Sunday, June 15, 2014

Management of Tuberculosis: Therapeutic Approach

Pulmonary tuberculosis (Tuberculosis of lungs) or Extra-pulmonary tuberculosis (Tuberculosis of organs other than lungs) in humans is caused by Mycobacterium tuberculosis, a human tubercle bacillus. Mycobacterium tuberculosis is an obligate anaerobic bacterium, whose natural reservoir is human beings. Mycobacterium tuberculosis (MTB) is non-motile and does not produce spores. The generation time of MTB is 15 to 20 hours, so it is also called slow growing bacterium.
Tuberculosis (TB) of any type remains a challenging clinical problem and important public health issue the world over. In the recent past the World Health Organization (WHO) has documented an annual incidence of 9.27 million new cases of TB with a prevalence of 13.7 million cases. Majority of TB cases exist in Africa and South East Asia. The annual incidence rate in Africa and South East Asia has been reported as 356 and 182 cases per 100,000 population respectively that is much higher than the global incidence rate.

The ‘gold standard’ in the diagnosis of TB has been the detection of Mycobacterium tuberculosis in the sputum smear or in the pathological lesions (by histopathological methods). The rapid diagnosis of TB is fundamental to clinical outcome. On general physical examination careful attention should be given to the presence of lymphadenopathy (swollen/enlarged lymphnodes), draining sinuses, non-healing ulcers, spinal or joint lesions etc.

Extensive research has been going on in the field of management of TB through anti-tubercular treatment (ATT) ever since the discovery of rifampicin in 1960s. The major objectives of research in anti-tubercular treatment (ATT) include the shortening of duration of therapy, preventing the emergency of drug resistance, avoiding toxicity and shortening the period of infectivity. Direct Observation Therapy-Short Course (DOTS) is the most effective strategy propagated for the management of tuberculosis. Several new drugs and non-pharmacological therapeutic modalities are under extensive study for the effective management of tuberculosis.

A)  Pharmacological Approach to Management of TB:

Pharmacological drugs can be classified as

Ø  Drugs susceptible for MTB.

Ø  Drugs susceptible for conventional ‘drug-resistant bacilli’, which include the followings:

·         Re-purposed drugs (e.g. Fluoroquinolones)

·         New dosages of already available drugs (e.g. Rifampicin rifamycin or high dose isoniazid)

·         New drugs (e.g. Bedaquiline for ‘multi drug resistant-TB).

B)  Preventive Approach to Management of TB:

Ø  Vaccination: The use of BCG vaccination is recommended. Recombinant BCGs are also under clinical trials.

Ø  Chemoprophylaxis for Latent-TB: Chemoprophylaxis is recommended for new born babies born to ‘sputum smear positive’ mothers. Chemoprophylaxis should also be recommended for the cases having ‘Latent-TB’. Interferon gamma release assay test (IGRAs) and Mantoux Test (a Skin Test) are useful tests for establishing a diagnosis of Latent-TB. However, these tests do not necessarily indicate the presence of active tuberculosis and requirement of ATT.

C)  Non-pharmacological Approach to Management of TB:

Ø  Non-pharmacological advances are based on immunomodulation and immunotherapy. Use of protective cytokines, anti-cytokine agents (such as thalidomide pentoxiphylline) and immune-enhancement with ‘heat killed Mycobacterium vaccine’ and other recombinant BCGs have been under clinical trials. These modalities have not been recommended for standard clinical practice.

Ø  Strategies for Airborne Infection Control:  ‘International Guidelines on Airborne Infection Control in Healthcare Settings’ should be adopted. These guidelines are very important in the isolation wards, multi-drug resistant-TB (MDR-TB) wards and the Medical Laboratories conducting TB tests, for prevention of spread of infection among health workers in hospitals.

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