tuberculosis n : infection transmitted by inhalation or ingestion of tubercle bacilli and manifested in fever and small lesions (usually in the lungs but in various other parts of the body in acute stages) [syn: TB, T.B.]

English

Etymology

Latin tuberculum (diminutive of tuber, lump) + -osis (diseased condition).

Noun

tuberculosis (plural tuberculoses)

1. An infectious disease of humans and animals caused by a species of Mycobacterium mainly infecting the lungs where it causes tubercles characterized by the expectoration of mucus and sputum, fever, weight loss, and chest pain. Transmission is through inhalation or ingestion of bacteria.

Synonyms

• phthisic

Translations

Derived terms

• pulmonary tuberculosis

Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) 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, bones, joints 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.

One-third of the world's current population has been infected by TB, and new infections occur at a rate of one per second. Not everyone infected develops the full-blown disease; asymptomatic, latent infection is most common. However, one in ten latent infections will progress to active disease, which, if left untreated, kills more than half of its victims.

In 2004, mortality and morbidity statistics included 14.6 million chronic active cases, 8.9 million new cases, and 1.6 million deaths, mostly in developing countries. 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. TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems. The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015.

Other names

In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and phthisis pulmonalis; scrofula (in adults), affecting the lymphatic system and resulting in swollen neck glands; tabes mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease, or gibbus of the spine and joints. Miliary tuberculosis – 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.

Symptoms

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.

Bacterial species

The primary cause of TB, Mycobacterium tuberculosis, 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. (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. MTB is a small rod-like bacillus that can withstand weak disinfectants 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.

Using histological stains 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). 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 mycobacteria: M. bovis, 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 pathogenic, it is possible that the prevalence of M. microti infections has been underestimated.

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.

Evolution

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 bacteria. 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.

Transmission

When people suffering from active pulmonary TB cough, sneeze, speak, 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. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and the inhalation of just a single bacterium can cause a new infection. People with prolonged, frequent, or intense contact are at particularly high 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.

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.

Pathogenesis

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%.

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus. Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. 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. All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.

Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts 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. T lymphocytes (CD8+) can also directly kill infected cells.

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.

In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. 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. Rapid and inexpensive diagnosis will be particularly valuable in the developing world.

Progression

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% - 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% - 23% of these latent cases, often many years after infection. 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.

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.

Treatment

details Tuberculosis treatment 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. 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.

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. While these particular remedies haven't been tested scientifically, it has been demonstrated that malnourished mice receiving a 2% protein diet suffer far higher mortality from tuberculosis than those receiving 20% protein receiving the same infectious challenge dose, and the progressively fatal course of the illness could be reversed by restoring the mice to the normal diet. Moreover, statistics for immigrants in South London reveal an 8.5 fold increased risk of tuberculosis in (primarily Hindu Asian) lacto vegetarians, who frequently suffer protein malnutrition, compared to those of similar cultural backgrounds who ate meat and fish daily.

Prevention

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 levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria gives some protection against TB.

Vaccines

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. However, mass vaccination with BCG did not start until after World War II. 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%.

In South Africa, the country with the highest prevalence of TB, BCG is given to all children under the age of three. 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:

Several new vaccines to prevent TB infection are being developed. 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 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. A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group led by Oxford University, and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines. In order to encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.

The Bill and Melinda Gates Foundation has been a strong supporter of new TB vaccine development. Most recently, they announced a $200 million grant to the Aeras Global TB Vaccine Foundation for clinical trials on up to six different TB vaccine candidates currently in the pipeline.

Epidemiology

Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 18,000 years before the present. However, whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor, is currently unclear. Skeletal remains show prehistoric humans (4000 BC) had TB, and tubercular decay has been found in the spines of mummies from 3000-2400 BC. Phthisis is a Greek term for tuberculosis; around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal. Genetic studies suggest that TB was present in South America for about 2,000 years. In South America, the earliest evidence of tuberculosis is associated with the Paracas-Caverna culture (circa 750 BC to circa 100 AD).

Folklore

Before the Industrial Revolution, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood. Another folk belief attributed it to being forced, nightly, to attend fairy revels, so that the victim wasted away owing to lack of rest; this belief was most common when a strong connection was seen between the fairies and the dead. Similarly, but less commonly, it was attributed to the victims being "hagridden"—being transformed into horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest. In the early 20th century, some believed TB to be caused by masturbation.

Study and treatment

The study of tuberculosis dates back to The Canon of Medicine written by Ibn Sina (Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease, the first to recognise the association with diabetes, and the first to suggest that it could spread through contact with soil and water. He developed the method of quarantine in order to limit the spread of tuberculosis.

Although it was established that the pulmonary form was associated with 'tubercles' by Dr Richard Morton in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named 'tuberculosis' until 1839 by J. L. Schönlein. During the years 1838–1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air: they died within a year. The first TB sanatorium opened in 1859 in Görbersdorf, Germany (today Sokołowsko, Poland) by Hermann Brehmer.

In regard to this claim, The Times for January 15, 1859, page 5, column 5, carries an advertisement seeking funds for the Bournemouth Sanatorium for Consumption, referring to the balance sheet for the past year, and offering an annual report to prospective donors, implying that this sanatorium was in existence at least in 1858. The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on March 24, 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it 'tuberculin'. It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis.

The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called 'BCG' (Bacillus of Calmette and Guérin). The BCG vaccine was first used on humans in 1921 in France, After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention.

It was not until 1946 with the development of the antibiotic streptomycin that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax technique—collapsing an infected lung to "rest" it and allow lesions to heal—a technique that was of little benefit and was largely discontinued by the 1950s. The emergence of multidrug-resistant TB has again introduced surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream, and is therefore thought to increase the effectiveness of the chemotherapy.

Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005. Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence in the late 1980s. The number of those failing to complete their course of drugs is high. NY had to cope with more than 20,000 "unnecessary" TB-patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid). The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization in 1993.

Infection of other animals

Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers. In some places, regulations aiming to prevent the spread of TB restrict the ownership of novelty pets; for example, the U.S. state of California forbids the ownership of pet gerbils.

Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand is underway. It has been found that herd infection is more likely in areas where infected vector species such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders. Controlling the vectors through possum eradication and monitoring the level of disease in livestock herds through regular surveillance are seen as a "two-pronged" approach to ridding New Zealand of the disease.

In the Republic of Ireland and the United Kingdom, badgers have been identified as one vector species for the transmission of bovine tuberculosis. As a result, governments have come under pressure from some quarters, primarily dairy farmers, to mount an active campaign of eradication of badgers in certain areas with the purpose of reducing the incidence of bovine TB. The UK government has not committed itself on the issue, not least because it fears public opinion: badgers are a protected species. The effectiveness of culling on the incidence of TB in cattle is a contentious issue, with proponents and opponents citing their own studies to support their position. A 9-year scientific study by an Independent Study Group of the likely efficacy of badger culling reported on 18 June 2007 that it was unlikely to be effective and could actually increase the spread of TB. The Independent Study Group was chaired by Sir John Bourne and included two statisticians, Professor Cristl Donnelly and Sir David Cox, the most distinguished statistician in the United Kingdom. Donnelly and Cox produced a sophisticated stochastic model of the badger population which was used to make detailed quantitative predictions about the effects of various policies. The recommendations of the Bourne report came as a surprise to Ministers. The UK Government's Chief Scientific Adviser, Sir David King convened a committee to re-examine the Bourne report. King's committee produced a report on 30 July, only one month after the publication of Bourne's 9-year study, whose conclusions flatly contradicted those of the Bourne report and recommended badger culling. The King committee did not include any statisticians and did not make use of the Donnelly & Cox statistical model. As a result, the issue of badger culling remains hugely controversial in the United Kingdom.

See also

• 2007 tuberculosis scare
• Abreugraphy
• ATC code J04 Drugs for treatment of TB
• Buruli ulcer and leprosy: other diseases caused by mycobacteria
• Latent tuberculosis
• List of tuberculosis victims
• Mycobacterium Tuberculosis Structural Genomics Consortium
• National Center for HIV, STD, and TB Prevention
• Nontuberculous mycobacteria
• Overcrowding
• Philip D'Arcy Hart
• The Global Fund to Fight AIDS, Tuberculosis and Malaria
• Tuberculosis in history and art
• UNITAID
• Nosocomial infection

References

Further reading

• The White Death
• Mountains Beyond Mountains A nonfiction account of treating TB in Haiti, Peru, Russia, and elsewhere.
• Consumption and Literature
• . First published in the United Kingdom as Tuberculosis: The Greatest Story Never Told.

External links

• Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated August 2003.
• Central Asia Health Review (CAHR). High Prevalence of Multi-Drug Resistant Tuberculosis in Uzbekistan
• (CDC) - Division of Tuberculosis Elimination News and updates.
• (CDC) - Questions and Answers About TB, 2007.
• Health Protection Agency, England
• BioHealthBase Bioinformatics Resource Center. Database of Mycobacterium tuberculosis genome sequences and related information.
• Kaiser Family Foundation. Tuberculosis. Globalhealthfacts.org.
• The Nobel Prize Website. Tuberculosis Educational Game
• United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical Assistance (TBCTA).
• World Health Organization (WHO). Tuberculosis.
• Tuberculosis and HIV: HIV InSite Knowledge Base chapter and related resources.

African lethargy, Asiatic cholera, Chagres fever, German measles, Haverhill fever, TB, acute articular rheumatism, aerogenic tuberculosis, ague, alkali disease, ambulatory plague, amebiasis, amebic dysentery, anthrax, bacillary dysentery, bastard measles, black death, black fever, black plague, blackwater fever, breakbone fever, brucellosis, bubonic plague, cachectic fever, cellulocutaneous plague, cerebral rheumatism, cerebral tuberculosis, chicken pox, cholera, colliquation, consumption, cowpox, dandy fever, deer fly fever, defervescing plague, dengue, dengue fever, diphtheria, disseminated tuberculosis, dumdum fever, dysentery, elephantiasis, encephalitis lethargica, enteric fever, epidemic, epiphytotic, epizootic, erysipelas, famine fever, five-day fever, flu, frambesia, glandular fever, glandular plague, grippe, hansenosis, hemorrhagic plague, hepatitis, herpes, herpes simplex, herpes zoster, histoplasmosis, hookworm, hydrophobia, infantile paralysis, infectious mononucleosis, inflammatory rheumatism, influenza, jail fever, jungle rot, kala azar, kissing disease, larval plague, lepra, leprosy, leptospirosis, loa loa, loaiasis, lockjaw, lupus vulgaris, madness, malaria, malarial fever, marsh fever, measles, meningitis, milzbrand, mumps, murrain, ornithosis, osteomyelitis, pandemia, pandemic, paratyphoid fever, parotitis, parrot fever, pertussis, pest, pesthole, pestilence, phthisis, plague, plague spot, pneumonia, pneumonic plague, polio, poliomyelitis, polyarthritis rheumatism, ponos, premonitory plague, psittacosis, pulmonary tuberculosis, rabbit fever, rabies, rat-bite fever, relapsing fever, rheumatic fever, rickettsialpox, ringworm, rubella, rubeola, scarlatina, scarlet fever, schistosomiasis, scourge, scrofula, scrofuloderma, septic sore throat, septicemic plague, shingles, siderating plague, sleeping sickness, sleepy sickness, smallpox, snail fever, splenic fever, spotted fever, strep throat, swamp fever, tetanus, thrush, tinea, trench fever, trench mouth, tuberculosis cutis, tuberculosis luposa, tuberculous meningitis, tularemia, typhoid, typhoid fever, typhus, typhus fever, undulant fever, vaccinia, varicella, variola, venereal disease, viral dysentery, white plague, whooping cough, yaws, yellow fever, yellow jack, zona, zoster