Transcript ppt 97-03 format Leish.

We work with the Leishmania
protozoan parasite Leishmania…
Leishmania
Discovery of the infectious agent
William Leishman
Etienne Sergent
Charles Donovan
Edmond Sergent
1921:extracel. promastigote
1900: intracellular amastigote
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Leishmania
• 88 countries/350 million at risk
• 12 million cases/2 million new infected
• 57,000 deaths annually/4 million DALY
• second to malaria in mortality and disability
• synergy with HIV co-infection
• no vaccine, limited treatment
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• emerging disease
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Leishmania
Introduction
According to disease burden estimates, leishmaniasis ranks third in
disease burden in disability-adjusted life years caused by neglected
tropical diseases and is the second cause of parasite-related deaths
after malaria
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Leishmania
Disability adjusted life years lost
• DALY: Number of years lost
due to ill health disability or
death
WHO Region
DALY (in thousands)
Africa
328
Americas
45
Eastern Mediterranean
281
Southeast Asia
1,264
Western Pacific
51
Total:
1,969
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Leishmania
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Leishmania
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Leishmania
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Leishmania: a
digenetic life cycle
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Leishmania: a
digenetic life cycle
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Stage specific adhesion of Leishmania promastigotes
to the Sand fly midgut
Procyclic promastigote
- LPG with galactose branching sugars
- Able to bind midgut epithelium
- non-infective stage
Metacyclic promastigote
http://www.youtube.com/watch?v=-HY_LbzQ9i4
- LPG with arabinose
substituting galactose
- LPG increases in size
(Gal-Man-PO4) repetitive units
- Not able to bind to midgut epithelium
- Infective stage
Pimenta et al (1992) Science 256:1812-1815
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Leishmania: a
digenetic life cycle
Forestier et al, (2011)
Cell Host Microbe
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Leishmaniasis
cutaneous
espundia
chiclero ulcer
white leprosy
Andean sickness
oriental sore
Jericho boil
Aleppo boil
L. major
uta
muco-cutaneous
L. tropica
L. braziliensis
L. mexicana
visceral
kala-azar
Burdwan fever
Shahib's disease
L. donovani
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Leishmaniasis
L. major
L. tropica
L. aethiopica
L. infantum
L. mexicana
L. guyanensis
L. venezuelensis
L. peruviana
L. amazonensis
L. chagasi
L. braziliensis
L. panamensis
Localized Cutaneous Leishmaniasis
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Leishmaniasis
Types of
Leishmaniasis
L. aethiopica
Diffuse Cutaneous Leishmaniasis
L. mexicana
L. venezuelensis
L. amazonensis
http://www.emedicine.com/DERM/topic219.htm
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Leishmaniasis
L. tropica
L. braziliensis
Recidivans Cutaneous Leishmaniasis
http://www.emedicine.com/DERM/topic219.htm
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Leishmaniasis
L. major
L. aethiopica
L. mexicana
L. guyanensis
L. amazonensis
L. braziliensis
L. panamensis
Mucocutaneous Leishmaniasis
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Leishmaniasis
L. donovani
L. tropica
L. infantum
L. infantum
Visceral Leishmaniasis
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Leishmaniasis
Amazon
India
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Leishmaniasis
Afghan
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Leishmaniasis
Afghan
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Leishmaniasis
Nepal
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Symptoms
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Symptoms of cutaneous leishmaniasis :
Breathing difficulty
Skin sores, which may become a skin ulcer that heals very slowly
Stuffy nose, runny nose, and nosebleeds
Swallowing difficulty
Ulcers and wearing away (erosion) in the mouth, tongue, gums, lips, nose, and inner nose
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Systemic visceral infection in children usually begins suddenly with:
Cough
diarrhea
Children
Fever
Vomiting
Abdominal discomfort
Fever that lasts for weeks; may come and go in cycles
Night sweats
Scaly, gray, dark, ashen skin
Thinning hair
Weight loss
ADULTS
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Diagnosis
• Direct visualization of amastigotes by hematological staining doing tissue biopsy.
• Enzyme linked Immunosorbent assay (ELISA).
• Antigen coated dipsticks.
• Direct agglutination test.
• Leishmania specific PCR assay.
• Indirect Immunofluorescent antibody test.
• Complete blood count.
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Treatment
Antifungal
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Treatment
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Miltefosine
First oral drug against leishmaniasis.
http://www.youtube.com/watch?v=yr-01IPiz0g
Originally developed for cancer.
Used in the case of visceral and cutaneous leishmaniasis.
Also target HIV infected macrophages.
Inhibit PI3K/AKT pathways.
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Vaccine
• No successful vaccine.
• There are several first generation and second generation vaccines which are under
clinical trial.
• 1st gen: use whole molecular organism
• 2nd gen: recombinant protein grown in bacteria; purified; then, take vaccine of
that purified vaccine.
• LACK antigen (Leishmania homologue of receptor for activated C kinase).
• LEISH-F1+MPL-SE Vaccine (Second generation vaccine) was in clinical trial for its
safety and immunogenicity (2011). Presently under clinical development.
• Infectious Disease Research Institute launched two phase-1 clinical trial of vaccine
against visceral Leishmaniasis.
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Preventions
• Vector
control intervention.
• Insecticidal treated nets.
• Indoor residual spraying.
• Screening windows.
• Wearing insect repellents.
• Wearing protective clothing.
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