Lecture 17 - More Malaria Flashcards
Greatest single factor contributing to infant death
Low birth weight
Percentage of cases that are mild malaria
~95%
Population at risk of P. falciparum
2.2 billion
Population at risk of P. vivax
2.6 billion
Type of plasmodium with a dormant liver stage
P. vivax
Malarial species with mild symptoms, limited geographic distribution
P. malariae and P. ovale
What is the main immune response to malarial infection?
Cellular and humoral response
Against blood stage
Symptoms of mild malaria
Flu-like symptoms
Fever, chills, headache, malaise
Severe malaria symptoms 1) 2) 3) 4) 5) 6) 7)
1) Severe anaemia
2) Cerebral complications
3) Respiratory distress
4) Metabolic acidosis
5) Hypoglycaemia
6) BLood clotting problems
7) Kidney damage
Severe malaria cerebral complications
Coma, convulsions, potential long-term neurological problems
Treatment for mild malaria
Three-day course of effective antimalarials
Aremisinin-combination therapy
Primaquine to clear P. vivax liver stage
Treatment for severe malaria
1)
2)
3)
1) 7-10 days IV anti-malarials (quinine or artemisinin)
2) IV fluids, blood transfusion if required
3) Intensive care
Peaks in malarial disease by age
1)
2)
3)
1) 0-5 years - Peak in severe malaria
2) 17-30 women - Pregnancy
3) Symptomatic malaria peaks between 0-5 years, declines rapidly as immunity mounts
Why does immunity to malaria develop slowly?
1) a, b, c
2) a, b, c
1) Parasite factors
a) Over 5000 genes - many antigenic targets
b) Antigenic diversity - major polymorphism in major targets
c) Antigenic variation - var genes can recombine to avoid immune response
2) Host factors
a) Poor immune response in young children
b) DEvelopment of irrelevant immune responses
c) Poor development of memory response
Development of malarial illness 1) 2) 3) 4)
1) Uncontrolled proliferation and release of merozoites in blood
2) Parasite accunulates in vital organs
3) Inflammatory responses
4) Destruction of red blood cells
Recrudescent infection
An infection that recurs from a dormant stage
EG: P. vivax
Do PfEMP1 genes vary between genomes?
Yes
Number of var genes in existence
Thousands exist between all Plasmodium parasites
Antigenic diversity of var genes compared to genetic sequences
Less diverse
Although around 60 var genes in a single parasite, there is a lot of redundancy, conserved sequences
Effect of different var genes
Bind to different markers on endothelial wall, detected by different antibodies, T cells, etc
Different PfEMP1 expression allows infection of different organs
Amount of blood volume going through spleen each minute
~5% of blood volume is processed by spleen each minute
Different immune responses to infection
1)
2)
1) Antibodies against merozoites - Prevents invasion of erythrocytes, growth.
2) Antibodies against infected erythrocytes - opsonisation, phagocytosis
Pregnancy and malaria
1)
2)
3)
1) Malaria infection occurs even if immunity is present
2) Greater density of parasitaemia
3) Risk of malaria decreases with each pregnancy
Why can an otherwise immune woman be infected with malaria when pregnant?
1) PfEMP1 expressed to CSA, HA in placental endothelial walls allows adherence in placenta
2) No antibodies have been made against this, as it hasn’t been encountered by the woman’s immune system
PfEMP1 variant that infects placenta
var2csa
Binds chondroitin sulphate A (CSA, a carbohydrate)
Possible malaria vaccines
1)
2)
1) Possible to make a vaccine for pregnant women, as placental malaria only express var2csa
2) Difficult to make general malaria vaccine, as would have to include many different PfEMP1 variants
