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Genital TB and how PCR is confusing gynecologists

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The abuse, misuse and overuse of TB PCR testing of the endometrium is causing confused gynecologists to overtreat infertile women with ant TB drugs

Published in: Health & Medicine

Genital TB and how PCR is confusing gynecologists

  1. 1. Dr Aniruddha Malpani, MD www.drmalpani.com
  2. 2. Gynecologists seem to be diagnosing endometrial TB at the drop of a hat for all infertile women.
  3. 3.  Tuberculosis is endemic in India  Genital TB can cause infertility  Can cause symptoms ( amenorrhea, pelvic pain, abnormal uterine bleeding)  Is often silent  Hard to confirm this diagnosis in the lab, because it's very difficult to grow the TB bacillus in vitro.
  4. 4.  HPE  AFB microscopy  Culture in L-J media  Bactec  Guinea pig inoculation
  5. 5.  Lots of false negatives  Pauci-bacillary TB  Empiric TB treatment based on clinical findings. If patient improves clinically, diagnosis is confirmed
  6. 6.  Clinical impression  “Suspect” tuberculosis on clinical grounds  “Doughy feel”  Thin endometrium on scans  Adhesions on laparoscopy  Repeated failed IVF cycles
  7. 7.  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.
  8. 8.  Detection is based on multiplication not of whole bacilli, as in culture, but of their genetic material, chromosomal DNA or ribosomal RNA  In principle, from one target sequence, of one bacillus, the reaction can produce millions of copies and thus yield a positive result 20
  9. 9.  Simple , Rapid and Sensitive Amplifies a DNA sequence which is unique to mycobacteria.  Positive test = Presence of mycobacterial DNA is present in the endometrium.  If TB PCR of endometrium is positive = patient has endometrial TB  Extremely logical , but very flawed. Let's see why by starting from first principles.
  10. 10.  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.
  11. 11.  The type of mycobacteria  The DNA sequence amplified is not specific only to M tuberculosis - it is found in many other mycobacterial species as well.  Are the mycobacteria alive or dead?  Where did the mycobacteria came from ? (contaminant from the OT or the lab)
  12. 12.  Not just Mycobacterium tuberculosis or Mycobacterium leprae  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).
  13. 13.  Environmental mycobacteria are found practically everywhere - even in the water in the lab which is used to clean the instruments
  14. 14.  Fools both pathologists and gynecologists  Pathologists are forced to report what they see – do not provide any clinical interpretation  Gynecologists – knee jerk reflex ! Positive test result = disease = treat !
  15. 15.  Fail to realize that a positive PCR report is very non specific  It’s because it so sensitive that it gives rise to so many false positives, which mislead both doctors and patients.
  16. 16.  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 .  These mycobacteria have created iatrogenic harm - Non pathogenic Ubiquitous Mycobacteria - NUM !
  17. 17.  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 !
  18. 18.  New class of in vitro assay that measure interferon (IFN-γ) released by sensitized T cells after stimulation by M. tuberculosis antigens.  Measures immune reactivity to M.tb. 31
  19. 19.  What happens if they give conflicting results ?  For example, one test may be positive and the other is negative !  Which should you trust ?
  20. 20.  Clinical suspicion confirmed !  Patient is happy that the doctor has finally found out why the endometrium is thin; or why the IVF cycles have failed .  Few patients may get pregnant after starting the antiTB medicines, this doesn't mean that there was a cause and effect relationship between the treatment and the pregnancy.
  21. 21.  Tragic ! Most of these patients don't have TB at all  Overdiagnosis causes havoc in the life of infertile couples  Unnecessarily exposed to nine months of toxic drugs  Time wasted , during which her ovarian reserve and fertility will go down.  Divorce
  22. 22.  Harming the country's TB control program  The misuse of antiTB drugs leads to drug- resistant TB ( MDR and XDR) , which is the man-made result of interrupted, erratic, or inadequate TB therapy.
  23. 23.  Can’t hurt !  Why take a chance ?  Patients want you to do something !  It’s expected that doctors will always prescribe medicines !  Doctors are scared that if they “do nothing” they will lose their patient
  24. 24.  Mindless overdiagnosis  Overtreatment  TORCH tests  NK cells  Pressure to test and treat – from both patient and doctor !  Marketing pressures

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