Infection 2: Pathogenesis of malaria Flashcards
Incidence of malaria
21% global decrease in malaria incidence between 2010 and 2015
219 million cases globally
Mortality of malaria
29% decrease in global malaria mortality rates between 2010 and 2015
435000 deaths
Malaria interventions
Insecticide treated mosquito nets
Indoor residual spraying
Diagnostics
Treatment
Prevention in pregnancy
Issues in UK
Malaria is the single most common imported infection in travellers
1792 UK cases notified in 2017
Approximately 6 deaths a year
Blood stage parasite of malaria
Gametocytes picked up during blood meal by anopheles mosquitos
Start another cycle of growth and multiplication in the mosquito
Mosquito takes another blood meal from another human
Infective sporozoites injected with saliva and start another human infection- infect liver cells first
From here enter blood stream as merozoites, then enter RBC for cycles of replication within the peripheral and microvasculature
Merozoites mature into trophozoites which mature into schizonts, which then rupture releasing more merozoites
Most common in UK
Plasmodium falciparum
Blood film diagnosis
Take blood sample and drop blood on slide
Dry, fix with alcohol
Dry, treat with Giema stain to stain parasites
Dry, look through microscope
Can identify species and number of parasites
- no fixative
- RBCs lyse
- increased sensitivity
- cell fixed intact in monolayer
Rapid diagnostic testing
Detects parasite specific antigens or enzymes
Less sensitive than microscopy
Useful if skilled microscpoist is not available
Uncomplicated
Parasitaemia <2% and no schizonts and no clinical complications
Severe
Parasitaemia >2%
Or
Parasitaemia <2% plus either scizonts reported on blood film or complications
Multi system disease
Rapid progression to death
Mortality of 10-40% in first 24 hours
Medical emergency
Plasmodium falciparum erythrocyte membrane PfEMP-1
On the surface of Infected RBC
Encoded by a family of 60 var genes. A single cell only expresses one of these at any time
The parasite regularly exchanges the expressed var gene, leading to antigenic variation. As an antibody response forms to 1 PfEMP, there is a switch of expression to alternative PfEMPs, escaping the immune response and maintaining infection
Clinical spectrum of severe malaria in childhood
Cerebral malaria
Anaemia
Jaundice
Respiratory distress
Renal impairment
Blackwater fever
Hypoglycaemia
Cerebral malaria
Unrousable coma in oresence of peripheral parasitaemia where other causes of encephalopathy excluded
In children, Blantyre coma score used
Diffuse cerebral dysfunctions, generalised convulsions
Focal neurological signs and brainstem signs
Abnormalities of posture and muscle tone
Differential diagnosis: meningitis
Effects of IV quinine
Hypoglycaemia
Arrhythmias
Potentially lethal hypotension in rapid infusion
Significant mortality still: cerebral malaria has a treated mortality rate of 15-20%
IV artesunate
Safer and easier to administer
Reduces parasite burden more rapidly
Kills circulating ring-stage parasites as well as schizonts
Sickle cell trate
HbS relatively protected
Duffy negative
Persons who are negative for the duffy blood group have RBC that are resistant to infection by P.vivax
P.vivax is rare in Africa south of the Sahara
Key drivers of antimalarial drug resistance
Unusual genetic structure of malaria parasites in regions known for antimalarial drug resistance
Artmisinin drug use without complementary combination treatment such as lumefantrine
Unregulated or poorly administered antimalarial drug use
Counterfeit or substandard treatments: cause 25% of all malaria deaths
Parasite factors
Drug resistance
Mulitplication rate
Invasion pathways
Cytoadherence
Rosetting
Antogenic polymorphism
Antigenic variation (PfEMP1)
Malaria toxin
Host factors
Immunity
Proinflammatory cytokines
Genetics (sickle cell trait, thalassaemia, ovalocytosis)
Age
Pregnancy
Geographical and social factors
Access to treatment
Cultural and economic factors
Political stability
Transmission to intensity
