Tuberculosis is a common human and animal infectious disease occurring worldwide caused by Gramm positive acid-fast bacteria. The most dangerous for people are typical strains Mycobacterium tuberculosis and Mycobacterium bovis. Every year around 8-9 mln of new cases are reported and 2 million people dies because of the infection and its complication. This places tuberculosis on the top of the leading infectious diseases, with regard to morbidity and mortality worldwide. Despite the fact that BCG vaccines are available, the situation is very serious because there are many problems i.a. difficulties in detecting myobacteria and its multidrugresistance . (1)
Until now the main and the most commonly used method was a tuberculin skin test (TST). It consisted in intradermal injection of PPD (purified protein derivate) tuberculin coming from Mycobacterium culture. The test results are positive if the size of the induration measured 48-72 hours after the injection is more than 12 mm. However, this method is highly imperfect since the results could be modified by a lot of causes, especially by a current condition of the immune system. Very frequently in cases of the HIV-possitive patients, during steroid or immunosuppressive therapy, cancer, cachectic patients, and also in bacterial, viral, lymphatic, and mycosis infections, or severe form of tuberculosis the outcomes can be falsely negative, what makes significant difficulties in the treatment. (2) The TST can be also falsely positive as a result of cross-reaction with MOTT (Mycobacterium other than tuberculosis) or Mycobacterium leprae – causing leprosy or after BCG vaccination.
To detect the tuberculosis, also a smear microscopy taken directly from the suspected of tuberculosis patient’s sputum may be used. From the sputum a culture of Mycobacterium is grown with the use of Lowenstein-Jensen base. However, the mycobacterium are problematic for cell culture. They divide slowly and they need special conditions. On the fly of the culture, species and drug resistance of bacteria can be defined but the findings come after 2-4 months. A sputum is harvested in a case of the most common form – lung tuberculosis. Sometimes it may be difficult to harvest correctly a sputum for the test. Also another tissues can be tested in that way.
Currently, since December 2010, WHO approbates another diagnostic method – Xpert MTB/RIF. It consists in detection of DNA of M. tuberculosis in a sputum, BAL (bronchoalveolar lavage), or bronchial secretion samples harvested from the patients, and finding of DNA mutation, caused by this pathogen. The test is based on real-time PCR. With the use of that automated test, after 2 hours it is known if the patient is infected and if the M. tuberculosis is rifampicin-resistant, because of detection of mutation in rpoB gene responsible to resistance to rifampicin. For detection of a multidrug resistant (MDR) strains it will be enough to detect only rifampicin resistance because there is a lot of selective isoniazid resistant mycobacterium. It does not happen very often that M. tuberculosis were only rifampicin resistant. There are mostly MDR. The sensitivity of the Xpert MTB/RIF vary between 72,5-98,7%, specificity is 99,2%. (3) A simplicity and high effectiveness of that test, as well as short time of duration, make it to be used willingly, especially in the developing countries where the prevalence of tuberculosis is the highest. Xpert MTB/RIF is effective in detecting tuberculosis in the HIV-positive patients who are a large group of TBC-patients, especially in endemic regions. (4)
To detect a latent forms of infectious Interferon Gamma Release Assay (IGRA) are used. They consist in measuring an interferon gamma release produced by activated T lymphocytes as a response to stimulation by mycobacterial antigene ESAT-6 and CFP-10, using ELISA (enzyme linked immunosorbent assay)- QuantiFERON-Tb Gold (a positive result by IFN concentration above 0,35 IU/ml) and ELISpot (enzyme linked immune-spot assay) – T-SPOT.TB (positive result in more than 6 stimulated limphocytes). These tests have big sensitivity and specificity and the BCG vaccine have no influence on the findings. (5,6)
To assess how diffuse is the focal change caused by M. tuberculosis imagination examinations are used, especially chest X-ray.
Currently Xpert MTB/RIF seems to be the most popular because of its high specificity, sensitivity and simplicity. Unfortunately, with an attempt to propagate the test, more and more corresponding problems and fears appear. To make a test on a patient who is not HIV infected is more expensive than making a test on infected one, what makes it not so price attractive for the countries with low HIV prevalence. Another thing that worries are new multidrug resistant strains, resistant to pirazinamide and ciprofloxacin, what couldn’t be detected by Xpert MTB/RIF. (4) Despite the problems, the values of the Xpert MTB/RIF seem to be bigger and one of those is a safety of technicians who make the test.
Written by: Magdalena Chorążka
Source:
1.Epidemiologia gruźlicy w perspektywie świata, Europy i Polski, Tomasz Jagielski, Ewa Augustynowicz-Kopeć, Zofia Zwolska, Wiadomości lekarskie, 2010,LXIII,3; 230-246
2.Choroby wewnętrzne, A. Szczeklik (red.), Kraków, wyd. Medycyna Praktyczna, 2005, t. I, s. 513,
3.Rapid Implementation of New TB Diagnostic Tests: Is It Too Soon for a
Global Roll-Out of Xpert MTB/RIF?, Daniela E. Kirwan*, María Kathia Cárdenas and Robert H. Gilman and Author Affiliations, Am J Trop Med Hyg. 2012 Aug
4.Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study, Lesley E. Scott et all, PLoS Med. 2011 July; 8(7): e1001061
5.Interferon gamma release assays: principles and practice. Lalvani A., Pareek M., Enferm Infecc Microbiol Clin. 2010 Apr;28(4):245-52. Epub 2009 Sep 24.
6.Is It Time to Replace the Tuberculin Skin Test With a Blood Test?
Philip A. LoBue, MD; Kenneth G. Castro, MD, JAMA. 2012;308(3):241-242. doi:10.1001/jama.2012.7511
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