Notes
Mycobacterium leprae (Hansen's Disease)
Sections
Mycobacterium leprae
Characteristics:
Acid-fast
Not grown in vitro; in the lab, it's often grown in mouse footpads.
14-day doubling time.
Human pathogen; also been found in armadillos and some other non-human primates.
Route of transmission is not entirely established.
Long-term contact is necessary; it is thought that respiratory, and possibly skin secretions, transmit the bacteria.
Prefers cooler temperatures:
— Tends to infect superficial structures such as the skin and peripheral nerves.
— In some individuals, the anterior eye chambers and nasal cavities are also affected.
Long incubation period: typically between 3-10 years.
Intracellular pathogen:
— Macrophages and the Schwann cells of peripheral nerves.
— In the histology image, we see foamy macrophages infected with Mycobacterium leprae
— Schwann cell invasion causes demyelination and reduced conduction.
— In the histology image, we see an example of a cutaneous nerve invaded by Mycobacterium leprae.
Hansen's Disease
Chronic, typically non-fatal disease.
Major cause of peripheral neuropathy in areas where infection is endemic.
Treatment can include administration of dapsone, rifampicin, and clofazimine.
Be aware that Mycobacterium lepromatosis is also associated with Hansen's disease; it causes diffuse lepromatous leprosy, and is endemic in Mexico and Costa Rica.
Infection produces a range of clinical manifestations.
Disease severity is determined by the host's cellular immune response, which is influenced by genetic components and environmental conditions.
Tuberculoid leprosy is the milder, less infectious form; Lepromatous leprosy is the more severe, disseminated, and infectious form; Borderline leprosy is in the middle, and is characterized as "immunologically unstable."
Individuals move along this spectrum according to shifts in their immune system responses.
Be aware that there are additional clinically recognized stages that we have omitted for simplicity.
Tuberculoid leprosy:
Associated with CD4+ T cell activation and type 1 cytokines, particularly IL-2 and interferon-gamma; this produces an effective immune response that restricts infection.
Low bacillary load = Paucibacillary Hansen's disease.
Negative slit-skin smear test.
Tuberculoid leprosy is characterized by 5 or fewer lesions with granulomatous inflammation.
— Over time, inflammation damages the peripheral nerves.
— Lesions are dry and scaly with irregular edges; the center of the lesions is typically hypo-pigmented.
Ultimately, nerve damage results in the loss of sensation; hair loss and reduced sweating ability can also occur.
Lepromatous leprosy:
Associated with CD8+ T cells and type 2 cytokines, particularly IL-4 and IL-10.
This response produces an ineffective cellular immune response that facilitates disseminated infection.
High bacillary load = Multibacillary Hansen's disease
Positive slit-skin test
Antibodies may be produced, but they form immune complexes that compound tissue damage.
Widespread lesions with thickened skin and nerve damage occurs.
— Facies leonina, aka, lion face, is the result of thickened skin around the ears, nose, and brows with loss of the eyebrows and eyelashes.
— Major nerves are commonly affected, including the median and ulnar nerves of the upper extremity, and the common fibular nerve and posterior tibial nerves of the lower extremity. The facial nerve is also often damaged.
— Nerve damage can lead to muscular atrophy and paralysis.
— Additionally, some patients experience testicular damage.
Leprosy reactions:
Immune reactions with acute inflammation that can cause permanent nerve damage, so they need to be treated right away.
Analgesics can help with pain, and corticosteroids are necessary to suppress the immune system if nerve damage is suspected.
Type 1 Reactions
Associated with tuberculoid and lepromatous leprosy
Reversal reactions are caused by delayed hypersensitivity immune responses.
Edema and inflammation.
Damage to the peripheral nerve trunks is a major concern.
Type 2 Reactions
Associated with lepromatous leprosy
Characterized by erythema nodosum leprosum that presents as subcutaneous nodules of inflammation on the extensor surfaces of the extremities.
Brought on by humoral immune responses that result in immune complex deposition.
Vasculitis and other complications that damage nerves and organs.
In patients where corticosteroids are contraindicated, thalidomide can be administered; however, this drug is associated with severe birth defects, so caution is warranted in women of child-bearing age.
References:
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. Medical microbiology. Philadelphia: Elsevier/Saunders. (2013).
Levinson, W. E. Review of Medical Microbiology and Immunology. 14th Ed. Lange (2016).
Wynn, T.A. (2015). Type 2 cytokines: mechanisms and therapeutic strategies. Nature Reviews Immunology 15:271-282.
Modlin, R.L. (2010). The innate immune response in leprosy. Curr Opin Immunol. 22(1): 48–54. doi:10.1016/j.coi.2009.12.001.
Han, X.Y. & Silva, F.J. (2014). On the age of leprosy. PLOS Neglected Tropical Diseases. 8(2): e2544.
Gulia, A., Fried, I., Massone, C. (2010). New insights in the pathogenesis and genetics of leprosy. F1000 Medicine Reports. 2:30 http://f1000.com/reports/medicine/content/2/30
Polycarpou, A., Walker, S.L., Lockwood, D.N. (2013). New findings in the pathogenesis of leprosy and implications for the management of leprosy. Current Opinion Infectious Diseases 26(5): 413-419.
Lockwood, D.N. & Saunderson, P.R. (2012). Nerve damage in leprosy: a continuing challenge to scientists, clinicians and service providers. International Health. 4:77-85.
Pinheiro, R.O., de Souza Salles, J., Sarno, E.N., Sampaio, E. P. (2011). Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview. Future Microbiol 6(2): 217-230.
Sinsimer, D., Fallows, D., Peixoto, B., Krahenbuhl, J., Kaplan, G., Manca, C. (2010). Mycobacterium leprae Actively Modulates the Cytokine Response in Naïve Human Monocyte. Infection and Immunity. 78(1): 293-300.
Bhat, R.M. & Prakash, C. (2012). Leprosy: An overview of pathophysiology. Interdisciplinary Perspectives on Infectious Diseases
Volume 2012, Article ID 181089, doi:10.1155/2012/181089.
Talhari, C., Talhari, S., Penna, G.O. (2015). Clinical aspects of leprosy. Clinics in Dermatology 33:26-37.
Images:
Leprosy in cutaneous nerve (CDC/Arthur E. Kaye).
Foamy macrophage w/Mycobacterium leprae (Wikipedia; Author Dr. Roshan Nasimudeen).
Facies leonina (Wikipedia; Pierre Arents).