Pathogenesis and lab diagnosis of Leprosy (Hansen’s disease)

Also known as Hansen’s disease, leprosy is a chronic infectious disease caused by acid fast bacillus, Mycobacterium leprae. In 1873, Dr. Hansen discovered bacteria in leprosy lesions, which rule out that leprosy is a hereditary disease or a punishment from the gods. Leprosy mainly affects skin, peripheral nerves and mucosa of upper respiratory tract (because their optimal temperature for growth is 30°C). It may affect any organs.
Some points to remember:
  1. Leprosy is not highly infectious /very contagious infection.
  2. Infection is acquired by prolonged contact with patients with lepromatous leprosy (heavy shedders) who discharge M. leprae in large numbers in nasal secretions and from skin lesions.
  3. Route of Transmission: Skin and inhalation.
  4. M. leprae multiplies very slowly (with a doubling time of 14 days; slowest growing human bacterial pathogen). # Remember: antibiotic therapy must be continued for a long time, usually several years.
  5. Incubation period of the disease is about five years. Symptoms can take as long as 20 years to appear.
  6. Leprosy is curable


M. leprae replicates intracellularly, typically within skin histiocytes, endothelial cells, and the Schwann cells of nerves. The cell mediated immunity plays the major part in determining the response of the host to the infection.
There are two distinct forms of leprosy-tuberculoid and lepromatous with several intermediate forms between the two extremes.
  1. Tuberculoid leprosy: very few acid fast bacilli in skin smear (paucibacillary disease) : Cell mediated immune (CMI) response  is adequate and lepromin test is positive.
  2. Lepromatous leprosy: large numbers of Mycobacterium leprae chiefly in masses within the lepra cells, often grouped together like bundles of cigars or arranged in a palisade (multibacillary disease).The cell mediated immune  (CMI) response to organism is poor and the lepromin test is negative.
Ridley and Jopling (1966) have introduced a scale for classifying the spectrum of leprosy into five groups-
1.       Tuberculoid (TT)
2.       Borderline tuberculoid (BT)
3.       Borderline (BB)
4.       Borderline Lepromatous (BL)
5.       Lepromatous (LL)
According to WHO, leprosy is divided into two groups, paucibacillary and multibacillary.
Comparison of tuberculoid and  lepromatous leprosy
Type of lesion
One or few lesions with little tissue destruction
Many lesions with marked tissue destruction
Number of acid fast bacilli
Likelihood of transmission
Cell Mediated response to M. Leprae
Reduced or latent
Lepromin skin test
Lepromin Skin Test: The lepromin skin test is not used to diagnose leprosy but to determine what type of leprosy a person has. Lepromin skin test is similar to tuberculin test.  An extract of M.leprae is injected intradermally and induration is observed 48 hours later in those whom a cell-mediated immune response against organism exist.
Lepromin test is employed mostly for the following two purposes.
1.       To classify the lesions of leprosy patients.
2.       To assess the prognosis and response to treatment.

Lab diagnosis:

Sample: Skin lesions or nasal scrapings or specimen from ear lobules.  Slit skin smears are usually taken from 6 routine sites (both earlobes, elbows, and knees)

a.  Microscopy (Slit-skin smear stained with modified Ziehl Neelsen stain: 4 to 5% sulphuric acid or 1% v/v Acid alcohol as decolourising agent).

M. leprae in stained smear
M. leprae in stained smear
  • For Lepromatous leprosy: lipid laden macrophages called ‘foam cells” containing many acid fast bacilli are seen in the skin.
  • For Tuberculoid leprosy: Very few acid fast bacilli are seen and appearance of typical granulomas is sufficient for diagnosis.

M. leprae are slightly curved filament 3-10 m in length containing irregular arrangements of dense material sometimes in the shape of rods. M. leprae which stain with carbol-fuchsin as solid acid-fast rods are believed to be viable (when they were inside the host body at the time of sample collection) and that bacilli which stain irregularly are probably dead and degenerating.

Based on the number of of M. lepare and their morphology in the stained slides Bacteriological index (BI) and  morphological index (MI) can be calculated. These indices are useful in assessing the amount of infection, viability of the organisms and also the progress of the patient under treatment.  Bacteriological index (BI) is an expression of the extent of bacterial loads Where as morphological index (MI) is calculated by counting the numbers of solid-staining acid-fast rods. According to WHO, a more accurate and reliable index of the bacillary content of a lesion is given by the logarithmic index of biopsies (LIB) is a more accurate and reliable index of the bacillary content of a lesion. These indices help to assess the state of patients at the beginning of treatment and to assess progress.

Nine banded armadillo
Nine banded armadillo

b. Culture

M. leprae has not yet been successfully cultured in vitro but it can be grown in the laboratory by injection into the foot pads of mice or nine-banded armadillo. It is a slow growing pathogen with the doubling time of 14 days.

c. Molecular diagnosis: Polymerase Chain Reaction (PCR) can be used as a means of diagnosis of leprosy and also as a tool for  drug assessment.

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