How is Leprosy Transmitted?

The bacillus Mycobacterium leprae causes leprosy. Mycobacterium leprae was discovered in 1873 by G.A. Hansen

(hence the disease was subsequently named after him).  At that time, it was the only bacterium that had been discovered to cause a human disease (Leprosy: the Disease, 2000). Rod-shaped with rounded ends, Mycobacterium leprae occurs in large numbers, often grouped in bundles, in the lesions of patients with lepromatous leprosy.  The bacilli also group in clumps surrounded by a capsule called globi, located both in intracellular and extra-cellular spaces.  Viable bacilli stain with carbol-fuchsin as solid rods, whereas bacilli that stain irregularly are probably dead (Microbiology of Mycobacterium leprae, 2000).  In the photograph to the left the top images are drawings of the human leprosy bacilli seen under a microscope in the bottom row.  The right images show that the bacillus is viable because it is uniformly stained.  Both the left images with beaded staining and the middle images with empty cell walls at the extremities are dead forms of the bacillus.  The Mycobacterium leprae grows in the vessicles within macrophages which must be activated by TH1 cells (Janeway, 1999).  Photograph courtesy of Wolstenholme et al

Two Subdivisions of Leprosy

the bacillus (Janeway, 1999). Very few bacilli can be detected in these areas.  (Photograph courtesy of LEPRA) As a result, very large nodules called tubercles are formed under the skin's surface.  The tubercles look like a dense dry spot which cannot sense hot, cold, or touch because the skin's nerve fibrils are involved as well.  As the disease slowly progresses, inflammation surrounds the main trunk of the nerve so that nerve impulses cannot travel up or down.  The infected individual looses pain sensation, blood circulation, and muscle power in the infected area (Encyclopaedia Britannica, 2000).  The

fingers become stuck in a clenched position which may be straighted either with plaster casts or, in the more severe cases, tendon transfer surgeries (Mooney, 1999).  If the affected nerve is in the lower leg, drop feet are common (Photograph courtesy of Mooney).  When this occurs, the individual is unable to lift his or her foot whenwalking.  Because the patient cannot sense pain, minor cuts go uncared for and turn into larger problems.  (Photograph courtesy of LEPRA).  As a result, the toes can be severly damaged by large, eroding ulcers.   Many times the toes either deteriorate on their own or are amputated (Mooney, 1999).   This entire process is caused by the immune response which, although it prevents the bacilli from spreading, causes immense tissue damage in the infected areas.   Interestingly,

(Transmission of Leprosy, 2000).  The second type of leprosy is lepromatous (or multibacillary) leprosy which has a much higher infectivity than tuberculoid leprosy.   Patients with lepromatous leprosy have CD8  T cells that suppress TH1 by producing IL-10 and tumor growth factor beta.  Thus the production TH2 cells are preferentially induced, producing mainly a humoral response.   Although antibodies are produced, they cannot make contact with the bacilli in the macrophages (Janeway, 1999).   As a result, large numbers of Mycobacterium leprae can be found under the skin in the infected areas.   The bacilli then travel through the lymphatic system to reach the rest of the body and cause widespread tissue damage.   Large nodules form all over the body, including the face (Encyclopaedia Britannica, 2000).   Multibacillary leprosy has symmetric lesions, plaques,and nodules.  In addition, the nasal mucosa is involved, producing nasal congestion and epistaxis (Morbidity and Mortality Weekly Report, 1999).  In lepromatous leprosy the skin on the face thickens and the disease often spreads to the hair follicles, causing loss of hair.   As the disease progresses, ulcers

Department of Health and Human Services, 1980).  This figure shows the macrophage and T-cell responses to Mycobacterium leprae during the two types of leprosy infections.  On the left is turberculoid leprosy, the less severe of the two.  TH1 cells are preferentially activated to control the infected areas.  These cells release IL-2, INF-gamma, and TNF-beta.  Granulomas are located inside the lesion.  Patients with tuberculoid leprosy experience local imflamation. On the right is lepromatous leprosy.  TH2 cells are activated so the bacilli grow unchecked inside the macrophages.  The infection therefore spreads throughout the body causing bone, cartilage, anf nerve damage.  The TH2 cells release IL-4, IL-5, and IL-10.          Permission requested from Janeway et al

Leprosy Around the World

Leprosy is often found in conditions connected with poverty: overcrowding, poor sanitation, and insufficient nutrition (<www.anandgram.org>).  According to current WHO data, the current global prevalence rate is around 1.4 cases per 10,000 people.  Around 500,000 new cases of leprosy are registered each year, about 300 of which are in the United States.  WHO has mounted a compaign to try to eliminate Hansen's disease .  Elimination is defined as less than one case per 10,000 people (Ahmad, 1999).  Of the twenty-four countries where leprosy is endemic, twelve will meet the elimination goal by the end of the year 2000.  These countries are Cameroon, Chad, Congo, Cote d'Ivoire, Ethiopia, Gabon, Gambia, Guinea Bissau, Mali, Papua New Guinea, Paraguay, and Sierra Leone.  The remaining twelve are Angola, Brazil, Central African Republic, Democratic Republic of the Congo, India, Indonesia, Guinea, Madagascar, Mozambique, Myanmar, Nepal, and Niger.  These coutries account for 90% of the global prevalence (www.who.int/inf-fs/en/
fact101.html, 2000).  India alone has about 500,000 infected people, which represents 63% of the global occurances and 87% of the cases for that region (Kumar, 1999).

Map showing where in the World leprosy is most prevalent

Treatment of Leprosy

In the 1940s, scientists discovered that the drug dapsone stopped the progress of leprosy.  Dapsone is an antibiotic inhibites "folic acid synthesis by inhibition of dihydropteroate synthetase" (www.hopkins-aids.edu/
publications/book/ch6_dapsone.html, 2000).  Treatment with this drug required that the patient take dapsone for many years.  Drug-resistant Mycobacterium leprae was found in the 1960s, thus the only treatment available became useless in some cases.  Luckily, soon afterwards, rifampicin and clofazimine were found to very effective.  Rifampin, an antitubular drug stops the progression of leprosy so that the individual is no longer contagious and clofazimine reduces the number of mycobacteria in circulation (www.aidsinfonyc.org/network/access/drugs/clof.html).

(photograph courtesy of LEPRA)  Some instances have been recorded where the bacilli has become drug resistant, but these times are typically when the drug treatment schedule is not followed correctly (Encyclopaedia Britannica, 2000).   In 1982, the World Health Organization (WHO) began recommending multidrug therapy (MDT) for leprosy patients.  MDT contains three drugs, clofazimine, dapsone, and rifampicin which kill "the germ, cures the patient and prevents the occurrence of drug resistance" (www.who.int/inf-fs/en/fact101.html, 2000).  !f MDT is started as soon as symptoms are detected, deformities can be avoided.  MDT is very effective for another reason; it makes the individual non-infectious after the first treatment.  Individuals with tuberculoid leprosy can be cured during a six month course of MDT while patients with lepromatous leprosy require twelve months (www.who.int/inf-fs/en/fact101.html, 2000).  In July of 1998 the U.S. Food and Drug Administration approved the use of thalidomide for leprosy  treatment as an

anti-inflammatory.  Thalidomide inhibits the production of TFN-alpha, which can be overproduced in leprosy.  When overproduced, TFN-alpha causes fever and night sweats (Wright, 2000).  A short time ago three new drugs were demonstrated to have bactericidal activity against M. leprae.  Collectively called ROM, the drugs are ofloxacin-a fluoroquinolone, minocycline-a tetracycline which is believed to have both anti-bacterial and anti-inflammatory properties, and clarithromycin-a macrolide.

Possibilities for the Future

In order for leprosy to be fully eliminated, many steps need to be taken to integrate the treatment of leprosy into the services for general health.  In addition, the stigma attached to be infected needs to be purged from all societies so that infected individuals will seek help rather than spreading the disease to more people.  Because cytokines regulate the delicate balance between T_H! and T_H2 cells, it could be possible to induce the less severe form of leprosy by giving the right cytokines.  In a patient with lepromatous leprosy, a cell-mediated response can be induced by administering T-cell growth factor IL-2 or IFN-gamma which induces macrophage activation.  Another way would be to give !L-12 which is normally produced by macrophages to induce T_H! cells.  The idea of injecting cytokines into lesions

shows promise because it has been shown to reverse the type of leprosy (Janeway, 1999). Moveover, a significant amount of research must be done because the methods of transmission continue to be unknown and also no one has been able to grow the bacillus in the laboratory.  It is possible to grow the leprosy bacillus in the footpads of mice.  This allows researchers to study the effects of drugs on the disease (Wolstenholme et al, 1963).  This photgraph is a section of nerves in the infected and deformed rear limb of a mouse that has been injected with the bacilli.  The section indicates nerve degeneration, showing proliferation of endoneural nuclei and fragmented fibers.   Courtesy of Wolstenholme et al

Links to Related Sites

- Link to Lepromin skin test
- Center for Disease Control (CDC) in Atlanta, Georgia.
- World Health Organization (WHO)
- Anand Gram: Village of Joy
- British Leprosy Relief Mission (LEPRA)
- Link to haikus about leprosy
- Summary of 7th WHO Expert Committee on Leprosy

- "About Leprosy." <www.anandgram.org> Accessed on April 17, 2000.
- Ahmad, Khabir 1999. "WHO initiates global leprosy health-care alliance." Lancet 354: 1802.
- "Clofazimine." <www.aidsinfonyc.org/network/access/drugs/clof.html> Accessed on April 20, 2000.
- "Dapsone." <www.hopkins-aids.edu/publications/book/ch6_dapsone.html> Accessed on April 20, 2000.
- Janeway, CA, P Travers, M Walport, JD Capra. Immunobiology: The Immune System in Health and Disease.  New York: Garland Publishers, 1999.
- Kumar, Sanjay 1999.  India falls short of World Health Organization leprosy targets.  Lancet 353: 652.
- LEPRA (British Leprosy Relief Mission). <www.lepra.org.uk/home.html> Accessed on April 16, 2000.
- "Leprosy." Morbidity and Mortality Weekly Report 48: 174 (1999).
- "Leprosy." <www2.adam.com/ency/article/001347.htm> Accessed on April 16, 2000.
- "Leprosy." <www.who.int/inf-fs/en/fact101.html> Accessed on April 17, 2000.
- "Leprosy: the Disease."  <www.who.int/lep/disease/disease.htm> Accessed on April 17, 2000.
- "Leprosy (Hansen's disease)."  Encyclopaedia Britannica. New York: Encyclopaedia Britannica, 1998.
- "Leprosy (Hansen's disease)."  Bethesda, MD: U.S. Department of Health and Human Services, 1980.
- "Microbiology of Mycobacterium leprae" and "Transmission of Leprosy." <www.who.int/lep/disease/
Microbiology.micro.htm> Accessed on April 16, 2000.
- Mooney, Virginia N. (1999).  The photographs and information were collected during a summer spent at the All Africa Leprosy & Rehabilitation Training Center (ALERT).  I performed operations on patients with leprosy (mainly amputations and tendon transfers) and worked in physical therapy to monitor the progress of the disease and to put plaster casts on the patients with claw hands.
- Wolstenholme, G.E. and M. O'Connor.  Pathogenesis of Leprosy.  Boston: Little, Brown and Company, 1963.
- Wright, Karen 2000. "Thalidomide is back."  Discover 21: 31-33.