There are around 200 million cases of malaria every year, and more than three-quarters of a million people, mostly children living in sub-Saharan Africa, die as a result of the infection, according to the World Health Organization (WHO). While there is currently no licensed vaccine, there is one promising candidate, called RTS,S, currently undergoing the final stage of clinical trials in infants and children in seven African countries.
Should the vaccine become licenced, what remains unclear is how to maximise its use. It is anticipated that it will be given to infants through the WHO's well-established Expanded Program on Immunization, but it could also be given to people of all ages through mass vaccination campaigns.
In recent years, many researchers have built various mathematical models to try to simulate how malaria is transmitted in a population and the effectiveness of different vaccination campaigns. Published January 17 in PLoS Medicine, this new study used ensemble modeling, combining simulations from 14 models to get a representative sample of possible future states. Ensemble modeling is often used in tasks such as weather forecasting.
“We used ensemble modeling because we thought that the results might depend a lot on assumptions about natural immunity to malaria, and on how much variation there is between people in how many mosquitoes bite them, or in how sick they get when they are infected with malaria,” said Tom Smith, from the Swiss Tropical and Public Health Institute and the University of Basel, and lead author on the paper.
The team of researchers simulated a population of 100,000 individuals, exposed to malaria-transmitting mosquitoes. Each malaria infection was simulated, with the chances of this causing severe illness or death calculated using data from various places in Africa. They used the volunteer computing project malariacontrol.netto run the simulations.
“These simulation experiments could be run on other high performance computing resources, but malariacontrol.net is by far the most powerful system we have access to,” said Nicolas Maire, a colleague of Smith, in Basel, Switzerland.
“More than 20,000 volunteers contributed to running the simulations for the study,” said Maire, “The simulations ran over several months. The bulk of the CPU time went into estimating parameters for the various models in the ensemble, whereas the predictions shown in the paper required only a few days to run.”
The researchers found that the results were broadly the same for all the different sets of assumptions. “This means we are much more convinced that our results are correct than we would have been if we only had one model,” said Smith.
Through this simulation, researchers showed that a vaccine is likely to be as useful in very low transmission areas (where people get two infectious bites per year or fewer) as in higher transmission settings (where people get 20 or more infectious bites per year or more). Previous modelling has shown that there may be little or no benefit in very high transmission settings.
“We would have expected to find that vaccination would be of less value in very lowest transmission settings, as fewer people there get ill or die of malaria than in higher transmission settings, so the possible benefits are less,” said Smith.
As a result of their unexpected discovery, “it would be worth considering strategies that involve vaccinating all ages of people, but only in settings where malaria transmission is already very low. It is clearly not realistic to do this everywhere, but it would be possible to start planning trials, with a view to implementing this selectively. The plans for using RTS,S currently envisage vaccinating only infants, and it would take quite a lot of careful preparation before trials of mass-vaccination strategies could be carried out.”