Tuberculosis (TB), a chronic infectious disease characterised by the formation of tubercles, is caused by Mycobacterium tuberculosis also called the tubercle bacillus. It is a potentially fatal disease, which primarily affects lungs (pulmonary TB) but can also target other organs and tissue types such as bones, meninges, kidney, liver, heart, spleen and genitourinary tract. TB was also known as phthisis, consumption, white plague, king's evil etc. in the past.
According to 2009 estimates of World Health Organisation (WHO) south-east Asia presented the largest number of cases of tuberculosis followed by Africa. Around the globe there were 9.4 million new TB cases including 1.4 million cases of HIV-TB co-infection and 1.8 million people died from tuberculosis in 2008. The estimated global incidence rate was 139 per 100 000 population. Estimated number of MDR-TB cases in 2007 is 500 000.
Dissemination, symptoms and precipitating factors
TB is a highly contagious and spreads through air. A person having infectious tuberculosis i.e. smear positive pulmonary infection can spread TB by coughing, sneezing, spitting and even talking. While the main portal of entry is the respiratory tract, bacteria may also enter the body through ingestion, open wounds or during sexual intercourse. Nosocomial tuberculosis outbreaks have also been reported from India and elsewhere (10-12). Everybody who is infected with the tubercle bacillus may not necessarily develop the disease. This type of infection is called latent TB and is harmful neither to the person infected nor to those in the vicinity. However, under circumstances such as AIDS, immune suppression etc latent infections may develop into active disease.
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Mycobacterium tuberculosis is an obligate aerobe so preferably infects lungs but can infect virtually every organ of the body and depending upon the organ infected symptoms may vary. Symptoms common to all types of tuberculosis include low grade fever, fatigue, loss of weight and loss of appetite. Productive cough for more than three weeks is obvious symptom of pulmonary tuberculosis. Infection in the genitourinary tract may lead to kidney failure and partial or complete infertility. Meningeal tuberculosis causes epilepsy. TB may also affect bones, lymphatic, heart, abdomen, spleen etc and cause dysfunction of respective organs (13,14). When the infection spreads from one organ to the blood then it is called miliary tuberculosis or disseminated TB (15).
Factors that increase the risk of developing TB are HIV infection (16), low socioeconomic status, alcoholism, crowded living conditions, immune system debilitating conditions and migration to areas with high incidence and latent TB (17).
Prevention, diagnosis and treatment
Clinical specimens collected from the site of infection are required for the laboratory diagnosis of TB. While, X-ray and microscopy are most widely and commonly used methods for the diagnosis of multibacillary TB, paucibacillary cases could only be detected using more efficient methods like nucleic acid amplification tests (NAAT), polymerase chain reaction (PCR) and immunoassays (18). Culture of all positive specimens is mandatory in order to perform drug susceptibility assays but, it may take upto 10 weeks to determine the sensitivity profile. There are rapid detection methods like NAAT, single strand conformation polymorphism (SSCP), DNA arrays, molecular beacons etc. used for determining MDR-TB but none of them is commercially available (19).
Bacille Calmette-Guérin (BCG) is the only vaccine available presently. It may prevent tuberculous meningitis in children, but does not as a rule protect against pulmonary tuberculosis.
If active disease develops, a 6-9 month chemotherapy regimen must be followed by patients. A combination of four drugs, rifampicin, isoniazide, ethambutol and pyrazinamide is given for two months to ensure killing of any potentially drug resistant bacteria. Thereafter, usually only two drugs are used (20) for additional 4-7 months depending upon the drug resistance profile of the patient. DOTS is classified into three categories, namely I, II and III given to primary, MDR and extra-pulmonary TB patients respectively. While DOTS allows TB to be treated in 6-9 months MDR TB can only be treated using more toxic and expensive second line drugs such as amikacin/kanamycin, flouroquinolones, cycloserine etc. for more than two years. Non-compliance at this stage leads to extensively drug resistant (XDR) tuberculosis for which there is no treatment available. XDR TB may be defined as the occurrence of TB in persons whose M. tuberculosis isolates are resistant to isoniazid and rifampin plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin) (20).
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In spite of the availability of the antibiotic streptomycin (STR) since 1947 (4), TB incidence has never dropped (5). Advent of more potent drugs like rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) and the Direct Observation Therapy Short-Course (DOTS) programme, once seemed to be promising in lowering the death rates but, ironically, lack of proper patient management and/or unavailability of drugs induced the emergence of multi drug resistant (MDR) TB (MDR is defined as resistance to at least INH and RIF). As a result, even after 60 years of the discovery of first anti-tubercular drug (6,7), one third of the world population is still infected with the disease (7,8).
More general reasons for the persistence of TB are inefficient implementation of DOTS, lack or insufficient allocation of funds, poor supply of drugs or supply of low quality generic drugs, lack of commitment from governments and human resource organizations, unbalanced epidemiological results, non-stringent quarantine laws, unavailability of highly efficient and rapid and inexpensive assays for the diagnosis of primary/MDR TB. One other important factor that has fundamentally altered the epidemiology of TB worldwide is HIV (Human immunodeficiency virus). The disease reactivates in 5-10% of AIDS (Acquired immune deficiency syndrome) patients per year (9). Intensified case-finding, isoniazid prevention therapy and infection control need urgent implementation to control primary, MDR and XDR-TB.