Sunday, 25 August 2019

Diag of genital Koch's





Diagnosis of genital Kochs & then prescribing ATD with confidence-where are we??

Forecast, Deep cloud  in the horizon & Apprehension:-There is unlikely to be a gold standard test for genital tuberculosis in foreseeable future,. The very nature of the disease in the sense  a) very few bact can damage the tube, cause peritoneum scarring , and adhesive disease , distortion of tubal end , endometrium  (paucibacillary,) , b) the monthly shedding of  endometrium (we used to prescribe Premarin continuously to grow the endometrium for 50 days  to retrieve a thick tissue of endoà reasonably adequate to stain )  so that and C0 Nonaccessibilty to primary site –endosalpinx –near 100% affected but misses the biopsy or evaluation/ tube is primary site of affection; makes it difficult to detect bacilli in endometrium tubes –Endosaplinx can’t be sampled easily for technichal  reasons.   Endometrial TB is a notoriously difficult diagnosis to confirm 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/ peritoneal  biopsy ) was required. However, one of the most popular tests today is a PCR test of the endometrium for mycobacterium tuberculosis.
In principle, 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. Isn't it then obvious that if the TB PCR is positive , this means the patient has endometrial TB which requires treatment ? Extremely logical , but very flawed. Let's see why by starting from first principles.
What does a positive PCR mean ? It 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.


 What is Mycobacteriae family?? What do we mean by MOTT  in modern times?? When most doctors of other disciplines think about mycobacteria, we the gynaecologits refer to Mycobacterium tuberculosis which causes tuberculosis; or , less commonly, Mycobacterium leprae which causes leprosy. However, the reality is that Mycobacteria are a diverse group of rod-shaped bacteria that include more than 100 different species. The others, which are far commoner, are called Nontuberculous mycobacteria (NTM), environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT). But the god news is that -all good labs now report MOTT separately in TB PCR or gene expert.

Where from MOTT come? Way there is so much Port infn??If we use Overhead tank water (tank located on the roof of OT premises)   or any tap water used for  cleaning instruments and autoclave then such environmental bact can be demonstrated in slides or culture(soiling of instrument)., MOTT contamination is rare. MOTT is most likely where codex is used for disinfection as glutaraldehyde is not caudal for MTB or MOTT.. They live in the soil and water throughout the world. Because they are protected by their waxy lipid-rich cell wall, mycobacteria are resistant to disinfectants. This is why they are ubiquitous inhabitants of the hospital environment ; and frequent contaminants in hospital settings, where they are often found in the water supply and even in the solutions in which the endometrial biopsy /peritoneal biopsy


. But fact remains that If the endometrial biopsy shows caseous granuloma on histopathology but AFB smear negative should pt be started ATT. I feel yes.

Do we enjoy liberty to initiate (or at least recommend initiation of ATD) if we as clinicians (from h/o contact, poor health,   low grade fever, Raised ESR,. Lympho count +ve, Hypomeno, caseous changes in Endo biopsy or HSG film exhibits radiological findings suggestible of  some signs  or Lap hyst signs are in favour of presumptive Kochs –should we strongly voice for Kochs drugs ?? Members opinion pl ??

Many believe that pt should be always put on trial ATT if TB is clinically suspected and see response. other basic test like CBC for lymphocytes%, ESR, Monteux, Culture etc. Transcription mediated amplification (TMA) and nucleic acid amplification (NAA ): This approach identifies the presence of genetic information unique Culture etc. Transcription mediated amplification (TMA) and nucleic acid amplification (NAA ): This approach identifies the presence of genetic information unique for infection.






The TB PCR test is highly flawed, because the DNA sequence which the PCR amplifies is common to both the mycobacterium tuberculosis as well as the other species of mycobacetria.
Since these mycobacetria 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 from the slide on which that sample was sent. When a specimen is reported as being PCR positive, it is important to discriminate between true infection and contamination. The molecular cross-reaction between the ubiquitous non-pathogenic environmental mycobacteria ( which are harmless colonizers) 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 !
Sadly, most gynecologists and pathologists are completely clueless about the prevalence of environmental mycobacteria; and when the TB PCR test result comes back as positive, their knee jerk reaction is to assume that the patient has genital TB ( when in reality, the result is much more likely to be a false positive, because of contamination). Because environmental mycobacteria are so prevalent ( they are found practically everywhere - even in the water in the lab which is used to clean the instruments !), the chances of the PCR test being positive because of contamination by environmental bacteria is much higher than because the patient actually has genital TB !
Environmental mycobacteria have always been around, so why wasn't this a problem in the past ? This is because modern PCR is so sensitive ! In the past, it was not easy to grow mycobacteria, which meant that even if a few contaminants were present in the specimen, these would fail to grow. However, PCR is super-sensitive, and will pick up the presence of even a few molecules of mycobacterial DNA.
With a positive TB PCR, the odds are that a positive result ( in an asymptomatic patient) means that there is something wrong with the test, not with the patient . In fact, I think we should coin a new term for these mycobacteria which have created so much iatrogenic harm - Non pathogenic Ubiquitous Mycobacteria - NUM !
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