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Tuberculosis
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(abbreviated as '''TB''' for ''tubercle bacillus'' or '''T'''u'''B'''erculosis) is a common and deadly
Infectious Disease caused by
Mycobacteria , mainly ''
Mycobacterium Tuberculosis ''. Tuberculosis most commonly attacks the lungs (as
Pulmonary TB) but can also affect the
Central Nervous System , the
Lymphatic System , the
Circulatory System , the
Genitourinary System ,
Bone s,
Joint s and even the
Skin . Other mycobacteria such as ''
Mycobacterium Bovis '', ''
Mycobacterium Africanum '', ''
Mycobacterium Canetti '', and ''
Mycobacterium Microti '' can also cause tuberculosis, but these species do not usually infect healthy adults.
1
Over one-third of the world's population now carries the TB bacterium, and new infections occur at a rate of one per second., latent TB infection is most common. However, one in ten latent infections will progress to active TB disease, which, if left untreated, kills more than half of its victims.
In most cases of this disorder, a person becomes infected with tubercle bacilli by inhaling tiny droplets of moisture that contain a specific bacteria. The primary infection by the bacilli may produce no symptons and may thus go undetected. In some cases,however, primary infection causes fever, swelling of the glands, and pneumonia. In advanced stages of the disease,the patient may cough up large quantities of blood. Other symptons of this advanced illness include chest pain,fever,sweating at night,fatigue,weight loss, and loss of appetite.
reference:world book encyclopedia
In 2004, mortality and morbidity statistics included 14.6 million chronic active TB cases, 8.9 million new cases, and 1.6 million deaths, mostly in
Developing Countries . In addition, a rising number of people in the
Developed World are contracting tuberculosis because their
Immune System s are compromised by
Immunosuppressive Drug s,
Substance Abuse or
HIV /
AIDS .
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis.
2 The emergence of
Drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to
Second-line Drugs .
3 TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems.
4 The
World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a
Global Plan To Stop Tuberculosis aiming to save 14 million lives between 2006 and 2015.
World Health Organization (WHO).
Stop TB Partnership. Retrieved on 3 October 2006.
In the past, tuberculosis was called , because it seemed to consume people from within, with a '' – now commonly known as '''disseminated TB'''– occurs when the infection invades the circulatory system resulting in lesions which have the appearance of
Millet seeds on X-ray.
Disseminated tuberculosis NIH Medical Encyclopedia. Accessed 09 Oct 06
When the disease becomes active, 75% of the cases are pulmonary TB. Symptoms include chest pain,
Coughing Up Blood , and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever, chills,
Night Sweats ,
Appetite Loss , weight loss, pallor, and often a tendency to fatigue very easily.
In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB more common in
Immunosuppressed persons and young children. Extrapulmonary infection sites include the
Pleura , the
Central Nervous System in
Meningitis , the
Lymphatic System in
Scrofula of the neck, the
Genitourinary System in urogenital tuberculosis, and bones and joints in
Pott's Disease of the spine. An especially serious form is disseminated TB, more commonly known as
Miliary Tuberculosis . Although extrapulmonary TB is not contagious, it may co-exist with pulmonary TB, which ''is'' contagious.
Centers For Disease Control And Prevention (CDC), Division of Tuberculosis Elimination.
Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated Aug 2003.
See Also: Mycobacterium tuberculosis
'']]
The primary cause of TB , ''
Mycobacterium Tuberculosis '' (MTB), is an
Aerobic Bacterium that
Divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.
5 (For example, one of the fastest-growing bacteria is a strain of ''
E. Coli '' that can divide roughly every 20 minutes.) Since MTB has a cell wall but lacks a
Phospholipid Outer Membrane , it is
Classified as a
Gram-positive bacterium. However, if a
Gram Stain is performed, MTB either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall.
6 MTB is a small rod-like
Bacillus that can withstand weak
Disinfectant s and survive in a
Dry State for weeks. In nature, the bacterium can grow only within the cells of a
Host organism, but ''M. tuberculosis'' can be cultured ''
In Vitro ''.
7
Using certain
Histological techniques on expectorate samples from
Phlegm (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an
Acid-fast Bacillus (AFB).
8 The most common staining technique, the
Ziehl-Neelsen Stain , dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an
Auramine-rhodamine Stain and
Fluorescent Microscopy .
The ''M. tuberculosis'' complex includes 3 other TB-causing '', ''
M. Africanum '' and ''
M. Microti ''. The first two only very rarely cause disease in
Immunocompetent people. On the other hand, although ''M. microti'' is not usually
Pathogen ic, it is possible that the
Prevalence of ''M. microti'' infections has been underestimated.
9
Other known pathogenic
Mycobacteria include ''
Mycobacterium Leprae '',
''Mycobacterium Avium'' and ''M. kansasii''. The last two are part of the
Nontuberculous Mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor
Leprosy , but they ''do'' cause pulmonary diseases resembling TB.
10
During its
Evolution , ''M. tuberculosis'' has lost numerous coding and non-coding regions in its
Genome , losses that can be used to distinguish between strains of the bacterium. The implication is that ''M. tuberculosis'' strains differ geographically, so their genetic differences can be used to track the origins and movement of each strain.
11
When people suffering from active pulmonary TB cough, sneeze, speak, kiss, or spit, they expel infectious
Aerosol droplets 0.5 to 5
µm in diameter. A single sneeze, for instance, can release up to 40,000 droplets.
12 People with prolonged, frequent, or intense contact are at highest risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per year. Others at risk include people in areas where TB is common, people who inject illicit drugs (especially when sharing needles), residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients
Immunocompromised by conditions such as
HIV /
AIDS , people who take immunosuppressant drugs, and health care workers serving these high-risk clients.
13
Transmission can only occur from people with active—not latent—TB. The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the
Virulence of the ''M. tuberculosis''
Strain . The chain of transmission can therefore be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with
Non-resistant active TB generally cease to be contagious.
'' (stained red) in sputum]]
About 90% of those infected with ''Mycobacterium tuberculosis'' have
Asymptomatic , latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease. However, if untreated, the death rate for these active TB cases is more than 50%.Onyebujoh, Phillip and Rook, Graham A. W.
World Health Organization Disease Watch: Focus: Tuberculosis. December 2004. Accessed 07 October 2006.
TB infection begins when the mycobacteria reach the
Pulmonary Alveoli , where they invade and replicate within alveolar
Macrophages .
14 The primary site of infection in the lungs is called the
Ghon Focus . Bacteria are picked up by
Dendritic Cell s, which do not allow replication, although these cells can transport the bacilli to local (
Mediastinal )
Lymph Node s. Further spread is through the bloodstream to the more distant tissues and organs where secondary TB lesions can develop in lung apices, peripheral lymph nodes, kidneys, brain, and bone.
15 All parts of the body can be affected by the disease, though it rarely affects the
Heart ,
Skeletal Muscle s,
Pancreas and
Thyroid .
16
Tuberculosis is classified as one of the
Granuloma tous inflammatory conditions.
Macrophage s,
T Lymphocytes ,
B Lymphocytes and
Fibroblast s are among the cells that aggregate to form a
Granuloma , with
Lymphocytes surrounding the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes (CD4+) secrete
Cytokines such as
Interferon Gamma , which activates macrophages to destroy the bacteria with which they are infected.
17 T lymphocytes (CD8+) can also directly kill infected cells.
Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of cell death, also called
Necrosis , in the center of
Tubercles . To the naked eye this has the texture of soft white cheese and was termed
Caseous Necrosis .
18
If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called
Miliary Tuberculosis . Patients with this
Disseminated TB have a fatality rate of approximately 20%, even with intensive treatment.
19
In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and
Fibrosis . Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages
Bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate
Antibiotic s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.
]]
Tuberculosis can be a difficult disease to diagnose, due mainly to the difficulty in culturing this slow-growing organism in the laboratory. A complete medical evaluation for TB must include a medical history, a chest X-ray, and a physical examination.
Tuberculosis Radiology is used in the diagnosis of TB. It may also include a
Tuberculin Skin Test, a
Serological test, microbiological smears and cultures. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppression.
Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to
Purified Protein Derivative s of ''M. tuberculosis''. Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection and thus the test must be used with caution, particularly with regard to persons from countries where TB immunization is common.
20 New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These use
Polymerase Chain Reaction detection of bacterial DNA and antibody assays to detect the release of
Interferon Gamma in response to mycobacteria.
21 Rapid and inexpensive diagnosis will be particularly valuable in the developing world.
Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and begin to multiply. In primary TB disease—1 to 5% of cases—this occurs soon after infection. However, in the majority of cases, a latent infection occurs that has no obvious symptoms. These dormant bacilli can produce tuberculosis in 2 to 23% of these latent cases, often many years after infection.
22 The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In patients co-infected with ''M. tuberculosis'' and HIV, the risk of reactivation increases to 10% per year.
Other conditions that increase risk include drug injection, mainly due to the lifestyle of
IV Drug Users ; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules;
Diabetes Mellitus ;
Silicosis ; prolonged
Corticosteroid therapy and other immunosuppressive therapy; head and neck cancers;
Hematologic and
Reticuloendothelial diseases, such as
Leukemia and
Hodgkin's Disease; end-stage kidney disease; intestinal bypass or
Gastrectomy ; chronic
Malabsorption syndromes; or low body weight.
Twin Studies in the 1950's showed that the course of TB infection was highly dependent on the genetics of the patient. At that time, it was rare that one identical twin would die and the other live.New Scientist, 16 June 2007
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Some drugs, including
Rheumatoid Arthritis drugs that work by blocking
Tumor Necrosis Factor-alpha (an inflammation-causing
Cytokine ), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB.
23
Treatment for TB uses
Antibiotics to kill the bacteria. The two antibiotics most commonly used are
Rifampicin and
Isoniazid . However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 12 months) to entirely eliminate mycobacteria from the body. Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing
Antibiotic Resistance .
24 People with these latent infections are treated to prevent them from progressing to active TB disease later in life. However, treatment using Rifampin and Pyrazinamide is not risk-free. The Centers for Disease Control and Prevention (CDC) notified healthcare professionals of revised recommendations against the use of rifampin plus pyrazinamide for treatment of latent tuberculosis infection, due to high rates of hospitalization and death from liver injury associated with the combined use of these drugs.
25
Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully-susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. and
Isoniazid .
Extensively Drug-resistant TB () is also resistant to three or more of the six classes of second-line drugs.
TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are
Vaccinated to protect them from TB. Unfortunately, no
Vaccine is available that provides reliable protection for adults. However, in tropical areas where the incidence of atypical mycobacteria is high, exposure to
Nontuberculous Mycobacteria gives some protection against TB.
26
Many countries use
BCG vaccine as part of their TB control programs, especially for infants. This was the first vaccine for TB and developed at the
Pasteur Institute in
France between 1905 and 1921.
27 However, mass vaccination with BCG did not start until after
World War II .
28 The protective efficacy of BCG for preventing serious forms of TB (e.g.
Meningitis ) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%.
29
In . However, the effectiveness of BCG is lower in areas where mycobacteria are less
Prevalent , therefore BCG is not given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria:
- Infants or children with negative skin-test result who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to Multidrug-resistant TB.
- Healthcare workers considered on an individual basis in settings in which high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and not successful.
Several new vaccines to prevent TB infection are being developed. The first given with conventional
Chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans.
30 A very promising TB vaccine,
MVA85A , is currently in
Phase II Trials in South Africa by a group led by
Oxford University ,
31 and is based on a genetically modified
Vaccinia virus. Because of the limitations of current vaccines, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and
Advance Market Commitments .Webber, David and Kremer, Michael.
Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives (PDF). ''Bulletin of the World Health Organization'' 79(8), 2001, pp. 693–801.Barder, Owen; Kremer, Michael; Williams, Heidi.
"Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases," ''The Economists' Voice'', Vol. 3 (2006) Issue 3.
(WHO).
Global tuberculosis control - surveillance, planning, financing WHO Report 2006. Retrieved on 13 October 2006.]] (WHO).
Global tuberculosis control - surveillance, planning, financing WHO Report 2006. Retrieved on 13 October 2006.]]According to the World Health Organization (WHO), nearly 2 billion people—one–third of the world's population—have tuberculosis. rate varies from 356 per 100,000 in
Africa to 41 per 100,000 in the
Americas . Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with
HIV /
AIDS .Stop TB Partnership.
London tuberculosis rates now at Third World proportions. ''PR Newswire Europe Ltd.'' 4 December 2002. Retrieved on 3 October 2006.
In 2004, the country with the highest incidence of TB was are in
Portugal (42 per 100,000) and
Spain (20 per 100,000). These rates compare with 113 per 100,000 in
China and 64 per 100,000 in
Brazil . In the United States, the overall tuberculosis case rate was 4.9 per 100,000 persons in 2004.
The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults. (CDC).
2005 Surveillance Slide Set. (September 12, 2006) Retrieved on 13 October 2006.
