Newsfeed display by CaRP What is Leprosy?

Leprosy (Hansen’s Disease), is a chronic infectious disease that primarily affects the peripheral nerves, skin, upper respiratory tract, eyes, and nasal mucosa. The disease is caused by a bacillus known as Mycobacterium leprae (M. leprae).

The Bacterium: Mycobacterium leprae

A bacillus, M. leprae, discovered by G.A. Hansen in Norway in 1873, is a slow growing obligate intracellular pathogen. The organism has never been grown in bacteriologic media or cell culture, and multiplies with an average doubling time of 12-14 days in a select group of animals. Armadillos and three species of monkeys -- chimpanzees, sooty mangabeys, and cynomolgous macaques -- are the only animals other than humans that have been found to become naturally infected with M. leprae. Armadillos and immunocompromised mice are the only two sources for growing the bacteria for research purposes.

The Disease

The mode of transmission of leprosy is unclear and has been assumed to be via the respiratory system mainly through nasal droplets; broken skin also remains a possibility. The primary tissues that are affected by M. leprae are the superficial sites of the skin and peripheral nerves because of preference to survive at low temperatures.

Leprosy has been described by Ridley and Jopling (giving rise to the Ridley-Joplin classification) as a continuous spectrum of disease. The course of human leprosy depends on the immunity of the infected persons. At one pole of the spectrum, patients with good T-cell immunity (Th1 type) exhibit tuberculoid (TT) leprosy or pauci-bacillary leprosy, while at the other pole, those with poor T-cell immunity harbor lepromatous (LL) leprosy, or multi-bacillary leprosy. In between these polar forms of leprosy are the borderline tuberculoid (BT), borderline-borderline (BB) and borderline lepromatous (BL) forms.

Nerve damage occurs at all stages of M. leprae infection. In TT leprosy, the sensory and motor nerves are affected, resulting in loss of sensation to touch and heat, while deeper cutaneous nerves are affected in LL leading to paralysis. LL leprosy, or multi-bacillary leprosy, is characterized by large numbers of organisms in the skin, many skin lesions with slight hypopigmentation, and less sensory loss in the lesions. While these individuals have high titre antibodies to M. leprae, they also have an impaired cellular immune response to the bacillus. Changes in immunity of the host and therapy can shift the clinical disease across the spectrum.

Diagnosis and Treatment
Diagnosis of leprosy is typically based on clinical symptoms, especially localized skin lesions that show sensory loss (loss of sensation to stimuli). Thickened enlarged peripheral nerves are also a hallmark of the disease. Diagnostic laboratory studies such as bacteriological (AFB, acid fast bacilli, in skin smear), and serological (for antibodies against M. leprae antigens, notably the M. leprae specific phenolic glycolipid I, known as PGL-I), are also used.

During the first half of the 20th century, many doctors treated leprosy with oil from the chaulmoogra nut. These injections were painful and the efficacy was questionable. In 1941, the sulfone drug, Promin was shown to successfully cure leprosy, but this also involved painful injections. During the 1950s, monotherapy with dapsone became the treatment of choice until the bacilli began to develop resistance in the 1970s.

Finally, drug trials led to an effective combination of drugs to treat the disease. In 1981, the World Health Organization (WHO) recommended multi-drug therapy (MDT) with dapsone, rifampicin and clofazimine. The regimen for multibacillary is monthly for a period of one year and for paucibacillary it is monthly doses of rifampicin and daily doses of dapsone for a period of six months. Several groups are now advocating uniform treatment for all forms of leprosy; however, this is being debated. With early diagnosis, leprosy can now be easily treated.

History of the Disease
Leprosy was well recognized in the oldest civilizations of China, Egypt and India. A cumulative total of the number of individuals who, over the millennia, have suffered its chronic course of incurable disfigurement and physical disabilities can never be calculated.

Since ancient times, leprosy has been regarded by the community as a contagious, mutilating and incurable disease. There are many countries in Asia, Africa and Latin America with a significant number of leprosy cases. It is estimated that one to two million people are visibly and irreversibly disabled due to past and present leprosy.
In 1921, the U.S. Public Health Service took over the hospital and established the Gillis W. Long Hansen’s Disease Center, which became known simply as “Carville.” Carville became a center of scientific research and testing in attempts to find a cure for Hansen’s Disease and to treat patients who lived there. In 1941, researchers identified Promin, a sulfone drug, as being effective against leprosy. This discovery became known as the “Miracle of Carville.”

During its century of service, Carville was home to more than a hundred patients, some of whom met and married there and spent a majority of their lives on the picturesque campus. When Carville closed in 1998, its few remaining patients were reluctant to leave. Since the early 1980s, when part of WHO was created to curtail and then to eliminate leprosy, there has been an extraordinary decline in disease prevalence.

Leprosy Today

At the beginning of 2002, the number of leprosy patients in the world was approximately 635,000, as reported by 106 countries (WHO) largely due to the success of multi-drug therapy (MDT). In the last 15 years since WHO initiated its Leprosy Elimination Project, more than 12 million cases have been cured. However, around 750,000 new cases are being detected annually, raising again the unanswered questions about source of infection, transmission, and incubation period. In other words, what is the basis of this steady stream of new cases in the midst of such a dramatic drop in disease prevalence?

Today, leprosy is found mainly in Angola, Brazil, India, Madagascar, Mozambique, Myanmar, and Nepal. These countries are taking steps to control leprosy through information campaigns and by providing diagnostic and treatment services to all communities, including the poor and underserved, and by incorporating leprosy diagnosis and treatment into the general health services.

Current Research
Clearly, innovative research measures are required to achieve the new goal of “leprosy elimination” by 2005 (less than one case per 10,000 population not only on a country basis but also over all national regions). Pragmatic research efforts in the areas of early detection (prior to developing clinical symptoms), prevention of nerve damage, surveying drug resistance and molecular epidemiological studies to address the questions of transmission and the true extent of leprosy incidence need to be addressed in a concerted manner involving laboratories in the United States, Europe, and endemic areas. The sequencing of the M. leprae genome in 2000 is helping to overcome challenges posed by the slow growth and inability of M. leprae to grow in vitro.

Since 1978, NIAID has been awarding contracts for the propagation of M. leprae in armadillos and the harvesting and fractionation of the bacillus to derive sizable quantities of M. leprae, its DNA, and antigens. The armadillo facility is located at the National Hansen’s Disease Program Laboratories, Louisiana State University, Baton Rouge and the M. leprae isolation facility at Colorado State University, Fort Collins. As part of this NIAID funded contract to develop leprosy research reagents and make them available to researchers worldwide, investigators at Colorado State University are also developing improved skin test antigens to detect leprosy. Trials to determine the safety of new skin test antigens were initially conducted in volunteers in the United States and are now being done at the Anandaban Hospital in Nepal to determine the clinical utility of a skin test in leprosy endemic regions.

The priorities for research in leprosy today are new immunological tests for pre-clinical diagnosis, and genetic probes for molecular epidemiology. The goals are to provide evidence on reservoirs of infections, routes of transmission, and incubation periods to allow prophylactic interventions and, ultimately, eradication of leprosy. There is still a case for vaccine development in light of the inability of MDT, despite its treatment success, to substantially diminish the emergence of new cases.

NIAID has been supporting leprosy research, both in the United States and throughout the world for a number of years and is funding seven major research projects on the disease. The following projects are currently funded through NIAID:
Develop and Evaluate New Leprosy and TB Vaccines.
Pathobiology of Human Leprosy.
Mycobacterium Leprae Antigens and Nerve Damage.
Leprosy Bacillus: from Genotype to Phenotype.
Role of Toll-Like Receptors in Skin.
Gene Knock-Out Mice as Models for the Leprosy Spectrum.
Determinants of TH1 Cytokine Responses in Leprosy.