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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) (同)TB, T.B.

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結核({略}TB,T.B.) / 肺結核
結核（性）の・ゲッカコウ(月下香)(ヒガンバナ科の球根植物)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/24 00:22:42」(JST)

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Tuberculosis, MTB, or TB (short for tubercle bacillus), in the past also called phthisis, phthisis pulmonalis, or consumption, is a widespread, and in many cases fatal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis.^[1] Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit respiratory fluids through the air.^[2] Most infections do not have symptoms, known as latent tuberculosis. About one in ten latent infections eventually progresses to active disease which, if left untreated, kills more than 50% of those so infected.

The classic symptoms of active TB infection are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss (the latter giving rise to the formerly common term for the disease, "consumption"). Infection of other organs causes a wide range of symptoms. Diagnosis of active TB relies on radiology (commonly chest X-rays), as well as microscopic examination and microbiological culture of body fluids. Diagnosis of latent TB relies on the tuberculin skin test (TST) and/or blood tests. Treatment is difficult and requires administration of multiple antibiotics over a long period of time. Social contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in multiple drug-resistant tuberculosis (MDR-TB) infections. Prevention relies on screening programs and vaccination with the bacillus Calmette-Guérin vaccine.

One-third of the world's population is thought to have been infected with M. tuberculosis,^[3] with new infections occurring in about 1% of the population each year.^[4] In 2007, an estimated 13.7 million chronic cases were active globally,^[5] while in 2013, an estimated 9 million new cases occurred.^[6] In 2013 there were between 1.3 and 1.5 million associated deaths,^[6]^[7] most of which occurred in developing countries.^[8] The total number of tuberculosis cases has been decreasing since 2006, and new cases have decreased since 2002.^[8] The rate of tuberculosis in different areas varies across the globe; about 80% of the population in many Asian and African countries tests positive in tuberculin tests, while only 5–10% of the United States population tests positive.^[1] More people in the developing world contract tuberculosis because of a poor immune system, largely due to high rates of HIV infection and the corresponding development of AIDS.^[9]

1 Signs and symptoms
- 1.1 Pulmonary
- 1.2 Extrapulmonary
2 Causes
- 2.1 Mycobacteria
- 2.2 Risk factors
3 Mechanism
- 3.1 Transmission
- 3.2 Pathogenesis
4 Diagnosis
- 4.1 Active tuberculosis
- 4.2 Latent tuberculosis
5 Prevention
- 5.1 Vaccines
- 5.2 Public health
6 Management
- 6.1 New onset
- 6.2 Recurrent disease
- 6.3 Medication resistance
7 Prognosis
8 Epidemiology
9 History
10 Society and culture
- 10.1 Public health efforts
- 10.2 Stigma
11 Research
12 Other animals
13 References
14 External links

Signs and symptoms

The main symptoms of variants and stages of tuberculosis are given,^[10] with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously.

Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis).^[11] Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB, as well.^[11]

General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue.^[11] Significant nail clubbing may also occur.^[12]

Pulmonary

If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases).^[9]^[13] Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic").^[9] Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or a Rasmussen's aneurysm, resulting in massive bleeding.^[11]^[14] Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones.^[11] The reason for this difference is not entirely clear.^[1] It may be due either to better air flow,^[1] or to poor lymph drainage within the upper lungs.^[11]

Extrapulmonary

In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB.^[15] These are collectively denoted as "extrapulmonary tuberculosis".^[16] Extrapulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with HIV, this occurs in more than 50% of cases.^[16] Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others. When it spreads to the bones, it is also known as "osseous tuberculosis".^[17] a form of osteomyelitis.^[1] Sometimes, bursting of a tubercular abscess through skin results in tuberculous ulcer.^[18] An ulcer originating from nearby infected lymph nodes is painless, slowly enlarging and has an appearance of "wash leather".^[19] A potentially more serious, widespread form of TB is called "disseminated" TB, commonly known as miliary tuberculosis.^[11] Miliary TB makes up about 10% of extrapulmonary cases.^[20]

Causes

Mycobacteria

Scanning electron micrograph of M. tuberculosis

The main cause of TB is Mycobacterium tuberculosis, a small, aerobic, nonmotile bacillus.^[11] The high lipid content of this pathogen accounts for many of its unique clinical characteristics.^[21] It divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour.^[22] Mycobacteria have an outer membrane lipid bilayer.^[23] If a Gram stain is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall.^[24] MTB 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 the laboratory.^[25]

Using histological stains on expectorated samples from phlegm (also called "sputum"), scientists can identify MTB under a regular (light) microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB).^[1]^[24] The most common acid-fast staining techniques are the Ziehl–Neelsen stain, which dyes AFBs a bright red that stands out clearly against a blue background,^[26] and the auramine-rhodamine stain followed by fluorescence microscopy.^[27]

The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti.^[28] M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa.^[29]^[30] M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries.^[1]^[31] M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants.^[32]^[33] M. microti is also rare and is mostly seen in immunodeficient people, although the prevalence of this pathogen has possibly been significantly underestimated.^[34]

Other known pathogenic mycobacteria include M. leprae, M. avium, and M. kansasii. The latter two species are classified as "nontuberculous mycobacteria" (NTM). NTM cause neither TB nor leprosy, but they do cause pulmonary diseases that resemble TB.^[35]

Risk factors

A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all people with TB are infected by the virus.^[8] This is a particular problem in sub-Saharan Africa, where rates of HIV are high.^[36]^[37] Of people without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes;^[12] in contrast, 30% of those coinfected with HIV develop the active disease.^[12]

Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty.^[9] Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients.^[38]

Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold.^[39] Those who smoke cigarettes have nearly twice the risk of TB compared to nonsmokers.^[40]

Other disease states can also increase the risk of developing tuberculosis. These include alcoholism^[9] and diabetes mellitus (three-fold increase).^[41]

Certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), are becoming increasingly important risk factors, especially in the developed world.^[9]

Also a genetic susceptibility element exists,^[42] for which the overall importance remains undefined.^[9]

Mechanism

Public health campaigns in the 1920s tried to halt the spread of TB.

Transmission

When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to 40,000 droplets.^[43] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection).^[44]

People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate.^[45] A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year.^[3] Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious.^[1] The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence of the M. tuberculosis strain, the level of immunity in the uninfected person, and others.^[46] The cascade of person-to-person spread can be circumvented by effectively segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others.^[45] If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others.^[47]

Pathogenesis

Microscopy of tuberculous epididymitis. H&E stain

About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI),^[48] with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease.^[49] In those with HIV, the risk of developing active TB increases to nearly 10% a year.^[49] If effective treatment is not given, the death rate for active TB cases is up to 66%.^[3]

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within endosomes of alveolar macrophages.^[1]^[50] Macrophages identify the bacterium as "foreign" and attempt to eliminate it by phagocytosis. During this process, the entire bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. M. tuberculosis actually reproduces inside the macrophage and will eventually kill the immune cell.

The primary site of infection in the lungs, known as the "Ghon focus", is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe.^[1] Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in the top of the lung.^[51] This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.^[1]^[52] All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid.^[53]

Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages, T lymphocytes, B lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system.^[54] However more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host's immune system. Macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed.^[55] Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granulomas is the development of abnormal cell death (necrosis) in the center of tubercles. To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis.^[54]

If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues.^[56] This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis.^[57] People with this disseminated TB have a high fatality rate even with treatment (about 30%).^[20]^[58]

In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis.^[54] Affected tissue is replaced by scarring and cavities filled with caseous 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, so can spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.^[54]

Diagnosis

M. tuberculosis (stained red) in sputum

Active tuberculosis

Diagnosing active tuberculosis based merely on signs and symptoms is difficult,^[59] as is diagnosing the disease in those who are immunosuppressed.^[60] A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks.^[60] A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation.^[60] Interferon-γ release assays and tuberculin skin tests are of little use in the developing world.^[61]^[62] IGRA have similar limitations in those with HIV.^[62]^[63]

A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.^[64] Thus, treatment is often begun before cultures are confirmed.^[65]

Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB.^[59] These tests, however, are not routinely recommended, as they rarely alter how a person is treated.^[65] Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.^[66]

Latent tuberculosis

Mantoux tuberculin skin test

The Mantoux tuberculin skin test is often used to screen people at high risk for TB.^[60] Those who have been previously immunized may have a false-positive test result.^[67] The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, or most notably, in those who truly do have active tuberculosis.^[1] Interferon gamma release assays (IGRAs), on a blood sample, are recommended in those who are positive to the Mantoux test.^[65] These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results.^[68] However, they are affected by M. szulgai, M. marinum, and M. kansasii.^[69] IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.^[70]

Prevention

Tuberculosis prevention and control efforts primarily rely on the vaccination of infants and the detection and appropriate treatment of active cases.^[9] The World Health Organization has achieved some success with improved treatment regimens, and a small decrease in case numbers.^[9]

Vaccines

The only available vaccine as of 2011 is bacillus Calmette-Guérin (BCG).^[71] In children it decreases the risk of getting the infection by 20% and the risk of infection turning into disease by nearly 60%.^[72]

It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated.^[9] The immunity it induces decreases after about ten years.^[9] As tuberculosis is uncommon in most of Canada, the United Kingdom, and the United States, BCG is administered to only those people at high risk.^[73]^[74]^[75] Part of the reasoning arguing against the use of the vaccine is that it makes the tuberculin skin test falsely positive, so is of no use in screening.^[75] A number of new vaccines are currently in development.^[9]

Public health

The World Health Organization declared TB a "global health emergency" in 1993,^[9] and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between its launch and 2015.^[76] A number of targets they have set are not likely to be achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis.^[9] A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs.^[77]

Management

Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective.^[78] The two antibiotics most commonly used are isoniazid and rifampicin, and treatments can be prolonged, taking several months.^[46] Latent TB treatment usually employs a single antibiotic,^[79] while active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance.^[9] People with latent infections are also treated to prevent them from progressing to active TB disease later in life.^[79] Directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the WHO in an effort to reduce the number of people not appropriately taking antibiotics.^[80] The evidence to support this practice over people simply taking their medications independently is poor.^[81] Methods to remind people of the importance of treatment do, however, appear effective.^[82]

New onset

The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months.^[9] Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.^[9]

Recurrent disease

If tuberculosis recurs, testing to determine to which antibiotics it is sensitive is important before determining treatment.^[9] If multiple drug-resistant TB is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.^[9]

Medication resistance

Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible TB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality medication.^[83] Drug-resistant TB is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. MDR-TB is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB is also resistant to three or more of the six classes of second-line drugs.^[84] Totally drug-resistant TB is resistant to all currently used drugs.^[85] It was first observed in 2003 in Italy, but not widely reported until 2012,^[85]^{[medical citation needed]} and has also been found in Iran and India.^[86] Bedaquiline is tentatively supported for use in multiple drug-resistant TB.^[87]

XDR-TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR-TB. Cases of XDR TB have been identified in more than 90% of countries.^[86]

Prognosis

Age-standardized disability-adjusted life years caused by tuberculosis per 100,000 inhabitants in 2004.^[88]

no data

≤10

≥10–25

≥25–50

≥50–75

≥75–100

≥100–250

≥250–500

≥500–750

≥750–1000

≥1000–2000

≥2000–3000

≥ 3000

Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection.^[1] However, in the majority of cases, a latent infection occurs with no obvious symptoms.^[1] These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.^[12]

The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.^[1] Studies using DNA fingerprinting of M. tuberculosis strains have shown reinfection contributes more substantially to recurrent TB than previously thought,^[89] with estimates that it might account for more than 50% of reactivated cases in areas where TB is common.^[90] The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995.^[9]

Epidemiology

In 2007, the prevalence of TB per 100,000 people was highest in sub-Saharan Africa, and was also relatively high in Asia.^[91]

Roughly one-third of the world's population has been infected with M. tuberculosis,^[3] with new infections occurring in about 1% of the population each year.^[4] However, most infections with M. tuberculosis do not cause TB disease,^[92] and 90–95% of infections remain asymptomatic.^[48] In 2012, an estimated 8.6 million chronic cases were active.^[93] In 2010, 8.8 million new cases of TB were diagnosed, and 1.20–1.45 million deaths occurred, most of these occurring in developing countries.^[8]^[94] Of these 1.45 million deaths, about 0.35 million occur in those also infected with HIV.^[95]

Tuberculosis is the second-most common cause of death from infectious disease (after those due to HIV/AIDS).^[11] The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002.^[8] China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate between 1990 and 2010.^[95] The number of new cases has declined by 17% between 2004–2014.^[86] Tuberculosis is more common in developing countries; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5–10% of the US population test positive.^[1] Hopes of totally controlling the disease have been dramatically dampened because of a number of factors, including the difficulty of developing an effective vaccine, the expensive and time-consuming diagnostic process, the necessity of many months of treatment, the increase in HIV-associated tuberculosis, and the emergence of drug-resistant cases in the 1980s.^[9]

In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1,200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases.^[5] In developed countries, tuberculosis is less common and is found mainly in urban areas. Rates per 100,000 people in different areas of the world were: globally 178, Africa 332, the Americas 36, Eastern Mediterranean 173, Europe 63, Southeast Asia 278, and Western Pacific 139 in 2010.^[95] In Canada and Australia, tuberculosis is many times more common among the aboriginal peoples, especially in remote areas.^[96]^[97] In the United States Native Americans have a fivefold greater mortality from TB,^[98] and racial and ethnic minorities accounted for 84% of all reported TB cases.^[99]

The rates of TB varies with age. In Africa, it primarily affects adolescents and young adults.^[100] However, in countries where incidence rates have declined dramatically (such as the United States), TB is mainly a disease of older people and the immunocompromised (risk factors are listed above).^[1]^[101] Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths.^[86]

History

Egyptian mummy in the British Museum – tubercular decay has been found in the spines of Egyptian mummies.

Tuberculosis has been present in humans since antiquity.^[9] The earliest unambiguous detection of M. tuberculosis involves evidence of the disease in the remains of bison in Wyoming dated to around 17,000 years ago.^[102] However, whether tuberculosis originated in bovines, then was transferred to humans, or whether it diverged from a common ancestor, is currently unclear.^[103] A comparison of the genes of M. tuberculosis complex (MTBC) in humans to MTBC in animals suggests humans did not acquire MTBC from animals during animal domestication, as was previously believed. Both strains of the tuberculosis bacteria share a common ancestor, which could have infected humans as early as the Neolithic Revolution.^[104]

Skeletal remains show prehistoric humans (4000 BC) had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000–2400 BC.^[105] Genetic studies suggest TB was present in the Americas from about 100 AD.^[106]

Phthisis is a Greek word for consumption, an old term for pulmonary tuberculosis;^[107] around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times. It was said to involve fever and the coughing up of blood, which was almost always fatal.^[108]

Before the Industrial Revolution, folklore often associated tuberculosis with vampires. When one member of a family died from it, the other infected members would lose their health slowly. People believed this was caused by the original person with TB draining the life from the other family members.^[109]

Although the pulmonary form associated with tubercles was established as a pathology by Dr Richard Morton in 1689,^[110]^[111] due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. It was not named "tuberculosis" until 1839, by J. L. Schönlein.^[112]

During 1838–1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of people with tuberculosis 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.^[113] Hermann Brehmer opened the first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko), Silesia.^[114]

Dr. Robert Koch discovered the tuberculosis bacillus.

The bacillus causing tuberculosis, M. tuberculosis, was identified and described on 24 March 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery.^[115] Koch did not believe the bovine (cattle) and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. Later, the risk of transmission from this source was dramatically reduced by the invention of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". While it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis.^[116]

Albert Calmette and Camille Guérin achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in France,^[117] but received widespread acceptance in the US, Great Britain, and Germany only after World War II.^[118]

Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as an endemic disease of the urban poor. In 1815, one in four deaths in England was due to "consumption". By 1918, one in six deaths in France was still caused by TB. After TB was determined to be contagious, in the 1880s, it was put on a notifiable disease list in Britain; campaigns were started to stop people from 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).^[114] Whatever the (purported) benefits of the "fresh air" and labor in the sanatoria, even under the best conditions, 50% of those who entered died within five years (circa 1916).^[114]

In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s, when it caused nearly 25% of all deaths.^[119] By the 1950s, mortality had decreased nearly 90%.^[120] Improvements in public health began significantly reducing rates of tuberculosis even before the arrival of streptomycin and other antibiotics, although the disease remained a significant threat to public health such that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research.^[121]

In 1946, the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. Prior to the introduction of this drug, the only treatment (except sanatoria) was surgical intervention, including the "pneumothorax technique", which involved collapsing an infected lung to "rest" it and allow tuberculous lesions to heal.^[122]

Because of the emergence of MDR-TB, surgery has been re-introduced as an option within the generally accepted standard of care in treating TB infections. Current surgical interventions involve removal of pathological chest cavities ("bullae") in the lungs to reduce the number of bacteria and to increase the exposure of the remaining bacteria to drugs in the bloodstream, thereby simultaneously reducing the total bacterial load and increasing the effectiveness of systemic antibiotic therapy.^[123]

Hopes of completely eliminating TB (cf. smallpox) from the population were dashed after the rise of drug-resistant strains in the 1980s. The subsequent resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization in 1993.^[124]

Society and culture

Public health efforts

The World Health Organization, Bill and Melinda Gates Foundation, and US government are subsidizing a fast-acting diagnostic tuberculosis test for use in low- and middle-income countries.^[125]^[126]^[127] In addition to being fast-acting, the test can determine if there is resistance to the antibiotic rifampicin which may indicate multi-drug resistant tuberculosis and is accurate in those who are also infected with HIV.^[125]^[128] Many resource-poor places as of 2011 only have access to sputum microscopy.^[129]

India had the highest total number of TB cases worldwide in 2010, in part due to poor disease management within the private and public health care sector.^[130] Programs such as the Revised National Tuberculosis Control Program are working to reduce TB levels amongst people receiving public health care.^[131]^[132]

A 2014 the EIU-healthcare report that the need to address apathy and urging for increased funding. The report cites among others Lucica Ditui "[TB] is like an orphan. It has been neglected even in countries with a high burden and often forgotten by donors and those investing in health interventions."^[86]

Slow progress has led to frustration, expressed by executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria – Mark Dybul: "we have the tools to end TB as a pandemic and public health threat on the planet, but we are not doing it."^[86] Several international organizations are pushing for more transparency in treatment, and more countries are implementing mandatory reporting of cases to the government, although adherence is often sketchy. Commercial treatment-providers may at times overprescribe second-line drugs as well as supplementary treatment, promoting demands for further regulations.^[86] The government of Brazil provides universal TB-care, which reduces this problem.^[86] Conversely falling rates of TB-infection may not relate to the number of programs directed at reducing infection rates, but may be tied to increased level of education, income and health of the population.^[86] Costs of the disease, as calculated by the World Bank in 2009 may exceed 150 billion USD per year in "high burden" countries.^[86] Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250M rural migrants in China.^[86]

Stigma

Slow progress in preventing the disease may in part be due to stigma associated with TB.^[86] Stigma may be due to the fear of transmission from affected individuals. This stigma may additionally arise due to links between TB and poverty, and in Africa, AIDS.^[86] Such stigmatization may be both real and perceived, for example; in Ghana individuals with TB are banned from attending public gatherings.^[133]

Stigma towards TB may result in delays in seeking treatment,^[86] lower treatment compliance, and family members keeping cause of death secret^[133] – allowing the disease to spread further.^[86] At odds is Russia, where stigma was associated with increased treatment compliance.^[133] TB stigma also affects socially marginalized individuals to a greater degree and varies between regions.^[133]

One way to decrease stigma may be through the promotion of "TB clubs", where those infected may share experiences and offer support, or through counseling.^[133] Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence.^[133] Despite this, studies on relationship between reduced stigma and mortality are lacking as of 2010, and similar efforts to decrease stigma surrounding AIDS have been minimally effective.^[133] Some have claimed the stigma to be worse than the disease, and healthcare providers may unintentionally reinforce stigma, as those with TB are often perceived as difficult or otherwise undesirable.^[86]

Research

The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing.^[134] A number of potential candidates are currently in phase I and II clinical trials.^[134] Two main approaches are being used to attempt to improve the efficacy of available vaccines. One approach involves adding a subunit vaccine to BCG, while the other strategy is attempting to create new and better live vaccines.^[134] MVA85A, an example of a subunit vaccine, currently in trials in South Africa, is based on a genetically modified vaccinia virus.^[135] Vaccines are hoped to play a significant role in treatment of both latent and active disease.^[136]

To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development, including prizes, tax incentives, and advance market commitments.^[137]^[138] A number of groups, including the Stop TB Partnership,^[139] the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research.^[140] Among these, the Aeras Global TB Vaccine Foundation received a gift of more than $280 million (US) from the Bill and Melinda Gates Foundation to develop and license an improved vaccine against tuberculosis for use in high burden countries.^[141]^[142]

A number of medications are being studied for multi drug resistant tuberculosis including: bedaquiline and delamanid.^[143] Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012.^[144] The safety and effectiveness of these new agents are still uncertain, because they are based on the results of a relatively small studies.^[143]^[145] However, existing data suggest that patients taking bedaquiline in addition to standard TB therapy are five times more likely to die than those without the new drug,^[146] which has resulted in medical journal articles raising health policy questions about why the FDA approved the drug and whether financial ties to the company making bedaquiline influenced physicians' support for its use ^[145]^[147]

Other animals

Mycobacteria infect many different animals, including birds,^[148] rodents,^[149] and reptiles.^[150] The subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals.^[151] An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful.^[152] Efforts in Great Britain have been less successful.^[153]^[154]

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^ Lalloo UG, Naidoo R, Ambaram A (May 2006). "Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis". Curr Opin Pulm Med 12 (3): 179–85. doi:10.1097/01.mcp.0000219266.27439.52. PMID 16582672.
^ "Frequently asked questions about TB and HIV". World Health Organization. Retrieved 15 April 2012.
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^ "WHO says Cepheid rapid test will transform TB care". Reuters. 8 December 2010.
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^ Lienhardt, C; Espinal, M; Pai, M; Maher, D; Raviglione, MC (November 2011). "What research is needed to stop TB? Introducing the TB Research Movement". PLoS medicine 8 (11): e1001135. doi:10.1371/journal.pmed.1001135. PMC 3226454. PMID 22140369.
^ Mishra, G (2013). "Tuberculosis Prescription Practices In Private And Public Sector In India". NJIRM 4 (2): 71–78.
^ Anurag Bhargava, Lancelot Pinto, Madhukar Pai (2011). "Mismanagement of tuberculosis in India: Causes, consequences, and the way forward". Hypothesis 9 (1): e7. doi:10.5779/hypothesis.v9i1.214.
^ Amdekar, Y (July 2009). "Changes in the management of tuberculosis". Indian journal of pediatrics 76 (7): 739–42. doi:10.1007/s12098-009-0164-4. PMID 19693453.
^ ^a ^b ^c ^d ^e ^f ^g Courtwright, A; Turner, AN (Jul–Aug 2010). "Tuberculosis and stigmatization: pathways and interventions.". Public health reports (Washington, D.C. : 1974). 125 Suppl 4: 34–42. PMID 20626191. |accessdate= requires |url= (help)
^ ^a ^b ^c Martín Montañés, C; Gicquel, B (March 2011). "New tuberculosis vaccines". Enfermedades infecciosas y microbiologia clinica. 29 Suppl 1: 57–62. doi:10.1016/S0213-005X(11)70019-2. PMID 21420568.
^ Ibanga H, Brookes R, Hill P, Owiafe P, Fletcher H, Lienhardt C, Hill A, Adegbola R, McShane H (2006). "Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design". Lancet Infect Dis 6 (8): 522–8. doi:10.1016/S1473-3099(06)70552-7. PMID 16870530.
^ Kaufmann SH (2010). "Future vaccination strategies against tuberculosis: Thinking outside the box". Immunity 33 (4): 567–77. doi:10.1016/j.immuni.2010.09.015. PMID 21029966.
^ Webber D, Kremer M (2001). "Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives". Bulletin of the World Health Organization 79 (8): 693–801.
^ Barder O, Kremer M, Williams H (2006). "Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases". The Economists' Voice 3 (3). doi:10.2202/1553-3832.1144.
^ Economic, Department of; Affairs, Social (2009). Achieving the global public health agenda : dialogues at the Economic and Social Council. New York: United Nations. p. 103. ISBN 978-92-1-104596-3.
^ Jong, [edited by] Jane N. Zuckerman, Elaine C. (2010). Travelers' vaccines (2nd ed.). Shelton, CT: People's Medical Pub. House. p. 319. ISBN 978-1-60795-045-5.
^ Bill and Melinda Gates Foundation Announcement (12 February 2004). "Gates Foundation Commits $82.9 Million to Develop New Tuberculosis Vaccines".
^ Nightingale, Katherine (19 September 2007). "Gates foundation gives US$280 million to fight TB".
^ ^a ^b Zumla, A; Hafner, R; Lienhardt, C; Hoelscher, M; Nunn, A (1 March 2012). "Advancing the development of tuberculosis therapy". Nature reviews. Drug discovery 11 (3): 171–2. doi:10.1038/nrd3694. PMID 22378254.
^ "J&J Sirturo Wins FDA Approval to Treat Drug-Resistant TB". Bloombeg. 31 December 2012. Retrieved 1 January 2013.
^ ^a ^b Avorn, J (April 2013). "Approval of a tuberculosis drug based on a paradoxical surrogate measure". JAMA 309 (13): 1349–1350. doi:10.1001/jama.2013.623. PMID 23430122.
^ US Food and Drug Administration. "Briefing Package: NDA 204–384: Sirturo".
^ Zuckerman, Diana; Jennifer Yttri (January 2013). "Antibiotics: When science and wishful thinking collide". Health Affairs.
^ Shivaprasad, HL; Palmieri, C (January 2012). "Pathology of mycobacteriosis in birds". The veterinary clinics of North America. Exotic animal practice 15 (1): 41–55, v–vi. doi:10.1016/j.cvex.2011.11.004. PMID 22244112.
^ Reavill, DR; Schmidt, RE (January 2012). "Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models". The veterinary clinics of North America. Exotic animal practice 15 (1): 25–40, v. doi:10.1016/j.cvex.2011.10.001. PMID 22244111.
^ Mitchell, MA (January 2012). "Mycobacterial infections in reptiles". The veterinary clinics of North America. Exotic animal practice 15 (1): 101–11, vii. doi:10.1016/j.cvex.2011.10.002. PMID 22244116.
^ Wobeser, Gary A. (2006). Essentials of disease in wild animals (1st ed.). Ames, Iowa [u.a.]: Blackwell Publ. p. 170. ISBN 978-0-8138-0589-4.
^ Ryan, TJ; Livingstone, PG, Ramsey, DS, de Lisle, GW, Nugent, G, Collins, DM, Buddle, BM (25 February 2006). "Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand". Veterinary microbiology 112 (2–4): 211–9. doi:10.1016/j.vetmic.2005.11.025. PMID 16330161.
^ White, PC; Böhm, M; Marion, G; Hutchings, MR (September 2008). "Control of bovine tuberculosis in British livestock: there is no 'silver bullet'". Trends in microbiology 16 (9): 420–7. doi:10.1016/j.tim.2008.06.005. PMID 18706814.
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External links

Wikimedia Commons has media related to Tuberculosis.

Tuberculosis at DMOZ
"Tuberculosis (TB)". Centers for Disease Control.
"Tuberculosis (TB)". UK Health Protection Agency.

UpToDate Contents

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1. 肺結核の臨床症状および評価 clinical manifestations and evaluation of pulmonary tuberculosis
2. HIV陰性患者における肺結核の治療 treatment of pulmonary tuberculosis in hiv negative patients
3. 小児における結核 tuberculosis disease in children
4. 肺外結核および粟粒結核の臨床症状、診断、および治療 clinical manifestations diagnosis and treatment of extrapulmonary and miliary tuberculosis
5. 結核の皮膚症状 cutaneous manifestations of tuberculosis

English Journal

Evaluation of specificity of tuberculosis diagnostic assays in caprine flocks under different epidemiological situations.

Bezos J, Alvarez J, Mínguez O, Marqués S, Martín O, Vigo V, Pieltain C, Romero B, Rodríguez S, Casal C, Mateos A, Domínguez L, de Juan L.SourceCentro VISAVET, Universidad Complutense de Madid, 28040 Madrid, Spain.
Research in veterinary science.Res Vet Sci.2012 Oct;93(2):636-40. Epub 2011 Nov 9.
The aim of this study was to evaluate the specificity of the most widely used tuberculosis (TB) diagnostic tests, single intradermal tuberculin (SIT) and single comparative intradermal tuberculin (SCIT) tests and interferon-gamma (IFN-γ) assay in 937 animals from eight TB-free caprine flocks under
PMID 22079129

Roles and underlying mechanisms of ESAT-6 in the context of Mycobacterium tuberculosis-host interaction from a systems biology perspective.

Yu X, Xie J.AbstractThe 6kDa early secreted antigenic target (ESAT-6), an important and intensively studied virulence factor of Mycobacterium tuberculosis, acts alone or in combination with CFP-10 to influence the outcome of the host-pathogen interaction. Secreted ESAT-6 can disturb the activation of macrophages, induce apoptosis and subvert host immunity. ESAT-6 mediated autophagosome formation and TLR signaling deviation lead to abnormal activation of NF-κB and subsequent erroneous expression of NF-κB-dependent genes. The C-terminal amino acid residues 90-95 in ESAT-6 are essential for the interaction with host. In-depth appreciation of the multiple roles of ESAT-6 upon host can inform improvements for novel vaccines and diagnostic tools for tuberculosis.
Cellular signalling.Cell Signal.2012 Sep;24(9):1841-6. Epub 2012 May 23.
The 6kDa early secreted antigenic target (ESAT-6), an important and intensively studied virulence factor of Mycobacterium tuberculosis, acts alone or in combination with CFP-10 to influence the outcome of the host-pathogen interaction. Secreted ESAT-6 can disturb the activation of macrophages, induc
PMID 22634089

Efficacy and safety of atovaquone-proguanil in treating imported malaria in Japan: The second report from the research group.

Kimura M, Koga M, Kikuchi T, Miura T, Maruyama H.SourceDepartment of Internal Medicine, Shin-Yamanote Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Parasitology international.Parasitol Int.2012 Sep;61(3):466-9. Epub 2012 Mar 29.
Malaria remains an important health risk among travelers to tropical/subtropical regions. However, in Japan, only 2 antimalarials are licensed for clinical use - oral quinine and mefloquine. The Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil in 1999, and reported
PMID 22484597

Japanese Journal

精神科医神谷美恵子の病跡とSpirituality

山田和夫
東洋英和大学院紀要 8, 1-6, 2012-03-15
… Furthermore, she contracted tuberculosis, a disease of death at the time, and recuperated alone at a villa in Karuizawa with feelings of despair.She fell into a deep depressive state and spent days of distress.In closed extreme situations, Kamiya had the mysteriousexperience of having her whole body bathed in divine light. …
NAID 110009209404

結核病棟で行われる患者教育に対する患者の受けとめ

秋原志穂 / 藤村一美
大阪市立大学看護学雑誌 8, 1-8, 2012-03-00
NAID 120003917972

結核病棟で行われる患者教育に対する患者の受けとめ

秋原志穂,藤村一美
大阪市立大学看護学雑誌 8, 1-8, 2012-03
NAID 110008896569

Related Pictures

★リンクテーブル★

リンク元	「100Cases 16」「結核」「マイコバクテリア感染症」「tuberculous」「TB」
拡張検索	「bovine tuberculosis」

「100Cases 16」

Tuberculosis
	Chest X-ray of a person with advanced tuberculosis: Infection in both lungs is marked by white arrow-heads, and the formation of a cavity is marked by black arrows.
Classification and external resources
ICD-10	A15–A19
ICD-9	010–018
OMIM	607948
DiseasesDB	8515
MedlinePlus	000077 000624
eMedicine	med/2324 emerg/618 radio/411
Patient UK	Tuberculosis
MeSH	D014376

　　[★]

☆case16　膝の痛み

■glossary

indigestion 消化障害、消化不良

■症例

80歳　男性

主訴：左膝の痛みと腫脹

現病歴：左膝の痛みを2日前から認めた。膝は発熱・腫脹しており、動かすと疼痛を生じる。時々胸焼けと消化不良が見られる。6ヶ月前のhealth checkで、高血圧(172/102mmHg)と血中クレアチニンが高い(正常高値)こと以外は正常といわれた。その4週間数回血圧を測定したが、高値が継続したため、2.5mg bendrofluamethizide(UK)/ベンドロフルメチアジド bendroflumethiazide(US)で治療を開始した。最近の血圧は138/84 mmHgであった。

喫煙歴：なし。

飲酒歴：一週間に平均4unit。

既往歴：股関節に中程度(mild)の変形性関節症

家族歴：特記なし

服薬歴：アセトアミノフェン(股関節の疼痛に対して)

身体所見 examination

　血圧 142/86mmHg。体温37.5℃。脈拍88/分。grade 2 hypertensive retinopathy(高血圧症性網膜症)。心血管系、呼吸器系に検査場異常なし。手にDIPにヘバーデン結節なし。

　左膝が発熱し腫脹している。関節内に液、patellar tap陽性。90℃以上膝関節を屈曲させると痛みを生じる。右の膝関節は正常に見える。

検査　 investigation

　生化学：白血球増多、ESR 上昇、尿素高値、グルコース高値

　単純X線：関節間隙やや狭小。それ以外に異常は認めない。

■problem list

　#1 左膝の痛み

　#2 胸焼け

　#3 消化不良

　#4 高血圧

　#5 クレアチニン正常高値

　#6 股関節の変形性リウマチ

　#7 高血圧性網膜症

■考え方

　・関節痛の鑑別診断を考える。

　・VINDICATEで考えてみてもよいでしょう。

　・関節痛の頻度としては　外傷＞慢性疾患(OAなど)＞膠原病＞脊椎疾患＞悪性腫瘍

■関節痛の鑑別疾患

DIF 282

V Vascular 血友病 hemophilia, 壊血病 scurvy, 無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

I Inflammatory 淋疾 gonorrhea, ライム病 lyme disease, 黄色ブドウ球菌 Staphylococcus, 連鎖球菌 Streptococcus, 結核 tuberculosis, 梅毒 syphilis, 風疹 rubella, 単純ヘルペス herpes simplex, HIV human immunodeficiency virus, サイトメガロウイルス cytomegalovirus

N Neoplastic disorders 骨原性肉腫 osteogenic sarcoma, 巨細胞腫 giant cell tumors

D Degenerative disorders degenerative joint disease or 変形性関節症 osteoarthritis

I Intoxication 痛風 gout (uric acid), 偽痛風 pseudogout (calcium pyrophosphate), ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide, gout syndrome of diuretics

C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.

A Autoimmune indicates (多い)関節リウマチ RA (可能性)血清病 serum sickness, 全身性エリテマトーデス lupus erythematosus, リウマチ熱 rheumatic fever, ライター症候群 Reiter syndrome, 潰瘍性大腸炎 ulcerative colitis, クローン病=限局性回腸炎 regional ileitis, 乾癬性関節炎 psoriatic arthritis (老人であり得る)リウマチ性多発筋痛症 polymyalgia rheumatica

T Trauma 外傷性滑膜炎 traumatic synovitis, tear or rupture of the collateral or cruciate ligaments, 亜脱臼 subluxation or laceration of the meniscus (semilunar cartilage), 脱臼 dislocation of the joint or patella, a 捻挫　 sprain of the joint, and fracture of the bones of the joint.

E Endcrine 先端肥大症 acromegaly, 閉経 menopause, 糖尿病 diabetes mellitus

■答え

　骨格筋系-関節炎-単関節炎-急性単関節炎

　痛風　尿酸　→　発熱、ESR↑、白血球↑

　偽痛風　ピロリン酸カルシウム

　高齢女性でチアジド系利尿薬の使用により痛風が誘発されやすい。特に腎機能低下、糖尿病の人はこのリスクが高まる。

■(BSTからの知識「)循環器領域での利尿薬

・心不全の治療において、循環血漿量を減らし、心臓の前負荷を軽減する。

・利尿薬は高尿酸血症を起こす。(けど、心不全の治療において高尿酸血症になったからといって痛風を発症している患者はみたことない)

・電解質異常を起こしやすいので、血液生化学の検査でモニタして注意する。たとえば低Kで不整脈のリスクが高まる。

・チアジド系の利尿薬は血糖を上げるし、尿酸を上げる

・長期の使用で腎機能を低下させる

■initial plan

　Dx 1. 関節液の吸引：関節液の一般検査、生化学検査、培養検査、

　　　　・白血球が増加していれば急性炎症性であることを示す。

　　　　・偏光顕微鏡で関節液を検鏡する。

　　　　　・尿酸の結晶：針状結晶。negatively birefringent

　　　　　・ピロリン酸カルシウムの結晶：positively birefringent

　Tx 1. 関節液の吸引：炎症が軽度改善

　　 2. NSAIDによる疼痛管理

　　 3. PPI：NSAID 潰瘍を予防するため

　　 4. ACE inhibitorの導入

「結核」

　　[★]

英: tuberculosis, TB
同: 結核症
関: 結核菌 Mycobacterium tuberculosis、抗結核薬; 肺結核、腸結核、脳結核腫

感染予防学 080423I,II
first aid step1 2006 p.135,137,143,162,172,173,181

Pott's disease = vertebral tuberculosis. constrictive pericarditis = tuberculosis

概念

二類感染症

病原菌

Mycobacterium tuberculosis

疫学

罹患率は男性の方が多い。

平成21年

参考3

結核患者の発生は未だ２万４千人以上である。結核罹患率は引き続き減少傾向にあるが、減少率は２％台と低い。

新登録結核患者数 24,170人

罹患率(人口10万人対の新登録結核患者数)　19.0　（対前年比0.4減）

80歳以上の結核罹患率は横ばいないし増加し、70歳以上の高齢結核患者は新登録結核患者の半数以上となった。

80歳以上の罹患率　88.3 (H20 87.6、H19 90.5、H18 93.0)

70歳以上の新登録結核患者の占める割合 50.1%(H20 48.9%、H19 47.9%、H18 47.0%)

世界的に見て、日本は依然として結核中まん延国である。

日本の罹患率（19.0）は、米国(4.3)の4.4倍、カナダ（4.7）の4.0倍、スウェーデン（5.4）の3.5倍、オーストラリア(5.5)の3.5倍。

感染の型

SPU.178

一次感染

初感染患者に形成される初期変化群の増悪による病変：全身性血行性散布(粟粒結核など)、肺原発巣の空洞化、リンパ節の穿孔による吸引性結核性肺炎、結核性胸膜炎

二次感染

初感染から長期間を経て発症するもの

症状

結核の皮膚病変

真性皮膚結核

結核疹

検査

「喀痰の抗酸菌検査では１日１回、連続して３日間検査することが推奨されている。抗酸菌検査では通常、塗抹検査と培養検査の２項目をオーダーするが、結核の疑いが強い場合には、健康保険診療上、結核菌核酸増幅法検査を１回行うことができる。」(ガイドライン1より引用)

診断

結核菌の診断を行う上では、あくまでも細菌学的検査(塗沫検査、培養検査)によることが原則である。(IRE.1034)
結核の疑いが強い場合にはPCR法により確定して、直ちに保健所に届けるのがよい。

治療

標準治療法：最初2ヶ月間4剤、次の4ヶ月間2-3剤の計6ヶ月間の治療

例：INH,RFP,EB,PZAで2ヶ月間(bactericidal phase)　→　INH,RFP(,EB)で4ヶ月間(continuation phase)
多剤耐性結核菌：少なくともINHとRFPに同時耐性を示す菌株

2009年に厚生労働省告示

A法

ピラジナミド（PZA）を使用できる場合には、まずイソニアジド（INH）、リファンピシン（RFP）およびPZAにストレプトマイシン（SM）またはエタンブトール（EB）を加えた４剤併用療法を２ｶ月間行い、その後INHおよびRFPの２剤併用療法を４剤併用療法開始時から６ｶ月を経過するまで行う。

B法

PZAを使用できない場合には、まずINHおよびRFPの2剤にSMまたはEBを加えてた３剤併用療法を２ないし６ヵ月間行い、その後INHおよびRFPの２剤併用療法を３剤併用療法開始時から９ヶ月を経過するまでに行う。INHまたはRFPを使用できない場合、症状が著しく重い場合、治療開始から２ｶ月を経ても結核菌培養検査陽性の場合、糖尿病、じん肺、HIV感染症等の疾患を合併する場合、または副腎皮質ホルモン剤を免疫抑制剤を長期にわたり使用している場合、などでは治療期間を３ヵ月間延長できる。

薬物療法：抗結核薬

感染経路

空気感染

公衆衛生

二類感染症であり、診断した場合、直ちに保健所長を経て知事に届け出る。(感染症法)

参考

1. 日本結核病学会

http://www.kekkaku.gr.jp/

2. 共益財団法人結核予防学会

http://www.jatahq.org/about_tb/index.html

3. 結核登録者情報調査【平成18年まで結核発生動向調査】｜厚生労働省

http://www.mhlw.go.jp/toukei/list/kekkaku_tourokusya.html

ガイドライン

1. 結核診療ガイドライン(の要点抜粋) 山岸文雄　独立行政法人国立病院機構千葉東病院病院長

http://www.kekkaku.gr.jp/ga/ga-59.htm

国試

105G029、103I049、099G058、097D058

「マイコバクテリア感染症」

　　[★]

英: mycobacterial infection, mycobacteriosis
関: マイコバクテリア感染

「tuberculous」

　　[★]

adj.

結核性の、結核の

関: TB、tuberculosis

「TB」

　　[★]

「bovine tuberculosis」

　　[★]

ウシ型結核、ウシ結核

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