Quiz: Answer quickly:-Pl do supplement the deficiencies in
my comments. What is meant by MOTT, NTM??
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)
A positive mycobacterium culture or the presence of tubercles in the histopathology
report (from an endometrial biopsy) was required.
b)
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. Quiz: 1:-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.
When most
doctors think about mycobacteria, we 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).
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).
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.
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 -
TB pcr positivity indeed seems
to be a breather for treating doctor to find some excuse for treatment in many
unexplained infertility!!Unfortunately most of infertility centre put Pt on ATT
in PCR ÷ve cases blindly.
PCR is reported as positive for M
tuberculosis or MOTT... and it is not positive in all cases if we consider that
it comes from hospital contamination... and if we consider the point you have
mentioned than it means we should not request this test at all....
But what if genuinely
positive. I think clinical correlation is imp to start ATT.
But then how many genuine cases will
be benefitted with ATT if damage has already occurred
Govt has banned TB pcr as per my knowledge and also
there is national TB registry which is being followed probably
If the endometrial biopsy
shows caseous granuloma on histopathology but AFB smear negative should pt be
started ATT
TB PCR IS not at all banned... The serological
tests Tb-IgG, IgM are banned. I believe pt should be always put on trial ATT if
TB is clinically suspected and see response. Other basic test like CBC for
lymphocytes%, ESR, Mantoux, Culture etc & advanced...
There is unlikely to be a gold
standard test for genital tuberculosis. The very nature of the disease:
paucibacillary, endometrium shed off every month and tube is primary site of
affection; makes it difficult to detect bacilli in endometrium. 
. Peasant Sir, thanks for wonderful post highlighting
MOTT. All good labs now report MOTT separately in TB PCR or gene expert. If we
use RO water for cleaning instruments and autoclave them, MOTT contamination is
rare. MOTT is most likely where codex is used for disinfection as
glutaraldehyde is not cidal for MTB or MOTT.
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