36. Parasitology (HT) Flashcards
Malaria, trypanosomiasis and leishmaniasis are caused by…
Unicellular parasites
Do infectious diseases have a greater impact on global deaths or on global disability adjusted life years (DALYs)?
DALYs, because they frequently affect young people, unlike, for example, ischaemic heart disease.
What parasite is responsible for malaria?
Plasmodium
What are the 5 Plasmodium species known to infect humans and cause malaria?
- P. falciparum
- P. vivax
- P. ovale
- P. malariae
- P. knowlesi
Describe the symptoms of malaria.
Common symptoms:
- Fever and chills -> Often cyclic, every 2-3 days.
- Headache
- Myalgias
- Arthralgias
- Weakness
- Vomiting, and diarrhoea
Other clinical features:
- Splenomegaly
- Anaemia
- Thrombocytopenia
- Hypoglycaemia
- Pulmonary
- Renal dysfunction
- Neurologic changes
The clinical presentation can vary substantially depending on the infecting species, the level of parasitaemia, and the immune status of the patient.
What are some species-specific symptoms of malaria?
P. falciparum:
- Can progress to severe potentially fatal cerebral malaria (central nervous system involvement), acute renal failure, severe anaemia and adult respiratory distress syndrome.
P. vivax:
- Complications tend to include splenomegaly and (rarely) splenic rupture.
P. malariae:
- Complications tend to include nephrotic syndrome.
Which of the Plasmodium parasites is the most common cause of malaria?
Plasmodium falciparum and Plasmodium vivax
How does age affect clinical presentation of malaria?
- Younger patients tend to have more severe symptoms
- Large majority of severe malaria and deaths are in young children (<5 years)
- Not just a function of age, also pre-exposure/accumulated resistance from living in endemic areas
Describe the life cycle of malaria (using Plasmodium falciparum as an example).
[IMPORTANT]
Human phase:
- Female mosquito releases sporozoites into human
- In the liver:
- Sporozoites enter liver hepatocytes and form schizonts (multinucleate cells)
- The schizonts undergo schizogony (several rounds of fission) and the hepatocytes rupture, releasing merozoites into the blood
- In RBCs:
- Asexual reproduction:
- Merozoites infect RBCs and become trophozoites and then schizonts.
- RBC rupture leads to the release of merozoites into the blood.
- Gametogenesis:
- Some of the infecting merozoites are programmed for gametogenesis.
- They become trophozoites and then gametocytes.
- Some are male (microgametes) and some are female (macrogametes).
- Asexual reproduction:
Mosquito phase:
- Male (microgamete) and female (macrogamete) gametocytes are taken up by a female mosquito.
- In the mosquito midgut, microgametes (male) penetrate the macrogametes (female), generating zygotes.
- The zygotes becomes an ookinete that is motile and invades the midgut wall, where it develops into an oocyst.
- The oocyts ruptures and releases sporozoites that enter the salivary gland of the mosquito, ready for transfer to the next human host.
What explains the waves of symptoms of malaria?
Asexual reproduction within erythrocytes takes around 48 hours and the RBCs rupture in waves every 2 days.
Summarise the cell types involved in the different stages of the malaria life cycle.
Human phase:
- Receive sporozoites
- In the liver:
- Sporozoites -> Schizonts -> Merozoites
- In RBCs:
- Asexual reproduction:
- Merozoites -> Trophozoites -> Schizonts -> Merozoites
- Gametogenesis:
- Merozoites -> Trophozoites -> Gametocytes
- Asexual reproduction:
Mosquito phase:
- Receive gametocytes
- In the midgut:
- 2 x Gametocytes -> Zygotes -> Ookinete -> Oocyst -> Sporozoites
- Sporozoites released from salivary gland.
What are some features of the malaria life cycle that make it an effective pathogen?
- Initial site of infection is liver cells -> Good site for maintaining a long-term asymptomatic infection
- Replication occurs as schizonts inside host cells -> Only short extracellular phases which are exposed to the immune system
- Sexual life cycle stage -> Allows effective genetic exchange
Describe the mechanism of Plasmodium invading erythrocytes.
- Plasmodium uses non-specific methods to attach to the erythrocyte, which leads to the rotation of the Plasmodium such that the apical complex is pointing to the erythrocyte
- Specific proteins on the Plasmodium (EBA and PfRH) interact with receptors on the erythrocyte, triggering a series of signalling events that lead to the secretion of the invasion machinery
- RON4 is secreted by the rhoptries and embeds in the erythrocyte membrane
- AMA1 is secreted by the micronemes and binds to the RON4 -> This is known as the moving complex
- The moving complex able to move outwards (using actin and myosin)
- This pulls the Plasmodium into the erythrocyte in a vacuole
What two parts of the invasion mechanism are highly conserved between Plasmodium species?
- Microneme
- Rhoptry
What is the role of the microneme in Plasmodium?
- Produces adhesins:
- Apical membrane antigen (AMA-1)
- Thrombospondin-related anonymous protein (TRAP)
- Produces proteases -> Involved in microneme protein processing
Stores and discharges adhesins in response to cell-cell contact.
Summarise the stages of Plasmodium falciparium life cycle in erythrocytes. Include the various organelles.
- Rapid invasion, entering a parasitophorous vacuole
- Plasmodium starts producing proteins, essentially forming new organelles
- This includes Maurer’s clefts, which are involved in forming knobs on the erythrocyte surface
- The knobs contain parasite adhesin PfEMP1
- There is also a waste organelle for sequestering the haem iron that is harmful to the parasites due to the formation of ROS
- The Plasmodium undergoes many rounds of division without cytokinesis, forming a schizont
Actual stages of development: Ring, Trophozoite, Schizont
What are surface knobs in malaria and what important protein do they contain?
- They are modifications on the surface of erythrocytes during a malaria infection.
- They make the erythrocytes more adherent and less mechanically deformable.
- The key protein to this is PfEMP1 surface receptor inserted there by the Plasmodium.
Describe how Plasmodium infecting erythrocytes leads to pathology.
- The infection leads to the expression of adhesion molecules, such as PfEMP1, on the surface of the erythrocyte
- These PfEMP1 molecules can allow the erythrocyte to adhese to various targets on the endothelium wall (e.g. ICAM1) and other erythrocytes (e.g. CR1)
- This can lead to blockage of blood vessels, particularly in the brain, placenta, etc.
- Adhesion leads to:
- Increased coagulation and platelet adhesion
- Increased inflammation and oxidative stress
- Increased endothelial leakage
- Reduced microvascular flow
What are some targets for malaria vaccines?
