36. Parasitology

Question 1

Malaria, trypanosomiasis and leishmaniasis are caused by…

Answer 1

Unicellular parasites

Question 2

Do infectious diseases have a greater impact on global deaths or on global disability adjusted life years (DALYs)?

Answer 2

DALYs, because they frequently affect young people, unlike, for example, ischaemic heart disease.

Question 3

What are Helminths?

Answer 3

Parasitic worms

Question 4

How many people worldwide are infected with helminths? Where do most of these people live?

Answer 4

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)

Question 5

How many people does malaria kill each year?

Answer 5

410,000 people (mostly in Africa)

Question 6

What are the barriers to generating effective vaccines for parasites?

Answer 6

-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

Question 7

What are the barriers to making effective drugs to treat parasites?

Answer 7

-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

Question 8

What parasite is responsible for malaria?

Answer 8

Plasmodium

Question 9

What are the 5 Plasmodium species known to infect humans and cause malaria?

Answer 9

• P. falciparum
• P. vivax
• P. ovale
• P. malariae
• P. knowlesi

Question 10

What is the vector for plasmodium?

Answer 10

Anopheles mosquito

Question 11

Describe the symptoms of malaria.

Answer 11

Cyclic (every 2-3 days) fever and chills
Headache
Vomiting
Myalgias (muscle pain)
Diarrhoea
Arthalgias (join pain)

Question 12

What are some species-specific symptoms of malaria caused by P. falciparum?

Answer 12

Can progress to severe potentially fatal cerebral malaria (central nervous system involvement), acute renal failure, severe anaemia and adult respiratory distress syndrome.

Question 13

What are some species-specific symptoms of malaria caused by P.vivax?

Answer 13

Complications tend to include splenomegaly and (rarely) splenic rupture.

Question 14

What are some species-specific symptoms of malaria caused by P.malariae?

Answer 14

Complications tend to include nephrotic syndrome.

Question 15

Which of the Plasmodium parasites is the most common cause of malaria?

Answer 15

Plasmodium falciparum and Plasmodium vivax

Question 16

Which age group is particularly affected by malaria?

Answer 16

Younger patients = tend to have more severe symptoms
Large majority of severe malaria and deaths are in young children (<5 years)

Question 17

Briefly describe the life cycle of malaria.

Answer 17

Question 18

What do merozoites infect?

Answer 18

RBCs

Question 19

What form does plasmodium rupture from the liver?

Answer 19

Merozoites

Question 20

What is ingested by female mosquitos during a blood meal of an infected person?

Answer 20

Male and female gametes
Microgametes (male) can swim to macrogametes to generate zygotes

Question 21

What occurs in liver cells once sporozoites have infected it?

Answer 21

They mature into schizonts

Question 22

What occurs in red blood cells?

Answer 22

Asexual stage
Merozoites –> trophozoites –> schizonts –> ruptured merozoites repeat
Some commit to sexual stages and mature into gametocytes

Question 23

What occurs in the mosquito?

Answer 23

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

Question 24

Where is the initial site of infection of plasmodium? By what?

Answer 24

Blood meal by female Anopheles inoculates sporozoites into a person
Sporozites infect liver cells

Question 25

What explains the waves of symptoms of malaria?

Answer 25

Asexual reproduction within erythrocytes takes around 48 hours and the RBCs rupture in waves every 2 days.

Question 26

What are some features of the malaria life cycle that make it an effective pathogen?

Answer 26

• 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

Question 27

What pathogenicity factors does plasmodium have to establish itself in a host?

Answer 27

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)

Question 28

What is the role of the microneme in Plasmodium?

Answer 28

• 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.

Question 29

What are surface knobs in malaria and what important protein do they contain?

Answer 29

• 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.

Question 30

How is antigenic variation possible in Plasmodium species?

Answer 30

• 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

Question 31

Why is it useful that replicaiton of schizonts occurs inside host cells?

Answer 31

Only short extracellular phases which are exposed to the immune system

Question 32

Which types of plasmodium are resistant to chloroquine?

Answer 32

P. falciparum
P.vivax resistance is growing

Question 33

Name a drug which has been used to treat malaria

Answer 33

Chloroquine

Question 34

Which form of plasmodium is chloroquine effective against?

Answer 34

Erythrocytic forms (schizonts, merozoites, trophozoites)

Question 35

Which forms of plasmodium is chloroquine not useful against?

Answer 35

Sporozoites (which infect liver cells)
Gametocytes
Hypnozoites (dormant in liver cells)

Question 36

How does chloroquine enter the parasite and what in particular happens as it enters which is useful for its action?

Answer 36

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

Question 37

What is the anti-protozoal effect of chloroquine?

Answer 37

Inhibits haem polymerase in the parasite (enzyme which polymerises toxic free haem to hemozoin)
Prevents parasite using amino acids from haemoglobin proteolysis