Leishmania and Trypansoma Flashcards

1
Q

Leishmania

A
  • Leishmania donovani - visceral disease (Kala Azar)
  • Leishmania major, Leishmania Mexicana, L major - cutaneous disease
  • Leishmania brasiliensis - mucocutaneous disease
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2
Q

Leishmania Life Cycle

A
  • Protozoan with a dimorphic life cycle.
  • Promastigote (elongate, motile form-1.5-3.5 µm by 15-200 µm) found in the sandfly digestive tract and proboscis, is transmitted into the skin of a mammalian host by female sand flies when they take a blood meal.
  • After inoculation, promastigotes are phagocytosed by macrophages, they transform into intracellular Amastigotes (3-5 µm in length) that lack a flagellum.
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3
Q

Leishmania Reservoirs and Vectors

A
  • Human
  • Dog
  • Gerbils
  • Hyrax
  • Expansion of vector areas (Italy)
  • Urban/sylvatic interface in the SA
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4
Q

Leishmania Life Cycles Cont.

A
  • They multiply by simple binary division inside phagolysosomes, rupturing the cell and invading other reticuloendothelial cells.
  • Amastigotes disseminate through regional lymphatics and the vascular system to infect mononuclear phagocytes.
  • Cycle is completed when female sand flies ingest parasitized cells.
  • In the digestive tract of the sand flies, Leishmania parasites develop through a series of flagellated intermediate stages to become infectious metacyclic promastigotes.
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5
Q

Leishmania Pathogenesis

A
  • Organism injected by bite of sandfly (painful bite)
  • Phagocytosis by macrophage
  • Organism replicates in parasitophorous vacuole
  • Control with TH1 response
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6
Q

Leishmania Clinical Disease: Visceral disease (Kala Azar) - L. donovani

A

•occurs in many tropical and subtropical regions of the east and west hemispheres, common in southern Sudan, disease typically develops after a several month of incubation period, most are immunocompetent but may have AIDS or impaired cell-mediated immunity, parasite burden is high and patients present with fevers and weight loss and typically have hepatosplenomegaly, Death usually occurs in the absence of treatment.

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7
Q

Leishmania Clinical Disease: Cutaneous disease - L. major, L. mexicana

A

•characterized by ulcerative lesions, which can be single or multiple., typically last from months to a year but subsequently heal even without treatment.

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8
Q

Leishmania Clinical Disease: Mucocutaneous disease - L. brasiliensis

A

•is characterized first by a primary nodule at the site of infection. This subsequently heals and months, or years, later destruction of nasal and mucosal tissue occurs with severe deformities.

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9
Q

Leishmania Diagnosis

A

• Identify microorganism

– Culture

– Histology

  • Serology (visceral disease)
  • Skin test
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10
Q

Leishmania Treatment

A
  • Amphotericin B
  • Azoles
  • Mifepristone
  • Sodium stibogluconate
  • Heat
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11
Q

Canine Leishmania in the US

A
  • 2009 Vet Clin North Am Small Anim Pract
  • Outbreak of leishmania in Foxhounds in NY kennel 1999
  • Competent vector, Lutzomyia shannoni, endemic to Southeast
  • Breeds of dogs from southern Mediteranean region harbor this parasite
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12
Q

Trypanosomes

A
  • Motile, fusiform protozoans of the blood (in tissue - different)
  • 15-30 µ in length
  • Trypomastigotes are found in humans
  • In leishmaniasis, amastigotes are found in humans
  • African Trypanosoma

– T. brucei gambiense, T. brucei rhodesiense, T. brucei brucei

• American Trypanosoma

– T. cruzi

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13
Q

African Trypanosomisis

A
  • 10-20,000 cases/year (since 1967 only several dozen in Americans)
  • T. brucei gambiense, T. brucei rhodesiense, T. brucei brucei
  • Epimastigotes in salivary glands mature for several weeks to trypomastigotes and passed in saliva
  • Highly Variable Glycoprotein (12-100s changes)
  • As parasitemia progresses, some lose flagella and present as short and stumpy forms.
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14
Q

How do East and West African trypanosomiasis differ?

A

• Epidemiology

– Savannah vs. riverine

– Reservoirs: antelopes vs. humans

• Clinical illness

– West more prolonged: small vessels of heart and CNS with immune complex disease, IgM, lymphadenopathy, rash, myocarditis and seizures

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15
Q

How is African trypanosomiasis diagnosed?

A
  • Agglutinin test
  • Aspirate of lymph node
  • Smear of blood
  • Check the CSF first—if abnormal will need other agents; otherwise surimi or gentamicin
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16
Q

T. cruzi Chagas Disease Epidemiology

A
  • Mexico to Middle Chile and Argentina
  • The reduviid bug (triatomine or kissing bug) is the insect host for T. cruzi.
  • Many different vectors: T. infestans, R. prolixus and emergent forms
  • The vector and the parasite have been found in Arizona
  • Foodborne, congenital
  • Maybe 300,000 thousand infected individuals in the US
17
Q

T. cruzi Chagas Disease Pathogenesis and Immunity

A
  • Insects bite and defecate on the bite site to pass trypomastigote
  • Invade epithelial cells and transforms to amastigote which replicates intracellularly, transforms into a trypomastigote, and is released into the bloodstream
  • Epimastigotes (form that replicates in the insect), metacyclic trypomastigotes (bloodstream form), and amastigotes (intracellular form) all activate alternative pathway of complement but only the epimastigote is killed • Nerve destruction and muscle inflammation and hypertrophy are the hallmarks of chronic Chagas’ disease. Changes in the heart include peripheral denervation, conduction system disturbances and muscle inflammation and hypertrophy. The gastrointestinal tract shows marked dilatation and muscular hypertrophy, a reduced number of myenteric neurons, with ganglion fibrosis, and parasympathetic denervation.
  • Cell-mediate immunity is important
18
Q

The 3 stages of American trypanosomiasis

A
  • Acute: may be asymptomatic or may develop acute disease lasting weeks to months, chagoma and local inflammation at the site of entry, illness is characterized by a high level of parasitemia, symptoms include lymphocytosis, lymphadenopathy, and fever, some develop meningoencephalitis or myocarditis, treatable
  • Indeterminate: some with acute infection (symptomatic or asymptomatic) enter the indeterminant phase, asymptomatic and with low-grade parasitemia, lasts many years and may resolve spontaneously or progress to chronic disease.
  • Chronic (organomegaly): affects two major organ systems: the cardiac and gastrointestinal systems, the latter is uncommon and may be strain-dependent. It occurs not uncommonly in northern Brazil.

– Cardiac involvement is manifested by ventricular arrhythmias and by dilated cardiomyopathy with congestive heart failure.

– GI tract - Any part of the GI tract from the esophagus to the colon may be involved, although colonic and esophageal involvement is the most common.

19
Q

Chagas Disease: Diagnosis

A

• Serology

– EIA

– RIPA

• Acute disease treated with benznidazole nifurtamox