00:01
How do we confirm the diagnosis?
Well frequently, the diagnosis is clinical
only. If you are in a developing world where
you don’t have access to the investigations
that we have in the industrialized countries,
then you may have to be reliant on clinical
diagnosis. Confirm diagnosis requires seeing
or culturing the bacteria in a sample from
the patient. And for lung disease what we
do is to present 3 morning sputums for culture
and microscopy. For extra pulmonary disease
we may be able to get a sample so for example
genital urinary disease, the urine might be
positive. Meningitis, the CSF might be positive
but we often have to do biopsies of the affected
tissue as well because that will give us a sample
for culture and also for looking histologically
for the characteristic granulomas that
I have mentioned earlier.
00:56
So microscopy, what we are looking for is
acid fast bacilli, there is a special stain
used for mycobacteria, and if they are present
they will be positive for that stain and show
up on the microscopy. And that shows there
is a mycobacteria present in that sample,
and sort of 95 times out of 100 that mycobacteria
will be tuberculosis, although occasionally
it is one of those non-tuberculosis mycobacteria
that I mentioned earlier in this talk.
01:24
Culture is very important because it confirms that
mycobacterium present in microscopy is
M.tuberculosis, and more importantly, it gives
you the resistance profile. Whether that bacteria
is a sedative M tuberculosis or resistant
to some of the drugs that we might use to treat
it. The big problem with culture is that it’s
slow, it takes 3 to 4 weeks. So you're often
left with a patient who has given a sample,
no acid fast bacilli have been seen in it
and you are waiting now for the culture to
occur, and you need to make a decision whether
the patient requires treatment for TB, because
you're rarely sure that they might have TB.
02:03
For example in one of the examples I showed
earlier, the Bengali man he would be treated
before we got the culture results back even
if he was AFB negative in sputum because the
clinical presentation was so clearly going
to be tuberculosis. But if it’s not clear,
then you are just left waiting. Patients with
pulmonary tuberculosis their sputum will be
culture positive for the Microbacterium in
60 to 70% of cases at least. However, for
extrapulmonary tuberculosis the chance of
culture being positive is not so high for
some diseases, nodal disease, lymphnode disease,
pleural tuberculosis and TB Meningitis.
02:46
The yield from culture is much lower.
Recently there is a polymerase chain reaction
which has been developed, which is useful
for identifying tuberculosis much more rapidly
than culture does and that’s actually positive
even in patients who are not AFB positive
and that has improved our ability to rapidly
recognize patients with tuberculosis. We also
use biopsies to try and prove that tuberculosis
is present. Now this is particularly important
for extrapulmonary disease and what the biopsy
will show is the presence of Ghon granulomas,
which has very specific histological appearance
that reflects the immunological response to
the presence of Mycobacterium tuberculosis.
And in fact with TB there are very specific
granulomas which have a central area of necrosis
and then that’s called caseating granulomas.
03:38
And we use biopsias of the pleura, abdominal
disease, the lymphnodes to confirm the patient
may have extrapulmonary tuberculosis. Now
the main difference with diagnosis when you
have histological show of granulomas is of
sarcoid. Now in most clinical circumstances
TB and sarcoid are not easily confused, the
main exception being the presence of mediastinal
lymphadenopathy. The difference between sarcoid
and tuberculosis is that the granulomas in
sarcoid tend to be not caseating and clearly,
you won’t grow the bacteria M.tuberculosis
from patients with sarcoidosis. We also
use immunological testing, and what
we use that for is to identify patients who
have previously been exposed to or infected
with tuberculosis, and this therefore identifies
latent infection. And we have two different
methods for testing for that, one is the Heaf
test or Mantoux where we inject a mixture
of tuberculosis antigens into the skin and
in patients who've previously been exposed
to tuberculosis that will stimulate their
immunological reaction and a painful lump
will form there. The other test is more recently
developed blood test where essentially we
do a very similar thing, you incubate the
patient’s blood with a tuberculosis antigen
and you see whether the white cells have a
response to that, and those are called the
Interferon Gamma Release Assays. Their main
advantage is that they are not confounded
by previous vaccination with BCG. So for example,
I have a reasonably strong Mantoux reaction
because I was vaccinated with BCG as a child
and that means it's very difficult to use
that skin test to identify patients who may
have been exposed to tuberculosis if they've
previously had BCG vaccination. However, the
Interferon Gamma Release Assay will only be
positive in patients with previous tuberculosis
exposure and is not affected by the BCG.