It was more than a century ago when Robert Koch made an observation
that if the number of victims which a disease claims is a measure
of its significance, then all diseases must rank far behind tuberculosis.
Even after more than hundred years, tuberculosis still remains one
of the major causes of morbidity and mortality. WHO has declared
tuberculosis as a global emergency. The disease has assumed alarming
dimensions in view of the emergence of multiple drug resistance
tuberculosis. According to a WHO estimate about 1.7 billion people,
one third of world's population, carry the tubercle bacillus, and
every year there are 8 million new cases of TB causing death to
3 million people. The problem is further compounded by the pandemic
of AIDS and increased incidence of multiple drug resistance TB.
In India it is estimated that there are 14 million patients of tuberculosis,
out of which at least 25% are sputum smear positive. Death rates
vary from 20-40 per 1,00,000/year depending on the availability
of diagnostics and treatment facilities.
Drug resistance has emerged as a major cause of failure of anti-tubercular
therapy. The risk of infection with resistant Mycobacteria is increasing,
posing a threat to control and eradication of this disease. The
main reasons for emergence of drug resistance in India are erratic
drug ingestion, mono-therapy, omission of one or more prescribed
agents, sub optimal doses and poor drug absorption. Anti TB drugs
are also freely available in the market, which leads to self-treatment
and improper regimen. Unless effective steps are taken to treat
and limit resistance, it may soon assume alarming proportions.
Overall the prevalence of initial drug resistance among adults is
about 20-30% for Isoniazid and 2-3% for Rifampicin. However, in
patients with acquired resistance i.e. those who have had chemotherapy
in the past, the rate of drug resistance is much higher i.e. 50-60%
for INH, 20-30% for Rifampicin.
Diagnosis of Drug Resistance Resistant
Tuberculosis
Early diagnosis and application of accurate chemotherapy is important
because absence of the same may
|
Propagate the resistance |
|
Cause unnecessary
drug toxicity |
|
Decrease chances of
cure |
|
Increase the cost of
therapy |
Laboratory Diagnosis of Drug Resistance
of Mycobacteria
|
Traditional
culture method for drug sensitivity tests The confirmation
of presence of drug resistance is obtained by culture and
sensitivity test. The traditional methods employs 7H10,
7H11, Middlebrook or on LJ Media. This usually takes 12
to 16 weeks. Since these traditional methods are time consuming
and may delay the treatment by at least 2 to 4 months, newer
and rapid methods of culture and sensitivity of the Mycobacteria
have been developed. |
|
Newer
rapid radiometric BACTEC 460 TB System for culture and drug
sensitivity. It is a radiometric detection of Mycobacteria
growth with the help of sophisticated gamma camera by using
radioactive 140C. It gives results of culture and sensitivity
within 10-14 days, thereby immensely aiding in early institution
of correct therapy |
|
Molecular
methods for drug resistance
Advances in the field of Molecular Biology have led to some
innovations, which may play an important role in the diagnosis
of MDR-TB. Mutations in rpoB gene determines resistance
to Rifampin and it is detected by single stranded conformation
polymorphism in conjunction with PCR [PCR-SSCP]. The SSCP-PCR
tests for isoniazid, rifampicin and streptomycin resistance
can be performed on clinical samples directly and requires
less than 2 days for the results. It is now established
that the mutations conferring multiple drug resistance in
the Indian strains of Mycobacterium tuberculosis are different
from the western strains and PCR protocols, which can pick
up the novel Indian mutations have been standardized |
The drugs available at Auroprobe laboratories
for sensitivity testing of Mycobacteria by BACTEC 460 TB system
are:
|
|
Streptomycin |
|
Isoniazid |
|
Rifampicin |
|
Ethambutol |
|
Pyrazinamide |
|
|
Second
line drugs |
|
Ofloxacin |
|
Kanamycin |
|
Capreomycin |
|
Cycloserine |
|
Leofloxacin |
|
Moxifloxacin |
|
Ethionamide |
|
PAS |
Bibliography
|
De
Beenhouwer H, et al. 1995. Rapid detection of rifampicin
resistance in sputum and biopsy specimens from tuberculosis
patients by PCR and line probe assay. Tubercle and Lung
Disease 88: 78-89 |
|
Sharma
SK. 1999. Multi drug resistant tuberculosis. JIMSA 12(1):
84-90 |
|
Thakker
H, Shah JR.1998. Multi drug resistant pulmonary tuberculosis.
Ind.J.Tub 45 : 131-139 |
|
Siddiqi
N, Shamim M, Jain NK, Rattan A, Amin A, Katoch VM, Sharma
SK, Hasnain SE. Mem Inst Oswaldo Cruz 1998 Sep; 93(5): 589-594 |
|
