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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

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slide1

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
slide2

Sandfly Transmission

  • transmitted via mouthparts
  • promastigotes regurgitated from anterior gut
  • factors in saliva enhance infectivity
    • immunosuppressive factor?
slide3

1) metacyclic promastigotes

2) phagocytosis by macrophage  amastigote

3) replication within macrophage

4) release and phagocytosis of amastigotes

slide4

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)
slide5

4) phagocytosis of amastigotes, or ingestion by vector

  • 5) procyclic promastigotes
    • replication
    • attachment to epithelium
  • 6) metacyclic promastigotes
slide6

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
slide8

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
slide10

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
  • occasionally satellite lesions and/or palpable lymph nodes

Chiclero Ulcer (L. mexicana)

slide11

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
  • occasionally satellite lesions and/or palpable lymph nodes

Chiclero Ulcer (L. mexicana)

slide12

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
slide13

chronic ulcerated, papular, or nodular lesion

  • occasionally satellite lesions
slide15

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
slide16

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
slide17

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

slide18

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
slide19

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
slide20

Diffuse Cutaneous Leishmaniasis

  • scaly, not ulcerated, nodules
  • chronic and painless
  • numerous parasites in lesions
  • seldom heal despite treatment

L. aethiopica

slide21

Diffuse Cutaneous Leishmaniasis

  • scaly, not ulcerated, nodules
  • chronic and painless
  • numerous parasites in lesions
  • seldom heal despite treatment

L. mexicana

slide22

Diffuse Cutaneous Leishmaniasis

  • scaly, not ulcerated, nodules
  • chronic and painless
  • numerous parasites in lesions
  • seldom heal despite treatment

New World (sp?)

slide23

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
slide24

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
slide25

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
slide26

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
slide27

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

slide29

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
slide30

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
slide31

Post Kala Azar

Dermal Leishmaniasis

  • due to inadequate treatment
  • nodular lesions
  • easily cured with treatment (in contrast to DCL)
slide32

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
slide33

susceptible mice strains exhibit Th2 responses

  • resistant mice strains exhibit Th1 responses
  • Th1 response stimulates macrophages
slide34

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?
slide43

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 48-72 hours
slide44

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)
slide45

Treatment

  • pentavalent antimonials (eg., glucantime, pentostan)
    • 20 mg/kg/day, 15-20 days
  • pentamidine for Sb5+ failures
  • amphotericin B
slide46

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