

Dr. Aniruddha Malpani
Dr. Aniruddha MalpaniMD, Malpani Infertility Clinic

TB or not TB

Mar 23, 2015, 04.22 PM IST

The menace of XDR ( extreme drug resistance) TB looms large over the country today. One of the little known reasons for this is the rampant overuse of anti TB drugs by gynecologists, who seem to be diagnosing endometrial TB at the drop of a hat for all infertile women.
Tuberculosis is endemic in India , and it’s a disease which can affect practically any organ system , including the reproductive tract. While genital TB (which damages the fallopian tubes) can cause infertility, it’s also extremely hard to confirm this diagnosis in the lab, because it's very difficult to grow the TB bacillus in vitro.

While in the past the diagnosis was often missed, today the problem is exactly the opposite ! Gynecologists are overdiagnosing genital TB, based on a positive endometrial TB PCR ( polymerase chain reaction) test result. The tragedy is that most of these patients don't have TB at all, because the vast majority of these results are false positives, but this overdiagnosis is causing havoc - not only in the life of infertile couples, but in the country's TB control program as well. The misuse of antiTB drugs leads to drug-resistant TB , which is the man-made result of interrupted, erratic, or inadequate TB therapy.

Where are all these false positive diagnoses coming from ? Tuberculosis of the genital tract is a notoriously difficult diagnosis to establish because it's very hard to grow mycobacteria in the lab. In the past, to make a definitive diagnosis of genital TB , a positive mycobacterium culture or the presence of tubercles in the histopathology report ( from an endometrial biopsy ) was required. However, what has started to happen is when doctors "clinically suspect" tuberculosis ( for example, when the endometrium remains thin, or the patient has failed multiple IVF cycles) , they send the endometrial tissue for all kinds of tests to confirm their clinical suspicion. One of the most popular tests is a PCR ( polymerase chain reaction) test for mycobacterium tuberculosis.

The problem with PCR

PCR is a simple and rapid test for use in the detection of Mycobacterium tuberculosis because it amplifies a DNA sequence which is unique to mycobacteria. Now if the test is positive , this means that mycobacterial DNA is present in the endometrium. However, this does NOT mean the patient has genital TB - all it tells us that a few molecules of mycobacterial DNA was found in the sample processed in the lab. It does not provide us with any information about the type of mycobacteria, because the DNA sequence which is being amplified is not specific only to M tuberculosis - it is found in many other other mycobacterial species as well; or whether the mycobacteria are alive or dead? or where the mycobacteria came from ? ( the clinical tissue ; or as a contaminant from the OT or the lab).

More about mycobacteria


The problem with false positives

Since these mycobacteria are so common, when the laboratory finds a positive PCR reaction , it doesn’t know whether the mycobacterial DNA is coming from the patient , or is a contaminant.. The molecular cross-reaction between the ubiquitous non-pathogenic environmental mycobacteria ( which are harmless colonisers) and M tuberculosis is what creates the diagnostic dilemma. Since they have a similar DNA structure, the presence of either will provide a positive result in a PCR test. The PCR test is quite a dumb test - it's not able to determine which type of mycobacteria is providing a positive signal !

Why gynecologists get fooled

Since the DNA PCR test is not specific only for mycobacterium tuberculosis, it’s very easy for the doctor to get fooled. To make a bad situation even worse, when the TB PCR test is positive, gynecologists then rely on even more unreliable tests ( such as Quantiferon Gold, TB PAMP testing, and TB IgG and IgM antibody tests) to "confirm" their diagnosis , even though the Government of India has banned many of these tests because they are so unreliable !




About Dr. Aniruddha Malpani


appiIMAIDAHealthcare Federation of IndiaAIMENeoCon2015