Basic facts about TB
source: WHO's "TB/HIVA CLINICAL MANUAL" p.19 (WHO/TB/96.200)

Mycobacterium tuberculosis
TB is a bacterial disease caused by Mycobacterium tuberculosis (and occasionally by Mycobacterium bovis and Mycobacterium africanum). These organisms are also known as tubercle bacilli (because they cause lesions called tubercles) or as acid-fast bacilli (AFB). When examining sputum containing tubercle bacilli stained with certain dyes under the microscope, the bacilli look red. This is because they are acid-fast (they have kept the dye even after washing with acid and alcohol). Tubercle bacilli can remain dormant in tissues and persist for many years.

Transmission of infection
Transmission occurs by airborne spread of infectious droplets. The source of infection is a person with TB of the lung who is coughing. TB of the lung is pulmonary TB (PTB). This person is usually sputum smear-positive (see Chapter 3). Coughing produces tiny infectious droplets (droplet nuclei). One cough can produce 3,000 droplet nuclei. Transmission generally occurs indoors, where droplet nuclei can stay in the air for a long time. Ventilation removes droplet nuclei. Direct sunlight quickly kills tubercle bacilli, but they can survive in the dark for several hours. Two factors determine an individual’s risk of exposure: the concentration of droplet nuclei in contaminated air and the length of time he breathes that air.

Risk of infection
An individual’s risk of infection depends on the extent of exposure to droplet nuclei and his susceptibility to infection. The risk of infection of a susceptible individual is therefore high with close, prolonged, indoor exposure to a person with sputum smear-positive PTB. The risk of transmission of infection from a person with sputum smear-negative PTB is low, and with extra-pulmonary TB is even lower. Risk of progression of infection to disease. Once infected with M.tuberculosis, a person stays infected for many years, probably for life. The vast majority (90%) of people without HIV infection who are infected with M.tuberculosis do not develop tuberculosis disease. In these healthy, asymptomatic, but infected individuals, the only evidence of infection may be a positive tuberculin skin test.

Infected persons can develop tuberculosis disease at any time. The chance of developing disease is greatest shortly after infection and then steadily lessens as time goes by. Various physical or emotional stresses may trigger progression of infection to disease. The most important trigger is weakening of immune resistance, especially by HIV infection. Disease can affect most tissues and organs, but especially the lungs.

Natural history of untreated TB
Without treatment, after 5 years, 50% of pulmonary TB patients will be dead, 25% will be healthy (self-cured by strong immune defence) and 25% will remain ill with chronic, infectious TB.

Epidemiology
M. tuberculosis infects a third of the world’s population. Worldwide in 1995 there were about 9 million new cases of TB with 3 million deaths. These deaths comprise 25% of all avoidable deaths in developing countries. 95% of TB cases and 98% of TB deaths are in developing countries. 75% of TB cases in developing countries are in the economically productive age group (15-50 years).

Primary infection
Primary infection occurs on first exposure to tubercle bacilli. Inhaled droplet nuclei are so small that they avoid the muco-ciliary defences of the bronchi and lodge in the terminal alveoli of the lungs. Infection begins with multiplication of tubercle bacilli in the lungs. This is the Ghon focus. Lymphatics drain the bacilli to the hilar lymph nodes. The Ghon focus and related hilar lymphadenopathy form the primary complex. Bacilli may spread in the blood from the primary complex throughout the body. The immune response (delayed hypersensitivity and cellular immunity) develops about 4-6 weeks after the primary infection. The size of the infecting dose of bacilli and the strength of the immune response determine what happens next. In most cases, the immune response stops the multiplication of bacilli. However, a few dormant bacilli may persist. A positive tuberculin skin test would be the only evidence of infection. The immuneresponse in a few cases is not strong enough to prevent multiplication of bacilli, and disease occurs within a few months.

Practical Point
Following primary infection, rapid progression to intra-thoracic disease is more common in children than in adults. Chest X-ray may show intrathoracic lymphadenopathy and lung infiltrates.

Post-primary TB
Post-primary TB occurs after a latent period of months or years after primary infection. It may occur either by reactivation or by reinfection. Reactivation means that dormant bacilli persisting in tissues for months or years after primary infection start to multiply. This may be in response to a trigger, such as weakening of the immune system by HIV infection. Reinfection means a repeat infection in a person who has already previously had a primary infection.

Post-primary TB usually affects the lungs but can involve any part of the body. The characteristic features of post-primary PTB are the followig: extensive lung destruction with cavitation; positive sputum smear; upper lobe involvement; usually no intrathoracic lymphadenopathy.

PULMONARY TB

e.g. cavities
upper lobe infiltrates
fibrosis
progressive pneumonia
endobronchial

EXTRA-PULMONARY TB

COMMON

Pleural effusion
Lymphadenopathy (usually cervical)
Central nervous system (meningitis, cerebral tuberculoma)
Pericarditis (effusion/constrictive)
Gastro-intestinal (ileocaecal, peritoneal)
Spine, other bone and joint

LESS COMMON

Empyema
Male genital tract (epididymitis, orchitis)
Female genital tract (tubo-ovarian, endometrium)
Kidney
Adrenal gland
Skin (lupus vulgaris, tuberculids,miliary)

source: WHO's "TREATMENT OF TUBERCULOSIS: GUIDELINES FOR NATIONAL PROGRAMMES. SECOND EDITION 1997" pp.26-29 (WHO/TB/97.220)

Note:

In Malaysia, the Ministry of Health is using twice-weekly regimens for intermittent phase.