TB presents initially as flu-like symptoms. As the disease progresses, it manifests itself with chronic cough with blood-tinged sputum, fever and night sweats. Patients also complain of weight loss, malaise, retrosternal pain and weakness. There may also be cutaneous lesions. Primary infection usually persists for 7-14 days.

Extrapulmonary tuberculosis most frequently presents with lymphadenitis. It may also cause leukocytosis and anemia, however, the findings are nonspecific. Tuberculous meningitis presents with persistent headache, altered mental status which may progress to coma and low grade fever. Skeletal TB most commonly affects the spine, called Potts disease.

Laboratory tests

Screening:

• Tuberculin skin test (using PPD)
• Interferon-Gamma release Assay (IGRA): IGRA assays offer certain advantages over tuberculin skin testing [6].

Suspected TB:

• Acid-fast staining of sputum or other specimens
• Culture in Lowenstein-Jensen agar
• Nucleic acid amplification tests
• Luciferase Assay which can detect drug resistant organisms [2]
• HIV serology

Imaging

Imaging studies include chest radiography and CT scan which can show pulmonary infiltrates. A biopsy can be performed, but is rarely needed.

Test results

On the basis of clinical evaluation and laboratory test results, TB can be definitively diagnosed. Susceptible individuals should also be screened for latent TB. The goal of testing for latent tuberculosis infection (LTBI) is to identify individuals who are at increased risk for the development of tuberculosis (TB) and therefore would benefit from treatment of LTBI [7].

Medication

Anti-tuberculous chemotherapy is the mainstay of treatment and highly effective. The most commonly used antibiotics used are isoniazid (INH) and rifampicin. The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is 6 months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months [8]. Only rifampicin and isoniazid need to be continued for the last four months.

Directly observed therapy

Patient compliance is generally found to be non satisfactory. To overcome this hurdle, directly observed therapy (DOT) has become an important part of treatment. Individual case management with DOT is very important for facilitating adherence and preventing the development of drug resistance and represents the standard of care in the United States today [9].

TB infection does not always progress to active TB disease, but since both active and latent TB responds well to antituberculous chemotherapy, it has an excellent prognosis. Identification and treatment of latent tuberculosis infection can reduce the risk of development of disease by as much as 90 percent [5].

Mycobacterium tuberculosis

The primary causative agent of tuberculosis is the slender, rod-shaped obligate aerobe called Mycobacterium tuberculosis (other mycobacteria can also cause this disease). It is acid-fast due to the high lipid content (up to 60%) of their cell walls. 3 important constituents include [2]:

• Long-chain fatty acids (C78-C90) called Mycolic acids which contribute to the acid-fastness.
• Wax D serves to enhance the immune response. 
• Phosphatides play a role in caseous necrosis.

Transmission

TB is an air-borne infection. It can be transmitted by coughing, sneezing, spitting and even speaking by a person with an active infection. All such actions result in expulsion of infectious aerosol particles or droplets that contain the bacteria which may be inhaled by anyone present in the vicinity. Since the infectious dose of TB is very low, inhalation of as little as 10 organisms can lead to the development of this disease. People in close contact with such a person are particularly at high risk.

Genetics

Many patients are genetically vulnerable to this disease. Polymorphisms in some genes, for example in NRAMP1 gene which encodes the NRAMP1 transmembrane protein that pumps divalent ions out of lysosomes, may result in ineffectual immune response of the host. NRAMP1 may inhibit microbacterial growth by limiting availability of ions needed by the bacteria [3]. So a genetic defect in this gene may make the host vulnerable to TB.

Incidence

TB is estimated to affect 1.7 billion individuals worldwide with approximately 1.6 million deaths annually. 

Age

Tuberculosis is typically a disease of older people. Immuno-compromised individuals, however, are at risk, irrespective of age.

Sex

The disease is found more in males than in females.

Race

TB is prone to develop in poverty stricken areas and so, in many regions of various third world countries this disease is a common occurrence. It has the highest occurrence in Asians, followed by Hispanics and then African-Americans. 

Mycobacterium tuberculosis enters macrophages by endocytosis mediated by several factors. Once inside, it begins to replicate in the pulmonary airspaces and alveolar macrophages. Despite bacteremia, most patients at this stage are asymptomatic. About 3 weeks after infection, a T-H1 response is mounted that activates macrophages to become bactericidal [4]. The activated T-H1 cells produce Interferon gamma which is critical in containing the infection. NK-1 cells also produce IFN-y. IFN-y enables macrophages to differentiate into epitheloid histiocytes which are characteristic findings of granulomas. Caseous necrosis ensues in an attempt to close off and destroy the bacteria.

The primary formed lesions are 1-1.5 cm areas of inflammation with consolidation called Ghon focus. They begin to caseate and some of the bacteria disseminate into regional lymph nodes. This caseated lesion along with lymph node involvement constitutes the Ghon complex. In subsequent weeks the tubercle bacteria disseminate to the rest of the body via both lymphatic and hematogeneous spread. The Ghon complex undergoes progressive fibrosis turning into calcified lesions called Ranke complex.

All this results in three major effects: Reduced breathing and vital capacity, reduced total respiratory membrane surface area and increased thickness of the respiratory membrane, and lastly, abnormal ventilation-perfusion ratio of the lung.

TB can be prevented with the use of BCG vaccine. This vaccine contains a strain of live, attenuated Mycobacterium bovis called bacillus Calmette-Guerin. It can also be prevented by living in well-aired, less crowded quarters and using boiled water and pasteurized milk. The PPD screening test should also be regularly performed in people belonging to susceptible demographics.

Tuberculosis (TB) is a multisystemic disease commonly affecting the lungs. It is due to an infection by bacteria of the Mycobacteria genus. It is transmitted when people who have an active TB infection cough, sneeze, or otherwise transmit respiratory fluids through the air [1]. It is one of the most common infectious diseases in the world and a source of high infection-associated mortality, second only to HIV. The World Health Organization is still attempting to eradicate the disease from the world and has been quite successful in significantly decreasing the incidence of TB in many developed countries.

Definition

Tuberculosis (TB) is an infectious disease that occurs due to transmission of bacteria from a person with an active TB infection to a healthy individual. Patients that are immune-compromised, for e.g HIV patients, are at higher risk of contracting this disease. 

Cause

TB is most commonly due to an infection by Mycobacterium tuberculosis. Other strains like Mycobacterium bovis may also cause TB. Transmission is through air, like during coughing or sneezing via aerosol droplets containing the infectious particles. 

Signs and symptoms

Signs and symptoms vary according to the type of TB. TB affecting the lungs presents with chronic cough with sputum, chest pain, fever, night sweats and weight loss. Skeletal TB presents with body aches, musculoskeletal pain and joint pain. Tuberculous meningitis presents with headache, altered mental status, fever and sometimes coma.

Diagnosis

Diagnostic evaluation for TB may be initiated in outpatient settings [10]. Patients that are susceptible to this disease should be screened. Diagnosis is made based on history, chest radiography and positive blood/sputum cultures. 

Treatment

Treatment is ideally a quadruple therapy of antibiotics that should be continued for 6 months to prevent recurrence.

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