Mycobacterium leprae
Definitions & Key takeaways
Mycobacterium leprae is a species of acid fast bacillus, obligate intracellular, aerobic bacteria, which primarily causes leprosy, a chronic and disfiguring skin disease. It is spread from person to person through contact with nasal secretions and skin lesions and can cause nerve damage and other organ damage if left untreated.
The diagnosis involves identifying Mycobacterium leprae bacteria in a skin biopsy with microscopy or PCR. Treatment typically involves a combination of antibiotics, such as dapsone or rifampin, and other drugs such as clofazimine or prednisone.
Mycobacterium leprae is a rod-shaped bacteria which was first discovered in 1873 by Hansen. Mycobacterium leprae is a non tuberculous mycobacteria and it causes a disease called leprosy, or Hansen disease.
In US, the animal reservoir for Mycobacterium leprae are armadillos. Now, Mycobacterium leprae it’s an acid-fast bacillus which means it’s resistant to decolorization by acids and it has a high content of mycolic acid in its cell wall, which makes it waxy, hydrophobic and impermeable to routine stain such as Gram stain.
So, it needs special staining methods to be visualized such as Ziehl-Neelsen staining which uses carbol fuchsin combined with phenol which is able to penetrate the waxy mycobacterial cell wall.
So, the stain binds to the mycolic acid in the mycobacterial cell wall and after staining, an acid decolorizing solution is applied which removes the red dye from the background cells, tissue fibres, and any organisms in the smear except Mycobacteria, which retain the dye.
So Mycobacterium leprae appears bright red on a blue background. Other staining methods can be used such as Kinyoun staining, in which the bacteria appear bright red on a green background and fluorescence microscopy using specific fluorescent dyes such as auramine-rhodamine stain.
Now, Mycobacterium leprae is an obligate intracellular microorganism, which means it can survive only inside cells, and it’s an obligate aerobe which means it can survive only in the presence of oxygen.
Finally, Mycobacterium leprae grows best at cool temperatures, between 27 to 33 degrees Celsius, and it proliferates slowly and it cannot be cultivated in vitro.
Instead, it can be inoculated in nine-banded armadillos, which have a much lower body temperature than most mammals and, like humans, are susceptible to leprosy.
Now, Mycobacterium leprae can enter the body through the lungs or broken skin. Once inside the body, it goes for regions in which the temperature is lower than the rest of the body such as skin, peripheral nerves and mucosa of the upper respiratory tract.
So, the bacteria goes for the Schwann cells of peripheral nerves. These cells wrap their plasma membrane around peripheral nerve axons forming the myelin sheath.
This is possible because of a virulence factor, called phenolic glycolipid 1, or PGL-1 for short, which attaches to a protein called laminin-2 which is found on the Schwann cells.
Binding to Schwann cells induces demyelination, affecting transmission of the electrical impulses through the nerve axon, and causing nerve injury.
Additionally, Mycobacterium leprae can also infect skin macrophages. So, the bacteria is ingested by macrophages and wrapped up in a vesicle called a phagosome, which would normally merge with another intracellular organelle called a lysosome.
Inside the phagolysosome, the bacteria would normally be destroyed. But, Mycobacterium leprae has the ability to inhibit the phagolysosomal fusion, which allows the bacteria to survive inside macrophages and replicate there.
Now, the host responds to leprosy through cell mediated immunity via T-helper cells. These cells help the activity of other immune cells by releasing T cell cytokines, and there are two types of T-helper cells - Th1 and Th2.
Depending on which T-helper cells are involved in the immune response, there are two major forms of leprosy - lepromatous and tuberculoid.
Now, this response is not effective in killing intracellular pathogens like Mycobacterium leprae, that can escape humoral immune mechanisms and replicate inside macrophages.
So, the inefficient immune response seen in the lepromatous form is sometimes also called a low cell mediated immunity response.
This leads to extensive skin involvement and symmetric nerve involvement, and the lepromatous form is also called multibacillary leprosy because of the large number of bacteria found in the lesions.
On the other hand, with is tuberculoid form, the infection induces a Th1 response, and Th1 cells secrete IL-2 and interferon-gamma.
So, IL-2 activates cytotoxic T-cells and interferon-gamma activates macrophages and natural killers to produce chemicals that destroy ingested bacteria directly, leading to a cell-mediated response.
This response is effective in destroying Mycobacterium leprae, so this immune response is sometimes also called a high cell mediated immunity response.
Hence, with the tuberculoid form, there’s a limited number of skin lesions, and nerve involvement is usually asymmetric.
This form is also called paucibacillary leprosy because of the low number of bacteria in the skin lesions. Ok, now, risk factors for developing leprosy include close contact with infected individuals and armadillos, as well as older age and immunosuppressive states, like diabetes, malignancy, or an underlying HIV infection.
With the lepromatous form, there are numerous raised, poorly demarcated skin lesions, that can be found on extensor surfaces of the extremities.
Within these skin patches there may be diminished sensation or a loss of sensation altogether. And overall, there is a loss of sensation in the limbs, with a glove and stocking distribution.
There may also be paresthesias which are abnormal dermal sensations like tingling or numbness in the hands or feet, lumps or swelling on the earlobes or face, which can result in a lion-like, or leonine facies, body hair loss, especially eyebrows and eyelashes.
Worst-case scenario, things progress towards the gradual destruction of the extremities - so the nose may collapse due to nasal septum destruction, and fingers and toes might necrose and fall off!
Yikes! With the lepromatous form, there can also be ocular involvement, in the form of chronic uveitis, meaning the inflammation of uvea, which is the pigmented layer of the eye.
There may also be facial nerve paralysis, that leads to lagophthalmos, which is the inability to close the eyelids completely.
This can result in corneal ulceration due to corneal exposure and eye drying. With the tuberculoid form, on the other hand, there are hypopigmented or reddish patches on the skin, which are rare and well-demarcated, and nerve involvement is usually mild, but there can be tender, enlarged peripheral nerves.
In late stages, there’s weakness of the hands with claw fingers, and foot drop which is the inability to lift the front of the foot.
On the bright side, no fingers are falling off in this case. Now, diagnosis can be done by identifying Mycobacterium leprae in a skin biopsy of an active lesion, and examining it under a microscope.
In the lepromatous form, there are lipid laden macrophages, called foam cells, containing many acid fast bacilli, while in the tuberculoid form, there very few acid fast bacilli, and granulomas, which are collections of immune cells.
This is when an extract of inactivated M. leprae is injected intradermally and if an induration appears after 48 hours it means that there is a cell-mediated immune response against organism.
So, this test is negative in lepromatous form and positive in tuberculoid form. Treatment for leprosy is done with multidrug therapy to prevent resistance.
So, the lepromatous form is treated with dapsone, rifampin and clofazimine for 12 months, while the tuberculoid form is treated with dapsone and rifampin for six months.
Alright, as a quick recap. Mycobacterium leprae is an acid fast bacillus, obligate intracellular, aerobe, which cannot be cultivated in vitro.
It has the ability to infect Schwann cells and skin macrophages and causes a disease called leprosy, or Hansen disease. According to the type of cell-mediated immunity response, there are two major forms of leprosy - lepromatous, which is a result of Th2 cell, or low cell mediated immunity, and tuberculoid, which is a result of Th1 cell, or high cell mediated immunity.
Diagnosis can be done by identifying Mycobacterium leprae in a skin biopsy with microscopy or PCR. Treatment is done with dapsone, rifampin and clofazimine for the lepromatous form, and dapsone and rifampin for the tuberculoid form.
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