Eukaryotic parasites 3: malaria Flashcards
What type of an infection is malaria?
Blood infection
How is malaria transmitted?
By mosquitos
Is malaria transmitted by person-to-person contact?
No
Which organs can malaria affect?
Brain
Lungs
Placenta
What are the 2 main types of malaria?
P. falciparum
P. vivax
What is the most common strain of malaria?
P. falciparum
Why are 90% of all p. vivax infections in the Asia Pacific region?
Genetic mutations in the African population confer resistance to P. vivax.
Which region is most affected by malaria globally?
Sub-Saharan Africa
Which region is most affected by malaria locally?
Papua New Guinea
Which groups of people are at greatest risk from Malaria?
Young children and pregnant women
How many die from malaria each year?
1 million
How many cases of malaria are there per year?
300-500 million
What is the leading cause of childhood deaths globally?
Malaria
What is the effect of malaria in pregnancy?
Low birth weight
Miscarriages and stillbirths
What is the biggest risk factor for early infant death?
Low birth weight due to malaria infection
What are the socioeconomic impacts of malaria?
Impedes economic development
Impacts on learning and education
Compounds poverty
Mostly affects resource-poor communities
What are the obstacles to combating malaria?
No highly effective control measures available
No vaccine
Drug resistance widespread and increasing
Insecticide resistant
Economic, social and political factors
Is there cross-spread among malaria species?
No
Human malaria doesn’t infect other species and vice-versa
Which species of malaria causes the majority of severe malaria disease and death?
P. falciparum
How much of the population is at risk from P. falciparum infection?
2.2 billion
How much of the population is at risk from P. vivax infection?
2.6 billion
Which strain of malaria has a dormant liver stage?
P. vivax
What are the 4 strains of malaria?
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlesi
Which of the malaria species can actually be a zoonotic infection?
P. knowlesi
Present in macaques throughout SE Asia
How is P. falciparum transmitted?
By female Anopheles mosquitos
Does malaria have animal reservoirs?
No
At what stage in the malaria lifecycle is disease present?
During the blood stage
What is the immune response to malarai infection primarily against?
Blood stage parasites
What is involved in the immune response to blood stage malaria infections?
Both humoral and cellular responses
What is the lifecycle for the malaria parasite?
Injected as sporozoites by mosquito
Travels to liver
Matures into merozoites
Released from liver in blood cells
Matures into gametocytes in blood
Transmitted to mosquito when feeding
Matures into gamete, then zygote and then ookinete in mosquito gut
What are the clinical features of uncomplicated (mild) malaria?
Flu-like illness
Fever, headaches and malaise
What are the clinical features of severe malaria?
Severe anaemia
Cerebral complications
Respiratory distress
Which cerebral complications exist in cerebral malaria?
Coma
Convulsions
Long-term neurological deficits
How does respiratory distress and metabolic acidosis manifest in severe malaria?
Reduced tissue perfusion
Lung damage
What is the treatment for mild malaria?
Short course of effective anti-malarial tablets
Which short course of effective anti-malarial tablets are used for mild malaria?
Artemisinin combination therapy (ACT)
E.g. Artemether-lumefantrine (AL)
Which drug is used to clear P. vivax in the liver stage?
Primaquine
Why does a patient need a 14 day course of primaquine?
Because p. vivax has a dormant stage in the liver
Which drug is used to treat severe malaria?
Intravenous artemisinin or quinine (7-10 days)
What else is required, other than IV artemisinin or quining, in severe malaria, if required?
IV fluids
Blood transfusion
Supportive treatment (Intensive care)
Has there been much of an improvement in mortality rate for malaria treatments?
No
When does immunity to malaria develop?
After many episodes of infection
What are the 3 main types of immunity to malaria?
Immunity that prevents severe malaria
Immunity that prevents any malaria
Immunity to malaria in pregnancy
Which two factors are responsible for slow development of immunity to malaria?
Parasite factors
Host factors
What parasite factors contribute to the slow development of malaria immunity?
Multiple antigenic targets (~5000 genes)
Antigenic diversity: major targets show substantial polymorphism
Antigenic variation: gene families allow switching to evade responses
What host factors contribute to the slow development of malaria immunity?
Inadequate response (especially young children)
Non-functional/irrelevant responses
Poor development of memory responses
What is the result of antigenic variation and diversity of plasmodium?
Chronic and recrudescent infections
Repeat infections
How does antigenic variation of plasmodium occur in the individual?
In antigenically distinct waves of parasitaemia
What are the antibody components of the immune response to malaria infection?
Neutralisation
Opsonisation
Complement
What are the cellular response components of the immune response to malaria infection?
CD4+ T cells
CD8+ T cells
Activated macrophages
What is the end result of immune response to malaria inflection?
Memory B and T cells
Which genetic factors contribute to immunity and resistance to malaria?
Sickle cell trait (haemoglobin defect)
Alpha-thalassemia (haemoglobin defect)
Blood groups
Which 3 components of innate immunity contribute to immunity and resistance to malaria?
Plasma factors
Innate cellular responses
Activated macrophages
Which plasma factors contribute to immunity and resistance to malaria?
Complement
Mannose-binding lectin
Which innate cellular responses contribute to immunity and resistance to malaria?
NK cells
Specific T cell subsets
What do antibodies against malaria do?
Inhibit infection of hepatocytes
Which immune cells are involved in the liver stage of malaria?
CD8+ T-cells against infected hepatocytes
Are antibodies effective in the liver stage of malaria?
No
Why is naturally-acquired immunity to liver stage malaria very limited?
Low parasite load
Short duration of infection
What are cell-mediated responses involved in in the blood stage of malaria?
Protection and disease pathogenesis
What role do RBCs play in the blood stage of malaria?
RBCs lack MHC molecules
Which T cells are involved in protection in blood stage malaria?
CD4+ T cells
Where are parasitised RBCs cleared?
In the spleen
Why cytokine is associated with protection in blood stage malaria?
IFNγ
Which cytokine response is associated with severe malaria?
Pro-inflammatory cytokine response (e.g. TNFα)
What is the role of monocytes and macrophages in blood stage malaria?
Clearance of infected RBCs (mainly in the spleen)
What is the role of antibodies in blood stage malaria?
Passive transfer of antibodies is protective
What are antibodies in blood stage malaria against?
Merozoites
What do antibodies in blood stage malaria do?
Inhibit RBC invasion and growth
Direct inhibition by antibodies
Antibody-dependent cell mediated inhibition of parasite growth
Antibodies to infected RBCs
Parasite antigens expressed on the surface of RBCs
Opsonization for phagocytosis
What can block invasion by plasmodium falciparum?
Antibodies and drugs
How does antibody-mediated killing of malaria blood-stage paraistes occur?
Antibodies opsonize merozoites and parasitized RBCs for killing by immune cells (monocytes, macrophages, neutrophils)
What blocks infection of RBCs?
Antibodies
Do antibodies to a specific antigen protect against malaria?
Yes
What may lack of effective immunity may arise from?
Wrong immune response
Wrong target antigen
Right antigens, wrong epitope
Right target, right epitopes → antigenic diversity
Inability to mount a response to a specific antigen/epitope
What blocks entry of sporozoites into the liver?
Antibodies
Prevents parasites entering blood stream
What role do CD8+ T cells play in the sporozoite/liver stage of malaria?
Inhibit parasite development in the liver
Prevents parasites entering blood stream
What blocks infection of RBCs by merozoites?
Antibodies
Opsonise merozoites for phagocytic clearance
Prevent replication in blood stream
What is the major antigen of sporozoites?
CS protein
What is the RTS,S vaccine?
Segment of CS protein
Presented in a virus-like particle (VLP) with hepatitis B surface antigen
What are nearly all malaria vaccines in trial against?
P. falciparum
Where do malaria parasites replicate?
In RBCs
What does acquired immunity to malaria predominantly target?
Blood-stages of Plasmodium, and liver stage to a lesser extent
What do the blood stage immune responses mainly involve?
Antibodies
What do the liver stage immune responses mainly involve?
T cells