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!
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)
What are the different kinds of
laboratory tests and methods to avoid contamination f the removed tissues from
women body??
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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