Plasmodium and Malaria (Franco Falcone) Flashcards
When should a patient be assessed for malaria?
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.
How long can Malaria present after travel?
Up to a year post trip
Is Malaria a notifiable disease?
Yes in the UK (Health Protection Notification Regulation 2010).
What kind of Malarias are there?
Plasmodium species Falciparum (subtertiana) Ovale (tertiana) Vivax (tertiana) Malariae (quartana) Knowlesi (quotidiana)
How is Plasmodium spread?
Spread by mosquitoes of the genus ANOPHELES
(= vector)
Anopheles deposits eggs in stagnating waters e.g. rice paddies, swamps, marshes
Rain season, puddles!
What is the life cycle of a mosquito?
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
Why is malaria proliferative in tropical countries?
Mosquitos need a minimum temperature to mature
What does Anthropophillic mean?
Preference for human blood
(There are different species of Anopheles, not all of them are anthropophillic, some have a preference for animal blood.)
How is Malaria transmitted from the anopheles mosquito?
The mosquito injects saliva
Contains an anti-coagulant
Plasmodium enters the blood within the infected saliva
What stage of disease leads to the symptoms of Malaria?
No symptoms associated with the liver stage.
Symptoms occur when red blood cell stages rupture cells and release malaria ‘toxins’ and pyrogens.
What are the hosts of Malaria?
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.
What are the symptoms of Malaria?
Fever, anaemia, diarrhoea, vomiting, splenomegaly, (dead and broken red blood cell fills the spleen, making it enlarged) jaundice (liver function impaired).
What causes, and when is Malaria Fever present?
Caused by host cytokines released in response to released pyrogens (upon RBC rupture).
There can be severe malaria without any fever!
What are Malarial Fever patterns?
After the initial few weeks, fever becomes a regular pattern. (Tertiana, subtertiana, quartana) as schizogony becomes synchronised.
What are the stages of fever? (Especially prevelant in P. vivax)
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
In which species of Plasmodium can Malaria relapse happen?
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.
Which is the most dangerous malaria parasite?
What are the associated complications?
P. falciparum
Altered consciousness or coma can be caused by hypoglycaemia, acidosis, seizures or very severe anaemia
What is the main cause of malaria death?
Cerebral malaria; large number of RBCs containing mature parasites found in capillaries and venules of brain and other organs
How does malaria cause hypoglycaemia?
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
How does malaria cause severe anaemia?
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
How does malaria cause acidosis?
Tissue anoxia (oxygen depletion in tissues), leads to anaerobic metabolism and the release of lactic acid.
Why are pregnant women particularly threatened by Malaria?
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
What is recrudescence of malaria?
When malaria is caused by a small number of parasites persisting in RBCs
What is malaria reinfection?
Malaria attack caused by new inoculation of parasites from infected vector.
What is relapse in malaria?
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).
In what age is mortality in malaria highest?
P. falciparum in 5-6 year olds or younger
Is immunity to malaria possible?
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)
What is the link between Malaria- HIV co-infection?
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.
Are there any non-immune protective factors in malaria?
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.
What is the Duffy Factor and how does it provide protection?
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.
What is sickle cell anaemia?
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.
What is thalassaemia?
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
What is serodiagnosis?
Detection of anti-malarial antibodies (e.g. IFAT; indirect fluorescent antibody test)
