Epidemiological Determinants of Leprosy

As per Park's Textbook of Preventive and Social Medicine

I. AGENT FACTORS

(a) The Agent - Mycobacterium leprae

• Leprosy is caused by M. leprae, an acid-fast bacillus that occurs in the human host both intracellularly and extracellularly.
• They occur characteristically in clumps or bundles called "globi".
• They have a particular affinity for Schwann cells and cells of the reticulo-endothelial system.
• They remain dormant in various sites and can cause relapse.
• The bacterial load is highest in lepromatous cases; as many as 2 to 7 billion bacilli were estimated in one gram of leproma.
• More than 20 antigens have been detected in M. leprae by electrophoretic techniques. The most important is phenolic glycolipid (PGL), which may be the specific M. leprae antigen.
• M. leprae has not yet been conclusively shown to grow in artificial medium. Large quantities are produced by multiplication in the 9-banded armadillo and nude mouse.

(b) Source of Infection

• Multibacillary cases (lepromatous and borderline lepromatous) are the most important source of infection in the community.
• Inapparent (subclinical) infections are also a source.
• The role of tuberculoid forms as sources is unclear; however, all patients with "active leprosy" must be considered infectious.
• Natural infections with M. leprae have been found in wild animals (armadillos, mangabey monkeys, chimpanzees), though whether this is a public health threat remains uncertain.

(c) Portal of Exit

• The nose is the major portal of exit. Lepromatous cases harbour millions of M. leprae in their nasal mucosa, discharged when they sneeze or blow their nose.
• Bacilli can also exit through ulcerated or broken skin of bacteriologically positive cases.

(d) Infectivity

• Leprosy is a highly infectious disease but of low pathogenicity.
• An infectious patient can be rendered non-infectious by:
  • Dapsone treatment for approximately 90 days, or
  • Rifampicin for 3 weeks
  • Local application of rifampicin (drops/spray) may destroy all bacilli within 8 days.

(e) Attack Rates

• Among household contacts of lepromatous cases, 4.4% to 12% are expected to show signs of leprosy within 5 years.
• This occurs despite treatment of the index case, as most cases are infectious for long periods before treatment is sought.

II. HOST FACTORS

(a) Age

• Infection can occur at any age depending on opportunities for exposure.
• Incidence rates generally rise to a peak between 20 and 30 years of age, then fall.
• In areas where leprosy is rare, first contact may not occur early in life, so the disease may appear late.
• High prevalence among children is of considerable epidemiological importance - it indicates active, spreading disease.

(b) Sex

• Both incidence and prevalence are higher in males than in females in most regions of the world.
• Sex difference is least in children below 15 years and more marked among adults.
• The excess in males is partly attributed to greater mobility and increased opportunities for contact.
• The difference is more marked among lepromatous cases than non-lepromatous cases.

(c) Migration

• Leprosy was historically a rural problem in India, but migration from rural to urban areas has created a significant problem in urban areas too.

(d) The Prevalence Pool

• The prevalence pool is in constant flux from inflow (new cases, relapses, immigration) and outflow (cure/inactivation, death, emigration).
• Of the factors influencing the prevalence pool, the importance of inactivation of disease and mortality are less well recognized.

(e) Inactivation of Disease

• Where treatment facilities exist, inactivation through specific treatment is the primary mode of elimination from the prevalence pool.
• Even without specific treatment, a majority of patients with tuberculoid and indeterminate types tend to cure spontaneously.
• A study in India showed spontaneous regression among children with tuberculoid leprosy was about 90% over 20 years.
• A South India study showed an inactivation rate of 10.9% per year among newly detected tuberculoid cases.

(f) Immunity

• Only a few persons exposed to infection actually develop the disease.
• Cell-mediated immunity (CMI) is the key defence mechanism against M. leprae.
  • Effective CMI leads to spontaneous healing or paucibacillary (PB) leprosy.
  • Deficient CMI leads to uncontrolled spread and multibacillary (MB) leprosy.
• In lepromatous leprosy, there is complete breakdown of CMI, and the lepromin test is negative.
• Humoral response is also present: antibodies (IgG, IgM) are more pronounced at the lepromatous end of the spectrum.
• The anergy of lepromatous leprosy is due to suppression of T cell production of interleukin-2 (T-cell growth factor).
• Subclinical infections are far more common than previously thought; they contribute to active immunity.
• A degree of cross-immunity is possible through infections with related mycobacteria (e.g., BCG, M. tuberculosis).

(g) Genetic Factors

• HLA-linked genes influence the type of immune response that develops, thereby affecting susceptibility and the form of disease.

III. ENVIRONMENTAL FACTORS

1. Presence of infectious cases in the environment - the most direct environmental risk factor.
2. Humidity - favours the survival of M. leprae outside the host:
   • M. leprae can remain viable in dried nasal secretions for at least 9 days.
   • In moist soil at room temperature, for up to 46 days.
3. Overcrowding and lack of ventilation within households - facilitates droplet transmission and close contact.
4. Socioeconomic factors - poverty, poor nutrition, and low living standards reduce host resistance and increase exposure risk.

Mode of Transmission (Related Environmental Context)

• (A) Droplet infection - Aerosols containing M. leprae from nasal discharge; the respiratory tract is increasingly recognized as the main portal of entry.
• (B) Contact transmission - Direct or indirect contact (with soil, contaminated clothes/linen). First lesions found on feet and legs in endemic hilly areas of India support this route.
• (C) Other routes - Insect vectors or tattooing needles cannot be ruled out, but are not considered important in nature.

Incubation Period

• Average of 3 to 5 years or more; symptoms can take as long as 20 years to appear.
• Some leprologists prefer the term "latent period" given the prolonged duration.

Reference: Park's Textbook of Preventive and Social Medicine, pp. 362-364 (Agent factors, Host factors, Environmental factors sections on Leprosy).

Epidemiological Determinants of Leprosy

(Park's Textbook of Preventive and Social Medicine)

I. AGENT FACTORS

1. Causative organism - Mycobacterium leprae, an acid-fast bacillus occurring intra- and extracellularly; characteristically forms clumps called globi; has special affinity for Schwann cells.
2. Source of infection - Multibacillary cases (lepromatous and borderline lepromatous) are the primary source; all patients with "active leprosy" are considered infectious.
3. Portal of exit - The nose is the major portal; millions of bacilli are discharged via nasal secretions during sneezing. Ulcerated or broken skin is a secondary portal.
4. Infectivity - Highly infectious but of low pathogenicity. Rendered non-infectious by dapsone (~90 days) or rifampicin (~3 weeks).
5. Attack rate - Among household contacts of lepromatous cases, 4.4% to 12% develop signs of leprosy within 5 years.
6. Bacterial load - Highest in lepromatous cases; up to 2-7 billion bacilli per gram of leproma. Key antigen is phenolic glycolipid (PGL).

II. HOST FACTORS

1. Age - Incidence peaks between 20-30 years; high prevalence in children indicates active, spreading disease in the community.
2. Sex - Incidence and prevalence are higher in males, attributed to greater mobility and increased contact opportunities; least difference in children under 15.
3. Immunity - Cell-mediated immunity (CMI) is the key defence. Effective CMI → paucibacillary leprosy or spontaneous cure; deficient CMI → multibacillary leprosy. Lepromatous leprosy shows complete CMI breakdown (lepromin test negative).
4. Spontaneous inactivation - Even without treatment, tuberculoid and indeterminate types tend to self-heal. Spontaneous regression in children with tuberculoid leprosy was ~90% over 20 years in Indian studies.
5. Genetic factors - HLA-linked genes influence the type of immune response, thereby determining susceptibility and the form of disease that develops.
6. Migration - Rural-to-urban migration has spread leprosy into urban areas, which was historically considered a purely rural problem in India.

III. ENVIRONMENTAL FACTORS

1. Presence of infectious cases - The most direct environmental risk; the greater the number of untreated multibacillary cases in a community, the higher the transmission risk.
2. Humidity and survival of bacilli - M. leprae survives in dried nasal secretions for at least 9 days and in moist soil at room temperature for up to 46 days, making the environment a reservoir.
3. Overcrowding and poor ventilation - Facilitate close contact and droplet transmission within households; a major driver in low-income communities.
4. Socioeconomic conditions - Poverty, malnutrition, and poor living standards reduce host resistance and increase prolonged exposure to infectious cases.
5. Soil contact - First lesions found on feet and legs in endemic hilly areas of India and 91% of first lesions on extremities in the Philippines support indirect transmission via soil contact.

Reference: Park's Textbook of Preventive and Social Medicine, pp. 362-364.