Leprosy: Etiology, Pathogenesis, Lab Diagnosis

By Acharya Tankeshwar •  Updated: 05/21/22 •  5 min read

Leprosy is an age-old disease, associated with social stigma; historical records and literature show that people afflicted with leprosy have often been ostracized by their communities and families. Also known as Hansen’s disease, leprosy is a chronic infectious disease caused by an acid-fast bacillus, Mycobacterium leprae.

A man with leprosy (image by J. L. Losting.)

In 1873, Dr. Hansen discovered bacteria in leprosy lesions, which rule out that leprosy is a hereditary disease not a punishment from the gods. Leprosy mainly affects the skin, peripheral nerves, and mucosa of the upper respiratory tract (because their optimal temperature for growth is 30°C). It may affect many organs.

Some points to remember:

  1. Leprosy is not a 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 1-2 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 with multidrug therapy (MDT). Three antibiotics (dapsone, rifampicin, and clofazimine) in combination are used for 6 months to 1 year based on the type of leprosy (paucibacillary or multibacillary).


M. leprae replicates intracellularly, typically within skin histiocytes, endothelial cells, and the schwann cells of nerves. Cell-mediated immunity (CMI) plays a major part in determining the response of the host to leprosy.

Pathogenesis of Leprosy

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 the 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 the 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 World Health Organization (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
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 in whom a cell-mediated immune response against the organism exists.

 The 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: Ideally, at least six sites should be sampled, including earlobes, eyebrows, elbow, knees, nasal mucosa, and skin lesions. Skin biopsy from edges of active patches and nerve biopsy from thickened nerves can also be collected.

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

M. leprae in stained smear
M. leprae in stained smear

M. leprae is a slightly curved filament 3-10 m in length containing irregular arrangements of dense material sometimes in the shape of rods. M. leprae which stains 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.

BI and MI are useful in assessing the amount of infection, the 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 whereas morphological index (MI) is calculated by counting the numbers of solid-staining acid-fast rods (viable during sample collection).

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). These indices help to assess the state of patients at the beginning of the treatment and to assess progress.

Find details about “Logarithmic Index of Bacilli In Biopsies Here”

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 footpads of mice or nine-banded armadillo. It is a slow-growing pathogen with a doubling time of 14 days.

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

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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