Despite several years of medical advances the worldis still a long way from exorcizing the medical demon of tuberculosis. When considering the worldwide scenario, nine million new cases are diagnosed annually and at least 1.5 million people succumb to the disease every year. Several reasons were stated in support of failure to curb the disease, like the lack of investment into diagnostic tools and treatment, persisting poverty, lack of access to medical care, increase in drug-resistant strains of TB, crowded living conditions and the most leading cause is the spread of HIV, the virus that causes AIDS. Infection with HIV suppresses the immune system, making it difficult for the body to control TB bacteria.
As a result, people with HIV are more prone to development of TB than who aren't HIV-positive. When talking about the treatment aspect, there is still no test that can instantly determine whether person has TB and treatment methods require a cocktail of drugs daily for at least six months and a length of time to which few patients can adhere.
Tuberculosis in India has not got the attention it deserves in part because it has mainly affected the poors. The usual victims are migrant labourers, slum dwellers, residents of the backward areas and the tribal pockets, secondly the diagnosis and treatment of TB is the biggest challenge.Book TB whole genome sequencing profile
Because the signs and symptoms seen in the TB is similar to the other diseases, such as carcinoma, pneumonia, sarcoiodosis, lymphoma, etc it's diagnosis becomes the toughest part. The diagnostic principle involves the detection of the direct causative agent Mycobacteria or its products and measurements of the humoral and cellular responses of the host against the bacteria, diagnosis is done through clinical finding, microscopy, culture, X ray, ESR, Mantoux test, serology or the more advanced PCR technique. But the conventional methods applied in the diagnosis comes with certain limitations which have restricted their use. The diagnosis procedure are listed.
SPUTUM EXAMINATION UNDER THE MICROSCOPY Though old fashioned, this method still remain the only and most valuable diagnostic method for TB.Whenever TB is suspected, at least 3 specimens of the sputum is collected and examined by microscopy to detect the Acid Fast Bacilli using the Ziehl Neelsen staining. The limit of detection of this method is that it requires at least 5 X 103 bacilli per ml sputum and various other factors like type of specimen, thickness of the s smear, extent of the decolourisation, type of counter stain used and the training and experience of the person examining the sputum affects the test results.
LABORATORY CULTURE of M. tuberculosis is quite sensitive as 10-100 organism per sample can be detected. The drawback of the culture is that it requires the complex cultivation media and takes 4-8 weeks to get the result. In view of the slow rate of the growth of tubercule bacilli attempts have been made to develop more rapid methods. Radiometry is one of these, which is based on the release of the radioactive carbon dioxide due to the bacterial metabolism. But the consumable cost is very high.
X RAY has its own merits and demerits. It is not uncommon to come across patients who have been started on anti tubercular chemotherapy relying solely on the X ray examination, neglecting sputum examination or ignoring the results, which is incorrect practice as radiographs may be misleading.
MANTOUX (Tuberculin skin Test) Also known as purified protein derivative(PPD) method put use up to find out whether the individual is infected or not. Where the liquid tuberculin is injected between the skin layers of forearm. After this the patient's arm examination is done for 48-72 hours, the swelling or redness, which is induration of the area indicates the positive results. But this method is brought in limited use as for its wrong interpretation of the results. It is not reliable method to be used in country like India, where there is high prevalence of exposure Infection to both the pathogenic as well as non- pathogenic forms of the TB bacillus. QuantiFERON-TB gold assay is a modern alternative method to the 175- year old skin test that measures the level of chemical called interferon against Mycobacteria specific antigens.POLYMERASE CHAIN REACTION Is an amplification technique that is rapid for directly detecting the mycobacterial DNA or RNA from clinical samples. Such assays have high potential, but at present only few meet the FDA approval. PCR kits for drug resistant forms are still in developing stage. Many issues are also associated with amplification assays such as expense, specificity and their clinical utility.
SEROLOGICAL TESTING It is the most widely employed diagnostic technique for tuberculosis, the method involve the measurement of the IgG and IgM antibodies. Factors like the easy- to-use, less time in results inter- pretation, the easiness in sample availability and modest testing cost makes it the highly recommended procedure for TB. But the reports published by the World health
Organization on 20th July 2011 in Geneva raised a questions against the accuracy interpretation of the tests results through the serological testing. They stated that the use of currently available commercial blood tests to diagnose active tuberculosis (TB) often leads to misdiagnosis, mistreatment and potential harm to public health.
The serological testing is lacking the sensitivity and specificity, which are the major tool of the diagnostic, where low sensitivity results in an unacceptably high number of patients being wrongly given the 'all clear' (i.e. a false-negative). This can lead to them dying from untreated tuberculosis, and the disease also being transmitted.
Low specificity leads to an unacceptably high number of patients being wrongly diagnosed with TB (i.e. a false positive). This can lead to them undergoing a six month course of unnecessary treatment, while the real cause of their illness remains un-investigated and undiagnosed.
Many a times a positive TB test does not necessarily mean that the person is having tuberculosis. There are several factors that can produce a false positive serological testing. Like BCG vaccination and Environmental Mycobacteria.
EFFECT OF BCG VACCINATION ON SEROLOGY REPORTS The BCG vaccine is given to children to prevent tuberculosis infection. It contains a live attenuated (weakened) form of Mycobacterium bovis, which is the bacterium that causes tuberculosis (TB). The vaccine is known as BCG because a strain of the bacterium known as Bacillus Calmette-Guerin is used. The vaccine works by stimulating the body's immune response to the bacteria, without actually causing the disease. Vaccines containing extracts or inactivated forms of bacteria stimulate the immune system to produce antibodies against them, but don't actually cause disease themselves. The antibodies produced remain in the body so that if the organism is encountered naturally, the immune system can recognize it and attack it. This prevents it from causing disease.
When such people are subjected to the TB serological (ELISA) testing, a test that compare the levels of antibody to M. tuberculosis in the IgG, IgM and IgA classes, the interpretation showed higher levels of the IgG, this is due to the previously existing antibodies which is raised against vaccination. As the IgG class was the most discriminative from the diagnostic point of view, this phenomenon reduced the usefulness of the test. But when the levels of the IgM is assayed it is not present. Ultimately leading to the wrong interpretations of the test results.Book Tuberculosis TGS Profile
EFFECT OF OTHER ENVIRONMENTAL MYCOBACTERIA ON RESULTS Although there are some other common species within the same genus that cause TB, there are many species also that does not cause tuberculosis at all. A person who has been infected with another member of this genus may show false positive results. As when our body is exposed to these species through various modes, our body recognizes these as a foreign antigen and raise an immune response towards it. On serological testing the antibodies IgG are detected, which is due to the antigenic similarity of other Mycobacterium species with M.tuberculosis. That causes cross reaction with the antigens in testing giving false results.
Even though, serological testing is known to give false positive results, India continues practising it as one of the diagnostic methods. However WHO recommends all countries to stop usage of the serological testing which are often inaccurate and instead urges people to rely on the microbiological and molecular tests.