Malaria Flashcards
Summarise the key species that cause malaria
Malaria is a blood-borne disease caused by infection with Plasmodium parasites aquired via female *Anopheles * mosquito vector transmission.
There are five main species of *Plasmodium * that cause disease:
P. falciparum
- Causes the most severe malarial disease and death
- Mainly located in Africa
- 2.2 billion people at risk of infection
P. vivax
- Increasingly recognised as a cause of severe illness
- Dormant liver stage
- Prevalent in Asia & South East Asia
- people in Africa have developed resistance to vivax type malaria
P. ovale & P. malariae
- limited distribution + mild disease
P. knowlesi
- Zoonotic infection (malaria is not normally transmitted between species - this is the exception)
- Present in macaques throughout SE Asia
Epidemiologically, in what populations is malaria particular prevalent?
Malaria is a disease that affects resource-poor communites that have poor standards of public health and sanitation
Young children and pregnant women are at greatest risk of contracting malaria in these communites. It is one of the leading causes of childhood death globally.
300-500 million new cases/year + 1 million deaths globally
Malaria in pregnancy is associated with low birth weight offspring, miscarriages and still-births.
It has a significant societal burden - impeding economic development, ability of children to learn and be educated and further compounds poverty.
List the obstacles to combatting malarial disease
No highly effective control measures availiable
- Only have partially effective measures and in areas of poverty/underdevelopment these measures are poorly applied
No vaccine
Drug resistance is widespread and increasing
Insecticide resistance is impeding efforts to prevent the transmission of malaria
Economic, political and social factors are barriers to malaria control
Outline the general life cycle of Plasmodium
Add detail and image
Stages of the life cycle:
Sporozoites which are injected by the mosquito vector into the host’s blood
Latent hypnozoites in the case of P. vivax which may rest undetected in the liver for up to 30 years;
Merozoites which infect the red cells (erythrocytes) of the blood
Trophozoites which grow in the red cells
Schizonts which divide in RBCs producing more merozoites which leave to infect more red cells
Gamatocytes that are of male and female sexual forms which are taken up by other mosquitoes.
What are the clinical features of malaria?
Mild/uncomplicated malaria
Flu like illness, fever, headaches malaise
Severe malaria
- Severe anaemia
- Cerebral complications (cerebral malaria)
- coma
- convulsions
- long-term neurological deficits
- Respiratory distress + metabolic acidosis
- lung damage
- reduced tissue perfusion
- Hypoglycemia
- Kidney failure
- Blood clotting problems
How does malaria illness develop?
Unrestricted replication of malaria parasites within the bloodstream leads to:
- Malaria parasites accumulate in vital organs
- Inflammatory responses
- Destruction of red blood cells
Leads to severe, multi-system illnesses of coma (cerebral malaria), severe anaemia, acidosis and respiratory distress.
How is malaria currently treated?
Treatment is effective if there is no resistance
Mild Malaria
Short course of effective anti-malarial tablets
-
Aremisinin combination therapy (ACT)
- e.g. Artemether-lumefantrine
- Primaquine for liver clearance of P. vivax
Severe Malaria
Intravenous artemisinin or quinine (7-10 days)
- IV fluids
- Blood transfusion if required
- Supportive treatment - intensive care
- Anti-convulsant, anticoagulant, anti-inflammatory drugs if needed
Can you develop immunity to malaria?
Immunity eventually develops after many episodes of malaria infection; of which there are three main types:
- Immunity that prevents severe malaria
- Immunity that prevents any malaria
- Immunity to malaria in pregnancy
What reasons contribute to the slow development of immunity to malaria?
Parasite Factors
- Multiple antigenic targets (~5000 genes)
- Antigenic diversity: major targets show substantial polymorphism
- Antigenic variation: gene families allow switching to evade immune system
Host Factors
- Inadequate response (especially in young children)
- Non-functional / irrelevant responses
- Poor immunological memory to malaria - only last months to a few years.
What effect does antigenic diversity and antigenic variation have on the likelihood to have continued malaria infections?
Antigenic diversity and antigenic variation leads to antigenically distinct waves of parasitemia
This leads to:
Chronic infections - lasting a long time
Recrudescent infections - A recurrence of symptoms in a patient whose blood stream infection has previously been at such a low level as not to be clinically demonstrable or cause symptoms
**Repeat infections **- subsequent reinfections with malaria
Discuss the factors (genetic, innate and aquired) involved in providing immunity and resistance to malaria
Genetic factors
- Sickle cell trait (haemoglobin defect)
- Alpha-thalassemia (haemoglobin defect)
- Blood groups
_Innate immunity _
- Plasma factors: Eg. Complement, mannose-binding lectin, others
- Innate cellular responses: NK cells, specific T cell subsets
- Activated macrophages
Acquired immunity
- Sporozoites: antibodies and T cells
- Infected hepatocytes: T cells
- Merozoites: antibodies
- Infected RBCs: antibodies and T cells
Discuss the immune response to malaria at the sporozoite stage of infection
The sporozoite stage of infection occurs as malarial parasites are first injected into the blood circulation by the anapheles mosquito
Antibodies inhibit sporozoite infection of hepatocytes
Discuss the immune response to malaria at the liver stage of infection
CD8+ T-cells react against infected hepatocytes as part of the immunity response
Antibodies aren’t effective due to the intracellular nature of malaria at this stage of the life cycle
Note: natural acquired immunity to liver stage parasites is limited. This is believed to be a consequence of the low parasite load and short duration of infection within the liver.
Explain the blood stage immune responses to malaria
Antibodies to merozoites
Direct inhibition of merozoite RBC invasion + antibody-mediated inhibition of parasite growth
Antibodies to infected RBC’s
Antibodies respond to parasite antigens expressed on the cell surface of infected RBCs - providing a target for opsonisation and subsequent phagocytosis by monocytes and macrophages
Cell mediated response
Play a supportive role compared to antibody responses
The cell-mediated response is involved in both protection and disease pathogenesis
-
CD4+ T cells involved in protection
- activation of macrophages and B-cell antibody help
- Production of IFN-gamma associated with protection
- Monocytes and macrophages are involved in the clearance of infected RBC’s - mainly in the spleen
- Pro-inflammatory cytokine responses (TNF-a etc.) are associated with severe malarial disease pathogenesis
Note: RBC’s lack MHC molecules thus CD8+ T-cells are not involved
What are three strategies of vaccine in development for malaria immunisation?
1. Targetting the sporozoite/liver stage
Generate an immune response that prevents sporozoites entering the liver once they are first exposed to circulation: antibodies to block liver entry and CD8+ T cell responses to hepatocyte parasites
2. Antibody response to merozoites
Block RBC invasion antigens + opsonise merozoites for phagocytic clearance
3. Prevent the sexual stage of malaria
Stop the infection of mosquitos to prevent the transmission of malaria between people = altruistic vaccine (has no effect on the individual with malaria). Would be used in conjuction with other vaccines/treatments
