ScienceDaily (June 23, 2004) — Vaccination programmes could create conditions which promote the evolution of virulent strains of malaria, according to a laboratory-based study of the malarial parasite Plasmodium in mice. The findings, published online in the open-access journal, PLoS Biology, are likely to spark debate among public health groups seeking to curb the disease, which claims up to two million lives each year and accounts for one child death every 30 seconds in Africa.

Vaccines are designed to protect people by boosting the immune system to kill parasites but, unless a malaria vaccine leads to the death of every single parasite, the ones that survive are likely to be the nastiest. The new research by Dr Margaret Mackinnon and Professor Andrew Read, of the University of Edinburgh's Institute of Cell, Animal & Population Biology, sought to investigate how vaccination can, in fact, lead to the evolution of more virulent strains of the disease.

Initially, the Edinburgh researchers directly injected two groups of mice with infectious parasites - "immunised" mice, which had been exposed to Plasmodium and then treated with the anti-malarial drug, mefloquine, and "nave" mice, which had not. They then transferred parasites via a syringe from host to host 20 times. The parasites thus evolved in the immune or non-immune environments. The parasites that evolved in the immunised mice were more virulent than parasites evolved in the naive mice.

The researchers then tested whether this increased virulence would be retained if parasites were transmitted by a mosquito, rather than through a syringe. Infection was not as severe after transmission through mosquitoes - an intriguing finding in itself - but the effect was still there. In other words, immunity accelerates the evolution of virulence in malaria, even after mosquito transmission, making them more dangerous to their non-immunised hosts.

Dr. Mackinnon said: "How does immune selection create more virulent pathogens? One possibility is that many parasites die in immunised hosts but those that win "the race to the syringe" - or the mosquito - are probably genetically equipped to stay ahead of the advancing immune system. Since the virulent strains showed no problems transmitting infection to new hosts, it's likely that such strains would spread throughout an immunised population.

"Many questions remain, but these results make a strong case that vaccine development aimed at containing infectious pathogens would do well to consider the evolutionary implications, or increased pathogen virulence could be an unintended consequence."

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Citation: Mackinnon M and Read AF (2004) Immunity promotes virulence evolution in a malaria model. PLoS Biol 2(9):e230.

The published article will be accessible to readers at: http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020230

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