Medicine for Africa - Medical Information Service

EPROSY

Definition:

Leprosy is also called ‘Hansen’s disease’ after Dr. Hansen, a Norwegian physician, who identified the causative agent – Mycobacterium leprae (M. leprae) – in 1873.  Leprosy is a chronic infectious disease caused by bacteria (M. leprae), which are rod-shaped, acid-fast positive bacilli, located within the cells (intracellular) and grow best in relative cool areas of the body – such as the skin, peripheral nerves, the mucosa of the upper respiratory tract, as well as the chamber of the eye, the testes and other organs.

Leprosy is usually (but not easily) transmitted from person to person by droplets from the respiratory mucosa or mouth to people in close contact; there is also evidence that it can be transmitted to humans when handling chimpanzees, monkeys or armadillos.  However, the exact manner of transmission is not yet completely understood. 

Leprosy is a chronic disease with an incubation period (time between infection and the appearance of symptoms) of as little as a few weeks to up to 30 years and more following exposure; the average incubation period is estimated to be between three and five years. 

A genetic predisposition to the infection is believed to exist since about 95% of people appear to be naturally immune to the infection.  While there is a relationship between the patient’s immune system and response to the bacteria, there is no connection between leprosy and HIV/AIDS, tuberculosis or other diseases based on a deficient immune system.  Within one month of treatment, leprosy patients are not infectious anymore to others and thus cannot spread the disease any further.

Leprosy consists of two major forms of disease, which are further subdivided – the two major categories are:

• Tuberculoid leprosy – is the less severe form, characterized by non-necrotizing granulomas, primarily in the skin and peripheral nerves (in an asymmetric fashion), with just a few acid-fast bacilli present, thus also called ‘pauci-bacillary (PB) leprosy (see picture – granulomas in the skin).

• Lepromatous leprosy – is the most severe form, characterized by an abundance of so-called foamy macrophages in the skin (dermis) and other sites, which are filled with acid fast bacilli, but no granuloma formation, also called multi-bacillary (MB) leprosy (see picture – many macrophages in the spleen).

Both forms produces skin lesions (see above), however, the most severe lepromatous form also produces large disfiguring nodules (lumps and bumps).

The WHO (World Health Organization) classification of 2009, bases the classification of leprosy on the number of skin lesions present:

• Pauci-bacillary (PB) leprosy – skin lesions do not reveal M. leprae bacilli in skin smears;
• Multi-bacillary (MB) leprosy – M. leprae bacilli are present in skin lesions and can be seen in a smear.

WHO further modified these two classifications with clinical criteria, in case there are no skin-smear services available.  The clinical classification is based on the number of skin lesions present and nerves involved:

• PB leprosy – less than five skin lesions identified;
• MB leprosy – more than five skin lesions present.

Ultimately, all forms will cause nerve damage in the arms/hands and legs/feet, causing sensory loss in the skin and muscle weakness.  In long lasting, untreated leprosy, repeated injuries to hands and feet due to a lack of sensation (no feeling of hot, cold or painful insults) may result in the loss of fingers and toes.

Research has shown that leprosy can occur in people with a defect in cell-mediated immunity that causes susceptibility to the disease; this defect is present in only a small percentage of people (>5%), who would be susceptible to contracting the disease.  Since the region of the affected DNA (des-oxy-ribonucleic acid) is also responsible for the development of Parkinson’s disease, it is thought that there may be a link between these two disorders somewhere on a biochemical level.  Also, the fact that DNA changes are involved in the development of leprosy, a genetic factor for susceptibility to the disease may be possible (leprosy is not hereditary).

Although leprosy can easily be treated, if recognized and appropriately treated early on (see Therapy), it is still prevalent almost worldwide in temperate, tropical and sub-tropical climates, including in India, China, Brazil, Nepal, several states in the USA and other countries.  In Africa, areas of high endemic occurrence remain in countries such as:

• Angola;
• Central African Republic, CAR;
• Democratic Republic of Congo, DRC;
• Madagascar;
• Mozambique (highest prevalence in Africa);
• United Republic of Tanzania.

            Historic Review

Leprosy was well known throughout history.  Research suggests that leprosy was present as early as 4000 BC; it was first referred to in Egypt at about 1550 BC and prevalent in other ancient civilizations such as China and India.  Since the disease was very disfiguring and there was no known treatment for it, it was considered to be a curse or punishment from the gods, thus afflicted people were often shunt by the community and left to be ‘treated’ by priests or other ‘holy men’.

Later on, Romans and Crusaders brought the disease to Europe, followed by the Europeans taking it to the Americas.

Until the first effective treatment (dapsone) was developed in the 1940s, leprosy patients were forced to live in seclusion, so-called ‘leper colonies’, which existed worldwide.

In 1995, the WHO (World Heath Organization) estimated that at that time, up to three million people worldwide were disabled due to leprosy.  Over the past 20 years, more than 15 million leprosy patients have been cured, and the prevalence rate of the disease has dropped by 90% – from 21.1 per 10,000 inhabitants to less than 1 per 10,000 inhabitants in 2000.  With proper treatment, isolation in leper colonies is not necessary; unfortunately, there are still leper colonies present, especially in India (more than 1,000), China, Egypt, Somalia, Liberia and many other countries.

Symptoms:

Early symptoms of leprosy develop very slowly over a long period of time, are rather subtle and sometimes difficult to distinguish from other diseases with a similar clinical picture, such as leptospirosis, syphilis and tetanus.  Symptoms include:

• Skin lesions – areas of lighter colored skin (hypopigmentation), which do not heal even after weeks and months, and express decreased sensation to touch, hot and cold temperatures and pain and pressure, often resulting in poorly healing painless ulcers and subsequent loss of fingers and toes;
• Peripheral nerve damages – resulting in numbness (absence of sensations) in arms and hands as well as legs and feet (see above);
• Eye damage – dry eyes, reduced blinking;
• Muscle weakness.

 As the disease progresses, the symptoms become more and more pronounced, especially in cool areas of the body (extremities), resulting in the loss of fingers and toes as well as the rather ‘classic’ facial disfigurement (see picture above), often falsely being termed ‘elephantiasis’, due to the thickening of peripheral nerve strands.

 
Diagnosis:

Leprosy is primarily endemic in developing countries, where laboratory services may be restricted or not available at all, thus, the proper recording of the patient’s medical history and symptoms, combined with a thorough physical examination are very important in order to arrive at the proper diagnosis.  Hypopigmented areas of skin (lighter colored skin) or reddish skin patches with loss of sensation and/or thickened peripheral nerves comprise some of the clinical findings of leprosy.

Other, laboratory methods of diagnosing leprosy include:

• Tuberculoid leprosy – pauci-bacillary leprosy:
• Scrapping of the skin lesions or skin biopsies may reveal non-necrotizing granulomas which may show no or only a few acid fast bacilli upon appropriately staining the smears/tissue slides;
• Lepromin test is positive;
• T lymphocytes – CD4+ helper T lymphocytes predominate over CD8+ suppressor T lymphocytes at sites of infection;
• Rich in TH1 cytokine mRNAs.

• Lepromatous leprosy – multi-bacillary leprosy:
• Scrapping of the skin lesions or skin biopsies may reveal foamy macrophages which may show many acid fast bacilli upon appropriately staining the smears/tissue slides;
• Lepromin test is negative;
• T lymophocytes – CD8+ suppressor T lymphocytes predominate over CD4+ helper T lymphocytes in areas of infection;
• Rich in TH2 cytokine mRNAs.

The best method for diagnosing leprosy consists of skin scrapings and/or biopsies with subsequent identification of the M. leprae bacilli – paucibacillary vs. multibacillary (see above).

The lepromin skin test is usually not used for diagnosing leprosy, but rather for distinguishing the tuberculoid form from the lepromatous form of leprosy.

 
Treatment:

Nowadays, leprosy is easily curable and if treatment is started in the early stages of the disease, disability can be averted.  However, if treatment is started after damages have already occurred, subsequent therapy cannot reverse already existing damages to peripheral nerves, skin areas and/or limbs.

The WHO recommended treatment, issued in 1993, consisting of a multidrug therapy, MDT, of two or three drugs:

• Pauci-bacillary leprosy (1-5 skin lesions, tuberculoid form): two antibiotic drugs – rifampicin and diaphenylsulfone (dapsone), for six months;
• Multi-bacillary leprosy (> 5 skin lesions, lepromatous form): three antibiotic drugs – rifampicin, clofazimine and diaphenylsulfone, for at least 12 months.

Since leprosy is considered a global health problem, MDT is available to national Ministries of Health in endemic countries, free of charge, from either the WHO or the manufacturer of MDT itself, Novartis Pharmaceutical, via the Novartis Foundation for Sustainable Development.

In addition, the WHO recommends a strategy of a single-dose MDT in endemic areas for patients with a single lesion of leprosy; this MDT consists of the antibiotics rifampicin, minocycline and ofloxacin.

To date, MDT remains very effective, safe and easy to use; relapse rates are low and no resistance has been reported as yet to the combined drug therapy.

Patients are not infectious to others following the first monthly treatment.

For patients with irreversible deformities, reconstructive surgery may be necessary.

Prevention:

There is no commercially available vaccine for the prevention of leprosy.

However, studies have shown that the BCG vaccine, often given against tuberculosis, offers some amount of protection against leprosy as well.

Rifampicin given as a single dose to close contacts of leprosy patients has shown to reduce the number of new cases to up to 75%, according to a recent trial.

The most important ‘prevention’ lies in identifying the disease as early as possible, which in turn requires increased awareness and appropriate education of local communities in endemic countries regarding the disease, in order to eliminate the still widely existing ‘taboos’ (‘unclean’, ‘curse of the gods’), which may prevent people from seeking early help against the disease.  In addition, healthcare related education to medial personnel is also necessary for achieving earliest possible detection and treatment enrollment of patients with leprosy.

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