Leprosy or Hansen's disease (HD), is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, 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 infection; infection results in tissue loss, so fingers and toes become shortened and deformed as the cartilage is absorbed into the body.
Although 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. Studies have shown that leprosy can be transmitted to humans by armadillos. Leprosy is now known to be neither sexually transmitted nor highly infectious after treatment. Approximately 95% of people are naturally immune and sufferers are no longer infectious after as little as 2 weeks of treatment.
The minimum incubation period reported is as short as a few weeks and this is 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 non-endemic areas. It is generally agreed that the average incubation period is between three and five years.
Leprosy has affected humanity for over 4,000 years, and was well-recognized in the civilizations of ancient China, Egypt, and India. In 1995, the World Health Organization (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy at that time. In the past 20 years, 15 million people worldwide have been cured of leprosy. Although the forced quarantine or segregation of patients is unnecessary in places where adequate treatments are available, many leper colonies still remain around the world in countries such as India (where there are still more than 1,000 leper colonies), China, Romania, Egypt, Nepal, Somalia, Liberia, Vietnam, and Japan. 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. It is now thought that many early cases of leprosy could have been syphilis.
The age-old social stigma, in other words, leprosy stigma associated with the advanced form of leprosy lingers in many areas, and remains a major obstacle to self-reporting and early treatment. Effective treatment for leprosy appeared in the late 1930s with the introduction of dapsone and its derivatives. Leprosy bacilli resistant to dapsone soon evolved and, due to overuse of dapsone, became widespread. It was not until the introduction of multidrug therapy (MDT) in the early 1980s that the disease could be diagnosed and treated successfully within the community.
MDT for multibacillary leprosy consists of rifampicin, dapsone, and clofazimine taken over 12 months. Dosages adjusted appropriately for children and adults are available in all Primary Health Centres in the form of blister packages. Single dose MDT for single lesion leprosy consists of rifampicin, ofloxacin, and minocycline. The move towards single dose treatment strategies has reduced the prevalence of disease in some regions since prevalence is dependent on duration of treatment.
World Leprosy Day was created to draw awareness to leprosy and its sufferers.
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 but they can become numb or diseased as a result of the disease.
Diagnosis in the U.S. is often delayed because health care providers are unaware of leprosy and its symptoms. Early diagnosis and treatment prevents nerve involvement, the hallmark of leprosy, and the disability it causes.
There are many kinds of leprosy but there are common symptoms. These include runny nose, dry scalp, eye problems, and muscle weakness.
Mycobacterium leprae and Mycobacterium lepromatosis are the causative agents of leprosy. M. lepromatosis is a relatively newly identified mycobacterium which was isolated from a fatal case of diffuse lepromatous leprosy in 2008.
An intracellular, acid-fast bacterium, M. leprae is aerobic and rod-shaped, and is surrounded by the waxy cell membrane coating characteristic of Mycobacterium species.
Due to extensive loss of genes necessary for independent growth, M. leprae and M. lepromatosis are unculturable in the laboratory, a factor which leads to difficulty in definitively identifying the organism under a strict interpretation of Koch's postulates. The use of non-culture-based techniques such as molecular genetics has allowed for alternative establishment of causation.
At highest risk are those living in endemic areas with poor conditions such as inadequate bedding, contaminated water and insufficient diet, or other diseases that compromise immune function. However, studies show that, oddly enough, HIV does not increase risk of leprosy infection. Presumably this is because of differences between the modes of immunity involved.
Recent research suggests that there is a defect in cell-mediated immunity that causes susceptibility to the disease. Less than ten percent of the world's population is actually capable of acquiring the disease. The region of DNA responsible for this variability is also involved in Parkinson disease, giving rise to current speculation that the two disorders may be linked in some way at the biochemical level. In early 2003, an international team of scientists conducted a genome scan in Vietnamese multiplex leprosy families and found that susceptibility to leprosy was significantly linked to region q25 on the long arm of chromosome 6. Further confirmation of the chromosome 6 locus was provided by high-resolution linkage mapping in simplex leprosy families. Now, in a continuation of these findings, the team has pinpointed the chromosome 6 susceptibility locus to the 5' regulatory promoter region shared by both the Parkinson's disease gene PARK2 and its co-regulated gene PACRG. According to The Leprosy Mission Canada, most people-–about 95% of the population-–are naturally immune to the disease.
The mechanism of transmission of leprosy is prolonged close contact and transmission by nasal droplet. In addition to humans, leprosy has been observed in nine-banded armadillo, (which, it has recently been confirmed, are among the primary sources of new cases of leprosy in Americans), and three species of primates. The bacterium can also be grown in the laboratory by injection into the footpads of mice. There is evidence that 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. It is estimated that due to genetic factors, only 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 are experiencing a severe allergic reaction 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 that is 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 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 there are reports of acid-fast bacilli being found in the desquamating epithelium (sloughing of superficial layer of skin) of the skin, Weddell et al. had reported in 1963 that they could not find any acid-fast bacilli in the epidermis, even after examining a very large number of specimens from patients and contacts. In a recent study, Job et al. found fairly large numbers of M. leprae in the superficial keratin layer of the skin of lepromatous leprosy patients, suggesting that the organism could exit along with the sebaceous secretions.
The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, particularly that of the ulcerated mucosa. The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000. Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose. Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.
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 and this is 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 non-endemic areas. It is generally agreed that the average incubation period is between three and five years.
The WHO Study Group's report on the Chemotherapy of Leprosy in 1993 recommended two types of standard MDT regimen be adopted. The first was a 24-month treatment for multibacillary (MB or lepromatous) cases using rifampicin, clofazimine, and dapsone. The second was a six-month treatment for paucibacillary (PB or tuberculoid) cases, using rifampicin and dapsone. At the First International Conference on the Elimination of Leprosy as a Public Health Problem, held in Hanoi the next year, the global strategy was endorsed and funds provided to WHO for the procurement and supply of MDT to all endemic countries.
Between 1995 and 1999, WHO, with the aid of the Nippon Foundation (Chairman Yōhei Sasakawa, World Health Organization Goodwill Ambassador for Leprosy Elimination), supplied all endemic countries with free MDT in blister packs, channelled through Ministries of Health. This free provision was extended in 2000 with a donation by the MDT manufacturer Novartis, which will run until at least the end of 2010. At the national level, non-government organizations (NGOs) affiliated to the national programme will continue to be provided with an appropriate free supply of this WHO supplied MDT by the government.
MDT remains highly effective, and patients 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 there is no known resistance to the combined drugs. The Seventh WHO Expert Committee on Leprosy, reporting in 1997, concluded that the MB duration of treatment—then standing at 24 months—could safely be shortened to 12 months "without significantly compromising its efficacy."
Worldwide, two to three million people are estimated to be permanently disabled because of leprosy. India has the greatest number of cases, with Brazil second and Burma third.
In 1999, the world incidence of Hansen's disease was estimated to be 640,000. In 2000, 738,284 cases were identified. In 2000, the World Health Organization (WHO) listed 91 countries in which Hansen's disease 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 Hansen's disease cases.
According to recent figures from the WHO, new cases detected worldwide have 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 prevalence of HD was 286,063 cases; 407,791 new cases were detected during 2004.
In the United States, Hansen's disease is tracked by the Centers for Disease Control and Prevention (CDC), with a total of 166 new cases reported in the U.S. in 2005. Most (100 or 60%) of these new cases were reported in the following states; California, Louisiana, Massachusetts, New York, and Texas. 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.
Although annual incidence—the number of new leprosy cases occurring each year—is important as a measure of transmission, it is difficult to measure in leprosy due to its long incubation period, delays in diagnosis after onset of the disease and the lack of laboratory tools to detect leprosy in its 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 generally unreliable, is very labor-intensive and is seldom done in recording these statistics.