Leprosy | cause | leprosy continuum | Treatment of leprosy | leprosy vaccine Resources
Leprosy, also called Hansen’s disease, is responsible for active disease or disability in about four million people worldwide. Caused by an unusual bacterium called Mycobacterium leprae, leprosy primarily affects humans. Leprosy is found in tropical areas, such as Africa, South and Southeast Asia, and Central and South America. In the United States, cases of leprosy have been reported in areas of Texas, California, Louisiana, Florida, and Hawaii. Leprosy can take many forms, but the most familiar form is characterized by skin lesions and nerve damage. Although active leprosy is curable with various antibiotic drug therapies, it remains a devastating illness because of its potential to cause deformity, especially in the facial features.
The cause of leprosy
M. leprae is an unusual bacterium for several reasons. The bacterium divides very slowly; in sometests, researchers have noted a dividing time of once every twelve days. This differs from the dividing time of most bacteria, which is once every few hours. M. leprae cannot be grown on culture media, and is notoriously difficult to culture within living animals. Because of these culturing difficulties, researchers have not been able to investigate these bacteria as closely as they have other, more easily cultured, bacteria. Questions remain unanswered about M. leprae; for instance, researchers are still unclear about how the bacteria are transmitted from one person to another, and are studying the role an individual’s genetic makeup plays in contracting and the progression of the disease.
Because M. leprae almost exclusively infects humans, animal models for studying leprosy are few. Surprisingly, a few species of armadillo can also be infected with M. leprae. Wild armadillos have been appearing with a naturally occurring form of leprosy. If the disease spreads in the armadillo population, researchers will not be able to use these animals for leprosy studies, since study animals must be completely free of the disease as well as the bacteria that cause it. Mice have also been used to study leprosy, but laboratory conditions, such as temperature, must be carefully controlled in order to sustain the infection in mice.
Scientists have been able to determine some facts about M. leprae from their experiments. M. lepraeis temperature-sensitive; it favors temperatures slightly below normal human body temperature. Because of this predilection, M. leprae infects superficial body tissues such as the skin, bones, and cartilage, and does not usually penetrate to deeper organs and tissues. M. leprae is an intracellular pathogen; it crosses host cell membranes and lives within these cells. Once inside the host cell, the bacterium reproduces. The time required by these slow-growing bacteria to reproduce themselves inside host cells can be anywhere from a few weeks to as much as 40 years. Eventually, the bacteria lyse (burst open) the host cell, and new bacteria are released that can infect other host cells.
Researchers assume that the bacteria are transmitted via the respiratory tract. M. leprae exists in the nasal secretions and in the material secreted by skin lesions of infected individuals. M. leprae may be transmitted by breathing in the bacteria, through breaks in the skin, or perhaps through breast-feeding.
The leprosy continuum
Leprosy exists in several different forms, although the infectious agent for all of these forms is M. leprae. Host factors such as genetic make up, individual immunity, geography, ethnicity, and socioeconomic circumstances determine which form of leprosy is contracted by a person exposed toM. leprae. Interestingly, most people who come in contact with the bacterium— about three-fourths—never develop leprosy, or develop only a small lesion on the trunk or extremity that heals spontaneously. Most people, then, are not susceptible to M. leprae, and their immune systems function effectively to neutralize the bacteria. But one-fourth of those exposed to M. leprae contract the disease, which may manifest itself in various ways.
Five forms of leprosy are recognized, and a person may progress from one form to another. The least serious form is tuberculoid leprosy. In this form, the skin lesions and nerve damage are minor. Tuberculoid leprosy is evidence that the body’s cellular immune response—the part of the immune system that seeks out and destroys infected cells—is working at a high level of efficiency. Tuberculoid leprosy is easily cured with antibiotics.
If tuberculoid leprosy is not treated promptly, or if a person has a less vigorous cellular immune response to the M. leprae bacteria, the disease may progress to a borderline leprosy, which is characterized by more numerous skins lesions and more serious nerve damage. The most severe form of leprosy is lepromatous leprosy. In this form of leprosy, the skin lesions are numerous and cause the skin to fold, especially the skin on the face. This folding of facial skin leads to the leonine (lionlike) features typical of lepromatous leprosy. Nerve damage is extensive, and people with lepromatous leprosy may lose the feeling in their extremities, such as the fingers and toes. Contrary to popular belief, the fingers and toes of people with this form of leprosy do not spontaneously drop off. Rather, because patients cannot feel pain because of nerve damage, the extremities can become easily injured. Sometimes these injuries are severe, and fingers and toes are cut off by sharp objects which the patient cannot even detect.
Lepromatous leprosy occurs in people who exhibit an efficient antibody response to M. leprae but an inefficient cellular immune response. The antibody arm of the immune system is not useful in neutralizing intracellular pathogens such as M. leprae; therefore, people who initially react to invasion by M. leprae by making antibodies may be at risk for developing more severe forms of leprosy. Researchers are not sure what determines whether a person will react with a cellular response or an antibody response; current evidence suggests that the cellular immune response may be controlled by a special gene. If a person has this gene, he or she will probably develop the less severe tuberculoid leprosy if exposed to M. leprae.
Treatment of leprosy
Treatments for leprosy have improved considerably over the past 40 years and contributed to the rapid decline of the disease. Beginning in the 1950s, an antibiotic called dapsone was used to treat leprosy, offering the first hope of a cure for persons with the disease. Dapsone’s main disadvantage was that the patient had to take the medication daily throughout his or her lifetime. In addition, the M. leprae in some patients underwent genetic mutations that rendered it resistant to the antibiotic. In the 1980s, the problem of resistance was tackled with the advent of multidrug therapy. Bacteria are less likely to become resistant to drugs given in combination. The new multidrug treatment time was also considerably shorter. Currently, mutidrug therapy (MDT) with rifampin, clofazimine, and dapsone for six months to one year is the standard.
One risk of treatment, however, is that antigens-the proteins on the surface of M. leprae that initiate the host immune response—are released from the dying bacteria. In some people, when the antigens combine with antibodies to M. leprae in the bloodstream, a reaction called erythema nodosum leprosum may occur, resulting in new lesions and peripheral nerve damage. Some leprosy experts are experimenting with the drug thalidomide to treat this reaction, with good results. But because thalidomide causes severe birth defects, women of childbearing age must be carefully monitored while taking the drug.
KEY TERMS
Antibody response— The part of the immune system that marks foreign cells, such as bacteria, for destruction by other immune cells.
Cellular immune response— The part of the immune system that destroys infected cells.
Lepromatous leprosy— The most severe form of leprosy, characterized by numerous lesions and extensive nerve damage.
Resistance— In bacteria, the acquisition of genetic mutations that render the bacteria invulnerable to the action of antibiotics.
Tuberculoid leprosy— The least severe from of leprosy, characterized by a few skin lesions and little nerve damage.
A leprosy vaccine?
An effective, readily available, and reliable vaccine to protect against leprosy does not yet exist. One vaccine tested in Venezuela combined a vaccine originally developed against tuberculosis, called Bacille Calmette-Guerin (BCG), and heat-killed M. leprae cultured from infected armadillos. Another vaccine tested in India used a relative of M. leprae called M. avium. The advantage of this vaccine is that M. avium is easy to culture on media and is thus, cheaper than the Venezuelan vaccine. Both vaccines have shown mixed results in human trials. The latest strategy involves testing plasmid DNA vaccines in mice with the goal of creating immunity against both leprosy and tuberculosis simultaneously.
See also Antibody and antigen.
Resources
BOOKS
Guld, Tony. A Disease Apart: Leprosy in the Modern World. New York: St. Martin’s Press, 2005.
Tayman, John. The Colony: The Harrowing True Story of the Exiles of Molokai. New York, Scribner’s, 2006.
OTHER
World Health Organization. “Leprosy Today.” <http://www.who.int/lep/en/> (accessed November 26, 2006).
Kathleen Scogna
