Host Genetics Flashcards
symptoms of malaria
- headache
- systemic fever
- muscular fatigue/pain
- chills and sweating
- dry cough
- spleen enlargement
- nausea and vomiting
severe malaria symptoms
- cerebral malaria
- coma
- severe anaemia
- acute kidney injury
- respiratory distress
- abnormal clotting
- spontaneous bleeding
- acidosis
- jaundice
- high parasite load
how does the immune response to malaria differ compared to other intracellular infectious diseases?
Normal immune response to intracellular pathogens is to identified through MHC1 and CD8+ T cells, RBCs do not have MHC1.
the Duffy antigen is an important host genetic factor conferring susceptibility/resistance to which Plasmodium species?
Vivax, Knowlesi
Duffy -ve = resistance
what is the Duffy antigen and why is it important in Vivax?
It is a chemokine receptor protein known as DARC (Duffy Antigen Receptor for Chemokines).
Encoded by the FY gene.
Found primarily on red blood cells, but also present on endothelial cells and some other tissues.
The Duffy antigen serves as the entry receptor for Plasmodium vivax and Plasmodium knowlesi merozoites to invade red blood cells.
Without the Duffy antigen, P. vivax cannot efficiently bind to and invade RBCs, preventing infection.
why does P. falciparum outcompete Vivax in sub-saharan africa?
Duffy -ve trait common there - 95-99% of the population
Duffy negativity provides natural resistance to P. vivax malaria, which explains the low prevalence of P. vivax in Africa compared to P. falciparum.
what might suggest that Vivax is evolving, and why is this concerning?
reports of Vivax cases in Duffy negative individuals in south saharan africa
parasite is evolving to invade erythrocytes via an alternative invasion pathway?
Duffy antigen -ve has given them natural resistance from vivax up until now, so they have no level of immunity against vivax. If it evolves to invade RBCs in another manner this population has no immunity or resistance against Vivax - could be epidemic problem
What could be an alternative suggestion to explain Vivax presence in duffy -ve hosts?
Vivax was only detected in duffy -ve people when the molecular tools became available to detect it, due to low parasitaemia in the duffy -ve individuals
it was only present in low levels so might not be causing symptomatic infection
it might have always been there, but we didn’t have the molecular tools to detect it due to low parasite levels
= duffy-ve could confer some level of resistance leading to lower parasitamae which is why it wasn’t previously detected, and Vivax might not be evolving at all, just the tools that we use to identify it
what was the theory about why vivax was mutating to invade reticulocytes using a non-duffy dependent route?
In places like madagascar, population is pretty equally split between Duffy -ve and Duffy +ve people
theory was that d
Duffy negativity is caused by a single point mutation where?
in the binding site for GATA1
