A 24-year-old man from Norway, infected with leprosy, 1886.
|Classification and external resources|
|eMedicine||med/1281 derm/223 neuro/187|
Leprosy //, also known as Hansen's disease (HD), is a chronic infection caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Initially, infections are without symptoms and typically remain this way for 5 to as long as 20 years. Symptoms that develop include granulomas of the nerves, respiratory tract, skin, and eyes. This may result in a lack of ability to feel pain and thus loss of parts of extremities due to repeated injuries. Weakness and poor eyesight may also be present.
The two main types of disease are based on the number of bacteria present: paucibacillary and multibacillary. The two types are differentiated by the number of poorly pigmented, numb skin patches present, with paucibacillary having five or fewer and multibacillary having more than five. The diagnosis is confirmed by finding acid-fast bacilli in a biopsy of the skin or via detecting the DNA by polymerase chain reaction. It occurs more commonly among those living in poverty and is believed to be transmitted by respiratory droplets. It is not very contagious.
Leprosy is curable with treatment. Treatment for paucibacillary leprosy is with the medications dapsone and rifampicin for 6 months. Treatment for multibacillary leprosy consists of rifampicin, dapsone, and clofazimine for 12 months. These treatments are provided for free by the World Health Organization. A number of other antibiotics may also be used. Globally in 2012, the number of chronic cases of leprosy was 189,000 and the number of new cases was 230,000. The number of chronic cases has decreased from some 5.2 million in the 1980s. Most new cases occur in 16 countries, with India accounting for more than half. In the past 20 years, 16 million people worldwide have been cured of leprosy. About 200 cases are reported per year in the United States.
Leprosy has affected humanity for thousands of years. The disease takes its name from the Latin word lepra, which means "scaly", while the term "Hansen's disease" is named after the physician Gerhard Armauer Hansen. Separating people in leper colonies still occurs in countries like India, with more than a thousand; China, with around hundreds; and in Africa. However, most colonies have closed. Leprosy has been associated with social stigma for much of history, which remains a barrier to self-reporting and early treatment. World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy.
- 1 Signs and symptoms
- 2 Cause
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Treatment
- 7 Epidemiology
- 8 History
- 9 Society and culture
- 10 References
- 11 External links
Signs and symptoms
Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes. Contrary to folklore, leprosy does not cause body parts to fall off, although they can become numb or diseased as a result of secondary infections; these occur as a result of the body's defenses being compromised by the primary disease. Secondary infections, in turn, can result in tissue loss causing fingers and toes to become shortened and deformed, as cartilage is absorbed into the body.
M. leprae and M. lepromatosis are the causative agents of leprosy. M. lepromatosis is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008.
Due to extensive loss of genes necessary for independent growth, M. leprae and M. lepromatosis are obligate pathogens, and unculturable in the laboratory, a factor that leads to difficulty in definitively identifying the organism under a strict interpretation of Koch's postulates. The use of nonculture-based techniques such as molecular genetics has allowed for alternative establishment of causation.
While the causative organisms have to date been impossible to culture in vitro, it has been possible to grow them in animals.
Several genes have been associated with a susceptibility to leprosy. Around 95% of people are believed to be naturally immune. Research suggests a defect in cell-mediated immunity causes susceptibility to leprosy. 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.
At highest risk are those living in areas with polluted water and poor diet or people suffering from diseases that compromise immune function. There appears to be little interaction between HIV and the risk of leprosy.
Although the mode of transmission of leprosy remains uncertain, M. leprae is probably spread from person to person in nasal droplets. Leprosy can be transmitted to humans by armadillos. Leprosy is not known to be either sexually transmitted or highly infectious after treatment. Sufferers are no longer infectious after as few as two weeks of treatment.
The precise mechanism of transmission of leprosy is unknown; however, both prolonged close contact and transmission by nasal droplets are thought to be implicated. In addition to humans, leprosy has been observed in the nine-banded armadillo, (which is among the primary sources of new cases of leprosy in the population of North America), and three species of non-human primates. The bacterium can also be grown in the laboratory by injection into the footpads of mice. Some evidence indicates not all people who are infected with M. leprae develop leprosy, and genetic factors have long been thought to play a role, due to the observation of clustering of leprosy around certain families, and the failure to understand why certain individuals develop lepromatous leprosy while others develop other types of leprosy. Due to genetic factors, an estimated 5% of the population is susceptible to leprosy. This is mostly because the body is naturally immune to the bacteria, and those persons who do become infected experience severe allergic reactions to the disease. However, the role of genetic factors is not entirely clear in determining this clinical expression. In addition, malnutrition and prolonged exposure to infected persons may play a role in development of the overt disease.
The most widely held belief is that the disease is transmitted by contact between infected persons and healthy persons. In general, closeness of contact is related to the dose of infection, which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one easily identified, although the incidence among contacts and the relative risk for them appear to vary considerably in different studies. In incidence studies, infection rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu, Philippines to 53 per 1000 per year in part of western India to 55.8 per 1000 per year in a part of southern India.
Two exit routes of M. leprae from the human body often described are the skin and the nasal mucosa, although their relative importance is not clear. Lepromatous cases show large numbers of organisms deep in the dermis, but whether they reach the skin surface in sufficient numbers is doubtful. Although reports have been made of acid-fast bacilli being found in the desquamating epithelium (sloughing of superficial layer of skin) of the skin, researchers reported they could not find any acid-fast bacilli in the epidermis, even after examining a very large number of specimens from patients and contacts. Fairly large numbers of M. leprae were found in the superficial keratin layer of the skin of lepromatous leprosy patients, suggesting the organism could exit along with the sebaceous secretions.
The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, in particular that of the ulcerated mucosa. The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated with counts ranging from 10,000 to 10,000,000. The majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose. Nasal secretions from lepromatous patients could yield as many as 10 million viable organisms per day.
The entry route of M. leprae into the human body is also not definitively known. The skin and the upper respiratory tract are most likely. While older research dealt with the skin route, recent research has increasingly favored the respiratory route. Experimental transmission of leprosy through aerosols containing M. leprae in immune-suppressed mice was accomplished, suggesting a similar possibility in humans. Successful results have also been reported on experiments with nude mice when M. leprae was introduced into the nasal cavity by topical application. In summary, entry through the respiratory route appears the most probable route, although other routes, particularly broken skin, cannot be ruled out.
In leprosy, both the reference points for measuring the incubation period and the times of infection and onset of disease are difficult to define, the former because of the lack of adequate immunological tools and the latter because of the disease's slow onset. Even so, several investigators have attempted to measure the incubation period for leprosy. The minimum incubation period reported is as short as a few weeks based on the very occasional occurrence of leprosy among young infants. The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas, but otherwise living in nonendemic areas. The average incubation period is generally believed to be between three and five years.
Per the World Health Organization, diagnosis in an endemic area is based on one of these cardinal signs:
- Skin lesion consistent with leprosy and with definite sensory loss
- Positive skin smears
Skin lesions can be single or multiple, usually hypopigmented, although occasionally reddish or copper-colored. The lesions may be macules (flat), papules (raised), or nodular. Sensory loss at the skin lesion is important because this feature can help differentiate from other causes of skin lesions such as tinea versicolor.
Thickened nerves are associated with leprosy and can be accompanied by loss of sensation or muscle weakness. However, without the characteristic skin lesion and sensory loss, muscle weakness is not considered a reliable sign of leprosy.
Diagnosis in the U.S. is often delayed because healthcare providers are unaware of leprosy and its symptoms. Early diagnosis and treatment prevent nerve involvement, the hallmark of leprosy, and the disability it causes.
Many kinds of leprosy are known, but some symptoms are common, including runny nose, dry scalp, eye problems, skin lesions, muscle weakness, reddish skin, smooth shiny diffuse thickening of facial skin, ear, and hand, loss of sensation in fingers and toes, thickening of peripheral nerves, and flat nose due to destruction of nasal cartilage. Also, phonation and resonation of sound occurs during speech. Often, atrophy of the testes and impotency happen.
Several different approaches for classifying leprosy exist, but parallels exist.
- The World Health Organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria.("pauci-" refers to a low quantity.)
- The SHAY scale provides five gradations.
- The ICD-10, though developed by the WHO, uses Ridley-Jopling and not the WHO system. It also adds an indeterminate ("I") entry.
- In MeSH, three groupings are used.
|WHO||Ridley-Jopling||ICD-10||MeSH||Description||Lepromin test||Immune target|
borderline tuberculoid ("BT")
|A30.1, A30.2||Tuberculoid||It is characterized by one or more hypopigmented skin macules and anaesthetic patches, where skin sensations are lost because of damaged peripheral nerves that have been attacked by the human host's immune cells.||Positive||bacillus (Th1)|
|Multibacillary||midborderline or borderline ("BB")||A30.3||Borderline||Borderline leprosy is of intermediate severity and is the most common form. Skin lesions resemble tuberculoid leprosy, but are more numerous and irregular; large patches may affect a whole limb, and peripheral nerve involvement with weakness and loss of sensation is common. This type is unstable and may become more like lepromatous leprosy or may undergo a reversal reaction, becoming more like the tuberculoid form.|
|Multibacillary||borderline lepromatous ("BL"),
and lepromatous ("LL")
|A30.4, A30.5||Lepromatous||It 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), but, typically, detectable nerve damage is late.||Negative||plasmid inside bacillus
 (Th2)
A difference in immune response to the tuberculoid and lepromatous forms is seen.
Leprosy may also be divided into::344–346
Medications can decrease the risk of those living with people with leprosy from acquiring the disease and likely those with whom people with leprosy come into contact outside the home. However, concerns are known of resistance, cost, and disclosure of a person's infection status when doing follow-up of contacts, thus the WHO recommends that people who live in the same household be examined for leprosy and only be treated if symptoms are present.
The Bacillus Calmette–Guérin (BCG) vaccine offers a variable amount of protection against leprosy in addition to tuberculosis. It appears to be 26 to 41% effective (based on controlled trials) and about 60% effective based on observational studies with two doses possibly working better than one. Development of a more effective vaccine is ongoing as of 2011.
A number of leprostatic agents are available for treatment. For paucibacillary (PB or tuberculoid) cases, treatment with daily dapsone and monthly rifampicin for six months is recommended. While for multibacillary (MB or lepromatous) cases, treatment with daily dapsone and clofazimine along with monthly rifampicin for twelve months is recommended.
Multidrug therapy (MDT) remains highly effective, and people are no longer infectious after the first monthly dose. It is safe and easy to use under field conditions due to its presentation in calendar blister packs. Relapse rates remain low, and no resistance to the combined drugs is seen.
Globally in 2012, the number of cases of leprosy was 180,000. In 2011, the approximate number of new cases diagnosed was 220,000. The number of cases has decreased significantly from the 1960s to the 2010s.
In 1995, two to three million people were estimated to be permanently disabled because of leprosy. India has the greatest number of cases, with Brazil second and Myanmar third. In 2000, the WHO listed 91 countries in which leprosy is endemic. India, Burma, and Nepal contained 70% of cases. India reports over 50% of the world's leprosy 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 leprosy cases. Although the number of cases worldwide continues to fall, 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.
While the number of cases of leprosy was in the tens of millions in the 1960s, a series of national (The International Federation of Anti-Leprosy Associations) and international (the WHO's "Global Strategy for Reducing Disease Burden Due to Leprosy") initiatives have reduced the total number and the number of new cases the disease.
Although the number of new leprosy cases occurring each year is important as a measure of transmission, it is difficult to measure due to leprosy's long incubation period, delays in diagnosis after onset of the disease, and the lack of laboratory tools to detect it in the very early stages. Instead, the registered prevalence is used. Registered prevalence is a useful proxy indicator of the disease burden, as it reflects the number of active leprosy cases diagnosed with the disease and receiving treatment with MDT at a given point in time. The prevalence rate is defined as the number of cases registered for MDT treatment among the population in which the cases have occurred, again at a given point in time.
New case detection is another indicator of the disease that is usually reported by countries on an annual basis. It includes cases diagnosed with onset of disease in the year in question (true incidence) and a large proportion of cases with onset in previous years (termed a backlog prevalence of undetected cases).
Endemic countries also report the number of new cases with established disabilities at the time of detection, as an indicator of the backlog prevalence. Determination of the time of onset of the disease is, in general, unreliable, is very labor-intensive, and is seldom done in recording these statistics.
Evidence of leprosy dates back to ancient Egypt in 4000 BC and was discussed by Hippocrates in 460 BC. It was recognized in the civilizations of ancient China, Egypt, Israel, and India. The earliest proven human case was verified by DNA taken from the shrouded remains of a man discovered in a tomb next to the Old City of Jerusalem dated by radiocarbon methods to 1–50 AD.
The term leprosy is derived from either the Indo-European term lap, which means the removal of scales, or the Greek word for "scales", lepia. Historically, people infected were often confined against their will in leper colonies and in Medieval Europe were required to carry a bell to identify their presence. Attempted treatments have included arsenic, elephants' teeth, creosote, and mercury.
The causative agent of leprosy, M. leprae, was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in humans. The first effective treatment (promin) became available in the 1940s. In the 1950s, dapsone was introduced. The search for further effective antileprosy drugs led to the use of clofazimine and rifampicin in the 1960s and 1970s. Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance. Multidrug therapy (MDT) combining all three drugs was first recommended by the WHO in 1981. These three antileprosy drugs are still used in the standard MDT regimens.
Leprosy was once believed to be highly contagious and was treated with mercury—all of which applied to syphilis, which was first described in 1530. Many early cases thought to be leprosy could actually have been syphilis. Effective treatment first appeared in the late 1940s. Resistance has developed to initial treatment. Until the introduction of MDT in the early 1980s, the disease could not be diagnosed and treated successfully within the community.
Many English translations of the Bible translate tzaraath as "leprosy," a confusion that derives from the use of the koine cognate "Λέπρα" (which can mean any disease causing scaly skin) in the Septuagint. Ancient sources such as the Talmud (Sifra 63) make clear that tzaraath refers to various types of lesions or stains associated with ritual impurity and occurring on cloth, leather, or houses, as well as skin. It may sometimes be a symptom of the disease described in this article, but has many other causes, as well.
Society and culture
Between 1995 and 1999, the WHO, with the aid of the Nippon Foundation, supplied all endemic countries with free multidrug treatment (MDT) in blister packs, channelled through ministries of health. This free provision was extended in 2000 and again in 2005 with donations by the MDT manufacturer Novartis through the WHO. In the latest agreement signed between the company and the WHO in October 2010, the provision of free MDT by the WHO to all endemic countries will now run until at least the end of 2015. At the national level, nongovernment organizations (NGOs) affiliated with the national programme will continue to be provided with an appropriate free supply of this WHO-supplied MDT by the government.
Stigma in India
People with leprosy in India, like many parts of the world, suffer under some of the worst conditions and stereotypes. Depending on the level of disfigurement, a leper receives varying stigma and ostracism. People with leprosy earn less: 16–44% of them report their pay dropped as a result of having leprosy. Women suffer greater restrictions and social stigma than men. Leprosy prevents mothers from getting too close to their children out of fear they could infect them. In a report, 49% of women stopped breast-feeding their babies as a result of having leprosy. Doctors and other health care providers and NGOs are working hard to educate people about the disease. In one study when leprosy treatment and education were mixed in with the local healthcare program, the attitudes towards the disease were somewhat alleviated as people had a better understanding of it. Now, the disease prevalence has been reduced to less than one per million population in most parts of the country.
- Saint Damien DeVeuster, a Roman Catholic priest from Belgium, ministered to the people with leprosy who had been placed under a government-sanctioned medical quarantine on the island of Molokaʻi in the Kingdom of Hawaiʻi.
- Baldwin IV of Jerusalem was a Christian king of Latin Jerusalem, afflicted with leprosy. Baldwin, and the effects of his disease, were portrayed in the film Kingdom of Heaven.
- Vietnamese poet Han Mac Tu
- Ōtani Yoshitsugu, a Japanese daimyo
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