1. Leishmaniasis a variety of disease manifestations
focal distribution throughout world, especially tropics and subtropics
new world: southern Texas to northern Argentina
old world: Asia, Africa, middle east, Mediterranean
transmitted by sand flies
new world: Lutzomyia
old world: Phlebotomus
350 million at risk
12 million infected
1.5-2 million clinical cases/year

2. Sandfly Transmission transmitted via mouthparts
promastigotes regurgitated from anterior gut
factors in saliva enhance infectivity
immunosuppressive factor?

3. 1) metacyclic promastigotes
2) phagocytosis by macrophage  amastigote
3) replication within macrophage
4) release and phagocytosis of amastigotes

4. Leishmania-Macrophage Interactions
attachment and entry
involves CR3 and surface molecules on parasite
entry is typical phagocytosis
phagosome fuses with lysosome
survival within phagolysosome
parasite is resistant to hydrolytic activities
shut down of respiratory burst (ROI)

5. 4) phagocytosis of amastigotes, or ingestion by vector
5) procyclic promastigotes
replication
attachment to epithelium
6) metacyclic promastigotes

6. Lypophosphoglycan (LPG)
complex glycolipid covering surface of promastigotes
mediates adherence to gut epithelia
galactose-specific lectin
LPG changes in metacyclics
cap (galactosearabinose)
increase disaccharide repeats
glycocalyx 7 17 nm
 complement resistance

8. Clinical Spectrum of Leishmaniasis
Cutaneous Leishmaniasis (CL)
most common form, relatively benign self-healing skin lesions (aka, localized or simple CL)
Diffuse Cutaneous Leishmaniasis (DCL)
rare cutaneous infection with non-ulcerating
nodules resembling lepromatous leprosy
Leishmaniasis Recivida
rare hypersensitive dermal response
Mucocutaneous Leishmaniasis (MCL)
simple skin lesions that metastasize, especially to nose and mouth region
Visceral Leishmaniasis (VL)
generalized infection of the reticuloendothelial system, high mortality

10. Cutaneous Leishmaniasis Chiclero Ulcer (L. mexicana)
incubation period: 2 weeks to several months
chronic ulcerated, papular, or nodular lesion
lesion is painless, non-tender, non-pruritic and usually clean
occasionally satellite lesions and/or palpable lymph nodes
Chiclero Ulcer (L. mexicana)

11. Cutaneous Leishmaniasis Chiclero Ulcer (L. mexicana)
incubation period: 2 weeks to several months
chronic ulcerated, papular, or nodular lesion
lesion is painless, non-tender, non-pruritic and usually clean
occasionally satellite lesions and/or palpable lymph nodes
Chiclero Ulcer (L. mexicana)

12. Cutaneous Leishmaniasis
incubation period: 2 weeks to several months
chronic ulcerated, papular, or nodular lesion
self-healing, months to years
lesion is painless, non-tender, non-pruritic and usually clean
occasionally satellite lesions and/or palpable lymph nodes

13. chronic ulcerated, papular, or nodular lesion
occasionally satellite lesions

14. metastasis via blood or lymphatic systems
especially L. braziliensis

15. Cutaneous Leishmaniasis
incubation period: 2 weeks to several months
chronic ulcerated, papular, or nodular lesion
lesion is painless, non-tender, non-pruritic and usually clean
self-healing, months to years
occasionally satellite lesions and/or palpable lymph nodes

16. Old World CL L. tropica (oriental sore) SW Asia, N. Africa dry lesion
urban/dogs
L. major
central Asia, middle East, Africa
wet lesion
rural/rodents
L. infantum
Mediterranea, Europe
L. aethiopica
highlands of Kenya and Ethiopia

17. Old World CL L. tropica (oriental sore) SW Asia, N. Africa dry lesion
urban/dogs
L. major
central Asia, middle East, Africa
wet lesion
rural/rodents
L. infantum
Mediterranea, Europe
L. aethiopica
highlands of Kenya and Ethiopia
hyper-pigmentation of scar

18. Old World CL L. tropica (oriental sore) SW Asia, N. Africa dry lesion
urban/dogs
L. major
central Asia, middle East, Africa
wet lesion
rural/rodents
L. infantum
Mediterranea, Europe
L. aethiopica
highlands of Kenya and Ethiopia

19. Old World CL L. tropica (oriental sore) SW Asia, N. Africa dry lesion
urban/dogs
L. major
central Asia, middle East, Africa
wet lesion
rural/rodents
L. infantum
Mediterranea, Europe
L. aethiopica
highlands of Kenya and Ethiopia

20. Diffuse Cutaneous Leishmaniasis
scaly, not ulcerated, nodules
chronic and painless
numerous parasites in lesions
seldom heal despite treatment
L. aethiopica

21. Diffuse Cutaneous Leishmaniasis
scaly, not ulcerated, nodules
chronic and painless
numerous parasites in lesions
seldom heal despite treatment
L. mexicana

22. Diffuse Cutaneous Leishmaniasis
scaly, not ulcerated, nodules
chronic and painless
numerous parasites in lesions
seldom heal despite treatment
New World (sp?)

23. Leishmaniasis Recidivans
aka, relapsing leishmaniasis or lupoid
often due to inadequate treatment
nodular lesions or rash around central healing
can persist for decades
variable expression
not easily cured

24. Mucocutaneous Leishmaniasis
primarily L. braziliensis (espudia)
two stages
simple skin lesion
2o mucosal involvement
can occur long after primary lesion (up to 16 years)
frequently in naso-pharyngeal mucosae
metastasis via blood or lymphatic systems
variable types and sizes of lesions
chronic and painless

25. Mucocutaneous Leishmaniasis
L. braziliensis (espudia)
two stages
simple skin lesion
2o mucosal involvement
can occur long after primary lesion (up to 16 years)
frequently in naso-pharyngeal mucosae
metastasis via blood or lymphatic systems
variable types and sizes of lesions
chronic and painless

26. Mucocutaneous Leishmaniasis
L. braziliensis (espudia)
two stages
simple skin lesion
2o mucosal involvement
can occur long after primary lesion (up to 16 years)
frequently in naso-pharyngeal mucosae
metastasis via blood or lymphatic systems
variable types and sizes of lesions
chronic and painless

27. Mucocutaneous Leishmaniasis
L. braziliensis (espudia)
two stages
simple skin lesion
2o mucosal involvement
can occur long after primary lesion (up to 16 years)
frequently in naso-pharyngeal mucosae
metastasis via blood or lymphatic systems
variable types and sizes of lesions
chronic and painless
tapir nose

29. Visceral Leishmaniasis
3 possibly related species
L. donovani (Asia, Africa)
India (kala azar)
L. infantum (Mediterranean, Europe)
L. chagasi (New World)
reticuloendothelial system affected
spleen, liver, bone marrow, lymph nodes
onset is generally insidious
progressive disease
75-95% mortality if untreated
death generally within 2 years

30. Clinical Presentation
incubation period
generally 2-6 months
can range 10 days to years
fever, malaise, weakness
wasting despite good appetite
spleno- and hepatomegaly, enlarged lymph nodes
depressed hematopoiesis
severe anemia
leucopenia
thrombopenia  petechial hemorrhages in mucosa

31. Post Kala Azar Dermal Leishmaniasis
due to inadequate treatment
nodular lesions
easily cured with treatment (in contrast to DCL)

32. L. infantum can cause either cutaneous or visceral disease
zymodeme analysis reveals dermotropic and visceraltropic strains
dermotropic strains result in visceral disease in AIDS patients

33. susceptible mice strains exhibit Th2 responses
resistant mice strains exhibit Th1 responses
Th1 response stimulates macrophages

34. Diagnosis of CL, MCL, DCL suspected because of:
geographical presence of parasite
history of sandfly bite
+ skin lesion:
chronic, painless, ‘clean’ ulcer
nasopharyngeal lesions
nodular lesions
amastigotes (scrapings, biopsy, aspirates)
in vitro culture (promastigotes)
inoculate into hamsters
demonstration of parasite
delayed hypersensitivity skin test
serology?

35. make incision in active part of lesion

36. scrape cells from incision

37. prepare Giemsa-stained smear

41. aspiration and culture

42. promastigotes following in vitro culture

43. Delayed Hypersensitivity Skin Test
aka leishmanin skin test, Montenegro reaction
intradermal inoculation of leishmanin
suspension of whole or disrupted promastigotes
preferably from local area
include negative control
induration ± erythema in hours

44. VL Diagnosis suspected because of: geographical presence of parasite
history of sandfly bite
prolonged fever, splenomegaly, hepatomegaly, anemia, etc.
amastigotes in bone marrow aspirates
in vitro culture of aspirates
serological tests
direct agglutination
ELISA dipstick (39 kDa Ag)

45. Treatment pentavalent antimonials (eg., glucantime, pentostan)
20 mg/kg/day, days
pentamidine for Sb5+ failures
amphotericin B

46. Control and Epidemiology
New World Dermal
zoonosis (arboreal mammals = reservoir)
lowland forest
occupational
Old World Dermal
urban = dog reservoir
rural = rodent reservoir
Visceral
India (Ld): human-fly-human
Africa (Ld): rodent reservoir
others: dogs (with lesions) are usual reservoir
depends on local transmission
avoid sandfly bites
bed nets
insecticides
destruction of dog reservoir
‘tropica vaccine’
historical inoculation in covered areas
risk of recidiva or VL