Malaria module Flashcards
Ways to measure malaria transmission intensity?
- Suitability maps using GIS
- Entomological inoculation rate
- Parasite measures eg parasite prevalence = rate PR, molecular
- Other community measures eg Hb levels, spleen rates, serological markers
- Symptomatic malaria (threshold ACD vs PCD)
- Severe malaria and mortality eg syndromic definitions, all cause vs specific
What is EIR?
Gold standard measure
Prevalence of infection in vector x vector human contact per unit time
eg Mos infected/Mos caught x Mos caught/’catching events’ x time
Usually thought of as infectious bites per person per year
Provides important ancillary information eg species, blood feeding and resting behaviour
Ways to measure EIR?
Mosquito trapping
- Human landing/biting catch
- light trap catches
- spray catches
- exit traps
Assessment of infectivity
- dissection
- ELISA
- PCR
What are the caveats of using EIR?
- Depends on intensity of sampling and sporozoite rate
- Difficult to capture the heterogeneity of transmission -> most trapping methods are for endophilic vectors
- Considered unreliable if EIR<5 and therefore, suited to measure and monitor transmission at higher levels
What is parasite prevalence?
Widely used
% of people that have a malaria parasite in them
- Suitable for collecting via a variety of approaches eg schools, ANC visits etc
Assess via:
- Microscopy
- RDTs
- PCR/NAAT
Advantages of serology for transmission measurement
Helpful in low levels of transmission or pre-elimination/elimination phases
Detection of hypnozoite carriers in vivax
Can tell you about reduction in exposure by right shift of age and serological prevalence curve
Disadvantages of serology for transmission measurement
No standardised assay
No consensus on what and how many Ags to use
Does not yet tell you about recent infections
Abs saturate at high transmission as everyone positive
Vector control methods for malaria and what they achieve?
Adult control:
- IRS (population level)
- ITNs (personal protection)
robust, standardised, affect density and longevity
Larval control:
- larviciding eg chemical, biological
- biological control
can only do if sites fixed and findable, must be closely adapted to local conditions
Personal protection:
eg nets
Genetic control:
- sterile males
- refractoriness genes
What are the two families of proteins on RBCs that parasites use for invasion?
1) Reticulocyte binding proteins (RBP or RHs)
2) Duffy binding like proteins (DBPs or EBAs)
What antigen does P vivax use to get into cells and how does this affect global populations?
Duffy
Geo: South America and Asia, esp South East
How is P Knowlesi able to jump species?
Possibility that P knowlesi has multiple ways of invading macaque RBCs compared to human cells -> if you put it in lab it will preferentially invade RBCs of macques than humans
P Knowlesi has 3 DBPs
- DBPalpha binds to DARC on both human and macaque cells
How is P Knowlesi mistaken for other plasmodium species?
Microscopy: similar to P malariae
Molecular: some cross reactivity with P vivax
What mutations are associated with artemisin resistance?
pfk13 mutations - reduced susceptibility to artemisin but not complete resistance
- although these might be marker of resistance rather than the causative mechanism
Most people at risk of what type of Malaria?
P vivax
NB: responds less well to vector control
Why is P vivax so widespread?
Sporogony can be completed at lower temperatures hence more widespread
Why is P vivax found less in West Africa?
P vivax selects Duffy positive Ag RBCs only -> most people Duffy negative in W Africa
What is the most common pathology of vivax infections and why?
Anaemia
Due to preference for reticulocytes
Diagnostic features of vivax?
Schuffner’s dots
Enlarged cells
Less merozoites than falciparum
What are P vivax hypnozoites?
Developmentally arrested liver stages that can remain dormant for weeks to months before reactivating causing relapse
–> time to first relapse and frequency of relapses differ among P vivax strains from different geographical areas as hypothesised to be linked to optimal transmission season
- Very small
- Metabolically inactive
- Signals for activation as yet unidentified
Why do P vivax infections not exceed parasitaemias of 1%?
Only 1-3% of all red cells have Duffy Ag
What reticulocytes does P.vivax exclusively invade?
CD71+ reticulocytes
Where does P vivax sequester?
98% of biomass of parasite of vivax out of blood
large amount found sequestered in the spleen, other reservoirs possible eg BM
Basic features of P vivax transmission in terms of gametocytes and vector uptake
- P vivax density of gametocytes closely correlated to parasitaemia
- Over a certain threshold most mosquitoes that feed become infected
- Sporogonic development can occur at lower temperatures eg than falciparum, but takes longer -> female mos must live long enough for sporozoites to develop and move to the salivary glands
- process takes a min of 9 days when temp around 30 degrees
Two options for treatment of P vivax hypnozoites
Primaquine
- requires 14 days of treatment
- slow/quick metabolisers eg CYP2D6 can affect mode of action
- big issue with adherence
Tafenoquine
- requires 1 dose
Both cause haemolytic anaemia in G6PD deficiency individuals
pregnant women and infants can’t be treated
= if foetus G6PD deficient, infants no dosing for PQ