Tuberculosis - tuberculosis

Japanese: 結核 - けっかく（英語表記）tuberculosis

It is an infectious disease caused by infection with the tuberculosis bacillus, also known as tuberculosis. The tuberculosis bacillus is present in the sputum, organs, tissues, etc. of tuberculosis patients. It was discovered in 1882 by the German bacteriologist Koch.

[Tomoyuki Yamaguchi]

Epidemiology

As society modernized with the Industrial Revolution that began in the late 18th century, tuberculosis spread rapidly throughout Europe and the United States. The tuberculosis epidemic spread from Britain, where the Industrial Revolution first began, to advanced industrialized countries, but in these countries the epidemic peaked and began to decline from the mid-to-late 19th century. It is believed that improvements in living standards were responsible for the decline in tuberculosis.

However, the number of tuberculosis patients worldwide is currently on the rise, and in 1993 the World Health Organization (WHO) declared a tuberculosis emergency and called for strengthened measures against tuberculosis worldwide. The number of new tuberculosis patients worldwide, estimated by the WHO based on factors such as the risk of tuberculosis infection, was 7,537,000 in 1990, 8,083,000 in 1998, and 9,157,000 in 2006. As a result, the total number of patients by 2006 was estimated to be 14,424,000. The countries with the highest number of patients are Asian and African countries, including India (1,933,000), China (1,311,000), Indonesia (534,000), South Africa (454,000), and Nigeria (450,000), accounting for approximately 80% of the world's tuberculosis patients.

In the United States, the influx of immigrants and refugees, the spread of HIV (human immunodeficiency virus), the decline of social security, and the concentration of population in cities have led to an increase in tuberculosis incidence since 1989, as well as an increase in multidrug-resistant tuberculosis and frequent cases of hospital-acquired infections caused by multidrug-resistant bacteria. Later, the introduction of DOT (Directly Observed Treatment) and progress in hospital infection control measures led to a decrease in incidence.

In Japan, tuberculosis has been increasing since the Meiji era when society began to modernize, and it was not until the 20th century that it reached its peak. During World War II, the disease was extremely prevalent, but after 1947 (Showa 22), it began to decline rapidly. The rate of decline in tuberculosis after World War II was almost the same as that of Western developed countries. However, while it was not until 1975 that the tuberculosis mortality rate in Japan fell below 10 per 100,000 people, many Western developed countries had already reached that level in the 1950s. This is why it is said that Japan's tuberculosis control measures are 10 to 20 years behind those of Europe and the United States. The incidence rate, which had been decreasing by about 11% each year since World War II, began to decrease at a slower rate around 1978 and 1979, and in 1997 (Heisei 9), it started to increase for the first time in 43 years, so in July 1999, the Minister of Health and Welfare (current Minister of Health, Labor and Welfare) declared a tuberculosis emergency. The rapid aging of the population has had a major impact on the increase in the number of elderly people already infected, leading to problems such as frequent outbreaks of group infections, tuberculosis in cheap lodgings in large cities and areas with many homeless people, and hospital-acquired infections. The number of new tuberculosis patients was 43,818 in 1999 (incidence rate per 100,000: 32.4), but in 2000 it decreased for the first time in four years to 39,384 (31.0), and has since shown a downward trend, to 31,638 (24.8) in 2003 and 26,384 (20.6) in 2006. However, tuberculosis is still spreading among the elderly, and the incidence rate is 4.4 times that of the United States and 4.0 times that of Australia (2006), both of which are high among developed countries, and Japan remains a country with a medium incidence rate.

[Tomoyuki Yamaguchi]

infection

Infection occurs when tuberculosis bacteria contained in droplets scattered when a patient coughs or sneezes are inhaled into the lungs. Infection from sources other than the respiratory tract is extremely rare. Even if tuberculosis bacteria are inhaled into the bronchi, they are sent back by the action of cilia that grow densely on the surface of the bronchial mucosa, and infection does not necessarily occur. It is only when they reach the alveoli that they settle and multiply, triggering a defense reaction in the body and causing infection.

The lesion that appears where the bacteria first enters the lungs is the primary infection site, and at the same time, the bacteria enter the lymphatic system and are carried to the hilar lymph nodes, causing lesions there as well; these two together are called the early change group. During this time, the human body becomes sensitized by the tuberculosis bacteria, and develops delayed-type hypersensitivity to tuberculin. T lymphocytes play the leading role in cellular immunity, such as tuberculosis immunity, and sensitized T lymphocytes release lymphokines upon contact with antigens, which are thought to activate macrophages (large phagocytes that ingest bacteria, foreign bodies, and cell components and function as scavenging cells) and cause the tuberculin reaction. It takes 2 to 10 weeks for immunity to develop after infection, and once immunity or hypersensitivity develops, the center of the tuberculous exudative lesion becomes necrotic, but this necrotic focus is different from the soluble necrosis caused by suppuration in general inflammation, and becomes coagulative necrosis, forming a necrotic material similar to yellow cheese (caseated). Granulation tissue in which epithelioid cells proliferate surrounds this caseated focus (caseated degeneration), and specific changes are observed, but most of the early change group heals as it is, and most infected people live their lives without developing the disease, with only a small proportion of them developing the disease.

[Tomoyuki Yamaguchi]

Onset of the disease

There are three routes by which the bacteria spread from the initial change group: intraductal, hematogenous, and lymphatic. When the bacteria enter the bloodstream from the pulmonary lesions and several mediastinal lymph nodes in succession soon after the initial infection, they cause lesions in the lungs, kidneys, and bones, but in most cases the disease heals naturally. However, the bacteria may survive in the lesions and begin to grow again several years or even decades after infection, causing active lesions. When chronic pulmonary tuberculosis occurs, the lesions become caseous, and the necrotic parts are dissolved and eliminated, forming cavities. There are a large number of bacteria in the cavities, which can become a source of infection for the surrounding area and a source of metastasis for the patient himself, but in this case the disease progresses intraductally via the bronchi and intestines.

[Tomoyuki Yamaguchi]

Symptoms

Symptoms include coughing, phlegm, bloody phlegm, coughing up blood, fever, night sweats, loss of appetite, chest pain, back pain, stiff shoulders, general fatigue, weight loss, and neurasthenia-like symptoms. Of these, except for local symptoms such as coughing, bloody phlegm, and coughing up blood, all of these symptoms are the result of the reaction between the tuberculosis bacteria and the body itself disrupting the nervous system (the nervous system that involuntarily controls and regulates vital phenomena such as breathing, excretion, and blood circulation), and in fact are often difficult to distinguish from the results of fatigue, mental distress, or life-related anguish. Symptoms become milder when the disease stabilizes, but they are quite likely to occur when the condition worsens. In particular, if coughing and phlegm persist for more than two weeks, it is possible that the tuberculosis is worsening, so it is important to see a doctor.

[Tomoyuki Yamaguchi]

diagnosis

Smear and culture tests are performed to prove the presence of tuberculosis bacteria in pathological materials such as sputum and diseased tissues. The culture method using Ogawa medium, developed in 1950 (Showa 25) by Tatsuji Ogawa (1906-94) of the Sanatorium attached to the Tuberculosis Research Institute (at the time), has been widely used nationwide as a method for culturing acid-fast bacteria, but with the advancement of molecular biology, testing methods have also advanced remarkably. Following the BACTEC method for rapid detection of acid-fast bacteria in 1983, the acid-fast bacteria identification method using DNA probes (specific fragments of DNA that make up genes) was developed in 1987, and the DDH (DNA-DNA Hybridization) method in 1988. The DDH method is a method for differentiating and identifying acid-fast bacteria by hybridization between the DNA of 18 clinically problematic acid-fast bacteria and the DNA of the sample, and can quickly and accurately identify the bacterial species in 3 to 4 hours per sample. In 1989, a method for identifying acid-fast bacteria using PCR (Polymerase Chain Reaction) was developed, and in 1990, the RFLP (Restriction Fragment Length Polymorphism) analysis method, which is said to be the so-called "fingerprint" of tuberculosis bacteria, was established. In the 1990s, the Mycobacterium Growth Indicator Tube (MGIT) method also came into use. The MGIT method is a method for culturing acid-fast bacteria in a test tube embedded with an oxygen-sensitive fluorescent sensor, which can detect tuberculosis bacteria in an average of 10 days, and has a higher detection rate when the number of bacteria is small than the conventional Ogawa medium. In terms of imaging diagnosis, in addition to conventional X-ray photography, helical CT was developed, which has made great progress in distinguishing it from lung cancer (embryocarcinoma).

The tuberculin reaction can tell whether or not someone is infected with tuberculosis, but because the tuberculin reaction is positive even in people who have been vaccinated with the BCG vaccine, it has relatively little diagnostic value in a situation where BCG vaccination is widespread, such as in Japan today. The Quanti-FERON-TB method (QFT method) is a method for diagnosing tuberculosis infection that is not affected by the BCG vaccination, and has been in practical use in Japan since 2006. For cervical lymph node tuberculosis, exploratory resection is required, for urinary tract tuberculosis, cystoscopy, and for meningitis, cerebrospinal fluid testing is required.

[Tomoyuki Yamaguchi]

Treatment

There are two types of treatment: surgery and chemotherapy. Since the discovery of streptomycin by the American microbiologist Waxman in 1944, new chemotherapy drugs have appeared one after another, and it has become possible to cure almost all cases of pulmonary tuberculosis with chemotherapy alone. With the advancement of chemotherapy, the value of the three principles of medical treatment - air, rest, and nutrition - has declined relatively, and the indications for surgical therapy have been significantly narrowed, and it has been limited to only those cases in which chemotherapy cannot stop the excretion of bacteria. However, surgical therapy is still often performed for bone tuberculosis, etc. There are currently more than 10 types of chemotherapy that can be used, but hydrazide and rifampicin are the most powerful, and in principle, the standard treatment is to combine these two drugs with pyrazinamide and streptomycin or ethambutol. With this type of treatment, 6 to 9 months of treatment is sufficient for the initial treatment, and the recurrence rate is low.

One of the factors that impedes the effectiveness of chemotherapy is the problem of drug-resistant bacteria. According to a nationwide survey conducted in 2002, 8.2% of patients in Japan who have never received treatment for tuberculosis are resistant to one of the major drugs (hydrazide, rifampicin, streptomycin, or ethambutol). Tuberculosis that is resistant to both hydrazide and rifampicin is called multidrug-resistant (MDR) tuberculosis, and tuberculosis that is also resistant to kanamycin, new quinolones, etc. is called extensively drug-resistant (XDR) tuberculosis.

In order to improve treatment outcomes, it is essential to prevent irregular or interrupted use of medication. For this reason, the WHO recommends DOTS (Directly Observed Treatment, Short-course), in which medical staff monitor patients as they take their medication. In Japan, various support programs are being implemented to ensure that patients take medication (Japanese version of DOTS strategy).

[Tomoyuki Yamaguchi]

prevention

Previously, the first thought to prevent infection was isolation of patients, but if chemotherapy can reduce the amount of bacteria excreted and the frequency of coughing, infection can be prevented, so treatment is essentially infection prevention, and even smear-positive patients can now get by with short-term hospitalization. There are two methods for preventing the disease: BCG vaccination, which is administered before infection, and chemical prevention, which is administered after infection. In Japan, BCG vaccination was switched from intradermal to percutaneous inoculation in 1967, and no longer leaves ulcers or large scars at the vaccination site that are difficult to heal. The vaccine was administered once in infancy until the age of four, and thereafter to first-year elementary school and junior high school students who had a negative tuberculin reaction, but in April 2003, tuberculin reaction tests and BCG vaccinations for elementary and junior high school students were abolished. Furthermore, in light of the declining incidence rate among young people, the harmful effects of false-positive tuberculin test results resulting from the loss of the opportunity to receive BCG vaccination, and the accumulation of medical knowledge regarding the safety of administering BCG directly, the system was revised and, from April 2005, tuberculin tests were completely abolished from routine vaccinations, with those under six months of age now receiving only one direct BCG vaccination. Chemical prevention can reduce the incidence of disease by more than half by having those thought to be infected take hydrazide for six months, and this effect is observed long after the administration of hydrazide has ceased.

Chemical prevention has traditionally been called "treatment of latent tuberculosis infection" or "multi-stage tuberculosis treatment," but in the United States it has been called "treatment of latent tuberculosis infection (LTBI treatment)" since 2000, and in Japan, following this, treatment costs have been publicly covered under this name since 2006.

Mass screening has been used for many years as a method of detecting cases, but as the number of tuberculosis patients has decreased, the efficiency of detection has decreased. Emphasis is now placed on detecting cases through screening of patients with respiratory symptoms, screening of contacts including patients' families, and screening of high-risk groups.

[Tomoyuki Yamaguchi]

history

The oldest human bones with lesions believed to be caused by tuberculosis infection, based on paleopathology, date back to Neolithic Europe around 5000 BC. Similar lesions have been found in an Egyptian child mummy from around 2700 BC, and in human bones from the Americas before the arrival of Columbus. Ancient clay statues and paintings thought to depict spinal deformities caused by spinal caries have been discovered in Egypt and Mexico. Among the oldest written descriptions of tuberculosis (pulmonary tuberculosis) are those found in the ancient Indian Vedas, the Jewish Talmud, the writings of the Greek Hippocrates, and medical books from the Sui Dynasty in China.

[Hideo Takei]

Disease name

The names of diseases that are presumed to be tuberculosis show well how people in premodern times understood tuberculosis. Hippocrates' "phlegm" is a derivative of a word meaning exhausted or debilitated. The word "consumption" used in Europe until the 1930s was based on the impression that the disease consumed and thinned the patient's blood. Although it was as fatal as the plague, it was also called the "white plague" because the skin turned pale and did not develop spots, and was feared. Although it is not clear from these names alone, many Greek and Roman doctors believed it to be a hereditary disease, partly because it often ran within families. The idea that tuberculosis was a hereditary disease was dominant not only among the general public but also among doctors in Europe, even after its contagious nature was proven in the 1860s. In Japan, the term "rougai," meaning weakness accompanied by coughing due to fatigue, has come into common use since the early modern period, but in ancient times it was called "denshi" or "denshi-ro," and was thought to be a hereditary form of weakness leading to death, and this idea of it being hereditary remained until after World War II.

[Hideo Takei]

Tuberculosis and society

Tuberculosis has existed worldwide since ancient times. However, it became evident as a social disease when it became prevalent after the Industrial Revolution. It is believed that tuberculosis was on the rise as urbanization progressed in the Middle Ages, but the increase was accelerated by the combination of excessive work, poor working conditions, unsanitary living conditions, malnutrition, and the underdeveloped immunity to tuberculosis among urban migrants brought about by the Industrial Revolution and rapid urbanization. John Bunyan already called tuberculosis "the general of man's death" at the end of the 17th century, but it is estimated that the death rate from tuberculosis in England peaked a century later, around the end of the 18th century. In proportion to the delay in the Industrial Revolution and urbanization, the death rate peaked in Europe and America from the late 19th century to the early 20th century. In Japan, as symbolized by "The Lamentations of a Factory Girl," the peak occurred at the end of the Meiji period, the Taisho period, and the early Showa period as a result of rapid industrialization after the Meiji period. The fact that the decline in death rates in developed countries was largely achieved prior to the appearance of anti-tuberculosis drugs through improvements in working conditions, urban environments, sanitary facilities, nutrition, etc., and that tuberculosis epidemics associated with this continue to this day in so-called developing countries where industrialization began in earnest in the second half of the 20th century, clearly demonstrate the social nature of tuberculosis epidemics. In both Europe and Japan, the tuberculosis epidemic was one of the greatest social shocks that prompted the proposal of "social medicine."

Although tuberculosis has existed since ancient times, it was during its epidemics, mainly in the 19th century, that tuberculosis was given rich cultural and social meaning. In Europe, tuberculosis was feared as the "white plague" with an unknown cause and certain death, but at the same time, it was a disease that was glorified by being linked to ideas of passion, sensuality, spiritual purification, superior sensitivity and creativity. As a treatment, tuberculosis sanatoriums treated tuberculosis patients as "guests" in society, a system that perfectly exemplified the privileged role of the sick. However, as a chronic disease that progresses and certainly brings death, tuberculosis made this role as a "guest" hopeless, and at the same time, it gave patients a social mark that would never disappear for the rest of their lives. This mark was often linked to discrimination. Even after World War II, there was a tendency in various parts of Japan to view "pulmonary disease lineages" as a problem and to avoid intermarriage. A notable example of this is the avoidance of intermarriage among families of the same family, known as "pulmonary disease make" in the Tohoku region. Regardless of whether or not there were people with tuberculosis in each family, by tracing the main family and branch family relationships, all the families of a certain lineage were identified as the same, and intermarriage became the subject of taboo. Now that tuberculosis has become a curable disease, its character as a social mark is disappearing.

[Hideo Takei]

"Treatment of Tuberculosis" by the World Health Organization and the International Union for the Prevention of Tuberculosis and Lung Disease, translated by Aoki Masakazu (1994, Japan Anti-Tuberculosis Association)" ▽ "Basic Knowledge of Tuberculosis" revised edition by the Japanese Society for Tuberculosis (1997, Japan Anti-Tuberculosis Association)" ▽ "Pathology of Tuberculosis" by Iwasaki Tatsuro (1997, Japan Anti-Tuberculosis Association)" ▽ "Knowledge of the Results of Happiness" revised edition edited by Shimao Tadao (1997, Japan Anti-Tuberculosis Association)" ▽ "Immunology of Tuberculosis" revised edition by Tsuyuguchi Izumio (1998, Japan Anti-Tuberculosis Association)" ▽ "Testing for Acid-Fast Bacilli" by Abe Chiyoji (1998, Japan Anti-Tuberculosis Association)" ▽ "Reader on Tuberculosis - What kind of disease is Tuberculosis?" new edition by Shimao Tadao (1998, Japan Anti-Tuberculosis Association)" ▽ "Modern Tuberculosis by Mori Toru - Why is this disease here now?" (1998, Newton Press)" ▽ "Why Tuberculosis Now?" by Mori Toru (1999, Iwanami Shoten)" ▽ "Guide to Strengthening Tuberculosis Control at Public Health Centers and Its Commentary" edited by Mori Toru (2000, Japan Anti-Tuberculosis Association)" ▽ "Nosocomial Infection of Tuberculosis by Aoki Masakazu, revised edition (1998, Japan Anti-Tuberculosis Association)" ▽ "Basic Knowledge of Tuberculosis by Aoki Masakazu, new edition (1998, Japan Anti-Tuberculosis Association)" ▽ "Mass Infection of Tuberculosis by Aoki Masakazu, revised edition (1999, Japan Anti-Tuberculosis Association)" ▽ "Infection, Onset and Prevention of Tuberculosis - Why is it a Threat Against Now?" (2000, Soboksha)" ▽ "Tuberculosis: Its Current State and Future, 3rd edition (2000, Japan Anti-Tuberculosis Association)" ▽ "The History of Tuberculosis - Its Relationship with Japanese Society, Past, Present and Future" by Aoki Masakazu (2003, Kodansha)" ▽ "Tuberculosis Management and Countermeasures in Hospitals and Clinics" by Suzuki Kiminori (1998, Japan Anti-Tuberculosis Association)" ▽ "The Fear of 'Tuberculosis'" by Koike Yusuke (1999, PHP Institute)" ▽ "Tuberculosis - A Fearful Infectious Disease Resurrected" by Sugita Hironobu (2000, Shinsei Publishing) ▽ "New Tuberculosis Terminology Dictionary" edited by the Terminology Committee of the Japanese Society for Tuberculosis (2001, Japan Anti-Tuberculosis Association)" ▽ "The Social History of Tuberculosis - Tracing the Organization of National Disease Countermeasures and the Realities of Tuberculosis Patients" by Aoki Junichi (2004, Ochanomizu Shobo) ▽ "Up to Date Tuberculosis" Revised Second Edition by Shimoto Hidetake and Kurashima Atsuyuki (2005, Nanzando)" ▽ "Tuberculosis Knowledge for Medical Professionals," 2nd edition, by Shimoto Hideki and Yamagishi Fumio (2005, Igaku-Shoin)" ▽ "Tuberculosis," 4th edition, edited by Izumi Takahide and compiled by Tomioka Hiromi (2006, Igaku-Shoin)" ▽ "Tuberculosis Countermeasures Under the Revised Infectious Diseases Law -- A Guide for Public Health Centers (2007)," published and edited by the Japan Anti-Tuberculosis Association (JTA) ▽ "Tuberculosis Statistics," annual editions, edited by the Health Bureau of the Ministry of Health, Labor and Welfare (JTA)" ▽ "The Human Body and Tuberculosis," by Kondo Koji (Iwanami Shinsho)" ▽ "The Age of Infectious Diseases," by Inoue Sakae (Kodansha Gendai Shinsho)" ▽ "The Culture of Tuberculosis -- A Comparative Cultural History of Disease," by Fukuda Masato (Chuko Shinsho)

How tuberculosis spreads in the body
©Shogakukan ">

How tuberculosis spreads in the body

Source: Shogakukan Encyclopedia Nipponica About Encyclopedia Nipponica Information | Legend

Japanese:

結核菌の感染によっておこる感染症で、結核症ともいう。結核菌は結核患者の喀痰(かくたん)や臓器、組織等に存在する。1882年ドイツの細菌学者コッホにより発見された。

［山口智道］

疫学

18世紀後半に始まった産業革命による社会の近代化に伴い、結核は欧米諸国に急速に広がっていった。結核蔓延(まんえん)の波は、産業革命が初めにおこったイギリスから先進工業諸国に広がったが、これらの国では19世紀中ごろから末にかけて蔓延の頂上を越え、結核は減少し始めた。生活水準の向上が結核の減少をもたらしたものと思われる。

　しかし世界的にみると結核患者は現在増加の傾向にあり、世界保健機関（WHO）は1993年に結核非常事態宣言をし、全世界に結核対策の強化を呼びかけた。WHOが中心となって結核感染危険率などに基づいて推定した世界の結核患者新発生数は1990年には753万7000人、1998年には808万3000人、2006年には915万7000人に上った。これにより2006年までの患者総数は推計1442万4000人となった。患者の発生数が多いのはインド（193万3000人）、中国（131万1000人）、インドネシア（53万4000人）、南アフリカ（45万4000人）、ナイジェリア（45万人）などアジア、アフリカの国々であり、全世界の結核患者の約8割を占めている。

　アメリカでは移民・難民の流入とHIV（ヒト免疫不全ウイルス）感染の拡大、社会保障の低下や都市への人口集中が影響して1989年から結核罹患(りかん)率が増加に転じ、多剤耐性結核の増加、多剤耐性菌による院内集団感染が多発した。その後、DOT(ドット)（直接監視下治療Directly Observed Treatment）の導入、院内感染対策の進展により罹患率は減少に転じた。

　日本では結核は、明治時代に入って社会が近代化を始めて以来増加がみられ、蔓延の頂点を迎えたのは20世紀に入ってからであった。第二次世界大戦中はたいへんな蔓延状態であったが、1947年（昭和22）以降は急速に低下し始めた。第二次世界大戦後の結核減少速度は、欧米先進国とほぼ同様である。しかし日本の結核死亡率が人口10万対10を割ったのは1975年であるのに、欧米先進国では1950年代にすでにその水準に達している国が少なくない。日本の結核対策が欧米に比し十数年から20年遅れているといわれるゆえんである。第二次世界大戦後毎年約11％ずつ減少してきた罹患率は、1978年、79年ごろから減少が鈍化し、97年（平成9）には43年ぶりに増加に転じたため、99年7月に厚生大臣（現厚生労働大臣）は結核緊急事態宣言を出した。人口の急速な老齢化による既感染の高齢者が増えたことによる影響が大きく、集団感染の多発、大都市の簡易宿泊所や住所不定者の多い地域での結核、院内感染などの問題を抱えている。なお新規結核患者は1999年に4万3818人（対10万罹患率32.4）であったが、2000年には4年ぶりに減少し3万9384人（31.0）となり、その後も2003年3万1638人（24.8）、2006年2万6384人（20.6）と減少傾向にある。しかし高齢者の結核は依然拡大しており、また罹患率もアメリカの4.4倍、オーストラリアの4.0倍（2006）と先進国のなかでは高く、依然中蔓延国にとどまっている。

［山口智道］

感染

排菌患者が咳(せき)、くしゃみなどをしたときに飛び散るしぶきの中に入っている結核菌を肺に吸い込むと感染する。呼吸器以外からの感染はきわめてまれである。結核菌が気管支内に吸い込まれても、気管支粘膜の表面に密に生えている線毛の働きによって送り戻され、かならずしも感染が成立するものではない。肺胞まで達して初めてそこに定着して増殖し、人体の防御反応が引き起こされて感染が成立する。

　肺内の初めて菌が入ったところに生じる病巣が初感染原発巣で、同時に菌はリンパの流れに入って肺門リンパ節に運ばれ、ここにも病変をおこし、両者をあわせて初期変化群という。この間に人体は結核菌によって感作(かんさ)され、ツベルクリンに対する遅延型過敏症を示すようになる。結核免疫のような細胞性免疫の主役を演じているのはTリンパ球で、感作Tリンパ球は抗原との接触によってリンホカインを出し、これがマクロファージ（大食細胞。細菌・異物・細胞成分などを摂取し、清掃細胞としての機能をもつ）を活性化したり、ツベルクリン反応を引き起こすと考えられている。感染後免疫が成立するまでの期間は2～10週で、免疫や過敏症が生じると、結核性滲出(しんしゅつ)性病変の中心部は壊死(えし)に陥るが、この壊死巣は一般炎症の化膿による融解壊死と異なり、凝固性の壊死となり、黄色調のチーズ（乾酪(かんらく)）に似た壊死物質を形成する。この乾酪化巣（乾酪変性）を囲んで類上皮細胞が繁殖する肉芽組織ができ、特異的変化を示すようになるが、初期変化群の大部分はそのまま治癒し、感染を受けた人の多くは発病することなく一生を送り、そのうち発病するのはごく一部である。

［山口智道］

発病

初期変化群から菌が広がっていく経路には管内性、血行性、リンパ行性の三つがあげられる。初感染後の早い時期に肺の病巣や、いくつかの縦隔リンパ節を次々に冒して最後に静脈角リンパ節（内頸(ないけい)静脈と鎖骨下静脈との合流点にあるリンパ節）から菌が血中に入ると、肺、腎(じん)、骨などに病変が生じるが、多くの場合自然に治癒する。しかし菌は病巣内に生き残って、感染後数年、ときには数十年後にふたたび増殖を始め、活動性病変を生じることがある。慢性肺結核を生じると、病巣は乾酪化し、壊死(えし)をおこした部分が融解排除されて空洞を生じる。空洞内には大量の菌があり、周囲に対する感染源ともなり、本人自身に対する転移源ともなるが、この場合は気管支や腸管を介して管内性に進展していく。

［山口智道］

症状

咳、痰(たん)、血痰、喀血(かっけつ)、発熱、寝汗、食欲不振、胸痛、背痛、肩こり、全身倦怠(けんたい)、体重減少、神経衰弱様症状などがある。これらのうち、咳、血痰、喀血などの局所症状を除くと、いずれも結核菌と生体側の反応によって植物神経系（呼吸、排泄(はいせつ)、血液の循環等、不随意に生命現象を統御・調節する神経系）を攪乱(かくらん)した結果おこる症状であって、実際には疲労や精神的あるいは生活上の苦悩などの結果と区別しにくいことが多い。病状が安定すると症状は軽くなるが、悪化の際にはかなり高率に症状がみられる。とくに咳、痰が2週間以上持続するときは結核の悪化が考えられるので、受診することが必要である。

［山口智道］

診断

喀痰(かくたん)などの病的材料、病変組織から結核菌を証明するため、塗抹、培養検査を行う。抗酸菌培養法としては、1950年（昭和25）に結核研究所附属療養所（当時）の小川辰次(たつじ)（1906―94）が開発した小川培地による培養法が、全国的に広く用いられてきたが、分子生物学の進歩を受けて検査法もめざましく進歩した。1983年のBACTEC(バクテック)法による抗酸菌迅速検出法に続き、87年にDNAプローブ（遺伝子を構成するDNAの特異的断片）による抗酸菌同定法、88年にはDDH（DNA‐DNA Hybridization）法が開発された。DDH法は、臨床上問題となる18種の抗酸菌のDNAと検体DNAとの間のハイブリダイゼーション（雑種形成）によって抗酸菌を鑑別・同定する方法で、1検体3～4時間で迅速・的確に菌種を同定できる。また1989年にはPCR（ポリメラーゼ連鎖反応Polymerase Chain Reaction）を利用した抗酸菌同定法も開発され、90年には結核菌のいわゆる「指紋」といわれるRFLP（制限酵素断片長多形Restriction Fragment Length Polymorphism）分析法も確立した。1990年代にはMGIT(ミジット)（Mycobacterium Growth Indicator Tube）法も利用されるようになった。MGIT法は、酸素感受性の蛍光センサーを埋め込んだ試験管で抗酸菌を培養する方法で、結核菌を平均十数日で検出でき、菌数が微量の場合の検出率は、従来の小川培地より優れている。画像診断の面では従来のX線写真に加え、ヘリカルCTが開発され、肺癌(はいがん)との鑑別のうえで大きく進歩した。

　ツベルクリン反応によって結核感染の有無を知ることができるが、BCGを接種した者でもツベルクリン反応は陽性に出るので、現在の日本のようにBCG接種が普及している場合には診断的価値が比較的乏しい。Quanti-FERON-TB法（QFT法）はBCG接種の影響を受けずに結核感染の診断を行う方法で、日本でも2006年（平成18）から実用化された。頸部リンパ節結核では試験切除、尿路結核では膀胱(ぼうこう)鏡、髄膜炎では髄液の検査などを行う必要がある。

［山口智道］

治療

治療には外科療法と薬剤による化学療法があるが、1944年アメリカの微生物学者ワックスマンがストレプトマイシンを発見して以来、次々と化学療法剤が現れ、肺結核ではほとんどすべて化学療法のみで治すことができるようになった。化学療法の進歩によって、療養の三原則といわれていた大気、安静、栄養の価値は相対的に低下し、外科療法の適応も著しく狭められ、化学療法でどうしても排菌を止められないものだけに適応が限られてきた。しかし骨結核などでは、なお外科療法が行われることも多い。現在用いることができる化学療法は10種類以上であるが、ヒドラジッドとリファンピシンがもっとも強力で、原則としてこの2剤にピラジナマイドおよびストレプトマイシンまたはエタンブトールを併用する治療法が標準療法である。このような治療法により初回治療の場合では6～9か月の治療で十分であり、その後の再発率も低い。

　化学療法の効果をさまたげる要因の一つとして耐性菌の問題が重要である。2002年の全国調査によると、日本では今まで結核の治療を受けたことのない患者でも主要薬剤（ヒドラジッド、リファンピシン、ストレプトマイシン、エタンブトール）のいずれかに耐性をもっている患者は8.2％である。ヒドラジッドとリファンピシンの両剤に耐性のあるものは多剤耐性結核Multidrug-resistant（MDR）とよび、さらにこの上にカナマイシン、ニューキノロン剤等の耐性も加わったものを超多剤耐性結核Extensively drug-resistant（XDR）とよんでいる。

　治療成績を向上させるためには、不規則に服用したり、中断したりするのを防ぐことが不可欠である。このためWHOでは患者が服用するのを診療側が確認しながら治療を行うDOTS(ドッツ)（Directly Observed Treatmennt,Short-course）をすすめている。わが国でも服薬を確実にするための種々の支援事業が行われている（日本版DOTS戦略）。

［山口智道］

予防

以前は感染防止といえば、まず患者の隔離が考えられたが、化学療法によって排菌量と咳の回数を減らすことができれば周囲への感染は防げるわけで、治療がすなわち感染予防となり、塗抹陽性患者でも短期の入院ですむようになった。発病予防には、感染する前に行われるBCG接種と、感染後に行われる化学予防の二つの方法がある。日本のBCG接種は1967年（昭和42）から皮内接種法から経皮接種法に切り換えられ、接種局所に治りにくい潰瘍(かいよう)や大きい瘢痕(はんこん)を残すことはなくなった。4歳までの乳幼児期に1回と、その後は小学校1年と中学校1年生のツベルクリン反応陰性者に接種していたが、2003年（平成15）4月より小中学生への集団でのツベルクリン反応検査、BCG接種は廃止された。さらに、若年者罹患率の低下、ツベルクリン反応偽陽性者のBCG接種機会の喪失の弊害、直接BCGを接種することの安全性についての医学的知見の蓄積などをふまえ制度が改正され、2005年4月からは定期予防接種におけるツベルクリン反応検査は全面的に廃止され、生後6か月未満の者を対象にBCGの直接接種が1回だけ行われることとなった。化学予防は、感染を受けたと思われる者にヒドラジッドを6か月服用させることにより発病を半分以下に減少させることができ、その効果はヒドラジッド服用終了後も長く認められる。

　化学予防は従来「初感染結核治療」「マル初」などとよばれてきたが、アメリカでは2000年から「潜在性結核感染治療treatment of latent tuberculosis infection（LTBI治療）」とよぶようになり、日本でもこれに従って2006年からこの名で治療費が公費負担の対象となっている。

　患者発見の方法としては集団検診が長年行われてきたが、結核の患者の減少に伴い発見の効率が悪くなってきた。呼吸器症状のある患者の検診、患者家族を含む接触者検診、ハイリスク・グループの検診による患者発見が重視されている。

［山口智道］

歴史

古病理学的に結核菌感染によると推定される病変の認められる最古の人骨は、紀元前5000年ごろの新石器時代のヨーロッパのものである。同様の病変は前2700年ごろのエジプトの子供のミイラ、コロンブス到達以前の南北アメリカ大陸の人骨などにも認められている。エジプト、メキシコなどでは、脊椎(せきつい)カリエスによる脊椎変形を表現したと考えられる古代の粘土像や絵画も発見されている。文献的に結核（肺結核）と推定される記述のうち古いものとして、古代インドのベーダ、ユダヤのタルムード、ギリシアのヒポクラテスの著作、中国隋(ずい)代の医書などに記されたものがある。

［武井秀夫］

病名

結核と推定される病気の病名は、近代以前の人々が結核をどのような病気として理解していたかをよく示している。ヒポクラテスの「肺癆(はいろう)」は、疲れきった、衰弱したという意味のことばの派生語である。ヨーロッパで1930年代まで使われた「消耗」は、この病気が患者の血液を食い尽くし、薄くするという印象に基づいている。また、ペストのように致死的であるが、皮膚が青白くなり、斑点(はんてん)も出ないところから「白いペスト」ともよばれ、恐れられた。これらの病名からだけでは明らかではないが、家族内での発病が多かったこともあって、ギリシアやローマの医師たちの多くはこれを遺伝病と考えていた。結核を遺伝病とする観念は、1860年代にその伝染性が証明されたのちでさえ、ヨーロッパの一般人のみならず医師の間でも支配的であった。日本では近世以降「労咳(ろうがい)」、つまり疲労によっておこる咳(せき)を伴う衰弱、という名称が一般化したが、古くは「伝屍(でんし)」あるいは「伝屍労」とよばれ、遺伝性の死に至る衰弱と考えられていたし、この遺伝性という観念は第二次世界大戦後にまで残存した。

［武井秀夫］

結核と社会

結核は古くから世界的な広がりをもって存在してきた。しかし、それが社会の病気としての性格を顕在化したのは産業革命以後の流行によってである。中世にも都市化の進行とともに結核が増加傾向にあったと推測されているが、産業革命と急速な都市化のもたらした過重な労働、劣悪な労働条件、不衛生な住環境、栄養不良と、都市移住者の間の結核に対する免疫性の未発達とが重なって、その増加はさらに加速された。ジョン・バンヤン（バニヤン）はすでに17世紀末に結核を「人間の死の大将」とよんだが、イギリスにおける結核による死亡率がピークに達したのは、さらに1世紀を過ぎた18世紀末ごろと推定されている。産業革命と都市化の遅れに比例するように、ヨーロッパ諸国、アメリカにおける死亡率のピークは19世紀後半から20世紀初頭にかけて訪れている。日本では『女工哀史』にも象徴されるように、明治以降の急速な産業化の結果、明治末、大正、昭和初期にピークが現れている。先進諸国における死亡率の減少が、抗結核剤の登場に先だって、労働条件、都市環境、衛生施設、栄養などの改善によっておおかたは達成されていること、20世紀後半になって産業化が本格化したいわゆる開発途上諸国では、それに伴う結核の流行が現在も続いていることなどは、結核流行の社会的性格をよく示している。ヨーロッパにおいても日本においても、結核の流行は「社会医学」の提唱を促した最大の社会的衝撃の一つであった。

　古くから存在したとはいえ、結核が豊富な文化的・社会的意味を与えられたのも、19世紀を中心とした流行の過程においてであった。ヨーロッパにおいて結核は、原因不明で確実に死をもたらす「白いペスト」として恐れられたと同時に、情熱と官能、霊的純化、優れた感受性と創造性などの観念に結び付けられて美化された病であった。治療としての結核サナトリウムは結核の患者を社会の「客」のように遇したが、それは病者の特恵的役割を絵にかいたような制度であったといえる。しかし、慢性的に進行して確実に死をもたらす病としての結核は、この「客」としての役割を絶望的なものとすると同時に、患者に終生消えることのない社会的刻印を与えた。この刻印は、しばしば差別に結び付いた。日本各地には第二次世界大戦後になっても「肺病の系統」を問題視し、通婚を忌避しようとする傾向が存在した。その著しい例は東北地方などの「肺病マケ」とよばれる同族家系に対する通婚忌避である。各家での発病者の有無にかかわらず、本家・分家関係をたどることで、ある家系のすべての家が同一視され、通婚忌避の対象となった。結核が治る病気になった現在、その社会的刻印としての性格は消滅しつつある。

［武井秀夫］

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