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Atypical Mycobacteria

Atypical mycobacteria

Nontuberculous mycobacteria (NTM), or atypical mycobacteria or mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or Hansen's disease (leprosy).

Introduction

See mycobacterium for more information about this genus and a list of species.

Medical classification

Mycobacteria can be classified into 3 main groups for purpose of diagnosis and treatment:
- M. tuberculosis complex which can cause tuberculosis: M. tuberculosis, M. Bovis, M. africanum, and M. micoti
- M. leprae which causes Hansen's disease or leprosy
- Nontuberculous mycobacteria (NTM) are all the other mycobacteria which can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease. See Reference for more information about diagnosis and treatment

Reference

- Diagnosis and Treatment of Disease Caused by Nontuberculous Mycobacteria. American Thoracic Society. Am J Respiratory and Critical Care Medicine. Aug 1997 156(2) Part 2 Supplement [http://www.thoracic.org/adobe/statements/nontuberc1-27.pdf PDF format]
- eMedicine Radiology © - pictures of X-ray and CT scan of various findings of NTM disease:
- [http://www.emedicine.com/radio/topic413.htm Lung, Nontuberculous Mycobacterial Infections] - cavity, volume loss, fibrosis, nodule, bronchiectasis, atelectasis, lymphadenopathy

Tuberculosis

Tuberculosis is an infection with the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (miliary TB), genitourinary system, bones and joints. Other names for the disease are:
- TB (short for tuberculosis and also for Tubercle Bacillus)
- Consumption (TB seemed to consume people from within with its symptoms of bloody cough, fever, pallor, and long relentless wasting)
- Wasting disease
- White plague (TB sufferers appeared markedly pale)
- Phthisis (Greek for consumption) and phthisis pulmonalis
- Scrofula (swollen neck glands)
- King's evil (so called because it was believed that a king's touch would heal scrofula)
- Pott's disease of the spine
- Miliary TB (x-ray lesions look like millet seeds)
- Tabes mesenterica (TB of the abdomen)
- Lupus vulgaris (the common wolf - TB of the skin)
- Prosector's wart, also a kind of TB of the skin, transmitted by contact with contaminated cadavers to anatomists, pathologists, veterinarians, surgeons, butchers, etc. Tuberculosis is the most common major infectious disease today, infecting two billion people or one-third of the world's population, with nine million new cases of active disease annually, resulting in two million deaths, mostly in developing countries. Most of those infected (90 percent) have asymptomatic latent TB infection (LTBI). There is a 10 percent lifetime chance that LTBI will progress to active TB disease which, if left untreated, will kill more than 50 percent of its victims. TB is one of the top three infectious killing diseases in the world: HIV/AIDS kills 3 million people each year, TB kills 2 million, and malaria kills 1 million. The neglect of TB control programs, HIV/AIDS, and immigration has caused a resurgence of tuberculosis. Multiple drug resistant strains of TB (MDR-TB) are emerging. The World Health Organization declared TB a global health emergency in 1993.

The bacterium

World Health Organization.]] The cause of tuberculosis, Mycobacterium tuberculosis (MTB), is a slow-growing aerobic bacterium that divides every 16 to 20 hours. This is extremely slow compared to other bacteria, which tend to have division times measured in minutes (among the fastest growing bacteria is a strain of E. coli that can divide roughly every 20 minutes). It is not classified as either Gram-positive or Gram-negative because it does not have the chemical characteristics of either, although it contains peptidoglycan in their cell wall. If a Gram stain is performed, it stains very weakly Gram-positive or not at all. It is a small rod-like bacillus which can withstand weak disinfectants and can survive in a dry state for weeks but, spontaneously, can only grow within a host organism (in vitro culture of M. tuberculosis took a long time to be achieved, but is nowadays a normal laboratory procedure). MTB is identified microscopically by its staining characteristics: it retains certain stains after being treated with acidic solution, and is thus classified as an "acid-fast bacillus" or "AFB". In the most common staining technique, the Ziehl-Neelsen stain, AFB are stained a bright red which stands out clearly against a blue background. Acid-fast bacilli can also be visualized by fluorescent microscopy, and by auramine-rhodamine stain. The M. tuberculosis complex includes 3 other mycobacteria which can cause tuberculosis: M. bovis, M. africanum, and M. microti. The first two are very rare causes of disease and the last one does not cause human disease. :Nontuberculous mycobacteria (NTM) are other mycobacteria (besides M. leprae which causes leprosy) which may cause pulmonary disease resembling TB, lymphadenitis, skin disease, or disseminated disease. These include Mycobacterium avium, M. kansasii, and others.

The disease

Transmission

TB is spread through aerosol droplets which are expelled when persons with active TB disease cough, sneeze, speak, or spit. Close contacts (people with prolonged, frequent, or intense contact) are at highest risk of becoming infected (typically 22 percent infection rate but everything is possible, even up to 100%). A person with untreated, active tuberculosis can infect an estimated 20 other people per year. Others at risk include foreign-born from areas where TB is common, immunocompromised patients (eg. HIV/AIDS), residents and employees of high-risk congregate settings, health care workers who serve high-risk clients, medically underserved, low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, and people who inject illicit drugs. Transmission can only occur from people with active TB disease (not latent TB infection). The probability of transmission depends upon infectiousness of the person with TB (quantity expelled), environment of exposure, duration of exposure, and virulence of the organism. The chain of transmission can be stopped by isolating patients with active disease and starting effective anti-tuberculous therapy.

Pathogenesis

While only 10 percent of TB infection progresses to TB disease, if untreated the death rate is 51 percent. TB infection begins when MTB bacilli reach the pulmonary alveoli, infecting alveolar macrophages, where the mycobacteria replicate exponentially. Bacteria are picked up by dendritic cells, which can transport bacilli to local (mediastinal) lymph nodes, and then through the bloodstream to the more distant tissues and organs where TB disease could potentially develop: lung apices, peripheral lymph nodes, kidneys, brain, and bone. Tuberculosis is classed 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 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 secrete cytokine such as interferon gamma, which activates macrophages and make them better able to fight infection. T lymphocytes can also directly kill infected cells. Importantly, bacteria are not eliminated with the granuloma, but can become dormant, resulting in a latent infection. Latent infection can be diagnosed only by tuberculin skin test, which yields a delayed hypertype sensitivity response to purified protein derivatives of M. tuberculosis in an infected person. Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis. If TB bacteria gain entry to the blood stream from an area of tissue damage they spread through the body and set up myriad foci of infection, all appearing as tiny white tubercles in the tissues. This is called miliary tuberculosis and has a high case fatality. In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are in continuity with the air passages bronchi. This material may therefore be coughed up. It contains living bacteria and can pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Affected areas are eventually replaced by scar tissue.

Progression

In those people in whom TB bacilli overcome the immune system defenses and begin to multiply, there is progression from TB infection to TB disease. This may occur soon after infection (primary TB disease – 1 to 5 percent) or many years after infection (post primary TB, secondary TB, reactivation TB disease of dormant bacilli – 5 to 9 percent). The risk of reactivation increases with immune compromise, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10 percent per year, while in immune competent individuals, the risk is between 5 and 10 percent in a lifetime. About five percent of infected persons will develop TB disease in the first two years, and another five percent will develop disease later in life. In all, about 10 percent of infected persons with normal immune systems will develop TB disease in their lifetime. Some medical conditions increase the risk of progression to TB disease. In HIV infected persons with TB infection, the risk increases to 10 percent each year instead of 10 percent over a lifetime. Other such conditions include drug injection (mainly because of the life style of IV Drug users), substance abuse, recent TB infection (within two years) or history of inadequately treated TB, chest X-ray suggestive of previous TB (fibrotic lesions and nodules), diabetes mellitus, silicosis, prolonged corticosteroid therapy and other immunosuppressive therapy, head and neck cancers, hematologic and reticuloendothelial diseases (leukemia and Hodgkin's disease), end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption syndromes, or low body weight (10 percent or more below the ideal). Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of causing a latent infection to become active due to the importance of this cytokine in the immune defense against TB. TB disease most commonly affects the lungs (75 percent or more), where it is called pulmonary TB. Symptoms include a productive, prolonged cough of more than three weeks duration, chest pain, and hemoptysis. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, and easy fatigability. The term consumption arose because sufferers appeared as if they were "consumed" from within by the disease. People from Asian and African descent may have more often lymph node TB than Caucasians. Extrapulmonary sites include the pleura, central nervous system (meningitis), lymphatic system (scrofula of the neck), genitourinary system, and bones and joints (Pott's disease of the spine). An especially serious form is "disseminated", or "miliary" TB, so named because the lung lesions so-formed resemble millet seeds on x-ray. These are more common in immunosuppressed persons and in young children. Pulmonary TB may co-exist with extrapulmonary TB.

Drug resistance

Drug-resistant TB is transmitted in the same way as drug-susceptible TB. Primary resistance develops in persons initially infected with resistant organisms. Secondary resistance (acquired resistance) may develop during TB therapy due to inadequate treatment regimen, not taking the prescribed regimen appropriately or using low quality medication.

Diagnosis

A complete medical evaluation for TB includes a medical history, a physical examination, a tuberculin skin test, a serological test, a chest X-ray, and microbiologic smears and cultures. The measurement of a positive skin test depends upon the person's risk factors for progression of TB infection to TB disease. :See: tuberculosis diagnosis, tuberculosis radiology

Treatment

Persons with TB infection (class 2 or class 4 TB), but who do not have TB disease (class 3 or class 5 TB), cannot spread the infection to other people. TB infection in a person who does not have TB disease is not considered a case of TB and is often referred to as latent TB infection (LTBI). This distinction is important because treatment options will be different for a person who has LTBI instead of active TB disease. :See: tuberculosis treatment

Prevention

Prevention and control efforts include three priority strategies:
- identifying and treating all persons who have TB disease
- finding and evaluating persons who have been in contact with TB patients to determine whether they have TB infection or disease, and treating them appropriately, and
- testing high-risk groups for TB infection to identify candidates for treatment of latent infection and to ensure the completion of treatment. In tropical areas where the incidence of atypical mycobacteria is high, exposure to nontuberculous mycobacteria gives some protection against TB.

BCG vaccine

Many countries use BCG vaccine as part of their TB control programs, especially for infants. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is high (greater than 80 percent). However, the protective efficacy for preventing pulmonary TB in adolescents and adults is variable, from 0 to 80 percent. In the United Kingdom, children aged 10-14 were typically immunized during school until 2005. (Routine BCG vaccination was stopped as it was no longer cost-effective. The incidence of TB in people born in the UK, and with parents and grandparents who were born in the UK, was at an all time low, and falling. Others continue to be offered BCG vaccination.) The effectiveness of BCG is much lower than in areas where mycobacteria are much less prevalent. In the USA, BCG vaccine is not routinely recommended except for selected persons who meet specific criteria:
- Infants or children with negative skin-test result who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to multidrug-resistant TB.
- Healthcare workers considered on individual basis in settings in which high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and not successful.

Tuberculosis vaccine

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). [http://www2.niaid.nih.gov/newsroom/releases/corixatbvac.htm] A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protecting against re-infection in mice; it may take four to five years to be available in humans. PMID 15690060. Because of the limitations of current vaccines, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.

Animals

Tuberculosis can be carried by many mammals. Domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers. As a result, many places have regulations restricting the ownership of novelty pets, possibly including such partially domesticated species as pet skunks; for example, the Canadian province of Quebec forbids the owning of hedgehogs as pets, and the American state of California forbids the ownership of pet gerbils. The strictness of such restrictions generally depends on the public health policies adopted for fighting tuberculosis. 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 both the Republic of Ireland and Northern Ireland, badgers have been identified as a vector species for the transmission of bovine tuberculosis. As a result, the government in both regions has mounted an active campaign of eradication of the species in an effort to reduce the incidence of the disease. Badgers have been culled primarily by snaring and gassing. It remains a contentious issue, with proponents and opponents of the scheme citing their own studies to support their position. [http://www.agriculture.ie/index.jsp?file=animal_health/TB.xml] [http://news.bbc.co.uk/1/hi/northern_ireland/4044897.stm] [http://www.badger-killers.co.uk/Ireland/Ireland_news.html]

History

Tuberculosis has been present in humans since antiquity, as the origins of the disease are in the first domestication of cattle (which also gave humanity viral poxes). Skeletal remains show prehistoric humans (4000 BC) had TB and tubercular decay has been found in the spines of Egyptian mummies from 3000-2400 BC. There were references to TB in India around 2000 BC and TB was present in The Americas from about 2000 BC Phthisis is a Greek term for consumption. Around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times which was almost always fatal. Due to the variety of its symptoms, TB was not identified as a unified 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 hopes of curing the disease with the constant temperature and purity of the cave air. The first TB sanatorium opened in 1859 in Poland, with another opening in the United States in 1885. The bacillus-causing tuberculosis, Mycobacterium tuberculosis, was described on March 24, 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine for this discovery in 1905. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which held back the recognition of infected milk as a source of infection. Later, this source was eliminated by pasteurization. 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 by von Pirquet for a test for pre-symptomatic tuberculosis. The first genuine success in immunizing against tuberculosis developed from attenuated bovine strain tuberculosis by Albert Calmette and Camille Guerin in 1906 was BCG (Bacillus of Calmette and Guerin). It was first used on humans on July 18, 1921 in France, although national arrogance prevented its widespread use in either the USA, Great Britain, or Germany until after World War II. Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as the endemic disease of the urban poor. In 1815 England one in four deaths were of consumption; by 1918 one in six deaths in France were still caused by TB. 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 rather resembled prisons. Whatever the purported benefits of the fresh air and labor in the sanatoria, 75% of those who entered were dead within five years (1908). In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons. In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics, although the disease's significance was still such that when the Medical Research Council was formed in Britain in 1913 its first project was tuberculosis. It was not until 1946 with the development of the antibiotic streptomycin that treatment rather than prevention became a possibility. Prior to then only surgical intervention was possible as supposed treatment (other than sanatoria), including the pneumothorax technique: collapsing an infected lung to "rest" it and allow lesions to heal, which was an accomplished technique but was of little benefit and was discontinued after 1946. Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, TB cases in Britain, numbering around 50,000 in 1955, had fallen to around 5,500 in 1987, but in 2001 there were over 7,000 confirmed cases. Due to the elimination of public health facilities in New York in the 1970s, there was a resurgence in the 1980s. The number of those failing to complete their course of drugs was very high. NY had to cope with more than 20,000 "unnecessary" TB-patients with many multi-drug resistant strains (i.e., 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. In 2003, by disabling a set of genes, researchers accidentally created a more lethal and rapidly reproducing strain of tuberculosis bacteria. Christmas Seals was started in 1904 in Denmark as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907-08 to help the National Tuberculosis Association, later called the American Lung Association. During the Industrial Revolution, tuberculosis was more commonly thought of 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 the cause of this was the original victim was draining the life from his/her family members. To cure this, people would dig up the body of what they thought was the vampire, open the chest and burn the heart, sometimes with the rest of the body. Furthermore, people who had TB exhibited symptoms similar to what people considered vampire traits (and may be where much of the common mythology of the vampire comes from) . People with TB often had symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin and would cough blood (which people often figured needed to be replenished because of the loss in this manner, i.e. sucking blood).

Tuberculosis in art, literature, history and film

It has been speculated that the real-life ubiquity of illness and death due to tuberculosis affected the portrayal of these issues in European art and literature as well as history. David Brainerd (born: April 20, 1718, died: October 9, 1747) only lived 29 years. His diary has been published and reflects his reliance upon God's faithfulness amidst his battle with consumption. Brainard's diary has proven historically very influential, particularly to the modern Christian missionary movement. He was a close friend of Theologian and Pastor Jonathan Edwards in New England. More information about Brainerd's life can be found detailed by contemporary pastor/theologian John Piper here[http://www.desiringgod.org/library/biographies/90brainerd.html], with Brainerd's diary being found here [http://www.ccel.org/ccel/edwards/works2.ix.html]. The Life and Death of Mr. Badman (1680) by John Bunyan - "Yet the captain of all these men of death that came against him to take him away, was the consumption, for it was that that brought him down to the grave." The pale, "haunted" appearance of tuberculosis sufferers has been seen as an influence on the works of Edgar Allan Poe and in vampire tales. In recent years, this aesthetic has been revived by the "Goth" subculture. The heroine, Mimi, of Puccini's opera La bohème suffers from tuberculosis (a theme carried over in the modern film adaptation Moulin Rouge!). Violetta, heroine of Verdi's La Traviata also dies of the disease. In Jane Eyre by Charlotte Bronte, Jane's best friend in school dies of consumption. It is indicative of the horrible conditions of these types of schools in the 1800s. In Sylvia Plath's novel The Bell Jar, the protagonist Esther's boyfriend Buddy Willard suffers from tuberculosis, much to her liking. Celestine, the heroine of Octave Mirbeau's Diary of a Chambermaid, attempts to contract tuberculosis from her dying lover, Monsieur Georges. In Nicholas Nickleby, by Charles Dickens, Nickleby's faithful companion Smike is beset by tuberculosis. Extensively, in The Magic Mountain, by Thomas Mann, where a three week visit to a sanitarium turns into a seven year sabbatical. Tuberculosis patients were frequent characters in 19th century Russian literature, and even inspired a character type; the consumptive nihilist, examples of which include Bazarov from Ivan Turgenev's Fathers and Sons, Katerina Ivanovna from Fyodor Dostoevsky's Crime and Punishment, Kirillov from Dostoevsky's Demons (aka The Possessed), and Ippolit and Marie from Dostoevsky's The Idiot. The hospitalized mother in the movie My Neighbor Totoro is thought to be suffering from tuberculosis (her ailment is not specifically named in the film, but tuberculosis is cited in the film's novelization). This is an autobiographical reference to the fact that writer/director Hayao Miyazaki's own mother spent several years of his childhood hospitalized with TB. The Sick Child (1886) by Edvard Munch, portrait of his deceased sister Sophie who died of TB at 16. [http://www.museumsnett.no/nasjonalgalleriet/munch/eng/innhold/ngm00839.html] In Hocus Pocus by Kurt Vonnegut, the protagonist contracts TB later in his lifetime. In "Long Day's Journey Into Night" by Eugene O'Neill character Edmund Tyrone is sick with consumption. In the film "Moulin Rouge!", Satine (the beautiful courtesan) is dying from the disease. In the film "Heavenly Creatures", directed by Peter Jackson, Juliet Hulme had TB, and her fear of being sent away 'for the good of her health' played a large role in determining the subsequent actions of herself and Pauline Parker. In the Swedish Film "My Life as a Dog" the protagonist Ingemar deals with his mother suffering from TB. In the Australian novel Seven Little Australians, Judy becomes consumptive after walking from the Blue Mountains to her home. In the 2002 film The Twilight Samurai, the leading character Seibei Iguchi's wife dies of consumption at the beginning of the story. At the end, his opponent tells of the death of his own wife and daughter of consumption. Famous gambler and gunslinger John "Doc" Holliday suffered from tuberculosis until his death in 1887. Doc and his bloody cough were masterfully portrayed by Val Kilmer in the 1993 film Tombstone. Alice Neel (1900-1984), T.B. Harlem, 1940, American. Oil on canvas. JAMA [http://jama.ama-assn.org/cgi/content/extract/293/22/2696 cover] June 8, 2005. Legendary father of country music, Jimmie Rodgers (1897 - 1933) sang the woes of having tuberculosis in the song T.B. Blues (co-written with Raymond E. Hall). Rodgers ultimately died of the disease days after a New York city recording session. Van Morrison's song "TB Sheets" (from the eponymous 1974 album) is about the narrator nursing a girl, who is dying of tuberculosis. The song is a reworking of the TB theme in American blues music. The Catholic Church canonized Saint Therese of the Child Jesus (1873-1897) in 1925, who died of tuberculosis. Holden Caulfield is sent to a sanitarium for potentially having TB in J.D. Salinger's Catcher in the Rye. English Romantic poet John Keats (1795-1821) and some of his family were taken by tuberculosis. In A Moveable Feast, Ernest Hemingway (1899-1961) recounts meeting Ernest Walsh, an Irish poet suffering from TB. "... I looked at him and his marked-for-death look and I thought, you con man conning me with your con."

References

- Core Curriculum on Tuberculosis: What the Clinician Should Know, 4th edition (2000). Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC). ([http://www.cdc.gov/nchstp/tb/pubs/corecurr/default.htm Internet version]updated Aug 2003).
- Joint Tuberculosis Committee of the British Thoracic Society. Control and prevention of tuberculosis in the United Kingdom: Code of Practice 2000. Thorax 2000;55:887-901 ([http://thorax.bmjjournals.com/cgi/content/abstract/55/11/887 fulltext]).
- Thomas Dormandy (1999). The White Death: A History of Tuberculosis. ISBN 0814719279 HB - ISBN 1852853328 PB
- Mountains Beyond Mountains: The Quest of Dr. Paul Farmer, a Man Who Would Cure the World. Tracy Kidder, Random House 2000. ISBN 0812973011. A nonfiction account of treating TB in Haiti, Peru, and elsewhere.
- Ha SJ, Jeon BY, Youn JI, Kim SC, Cho SN, Sung YC. Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis. Gene Ther. 2005 Feb 03; [Epub ahead of print] PMID 15690060
- Blumberg HM, Leonard MK Jr, Jasmer RM. Update on the treatment of tuberculosis and latent tuberculosis infection. JAMA 2005 Jun 8;293(22):2776-84. PMID 15941808
- Nemery B, Yew WW, Albert R, Brun-Buisson C, Macnee W, Martinez FJ, Angus DC, Abraham E. Tuberculosis, nontuberculous lung infection, pleural disorders, pulmonary function, respiratory muscles, occupational lung disease, pulmonary infections, and social issues in AJRCCM in 2004. Am J Respir Crit Care Med. 2005 Mar 15;171(6):554-62. PMID 15753485

External links

Organizations
- [http://www.cdc.gov/nchstp/tb/default.htm Division of Tuberculosis Elimination] Centers for Disease Control and Prevention Fact sheets, data, and other resources
- [http://www.stoptb.org/ The Stop TB Partnership] international organization. World TB Day.
- [http://www.tbcta.org/ The Tuberculosis Coalition for Technical Assistance - TBCTA] The main purpose of TBCTA is to assist the U.S. Agency for International Development (USAID) and its local (public, private, NGO) partners to improve TB control programs and accelerate the implementation of the Directly Observed Treatment Short Course (DOTS) strategy. With other global TB partners, TBCTA contributes to accelerate the pace of DOTS expansion.
- [http://www.who.int/gtb/ World Health Organization Tuberculosis] home page at World Health Organization - Strategy & Operations, Monitoring & Evaluation Other
- [http://www.umdnj.edu/ntbcweb/history.html Brief History of Tuberculosis] from New Jersey Medical School National Tuberculosis Center
- [http://www.cdc.gov/nchstp/tb/faqs/qa.htm Questions and Answers About TB] from the Centers for Disease Control and Prevention, Division of Tuberculosis Elimination
- [http://jama.ama-assn.org/cgi/content/full/284/21/2789 The New White Plague] David Walton; Paul Farmer, MD, PhD msJAMA December 6, 2000
- [http://www.nlm.nih.gov/medlineplus/tuberculosis.html Tuberculosis] from MedlinePlus an excellent resource for the public from US National Library of Medicine
- [http://blogs.cgdev.org/vaccine Vaccines for Development]
- [http://www.healthdiaries.com/news/infectiousdisease/archives/tuberculosis/ Tuberculosis News] Category:Infectious diseases Category:Pulmonology Category:Tuberculosis zh-min-nan:Hì-lô-pēⁿ ko:결핵 ms:Penyakit Batuk Kering ja:結核 simple:Tuberculosis

Leprosy

:This article is about the infectious disease also known as Hansen's disease.
For the malady found in the Hebrew Bible, see the article Tzaraath.
For the album Leprosy by Death see the article Leprosy (album). Leprosy (album) and also died of the disease.]] Leprosy, sometimes known as Hansen's disease, is an infectious disease caused by Mycobacterium leprae, an aerobic, acid fast, rod-shaped mycobacterium. The modern term for the disease is named after the discoverer of the bacterium, Gerhard Armauer Hansen. Sufferers of Hansen's disease have historically been known as lepers, however this term is falling into disuse as a result of the diminishing number of leprosy patients and the pejorative connotations of the term. The terms "leprosy" and "lepers" can also lead to public misunderstanding because the Bible uses these terms in reference to a wide range of incurable skin conditions other than Hansen's disease. Historically, leprosy was an incurable and disfiguring disease. Lepers were shunned and sequestered in leper colonies. Today, leprosy is easily curable by multidrug antibiotic therapy. The main challenges in the eradication of Hansen's disease is in reaching populations that have not yet received multidrug therapy services, improving detection of the disease, and providing patients with high-quality services and affordable drugs. Other than humans, the only animals known to be susceptible to leprosy are the armadillo and mice (on their footpads).

History

Hansen's disease has been recognized as a problem since the beginning of recorded history. It has been reported as early as 1350 BC in Egypt, making it the oldest recorded disease known according to Guinness World Records. Lepers have frequently lived on the edge of society, and the disease was believed for a long time to have been caused by a divine (or demonic) curse or punishment. However, in the Middle Ages it was believed that lepers are cursed by humans, but loved by God. During the Middle Ages, it was believed that leprosy was highly contagious and could be spread by the glance of a leper or an unseen leper standing upwind of healthy people. Nowadays, it is known that leprosy is only weakly contagious. Minorities like the Navarrese agotes or French cagots were accused of being lepers.

Clinical features

The disease is caused by a mycobacterium which multiplies very slowly and mainly affects the skin, nerves, and mucous membranes. The organism has never been grown in bacteriologic media or cell culture, but has been grown in mouse foot pads and more recently in nine-banded armadillos. It is related to M. tuberculosis, the mycobacterium that causes tuberculosis. The difficulty in culturing the organism appears to be due to the fact that the organism is an obligate intra-cellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes mycobacterium family difficult to destroy is apparently also the reason for the extremely slow replication rate. The mode of transmission of Hansen's disease remains uncertain. Most investigators think that M. leprae is usually spread from person to person in respiratory droplets. What is known is that the transmission rate is very low. In addition, it appears that a majority of the population is naturally immune. Also, contrary to popular belief, Hansen's disease does not cause rotting of the flesh; however, due to the body's extensive attempts to rid itself of the bacterium, defense such as inflammation, cytokines, activated macrophages and other mechanisms cause tissue destruction and regeneration leading to excessive growth and eventually horrifying mutilation. This chronic infectious disease usually affects the skin and peripheral nerves but has a wide range of possible clinical manifestations. Patients are classified as having paucibacillary (tuberculoid leprosy) or multibacillary Hansen's disease (lepromatous leprosy). Paucibacillary Hansen's disease is milder and characterized by one or more hypopigmented skin macules. Multibacillary Hansen's disease is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and epistaxis (nose bleeds).

Incidence

According to recent figures from the World Health Organization (WHO) new cases detected worldwide has decreased by approximately 107,000 cases or 21% from 2003 to 2004. This decreasing trend has been consistent for the past three years. In addition the "global registered prevalance" of leprosy was 286,063 cases with 407,791 new cases being detected during 2004. In 1999, the world incidence of Hansen's disease was estimated to be 640,000; and in 2000, 738,284 cases were identified. In 1999, 108 cases occurred in the United States. In 2000, the World Health Organization (WHO) listed 91 countries in which Hansen's disease is endemic, with India, Myanmar, and Nepal having 70% of cases. In 2002, 763,917 new cases were detected worldwide, and in that year the WHO listed Brazil, Madagascar, Mozambique, Tanzania and Nepal as having 90% of Hansen's disease cases. Worldwide, one to two million people are permanently disabled because of Hansen's disease. However, persons receiving antibiotic treatment or having completed treatment are considered free of active infection. Hansen's disease is one of the infectious diseases tracked passively by the Centers for Disease Control and Prevention. Its prevalence in the United States has remained low and relatively stable. There are decreasing numbers of cases worldwide, though pockets of high prevalence continue in certain areas such as Brazil, South Asia (India, Nepal), some parts of Africa (Tanzania, Madagascar, Mozambique) and the western Pacific.

Risk groups

Those having close contacts with patients with untreated, active, predominantly multibacillary disease, and persons living in countries with highly endemic disease are at risk of contracting the disease. Recent research suggests that there is genetic variation in susceptibility. The region of DNA responsible for this variability is also involved in Parkinson's disease, giving rise to current speculation that the two disorders may be linked in some way at the biochemical level.

Asylums

There are still a few leper colonies around the world, in countries such as India and the Philippines. Western humanitarian and church organizations regularly send relief supplies, including handmade "leper bandages" to these colonies. Leper bandages are knitted or crocheted out of cotton, for better breathing than traditional gauze, and more durability—the bandages can be washed, sterilized, and reused. The bandages can be machine made, but the colony inhabitants appreciate handmade bandages. In 2001, government-run leper colonies in Japan came under judicial scrutiny, leading to the determination that the Japanese government had mistreated the patients, and the District Court ordered Japan to pay compensation to former patients. [http://news.bbc.co.uk/1/hi/world/asia-pacific/1350630.stm] In 2002, a formal inquiry into these colonies was set up, and in March of 2005, the policy was strongly denounced. "Japan's policy of absolute quarantine... did not have any scientific grounds." Many children of those with Hansen's disease were executed by staff at colonies up to the 1950s. [http://news.bbc.co.uk/2/hi/asia-pacific/4311679.stm]

Famous Lepers

Baldwin IV, King of Jerusalem

References

- Icon Health Publications. Leprosy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego: Icon Health Publications, 2004. ISBN 0597840067.

External links

- [http://www.who.int/topics/leprosy/en/ Leprosy] - World Health Organization
- [http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hansens_t.htm Hansen's Disease (Leprosy)] - Centers for Disease Control and Prevention
- [http://www.infolep.org INFOLEP Leprosy Information Services]
- [http://bphc.hrsa.gov/nhdp/ National Hansen's Disease Programs (NHDP)] United States Department of Health and Human Services
- [http://bphc.hrsa.gov/nhdp/MEDICAL_TREATMENT_OF_HD_MAIN_PAGE.htm Medical Treatment] - more clinical pictures at [http://bphc.hrsa.gov/nhdp/Classification_for_Treatment.htm Classifications]
- [http://www.leprosy-ila.org/ International Leprosy Association]
- [http://www.leprosyhistory.org/ ILA Global Project on the History of Leprosy]
- [http://www.leprosyjournal.org/lepronline/?request=index-html International Journal of Leprosy and Other Mycobacterial Diseases] online
- [http://www.leahpattison.org/ START - Leprosy Charity]
- BBC News story: [http://news.bbc.co.uk/2/hi/health/4540461.stm Slave trade key to leprosy spread]
- How to make [http://www.bevscountrycottage.com/bandages.html crocheted or knitted tropical sore bandages] Category:Infectious diseases zh-min-nan:Hansen ê pīⁿ ms:Penyakit kusta ja:ハンセン病

Mycobacterium

see text Mycobacterium is the a genus of actinobacteria, given its own family, the Mycobacteriaceae. It includes many pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy. Most mycobacteria are classified into two categories, the fast-growing kind and the slow-growing kind, and most mycobacteria share some common characteristics:
- They are widespread organisms, typically living in water (including tap water treated with chlorine) and food sources.
- They can colonize their hosts without the hosts showing any adverse signs. For example, millions of people around the world are infected with M. tuberculosis but will never know it because they will not develop symptoms.
- All mycobacteria are aerobic and acid fast. As a genus, they share a characteristic cell wall, thicker than in many other bacteria, hydrophobic, waxy and rich in mycolic acids/mycolates. The mycobacterial cell wall makes a substantial contribution to the hardiness of this genus.
- Mycobacterial infections are notoriously difficult to treat. The organisms are hardy and due to their cell wall, which is neither truely gram negative or positive and unique to the family, they are naturally resistant to a number of antibiotics which utilize the destruction of cell walls such as penicillin. Also, because of this cell wall, they can survive long exposure to acids, alkalis, detergents, oxidative bursts, lysis by complement and antibiotics which naturally leads to antibiotic resistance. Most mycobacteria are susceptible to the antibiotics clarithromycin and rifamycin, but antibiotic-resistant strains are known to exist.
- Mycobacteria tend to be fastidious (difficult to culture), sometimes taking over two years to develop in culture. As well as being fastidious, some species also have extremely long reproductive cycles (M. leprae, for example, may take more than 20 days to proceed through one division cycle; E. coli, for comparison, takes only half an hour ), making laboratory culture a slow process.

Medical classification

Mycobacteria can be classified into several major groups for purpose of diagnosis and treatment:
- M. tuberculosis complex which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, and M. micoti
- M. leprae which causes Hansen's disease or leprosy
- Nontuberculous mycobacteria (NTM) are all the other mycobacteria which can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease.

Species

- M. abscessus, which is also a common water contaminant and was until recently thought to be a subspecies of M. chelonae.
- M. africanum
- M. asiaticum
- M. avium complex (MAC), which is a significant cause of death in AIDS patients. This complex also includes M. avium paratuberculosis, which has been implicated in Crohn's disease in humans and Johne's disease in sheep.
- M. bovis
- M. chelonae, which is a common water contaminant and can also infect wounds.
- M. fortuitum
- M. gordonae
- M. haemophilum
- M. intracellulare
- M. kansasii, which can cause life-threatening infections in people with compromised immune systems
- M. lentiflavum
- M. leprae, which causes leprosy
- M. malmoense
- M. marinum
- M. microti
- M. phlei
- M. scrofulaceum
- M. smegmatis
- M. triplex
- M. tuberculosis, which causes tuberculosis
- M. ulcerans, which causes the "Buruli", or "Bairnsdale, ulcer"
- M. uvium
- M. xenopi
Staining

- Fite’s stain
- Ziehl-Neelsen stain
- Kinyoun stain
Reference

- Diagnosis and Treatment of Disease Caused by Nontuberculous Mycobacteria. American Thoracic Society. Am J Respiratory and Critical Care Medicine. Aug 1997 156(2) Part 2 Supplement [http://www.thoracic.org/adobe/statements/nontuberc1-27.pdf PDF format]
See also

- Leprosy (Hansen's disease)
- Tuberculosis Category:Actinobacteria

Genus

In biology, a genus (plural genera) is a grouping in the classification of living organisms having one or more related and morphologically similar species. In the common binomial nomenclature, the name of an organism is composed of two parts: its genus (always capitalized) and a species modifier. An example is Homo sapiens, the name for the human species which belongs to the genus Homo. See scientific classification for more details of this system. The type genus of a taxon is usually the first genus to be named and described. Families, and in plants all taxa up to division, are named after the type genus. The genus and these higher taxa are typified by a specimen that shows the characteristics of the genus. The specimen used to describe this species is preserved as the holotype and designated as a generitype in a zoological museum or a herbarium to be available for further study. A generic name in one kingdom is allowed to bear the same name as a genus or other taxon name in another kingdom (though this is discouraged by the International Code of Zoological Nomenclature). For instance, Anura is a genus of plants in the family Asteraceae and the order of frogs; Aotus is the genus of golden peas and night monkeys; Oenanthe is the genus of wheatears and water dropworts, and Prunella is the genus of accentors and self-heal. It is, however, not allowed for two genera within the same kingdom to have the same name. This explains why the platypus genus is Ornithorhynchus — although the name Platypus was chosen by George Shaw in 1799, that name had already been given to the ambrosia beetle by Johann Friedrich Wilhelm Herbst in 1793. Since beetles and platypuses are both member of the kingdom Animalia, the name Platypus could not be used for both. Johann Friedrich Blumenbach published the replacement name Ornithorhynchus in 1800.

Tuberculosis

The bacterium

The disease

Transmission

Pathogenesis

Progression

Drug resistance

Diagnosis

Treatment

Prevention

BCG vaccine

Tuberculosis vaccine

Animals

History

Tuberculosis in art, literature, history and film

References

External links

X-ray

] ] An X-ray or Röntgen ray is a form of electromagnetic radiation with a wavelength in the range of 10 nanometers to 100 picometers (corresponding to frequencies in the range 30 PHz to 3 EHz). X-rays are primarily used for diagnostic medical imaging and crystallography. X-rays are a form of ionizing radiation and as such can be dangerous.

Physics

X-rays with a wavelength approximately longer than 0.1 nm are called soft X-rays. At wavelengths shorter than this, they are called hard X-rays. Hard X-rays overlap the range of "long"-wavelength (lower energy) gamma rays, however the distinction between the two terms depends on the source of the radiation, not its wavelength: X-ray photons are generated by energetic electron processes, gamma rays by transitions within atomic nuclei. The basic production of X-rays is by accelerating electrons in order to collide with a metal target (tungsten usually). Here the electrons suddenly decelerate upon colliding with the metal target and if enough energy is contained within the electron it is able to knock out an electron from the inner shell of the metal atom and as a result electrons from higher energy levels then fill up the vacancy and X-ray photons are emitted. This causes the spectral line part of the wavelength distribution. There is also a continuum bremsstrahlung component given off by the electrons as they are scattered by the strong electric field near the high Z (proton number) nuclei. Nowadays, for many applications, X-ray production is achieved by synchrotrons (see synchrotron light).

Detectors

Photographic plates

The detection of X-rays is based on various methods. The most commonly known method are a photographic plate and a fluorescent screen. The X-ray photographic plate is frequently used in hospitals to produce images of the internal organs and bones of a patient. The part of the patient to be X-rayed is placed between the X-ray source and the photographic plate to produce what is a shadow of all the internal structure of that particular part of the body being X-rayed. The X-rays are blocked by dense tissues such as bone and pass through soft tissues. Where the X-rays strike the photographic plate it turns black when it is developed. So where the X-rays go through "soft" parts of the body like organs and skin the plate turns black. Contrast compounds containing barium or iodine can be injected in the artery of a particular organ. The contrast compounds strongly block the X-rays and hence the circulation of the organ can be more readily seen. Another method of detecting X-rays is a fluorescent plate. In modern hospitals a special plastic sheet is used in place of the photographic plate. The plastic sheet is read by a scanning laser beam. The resultant image is then stored in a computer. The plastic sheet can be used over and over again.

Geiger counters

Initially, most common detection methods were based on the ionisation of gases, as in the Geiger-Müller counter: a sealed cylinder with a polymer window contains a gas, and a wire, and a high voltage is applied between the cylinder (cathode) and the wire (anode). When an X-ray photon enters the cylinder, it ionizes the gas which becomes conducting, creating a current flow (a kind of flash); this peak of current is detected and is called a "count". When the high voltage between anode and cathode is decreased, the detector is no longer saturated, and the height of the current peak is proportional to the energy of the photon; it is thus called a "proportional counter". Most of time, the cylinder is not sealed but is constantly fed with "fresh gas", is thus called a "flow counter". This proportionality property allows filtering the "interesting" peaks from the noise and other photons, but the resolution in energy is not enough to determine the energy spectrum; such a feature requires a diffracting crystal to first separate the different photons, the method is called wavelength dispersive X-ray spectroscopy (WDX or WDS).

Scintillators

Some materials such as NaI can "convert" an X photon to a visible photon; an electronic detector can be built by adding a photomultiplier. These detectors are called "scintillators", filmscreens or "scintillation counters". The main advantage of using these is that an adequate image can be obtained while subjecting the patient to a much lower dose of X-rays.

Direct semiconductor detectors

Since the 1970s, new semiconductor detectors have been developed (silicon or germanium doped with lithium, Si(Li) or Ge(Li)). X-ray photons are converted to electron-hole pairs in the semiconductor and are collected to detect the X-rays. When the temperature is low enough (the detector is cooled by Peltier effect or best by liquid nitrogen), it is possible to directly determine the X-ray energy spectrum; this method is called energy dispersive X-ray spectroscopy (EDX or EDS); it is often used in small X-ray fluorescence spectrometers. These detectors are sometimes called "solid detectors". Cadmium telluride (CdTe) and its alloy with zinc, cadmium zinc telluride detectors have have an increased sensitivity, which allows lower doses of X-rays to be used. Silicon drift detectors (SDDs), produced by conventional semiconductor fabrication, now provide a cost-effective and high resolving radiation measurement. They replace conventional X-ray detectors, such as Si(Li)s, as they do not need to be cooled with liquid nitrogen.

Scintillator + Semiconductor detectors

With the advent of large semiconductor array detectors it has become possible to design detector systems using a scintillator screen to convert from X-rays to visible light which is then converted to electrical signals in an array detector.

Visibility to the Human Eye

It is commonly thought that X-rays are invisible to the human eye, and for almost all everyday uses of X-rays this may seem true; however, very strictly speaking, it is actually false. In special circumstances, X-rays are in fact visible to the "naked eye". An effect first discovered by Brandes in experimentation a short time after Röntgen's landmark 1895 paper; he reported, after dark adaptation and placing his eye close to an X-ray tube, seeing a faint "blue-gray" glow which seemed to originate within the eye itself.[http://www.orau.org/ptp/articlesstories/invisiblelight.htm] Upon hearing this, Röntgen reviewed his record books and found he in fact, also saw the effect. When placing an X-ray tube on the opposite side of a wooden door Röntgen saw the same blue glow seeming to emanate from the eye itself, but thought his observations were spurious due to the fact that he only saw the effect when he used one type of tube. Later he realized that the tube which created the effect was the only one which produced X-rays powerful enough to make the glow plainly visible and the experiment was thereafter repeated readily. The fact that X-rays are actually faintly visible to the dark-adapted naked eye has largely been forgotten today is probably due to the lack of desire to repeat what we would now see as a recklessly dangerous and harmful experiment with ionizing radiation