Mycobacterium leprae

Categorization
Cell Wall: Acid-fast Shape: Rod
Life Cycle: Facultative Intracellular
Transmission
  • The route of M. leprae transmission is unknown but in most cases is associated with extended, intimate contact with infected individuals. It appears that most humans are naturally immune to this organism. Leprosy is largely observed in impoverished areas of developing countries. In the US, M. leprae naturally occurs among Texan armadillos; however, transmission to humans is highly rare.
Immune Response
  • Overview
    • The clinical consequences and morphological manifestation of leprosy is highly dependent on the nature of the host immune response. Humans appear to respond to infection across a spectrum ranging from one extreme with a strong tilt toward cell-mediated immunity and on the other extreme with a strong tilt toward humoral immunity. Likely because M. leprae is a facultative intracellular organism and since antibodies do not appear to be very protective, individuals whose immune system tilts toward a cell-mediated response develop much less pathology than those whose immune system tilts toward a humoral response. Below we describe the possible immune responses at either extreme and discuss their corresponding clinico-pathological consequences in the next section.
  • Cell-mediated Tilt
    • Individuals whose immune response tilts toward cell-mediated immunity develop antigen-specific CD4+ T-cells of the Th1 subtype. Similar to the immune response described for M. tuberculosis, the CD4+ Th1 Cells secrete cytokines such as IFN-gamma which stimulate macrophages to effectively kill phagocytosed organisms. The clinico-pathological syndrome which is observed in this immune scenario is described as "Tuberculoid Leprosy".
  • Humoral Tilt
    • Individuals whose immune response tilts toward humoral immunity develop antigen-specific CD4+ T-cells of the Th2 subtype which secrete cytokines such as IL-4 and IL-5 which stimulate development of antigen-specific B-cells. Sadly, M. leprae-specific antibodies do not appear effective in providing immunity to this organism. The clinico-pathological syndrome which is observed in this immune scenario is described as "Lepromatous Leprosy".
Clinical Consequences
  • Overview
    • Clinico-pathological consequences may occur years after initial inoculation and develop slowly. As described above, the nature of the host immune response shapes the clinico-pathological syndrome which arises following M. leprae infection. Tuberculoid and Lepromatous Leprosy represent the two clinico-pathological ends of the spectrum associated with an immune response dominated by cell-mediated immunity or humoral immunity, respectively. It is important to point out that many patients display intermediate features along this range which are termed "Borderline Tuberculoid", "Mid-borderline", or "Borderline Lepromatous". M. leprae appears to proliferate better at low temperatures; consequently, disease is most often associated with superficial areas of the body far from the body's core.
  • Tuberculoid Leprosy
    • Tuberculoid Leprosy usually manifests as only a few well-defined skin lesions which appear as hypo-pigmented macules or plaques. Hypo-pigmented areas display diminished sensation and generally lack accessory organs such as apocrine glands and hair follicles. Tuberculoid patients may also display asymmetric enlargement of a few peripheral nerves which usually typically affect those in the extremities. Histologically, these skin and peripheral nerve lesions display large numbers of T-cells and few M. leprae bacilli. Patients with Tuberculoid Leprosy are generally not very infectious and often spontaneously eliminate the organism.
  • Lepromatous Leprosy
    • Lepromatous Leprosy is the clinico-pathological manifestation of Leprosy which comes to the mind of most when the word "Leprosy" is uttered and why the disease has been stigmatized for millenia
    • Skin: Numerous bacilli are observed in the dermis which, together with the inflammatory reaction, can cause expansion of the skin, generating nodules, plaques, or diffuse expansion of wide areas
    • Face: Dermal infiltration can cause severe deformity of the face, termed "Leonine Facies", and characteristically causes loss of the eyelashes as well as outer half of eyebrows
    • Nose: Infiltration of the nasopharyngeal mucosa may cause destruction of the nasal cartilage and sinking in of the nose, termed a "Saddle-nose Deformity"
    • Peripheral Nerves: Peripheral nerves can also become symmetrically infiltrated with M. leprae, leading to their enlargement and a peripheral neuropathy with consequent sensation loss in a stocking-glove distribution
    • Fingers and Toes: The loss of sensation in the extremities due to peripheral neuropathy probably causes destruction of the fingers and toes due to repeated accidental trauma and secondary infection
    • Eye: Infection of the eye may result in blindness
    • Testes: Infection of the testes in men causes infertility (Recall that the testes reside at a lower temperature than most of the body)
    • Blood: M. leprae can also be found at high levels in the blood and most organs; strikingly however, Lepromatous Leprosy is not associated with any organ dysfunction
Treatment
  • Successful treatment of M. leprae requires multi-therapy with combinations of Rifampin, Clofazimine, or Dapsone for 6 months or more.