19. Protozoa (Leishmania) Flashcards
who is in the class kinetoplastida?
- leishmania
- trypanosoma
what unique feature do kinetoplastids have?
the unique organelle, the kinetiplast
what is a kinetoplast?
a disk shaped mass of circular DNA inside a large mitochondrion that contains many copies of the mitochondrial genome
how does kinetoplast DNA look?
it is relatively abundant and is a tighly packed mass of DNA
the kinetoplastid genome is composed of ______.
ktDNA
the two types of ktDNA occur in a _________ and are called ______ and _______.
linked mass within the mitochondrion
mini-circles; maxi-circles
what do maxi circles encode?
mitochondrial genes and they are more or less equivalent to the mtDNA
mini-circles are ________ and rapidly evolving, and their function is less clear.
heterogenous
what do mRNAs expressed from maxi-circles require?
extensive RNA editing
what is RNA editing in maxi-circles mediated by?
several multi-protein complexes but the information comes from small guide RNAs that are encoded on mini-circles
what is special and novel about kinetoplastid DNA?
that there are 2 genomes in the mitochondrion, one of which contains sequence information that corrects errors in the other
how are the errors on the maxi-circles corrected?
they need to be edited
where does editing of the maxi-circles take place?
in the mitochondrion of kinetoplastids
what does the extent of editing correlate with?
the stage in the parasitic life cycle and the corresponding metabolic changes - such as aerobic/anarobic
what is mini-circle DNA used for in practice?
parasite detection and differentiating between various isolates
what is a glycosome?
a peroxisome-like organelle in which glycolysis occurs (conversion of glucose to pyruvate)
how many membranes does a glycosome have?
1
what does the glycosome change in comparison to other eukaryotic organisms?
it sequesters a large number of glycolytic enzymes that would otherwise be located in the cytosol
the glycosome of kinetoplastids shares some enzymes with _________ and __________ of other protists, plants and animals.
peroxisomes; glyoxysomes
what are the four major morphological forms of kinetoplastids, which are associated with the different life cycle stages in various species that cause disease in humans?
- trypomastigote
- amastigote
- promastigote
- epimastigote
where is the kinetoplast located in the trypomastigote?
on the posterior
where is the flagellum in a trypomastigote?
it emerges from the posterior end of the parasite (basal body, bb) and extends the length towards the anterior where the extension of the free flagellum emerges from the anterior end
how long is the undulating membrane in a trypomastigote?
it spans the length of the parasite
what is the use of the undulating membrane trypomastigote?
it functions like a fin and increases the motility of the organism
how does the amastigote look like?
spherical in shape and no free flagellum
the _____ and the ______ are present in the amastigote
basal body; base of the flagellum
what is the kinetoplast identified as in microscopy
a dark staining body near the nucleus
is the amastigote motile?
no
what is the morphology of the promastigote?
the kinetoplast is towards the anterior and a free flagellum with no undulating membrane emerges where it will pull the organism from
what is the morphology of the epimastigote?
The kinetoplast is more centrally located, usually just anterior to nucleus, and the flagellum emerges from the middle and forms a shorter undulating membrane than in trypomastigotes
who is noticeably more motile, epimastigotes or trypomastigotes?
trypomastigotes
what are the 4 types of leishmaniasis?
- cutaneous leishmaniasis
- mucosal leishmaniasis
- visceral leishmaniasis
- nodular post-kala-azar dermal leishmaniasis (PKDL)
how is Leishmania spp. transmitted
by the bite of certain species of sandflies
- Phlebotomus (old world)
- Lutzomia (new world)
most forms of Leishmania are only spread through ______ but some can be spread between humans
animals, as a zoonosis
how many species of Leishmania cause human infection
21/30 that can infect mammals
how are different species of Leishmania distinguished?
they are morphologically indistinguishable, they can be distinguished by isoenzyme analysis, DNA seq analysis, or monoclonal antibodies
which parasite causes visceral leishmaniasis?
L. donovani
which parasites cause cutaneous leishmaniasis?
L. tropica; (L. t. major, minor and ethiopia)
which parasite causes mucocutaneous leishmaniasis?
L. braziliensis, also L. mexicana and L. peruviana
what is visceral leishmaniasis also called?
Kala-azar, black fever, dum-dum fever
what is cutaneous leishmaniasis also called?
oriental sore, Delhiulcer, Aleppo, Delhi or Baghdad boil
what is mucocutaneous leishmaniasis also called?
espundia, Uta, chiclero ulcer
how many countries is leishmaniasis found in?
88
what kind of life cycle does Leishmania have?
a digenetic one; with 2 hosts
what are the 2 morphological forms of Leishmania?
- promastigote- in the sandfly vector
- amastigote- in the host (e.g. human)
where is Leishmania found in cutaneous leishmaniasis?
intracellularly in macrophages in skin lesions
where is leishmania found in visceral leishmaniasis?
in the mononuclear phagocyte system of blood, liver, lymph nodes, spleen
what are the features of the promastigote stage of leishmania?
- insect stage
- motile
- midgut
what are the features of the amastigote stage of leishmanis?
- mammalian stage
- non-motile
- intracellular
where does sexual reproduction occur for Leishmania?
in sand flies, the natural vector of leishmania
how is leishmania transmitted?
the bite of the infected female sandfly
which stage do the sandflies inject into the host during their blood meals?
the infective stage - the promastigotes
what part of the sandfly transmits the parasite?
the proboscis
what happens to promastigotes that reach the puncture wound?
they are phagocytised by macrophages and other types of mononuclear phagocytic cells
what do promastigotes transform into in the phagocytes?
into the tissuestage - the amastigotes
how do amastigotes multiply?
by simple division
what do amastigotes do after multiplying?
proceed to infect other mononuclear phagocytic cells
what is the pathogenesis of leishmaniasis due to?
an immune reaction to the pathogen, particularly cell-mediated immunity
what does lab examination of the blood show in leishmaniasis?
- marked decrease in white blood cells
- relative increase in monocytes and lymphocytes
- reduced platelets
- anemia
- IgM and IgG levels are extremely elevated
why are IgM and IgG antibodies extremely elevated?
due to both specific antibodies and polyclonal activation
what is seen in clinical disease of cutaneous leishmaniasis?
- it is generally self-healing
- seen in skin
- mucous membranes
what is seen in the clinical disease of visceral leishmaniasis?
- it is fatal, up to 90% if untreated
- liver
- spleen
- bone marrow
what causes cutaneous leishmaniasis in the old world?
L. tropica
L. major
L. ethiopia
what causes cutaneous leishmaniasis in the new world?
L. mexicana
which is the most common form of leishmaniasis?
cutaneous
how is cutaneous leishmaniasis characterized?
one or more sores, papules, or nodules on the skin
what are the sores of cutaneous leishmaniasis often described as?
a volcano with a raised edge and central crater
what may be observed near the sores?
swollen lymph nodes
where are the swollen lymph nodes if the sore is on the arm or the hand?
under the arm
how long after the bite is a nodule produced?
2-8 weeks
is the papule painful?
no, relatively painless
the center of the papule _____ while _____ develop at the periphery
encrusts; satellite papules
how long the the ulcer take to heal?
2-10 months - but leaves a scar
which parasite causes mucocutaneous leishmanisis?
L. braziliensis
what are the clinical features of mucocutaneous leishmaniasis?
- the same as those of cutaneous leishmaniasis, except that in this disease the organism can metastasize and the lesions spread to mucoid tissues (oral, pharyngeal and nasal) and lead to their destruction and hence sever deformity.
how long after the original skin lesion can the deformities occur in mucocutaneous leishmaniasis?
months to years after
which parasite causes visceral leishmaniasis?
- L. donovani and L. d. infantum in the old world
- L. donovani chagasi in the new world
who does L. donovani infect?
people of all ages
who does L. d. infantum infect?
young children as well as infants
where is visceral leishmaniasis usually the least severe?
from the Middle East
what is usually associated with visceral leishmaniasis?
fever, weight loss, and an enlarged spleen and liver
why is there usually a delay in diagnosis of visceral leishmaniasis?
because the symptoms are not specific
when should visceral leishmaniasis always be considered?
in patients with a chronic fever whom are from an endemic area
what is the causative organism of New World visceral leishmaniasis?
L. d. chagasi
why is there rarely a local lesion in visceral leishmaniasis?
because the L. donovani organisms are rapidly eliminated from the site of infection
where do the parasites multiply in visceral leishmaniasis
in the mononuclear phagocytic cells of the spleen, live, lymph nodes, bone marrow, intestinal mucosa and other organs
what are the symptoms 1-4 months after infection in visceral leishmaniasis?
- occurrence of fever with a daily rise to 39-40°C, +chills and sweating
- the spleen and liver progressively become enlarged
what is the issue with chronic disease?
it renders patients susceptible to other infections
what happens in untreated disease?
result is death
what can happen to the hands/skin of a patient with visceral leishmaniasis?
jaundice
how is diagnosis done for leishmaniasis?
- based on a history of exposure to sandflies
- synmptoms
- isolation of the organisms from the lesion aspirate or biopsy, by direct examination or culture
what is done in the laboratory?
the use of a biopsy, and examination of Giemsa stained slides of the relevant tissue is the most common technique
what is antibody detection good for? what is it not useful for?
useful in visceral leishmaniases
limited value in cutaneous disease
what methods exist for parasite detection/species identification?
biochemical (isoenzymes)
immunological (immunoassays)
molecular (PCR)