lecture 16 Flashcards
- parasite's resposne to the development of immunity to PfEMP1 - parasite switches to use different var genes (which encode PfEMPS1s) - ~ 60 copies in genome - clonal antigenic variation - results in recrudescence - parasite persistance - different P. falciparum lines have a complement of var genes that are more different than you expect, why?
1
Q
What are pandemics?
A
- global outbreaks of infectious diseases
- major historical pandemics include: typhoid, plague, smallpox, cholera, 1918 ‘Spanish’ flu, tuberculosis, malaria
- major current pandemics: HIV/AIDS, tuberculosis, malaria
- infectious diseases that have shaped our history
- we tend to think of them as something of our past
- don’t tend to be as scared of them in our western society
- threat to us in australia is flu
- major current pandemics really keep countries poor
2
Q
What are the top causes of mortality around the world?
A
- e.g. HIV/AIDS = 4
- Malaria = 8
- single cause infections
- pneumonia and diarrhoea have multiple causes
(report from 2003)
3
Q
Who suffer the primary burden of infectious diseases?
A
- children under 5
4
Q
What is the major infectious killer of children under five?
A
- one malaria species: malaria falciparum
5
Q
What is some history of malaria?
A
- ancient problem
- most lethal infectious organism in history
- still a major problem
- discovery in the blood ~1880 by Charles Laveran (Nobel Prize in 1907)
- discovery of transmission by mosquitoes in 1897 by Ronald Ross (Nobel Prize in 1902)
6
Q
What is the taxonomic classification of malaria?
A
- phylum: Apicocomplexa (a lot of pathogenic plasmodiums belong to this phylum, single celled and polar, apical-complex important for invading host cells) e
- genus: Plasmodium
- 4 species infect humans: P. falciparum, P. vivax, P. ovale, P. malariae (recently a 5th, P. knowlesi)
- many other species infect animals
7
Q
Where are people most affected by malaria?
A
- Africa: particularly equatorial countries
- other countries located around the equator
- e.g. myanmar, papua new guinea
- a lot of disease but not death is caused by non-falciparum malaria so you get a more widespread burden of disease across the globe (as opposed to death which is concentrated in africa)
- p. vivax causes disease without death and is predominant in south america
8
Q
How important is malaria now?
A
- est. 300-500 million cases/year (110 million reported)
- 1 million deaths/year (mostly children)
- malaria seriously hinders social and economic development
- est. $12 billion in direct costs
- 10% of yearly household spending in Africa
- work and school absenteeism as high as 28% in some areas)
- how does it compare to other diseases?
- still very significant?
9
Q
What is the life cycle of the malaria plasmodium?
A
- begins in the mosquito and ends in the blood
- parasite in a blood cell that is maturing
three stages:
1. mosquito state: sexual reproduction
- liver stage - asexual reproduction
- blood stage: asexual reproduction, major mplification stage
10
Q
What is a diagnostic feature of malaria?
A
- characteristic is gold particulate matter - as it matures inside the red blood cell, it invades and matures for 48 hours before it is replicated and comes back out again
- red blood cells are packed full of haemoglobin –> eats this, but the haem compound is toxic to the parasite, so it crystallises the haem compound into a material haemazoan
- this gold particle is diagnostic of malaria
11
Q
What is the mosquito stage of malaria?
A
- this is where the malaria starts
- the parasite inside a mosquito has a sophisticated life cycle
- the mosquito doesn’t just carry the parasite
- in parasitology we’d call the mosquito the definitive host –> this is where sex happens
- parasite becomes diploid
- meiosis occurs to form sporozoites (haploid)
12
Q
What happens in the liver stage?
A
- sporozoite enters the liver
- very few parasites get to the liver and infect a few hepatocytes (1, 2, 10… maybe 100 but not many)
- and it replicates inside those hepatocytes
- no disease
- still a mystery why it has a liver stage
- released as a merozoite
13
Q
What is the blood stage of the p. falciparum?
A
- infect blood cells very quickly
- go from one parasite to 16 or 30 within a 48 hour period
- amplify up from the 10^3 blood cells initially infected to 10^11 red blood cells
- (we have about 10^13)
- huge biomass of infection
- this is where disease happens
- this is also the stage most drugs target
14
Q
What are the ‘egg and sperm’ of the malaria parasite?
A
- gametocytes
- the liver/blood stage is haploid
- something happens in the blood where they become male and female gametocytes
- end up back in the insect - become gametes
- fertilise inside the mosquito
- if the mosquito has bitten two different people it can cross fertilise
15
Q
What are important aspects of lifecycle and spread?
A
- sexual stage in the female Anopheles mosquito (1-2 weeks)
- injected sporozoites enter hepatocytes via the skin (~30 mins)
- asexual liver stage (1-2 weeks)
- asexual blood stage cycle is relatively synchronous and takes 2-3 days
- disease occurs a week to a month after infection
- gametocytes form in the blood and are taken up by a feeding mosquito
