Mycobacterium leprae Flashcards
(20 cards)
Briefly describe Mycobacterium leprae
- Causative agent of leprosy aka Hansen’s disease
- Described by Armauer Hansen in 1873
- Presents with disfiguring of skin and peripheral nerves
- Leprosy is a chronic, granulomatous, and debilitating disease
- M. leprae is an obligate intracellular pathogen with tropism for
macrophages and Schwann cells. - It cannot be propagated in culture
What is the epidemiology?
- 208,619 new cases in 2018 (WHO) – Southeast Asia
- Adolescents aged 10-19 years of age are the most susceptible, followed by a second peak at the age of 30 years or older
- Men>women
- Contact with multi-bacillary px
- Endemic in Nigeria
- Seen globally – Active in 120 countries
- With India contributing 58%, Brazil 16%, and Indonesia 9% to all new cases detected, these
three countries contributed 83% of the new cases detected globally in 2011
Discuss the transmission of M.leprae
MCQ What is it’s generation time?
What is its incubation time?
It has a predilection for what body parts?
Where are they located in large numbers?
What is their natural host?
- Requires prolonged contact
- Source from nasal discharge or secretions from persons with Multibacillary leprosy
- Acquisition of infection is by droplets or remotely through skin contact – 107 viable bacilli per day can be shed in respiratory secretions of people with multibacillary leprosy
- Generation time=13days
- Incubation period=3-5years
- Slow growing obligate intracellular parasite
- Has predilection for body parts with low temperature e.g. ear lobe, nose, mouth, testes, eyes, skin
- Found in large numbers in Schwann cells of peripheral nerves and mononuclear phagocytes – cause demyelination of peripheral nerves
- Man is the natural host
PATHOGENESIS
What causes dennervation of cells?
- Not much is known
- No toxin has been identified
- Phenolic glycolipid-1 (PGL-1) does the damage causing Apoptosis of schwann cells (resulting in dennervation of cells)
- Nerve damage is due to cell infiltration by M. leprae and allergic inflammation
- Marked peripheral nerve thickening (especially in superficial nerves, such as the ulnar, median, and posterior tibial nerves)
- Neurologic disturbances are manifested by nerve infiltration and thickening, with resultant anesthesia, neuritis, paresthesia, trophic ulcers, and bone resorption and shortening of the digits
- The skin lesions may occur as pale, anesthetic macular lesions 1–10 cm in
diameter; diffuse or discrete erythematous, infiltrated nodules 1–5 cm in
diameter; or a diffuse skin infiltration
Classify leprosy using the Ridley-Jopling classification (clinical, microbiology and histopath) Q
Ridley-Jopling classification:
– Clinical manifestations (number and appearance of skin lesions, peripheral
nerve thickening/impairment and systemic or mucosal involvement),
– the bacillary load: paucibacillary or multibacilllary
– and histopathology: inability to differentiate between paucibacillary and multibacilllary
* Fite staining of biopsy material (stain used to detect m.leprae)
* Two major poles:- TUBERCULOID AND LEPROMATOUS – Dependent on the Cell-mediated immunity
5 Clinical types of leprosy
Type symbol Immune response
1.Tuberculoid leprosy TT GOOD
2. BORDERLINE TUBERCULOID BT FAIR
3. MID BORDERLINE BB PARTIAL
4. BORDERLINE LEPROMATOUS BL POOR
5.LEPROMATOUS LL NIL
Discuss RR, ENL and lucio phenomenon (leprosy reactions)
lucio phenomenon resembles what?
- Reversal reactions, present most often with increased erythema of preexisting
skin lesions and progressive peripheral neuropathy (type 1) - Erythema nodosum leprosum (ENL), which presents with systemic signs and
painful erythematous skin nodules (type 2) – antigen-antibody complex deposition in the skin with the subsequent activation of
complement
– malaise and fever up to 40°C.
– In severe cases, ENL can be life-threatening, presenting with features similar to septic shock
– Thalidomide ± steroids (treatment) - Lucio’s phenomenon (also referred to as erythema necroticans) - resembles a necrotizing fascitis
Discuss TUBERCULOID LEPROSY (TT)
TUBERCULOID LEPROSY (TT)
* Marked thickening of affected nerves ,e.g. ulnar nerve palpated above the elbow, may lead to deformities like clawed hand/toe
* No bacilli are found in skin and nasal smears hence the term PAUCIBACILLARY LEPROSY
* Biopsy will show few organisms and the typical tubercle:- epitheloid cells, macrophages, lymphocytes, few organisms and langhans giant cells
Discuss BORDERLINE LEPROSY(BT,BB,BL)
- Cellular immunity ranges from less good to poor
- Number of lesions range from few (BT)to several(BB) or many(BL)
- In BT, there is moderate to marked loss of pigment, perspiration and feeling
- Skin smears show very few or no bacilli (BT), several to many (BB and BL)
- Biopsy may be required to confirm diagnosis and classification of patients
Diagnosis
Mainly Clinical
* Peripheral nerves should be palpated for nerve thickness and tenderness,
and both motor and sensory function (particularly for temperature and
light touch) should be carefully evaluated
* macules, plaques, diffuse infiltrated lesions, or subcutaneous nodules
(“lepromas”)
Discuss LEPROMATOUS LEPROSY(MULTBACILLARY)
LEPROMATOUS LEPROSY(MULTBACILLARY)
* No cellular immunity
* Wide spread area of infection.
* Lesions are small, many, and shiny
* symmetrical nonscaling infiltrative dermopathy
Symmetrical skin lesions
* No loss of feeling, nodules may be present on the face and trunk
* Facial nodules present a bumpy face called LEONINE FACES lion-like with loss of eye lashes
* Lesions in the nose/earlobe contain large number of bacilli and in the macrophages of the skin
- COMPLICATIONS result from involvement of various organs
- Larynx——vocal changes
- Eye———-ciliary madarosis, blindness
- Extremities—amputation of toe and fingers, chronic ulcers
- Testes—orchitis, testicular atrophy, infertility
- Ovaries —oophoritis, infertility
- LEPROMATOUS LEPROSY
- Paralysis and death
- Granuloma is formed by bacilli filled macrophages called LEPRA CELLS
- High level of ineffective antibody leading to immune complex (type 2) hypersensitivity e.g. ERYTHEMA NODOSUM LEPROSUM, these are nodules containing, antibody, mycobacterial antigen and complement
- Other complications :-arthritis, glomerulonephritis, amyloidosis
Differential diagnosis
- A biopsy distinguish leprosy from other infiltrative disorders:
– cutaneous tuberculosis
– sarcoidosis,
– swimming pool granuloma (Mycobacterium marinum)
– granuloma annulare
– granuloma multiforme
– ANCA-associated (formerly Wegener’s) granulomatosis
– tertiary syphilis
– cutaneous or post kala-azar leishmaniasis
– Lyme disease
– deep fungal infections
onchocerciasis
– lupus profundus
– cutaneous lymphomas. - pityriasis versicolor or dermatophyte infections -scaly
Lab diagnosis
- MICROSCOPY:-(Modified ZIEHL NEELSEN STAIN)
- AFB stain of skin-slit smears or skin biopsy material
- Organism is less alcohol fast and less heat tolerant
- Carbol fuchsin stain
- 1% acid alcohol (lesser)
- Malachite green/methylene blue
- Result :- red bacilli, beaded or massed as globi
- Other stains: – Fite or modified Fite stain is – hematoxylin and eosin /immunohistochemistry
- Biopsy is important in the diagnosis of TT/BT leprosy, where organisms
are absent or scanty but otherwise in LL - It utilizes interpretation of cellular response and invasion of nerve tissue
by inflammatory cells - OTHER METHODS OF DIAGNOSIS
- Fluorescent leprosy antibody absorption test
- DNA amplification
- Serology: ELISA (less helpful)
Culture
- CANNOT grow on artificial media
- Has been cultivated on the foot pad of mice, rat and 9-banded armadillo
- LEPROMIN TEST
- Lepromin is autoclaved lepromatous tissue containing killed leprosy
bacilli, when injected intradermally, three types of reaction may occur,
FERNANDEZ,MITSUDA & MEDINE - Medine reaction: 4 to 6 hr. ‘’ Fernandez reaction: 48 hr. `Mitsuda
reaction: 21 to 28 days
Lepromin Test
- The Fernández reaction occurs within the first 2 days and represents a delayed
type hypersensitivity reaction - At 3 weeks, the Mitsuda reaction is measured. A positive Mitsuda reaction is
described as an indurated lesion of more than 4 mm that histologically shows
granuloma formation. A positive reaction corresponds to the acquisition of cell
mediated immunity against the M. leprae and occurs in
tuberculoid leprosy patients and most leprosy contacts. - Borderline leprosy patients show an indurated skin lesion of less than 3 mm and
lepromatous patients have negative reaction
Reason for lingering leprosy
- Low awareness
- Misdiagnosis
- stigmatization
TREATMENT & CONTROL
- Treatment consisted of isolating patients in leprosaria
- Dapsone (4’4’diamino-diphenyl sulphone)
- Rifampicin
- clofazimine
- The drugs are given in combination to reduce the incidence of resistance
- Duration depends on the clinical type
- Children of active patients need one year prophylactic treatment while house hold contacts should also be treated
- Paucibacillary leprosy: Dapsone 100mg/day plus rifampin 600mg/day
for 12 months. - Multibacillary leprosy: Dapsone 100mg/day plus rifampin 600mg/day
plus clofazimine 50mg/day for 24 months - In the event of resistance developing (rare), the Quinolones are added
- The is no effective vaccination yet – BCG – a little protective
Complications
Hand and finger ulcers
Leg ulcers
Largophthalmos
Clawed hand
Preventing complications
- Wearing protecting materials
- Constant examination of affected areas
- Giving appropriate medication
- Protecting population at risk
- Screening and early commencement of therapy
- Rehabilitation
Q 10 Examples of granulomatous diseases
- Tuberculosis
- Sarcoidosis
- Leprosy
- Crohn’s disease
- Syphilis
- Cat-scratch disease
- Histoplasmosis
- Brucellosis
- Granulomatosis with polyangiitis
- Berylliosis
