Malaria imposes a huge disease burden, especially in the poorest areas of the world. According to the WHO, there were 219 million malaria cases and 660 000 malaria deaths in 2010, 90% of which occurred in Africa.
Malaria is caused by Plasmodium parasites, transferred to humans via bites from infected mosquitoes. The parasite infects the host’s liver cells before moving on to its red blood cells, ready to be transferred to a mosquito again to complete its lifecycle. Symptoms include the well-known fever attacks, but malaria can also cause serious brain damage or organ failure, in many cases fatal.
So how can we stop malaria? The use of mosquito nets and insecticide is important to avoid bites by infected mosquitos in the first place. Anti-malarial medications are also available. These are often used by tourists as prophylaxis; that is, to stop any infection before the actual disease develops, but can also be used to treat malaria if infection does occur. Worryingly though, cases of drug resistant Plasmodium parasites have been reported in several countries, suggesting that we may not be able to rely on these medicines forever.
What about a vaccine, then? Well, Plasmodium isn’t your standard simple germ – actually this single-cell organism is a eukaryote, meaning that its cells are more like ours than like a bacterium’s. And it has many dirty tricks up its sleeve…
A vaccine works because you expose the immune system to the infectious agent in a low dose or an inactive form, so that it will not cause any disease but still give the immune cells something to practice on. Then if we actually get infected with “the real thing”, the immune system will remember what it learnt, recognise the infecting agent as a harmful intruder and initiate a prompt response to eliminate it.
But Plasmodium is a master of disguise; it will produce a protein called PfEMP1 that is transported to the surface of the infected blood cell. This protein is under the control of the Var genes and comes in 60 slightly different varieties; however, only one variety is used at a time. Effectively, the parasite can slip on one of 60 different costumes so that it can sneak past the immune system unnoticed. And when the immune system is finally about to blow the parasite’s cover, it will just switch to one of the other 59 costumes and go free.
Recently, Jiang et al. has found out more about how this masquerading actually works. Their research shows that another gene, pfSETvs, silences all Var genes - except one at any one time. It does this by putting molecular flags, called methyl groups, onto the Var genes. This type of flagging of genes to silence or activate them is called epigenetics. The researchers then deleted the pfSETvs gene in a genetically modified parasite and voilà: the silence was broken and all 60 Var genes were expressed at once, so that all costumes were revealed in one go. According to the researchers, this modified parasite could be used as a vaccine since it would give the immune system inside knowledge of all the parasite’s disguises at once. Hopefully, this will bring us one step closer to a malaria vaccine that could save millions of lives.
WHO, World Malaria Report 2012
Scherf A, Lopez-Rubio JJ, Riviere L. Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol. 62:445-70 (2008)
Jiang, L. et al. PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. Nature 499, 223–227 (2013).