Can malaria be transmitted person to person?
No
What happens if malaria is not treated?
Often fatal Affects - Brain - Lungs - Placenta - Other organs
What are the two main types of malaria?
Plasmodium falciparum
Plasmodium vivax
Which type of malaria is most relevant to the Asia-Pacific region?
P vivax
Which region has the greatest burden of P falciparum?
Sub-Saharan Africa
Which regions have the greatest burden of P vivax?
Asia-Pacific
South America
Which demographics are at the greatest risk?
Young children
Pregnant women
What are the effects of malaria in pregnancy?
Infection can get into placenta
Low birth weight
Miscarriages and stillbirths
What is the socio-economic burden of malaria?
Impedes economic development
Impacts on learning and education
Compounds poverty
What are the obstacles to combating malaria?
No highly effective control measures - Partially effective measures - Poorly applied No vaccine Drug resistance widespread and increasing Insecticide resistance Economic, political, and social factors
What are the species of Plasmodium that infect humans?
P falciparum P vivax P ovale P malariae P knowlesi
Which species of Plasmodium causes the majority of severe malaria disease and death?
P falciparum
Which species of Plasmodium has a dormant liver stage that can reactivate at any time after treatment?
P vivax
Which species of Plasmodium has a limited distribution and causes mild disease?
P ovale
P malariae
Which species of Plasmodium is a zoonotic infection, that is present in macaques throughout south-east Asia?
P knowlesi
What is the vector for malaria?
Female Anopheles mosquito
What is the animal reservoir for malaria?
None, except for P knowlesi
How long is the P falciparum cycle?
48 hours
What is the dormant liver stage of malaria?
In P vivax
Some infected hepatocytes remain infected and dormant
When does disease occur during the malaria cycle?
During blood stage
What are the immune responses primarily against in malaria?
Blood stage parasites
Involve humoral and cellular responses
What is the life cycle of Plasmodium?
- Malaria infected mosquito inoculates sporozoites into human
- Sporozoites infect liver cells
- Mature into schizonts
- Rupture and release merozoites
- Merozoites infect RBCs
- Inside RBC: immature trophozoite (ring-stage) > mature trophozoite > schizont > ruptured schizont > release merozoites
- Some immature trophozoites differentiate into gametocytes
- Gametocytes ingested by mosquito via blood meal
- Zygotes generated in mosquito’s stomach
- Become motile ookinetes
- Invade midgut wall > develop oocysts
- Oocysts grow > rupture > release sporozoites > travel to mosquito’s salivary glands
What are the clinical features of uncomplicated (mild) malaria?
Flu-like illness
Fever
Headache
Malaise
What are the clinical features of severe malaria?
Severe anaemia Cerebral malaria - Coma - Convulsions - Long-term neurological deficits Respiratory distress and metabolic acidosis - Reduced tissue perfusion - Lung damage Other - Hypoglycaemia - Kidney failure - Blood clotting problems
What is the treatment for mild malaria?
Short course of effective anti-malarial tablets
Artemisinin combination therapy (ACT)
Clearance of P vivax liver stage
Which artemisinin combination therapy is most widely used?
Artemether-lumefantrine
Which drug is used to clear the liver stage in a P vivax infection?
Primaquine
What is the treatment for severe malaria?
Anti-malarials - IV artemisinin/quinine for 7-10 days IV fluids Blood transfusion if needed Supportive treatment Anticonvulsant Anticoagulant
What is the pathogenesis of severe malaria?
Unrestricted replication of malaria in bloodstream > Accumulate in vital organs Inflammatory responses Destruction of RBCs > Severe illness
Does immunity to malaria exist?
Eventually develops after many episodes
What are the types of immunity that develop to malaria?
Prevents severe malaria
Prevents any malaria
In pregnancy
What are the parasite factors that contribute to slow development of immunity to malaria?
Multiple Ag targets
Ag diversity = major targets show substantial diversity
Ag variation = gene families allow switching to evade responses
What are the host factors that contribute to slow development of immunity to malaria?
Inadequate response, especially in young children
Non-functional/irrelevant responses
Poor development of memory responses
What does antigenic variation and diversity in Plasmodium enable?
Chronic and reactivated infections
Repeat infections
What genetic factors confer immunity and resistance to malaria?
Sickle cell trait
Alpha thalassemia
Blood groups
What innate immune factors confer immunity and resistance to malaria?
Plasma factors - Complement - Mannose-binding lectin Innate cells - NK cells - Specific T cell subsets
Which immune cells target sporozoites?
Abs > inhibit infection of hepatocytes
T cells
Which immune cells target infected hepatocytes?
CD8 T cells
Which immune cells target merozoites?
Abs
Which immune cells target infected RBCs?
Abs
T cells
What are the cell-mediated responses to the blood stage of malaria?
RBCs lack MHC molecules
CD4 T cells involved in protection
Splenic clearance of parasitised RBCs by macrophages
IFN-gamma production associated with protection
Excessive pro-inflammatory cytokines associated with severe disease
What are the humoral responses to the blood stage of malaria?
Passive transfer of Abs protective Abs to merozoites - Inhibit RBC invasion and growth Abs to infected RBCs - Parasite Ags expressed on surface of RBCs - Opsonisation for phagocytosis
What are the immune mechanisms behind building a vaccine to the sporozoite/liver stage of malaria?
Abs block entry to liver
CD8 T cells inhibit parasite development in liver
Prevent parasites entering bloodstream
What are the immune mechanisms behind building a vaccine to the merozoite/blood stage of malaria?
Block infection of RBCs - Directly - Via interaction with complement Opsonise merozoites for phagocytic clearance Prevent replication in bloodstream