Despite several years of medical advances the worldis still a long way from exorcizing the medical demon of tuberculosis.
When considering the
worldwide scenario, nine million new cases are
diagnosed annually and at least 1.5 million people
succumb to the disease every year. Several reasons were
stated in support of failure to curb the disease, like the
lack of investment into diagnostic tools and treatment,
persisting poverty, lack of access to medical care,
increase in drug-resistant strains of TB, crowded living
conditions and the most leading cause is the spread of
HIV, the virus that causes AIDS. Infection with HIV
suppresses the immune system, making it difficult for
the body to control TB bacteria.
As a result, people with HIV are more prone to
development of TB than who aren't HIV-positive. When
talking about the treatment aspect, there is still no test
that can instantly determine whether person has TB
and treatment methods require a cocktail of drugs
daily for at least six months and a length of time to
which few patients can adhere.
Tuberculosis in India has not got the attention it
deserves in part because it has mainly affected the
poors. The usual victims are migrant labourers, slum
dwellers, residents of the backward areas and the
tribal pockets, secondly the diagnosis and treatment of
TB is the biggest challenge.
Because the signs and symptoms seen in the
TB is similar to the other diseases, such as
carcinoma, pneumonia, sarcoiodosis, lymphoma, etc it's
diagnosis becomes the toughest part. The diagnostic
principle involves the detection of the direct causative
agent Mycobacteria or its products and measurements
of the humoral and cellular responses of the host against
the bacteria, diagnosis is done through clinical finding,
microscopy, culture, X ray, ESR, Mantoux test, serology
or the more advanced PCR technique. But the
conventional methods applied in the diagnosis comes
with certain limitations which have restricted their use.
The diagnosis procedure are listed.
SPUTUM EXAMINATION UNDER THE MICROSCOPY
Though old fashioned, this method still remain the only
and most valuable diagnostic method for TB.
Whenever TB is suspected, at least
3 specimens of the sputum is
collected and examined by
microscopy to detect the Acid Fast
Bacilli using the Ziehl Neelsen
staining. The limit of detection of
this method is that it requires at
least 5 X 103 bacilli per ml sputum
and various other factors like type
of specimen, thickness of the s
smear, extent of the decolourisation, type of counter
stain used and the training and
experience of the person
examining the sputum affects the
test results.
LABORATORY CULTURE
of M. tuberculosis is quite sensitive
as 10-100 organism per sample can
be detected. The drawback of the
culture is that it requires the
complex cultivation media and
takes 4-8 weeks to get the result. In
view of the slow rate of the growth
of tubercule bacilli attempts have
been made to develop more rapid
methods. Radiometry is one of
these, which is based on the
release of the radioactive carbon
dioxide due to the bacterial
metabolism. But the consumable
cost is very high.
X RAY
has its own merits and demerits. It
is not uncommon to come across
patients who have been started on
anti tubercular chemotherapy
relying solely on the X ray examination, neglecting sputum examination or ignoring the results,
which is incorrect practice as
radiographs may be misleading.
MANTOUX (Tuberculin skin Test)
Also known as purified protein
derivative(PPD) method put use up
to find out whether the individual is
infected or not. Where the liquid
tuberculin is injected between the
skin layers of forearm. After this
the patient's arm examination is
done for 48-72 hours, the swelling
or redness, which is induration of
the area indicates the positive
results. But this method is brought
in limited use as for its wrong
interpretation of the results. It is
not reliable method to be used in
country like India, where there is
high prevalence of exposure
Infection to both the pathogenic as
well as non- pathogenic forms of
the TB bacillus. QuantiFERON-TB
gold assay is a modern alternative
method to the 175- year old skin
test that measures the level of
chemical called interferon against
Mycobacteria specific antigens.
POLYMERASE CHAIN REACTION
Is an amplification technique that
is rapid for directly detecting the
mycobacterial DNA or RNA from
clinical samples. Such assays have
high potential, but at present only
few meet the FDA approval. PCR
kits for drug resistant forms are
still in developing stage. Many
issues are also associated with
amplification assays such as
expense, specificity and their
clinical utility.
SEROLOGICAL TESTING
It is the most widely employed
diagnostic technique for tuberculosis, the method involve the measurement of the IgG and IgM
antibodies. Factors like the easy-
to-use, less time in results inter-
pretation, the easiness in sample
availability and modest testing
cost makes it the highly recommended procedure for TB. But the
reports published by the World
health
Organization on 20th July 2011 in
Geneva raised a questions against
the accuracy interpretation of the
tests results through the
serological testing. They stated
that the use of currently
available commercial blood tests to
diagnose active tuberculosis (TB) often leads to
misdiagnosis, mistreatment and potential harm to
public health.
The serological testing is lacking the sensitivity and
specificity, which are the major tool of the diagnostic,
where low sensitivity results in an unacceptably high
number of patients being wrongly given the 'all clear'
(i.e. a false-negative). This can lead to them dying from
untreated tuberculosis, and the disease also being
transmitted.
Low specificity leads to an unacceptably high number
of patients being wrongly diagnosed with TB (i.e. a
false positive). This can lead to them undergoing a six
month course of unnecessary treatment, while the real
cause of their illness remains un-investigated and
undiagnosed.
Many a times a positive TB test does not necessarily
mean that the person is having tuberculosis. There are
several factors that can produce a false positive
serological testing. Like BCG vaccination and Environmental Mycobacteria.
EFFECT OF BCG VACCINATION ON SEROLOGY
REPORTS
The BCG vaccine is given to children to prevent
tuberculosis infection. It contains a live attenuated
(weakened) form of Mycobacterium bovis, which is
the bacterium that causes tuberculosis (TB). The
vaccine is known as BCG because a strain of the
bacterium known as Bacillus Calmette-Guerin is used.
The vaccine works by stimulating the body's immune
response to the bacteria, without actually causing the
disease. Vaccines containing extracts or inactivated
forms of bacteria stimulate the immune system to
produce antibodies against them, but don't actually
cause disease themselves. The antibodies produced
remain in the body so that if the organism is encountered naturally, the immune system can recognize it
and attack it. This prevents it from causing disease.
When such people are subjected to the TB serological
(ELISA) testing, a test that compare the levels of
antibody to M. tuberculosis in the IgG, IgM and IgA
classes, the interpretation showed higher levels of the
IgG, this is due to the previously existing antibodies
which is raised against vaccination. As the IgG class
was the most discriminative from the diagnostic point
of view, this phenomenon reduced the usefulness of the
test. But when the levels of the IgM is assayed it is not
present. Ultimately leading to the wrong interpretations of the test results.
Book Tuberculosis TGS Profile
EFFECT OF OTHER ENVIRONMENTAL
MYCOBACTERIA ON RESULTS
Although there are some other common species within
the same genus that cause TB, there are many species
also that does not cause tuberculosis at all. A person
who has been infected with another member of this
genus may show false positive results. As when our
body is exposed to these species through various
modes, our body recognizes these as a foreign antigen
and raise an immune response towards it. On
serological testing the antibodies IgG are detected,
which is due to the antigenic similarity of other
Mycobacterium species with M.tuberculosis. That
causes cross reaction with the antigens in testing
giving false results.
Even though, serological testing is known to give false
positive results, India continues practising it as one of
the diagnostic methods. However WHO recommends
all countries to stop usage of the serological testing
which are often inaccurate and instead urges people to
rely on the microbiological and molecular tests.
