Eukaryotic parasites 3: malaria Flashcards
Can malaria be trasnmitted through person-to-person contact?
No
Transmitted by mosquitoes
What are the two major types of malaria?
P.falciparum
P.vivax
Which populations are at the greatest risk of malaria?
Young children
Pregnant women
Briefly describe the global burden of malaria?
Up to 1 million deaths per year
300-500 million cases per year
A leading cause of childhood deaths
Compounds poverty
Impedes economic development and education
Describe the consequences of malaria during pregnancy?
Low birth weight
Miscarriages and stillbirths
Which communities are most affected by malaria?
Resource-poor communities
Describe the major obstacles to combatting malaria?
No highly effective control measures available
No vaccine
Drug resistance
Insecticide resistance
Which Plasmodium species causes the majority of severe malaria and death?
P.falciparum
Which Plasmodium species has a dormant liver stage?
P.vivax
Which type of mosquito transmits malaria?
Female Anopheles mosquitoes
During which stages of the malaria life cycle is disease present?
Only during the blood stage
Describe the life cycle of P.falciparum?
Mosquito injects sporozoites > travel to liver> incubate 7-10 days in hepatocyte, replicate > merozoites burst out of liver > infect RBCs
What are the immune responses to malaria mainly directed against?
Blood stage parasites
What are the two clinical types of malaria?
Uncomplicated/mild malaria
Severe malaria
Describe the clinical features of uncomplicated/mild malaria?
Flu-like illness
Fever, headaches, malaise
Describe the clinical features of severe malaria?
3 MAIN FEATURES
Severe anaemia
Cerebral complications (coma, convulsions)
Respiratory distress and metabolic acidosis
OTHER
Hypoglycaemia, kidney failure, blood clotting problems
Describe the treatment of uncomplicated/mild malaria?
Short course of anti-malarial tablets (3 days)
Clearance of P.vivax liver stage (14 days)
What is the problem with using anti-malarial tablets?
Resistance emerging
Access
Counterfeit drugs
Describe the treatment for severe malaria?
Anti-malarials: IV artemisinin or quinine (7-10 days)
Supportive treatment: fluids, blood transfusion, etc.
Describe how severe malaria develops?
Unrestricted replication> parasites accumulate in vital organs, inflammatory response, RBC destruction > severe illness
Describe the three main types of immunity to malaria?
1) Immunity that prevents severe malaria
2) Immunity that prevents any malria
3) Immunity to malaria in pregnancy
Is the development of immunity to malaria slow or rapid?
Why?
Slow
PARASITE FACTORS
Multiple antigenic targets
Antigenic diversity
Antigenic variation
HOST FACTORS
Inadequate response
Non-functional/irrelevant responses
Poor development of memory
Describe the factors which contribute to immunity and resistance to malaria?
Genetic: sickle-cell trait, alpha-thalassemia
Innate immunity: plasma factors (e.g. complement), innate cellular responses (e.g. NK cells), activated macrophages
Acquired immunity
Describe the targets, and their mediators, of acquired immunity to malaria?
Sporozoites: Abs and T cells
Infected hepatocytes: T cells
Merozoites: Abs
Infected RBCs: Abs and T cells
Describe the immune responses to sporozoites?
Abs inhibit infection of hepatocytes
Describe the immune response to the liver stage of malaria?
CD8 T cells against infected hepatocytes
Describe the immune responses to the blood stage of malaria?
CELL-MEDIATED RESPONSES
CD4 T cells for protection
Splenic clearnace of parasitsed RBCs (monocytes and macrophages)
IFNY production for protection
Pro-inflammatory cytokine production in severe disease
ANTIBODIES TO MEROZOITES
Inhibit RBC invasion and growth
ANTIBODIES TO INFECTED RBCs
Opsonisation for phagocytosis
What part of the immune response to malaria is the key focus of most vaccines?
Abs to merozoites
How can invasion of RBCs by malaria parasites be inhibited?
Antibodies
Drugs
Describe why a lack of effective immunity to malaria may arise?
Wrong immune response e.g. Abs to liver stage of P.falciparum
Wrong target antigen e.g. antigens that are not essential for invasion or attachment
Right antigens, wrong epitope e.g. sites that are not involved in invasion/attachment
Antigenic diversity
What are the three strategies to developing a vaccine against malaria?
1) Sporozoites/liver stages
2) Merozoites
3) Transmission blocking vaccines
Describe the sporozoite/liver stage strategy to developing a vaccine for malaria?
Abs block entry to liver
CD8 T cells inhiibt parasite development in liver
Prevents parasites from entering bloodstream
Describe the merozoite approach to developing a vaccine for malaria?
Abs opsonise merozoites for phagocytic clearance
Blocks infection of RBCs, prevents replication in bloodstream
Describe the transmission blocking approach to developing a vaccine for malaria?
Stop infection of mosquitoes
Stops transmission, but does not help host
Which is currently the most advanced vaccine for malaria?
RTS,S vaccine
Phase 3 trial
Describe the RTS,S vaccine?
Segment of CS protein (major Ag of sporozoites)
Presneted in virus like particle with Hep B surface Ag
Uses potent adjuvants
Describe the difference in the acquired immune response to the blood stage and liver stage of malaria?
Blood stages mainly involve antibodies
Liver stages mainly involve T cells
