; they include interferon γ assays (QuantiFERON-TB, Quantiferon- TB Gold, T-SPOT-TB), which use Purified Protein Derivate (PPD), Early Secretory Antigen Target 6 (ESAT6), and Culture Filtrate Protein 10 (CFP10). The latter two antigens are coded by genes of region of difference 1 (RD1) locus of M. tuberculosis and are more specific for MT (exception is Mycobacterium marinum, Mycobacterium kansassi and Mycobacterium sulzagi (1, 7, 8).

1.2. Methods for Bacilloscopy

Kinyoun modification, auramine O, and rhodamine stains are used for direct examination of M. tuberculosis (1, 2).

1.3. New Methods for Culture

However, the gold standard for diagnosis is a positive culture of MT from clinical specimens collected from the suspected cases (1, 9). Various culture media used to detect and grow MT include (10):

1) BACTEC radiometric system

2) Mycobacteria growth indicator tube (MGIT)

3) BACTEC MGIT 960 system

4) MB-Redox based on the reduction of a tetrazolium salt indicator, ESP culture system 2 based on the detection of pressure changes and MB/BacT system that relies on colorimetric detection of carbon dioxide

5) Phage-based assay based on the ability of MT to support production of mycobacteriphage (like FASTPlaque TB test) (1, 2, 8).

1.4. New Methods for Drug Susceptibility Testing

It is prudent to perform drug susceptibility testing (DST), especially in areas with a high rate of MDR TB. Various methods are devised for DST including the proportion, the resistance ratio, the absolute concentration methods and BACTEC radiometric system divided into genotypic and phenotypic methods. The former include molecular nucleic acid amplification (amplified MT direct test, AMTD and Amplicor MT), real-time Polymerase Chain Reaction (PCR), and strand-displacement amplification methods (1, 2, 9, 10).

The latter include various metabolic tests such as color indicators and oxygen consumption, visualization of micro-colonies, nitrate reduction assay, and use of phages. Examples are Mycobacteria growth indicator tube (MGIT), E-test, MB/bacT system, and ESP culture system 2 (1, 2, 11).

1.5. Molecular Epidemiology Techniques

Recent advances of molecular epidemiology use techniques which include DNA finger printing, like the restriction fragment length polymorphism, RFLP, spacer oligotyping and spoligotyping, genomic deletion analysis, and Mycobacterial interspersed repetitive units (MIRU) (1, 2).

1.6. Serological Diagnosis of TB

The main purpose of these tests is increasing the ability to diagnose latent infection (1, 2).

1.7. Non-Microbiological Diagnostic Techniques

Detection of adenosine deaminase (ADA) is an easy, rapid, low cost test but can be used as an extra tool for Tuberculosis pleural effusions and meningitis according to its low accuracy (1, 2). The major problems encountered in rapid diagnosis of TB and differentiation of infection from the disease includes unavailability of advanced tests and inaccuracy of available tests. In immune compromised patients, especially those with HIV infection, results of diagnostic tests are equivocal, thus making a definite diagnosis becomes even more difficult.

1.8. Conclusions

1) In every setting, high index of suspicion is required for rapid diagnosis of TB, and physicians should take the epidemiological, clinical and paraclinical data into account to gauge the probability of active disease to order feasible, accurate and cost effective diagnostic tests.

2) In high endemic areas, TB should be suspected early and steps should be taken for prompt diagnosis and treatment.

3) In every setting, PPD, X-ray, smear, and culture are requested in suspected cases and if available more sensitive tests are required according to the site of infection. In resource-limited countries the priority is to ensure a network of quality-controlled microscopy for AFB in clinical samples, most often sputum.

4) It is recommended to request HIV testing in every child with Tuberculosis.

5) It is better to request drug susceptibility test on all obtained isolates, unless the result of this test in isolates from the index case is available. This policy can help to prevent the emergence of MDR and its transmission.

6) The decision to treat a child should be carefully considered, and once such a decision is made the child should be treated with a full course of therapy.

7) A majority of TB diagnostic studies are focused on test accuracy and not on outcomes such as accuracy of diagnostic algorithms. Revised clinical algorithms for TB diagnosis may demonstrate the impact of these new tools.



  • 1.

    Palomino JC. Nonconventional and new methods in the diagnosis of tuberculosis: feasibility and applicability in the field. Eur Respir J. 2005; 26(2) : 339 -50 [DOI][PubMed]

  • 2.

    Mathur JN. What is New in Diagnosis of Tuberculosis? Part I : Techniques for Diagnosis of Tuberculosis. Indian Council of Medical Research. 2002; 32(8)

  • 3.

    Tuberculosis (TB) 2014;

  • 4.

    Stop TBPCTBSWHO. Guidance for National Tuberculosis Programmes on the management of tuberculosis in children. Chapter 1: introduction and diagnosis of tuberculosis in children. Int J Tuberc Lung Dis. 2006; 10(10) : 1091 -7 [PubMed]

  • 5.

    MacPherson P, Houben RM, Glynn JR, Corbett EL, Kranzer K. Pre-treatment loss to follow-up in tuberculosis patients in low- and lower-middle-income countries and high-burden countries: a systematic review and meta-analysis. Bull World Health Organ. 2014; 92(2) : 126 -38 [DOI][PubMed]

  • 6.

    National Collaborating Centre for Chronic Conditions and the Centre for Clinical Practice at NICE,Tuberculosis,Clinical diagnosis and management of tuberculosis, and measures for its prevention and control 2011 2011;

  • 7.

    Rhodes S, Holder T, Clifford D, Dexter I, Brewer J, Smith N, et al. Evaluation of gamma interferon and antibody tuberculosis tests in alpacas. Clin Vaccine Immunol. 2012; 19(10) : 1677 -83 [DOI][PubMed]

  • 8.

    Simsek H, Alpar S, Ucar N, Aksu F, Ceyhan I, Gozalan A, et al. Comparison of tuberculin skin testing and T-SPOT.TB for diagnosis of latent and active tuberculosis. Jpn J Infect Dis. 2010; 63(2) : 99 -102 [PubMed]

  • 9.

    WHO, Global tuberculosis controlGeneva. World Health Organization 2011;

  • 10.

    Dorman SE. New diagnostic tests for tuberculosis: bench, bedside, and beyond. Clin Infect Dis. 2010; 50 Suppl 3 : S173 -7 [DOI][PubMed]

  • 11.

    Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med. 2006; 355(15) : 1539 -50 [DOI][PubMed]

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