Plasmodium and Malaria (Franco Falcone)

Question 1

When should a patient be assessed for malaria?

Answer 1

Any patient with a recent history of travel to an endemic country, or has been to an international airport, presenting with fever.
Any patient with a risk of contracting regardless of gender, age, ethnicity or country of birth.

Question 2

How long can Malaria present after travel?

Answer 2

Up to a year post trip

Question 3

Is Malaria a notifiable disease?

Answer 3

Yes in the UK (Health Protection Notification Regulation 2010).

Question 4

What kind of Malarias are there?

Answer 4

Plasmodium species
Falciparum (subtertiana)
Ovale (tertiana)
Vivax (tertiana)
Malariae (quartana)
Knowlesi (quotidiana)

Question 5

How is Plasmodium spread?

Answer 5

Spread by mosquitoes of the genus ANOPHELES
(= vector)
Anopheles deposits eggs in stagnating waters e.g. rice paddies, swamps, marshes
Rain season, puddles!

Question 6

What is the life cycle of a mosquito?

Answer 6

Female mosquitos can lay 50-200 eggs at a time (She must take a blood meal beforehand.)
Eggs are laid on still water and develop into aquatic larvae in 2-3 days.
Larvae go through 4 stages of development called instars
Pupae - during the last larval instar, the larvae develop into pupae.
After 1-2 days the adult mosquito emerges from water

Question 7

Why is malaria proliferative in tropical countries?

Answer 7

Mosquitos need a minimum temperature to mature

Question 8

What does Anthropophillic mean?

Answer 8

Preference for human blood
(There are different species of Anopheles, not all of them are anthropophillic, some have a preference for animal blood.)

Question 9

How is Malaria transmitted from the anopheles mosquito?

Answer 9

The mosquito injects saliva
Contains an anti-coagulant
Plasmodium enters the blood within the infected saliva

Question 10

What stage of disease leads to the symptoms of Malaria?

Answer 10

No symptoms associated with the liver stage.

Symptoms occur when red blood cell stages rupture cells and release malaria ‘toxins’ and pyrogens.

Question 11

What are the hosts of Malaria?

Answer 11

two types of hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites (“merozoites”) that continue the cycle by invading other red cells.

Question 12

What are the symptoms of Malaria?

Answer 12

Fever, anaemia, diarrhoea, vomiting, splenomegaly, (dead and broken red blood cell fills the spleen, making it enlarged) jaundice (liver function impaired).

Question 13

What causes, and when is Malaria Fever present?

Answer 13

Caused by host cytokines released in response to released pyrogens (upon RBC rupture).

There can be severe malaria without any fever!

Question 14

What are Malarial Fever patterns?

Answer 14

After the initial few weeks, fever becomes a regular pattern. (Tertiana, subtertiana, quartana) as schizogony becomes synchronised.

Question 15

What are the stages of fever? (Especially prevelant in P. vivax)

Answer 15

Cold stage 15-60 min; shivers or shows rigor
Hot stage 2-6 hours; patient becomes flushed, has rapid pulse and high temperature
Sweating stage 2-4 hours; patient sweats abundantly and temperature drops

Question 16

In which species of Plasmodium can Malaria relapse happen?

Answer 16

P. ovale and P. vivax, the hynozoites can survive in the liver cells for years or decades, lying dormant, but this can lead to relapse.

Question 17

Which is the most dangerous malaria parasite?

What are the associated complications?

Answer 17

P. falciparum

Altered consciousness or coma can be caused by hypoglycaemia, acidosis, seizures or very severe anaemia

Question 18

What is the main cause of malaria death?

Answer 18

Cerebral malaria; large number of RBCs containing mature parasites found in capillaries and venules of brain and other organs

Question 19

How does malaria cause hypoglycaemia?

Answer 19

Common complication of P. falciparum untreated (especially in children)
Cytokine-induced impairment of gluconeogenesis in the liver and additional glucose consumption by millions of parasites.
Quinine (used in Tx) can induce insulin production, reducing glucose further

Question 20

How does malaria cause severe anaemia?

Answer 20

Direct destruction of RBC when schizonts rupture and immune-mediated haemolysis occurs. In addition, the cytokines produced, affect red blood cell formation (erythropoeisis) in the blood marrow

Question 21

How does malaria cause acidosis?

Answer 21

Tissue anoxia (oxygen depletion in tissues), leads to anaerobic metabolism and the release of lactic acid.

Question 22

Why are pregnant women particularly threatened by Malaria?

Answer 22

All types of malaria can lead to abortion
Can cause anaemia (blood loss during birth problematic), low birth weight
Parasites are not normally transmitted from mothers to the new-born in endemic areas but possible outside of endemic areas
Not all drugs can be used in pregnancy e.g. Primaquine should not be used

Question 23

What is recrudescence of malaria?

Answer 23

When malaria is caused by a small number of parasites persisting in RBCs

Question 24

What is malaria reinfection?

Answer 24

Malaria attack caused by new inoculation of parasites from infected vector.

Question 25

What is relapse in malaria?

Answer 25

When hypnozoites in liver are reactivated and initiate a new cycle of RBC infection even after elimination of all parasites from blood (P. vivax and P. ovale).

Question 26

In what age is mortality in malaria highest?

Answer 26

P. falciparum in 5-6 year olds or younger

Question 27

Is immunity to malaria possible?

Answer 27

Children that survive a bout of P. falciparum in endemic countries develop a degree of immunity.
They can limit parasitemia by producing parasite specific IgG.
This protection requires frequent re-exposure and is lost when living in non-endemic areas (1-2 yr)

Question 28

What is the link between Malaria- HIV co-infection?

Answer 28

As CD4+ counts progressively decrease in HIV-infected individuals, they become more susceptible to malaria infection and will develop higher parisitaemia.
Conversely malaria increased plasma viral loads in HIV-infected people
There is some evidence that malaria may enhance mother-child (vertical) transmission of HIV.
The two diseases reinforce each other and exacerbate the pathology of each respectively.

Question 29

Are there any non-immune protective factors in malaria?

Answer 29

Duffy factor
Sickle cell anaemia
Thalassaemia
Glucose-6-phosphate dehydrogenase deficiency

All of these genetic mutations affect RBC phsiology
They are relatively frequent in malarial countries (Med and Africa)
Protection is bough at a prize; homozygous carriers of mutations usually suffer from disease.

Question 30

What is the Duffy Factor and how does it provide protection?

Answer 30

Duffy antigen / chemokine receptor (DARC) is a glycoprotein on the surface of RBCs which is used by P. vivax merozoites for RBC invasion. PvDBP (P. vivax Duffy Binding Protein) is the ligand for DARC
DARC does not occur in the sub-Saharan African population (resistant to P. vivax infection). PvDBP is a candidate for anti-invasion vaccine.

Question 31

What is sickle cell anaemia?

Answer 31

A genetic disease caused by a single point mutation (GAG –> GTG) resulting in distorted RBC shape and the B-globin forms long stacks
Sickle cells have a shorter life-span and are not replaced as rapidly as normal RBCs, resulting in anaemia.

Question 32

What is thalassaemia?

Answer 32

Genetic disorder affecting haemoglobin synthesis
Mutations can be either in alpha or beta chain
If the mutation is in the alpha chain, one or two of the alpha genes are deleted from chromosome 16 (non-life threatening anaemia)
This confers protection against malaria but the mechanism is not fully understood

Question 33

What is serodiagnosis?

Answer 33

Detection of anti-malarial antibodies (e.g. IFAT; indirect fluorescent antibody test)