Mycobacterium Leprae

Leprosy affects more than ten million people living mostly in developing countries of the tropics. In Asia there are 62% of lepers and Africa 34%, but the prevalence of the disease is 3 times higher in Africa than in Asia.


Mycobacterium leprae
Mycobacterium leprae

A – Description:

The causative agent of the disease is Mycobacterium leprae (or Hansen bacillus, 1873) is a weakly acid-resistant germ; it is much more easily bleachable by acid and alcohol that Mr. tuherculosis. It is not cultivable.

This is a bacillus January-August microns long and 0.3 to 0.5 microns wide, with parallel edges and rounded ends, colored homogeneously; it is immobile.

Bacilli in the tissues are grouped into globi or stored bacilli groups together.

B – biochemical characters:

Hansen’s bacilli harvested from human tissue or armadillo possess cytochromes, NADH reductase, alkaline phosphatase and a specific enzyme Mr. leprae, diphenol oxidase capable of oxidizing D-DOPA. They oxidize glucose CO2 have the Krebs cycle components and are able to produce their own energy. They include superoxide dismutase, but not catalase. Optimal physicochemical conditions favoring their metabolism are a temperature of 33 ° C and an acid pH (5.6).


The bacillus can multiply in the footpads of mice (especially Swiss mice G) or hamster. In these in vivo cultureconditions, their generation time is 20 to 30 days. Germs do not invade the deeper tissues and multiplication can be inhibited by various drugs (eg sulfone).

After inoculation of 103 seeds, the number of bacilli growing slowly in 6-9 months to reach the maximum figure of 106 bacilli and remains stationary.

Transmission germ immunosuppressed mice (“nude” athymic) performs infection model resembling lepromatous leprosy and obtainable 1010-1011 germs in the footpads.

M. leprae can also develop in the nine-banded armadillo and armadillo (Nine-banded armadillo) producing a similar disease to human lepromatous leprosy. In this animal many organs are affected (particularly the liver and spleen) and contain numerous bacilli. The intradermal or intravenous inoculation product disease in half the animals after 18 to 24 months of incubation. Other armadillo species are more or less susceptible to M. leprae.

The mangabey monkeys can be naturally infected with M. leprae and leprosy has also been experimentally transmitted to rhesus monkey.


Leprosy is a disease that is transmitted from human to human.

The endemic leprosy occurs in all countries of the tropics: Monsoon Asia, Oceania, Africa, Latin America; Europe still Icelandic homes, Baltic and Portuguese.

Leprosy, which was common in Europe in the Middle Ages, has almost disappeared for not fully elucidated reasons.

In France we observed only imported cases, especially among West Indians, Africans and Portuguese.

It seems that a latent infection intervene frequently in new subjects arriving by leprosy-endemic area and the intense contact with the bacillus depresses resistance to M. leprae. It is estimated that 200 people infected with M. leprae,only present a clinically overt leprosy.

In 40-50% of cases of leprosy shrinks before the age of 20 years. Contamination occurs through skin or mucosal route, from the nasal mucus of patients with lepromatous leprosy. It could also be transmitted during breaks in the skin barrier and arthropods has been implicated as agents promoting the spread of the disease. The incubation period is between a few months to 10 years. The factors favoring the spread of the disease are poor hygiene, overcrowding, malnutrition and tropical climate.


Mycobacterium leprae is an intracellular parasite strict man that is prevalent at the hairless skin (convex surfaces exposed) and peripheral nerves.

A – Clinical appearance:

Clinical signs observed in leprosy resulting from bacterial proliferation, immune response of the infected individual and peripheral neuritis associated with the two preceding process. Leprosy still affects the peripheral nerves, almost always the skin and often mucous membranes. The three cardinal signs of leprosy are skin lesions, cutaneous anesthesia and large peripheral nerves.

Leprosy has a complex clinical polymorphism. The transition from one form of leprosy to the other occurs either spontaneously or under the influence of treatment. Forms “polar”, that is to say, lepromatous and tuberculoid, are the most stable forms spontaneously.

Mycobacterium leprae

1. Indeterminate leprosy:

It is a form of beginning with one or more hypopigmented macules and hypoaesthetic. It evolves towards healing in 3/4 of the cases. It can also remain long under indeterminate form or evolve into one of three clinical forms described below.

2. Leprosy tuberculoid (TT):

It is a localized form abacillaire or pauci-bacillary due to effective cell-mediated immunity in. This is a skin and nerve disease, sometimes just nervous. This form stability.

a / Léprides tuberculoid:

These are skin lesions cupboards, rare, with sharp, superficial edges, discolored, with overall sensory disorders and vasomotor disturbances (bolt sweating). That are either simple macules or wider plates projecting edge (= extension field).

b / Nerve damage: very marked

It affects the superficial cervical plexus, ulnar nerve at the elbow, the median nerve (forearm) and the peroneal nerve at the fibular head.

The nerves are enlarged, irregular, moniliform, causing muscle atrophy.

Thus was created the ulnar claw and foot drop paralytic.

Also add sensory disturbances of the extremities: Global distal anesthesia areas thermo-algesic dissociation (first thermal anesthesia and pain).

The abolition of the sensation of pain allows the patient to use an injured or infected end. The result of secondary infection osteomyelitis, septic bone destruction with secondary deformities. These disorders result in large mutilating leprosy.

3. Lepromatous (LL):

This is a general disease, bacillary highly; the cellular immune system is reached. It is a form with some clinical stability.

The lesions observed result from an accumulation of bacilli and macrophages.

a / Skin lesions: it is the main achievement

– Lepromas circumscribed or tuberous: they are more or less voluminous nodules protruding under the skin. They are embedded in an inflammatory response and sit on the face (especially helix of the ear and nostrils) and are accompanied by the fall of the beard and tail of the eyebrows, realizing the “leonine facies”. The upper and lower members are also affected

– Lepromas strip or lepromatous léprides: they sit mostly on the trunk.

If treatment is started early, these lesions are not mutilating and resolve without sequelae. As against these lesions become mutilating during leprosy reactions (see below) or when treatment is started late. These lesions contain a very large number of bacteria (1010 or more per gram of tissue)

b / Achievement mucosa:

Lepromatous rhinitis is the main injury; purulent nasal discharge is rich in bacilli and plays a role in the spread of the disease; laryngeal mucosa and cornea (especially the anterior third of the eyeball, of lower temperature) can also be affected.

c / Other affected organs:

Enlarged peripheral nerves is noted, lymph nodes, spleen and testis. Liver Kupffer cells are filled with bacilli globi.

A biological inflammatory syndrome accompanies this form of leprosy.

These lesions contribute to bacillary dissemination.

The evolution towards my is done in 5-6 years cachexia, visceral amyloidosis or other intercurrent diseases.

Stopping or sudden resumption of antibacterial therapy can lead to the development of complex accidents allergic type Arthus reaction and called fever or leprosy reaction. They result in symptoms such as erythema nodosum, exacerbation of lesions or fever.

Reaction called reverse an increased level of specific delayed hypersensitivity, which results in an inflammatory reaction to neuritis and nerve compression in bone gutters. This requires a specific surgery. These immunological reactions jeopardize the continuation of leprosy specific treatment.

4. leprosy interpolar (or intermediate):

These are lepers in unstable immune system, polymorphic evolution and play a role in the epidemiology because their character is bacillary often misunderstood. We distinguish:

Interpolar tuberculoid leprosy (BT). It looks like tuberculoid leprosy. The number of skin lesions is more important and the edges of these lesions are less clear and sometimes surrounded by satellite lesions. These nerve damage are more diffuse than in tuberculoid leprosy.

Interpolar lepromatous leprosy (BL). It resembles lepromatous but all skin lesions are not anesthetics. Also some have a sharp edge. The trunks of the peripheral nerves are more affected than in lepromatous leprosy.

B – Pathophysiology:

Two opposite immune mechanisms determine the clinical forms and the evolution of the disease.

1. Tissue Immunity:

The reaction lepromin (Mitsuda, 1919) corresponds to the intradermal injection of an autoclaved suspension of leprosy bacilli obtained lepromas (= Lepromin).

Two types of response are identified:

– An early response (48-72 th hour) called reaction Fernandez: This is a delayed hypersensitivity reaction, poorly correlated with the form of the disease,

– A delayed reaction (21-28e day) called Mitsuda reaction (tuberculoid leprosy). We observe the emergence of a granuloma that actually then reflects the subject’s resistance state and is well correlated with the form of the disease.By biopsy of the granuloma found histologically the form of the disease.

a / lepers environment:

Lepromatous: negative Mitsuda reaction,

Tuberculoid leprosy: positive Mitsuda reaction (more than 5 mm in diameter)

Leprosy interpolar: Mitsuda reaction questionable or negative,

The subjects free environment lepers leprosy have positive Mitsuda reaction because these topics are a primary infection usually heals spontaneously.

b / In non lepers environment:

TB patients and BCG vaccinated: sometimes positive Mitsuda reaction.

Subjects free from bacterial aggression negative Mitsuda reaction.

Thus there is a deficit of specific cellular immunity vis-à-vis Mr. leprae and a modest decline in the general level of cellular immunity in lepromatous leprosy; Moreover, in tuberculoid leprosy, the absence of correlation between the reaction Fernandez (delayed hypersensitivity reaction) and Mitsuda reaction (immunity test) shows that these two types of immune responses are dissociated.

The Mitsuda reaction has no diagnostic value (because it is positive in people-contact), but contributes to the classification of the cases observed, and thus prognosis.

2. humoral immunity:

This immunity may be demonstrated by immunofluorescence reaction MerkIen-Cottenot performed with Stefansky bacillus (Mycobacterium lepraemurium). Healthy or TB patients may show positive reactions. Therefore the sera of patients to be absorbed by the BCG

Mycobacterium vaccae and to increase the specificity of the reaction. The results vary depending on the type of leprosy:

Lepromatous until 1/1024

1/128 to 1/256 tuberculoid leprosy

Leprosy treated 1/32 to 1/128

Healthy subjects less than 1/32.

It is as if the rate of circulating antibody was proportional to the number of bacilli. These circulating antibodies are not protective, but responsible for allergic accidents related to an Arthus such as kidney disease or as ENL.

Specific antigens of M. leprae were characterized. They could afford the serological diagnosis of certain forms of leprosy.


1. bacillary forms (lepromatous):

The bacilli are easy to identify in the nasal mucus and dermal juice collected at the lepromas (back, arms, thighs, earlobe).

Bacteriological identification of the organism based on 3 criteria:

– Acid-fast staining,

– Inability to cultivate the seeds on bacteriological media,

– Limited ability to increase in the footpad of mice.

ZiehI-Neelsen staining was used cold. Fuchsin staining must be long (20 min), but the discoloration should be brief (seconds) due to the low acid-resistance of the organism.

We distinguish:

– A bacteriological index of 1+ 6+ side according to the riches bacillary per microscope field.

The higher this index, the higher leprosy is scalable. The decline in the index under treatment, even effective, is still slow.

– A morphological index: some bacilli are evenly colored; others illegally tinted fuchsin or even frankly are grainy.The former are considered alive, others as dead. The morphological index represents the percentage of uniformly colored bacilli. This morphological index is high in active untreated leprosy, but rarely exceeds 50.

This index decreases rapidly as effective treatment; it is the vital clue monitoring therapeutic efficacy.

The staining technique auramine can be used in the detection of leprosy; bacilli are small and grouped globi.

2. cutaneous nerve forms (tuberculoid):

Suspicious clinical signs are: skin nodules, large nerves, sensory disturbances warm and cold, vasomotor disorders.

Is not highlighted Hansen bacilli in the nasal mucosa nor in biopsies of skin lesions. The differential diagnosis is difficult with certain nerve acropathies diabetes, Thévenard disease, Breton pseudo-leprosy Office Barrier Portuguese para-amyloidosis.

3. Histopathology:

The diagnosis is provided by the deep skin biopsy done on the outskirts of suspicious skin lesion. In no skin involvement forms will be performed biopsies nerves or ganglia.

The histological study is therefore an essential complement to the diagnosis and allows the classification of the form of leprosy.

– Indeterminate leprosy: lympho-histiocytic infiltrates undifferentiated sitting in the dermis and having an affinity for the nerves.

– Leprosy tuberculoid: épithélio’ide infiltrate and / or giant cell of the superficial dermis and the basal layer of the epidemic with attack deep skin appendages (sweat glands, sebaceous glands) and nerves.

– Leprosy lé macrophage granulomas and large vacuolated cells with bacillary globi (Virchow cells).Many such cells are separated from the skin by a clear zone. The nerves are degenerative lesions.

– Leprosy tuberculoid interpolar: the infiltrate is often similar to that seen in tuberculoid leprosy, but it does not include the basal layer of the epidemic.

– Lepromatous leprosy interpolar: we observe numerous macrophages associated with lymphocytes. The number of bacilli observed is lower than in lepromatous.

4. ginique vitro amplification (PCR):

This methodology could be a sensitive and powerful tool that microscopic examination for the diagnosis of leprosy, as shown by preliminary studies on frozen or formalin-fixed biopsies.


A – Curative treatment:

1. Drugs:

a / dapsone (DDS or diaminodiphényisulfone sulfone or parent)

In some parts of the world, 50% of strains resistant to sulfones.

b / Clofazimine (Lamprène®)

This substance is useful for the reaction forms but colors the seed coat in yellow-orange.

c / Rifampicin:

She is very active in the forms highly bacillus (much more active than sulfone), but its cost is high.

d / thioethers (ethionamide or prothionamide)

Clarithromycin and could also be used in the future.

2. Susceptibility:

A “antibiogram in vivo” can be achieved by injection of Mycobacterium leprae bacilli in mouse footpads treated or untreated with antibiotics and by comparing the morphological and bacteriological indices between them. This technique is also used to determine whether two drugs are synergistic or antagonistic therebetween.

3. Completion of treatment:

Many regimens are currently recommended. That recommended by the World Health Organization is:

a / bacillary forms:

To reduce resistance, the use of combination chemotherapy is currently recommended.

They will be treated for 2 years with a triple chemotherapy with 100 mg daily and 50 mg of sulfone and clofazimine each month rifampicin 600 mg and 300 mg of clofazimine. Treatment should be continued until no longer detect germs in dermal pulp smear.

b / Paucibacillary or abacillaires:

They will be treated for 6 months with a daily dose of 100 mg once monthly and sulfone 600 mg rifampicin.

c / immuno stimulant treatments:

Iterative BCG two years of biweekly injections, leading to cutaneous sequelae.

d / Lepra reactions: anti-inflammatory treatment:

We must fight against allergic phenomena:

– The Arthus reaction (erythema nodosum associated with fever, arthralgia, orchitis or iridocyclitis) is treated with thalidomide, possibly steroid eye drops.

– The reverse reaction, common in some forms interpolar on treatment requires the use of steroids and the reduction or interruption of specific chemotherapy because of neuritic risk. However, one can increase the clofazimine doses because of their antituberculous action and antiinflammatory.

e / Prevention of secondary infections anesthetized ends:

Injured or infected ends will be immobilized by splints until complete healing to prevent secondary infection osteomyelitis.

f / treatment effects:

Nerve release surgery, sympathectomy, orthopedics, rehabilitation.

B – Prophylactic treatment:

– School screening for the detection of leprosy before the onset of irreversible damage.

– BCG associated with sulfone chemoprophylaxis in children lepers environment; the effectiveness of BCG alone is still controversial.

– The search for serum antibodies against a specific phenolic glycolipid Mr. leprae should allow early diagnosis of subjects still in leprosy incubation period. These topics could benefit from preventive treatment of disease.

– A vaccine consisting of M. leprae killed by heating after being taken from the armadillo is being piloted in Malawi.The combination of BCG vaccine is also being evaluated.