Mycobacterium leprae is an unusual bacterium for several

reasons. The bacterium divides slowly; in some tests,

researchers have noted a dividing time of once every twelve
days. This differs from the dividing time of most bacteria,
which is about 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 not sure about the
role an individuals genetic make up plays in 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.
Recently, however, 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. M. leprae is 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 has also been found in the breast milk of
infected nursing mothers. M. leprae may be transmitted by
breathing in the bacteria, through breaks in the skin, or perhaps
through breast-feeding.
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 to M. 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
bodys cellular immune responsethe part of the immune
system that seeks out and destroys infected cellsis 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
(lion-like) 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.
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 asM. 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.
Treatments for leprosy have improved considerably
over the past 40 years. In fact, some experts are encouraged
that the drug regimens being tested in various trials throughout
the world (including the United States) may eradicate leprosy
completely by the year 2010. 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. Dapsones
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 1960s, the problem of
resistance was tackled with the advent of multidrug therapy.
Bacteria are less likely to become resistant to several drugs
given in combination. The new multidrug treatment time was
also considerably shorter-typically about four years.
Currently, researchers offer a new drug combination that
includes an antibiotic called oflaxicin. Oflaxicin is a powerful
inhibitor of certain bacterial enzymes that are involved in DNA
coiling. Without these enzymes, the M. leprae cannot copy the
DNAproperly and the bacteria die. The treatment time for thiscurrent regimen is about four weeks
or less, the shortest treatment
duration so far.
One risk of treatment, however, is that antigensthe
proteins on the surface of M. leprae that initiate the host

immune responseare 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. In the late 1990s, the drug thalidomide was
approved to treat this reaction, with good results. Because
thalidomide may cause severe birth defects, women of childbearing
age must be carefully monitored while taking the drug.
A promising development in the treatment and management
of leprosy is the preliminary success shown by two different
vaccines. 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. The other vaccine uses a
relative of M. leprae called M. avium. The advantage of this
vaccine, currently being tested in India, is that M. avium is
easy to culture on media and is thus cheaper than the
Venezuelan vaccine. Both vaccines have performed well in
their clinical trials, leading many to hope that a vaccine
against leprosy might soon be available.
The World Health Organization announced in January,
2002, that during the previous decade, the number of active
cases of leprosy worldwide had been reduced by 90%. Control
of leprosy still eludes six countries, Brazil, India, Madagascar,
Mozambique, Myanmar and Nepal, with approximately 700,