What is leprosy?

Causes and Symptoms

Leprosy, also known as Hansen’s disease, is caused by the bacterium Mycobacterium leprae (M. leprae). Humans are the only natural host for this bacterium; it can be found only in leprosy victims. Most people who are exposed to this bacterium are unaffected by it; in the remainder, the bacterium grows inside skin and nerve cells, causing a wide range of symptoms that depend upon the person’s immune response to the growth of the bacteria.

M. leprae is an obligate intracellular parasite, which means that it can grow only inside other cells. M. leprae has a unique waxy coating that helps to protect it while it is growing inside human skin and nerve cells. The bacterium grows very slowly, dividing once every twelve days, whereas the average bacterium will divide every twenty to sixty minutes. M. leprae grows best at temperatures slightly below body temperature (37 degrees Celsius). The leprosy bacterium is the only bacterium known to destroy peripheral nerve tissue (nerves that are not a part of the central nervous system) and will also destroy skin and mucous membranes. This bacterium is closely related to the bacterium that causes tuberculosis: Mycobacterium tuberculosis.

Leprosy is not very contagious. Several attempts to infect human volunteers with the bacteria have been unsuccessful. It is believed that acquiring leprosy from an infected person requires prolonged intimate contact with that person, such as living in the same house for a long time. Although the precise mode of transmission of M. leprae bacteria is unclear, it is highly probable that the bacteria are transferred from the nasal or respiratory secretions of the victim to the nasal passages or a skin wound of the recipient.

Once inside a person, M. leprae will grow and reproduce inside skin and nerve cells and destroy tissue. The exact mechanism of tissue destruction is not understood, but it probably results from a combination of nerve damage, massive accumulation of bacteria, and immunological reactions. Because the bacteria grow so slowly, the length of time from infection to appearance of the symptoms (the incubation period) is quite long. The average incubation period is two to seven years, but incubation can range from three months to forty years. Since the bacteria prefer temperatures slightly lower than normal body temperature, symptoms appear first in the cooler parts of the body, such as the hands, fingers, feet, face, nose, and earlobes. In severe cases, symptoms also appear in the eyes and the respiratory tract.

The symptoms associated with leprosy can range from very mild to quite severe, and the symptoms that a person gets depend heavily on that person’s ability to mount a cellular immune response against the bacteria. In a normal infection, the human body is capable of defending itself through two processes of the immune system; the humoral immune response and the cellular immune response. The humoral response produces chemicals called antibodies that can attack and destroy infectious agents that are present in body fluids such as the blood. The cellular response produces white blood cells that can destroy infectious agents that are associated with cells. Since M. leprae hides and grows inside human cells, a cellular response is the only type of immune response that can be of any help in fighting the infection. The ability to generate a cellular immune response against M. leprae is dependent upon the genetic makeup and overall health of the victim, as well as the number of infecting bacteria and their ability to invade the body and cause disease. A quick and strong cellular response by a person infected with M. leprae will result in no symptoms or in the mild form of the disease: tuberculoid leprosy. A
slow or weak cellular response by a person exposed to leprosy may result in the more severe form of the disease: lepromatous leprosy.

Only one in two hundred people exposed to leprosy will get some form of the disease. The earliest symptom is a slightly bleached, flat lesion several centimeters in diameter that is usually found on the upper body or on the arms or legs. About three-fourths of all patients with an early solitary lesion heal spontaneously; the rest progress to tuberculoid or lepromatous leprosy or to one of the many forms that fall between these two extremes.

Tuberculoid leprosy is characterized by flat skin lesions five to twenty centimeters in diameter. The lesions are lighter in color than the surrounding skin and are sometimes surrounded by nodules (lumps). The lesions contain only a few bacteria, and they, along with the surrounding tissue, are numb. These lesions are caused by a hypersensitive cellular immune response to the bacteria in the nerves and skin. In an attempt to destroy the bacteria, the immune system overreacts, and some of the surrounding nerve and skin tissue is damaged while the bacteria are being killed. This causes the areas of the skin to lose pigment as well as sensation. Often, tuberculoid leprosy patients can experience more extensive physical damage if the numbness around the lesions leads to accidental loss of digits, skin, and so forth. Leprosy victims may burn and cut themselves unknowingly, since they have no feeling in certain areas of their bodies.

In lepromatous leprosy, the bacteria grow unchecked because of the weak cellular immune response. Often, there are more than 100 million bacterial cells present per square centimeter of tissue. These bacteria cause the formation of tumorlike growths called lepromas as well as tissue destruction of the skin and mucous membranes. Also, the presence of so many bacteria causes large numbers of antibacterial antibodies to be produced, but these antibodies are of no benefit in fighting off the infection. Instead, they can contribute to the formation of lesions and tissue damage both internally and on the skin through a process called immune complex hypersensitivity. This is a process whereby the large number of antibodies bind to the large number of bacteria in the body and form immune complexes. These complexes can be deposited in various parts of the body and trigger a chemical reaction that destroys the surrounding tissue. The large number of bacteria puts pressure on the nerves and destroys nerve tissue, which causes loss of sensation and tissue death.

The initial symptoms of lepromatous leprosy are skin lesions that can be spread out or nodular and are found on the cooler parts of the body, such as the inside of the nose, the front part of the eye, the face, the earlobes, the hands, and the feet. Often, the victim loses all facial features because the nodules enlarge the face, and the eyebrows and nose deteriorate, giving the victim a characteristic lionlike appearance. Severe lepromatous leprosy erodes bones; thus, fingers and toes become needlelike, pits form in the skull, nasal bones are destroyed, and teeth fall out. Also, the limbs become twisted and the hands become clawed. The destruction of the nerves leads to the inability to move the hands or feet, deformity of the feet, and chronic ulceration of the limbs. In addition, as is the case with tuberculoid leprosy, destruction of the small peripheral nerves leads to self-inflicted trauma and secondary infection (infection by another bacterium or virus). As the disease progresses, the growth of bacteria in the respiratory tract
causes larynx problems and difficult breathing. Deterioration of the optic nerve leads to blindness. Bacteria can invade the bloodstream and spread infection throughout the whole body except the central nervous system. Death associated with leprosy usually results from respiratory obstruction, kidney failure, or secondary infection.

Treatment and Therapy

A physician can tell whether a person has leprosy by looking for characteristic symptoms (light-colored and numb lesions, nodules, and so forth) and by determining whether the patient may have been exposed to someone with leprosy. In addition, samples of scrapings from skin lesions, nasal secretions, fluid from nodules, or other tissue secretions can be examined for the presence of M. leprae. Samples are treated with a procedure called the acid-fast technique. Because of M. leprae’s waxy coating, these bacteria retain a pink stain after being washed in an acid-alcohol mixture, whereas all other bacteria lose the pink stain. Therefore, pink, rod-shaped bacteria observed in samples treated with the acid-fast technique indicate the presence of M. leprae. It is easy to find the acid-fast M. leprae in lepromatous leprosy patients because they have so many bacteria in their lesions, but the bacteria are more difficult to find in the lesions of tuberculoid leprosy patients.

The lepromin test was originally developed to be used as a diagnostic tool for leprosy, in the same way that the tuberculin test is used as a diagnostic tool for tuberculosis. Lepromin, which is heat-killed M. leprae taken from nodules, is injected under the skin in the lepromin test. Two reactions are possible: an early reaction that appears twenty-four to forty-eight hours later and a late reaction that appears three to four weeks later. In both reactions, a hard red lump at the injection site indicates a positive lepromin test. This test is not specific for leprosy, however, because a person who has been exposed to M. leprae, M. tuberculosis, or the tuberculosis vaccine,
Bacillus Calmette-Guérin (BCG), will show a positive early reaction. Even though this test is not useful as a diagnostic tool, it is useful in determining whether a patient has a strong or a weak cellular immune response to M. leprae. Tuberculoid leprosy patients show both the early and late reactions, while lepromatous leprosy patients show no reaction at all.

Leprosy can be treated with antibiotics. The antibiotic dapsone began to be used on a wide scale in the treatment of leprosy in 1950. Since that time, however, many dapsone-resistant strains of M. leprae have appeared. This means that, for some victims, this drug is no longer helpful in fighting the disease. In 1981, in response to the problem of dapsone-resistant strains, the World Health Organization (WHO) recommended a multidrug regimen for leprosy victims. For lepromatous leprosy patients, dapsone, rifampin, and clofazimine are recommended, whereas tuberculoid leprosy patients need take only dapsone and rifampin. For patients who are intolerant of one or more of the standard antibiotics or who suffer from infections unresponsive to these medications, doxycycline and moxifloxacin are additional antibiotics that have been found to be effective. Treatment is expected to continue until skin smears are free from acid-fast bacteria, which can last from two years up to the lifetime of the patient. Since 1989, the US recommendations for tuberculoid leprosy are six months of rifampin and dapsone daily, then dapsone alone for three years. For lepromatous leprosy, the recommendation is to use rifampin and dapsone daily for three years, then dapsone only for the rest of the person’s life.

Often, antibiotics are given to family members of leprosy patients to prevent them from contracting the disease. Antibiotic therapy can make a leprosy victim noncontagious, stop the progress of the disease, and in some cases cause a reversal of some of the symptoms. Until treatment is complete, however, it is recommended that patients sleep in separate bedrooms, use their own linens and utensils, and not live in a house with children. Thus, leprosy victims can lead nearly normal lives without fear of infecting others in the community.

The best ways to keep from getting leprosy are to avoid exposure to leprosy bacteria and to receive antibiotic therapy following exposure. It should be possible to control and, eventually, eliminate leprosy. If every case of leprosy were treated, the disease could not spread and the bacteria would die out with the last leprosy victim. Progress in this direction is slow, however, because of ignorance, superstition, poverty, and overpopulation in areas with many leprosy cases. The first strategy in controlling leprosy is to treat all leprosy cases with antibiotics. As of 1991, about 50 percent of all leprosy victims were not receiving drug therapy. Second, the early detection and rigid isolation of lepromatous leprosy patients are important, as is preventive antibiotic therapy for individuals in close contact with those patients. Finally, even in the early twenty-first century, too many countries lack adequate basic health resources, and too many patients disabled by leprosy are not receiving adequate care. The development of a vaccine for leprosy would aid control efforts.

A global effort for the production of a vaccine for leprosy is being made under the auspices of WHO. The first problem with vaccine development is that, until recently, it was not possible to grow M. leprae bacteria outside a leprosy victim; therefore, not much is known about the nature of the bacteria. Even though this bacterium was the first to be associated with a disease, it cannot be grown on an artificial laboratory medium, whereas nearly all other bacteria known can be grown artificially. It was not until 1960 that scientists at the Centers for Disease Control (CDC) discovered that the bacterium could be grown in the footpads of mice. Finally, in 1969, scientists at the National Hansen’s Disease Center in Carville, Louisiana, found that the bacteria would grow in the tissues of the nine-banded armadillo. Several potential vaccines for leprosy have been tested since that time. One vaccine being tested is BCG, a live bacterial vaccine of the bacteria Mycobacterium bovis, which is a close relative of M. leprae. In four major trials with BCG, a range of 20 to 80 percent protection from leprosy was obtained. It is not known why there was such a wide variation in results. Recent strategies for vaccine development include making a modified BCG that contains M. leprae cell wall antigens. It is more advantageous to use BCG than M. leprae in a vaccine because BCG is much easier to grow. In addition, scientists are trying to find a way to grow M. leprae artificially so that larger quantities will be available to be used for a vaccine. In 1999, WHO set up a strategic plan titled “The Final Push Toward Leprosy Elimination: 2000–2005” and the Global Alliance for the Elimination of Leprosy was launched.

Perspective and Prospects

Leprosy is one of the oldest known diseases. References to leprosy are contained in Indian writings that are more than three thousand years old. The Bible refers to leprosy and the isolation of lepers, although the term refers to other skin diseases as well. The examination of ancient skeletons has provided insights into how leprosy spread in past centuries. Early evidence suggests that the disease was highly contagious and that leprosy was widespread in Europe during the Middle Ages. Leprosy was so prevalent, in fact, that both governments and churches moved to deal with the problem. At that time, the cause of leprosy was unknown, and the disease was generally believed to be a punishment for some personal sin. Lepers were treated as outcasts and required to shout “unclean.” They were required to wear gloves and distinctive clothes and carry a bell or clapper to warn people of their approach. They were forbidden to drink from public fountains, speak loudly, eat with healthy people, or attend church. Some lepers were even pronounced legally dead, burned at the stake, or buried alive. Later, they were isolated in asylums called leprosaria, and at one time about nineteen thousand leprosaria existed—mostly in France.

There was a sharp decrease in the number of leprosy cases in the sixteenth century. Several factors may have contributed to this decline, including the isolation of lepers, a better diet, warmer clothes, the plague epidemic, and the increase in tuberculosis, which may have provided resistance to leprosy. Leprosy is no longer as deadly or contagious as it once was, yet the stigma attached to this disease has remained. In an effort to alleviate the social stigma, the Fifth International Congress on Leprosy in 1948 banned the use of the word leper and encouraged the use of the term Hansen’s disease instead of leprosy. M. leprae, the causative agent of leprosy, was first identified in the tissues of leprosy patients by the Norwegian physician Gerhard Armauer Hansen in 1873—hence the alternate name, Hansen’s disease. Today, victims of leprosy are referred to as Hansenites or Hansenotic.

From the 1960s to the 1980s, estimates of the number of cases of leprosy worldwide ranged from 10 to 12 million. In 2001, at the Fifty-fourth World Health Assembly, it was announced that the global prevalence of leprosy had fallen to below one case per ten thousand by the end of 2000 and health experts believed that eliminating leprosy in all countries was an attainable goal by the year 2005. More than 600,000 new cases of leprosy were reported globally in 2002. A new combination of drugs known as multidrug therapy has been used to treat and completely cure patients. The drugs are donated free through foundations, and since these donations began in 2000, millions of the “blister packs,” each of which provides one month’s treatment to one patient, have been shipped. By 2008, some countries had achieved elimination, but leprosy remained endemic in others. And, although the disease has not been completely eliminated, its incidence has decreased dramatically. The World Health Organization reports that, worldwide, about 219,000 new cases of leprosy were reported in 2011 and that about 182,000 people had the disease in early 2012.

Leprosy is prevalent in tropical areas such as Africa, Southeast Asia, and South America. In the United States, most cases occur in Hawaii and small parts of Texas, California, Louisiana, and Florida. The number of new cases in the United States annually—mostly from foreign-born immigrants from leprosy-prone areas—has been very low in the last several decades.

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