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We work with the protozoan parasite Leishmania…. Leishmania. Leishmania. Discovery of the infectious agent. Etienne Sergent. Edmond Sergent. William Leishman. Charles Donovan. 1921:extracel. promastigote. 1900: intracellular amastigote. Med Mol Para. Leishmania. - PowerPoint PPT Presentation
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We work with the protozoan parasite Leishmania
Leishmania
Discovery of the infectious agent
1921:extracel. promastigote
1900: intracellular amastigoteWilliam LeishmanCharles Donovan
Edmond Sergent
Etienne Sergent
Leishmania Med Mol Para
2
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
33Introduction
Leishmania
4According to disease burden estimates, leishmaniasis ranks third in disease burden in disability-adjusted life years caused by neglectedtropical diseases and is the second cause of parasite-related deaths after malariaMed Mol Para
Disability adjusted life years lostWHO RegionDALY (in thousands)Africa328Americas45Eastern Mediterranean281Southeast Asia1,264Western Pacific51Total:1,969DALY: Number of years lost due to ill health disability or death
Leishmania 5Med Mol Para
Leishmania 6
Med Mol Para
Leishmania 7
Med Mol Para
Leishmania 8
Med Mol Para
Leishmania: a digenetic life cycle
9Med Mol Para
Leishmania: a digenetic life cycle10Med Mol Para
Procyclic promastigote - LPG with galactose branching sugars- Able to bind midgut epithelium- non-infective stageMetacyclic promastigote- LPG with arabinose substituting galactose- LPG increases in size (Gal-Man-PO4) repetitive units- Not able to bind to midgut epithelium- Infective stagePimenta et al (1992) Science 256:1812-181511http://www.youtube.com/watch?v=-HY_LbzQ9i4
Stage specific adhesion of Leishmania promastigotes to the Sand fly midgutMed Mol Para
Leishmania: a digenetic life cycle12Med Mol Para
Forestier et al, (2011) Cell Host Microbe Jericho boilAleppo boil oriental sore
L. major
Leishmaniasiscutaneous
Burdwan fever Shahib's diseasekala-azar
L. donovanivisceral
L. tropicachiclero ulcerespundiaAndean sicknessutawhite leprosy
L. braziliensisL. mexicanamuco-cutaneous
13Med Mol Para
Localized Cutaneous LeishmaniasisL. majorL. tropicaL. aethiopicaL. infantumL. mexicanaL. venezuelensisL. amazonensisL. braziliensisL. panamensisL. guyanensisL. peruvianaL. chagasi
Leishmaniasis Med Mol Para
Diffuse Cutaneous LeishmaniasisL. aethiopicaL. mexicanaL. venezuelensisL. amazonensishttp://www.emedicine.com/DERM/topic219.htm
15 Types of Leishmaniasis
LeishmaniasisMed Mol Para
Recidivans Cutaneous LeishmaniasisL. tropicaL. braziliensishttp://www.emedicine.com/DERM/topic219.htm
16
Leishmaniasis16Med Mol Para
Mucocutaneous LeishmaniasisL. majorL. aethiopicaL. mexicanaL. amazonensisL. braziliensisL. panamensisL. guyanensis
LeishmaniasisMed Mol Para
Visceral LeishmaniasisL. donovaniL. tropicaL. infantumL. infantum
18
LeishmaniasisMed Mol Para
Leishmaniasis
Amazon
IndiaMed Mol Para
20
Leishmaniasis
AfghanMed Mol Para
Leishmaniasis
AfghanMed Mol Para
22
Leishmaniasis
NepalMed Mol Para
Symptoms of cutaneous leishmaniasis :Breathing difficultySkin sores, which may become a skin ulcer that heals very slowlyStuffy nose, runny nose, and nosebleedsSwallowing difficultyUlcers and wearing away (erosion) in the mouth, tongue, gums, lips, nose, and inner nose
Systemic visceral infection in children usually begins suddenly with:CoughdiarrheaFeverVomiting Symptoms
Abdominal discomfortFever that lasts for weeks; may come and go in cyclesNight sweatsScaly, gray, dark, ashen skinThinning hairWeight lossADULTS
Children
23Med Mol Para
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.
Diagnosis2424Med Mol Para
Treatment
Antifungal252525Med Mol Para
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.262626http://www.youtube.com/watch?v=yr-01IPiz0gMed Mol Para
VaccineNo successful vaccine.
There are several first generation and second generation vaccines which are under clinical trial.1st gen: use whole molecular organism2nd 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.
272727Med Mol Para
Preventions
Vector control intervention.
Insecticidal treated nets.
Indoor residual spraying.
Screening windows.
Wearing insect repellents.
Wearing protective clothing.2828282828Med Mol Para