Leprosy
Leprosy, also known as Hansen's disease, is a long-term infection by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damage may result in the loss of nociception, which can lead to the loss of parts of a person's extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and loss of eyesight. Leprosy symptoms may begin within one year or take 20 years or more.
Leprosy is spread between people, although extensive contact is necessary. Leprosy has a low pathogenicity, and 95% of people who contract or who are exposed to M. leprae do not develop the disease. Spread is likely through a cough or contact with fluid from the nose of a person infected by leprosy. Genetic factors and baseline immune function play a role in how easily a person catches the disease. Leprosy is not spread during pregnancy to the unborn child or through sexual contact. There are two main types of the disease—paucibacillary and multibacillary, which differ in the number of bacteria present. A person with paucibacillary disease has five or fewer poorly pigmented, numb skin patches, while a person with multibacillary disease has more than five skin patches. The diagnosis is confirmed by finding acid-fast bacilli in a biopsy of the skin.
Leprosy is curable with multidrug therapy. Treatment of paucibacillary leprosy is with the medications dapsone, rifampicin, and clofazimine for six months. Treatment for multibacillary leprosy uses the same medications for 12 months. Several other antibiotics may also be used. These treatments are provided free of charge by the World Health Organization.
Leprosy is not highly contagious. People with leprosy can live with their families and attend school and work. In the 1980s, there were 5.2 million cases globally, but by 2020 this decreased to fewer than 200,000. Most new cases occur in one of 14 countries, with India accounting for more than half of all new cases. In the 20 years from 1994 to 2014, 16 million people worldwide were cured of leprosy. Separating people affected by leprosy by placing them in leper colonies is not supported by evidence but still occurs in some areas of India, China, Japan, Africa, and Thailand.
Leprosy has affected humanity for thousands of years. The disease takes its name from the Greek word , from , while the term "Hansen's disease" is named after the Norwegian physician Gerhard Armauer Hansen. Leprosy has historically been associated with social stigma, which continues to be a barrier to self-reporting and early treatment. Leprosy is classified as a neglected tropical disease. World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy.
The study of leprosy and its treatment is known as leprology.
Signs and symptoms
Common symptoms present in the different types of leprosy include a rhinorrhea; dry scalp; vision problems; skin lesions; muscle weakness; reddish skin; smooth, shiny, diffuse thickening of facial skin, ear, and hand tissues; loss of sensation in fingers and toes; thickening of peripheral nerves; a flat nose from the destruction of nasal cartilage; and changes in phonation and other aspects of speech production. In addition, atrophy of the testes and erectile dysfunction may occur.Leprosy onset varies between individuals. The average incubation period is five years, but the infected may begin to notice symptoms within the first year or up to 20 years after infection. Oftentimes, the first noticeable sign of leprosy is the development of pale or pink-coloured patches of skin that may be insensitive to temperature or pain. Patches of discolored skin are sometimes accompanied or preceded by nerve problems, including numbness or tenderness in the hands or feet. Secondary infections can result in tissue loss, causing fingers and toes to become shortened and deformed as cartilage is absorbed into the body. Baseline immune function drives at least some parts of pathogenesis variability.
Approximately 30% of individuals affected by leprosy experience nerve damage. The nerve damage sustained is reversible when treated early, but becomes permanent when appropriate treatment is delayed by several months. Damage to nerves may cause loss of muscle function, leading to paralysis. It may also lead to sensation abnormalities or numbness, leading to additional infections, ulcerations, and joint deformities.
Cause
''Mycobacterium leprae'' and ''M. lepromatosis''
Mycobacterium leprae and Mycobacterium lepromatosis are the mycobacteria that cause leprosy. M. lepromatosis is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008. M. lepromatosis is indistinguishable clinically from M. leprae. M. leprae is an aerobic, rod-shaped, acid-fast bacterium with a waxy cell envelope characteristic of the genus Mycobacterium. M. leprae and M. lepromatosis are obligate intracellular pathogens and cannot grow or be cultured outside of host tissues. However, they can be grown using research animals such as mice and armadillos.Naturally occurring infections have been reported in nonhuman primates, armadillos, and red squirrels. Multilocus sequence typing of the armadillo M. leprae strains suggests that they were of human origin for at most a few hundred years. Thus, it is suspected that armadillos first acquired the organism incidentally from early European explorers of the Americas. This incidental transmission was sustained in the armadillo population. It may be transmitted back to humans, making leprosy a zoonotic disease.
Red squirrels, a threatened species in Great Britain, were found to carry leprosy in November 2016. It has been suggested that the trade in red squirrel fur, highly prized in the medieval period and intensively traded, may have been responsible for the leprosy epidemic in medieval Europe. A pre-Norman era skull excavated in Hoxne, Suffolk, in 2017 was found to carry DNA from a strain of M. leprae which closely matched the strain carried by modern red squirrels on Brownsea Island.
Risk factors
The greatest risk factor for developing leprosy is contact with another person infected with leprosy. People who are exposed to a person who has leprosy are 5–8 times more likely to develop leprosy than members of the general population. Leprosy occurs more commonly among those living in poverty. Not all people who are infected with M. leprae develop symptoms.Conditions that reduce immune function, such as malnutrition, other illnesses, or genetic mutations, may increase the risk of developing leprosy. Infection with HIV does not appear to increase the risk of developing leprosy. Certain genetic factors in the person exposed have been associated with developing lepromatous or tuberculoid leprosy.
Transmission
Transmission of leprosy occurs during close contact with those who are infected. Transmission of leprosy is through the upper respiratory tract. Older research suggested the skin as the main route of transmission, but research has increasingly favored the respiratory route. Transmission occurs through inhalation of bacilli present in upper airway secretion.Leprosy is not sexually transmitted and is not spread through pregnancy to the unborn child. The majority of people who are exposed to M. leprae do not develop leprosy; casual contact such as shaking hands and sitting next to someone with leprosy does not lead to transmission. People are considered non-infectious 72 hours after starting appropriate multi-drug therapy. Two exit routes of M. leprae from the human body that are 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. Humans can acquire a leprosy infection from armadillos by handling them or consuming armadillo meat. The mechanism is not fully understood.
Genetics
Not all people infected or exposed to M. leprae develop leprosy, and genetic factors are suspected to play a role in susceptibility to an infection. Cases of leprosy often cluster in families, and several genetic variants have been identified. In many who are exposed, the immune system can eliminate the leprosy bacteria during the early infection stage before severe symptoms develop. A genetic defect in cell-mediated immunity may cause a person to be susceptible to develop leprosy symptoms after exposure to the bacteria. 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 at the biochemical level.Pathogenesis
Most leprosy complications are the result of nerve damage. The nerve damage occurs due to direct invasion by the M. leprae bacteria and a person's immune response, resulting in inflammation. The molecular mechanism underlying how M. leprae produces the symptoms of leprosy is not clear, but M. leprae has been shown to bind to Schwann cells, which may lead to nerve injury including demyelination and a loss of nerve function. Numerous molecular mechanisms have been associated with this nerve damage including the presence of a laminin-binding protein and the glycoconjugate on the surface of M. leprae that can bind to laminin on peripheral nerves.As part of the human immune response, white blood cell-derived macrophages may engulf M. leprae by phagocytosis. In the initial stages, small sensory and autonomic nerve fibers in the skin of a person with leprosy are damaged. This damage usually results in hair loss to the area, a loss of the ability to sweat, and numbness. Further peripheral nerve damage may result in skin dryness, more numbness, and muscle weakness or paralysis in the affected area. The skin can crack, and if the skin injuries are not carefully cared for, there is a risk for a secondary infection that can lead to more severe damage.