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Malaria in the mosquito, and its critical place
in formulating eradication strategies.
R.E.Sinden DSc, FMedSci. The Malaria Research
Centre Imperial College London
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Malaria Research CentreResearch underpinning
Intervention

• The Biology of Transmission
• Parasite - Vector interactions
• Systems analysis
• Development of transmission blocking drugs and
  vaccines

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What is (human) malaria?

• 5 species of parasite. P.falciparum P.
  vivax P. malariae P. ovale P.knowlesi
• Transmitted by 51/470 mosquito species

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The dual drivers treatment and control

• There is a clear and urgent need to save the life
  of each infected individual, but unless we stem
  the input of new cases such campaigns are
  unsustainable.
• Elimination/eradication, as an objective,
  refocuses our attention on the critical need to
  break the parasite transmission cycle (Ro). If
  Ro 100, blocking transmission from one patient
  saves the costs of 100 treatments.

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Why target malaria in the mosquito?

• Experience says vector control can reduce
  transmission.
• Average infection 5 parasites (vs 109 -1012 in
  human).
• Extracellular for 24hrs vs. 15 sec in man.
  (window-of-opportunity)
• The target of T-B vaccines are remarkably
  invariant.

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Why attacking (malaria in) the mosquito is an
effective strategy
Ro- the basic reproductive rate, is defined as
the number of secondary cases derived from one
individual. For malaria this can be as high as
200, but must be lt1 to reduce the number of
persons infected.
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What factors determine the value of Ro?
Proportion of mosquitoes that are infectious
Mosquito biting rate
Mosquitoman ratio
Days taken for parasite in mosquito to become
infective
Ro
r(-logep)
Mosquito daily survival rate
The daily proportion of infected people who
become non-infectious to the mosquito
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Repellents Deterrents ITN GM-Olfaction
mutants Clothing Housing GM-Biological clocks
Parasite-vector interactions Vector
immunity Sporontocidal drugs GM technologies
Environment mgmt Insecticides Larvicides SIT/RIDL
Biological control GM-sex ratio
Ro
r(-logep)
Terminator genes ITN/IRS
Transmission-blocking vaccines and
drugs Gametocytocidal drugs Effective liver/ABS
drugs/vaccines
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Why target malaria in the mosquito?

• Past experience says vector control can be very
  effective.
• Average infection 5 parasites (vs 109-1012 in
  human).
• Extracellular for 24hrs vs. 15 sec in man.
  (Window-of-opportunity)
• The target of T-B vaccines are remarkably
  Invariant.

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Population bottlenecks
With thanks to Georgos Christophides
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Why target malaria in the mosquito?

• Past experience says vector control can be very
  effective.
• Average infection 5 parasites (vs 109 -1012 in
  human).
• Extracellular for 24hrs vs. 15 sec in man.
  (Window-of-opportunity)
• The targets of T-B vaccines are remarkably
  Invariant.

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Timing of Plasmodium development in the mosquito
15 min
1 hour
12 hour
12-20 day
24-36 hour
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• Drugs to target signalling pathways
• Provide insights into life cycle regulation
• Identify essential genes for prioritisation as
  drug targets

Billker et al.,
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Surface/secreted molecules with potential for
transmission-blocking vaccine development
P25 P28
P230 P48/45 Fuse M
P47
Chitinase WARP MAOP CTRP
Fertilization
Ookinete
Epithelial invasion