Leishmania Flashcards

1
Q

neglected tropical disease

A

leishmania

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2
Q

the Rose of Jericho

A

Leishmania

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3
Q

leishmania parasite

A
  • single cell
  • genus: Leishmania
  • flagellate
  • Trypanosomatidae family
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4
Q

vector for Leishmania

A

female sand fly

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5
Q

reservoirs for Leishmania

A

canines, rodents, humans

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6
Q

visceral leishmaniasis

A

most severe form of leishmania

often seen in countries with lower standards of healthcare

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7
Q

disease manifestations of leishmania

A

partly due to parasite = presence of RNA virus in parasite and immune response

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8
Q

life cycle of leishmania

A

2 stages
- stages in human and stages in sandfly (bio vector)
- human stage = starts after being bitten; sandflies inject saliva after bloodmeal; saliva = inflammation = calls macrophages bc parasites want to be phagocytosed to hitch a ride
- stage of parasite transmitted to humans via sand fly = promastigote
- will transform into amastigotes in macrophages (human stage)
- after bursting = sandfly stage starts; sand fly will ingest macrophages parasite
- amstogotes turn into promastogotes of sandfly
- will divide in midgut and go to proboscis waiting to take another bloodmeal

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9
Q

T or F. Leishmania has a sexual stage

A

F! not yet identified if there is one

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10
Q

leishmania disease manifestations

A

cutaneous or mucocutaneous
- L. major, L. tropica, L. aethiopica (most popular)

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11
Q

visceral leishmaniasis

A
  • most severe
  • often caused by L. donovani, L. infantum
  • Ganges, southern Nepal, Bangladesh, Brazil, etc.
  • black sickness, black fever, etc.
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12
Q

T or F. A single species of Leishmania can cause more than one type of syndrome

A

T! AND a syndrome can be caused by more than one species
it all depends on host-parasite interactions

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13
Q

two types of Leishmania promastigotes

A

these are in sandfly
- motile
- metacyclic

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14
Q

metacyclic vs motile Leishmania promastigotes

A

after amastigote stage in humans, motile promastigotes (non-infective insect form) will attach to insect gut, then transform to non-dividing infectious forms (metacyclic promastigotes)

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15
Q

transformation stimulus of Leishmania promastigotes depends on many factors, including…

A

temperature

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16
Q

risk factors Leishmania

A
  • poor rural housing conditions, cracked walls, earthen floors
  • poor sanitation = garbage attracts sandflies and dogs
  • lack of accessible medicines
  • if there is conflict = hard to perform vector control and movement of troops
  • HIV
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17
Q

how to be a good reservoir for leishmaniasis

A
  • Be in close contact with sandflies
  • Should be susceptible to the infectious agent
  • Should allow replication of the infectious agent to ensure delivery of large numbers to the victim
  • Should ideally be the main source of food for the fly
  • Disease should develop as a chronic disease giving time for the next transmission season
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18
Q

zoonotic leishmaniasis

A

rural areas
animals to humans via sandflies (mostly skin manifestations)

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19
Q

anthroponotic leishmaniasis

A

densely populated areas
- humans to humans and animals via vector (mostly visceral)

20
Q

how does Leishmania alter the feeding behaviour of sand fly

A

it makes fly hungrier
- secretes gel-like substance that forms a plug that blocks stomach = allows multiplication of parasites
- nutrient and food doesn’t get through until gel is disturbed
- timing of blood feeding correlated to numbers of metacylic promastigotes (increased biting when numbers of infective parasites increase)

21
Q

how does Leishmania adapt to 2 different hosts to complete its life cycle?

A
  • STAGE SPECIFIC VIRULENCE DETERMINANTS = PHOSPHOGUCANS
    > repeating GalB1, 4Manalpha1-PO4
    > membrane bound lipophosphoglycan (LPG) important for delaying macrophage phagosome-lysosome fusion and for attachment/detachment from insect midgut epithelium
    > number of repeating units vary in the different functional stages (ex: 15 repats in promastigotes increases to 30 repeats in metacyclic promastigotes, elongation facilitates detachment from gut)
22
Q

what are phosphoglucans

A

they are secreted acid phosphatase + phosphoglycan

23
Q

Leishmania promastigotes characteristics

A

increased surface glycoprotein GP63 (found on the parasite membrane and aids in internalization of promastigotes)
flagellated
prefers alk pH (sandfly gut)
prefers high glucose conctn

24
Q

what is GP63

A

a zinc proteinase
also called leishmaniolysin

25
Leishmania amastigote characteristics
reduced GP63 (don't need it in human host) if they have flagella, it's rudimentary prefers acid pH (macrophages) prefer sparse glucose conctn (shift metabolizing fats and proteins)
26
T or F. Monoclonal antibodies made to one promastigotes can react with amastigotes
F! no cross-reaction as they have different expressions of protein, different metabolism and different drug targets should be made for different forms
27
how do Leishmania parasites get in macrophages?
receptor-mediated phagocytosis - macs have surface components (ex: complement receptors CR1, CR3, mannose fucose receptor) = helps the binding of cell to promastigote (MAINLY LPG POTION) - parasites use macrophages as replication vessel
28
Hsp100 is an important virulence factor for which Leishmania species?
L. donovanii and L. major
29
steps to internalization of Leishmania promastigotes
- LPG influence on the phagocytic mechanisms: attachment & hindering endosome-lysosome fusion - Promastigotes internalized in phagosome (survival is dependent on LPG which activates F actin and proteins that delay the interaction of phagosomes with endosomes and lysosomes) - Production of heat shock proteins to protect parasite & contribute to resistance to oxidants Differentiate into amastigotes in phagosomes
30
how does Leishmania destroy macrophages?
- Replicating Leishmania destroy macrophages - Depending on the species, they stay in the lymphatics (cutaneous and mucocutaneous) or disseminate through the reticuloendothelial system (macrophage system) to liver, spleen, and cause further damage and recruitment of T cells (visceral) (granuloma formation) - Decreased numbers of tissue and circulating macrophages cause a type of immunosuppression and shift to Th2 response which furthers the spread of infection - Visceral leishmaniasis is a problem in HIV + individuals
31
Role of the immune system in protection from leishmaniasis
- Abs have no protrective effect; associated with non-healing type of disease syndrome - control of infection has to be mediated by CMI = CD4 T cells esp. important!! - spleen = major site for killing parasites and removal of infected macs and neutrophils
32
tegumentary vs visceral leishmaniasis
disease progression: cutaneous to mucocutaneous to visceral lab diagnosis difficult = unless bone marrow aspirate shows macs with parasites **NEGLECTED DISEASE in Africa**
33
ATL (american tegumentary leishmaniasis)
Disease manifestations: LCL: immunocompetent patients, normally 1-10 ulcerated lesions Diffuse CL: nodules on at least 2 body parts MCL: extensive lesions prone to relapse Disseminated L: immunodeficient patients, numerous nodules, papules and plaques
34
this RNA virus is correlated to clinical severity of leishmaniasis
LRV1
35
localized cutaneous leishmaniasis characteristics
- Well-defined round painless ulcer with raised edges and central crust - May heal spontaneously after ~2 months - Ulcer develops to a typical epitheloid granuloma, predominance of Th1 response - Often leaves a hypopigmented smooth thin scar
36
diffuse cutaneous leishmania characteristics
- ofteen seen in anergic individuals (don't response to immune system), lifelong - Subcutaneous nodules that do not usually ulcerate unless trauma - No cell-mediated immunity that responds to leishmania but might have some antibody production - Invasion of nasal mucosa if disease persists
37
disseminated cutaneous leishmaniasis
- worst of cutaneous leishmaniasis - 10-300 pleomorphic lesions in > 2 different sites of the body - Mucocutaneous lesions found in about 30% of the cases
38
mucocutaneous Leishmanaisis characteristics
- Upper respiratory tract mucosa commonly affected: destruction of walls of oral-nasal and pharyngeal cavities - Usually L. braziliensis; often seen in south America - Can appear years after onset of cutaneous leishmania
39
visceral leishmaniasis
- spleen and liver enlarged - Kala-azar (black fever or fatal illness in Hindi) - Usually “old world leishmaniasis” caused by L. donovani and L. infantum - .5 million new cases/yr, most in India/Nepal - Systemic and most severe form of leishmania - If untreated ~100% mortality rate
40
PKDL
post kala-azar dissimentated leishmaniasis - chronic - granulomatous syndrome that happens after treated VL - we don't know why this happens, autoimmune?; 10% of treated VL
41
HIV & Leishmania
- HIV has changed the profile of Leishmania disease, both diseases target similar immune cell; together are much worse than individually - HIV infection increases risks of getting VL and reduces the chances for successful treatment - VL progresses faster in HIV positive individuals - Co-infected patients are a possible source of drug resistant parasites
42
why is leishmania diagnosis a challenge?
- Disease can mimic malaria, typhoid fever, tuberculosis, sporotrichosis, etc - Parasites sequestered in spleen and lymph nodes = invasive biopsies required to get a good specimen - Molecular techniques are very good, but not practical in many areas with leishmaniasis – resources are not there. - Antibodies – not always present, especially in immunocompromised. Cannot reliably diagnose recurrent disease - Severity is due to several factors – including state of the adaptive immune system and presence of the LRV1 virus in the parasite.
43
how to diagnose leishmania
- could confirm if there is lesion! but very insensitive!! - only 10-30% sensitive by direct smear - ~50% by culture; - PCR is best but only done in reference centres - indirect method = antibodies > BUT sensitivity low, some cross-reactivity with other organisms; IFA, ELISA *problem = many species!*
44
treatment of leishmania
- can clean with topical antiseptics - can treat 2ry bacterial infections - reconstruct damaged tissues **treatment failure common due to complex factors = host, parasite species, drug factors, simultaneous infection of parasite with LRV1**
45
important vaccine considerations for Leishmania vaccine
- vaccine must be feasible since patients get immunity to the particular parasitic species after an infection - need to activate the Th1 arm: (IFNy and IL-12 = CELL IMMUNITY) and not Th2 (Ab)
46