Parasitology Flashcards
organisms that cause diseases in humans
virus
bacteria
unicellular eukaryotes that are parasites (microparasites)
Multicellular eukaryotes that are parasites (macroparasites)
cryptosporidium lifecycle
a unicellular parasite acquired by ingestion of contaminated food or water (causes diarrhoea)
zoonotic parasites
zoonoses- a disease that can be transmitted from animals to humans
diagnosis of malaria
it is once the parasites in the blood you start to become sick.
Giemsa stained blood smear- considered gold standard
requires trained and experienced use
can diagnose different parasite species
presumptive diagnosis- no longer recommended in most regions
leads to misuse of drugs and un-necessarily high drig pressure in the population
The HRP2 rapid diagnostic test
HRP2 is synthesised in the parasite and exported in the RBC
- released into the blood during parasite egress
- reaches very high levels in infected blood
- function of the protein is unclear
- this protein is used in many rapid diagnostic tests
- when the red blood cell bursts, the HRP2 is released into the blood
on the strip: lysed blood and anti HRP2 start to soak into strip, strip has antibody that recognised hrp2, strip as another antibody, recognises anti hrp2 antibody
Antigenic variation
Trypansoma brucei-sleeping sickness
1000s variant surface glycoprotiens, DNA recombination and chromatin silencing, almost infinite repertoire
Plasmodium falciparum-malaria: Approx 60 PfEMP1 proteins, chromatin silencing and recombination
Trypanosoma brucei
sleeping sickness
parasite is extracellular in blood
1000s variant surface glycoprotein encoding genes
many are incomplete or pseudogenes
parasites replicate in blood during infection. T.brucei repliactes in about 5 hours. In blood look for VSG RNA
Mechanism 1
Switching blood stream expression site can switch VSG expression. switch off- silent histone modification (no transcription), switch on - histone modification allow active transcription. Trypanosome VSGs are expressed from blood stream expression sites but coding sequences are also found elsewhere in the genome
Mechanism 2
array conversion- silent VSG gene is copied from a silent VSG array into active expression site
Silent VSG not in bloodstream expression sites. ‘Red’ VSG DNA is copied into the active blood stream expression site. Parasite now expressed ‘red’ VSG
Mechanism 3
Telomeric coversion. Silent VSGs in a silent bloodstream expression site. Entire telomere (repeats, VSGs, telomeric repeats) replace equivalent sequence in the Active blood stream expression site. Parasite now expressed ‘red’ VSG
Mechanism 4
Segmental conversion. Silent VSGs not in bloodstream expression sites (some may be partial genes or pseudogenes). Parts of several VSG genes are assembled in the Active vlood stream expression site to assemble an entirely new VSG (contains parts of multiple VSGs)
Anti-parasitic vaccines
The RTS, S vaccine
- first malaria vaccine to go beyond phase III clinical trials. currently undergoing large trials in Africa. based on the CS protein (surface of sporozoites)
protection is partial and wares over time
some indications that sequence variation in CS protein may be problematic
New vaccine approaches
Attenuated sporozoites are very promising vaccine candidates, attenuated by irradiation, genetic attenuation
Aim: develop a malaria parasite that does not cause disease but can illicit an immune response without causing malaria
1) find a gene that is essential for parasite growth in the liver, knockout the gene
parasites can invade hepatocytes but not mature
invasion blocking vaccine
recruitment of complement proteins including proteins that will make pore in the parasite membrane, phagocytosis by immune cells. Parasite protein RH5 and basigin interaction critical, anti RH5 antibodies block this
Transmission blocking vaccines
antibodies target proteins on the surface of gametocytes or gametes
