Tuberculosis is an infection
with the bacterium Mycobacterium tuberculosis, which most commonly affects the
lungs (pulmonary TB) but can also affect the central nervous system
(meningitis), lymphatic system, circulatory system (miliary TB), bones and
Tuberculosis is the most
common major infectious disease today, infecting two billion people or one-third
of the world's population, with nine million new cases of active disease
annually, resulting in two million deaths, mostly in developing countries.
Most of those infected (90
percent) have asymptomatic latent TB infection (LTBI). While only 10 percent
of TB infection progresses to TB disease, if untreated the death rate is 50
percent. TB is the second largest killing disease in the world.
The neglect of TB control
programs and immigration has caused a resurgence of tuberculosis. Multiple
drug resistant strains of TB are also increasing. The World Health
Organization declared TB a global health emergency in 1993.
The cause of tuberculosis,
Mycobacterium tuberculosis (MTB), is a slow-growing Gram-positive aerobic
bacterium that divides every 16 to 20 hours. This is extremely slow
compared to other bacteria. It is a small rod-like bacillus that can
withstand weak disinfectants and can survive in a dry state for weeks but
can only grow within a host organism.
MTB is identified
microscopically by its staining characteristics: it retains certain stains
after being treated with acidic solution. In the most common staining
technique, MTB are stained bright red, which stands out clearly against a blue
background. It can also be visualized by fluorescent microscopy.
TB is spread through water
droplets that are expelled when persons with infectious TB disease cough,
sneeze or speak. People who live close to patients affected with active TB
are at high risk.
The probability of
transmission depends upon: infectiousness of the person with TB,
environment of exposure, duration of exposure, and virulence of the
organism. The chain of transmission can be stopped by isolating patients
with active disease and starting effective anti-tuberculous therapy.
TB infection begins when TB
bacilli reach the pulmonary alveoli, from which they may spread to local
lymph nodes, and then through the bloodstream to the more distant tissues
and organs where TB disease is likely to develop: lungs, lymph nodes,
kidneys, brain, and bone.
Usually the immune system is
able to halt the multiplication of TB bacilli, preventing further spread in
about 90 percent of cases. However if a person has a weak immune system or
is poorly nourished, bacteria are not eliminated and proliferate. The
tubercles enlarge and there is local tissue destruction. Another feature of
tuberculosis is the development of cell death, necrosis, in the center of tubercles.
This has the texture of soft white cheese and was termed caseous necrosis.
If TB bacteria gain entry to
the blood stream from an area of tissue damage, they spread through the
body and infect the tissues, appearing as tiny white tubercles. This is
called miliary tuberculosis and has a high case fatality.
In many patients the
infection waxes and wanes. Healing and fibrosis balance tissue destruction
and necrosis. Affected tissue is replaced by scarring and cavities filled
with cheese-like white necrotic material. In the lung some of these
cavities are in continuity with the air passages bronchi. This material may
therefore be coughed up. It contains living bacteria and can pass on
Treatment with appropriate
antibiotics kills bacteria and allows healing to take place. Affected areas
are eventually replaced by scar tissue.
In those people in whom TB
bacilli overcome the immune system defenses and begin to multiply, there is
progression from TB infection to TB disease. This may occur soon after
infection (primary TB disease - 1 to 5 percent) or many years after
infection (post primary TB, secondary TB, reactivation TB disease of
dormant bacilli - 5 to 9 percent).
About five percent of infected
persons will develop TB disease in the first two years, and another five
percent will develop disease later in life. In all, about 10 percent of
infected persons with normal immune systems will develop TB disease in
their lifetime. A complete medical evaluation for TB includes a medical
history, a physical examination, a tuberculin skin test, a chest X-ray, and
microbiologic smears and cultures.
TB disease most commonly
affects the lungs (75 percent or more), where it is called pulmonary TB.
Symptoms include a productive, prolonged cough of more than three weeks
duration, chest pain, and hemoptysis. Systemic symptoms include fever,
chills, night sweats, appetite loss, weight loss, and easy fatigability.
Persons with TB infection
(class 2 or class 4 TB), but who do not have TB disease (class 3 or class 5
TB), cannot spread the infection to other people. TB infection in a person
who does not have TB disease is not considered a case of TB and is often
referred to as latent TB infection (LTBI). This distinction is important
because treatment options will be different for a person who has LTBI
instead of active TB disease.
Prevention and control
efforts include three priority strategies:
· Identifying and treating
all persons who have TB disease
· Finding and
evaluating persons who have been in contact with TB patients to determine
have TB infection or disease, and treating them appropriately, and
· Testing high-risk groups
for TB infection
In tropical areas where the
incidence of atypical mycobacteria is high, exposure to nontuberculous
mycobacteria gives some protection against TB.
Drug-resistant TB is
transmitted in the same way as drug-susceptible TB. Primary resistance
develops in persons initially infected with resistant organisms. Secondary
resistance (acquired resistance) develops during TB therapy due to
inadequate treatment regimen, not taking the prescribed regimen
appropriately or using low quality medication.
Many countries use BCG
vaccine as part of their TB control programs, especially for infants. The
protective efficacy of BCG for preventing serious forms of TB (e.g.
meningitis) in children is high (greater than 80 percent). However, the
protective efficacy for preventing pulmonary TB in adolescents and adults
is variable, from 0 to 80 percent. The effectiveness of BCG is much lower
than in areas where mycobacteria are much less prevalent.
The first recombinant tuberculosis
vaccine entered clinical trials in the United States in 2004 sponsored by
the National Institute of Allergy and Infectious Diseases (NIAID). A 2005
study showed that a DNA TB vaccine given with conventional chemotherapy
could accelerate the disappearance of bacteria as well as protecting
against re-infection in mice; it may take four to five years to be
available in humans.