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Pathology => Human Diseases => Leprosy
Leprosy
INTRODUCTION
Leprosy or Hansen's Disease, chronic infectious disease caused by the bacterium Mycobacterium leprae. Leprosy can be treated effectively with several drugs, but if left untreated, the disease can result in severe disfigurement, especially of the feet, hands, and face. It is rarely fatal.
Leprosy has long been one of the most feared diseases worldwide. The stigma attached to leprosy has often caused those who contracted the disease to be shunned by family, friends, and society. For example, in Europe during the Middle Ages (5th century to 15th century), people with leprosy were declared dead and were banished after witnessing their own funeral and symbolic burial. Confined to a leprosarium or forced to wander and beg to survive, these outcasts were required to warn others of their presence with a bell or clapper.
Although leprosy was once widespread throughout the world, today it is primarily a tropical disease. More than 90 percent of leprosy cases occur in just 16 nations, and India and Brazil have the largest numbers of cases. Due to effective treatment and leprosy eradication programs, the prevalence of the disease has declined dramatically in recent years. According to the World Health Organization (WHO), in 1985 there were 5.4 million registered cases of leprosy and an estimated 10 to 12 million total cases worldwide. By 1997, there were only 900,000 registered cases and an estimated 1.2 million total cases of leprosy worldwide. Fewer than 7,000 registered cases of leprosy currently exist in the United States. The vast majority of these patients are immigrants who acquired the disease in their home countries.
CAUSE
Most bacteria that cause disease in humans thrive in the warm environment in the interior of the human body, but the leprosy bacterium prefers to live in cooler surroundings. For this reason, leprosy primarily affects cooler, surface areas of the body, such as the skin, nerves near the skin, and the surface membranes of the nose and mouth. Early in the disease, a principal symptom is skin lesions, light-colored patches of skin that often develop anesthesia, or loss of sensation. Patients may also develop enlarged peripheral nerves, usually near joints such as the wrist, elbow, and knee. These enlarged nerves can sometimes be felt through the skin and may also be tender.
Leprosy has two main forms, known as tuberculoid and lepromatous disease. In tuberculoid leprosy, the skin lesions are few and small, with only a few bacteria present in each. In lepromatous leprosy, the more severe form of the disease, the lesions may be much more widespread and contain many leprosy bacteria. As lepromatous leprosy progresses, hard nodules and folds of skin may form on the face and the nose may collapse, giving a person a characteristic lionlike appearance.
The symptoms of leprosy may be caused by proliferation of the bacteria in lepromatous leprosy or by the body's immune response to the bacteria in tuberculoid leprosy. In both forms of leprosy, there is usually some degree of irreversible nerve damage resulting from either of these two processes. Because of the lack of sensation in affected areas of the skin, people with leprosy often do not notice burns and injuries to their fingers and toes and fail to treat them. These injuries can then become infected with other types of bacteria that cause tissue damage. Gradually, damaged tissue and bone are resorbed by the body, causing the digits to become shorter. However, leprosy does not, as myth would have it, cause parts of the body to fall off. Damage to nerves in the hands and feet may also cause the fingers and toes to become stiff and curl inward, and some patients become unable to walk. Both forms of the disease may also lead to blindness.
Throughout much of history, people believed leprosy to be a highly contagious disease, fearing that merely touching an infected person could spread the disease. Today scientists know that leprosy is not easily transmitted, but they are still not sure how it is spread from person to person. Nasal droplets released when a person with untreated lepromatous disease sneezes may contain large numbers of leprosy bacteria. Conceivably, these released bacteria could infect a new person who inhales the droplets, or the bacteria could invade through a cut or abrasion in the person's skin. Scientists suspect that these processes may be the primary means of spreading the disease, but do not know for certain. In any event, the well-known case of Father Damien, a Belgian missionary who contracted the disease while caring for leprosy patients on the Hawaiian island of Molokai during the late 1800s, appears to be the exception rather than the rule. Only very rarely do health-care workers who care for patients with leprosy develop the disease themselves.
Scientists estimate that less than 5 percent of people who are infected with Mycobacterium leprae actually develop leprosy. In most cases, the immune system easily fights off the infection. Scientists do not know why a few individuals develop the disease while most people are naturally immune. Those who develop leprosy do not have weak immune systems in general-for example, they do not have an increased susceptibility to other infections or to cancer.
Even in people who do develop symptoms, the leprosy bacterium appears to be a relatively weak disease-causing agent. Though the complications of leprosy can be devastating, the disease is rarely fatal. In fact, the symptoms are surprisingly mild given the large numbers of bacteria that are often found in the skin lesions. The leprosy bacterium multiplies very slowly-once every 2 weeks, compared with once every 24 hours for the closely related bacterium that causes tuberculosis, and once every 20 minutes for certain other bacteria. This slow rate of reproduction also means that the disease develops very slowly-2 to 10 or more years can go by before an infected person develops symptoms.
TREATMENT AND PREVENTION
The first effective drug for treating leprosy, called promin, was developed in the mid-1940s by scientists at the United States Public Health Service Hospital in Carville, Louisiana. Within several years, painful daily promin injections were replaced with oral doses of a related drug, called dapsone. By the early 1980s, strains of the leprosy bacterium resistant to dapsone had become widespread, and multidrug therapy, a combination of several medications, became necessary to treat the disease. Three antibiotics, dapsone, rifampin, and clofazimine, are currently used to treat leprosy. The drugs must be taken for a long period, typically six months in cases of tuberculoid leprosy and two years for lepromatous leprosy. Treating leprosy using multidrug therapy is much more effective than using any one drug alone, and this treatment helps ensure that a drug-resistant form of the leprosy bacterium will not develop. These drugs cannot reverse the nerve damage and deformities of the hands, feet, and face that are characteristic of the disease. However, they can often halt the progression of the disease and help prevent it from being passed on to anyone else.
Leprosy treatment can cause severe side effects. These side effects are not the result of antileprosy drugs themselves but of inflammation that develops when large numbers of leprosy bacteria are killed and broken down inside the body. The inflammation must be treated with anti-inflammatory drugs, such as corticosteroids, to minimize additional nerve damage. Some patients develop a reaction known as erythema nodosum leprosum (ENL) after they begin antibiotic treatment. The painful skin sores characteristic of ENL are thought to be a result of abnormal immune reactions to the killed bacteria. Since the 1970s studies have shown that ENL can be effectively treated with the notorious drug thalidomide. This drug does not attack the leprosy bacteria directly but helps relieve the inflammation and heal the skin sores in patients with ENL. In July 1998 the Food and Drug Administration (FDA) approved thalidomide for the treatment of ENL. This approval has been controversial because in the early 1960s the drug was found to cause severe birth defects in thousands of babies born in Europe, where thalidomide was often prescribed for pregnant women suffering from morning sickness.
Currently the only strategy for preventing the spread of leprosy is treatment of existing cases. Development of a test to detect infection with the leprosy bacterium before signs and symptoms appear would bolster this strategy. A vaccine developed to fight tuberculosis, which is caused by a bacterium closely related to the leprosy bacterium, appears to offer some protection against leprosy. Although the vaccine is not very effective against tuberculosis itself, scientists hope that improved antituberculosis vaccines currently being developed will also offer protection against leprosy. In addition, they are continuing to search for a vaccine directed specifically against leprosy.
HISTORY
Leprosy is an ancient disease and is even mentioned in the Old Testament of the Bible. However, these biblical descriptions do not resemble leprosy as we know it today. It is likely that the term referred to a number of different skin ailments that were considered to be a punishment from God for sin and that marked the sufferer as unclean. Authentic descriptions of leprosy are found in documents from India dating back to 600 BC.
Leprosy probably originated in India and was distributed throughout the world by various travelers, including Roman Legionnaires, Crusaders, Spanish conquistadors, Asian seafarers, and Arab, African, and American slave traders. Some historians believe that Alexander the Great's troops brought leprosy from India to Europe during the 300s BC. In Western Europe, the prevalence of leprosy peaked between AD 1100 and 1300, then began to decline as living conditions improved. As recently as 1900 leprosy could be found in northern Europe. Today the disease is found primarily in tropical areas.
Mycobacterium leprae was first identified as the cause of leprosy in 1874 by Gerhard Henrik Armauer Hansen, a Norwegian physician. Hansen was frustrated in his work because he was unable to culture the bacterium in the laboratory-a feat that scientists still have not accomplished today. Although Mycobacterium leprae cannot be grown in laboratory culture dishes, scientists have developed ways to obtain populations of the bacteria for use in scientific studies. The bacteria can grow to a limited extent in the relatively cool hind footpad of the mouse, allowing scientists to test new anti-leprosy drugs. It grows in enormous numbers throughout the body of the nine-banded armadillo, an animal that has a body temperature several degrees cooler than that of humans. In fact, recent studies have shown that, in some areas of Louisiana and Texas, one-quarter of the wild population of armadillos is infected with the leprosy bacterium. Growth of the bacteria in the spleen, liver, and other internal organs can eventually prove fatal for these animals. Scientists do not know whether armadillos can transmit the disease to humans. But even if they can do so, they are not essential in spreading the disease because they do not live in Africa, Asia, or India, where the disease is most prevalent. Although the bacteria will grow in mice and armadillos, neither of these animals develops nerve damage and other symptoms typical of human leprosy. This means that although the animals can help test new drugs or serve as bacteria "factories," they are poor models to help scientists understand how the disease develops in humans.
In 1991 WHO launched a leprosy elimination program to provide multidrug therapy to leprosy patients all over the world. The goal of the program was to reduce the prevalence of leprosy to 1 in 10,000 people in 122 countries by the year 2000. By 1998 the goal had been met in 90 of those countries. However, new leprosy cases have continued to emerge at a rate of 500,000 to 600,000 per year. The disease has proven difficult to eliminate for several reasons. One reason is that scientists do not understand how the bacterium is transmitted from person to person. Also, scientists do not know how to identify people who are infected but have not yet developed the disease. Efforts to eliminate leprosy are also hampered by the stigma still attached to the disease: Many patients are reluctant to seek treatment for fear of being abandoned by their family and ostracized by society in general.
Scientists have made enormous strides in understanding how the leprosy bacterium causes disease, developing an effective treatment that will not lead to drug-resistant bacteria, and preventing or even surgically correcting deformities caused by the disease. Scientific understanding and effective drug therapy have debunked many of the myths surrounding leprosy, and life for most patients today is quite different than it was in Medieval Europe. However, the stigma long associated with the disease does still exist. In some countries, people who develop leprosy are often forced to leave home, and many end up in the slums of large cities, where they must beg to survive. In the United States, some elderly patients continue to live at two leprosaria--at the Gillis W. Long Hansen's Disease Research Center in Louisiana, where antibiotic treatment was begun, and on Molokai island in Hawaii where Father Damien worked-because they fear that the stigma of leprosy may prevent them from being accepted on the outside. Only a better-informed public can eliminate the stigma of the disease.
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