Vaccines and volunteers: preventing malaria with a cup of mosquitoes
In her runner-up article for the 2014 Max Perutz Science Writing Award Wiebke Nahrendorf, a PhD student at the MRC National Institute for Medical Research, explains why she’s been infecting volunteers with malaria in the name of research.
Nijmegen, The Netherlands. It is cold and a slight drizzle makes it uncomfortable to roam the campus of Radboud University. It seems like an unlikely place to study a tropical disease. And yet behind the walls of the university medical centre an angry buzz emerges from cups, which look just like the ones for take-away coffee ― only with a bit of white netting on top. The source of the buzzing: fifteen mosquitoes in each pot. These mosquitoes are infected with the deadliest parasite on earth: Plasmodium, which causes malaria. And they are hungry. For human blood.
In the waiting room two dozen volunteers are about to be called in to put their left arm on to a cup filled with these mosquitoes, which, while sucking blood, will infect them with malaria. But HOLD ON! That seems like a terrible idea! Of course, these brave volunteers knew what they were in for and there is a whole battalion of dedicated doctors to check on them 24/7 and treat them if necessary, but still… Why are we infecting healthy Dutch people with malaria?
Malaria is a leading cause of death in many countries of Africa. Almost half of the world’s population is at risk of getting the disease. The tiny, single-cell Plasmodium parasite is unfortunately very successful in evading drugs and efforts to get rid of the mosquitoes that pass it on, because it changes its shape and habitat all the time.
After injection of a few parasites into the skin during a mosquito bite, Plasmodium first heads to the liver, where it cunningly hides causing no signs of illness. In the liver the parasite builds up strength to initiate the real threat: the infection of red blood cells. Parasite-infected red blood cells can cause flu-like symptoms: headaches, sweats and fever.
Things also get worse quickly: many red blood cells get destroyed by the malaria parasite and infected red blood cells stick together and block blood vessels. These blockages, particularly in brain, kidneys and lungs, lead to seizures, unconsciousness and death. Parasites in the blood can also be taken up by a biting mosquito, ready to be passed on to another person, creating a cycle.
Malaria is most dangerous to people who never had it before: especially for young children in Africa but also for travellers from Europe. The World Health Organization estimates that 482,000 children under the age of five died from malaria in 2012. Scientists all over the globe agree that the most effective way to wipe out malaria is to develop a vaccine. This has unfortunately been proven to be much more difficult for malaria compared to other less complicated diseases like Tetanus.
On our quest to find out how to make an effective vaccine against malaria, we need to understand how the immune system combats the disease. And this is where our brave Dutch volunteers come in; because we have found a way to protect them from malaria by exposing them to mosquito bites.
Once a month our volunteers come into the clinic and put their arm on to a cup with fifteen malaria-infected mosquitoes. At the same time we give them a tablet of an antimalarial drug, which kills the parasite as soon as it reaches the blood stream. After the third round of bites-and-drug we wait for five months, before infecting the volunteers again- this time without the drug as a safety net. And amazingly, they do not show any signs of illness from malaria and have no parasites in their blood stream!
This means that Plasmodium was stopped in the liver. Why does this matter? If we could design a vaccine that protects in the same way, it would have a dual role in preventing malaria; keeping parasites out of the blood means the person will not get sick and there will be no parasites for a mosquito to pick up, breaking the cycle. So vaccinated people would not only protect themselves from the disease, but also help to reduce the amount of infected mosquitoes in their area. Both effects together would finally put a hold on malaria.
It is of course not very practical to ship millions of take-away coffee cups full of mosquitoes to protect everybody in Africa the way we did with our volunteers. But by studying how their immune system kills the parasite to protect them from malaria, we can take essential steps towards the development of a safe and effective vaccine.
So maybe it is not so crazy that Dutch volunteers put their arm on a pot with hungry mosquitoes, because they contribute to the huge efforts made worldwide to find a malaria vaccine and save millions of lives.