Post on 16-Apr-2017
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LeprosyDipendr
a Bhusal
Leprosy0Hansen’s disease
0It is a non fatal, chronic infectious ds caused by Mycobacterium leprae, whose clinical manifestations are largely confined to the skin, peripheral nervous system, upper respiratory tract, eyes and testes
0Almost exclusively a disease of the developing world.
M. leprae 1st bacterial pathogen of humans to be described (Hansen 1868)Morphology
0 Obligate intracellular bacillus (0.3-1µm ×1-8µm)0 Acid fast (with 5% sulphuric acid), but less so than M.
tuberculosis
0 Not alcohol fast0 Arranged singly; in parallel bundles or in globular masses0 The bacilli are slender slightly curved or straight rods
0 In tissue sections, are arranged in clumps resembling cigarette ends and often found in the endothelial cells of blood vessels or in mononuclear cells.
Estimated prevalence of leprosy at the turn of the millennium.
Cultivation So far, not possible to cultivate either in bacteriological
media or in tissue culture
In animals:Foot pads of miceNine banded-armadillo (Dasypus novemcinctus)
Resistance Can survive in warm humid environment for 9-16 days, in
moist soil for 46 days and ultra violet light for 30 minutes.
PathogenesisReplicates intracellularly, within skin histiocytes, endothelial cells, and
the Schwann cells of nerves.nerve damage is the result of 2 processes: damage caused by direct
contact with bacterium and damage caused by CMI attack on nerves.
Incubation period: vary between 2-40 yrs (Av. 5-7 yrs)Source of infection:
0 Nasal discharge from an infective patient0 Skin lesion0 Infected soil
Route of entry: 0 Inhalation of infectious aerosol0 Prolonged close contact with infective patient0 Dermal inoculation of infected soil
Pathogenesis Grows best in cooler tissues (Skin, peripheral nerves, anterior
chamber of eye, upper respiratory tract and testes)
Only bacterium to invade peripheral nerves
Most common nerve affected: Ulnar, posterior auricular, lateral and posterior tibial
Principal target cell: Schwann cell
Unique trisaccharide of M. leprae binds with the basal lamina of Schwann cell
Result in nerve damage with the manifestation of anesthesia and muscle paralysis
Clinical types0 Clinical manifestation is determined by cellular immune response of the
individual to the bacilli
0 Cardinal signs of leprosy (WHO 2010):0 Characteristic skin lesion with partial or total loss of sensation in affected
skin lesion or in area of skin supplied by peripheral nerve involved with or without presence of thickened nerves
0 Presence of AFB in skin smears
0 Two major forms of leprosy:0 Tuberculoid leprosy (With high degree of CMI) and 0 Lepromatous leprosy (with CMI either deficient or absent)
Clinical typesCharacters Lepromarous leprosy Tuberculoid leprosy
Lesions Patches or nodules of 1-2 cmFirst involves face, ear lobes then to extremities
Assymetrical patches with well defined marginInvolves face, gluteal regions and limbs
Nerve involvement Mild and symmetrical anesthesia (late sign)
Thickened peripheral nerves common, usually assymetric
Lepra bacilli in lesion Numerous Scanty
Infectivity Highly infectious Usually non infective
CMI Deficient/absent Adequate
Lepromin test Negative Positive
Prognosis Bad Good
Clinical typesRidley and Jopling’s classification:
Tuberculoid (TT) Borderline tuberculoid (BT) Borderline (BB) Borderline lepromatous (BL) Lepromatous (LL).
WHO classification Paucibacillary: Include all cases of tuberculoid types Multibacillary: Include all cases of lepromatous types and some
cases of borderline types
Immunity0 High degree of innate immunity in man0 Cell mediated immunity determines the response of host to
the infection
Lepromin test 0.1 ml of lepromin (boiled extract of lepromatous tissue,
40 millions dead lepra bacilli) injected intradermally, produces an area of nodular infiltration at the site of injection in skin.
2 types of reactions occur:Early or Fernandez reaction: Erythema and
induration of 10-30 mm in diam. appear after 24-48 hrs after injection
Delayed or Mitsuda reaction: Erythematous nodular lesion of 3-5 mm diameter develops at the site of inoculation in 3-5 weeks.
Lepromin test (Contd.) Lepromin test is negative in lepromatous leprosy but
positive in tuberculoid leprosy
Significance of lepromin testClassification of leprosyPrognostic significance: prognosis better in positive
cases
Lab dx of Leprosy
Diagnosis of leprosy is based primarily on clinical signs and symptoms
Specimens: 0 Skin biopsy and 0 Scrapings: From lesions (patches), nasal mucosa, ear
lobes, eye brows, normal skin
Methods:
1. Direct evidences Direct slit skin smear and acid fast staining
Slit skin smears stained by modified Ziehl-Neelsen (Z-N) method using 5% sulphuric acid as decolourising agent
Smears may show Acid fast bacilli (AFB) arranged in parallel bundles within Macrophage (Lepra cell)
Living bacilli stain uniformly while dead bacilli look fragmented and irregular or granular.
Bacteriological index and Morphological index determined.
Morphological index: Defined as the percentage of uniformly stained bacilli out of the total bacteria present in tissue.
Skin and nerve biopsy: Skin biopsy is collected from active edges of the patches
(lesions) and
Nerve biopsy from the thickened nerve
o for histological confirmation of tuberculoid leprosy when AFB can not be demonstrated in direct smear
2. Indirect evidences: Serological tests:
Detection of antiphenolic glycolipid-1 (anti PGL) antibodies
Tests: Latex agglutination, Mycobacterium leprae particle agglutination (MLPA) test and ELISA
TreatmentWHO recommendations: Multidrug therapy for all
leprosy cases0 Paucibacillary type of leprosy: Rifampin (monthly) and
Dapsone (daily) [For 6 months]
0 Multibacillary type of leprosy: Rifampin, Dapsone and Clofazimine (For 2 years or more)
ControlVaccination
So, far no effective vaccine for leprosy Vaccination with BCG at birth has proved variably
effective in preventing leprosy (results ranging from total inefficacy to 80% efficacy)
gas gangrenegas gangrene
Gas Gangrene (Clostridial myonecrosis, Anaerobic myositis)
Definition: Rapidly spreading oedematous myonecrosis
Characteristically occuring in association with severe wounds of extensive muscle masses contaminated with pathogenic clostridia
Microbiology
0 Causative agents:
Clostridia;
C. perfringens 80% ,
C. septicum, C. novyi, C. sordelli,
C. fallax, C. histolyticum, C. bifermentans
Gram positive Bacilli, Anaerobic, Spore forming
Morphology
Gram stain-Tissue Smear
Resistance
Spores: Boiling < 5 min, 1210C 20 min.
Formaldehyde, 2%
Glutaraldehyde, 2%
Iodine 1%
Toxins
Major Toxins
0α A-E Lecithinase, Necrotising, Haemolytic0β B,C Necrotising0ε B,D Permease0 Iota E Dermonecrotic
Minor Toxins
0δ B, Haemolysin0θ A-E Haemolysin, Cytolysin0κ A-E Collagenase, Gelatinase, Necrotising0λ B,D,E Protease0 µ A-E Hyaluronidase0 ν A-E Deoxyribonuclease, Leucocidin, Hemolytic,
Necrotising
Pathogenesis
0Implantation of clostridial spores/ organism
0Germination/ multiplication
0Fermentation Gas Distention Hypoxia +Toxins
0Necrosis, invasion, Extension
Pathogenesis
Clinical features
0 Incubation period; 10-48hrs0 Pain, Oedema, Gas crepitant
0 Skin- pale bronze, bullae0 Discharge- thin, serosanguinous, offensive
0 Systemic: Diaphoresis (Salty fluid secreted by sweat glands), Tachycardia, Low or no fever
0 Complications: I/V Hemolysis, Haemoglobinuria, Renal failure, Hypotension, Metabolic acidosis, coma
Gas gangrene
Lab diagnosis
0Specimens: Discharge, pus, tissue0Gram stain: GPB, few or no WBC
No or few spore, polymicrobial0Culture:
-RCM
-Blood Agar - double hemolysis
-Egg Yolk Agar- Opalescence
Tissue smear
Anaerobic Jar (Gas Pack System)
Clostridium perfringens
Growth in Blood agar Gram stain- culture
Proof of lecithinase on egg-yolk agar plate
Cont:
Biochemical reaction
Stormy fermentation in litmus milk
Toxin detection
Nagler reaction
D/D Streptococcal fascitis
Nagler reaction- Toxin detection
Management Debridement
Antibiotics: Penicillin G Chloramphenicol, Metronidazole,
Imipenam Antitoxin: C. perfringens 10,000,
C. oedematiens 10,000 C. septicum 5,000 Hyperbaric 02 : 02 conc. arrest multiplication,
toxin production
Hyperbaric oxygen chamber
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