1. What measures of malaria do we need to monitor elimination?
Chris Drakeley

2. The Spectrum of Malaria Infection
Infectious bite
Biological parameters for assessing
transmission intensity
Infection
Clinical malaria
Less Common events:
identified via health facilities or
DSS
Severe malaria
Death
(Greenwood et al. Parasitology Today 1992;7,277.)

3. Figure 1.P. falciparum Malaria Risk Defined by Annual Parasite Incidence (top), Temperature, and Aridity (bottom)
Areas were defined as stable (dark-red areas, where PfAPI ≥ 0.1 per thousand pa), unstable (pink areas, where PfAPI < 0.1 per thousand pa), or no risk (light grey). The few areas for which no PfAPI data could be obtained, mainly found in India, are coloured in dark grey. The borders of the 87 countries defined as P. falciparum endemic are shown. Highland areas where risk was excluded due to temperature appear in light grey. The aridity mask excluded risk in a step-wise fashion, reflected mainly in the larger extents of unstable (pink) areas compared to the top panel, particularly in the Sahel and southwest Asia (southern Iran and Pakistan).
(Guerra et al Plos Med 2008)

4. Entomological monitoring
Requires long term, regular monitoring
Sampling needs to be increasingly intense as the number of mosquitoes (and infected mosquitoes) decreases.

5. Mosquito human dynamics
Routine entomology remains key for monitoring changes in vector behaviour
What species are they?
Do mosquitoes bite earlier?
Do they bite outside?
Are they resistant to insecticide?
(Killeen et al BMC ID 2006)

6. Measuring parasites The gold standard measure
Allows detection and enumeration of parasites
Allows speciation and identification of potentially infectious individuals

7. Limitations of microscopy
This method is limited by how much of a blood film can be read…….
Ideally we need to identify all those infected (& infectious)
RDT have similar sensitivity to microscopy

8. Progress with molecular methods
Two new methods the LAMP (above)
& NALFIA have 5 fold better sensitivity
that microscopy or RDT.
Species, density and gametocytes remain issues
Figure 3 | Detection of the loop-mediated isothermal amplification (LAMP)
reaction using fluorescent metal indicator. (a) Irradiating the tube using a
handheld-UV lamp (wavelength: 365 nm) from the bottom. (b) Under
daylight. Plus sign denotes positive reaction (with target DNA), minus sign
denotes negative reaction (without target DNA).
Fig. 2. Example of positive and negative NALFIA. The left stick shows the
negative control sample that does not contain targetDNA.Only the control line
becomes positive. The stick on the right shows a NALFIA with the amplified
Plasmodium product (lower band) and the control line (upper band).

9. Serological alternatives
Detecting anti malarial antibodies in the blood of people who have been exposed to malaria is another approach
Antibodies last for a long time and represent cumulative exposure to malaria
Cheap, easy and high through-put
Modern techniques are sensitive and specific

10. Identification of transmission sites: regional level
Blue bars –parasite prevalence , purple bars -sero prevalence
Data from the Thai-Cambodia boarder
Increased sensitivity of serology to allows
Identification of potential foci of infection for the control of drug resistance
Cook et al unpublished

11. Identification of transmission sites: village level
Data from Kenya showing that individuals closer to mosquito breeding sites have more antibodies or malaria exposure.
Malaria transmission remains heterogenous and
Identification and targeting high transmission foci within a village will be key.
Wilson et al BMC ID 2006

12. Monitoring progress of the elimination effort
Historical precedents for serological evaluation of malaria eradication attempts
-Mauritius
-Greece
Antibodies to detect changes in exposure to both P.falciparum and P.vivax.

15. Monitoring will require a combination of approaches
When & how to measure?
Monitoring will require a combination of approaches
Rapid situational assessments to identify key areas leading to
Detailed surveys (MIS) for risk factor analysis
Sentinel site monitoring for vector studies and parasite and vector resistance

16. Biological tools for the eradication toolbox
Use of existing tools to monitor entomological, parasitological and serological changes.
Technological developments to increase the sensitivity
Develop appropriate sampling frames for representative sample collection