13 Bacteria: Kinetoplastidae Flashcards
Kinetoplast
all Kinetoplastidae have kinetoplast, mitochondrium with many copies of circular mitochondrial DNA
Maxicircles: 50kb, 50 copies of mitochondrial genome
Minicircles: 1kB, 10.000 copies that encodes guide RNA that makes it possible to read maxicircle DNA information through insertion of uridine residues
Leishmania
life cycle in detail
Infective stage
1. Infected Sandfly takes blood meal, injecting promastigotes into human
- Neutrophil-chemotactic factors released
- Neutrophil recruitment
- Parasite sequestration via phagocytosis and NET formation
- Phagocytosis by macrophages (direct or indirect via trojan horse modell)
Diagnostic Stage
- Promastigots differentiates into amastigot (obligate intracellular form)
- Replication in cells (also macropahges) of various tissues
Vector
9. Sanfly takes infected macrophage blood meal
- Amastigots released
- Differentiation into procyclic promastigotes in midgut
- Multiply in midgut and transform into infectious metacyclic promastigotes after 1-2 weeks
Leishmania
Species and disease
Geographical distribution
Reservoir (non human)
Visceral
kala-azar:
donovani (human to human)
e.g. big belly: infected macrophages spleen, liver, ….
Cuteaneous
oriental sore:
tropica, major
Mucocutaneous
espundia:
braziliensis complex
Can be localized or diffuse
Geographical distr.
Mediterannean, South America Middle East, Africa (not south)
Reservoir
hyrax
dogs
both sandfly as vector
human is accidental, human to human transmission for L. donovani most likely
Differentiation of Leishmania promastigotes in sandfly
Evasion of immune system
Procyclic promastigots covered with pre-form of LPG (Lipo-phospho-glycan) that leads to binding to midgut receptor > replication phase
Maturation of LPG (mostly Arabinose) in metacyclic promastigots that leads to promastigots being able to reach mouthparts for transmission to next host
Evasion
LPGs prevents assembly of membrane attack complex, metacyclic LPG is very long and therefore prevents C9 from reaching Leishamnia cell membrane to from MAC
also inhibtion of C3b by Leishmania protei. GP63
still enables CR-mediated phagocytosis by host phagocytes
Polarized course of infection
human
mice
Human
can be local (TH1) or diffuse (TH2)
Mice
BALB/c: TH2 dominant -> susceptible
C57BL/6: TH1 domiant -> resistant
but: parasites persist after clinical cure
Diagnosis
Patient samples
direct methods
indirect methods
Patient samples
visceral: spleen biopsy
cutaneous: skin biopsy/smear
Direct methods:
Histology
Culture:
patient sample in blood containing culture medium, room temperature = growth of promastigots (sandfly temperature)
PCR
Indirect methods:
Skin test for cellular immune response (loc. cutaneous)
serological test for antibodies in serum (visceral)
Delayed type hypersensivity
which test and mechanism?
Tuberculin skin test to test prior Leishmaniasis
Antigen injected into subcutaneous tissue, APC react to induce TH1 response leasing to visible lesions
Best protection against Leishmania infection
Bednets impregnated with incecticides
Vector control
no stay at night in free
long trousers and longarm shirts
Drugs against Leishmania
Pentamidine to inhibit DNA, RNA and protein synthesis
Amphotericin B to interact with cell membrane component ergosterol
Miltefosine to inhibit sterol and phospholipid synthesis
Vaccine against Leishmania
Name
Mechanism
Canileish
excreted secreted proteins of Leishmania infantum, major immunodominant active constituent is Parasite surface antigen
supports TH1-dominated protective immune response in dogs (so far)
Trypanosoma
2 different diseases and species
African Trypanosomiasis
Sleeping sickness:
T. brucei
400k affected, 50k deaths/year
American Trypanosomiasis
Chagas Disease:
T. cruzi
11M affected, 50k deaths/year
African Trypanosomiasis
Transmission
Diagnosis
Transmission
vector: tse tse fly
mother to child (perinatal death)
Blood transfusion
Sexual contact
Diagnosis
microscopic examination of blood smear
African Trypanosomiasis
Pathogenesis ( 2 stages)
Reason for Parasitemia fluctuating levels
Stage 1
Haemolymphatic stage (acute)
mostly asymptomatic, flu-like symptoms
Stage 2 Meningoencephalitic stage (chronic)
Sleeping sickness because it crossed blood brain barrier
Reason for Parasitemia fluctuating levels
Variant Surface glycoprotein with variable n terminal region exposed to immune system:
only one single VSG gene expressed but 1000 VSG genes possible, once antibodies against a certain VSG produced destruction by host but another variant proliferates, therefore parasitemia levels like a wave
African Trypanosomiasis
Treatment for 2 strains
Prevention
Treatment
brucei gambiense: Pentamidine
brucei rhodesiense: Suramin
but side effect can be severe like bone marrow supression, …
Prevention
Insecticides DDT
Education
Vector control
Public awareness
American Trypanosomiasis
Transmission
Disease
Diagnosis
Transmission
Kissing bug
Disease
Chagas Disease with acute stage (1%) severe for infants, resolves after weeks/months
chronic stage (10-20 years later) 30-40% with enlarged heart (30-40%)) that can result in heart failure etc
Treatment
no
Diagnosis
Microscopic examination of blood smear
serology
Isolation of the agent to inoculate in culture with specialized media
