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Leishmaniasis
Leishmaniasis
Leishmania donovani (complex)
Leishmania donovani (complex)
(VL)
(VL)
Leishmania tropica (CL)
Leishmania tropica (CL)
Leishmania major (CL)
Leishmania major (CL)
Leishmania aethiopica (CL)
Leishmania aethiopica (CL)
Leishmania mexicana (Complex)
Leishmania mexicana (Complex)
(CL)
(CL)
Leishmania brazilliensis (complex)
Leishmania brazilliensis (complex)
(MCL)
(MCL)
Leishmania peruriana
Leishmania peruriana
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The Parasite
The Parasite
•
Phylum
Phylum
•
Order
Order
•
Family
Family
•
Genus
Genus
Sarcomastigophor
Sarcomastigophor
a
a
Kinetoplastida
Kinetoplastida
Trypanosomatidae
Trypanosomatidae
Leishmania
Leishmania
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Morphology
Morphology
•
Promasitogte
Promasitogte
•
Insect
Insect
•
Motile
Motile
•
Midgut
Midgut
•
Amastigote
Amastigote
•
Mammalian
Mammalian
stage
stage
•
Non-motile
Non-motile
•
Intracellular
Intracellular
Digenetic Life Cycle
Digenetic Life Cycle
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Morphology
Morphology
•
Promastigote
•
Amastigote
Flagella
Kinetoplast
Golgi
Nucleus
Cytoskeleton
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Promastigote
6
•
Amastigotes
(*) of
Leishmania
donovani in
the cells of a
spleen. The
individual
amastigotes
measure
approximately
1 µm in
diameter.
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Amastigote
8
•
Amastigotes of
Leishmania in a
macrophage
from a lymph
node of a dog.
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•
Leishmania
(Leishman-
Donovan or LD
bodies). Lying in
macrophage cells
from liver.
Giemsa. ×12000.
Enlarged by 9.6.
10
•
A
macrophage
filled with
Leishmania
amastigotes.
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Life cycle
Life cycle
•
The organism is transmitted by the bite of
The organism is transmitted by the bite of
several species of blood-feeding sand flies
several species of blood-feeding sand flies
(Phlebotomus) which carries the promastigote
(Phlebotomus) which carries the promastigote
in the anterior gut and pharynx. It gains
in the anterior gut and pharynx. It gains
access to mononuclear phagocytes where it
access to mononuclear phagocytes where it
transform into amastogotes and divides until
transform into amastogotes and divides until
the infected cell ruptures. The released
the infected cell ruptures. The released
organisms infect other cells. The sandfly
organisms infect other cells. The sandfly
acquires the organisms during the blood meal,
acquires the organisms during the blood meal,
the amastigotes transform into flagellate
the amastigotes transform into flagellate
promastigotes and multiply in the gut until the
promastigotes and multiply in the gut until the
anterior gut and pharynx are packed. Dogs
anterior gut and pharynx are packed. Dogs
and rodents are common reservoirs.
and rodents are common reservoirs.
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Mammalian Hosts
Mammalian Hosts
•
Rodents
Rodents
•
Gerbils
Gerbils
•
Hyraxes
Hyraxes
•
Bats
Bats
•
Porcupines
Porcupines
•
Opossums
Opossums
•
Sloths
Sloths
•
Primates
Primates
•
Dogs
Dogs
•
Foxes
Foxes
•
Anteaters
Anteaters
•
. . . .
. . . . .
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Vectors
Vectors
Phlebotomine Sandflies
Phlebotomine Sandflies
6 genera world wide distribution
6 genera world wide distribution
Phlebotomus & Lutzomia
Phlebotomus & Lutzomia
500 species
500 species
Females Haematophagus
Females Haematophagus
Males sap feeders
Males sap feeders
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Clinical Disease
•
Visceral
• Fatal (90%
untreated)
• Liver
• Spleen
• Bone marrow
•
Cutaneous
• Generally Self-
healing
• Skin
• Mucous membranes
SPECTRUM OF DISEASE
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Initial Infection
•
Similar in all species
•
Inoculation of promastigotes
•
Inflammation & chemotaxis
•
Receptor mediated
phagocytosis
Promastigote
Amasitgote
Transformation
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Parasite Spread
Parasite Spread
Macrophage lysis & parasite
Macrophage lysis & parasite
release
release
Lymphatic spread
Lymphatic spread
Blood spread
Blood spread
Target organs
Target organs
Skin/lymph nodes/spleen/liver/
Skin/lymph nodes/spleen/liver/
bone marrow
bone marrow
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Visceral Leishmaniasis
Visceral Leishmaniasis
•
1903
1903
•
1920
1920
•
1931
1931
William Leishman
William Leishman
Pentavalent antimony
Pentavalent antimony
Experimental
Experimental
transmission
transmission
Leishmania donovani (Complex)
Leishmania donovani (Complex)
L.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantum
L.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantum
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VL - Clinical
VL - Clinical
Manifestation
Manifestation
Variable - Incubation 3-100+ weeks
Variable - Incubation 3-100+ weeks
Lowgrade fever
Lowgrade fever
Hepato-splenomegaly
Hepato-splenomegaly
Bone marrow hyperplasia
Bone marrow hyperplasia
Anemia, Leucopenia & Cachexia
Anemia, Leucopenia & Cachexia
Hypergammaglobulinnemia
Hypergammaglobulinnemia
Epistaxis , Proteinuria, Hematuria
Epistaxis , Proteinuria, Hematuria
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•
Profile view of a
teenage boy
suffering from
visceral
leishmaniasis.
The boy exhibits
splenomegaly,
distended
abdomen and
severe muscle
wasting.
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•
A 12-year-old
boy suffering
from visceral
leishmaniasis.
The boy
exhibits
splenomegaly
and severe
muscle wasting.
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•
Jaundiced
hands of a
visceral
leishmaniasis
patient.
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•
Enlarged spleen
and liver in an
autopsy of an
infant dying of
visceral
leishmaniasis.
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Post Kala Azar Dermal
Post Kala Azar Dermal
Leishmanoid
Leishmanoid
Normally develops <2 years
Normally develops <2 years
after recovery
after recovery
Recrudescence
Recrudescence
Restricted to skin
Restricted to skin
Rare but varies geographically
Rare but varies geographically
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Cutaneous leishmaniasis
of the face.
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A cutaneous leishmaniasis
lesion on the arm.
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INFECTION
INFECTION
Sub-clinical or inapparent
Sub-clinical or inapparent
infection
infection
Recovery Death
Immune to reinfection Concurrent
infection
PKDL
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Diagnosis
Diagnosis
Clinical signs & symptoms
Clinical signs & symptoms
Hypergammaglobulinemia
Hypergammaglobulinemia
ELISA/Formol gel
ELISA/Formol gel
Bone marrow biopsy
Bone marrow biopsy
Spleen or liver biopsy
Spleen or liver biopsy
Culture & Histology
Culture & Histology
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Speciation
Speciation
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Similar morphology
Similar morphology
•
Isoenzyme profiles -
Isoenzyme profiles -
Zymodemes
Zymodemes
•
Monoclonal antibodies
Monoclonal antibodies
•
DNA hybridisation - PCR
DNA hybridisation - PCR
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Treatment
Treatment
Good nursing
Good nursing
Diet
Diet
Antibiotics
Antibiotics
Pentavalent antimony
Pentavalent antimony
Pentamidine
Pentamidine
New drugs - New delivery
New drugs - New delivery
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Control
Control
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Vector control
Vector control
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Reservoir control
Reservoir control
•
Treatment of active cases
Treatment of active cases
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Vaccination
Vaccination