Mycobacterium tuberculosis

Tuberculosis is an ancient disease which has continued to attack human health for thousands of years. The earliest evidence of tuberculosis has been found in Egyptian mummies dating as far back as 2000 BC. It later came to be identified as an infectious disease transmitted by airborne droplets. Robert Koch in the year 1882 discovered the tubercle bacillus. Later, the microorganism producing disease in humans was designated as Mycobacterium tuberculosis while the bovine type was called Mycobacterium bovis.

The estimated global incidence of tuberculosis is 136 per lac population with the highest incidence of 343 per lac population in Africa. According to the World Health Organization, the global prevalence of tuberculosis was 217 per lac population in 2005 This could only be the tip of the iceberg as a large number of cases go undiagnosed especially in countries with inadequate diagnostic facilities. The global mortality rate of tuberculosis is 24 per one lac population with deaths rates being highest in Africa (74 per lac) followed by South East Asia (31 per lac).

Tuberculosis is primarily a disease which is manifested whenever the immunocompromised host. The cell-mediated arm of the immune system plays a major role in protecting the host from disease. The tubercle bacilli thrive intracellularly within the macrophages. When the immune system of the host is intact, the mycobacterial proteins are presented to the cellular arm which produces chemokines and induces immunity to the disease. With failing cell- mediated immunity, the tubercle bacilli continue to multiply within the macrophages and spread through the hematogenous route to produce disseminated disease or miliary tuberculosis.

Structure

Mycobacteria are thin, rod shaped organisms (3µm X 0.3µm) occasionally appearing as branching filaments which may resemble the fungal mycelium. Therefore, they have been named ‘Mycobacteria’, meaning fungus-like bacteria. Mycobacterium tuberculosis resists decolorisation with dilute acids such as 20% sulphuric acid, therefore it is also known as ‘acid fast bacillus’. The cell wall of Mycobacterium tuberculosis is rich in lipids and wax. An unsaponifiable wax called mycolic acid contributes to the acid fastness of these organisms. They grow very slowly and are obligate aerobes.

Route of transmission

About one third of the world’s population is affected by tuberculosis. Mycobacterium tuberculosis is an airborne pathogen and it often affects the respiratory system. Coughing, sneezing and even speaking releases thousands of droplets into the air .Though airborne infection is the main mode of transmission, inoculation at the site is another means to acquire infection. This is particularly important in nosocomial transmission where equipment such endoscopes or other invasive instruments are not disinfected properly.

Resistance

M.tuberculosis is not particularly heat resistant and can be easily killed at 60° C in 15 to 20 minutes. When exposed to direct sunlight, they can be destroyed within 2 hours. This is an effective way of preventing nosocomial infections in resource limited countries where facilities for the treatment of air may not be feasible. The World Health Organization recommends large, well ventilated rooms with good natural sunlight for such areas.

Mycobacterium tuberculosis is relatively resistant to chemical disinfectants. It can easily survive exposure to 5% phenol, 15% sulphuric acid, 3% nitric acid, 5% oxalic acid and 4% sodium hydroxide. But it is sensitive to aldehydes such as formaldehyde and gluteraldehyde. A 2% solution of gluteraldehyde effectively destroys Mycobacterium tuberculosis when exposed for 35 to 45 minutes. These act as high level disinfectants and must be used for disinfection of semi-critical and critical instruments such as endoscopes. A new aldehyde, Ortho-phthalaldehyde (OPA), has also been used against Mycobacterium tuberculosis. Other agents used for high level disinfection are hydrogen peroxide, stabilized hydrogen peroxide and peracetic acid.

The growing concern about tuberculosis

Antitubercular therapy has been available only for the last 50 years with streptomycin becoming the first available drug. But, soon after its use, the TB bacilli became resistant to this drug. Eventually, with more drugs becoming available, multi-drug therapy prescribed for at least 6 months has been the mode of therapy used to cure tuberculosis. We now have multi-drug drug resistant strains of Mycobacterium tuberculosis making the treatment of tuberculosis prolonged and difficult. Multi-drug resistant strains (MDR-TB) are those which are resistant to isoniazid and rifampicin, the two powerful bactericidal drugs used for treatment. In some countries such as the former Soviet Union, the rate of MDR-TB is very high and this threatens the efforts towards global tuberculosis control.

Some strains of Mycobacterium tuberculosis are now resistant to even the second line drugs like fluoroquinolones and aminoglycoisdes in addition to the drugs used for first line therapy. These are known as extensively drug resistant strains (XDR-TB). With no drugs available to treat such patients, they are potential sources for the spread of resistant bacilli in the community. The increasing incidence of primary and acquired drug resistance has become a cause of concern, as newer antimicrobial agents to treat tuberculosis are not becoming available and research for antimycobacterial agents is still only in the preliminary stages.

The global HIV epidemic has also contributed to the increasing concern over tuberculosis control. HIV destroys the immune system, especially the cellular arm, and exposes patients to opportunistic pathogens. Tuberculosis and HIV have now become a lethal combination with TB being the leading cause of death in HIV infected individuals. According to the Centers for Disease Control and Prevention (CDC), the risk of developing active disease in HIV infected patients with untreated latent infection is about 1.7 to 7.9 tuberculosis cases per 100 persons per year.

Diagnosis

Sputum microscopy is a very simple and inexpensive method used to identify infectious patients who can then immediately be started on four drug therapy. Chest radiography appears to be nonspecific unless it can be correlated with the clinical features of the patient. The tuberculin skin test has been used for diagnosis of latent tuberculosis. Since this is done using proteins derived from BCG, false positive results are likely to occur with other mycobacterial infection or with recent history of BCG vaccination. The Interferon Gamma Release Assay (IGRA) is a new method used to identify latent tuberculosis infection which uses antigens specific to M.tuberculosis only. This is an invitro assay in which the patient’s blood is incubated overnight with mycobacterial antigens (ESAT -6 & CFP10) and the release of interferon gamma by the patient’s lymphocytes is quantified. This assay is called the QuantiFERON-TB Gold Test and is manufactured by Cellestis.  It has been approved by the United States FDA.