We work with the protozoan parasite Leishmania Leishmania
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Discovery of the infectious agent 1921:extracel. promastigote
1900: intracellular amastigote William LeishmanCharles Donovan
Edmond SergentEtienne Sergent Leishmania Med Mol Para 2
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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 emerging disease Leishmania Med Mol Para 3
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Introduction Leishmania 4 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 Med Mol Para
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Disability adjusted life years lost WHO RegionDALY (in
thousands) Africa328 Americas45 Eastern Mediterranean281 Southeast
Asia1,264 Western Pacific51 Total:1,969 DALY: Number of years lost
due to ill health disability or death Leishmania 5 Med Mol
Para
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Leishmania 6 Med Mol Para
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Leishmania 7 Med Mol Para
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Leishmania 8 Med Mol Para
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Leishmania: a digenetic life cycle 9 Med Mol Para
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Leishmania: a digenetic life cycle 10 Med Mol Para
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Procyclic promastigote - LPG with galactose branching sugars -
Able to bind midgut epithelium - non-infective stage Metacyclic
promastigote - 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 11 http://www.youtube.com/watch?v=-HY_LbzQ9i4 Stage
specific adhesion of Leishmania promastigotes to the Sand fly
midgut Med Mol Para
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Leishmania: a digenetic life cycle 12 Med Mol Para Forestier et
al, (2011) Cell Host Microbe
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Jericho boil Aleppo boil oriental sore L. major Leishmaniasis
cutaneous Burdwan fever Shahib's disease kala-azar L. donovani
visceral L. tropica chiclero ulcer espundia Andean sickness uta
white leprosy L. braziliensis L. mexicana muco-cutaneous 13 Med Mol
Para
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Localized Cutaneous Leishmaniasis L. major L. tropica L.
aethiopica L. infantum L. mexicana L. venezuelensis L. amazonensis
L. braziliensis L. panamensis L. guyanensis L. peruviana L. chagasi
Leishmaniasis Med Mol Para
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Diffuse Cutaneous Leishmaniasis L. aethiopica L. mexicana L.
venezuelensis L. amazonensis
http://www.emedicine.com/DERM/topic219.htm 15 Types of
Leishmaniasis Leishmaniasis Med Mol Para
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Recidivans Cutaneous Leishmaniasis L. tropica L. braziliensis
http://www.emedicine.com/DERM/topic219.htm 16 Leishmaniasis 16 Med
Mol Para
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Mucocutaneous Leishmaniasis L. major L. aethiopica L. mexicana
L. amazonensis L. braziliensis L. panamensis L. guyanensis
Leishmaniasis Med Mol Para
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Visceral Leishmaniasis L. donovani L. tropica L. infantum 18
Leishmaniasis Med Mol Para
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Leishmaniasis Amazon India Med Mol Para
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20 Leishmaniasis Afghan Med Mol Para
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Leishmaniasis Afghan Med Mol Para
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22 Leishmaniasis Nepal Med Mol Para
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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 Systemic visceral infection in children usually begins
suddenly with: Cough diarrhea Fever Vomiting Symptoms 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 Children 23 Med Mol Para
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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. Diagnosis 24 Med Mol Para
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Treatment Antifungal 25 Med Mol Para
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Treatment Miltefosine First oral drug against leishmaniasis.
Originally developed for cancer. Used in the case of visceral and
cutaneous leishmaniasis. Also target HIV infected macrophages.
Inhibit PI3K/AKT pathways. 26
http://www.youtube.com/watch?v=yr-01IPiz0g Med Mol Para
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Vaccine No successful vaccine. There are several first
generation and second generation vaccines which are under clinical
trial. 1 st gen: use whole molecular organism 2 nd 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. 27 Med Mol Para
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Preventions Vector control intervention. Insecticidal treated
nets. Indoor residual spraying. Screening windows. Wearing insect
repellents. Wearing protective clothing. 28 Med Mol Para