Sunday, 25 August 2019

:-Tuberculosis of female genital tract is not an uncommon disease; in some provinces of India the prevalence may be as high as 5-15% of all infertile women.


2. When to suspect that one is suffering from Kochs? The index of suspicion will be high in following clinical situations:-
1) Family of Kochs or else H/O contact with Koch’s in office settings or close relatives particularly in close family members,
 2) Next index of suspicion:  unexplained slow response in cases with antibiotics in a clinically diagnose PID,
3) Unexplained long lasting Low back pain for which no cause is demonstrable, (LBP or say CPP i.e. Chr. Pelvic pain 3) Hypomenorrhoea, / Long standing white discharge –resistant to conventional TR and or unexplained menorrhagia. 4) resident / domiciled in endemic areas, 5) unexplained (non-neoplastic unilateral Adnexal Mass, 6) unexplained subfertility, 7) persistent demonstration of free fluid in POD even in unmarried girsl.etc, etc)—9) Persistent Thin ET and no withdrawal bleeding / In ART settings if Receptivity of Endometrium is suboptimal / Rec implantation failure.10) During Hysteroscopy if Synechiae is visible or at Diag Lap for some other easy tubercles are observed at gut wall, POD, on the surfaces of F Tube. 11) Exacerbation of PID component after ant uterine / Tubal procedures –say HSG .9) TC of Blood, raised Lymphocytes count, and ESR, 10) raised MT > 10mm if her age is < 20 yr
.
TB germs are of many kinds. That IU the major hindrance in Laboratory diagnosis of TB germs from tissues removed from human body. What are the different types of Mycobacteria exist in and around Humans?
Mycobacteria are a diverse group of rod-shaped bacteria that include more than 100 different species. The others, which are far commoner, environmental mycobacteria; and when the TB PCR test. But quite often contaminations occur e.g. tap water, slides etc and giving a false + ve DNA –PCR +ve. AS such, it is important to discriminate between true infection and contamination. The molecular cross-reaction between the ubiquitous non-pathogenic environmental mycobacteria (which are harmless colonisers) and M tuberculosis is what creates the diagnostic dilemma.
One decade back it was thought that the diagnostic of this diseases & prevailing dilemma has come to full stop with the advent of PCR method.
Sadly, later it was known that -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 mycobacteria.


Surprisingly Leprosy –a disease which primarily affects skin & nerves of Men & Women in some poverty stricken districts of India also is caused by the same family of germs: We refer to Mycobacterium tuberculosis which causes 1) tuberculosis; or Mycobacterium leprae which causes leprosy. What is meant by nontuberculous   mycobacteria (NTM), environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT)?

A)Characteristics of Myco Tuberculosis? 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 is sent to the lab for PCR testing).
3)

The ways & means of diagnosis of TB Endometrium.

Endometrial TB is a notoriously difficult diagnosis to confirm because it's very hard to grow mycobacteria in the lab.

a) Earlier what was the policy in diagnosing Female genital TB ?In the past, to make a definitive diagnosis of genital TB, A) positive mycobacterium culture or B) the presence of tubercles/ giant cells in the histopathology report (from an endometrial biopsy) was required.

What about PCR? 

Quite often people do TB PCR from DNA of tee excise sample /removed endometrium and send for TB-PCR-DNA. PCR is super-sensitive, and will pick up the presence of even a few molecules of mycobacterial DNA.

This technology amplifies a DNA sequence which is unique to mycobacteria. But quite often contaminations occur e.g. tap water, slides etc and giving a false + ve DNA –PCR +ve. AS such, it is important to discriminate between true infection and contamination. The molecular cross-reaction between the ubiquitous non-pathogenic environmental mycobacteria (which are harmless colonisers) and M tuberculosis is what creates the diagnostic dilemma. 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!

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 mycobacteria.



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 from the slide on which that sample was sent. 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). To make a definitive diagnosis of genital TB, a) positive mycobacterium culture or b) the presence of tubercles/ giant cells in the histopathology report (from an endometrial biopsy) was required

Environmental mycobacteria lead to confusion:
As 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 & what are Non pathogenic Ubiquitous Mycobacteria - NUM!??
Such environmental Bact 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!
TB PCR positive


But now following tests are collectively done to arrive at a definitive diagnosis. Many tests are done to prove or exclude. Fallacies of Lab diag of Kochs But , CBnet Gene expert only reliable(



Lab diag of Kochs & Limitations of such Tests:-,-There are limitations of Lab diag of Kochs particularly genital Kochs(TB).—honestly speaking most of the genital cases, in my opinion, have to be diagnosed from history and sorry to say sometimes we have to initiate empirical treatment based on clinical suspicion
 At least that is my belief as almost all available Lab tests are to some extent is not full proof. All Lab tests have its limitations. That is the most important draw backs of diagnostic tests...In my opinion; - HSG is forbidden in a case of presumed/confirmed case of genital Kochs. B) Secondly, what we diagnose as genital Koch’s may be misdiagnoses/ inappropriate... It is difficult to be very certain about Koch’s as there is no specific serum marker till date.
What about. PCR??
 ---so long we trusted on PCR test results. But, of late such PCR test has   much has fallen to disrepute. C) Thirdly, it is our duty to refer to a Pulmologist if available / affordable. .

What doctors can do: At this juncture i.e. -when clinical / presumed diagnosis is very strong??-1) Firstly,   to use barrier method if seriously considers Koch’s from history. To ask the couple to use barrier contraceptives till the ATD course is completed or diagnosis of TB is excluded with reasonable certainty.
2) If one have doubt one should not hesitant to proceed for Lap-Hysteroscopy (an endoscopy procedure under anesthesia & peritoneal/ Lymph node biopsy (because pick up rate of Koch’s seems very high-if hysteroscopy or Laparoscopy is done. This is an important means of documentation prior to initiation of ATD).


Then, what may be ideal economically affordable solutions of the problem: - i.e. difficulties in diagnosis of Genital Kochs??

 I am personally more in favour of Lap & hysteroscopy if serious doubt exists in a given case.
Because, by doing Lap & hysteroscopy one can collect many portions of samples from many sites(hopefully now without any environmental  contamination-as happens in Mens Blood collection) and I prefer to order following testsà All reports collectively, hopefully can exclude / confirm the diagnosis of TB :-After removing tissues from womb or tummy one can put such excised tissues for following investigations:
Such tests for TB are 1) Conventional   Histological diagnosis –Cornual region biopsy -can be performed with fair degree of accuracy-Z-N stain, & Normal saline stain AFB smear,, 2) Rapid culture-Bactec-460 in Co incubator, 3)  Delayed culture-in L-J media –such growth of bacteria in a special media will be of considerable help  to confirm  initial diagnosis’ based on H/O contact with Koch’s (particularly in close family members,) and 4) blood count :-raised TC & Lymphocytosis 
Firstly, No ATD based on Menst blood report only:-I don’t consider that ATD should ever be prescribed based on Menst Blood report. If there is +ve family history of Koch’s or say  H/O contact and irregular fever, loss of wt then one can at best  advise Chest X-ray & diag Endo biopsy / Hysteroscopy & endometrial assessment for Koch’s 1)  by Conventional,(should I call traditional)  AFB satin -Z-N Stain) ,. Culture for Koch’s bacilli includes 2) Bactec Test; 3) Rapid &4) Delayed cultures à followed by drug sensitivity tests which is often omitted by us. ,

, 7) G Pig inoculation of excised sample –delayed growth, 8) PCR from removed tissues without any contamination & DNA analysis specially by adopting the technique by RFLP technology --DNA 6110-mpt 64.-nested DNA, 9)?? PET scan very rare cases (trial are on), 10) MGIT Myco Growth Indicator Tube,



In case she falls preg during the course of anti-Koch’s- one should not advocate termination of Pregnancy (TOP).

 G) INH is notorious to cause peripheral Neuritis - Suppl. of vit B6 will help/ameliorate. In conclusion to avert MDR Koch’s it is our noble duty to motivate her to continue the ATD in consultation with Pulmologist. This is our patriotic duty.
 MDR Koch’s-- enough is enough. All these are my personal opinion invalidated by any Sc evidence or RCT. Personal Regards. Dr S K Pal Kolkata.
What is your view on TB-PCR? How sensitive or specific is that test? Can u pl. enlighten us?

·          




Monday, 9 January 2017
Environmental mycobacteria & What is Non pathogenic Ubiquitous Mycobacteria - NUM!??
 Why PCR (Polymerase Chain Reaction from peripheral blood-A noninvasive method to diagnose many a diseases of human body) is not reliable? Such environmental Bact have always been around, so why wasn't this a problem in the past? This is becausemodern 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!
Top of Form
Bottom of Form
TB PCR positive:-What to do?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 is sent to the lab for PCR testing



, 7) G Pig inoculation of excised sample –delayed growth, 8) PCR from removed tissues without any contamination & DNA analysis specially by adopting the technique by RFLP technology --DNA 6110-mpt 64.-nested DNA, 9)?? PET scan very rare cases (trial are on), 10) MGIT Myco Growth Indicator Tube,



In case she falls preg during the course of anti-Koch’s- one should not advocate termination of Pregnancy (TOP)
Then, what may be ideal economically affordable solutions of the problem: - i.e. difficulties in diagnosis of Genital Kochs??

 I am personally more in favour of Lap & hysteroscopy if serious doubt exists in a given case.
Because, by doing Lap & hysteroscopy one can collect many portions of samples from many sites(hopefully now without any environmental  contamination-as happens in Mens Blood collection) and I prefer to order following testsà All reports collectively, hopefully can exclude / confirm the diagnosis of TB :-After removing tissues from womb or tummy one can put such excised tissues for following investigations:
Such tests for TB are 1) Conventional   Histological diagnosis –Cornual region biopsy -can be performed with fair degree of accuracy-Z-N stain, & Normal saline stain AFB smear,, 2) Rapid culture-Bactec-460 in Co incubator, 3)  Delayed culture-in L-J media –such growth of bacteria in a special media will be of considerable help  to confirm  initial diagnosis’ based on H/O contact with Koch’s (particularly in close family members,) and 4) blood count :-raised TC & Lymphocytosis  (raised -level of one type of blood cells).

Firstly, No ATD based on Menstrual  blood report only:-Such blood test was very popular and still practiced all over world as because e as it is a noninvasive tests.. But I don’t consider that ATD should ever be prescribed based on Menstrual  Blood report. If there is +ve family history of Koch’s or say  H/O contact and irregular fever, loss of wt then one can at best  advise Chest X-ray & diag Endo biopsy / Hysteroscopy & endometrial assessment for Koch’s 1)  by Conventional,(should I call traditional)  AFB satin -Z-N Stain) ,. Culture for Koch’s bacilli includes 2) Bactec Test; 3) Rapid &4) Delayed cultures à followed by drug sensitivity tests which is often omitted by us. , 
What  doctors  can do: At this juncture i.e. -when clinical / presumed diagnosis is very strong??-1) Firstly,   to use barrier method if seriously considers Koch’s from history. To ask the couple to use barrier contraceptives till the ATD course is completed or diagnosis of TB is excluded with reasonable certainty.

2) If one have doubt one should not hesitant to proceed for Lap-Hysteroscopy (an endoscopy procedure under anesthesia & peritoneal/ Lymph node biopsy (because pick up rate of Koch’s seems very high-if hysteroscopy or Laparoscopy is done . This is an important means of documentation prior to initiation of ATD).
Lab diag of Kochs & Limitations of such Tests:-,-There are limitations of Lab diag of Kochs particularly genital Kochs(TB).—honestly speaking most of the genital cases, in my opinion, have to be diagnosed from history and sorry to say sometimes we have to initiate empirical treatment based on clinical suspicion
 At least that is my belief as almost all available Lab tests are to some extent is not full proof. All Lab tests have its limitations. That is the most important draw backs of diagnostic tests...In my opinion; - HSG is forbidden in a case of presumed/confirmed case of genital Kochs. B) Secondly, what we diagnose as genital Koch’s may be misdiagnoses/ inappropriate... It is difficult to be very certain about Koch’s as there is no specific serum marker till date.(contd) .

The ways & means of diagnosis of TB Endometrium.

Endometrial TB is a notoriously difficult diagnosis to confirm because it's very hard to grow mycobacteria in the lab.


 Earlier what was the policy in diagnosing Female genital TB ?

In the past, to make a definitive diagnosis of genital TB
 A) positive mycobacterium culture or B) thepresence of tubercles/ giant cells in thehistopathology report (from an endometrial biopsy) was required.But now following tests are collectively done to arrive at a definitive diagnosis. Many tests are done to prove or exclude. Fallacies of Lab diag of Kochs(se next post).

Surprisingly Leprosy –a disease which primarily affects skin & nerves of Men & Women in some poverty stricken districts of India also is caused by the same family of germs: We refer to Mycobacterium tuberculosis which causes 1) tuberculosis; or Mycobacterium leprae which causes leprosy. What is meant by nontuberculous   mycobacteria (NTM),environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT)?


A)Characteristics of Myco Tuberculosis? 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 is sent to the lab for PCR testing).


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