Leprosy microbiology

Leprosy- classification(ridley jopling, madrid, indian), differences between lepromatous and tuberculoid leprosy, Complication(lepra reaction 1and 2), and lab diagnosis.
Lab diagnosis- specimen, microscopy, grading, antibody detection, and lepromin test.
Treatment of leprosy(pauci/multibacillary)

1. LEPROSY

2. Leprosy
•A chronic mycobacterial disease
of ancient world.
•First bacterial pathogen of
human to have been described.

3. Leprosy (Hansen’s Disease)
Gerhard Henrik Armauer Hansen
was a physician who first
identified Mycobacterium leprae
as the cause of leprosy in 1873

4. MYCOBACTERIUM LEPRAE
History:recognized since Vedic times in India (described
as KushtaRogain SushrutaSamhita, 600 BC
G. H. ArmauerHansen (1873) -discovered of
lepra bacilli
Shepard (1960) –multiplying lepra bacilli in
footpads of mice kept at a low temperature .

5. Not cultivable -can be
maintained nine
banded armadillo &
foot pad
Intracellular & strict
aerobe
Less acid fast
compared to tubercle
bacilli -5% sulfuric acid
Cigar-like bundles in
Virchow’s lepra cells
Grow in cooler areas of
the body -skin,
peripheral nerves,
upper respiratory tract,
eyes
Generation time -12–
13 days

6. Classification of Leprosy
Ridley Jopling classification
(1966)
Madrid classification (1953)Indian classification (1981,
Leprosy association of India)
Lepromatous leprosy (LL)Lepromatous typeLepromatous type
Borderline Lepromatous leprosy
(BL)
Borderline Borderline
Borderline leprosy (BB)Indeterminate typeIndeterminate type
Borderline Tuberculoid leprosy
(BT)
Tuberculoid typePure neurotic type
Tuberculoid leprosy (TT)- Tuberculoid type

7. Lepromatous v/s
Tuberculoid Leprosy
CharactersLepromatous leprosy (LL)Tuberculoid leprosy (TT)
Skin lesionsMany, symmetrical,
Margin is irregular,
1.Multiple nodules (lepromata)
2. Plaques
3. Xanthoma-like papules
Leonine facies and eyebrow alopecia
One or few, asymmetrical
Margin is sharp
Lesions-Hypopigmented, annular macules
with elevated borders
Tendency towards central clearing

8. Lepromatous v/s
Tuberculoid Leprosy
CharactersLepromatous (LL)Tuberculoid leprosy (TT)
Bacillary loadMultibacillaryPaucibacillary
Bacteriological index4–6+ 0–1+
Nerve lesionAppear late
Hypoesthesia is a late sign
Early anesthetic skin lesion,
Enlarged thickened nerves,
Nerve abscess seen (common in BT)
Cell mediated immunityCMI lowCMI normal

9. Lepromatous v/s
Tuberculoid Leprosy
CharactersLepromatous (LL)Tuberculoid leprosy (TT)
Lepromin testNegativePositive
CD4/CD8 T cell ratio1:22:1 (normal)
Humoral immunityExaggeratedNormal

10. Lepromatous v/s Tuberculoid Leprosy
CharactersLepromatous leprosy (LL)Tuberculoid leprosy (TT)
Auto AntibodiesElevated Not seen
Antibodies to PGL-1Elevated in 95% of casesElevated in 60% of cases
MacrophagesFoamy type (lipid laden)Epithelioid type
Langhans giant cellsNot seenFound

11. Skin Lesions of
Leprosy
•Nodular lesions of lepromatous leprosy
•Hypopigmented skin lesions of tuberculoid leprosy

12. Other
Categories of
Leprosy
•Characteristics in between tuberculoid and
lepromatous types
•May shift to either TT or LL type with chemotherapy or
alterations in host resistance
Borderline type:
•Early unstable cases with one or two hypopigmented
macules
•definite sensory impairment
•bacteriologically negative
Indeterminate type:
•Neural involvement without any skin lesion
•Bacteriologically negative
Pure neurotic type:

13. IMMUNITY
Humoral antibodies are produced. Minor
role in disease control as bacilli are
intracellular
CMI: vital role in control of the disease
People with low CMI usually develop LL type
of lesions-Lepromin test Negative
People with intact CMI usually develop TT
type lesions –lepromin test positive

14. -TT patients -release of TH1 specific cytokines (IL2,
interferon γ) àmacrophage activation àphagocytose
and kill bacilli

15. Epidemiology
Source: Multibacillary (LL and
BL) cases
Mode of transmission: .
Aerosols containing M.leprae
Portal of entry -nose or skin
Contact transmission (skin):
•Direct contact from person to
person
•Indirect contact with infected soil,
fomites (clothes, linens)
•Direct dermal inoculation during
tattooing.

16. Complications –Lepra
Reactions
CharactersLepra Reaction Type ILepra Reaction Type II
Hypersensitivity
reaction
Type IV (delayed hyper sensitivity)Type III (immune complex mediated)
Seen with Borderline leprosyLepromatous variety (BL,LL)
Manifests asInflammation of previous lesions, new skin lesions and
neuritis
Crops of painful erythematous papules which
become nodular
T helper responseTH1 predominatesTH2 predominates
Other organsUsually not affectedEyes, testes and kidney are affected

17. Complications
CHARACTERSLEPRA REACTION TYPE ILEPRA REACTION TYPE II
Progresses as If occurs before treatment –Progresses towards
LL (down grading reaction)
If occurs after treatment-Progress towards TT
(reversal reaction)
It usually occurs following the start of
chemotherapy.
TreatmentGlucocorticoidGlucocorticoid, thalidomide,
clofazimine and antipyretics

18. Complications -
Deformities
•About 25% of untreated cases develop deformities
•Due to—nerve injury, disease process, injury
-Face: Leonine facies, sagging face, loss of eyebrow/eye lashes, saddle
nose and corneal opacity and ulcers
-Hands: Claw hand and wrist drop
-Feet: Foot drop, clawing of toes, inversion of foot, and plantar ulcers

19. Deformities
seen in
untreated
lepromatous
leprosy

20. Laboratory
Diagnosis
Specimen Collection
•-Six samples –four skin (forehead,
cheek, chin and buttock), one from
ear lobe and nasal mucosa by
nasal blow/scraping
•Slit skin smear
•Nasal scraping
•Biopsy -thickened nerves and
nodular lesions

21. Microscopy
•Ziehl–Neelsen(5% sulfuric acid)
•Acid fast bacilli
•Singly or in groups (cigar like
bundles)
•Globiin Virchow‘s lepra cells or
foamy cells
•Live bacilli -uniformly stained
with parallel sides
•Dead bacilli -less uniformly
stained, fragmented & granular

22. Grading
of the
Smear
1–10 bacilli in 100
OIF =1+
1–10 bacilli in 10
OIF = 2+
1–10 bacilli per OIF
= 3+
10–100 bacilli per
OIF = 4+
100–1000 bacilli
per OIF = 5+
>1000 bacilli or
bacilli in clumps
and globi in each
OIF = 6+

23. Indices
Bacteriological index (BI): Total
number of bacilli (live and dead) per oil
immersion field
Morphological index (MI): Percentage
of uniformly stained bacilli out of the
total number of bacilli counted
-MI is a better marker to monitor the
treatment response

24. Antibody Detection
•FLA-ABS (Fluorescent leprosy antibody
absorption test):
•ELISA detecting IgM antibodies to PGL-1
(phenolic glycolipid-1) antigen of M.
Leprae

25. Lepromin test
Lepromin –A Antigen
0.1mL injected
intradermally
Early or Fernandez
reaction: >24–48
hours
Induration
surrounded by
erythema. >10 mm
diameter -positive
DTH, Indicates past
exposure to lepra
bacilli
Late or Mitsuda
reaction: After 21 days
indicates patient’s CMI
is intact
: Nodule >5 mm
àulcerates

26. WHO Treatment regimens
CriteriaPaucibacillaryMultibacillary
Treatment
regimen
1)Dapsone (100mg) given daily,
self administered
2)Rifampicin (600mg) given
once a month under
supervision
1)Dapsone (100mg) daily
2)Rifampicin (600mg) once a month
3)Clofazimine–300mg once a month
under supervision, à50mg daily, self
administered
Duration of
treatment
Up to 6monthsUpto 1 yr or till smear negative
Follow upAnnually till 2 yrsAnnually till 5 yrs