leishmaniasis a variety of disease manifestations focal distribution throughout world, especially...
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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• old world: Phlebotomus
• 350 million at risk• 12 million infected• 1.5-2 million clinical
cases/year
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Sandfly Transmission
• transmitted via mouthparts• promastigotes regurgitated
from anterior gut• factors in saliva enhance
infectivity• immunosuppressive factor?
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1) metacyclic promastigotes
2) phagocytosis by macrophage amastigote
3) replication within macrophage
4) release and phagocytosis of amastigotes
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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)
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4) phagocytosis of amastigotes, or ingestion by vector
5) procyclic promastigotes• replication• attachment to
epithelium
6) metacyclic promastigotes
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Lypophosphoglycan (LPG)
• complex glycolipid covering surface of promastigotes
• mediates adherence to gut epithelia• galactose-specific lectin
• LPG changes in metacyclics• cap (galactosearabinose)• increase disaccharide repeats
• glycocalyx 7 17 nm complement resistance
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Clinical Spectrum of LeishmaniasisCutaneous 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
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Some Leishmania Species Infecting Humans
New World Cutaneous,Mucocutaneous, and
Diffuse Leishmaniasis
Old World Cutaneous,Recidivans, and
Diffuse LeishmaniasisVisceral
Leishmaniasis
Mexicana ComplexL. mexicanaL. amazonensis
Braziliensis ComplexL. braziliensisL. panamensisL. guyanensis
L. tropica
L. major
L. aethiopica
L. infantum*
L. donovani
L. infantum*
L. chagasi**
*Both dermotrophic and viscerotrophic strains exist.**L. chagasi (Americas) may be the same as L. infantum (Mediteranean)
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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)
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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)
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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
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• chronic ulcerated, papular, or nodular lesion
• occasionally satellite lesions
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• metastasis via blood or lymphatic systems
• especially L. braziliensis
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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
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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
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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
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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
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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
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Diffuse Cutaneous Leishmaniasis
• scaly, not ulcerated, nodules
• chronic and painless• numerous parasites in
lesions• seldom heal despite
treatment
L. aethiopica
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Diffuse Cutaneous Leishmaniasis
• scaly, not ulcerated, nodules
• chronic and painless• numerous parasites
in lesions• seldom heal despite
treatment
L. mexicana
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Diffuse Cutaneous Leishmaniasis
• scaly, not ulcerated, nodules
• chronic and painless• numerous parasites in
lesions• seldom heal despite
treatment
New World (sp?)
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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
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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
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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
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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
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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
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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
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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
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• due to inadequate treatment• nodular lesions• easily cured with treatment
(in contrast to DCL)
Post Kala Azar Dermal Leishmaniasis
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Some Leishmania Species Infecting Humans
New World Cutaneous,Mucocutaneous, and
Diffuse Leishmaniasis
Old World Cutaneous,Recidivans, and
Diffuse LeishmaniasisVisceral
Leishmaniasis
Mexicana Complex
Braziliensis Complex
L. tropicaL. majorL. aethiopicaL. infantum*
L. donovaniL. infantum*L. chagasi**
• 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
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• susceptible mice strains exhibit Th2 responses• resistant mice strains exhibit Th1 responses• Th1 response stimulates macrophages
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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
• demonstration of parasite
• delayed hypersensitivity skin test
• serology?
• amastigotes (scrapings, biopsy, aspirates)
• in vitro culture (promastigotes)
• inoculate into hamsters
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make incision in active part of lesion
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scrape cells from incision
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prepare Giemsa-stained smear
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aspiration and culture
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promastigotes following in vitro culture
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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
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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)
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Treatment• pentavalent antimonials (eg.,
glucantime, pentostan)• 20 mg/kg/day, 15-20 days
• pentamidine for Sb5+ failures
• amphotericin B
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Control and Epidemiology
• 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
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