36. Parasitology 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 are Helminths?
Parasitic worms
How many people worldwide are infected with helminths? Where do most of these people live?
More than 1.5 billion people (24% population)
(Infections are widely distributed in tropical and subtropical areas, with the greatest numbers occurring in sub-Saharan Africa, the Americas, China and East Asia)
How many people does malaria kill each year?
410,000 people (mostly in Africa)
What are the barriers to generating effective vaccines for parasites?
-Antigenic variation
-Limited natural immunity
-Trypanosoma has a one protein coat and in each wave of parasitaemia is switches its coat to a different variant
-Occupy several niches in the body and undergo life cycle changes
What are the barriers to making effective drugs to treat parasites?
-Most parasitic infections are in low income countries and not in the rich west, so drug companies do not make any money and are not investing in the drugs
-Hard to distribute drugs to countries with a poorly established health care system
-Preclinical research not considered worthwhile
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
What is the vector for plasmodium?
Anopheles mosquito
Describe the symptoms of malaria.
Cyclic (every 2-3 days) fever and chills
Headache
Vomiting
Myalgias (muscle pain)
Diarrhoea
Arthalgias (join pain)
What are some species-specific symptoms of malaria caused by P. falciparum?
Can progress to severe potentially fatal cerebral malaria (central nervous system involvement), acute renal failure, severe anaemia and adult respiratory distress syndrome.
What are some species-specific symptoms of malaria caused by P.vivax?
Complications tend to include splenomegaly and (rarely) splenic rupture.
What are some species-specific symptoms of malaria caused by 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
Which age group is particularly affected by malaria?
Younger patients = tend to have more severe symptoms
Large majority of severe malaria and deaths are in young children (<5 years)
Briefly describe the life cycle of malaria.
What do merozoites infect?
RBCs
What form does plasmodium rupture from the liver?
Merozoites
What is ingested by female mosquitos during a blood meal of an infected person?
Male and female gametes
Microgametes (male) can swim to macrogametes to generate zygotes
What occurs in liver cells once sporozoites have infected it?
They mature into schizonts
What occurs in red blood cells?
Asexual stage
Merozoites –> trophozoites –> schizonts –> ruptured merozoites repeat
Some commit to sexual stages and mature into gametocytes
What occurs in the mosquito?
Sexual fertilisation of macrogametes by microgametes to form a zygote
Develop into oocysts
Oocysts grow and rupture releasing sporozoites, which make their way to the mosquito salivary glands ready to inoculate a new person
Where is the initial site of infection of plasmodium? By what?
Blood meal by female Anopheles inoculates sporozoites into a person
Sporozites infect liver cells
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.
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
What pathogenicity factors does plasmodium have to establish itself in a host?
Has special erythrocyte receptors which binds to ligands to allow entry into RBCs
Can cause erythrocyte adhesion to endothelial cells resulting in coagulation and platelet adhesion, oxidative stress and reduced microvascular flow
Parasite proteins (PfEMP1 can bind to host proteins)
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.
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.
How is antigenic variation possible in Plasmodium species?
- Many variants of PfEMP1 (the protein involved in erythrocyte knobs) are encoded by the parasite var multigene family.
- Specific adhesion properties depends on the particular var gene expressed -> Differenet PfEMP1 variants bind to different targets
- There is a library of around 60 var genes -> The Plasmodium can change which is expressed during a chronic infection, making antigenic variation possible
Why is it useful that replicaiton of schizonts occurs inside host cells?
Only short extracellular phases which are exposed to the immune system
Which types of plasmodium are resistant to chloroquine?
P. falciparum
P.vivax resistance is growing
Name a drug which has been used to treat malaria
Chloroquine
Which form of plasmodium is chloroquine effective against?
Erythrocytic forms (schizonts, merozoites, trophozoites)
Which forms of plasmodium is chloroquine not useful against?
Sporozoites (which infect liver cells)
Gametocytes
Hypnozoites (dormant in liver cells)
How does chloroquine enter the parasite and what in particular happens as it enters which is useful for its action?
Chloroquine is uncharged at a neutral pH and can diffuse freely into the parasite lysosome
Acid pH of lysosome converts it to its protonated form and it is trapped inside of the lysosome
What is the anti-protozoal effect of chloroquine?
Inhibits haem polymerase in the parasite (enzyme which polymerises toxic free haem to hemozoin)
Prevents parasite using amino acids from haemoglobin proteolysis
