Radboud university medical center researcher and epidemiologist Teun Bousema has received a Vici grant of €1.5 million from the Netherlands Organization for Scientific Research (NWO) for research into resistance to a malaria drug.
There are 220 million cases of malaria each year, all of which require treatment with some form of the malaria drug Artemisinin. ‘This is the most important ingredient in malaria medicines’, says researcher Teun Bousema. To the great concern of the medical world, resistance to this drug is beginning to emerge in Africa. ‘Resistance has already developed against a malaria drug that was used on a large scale,’ says Bousema. ‘Because of that resistance and the delay in switching to a new drug, at least one million extra deaths have occurred.’
Bousema has received a Vici grant from the NWO to conduct research into resistance to malaria medicine. This money goes to the so-called SPARTAN project that he coordinates with researchers in Nijmegen and Uganda. This project investigates how resistance has arisen in Uganda and how quickly it can spread. In addition, we are looking at what can be done about it: ‘If Artemisinin really stopped working in large parts of Africa, this would be a disaster scenario,’ says Bousema.
Resistance
At present, resistance to the malaria drug is limited to a very small area in East Africa, but the concern is that it will spread. Until now, the hypothesis has been that resistance can only develop in areas where many people use and perhaps misuse drugs, where there is little immunity and where parasites have little competition from other parasites. ‘The latter is important because resistant parasites are often less fit,’ explains Bousema. However, how resistance could have developed in East Africa is a mystery because many people in this area are immune, the drug pressure is low and there are many parasites circulating. Bousema does have an idea how it originated and also has indications for it. ‘It appears that drug-resistant parasites spread more quickly, even in the absence of drug pressure. This means that the parasite makes more stages of transmission that can infect mosquitoes.’
The reproduction number can be greater than one hundred. “This is a number that pales that of covid.”
Bousema explains that the malaria parasites have a complicated life cycle. ‘You have a completely different form of parasite that makes people sick than the parasite that infects the mosquito.’ The researcher says that this is a conscious process of the malaria parasite. ‘How much am I going to invest in living on in the human bloodstream and how much am I going to invest in spreading it via the mosquito?’ It appears that resistance to Artemisinin is directly linked to the ability to make transmission stages. ‘This would mean that resistant parasites are more infectious to mosquitoes than other drug-sensitive parasites’, says the researcher. This would be a major concern and mean that resistance is likely to spread very quickly. The spread of Malaria is very efficient anyway. The reproduction number can be greater than one hundred. “This is a number that really pales that of covid.”
Research
Bousema’s research will be a combination of laboratory work in Nijmegen and fieldwork in Uganda. A lab is currently being finalized in Uganda. The researcher explains why this rural location was specifically chosen: ‘It is in an area where there is a resistance hotspot.’
The first step in the research is to breed mosquitoes that do not carry malaria parasites. ‘We will then take blood samples from people with resistant parasites and people with normal drug-sensitive parasites to see what the difference is in the spread of the parasites’, says the researcher. It is also mathematically investigated with a model by filling in all factors and seeing where the best predictive factor lies. If that goes well, the research team will undertake this on a large scale and look at infections that they will monitor over a longer period of time. They will also investigate the human factors that play a role. ‘Is it true that in people who may have slightly less immunity to malaria, those resistant parasites are more likely to remain?’
The results are important to find out what can be done about the resistance.
The results of the research are important to find out what can be done about resistance. ‘For example, we want to find out whether a drug that kills the spreading stages of malaria can contain the spread and find out whether better treatment of clinical malaria can already push back much of it.’ Moreover, other scenarios are also taken into account: ‘Perhaps we should also actively look for malaria infections in the village in order to clear malaria-resistant parasites.’
Bousema points out that the research has a high priority. ‘We are really trying to do this very quickly with a group of Ugandan researchers and every year we also have meetings with the Ministry of Health if we think our findings are relevant for interventions or for the approach.’ In this way, the Ministry does not have to wait for the publication, but is immediately pushed to it, which means that there is more time for a public health intervention if necessary.
Vici-beurs
According to the researcher, the Vici grant application was a long process. “You have to make a plan in few words to convince the jury to give you a million and a half.” He explains that about 10 percent of applications are approved. ‘When you consider that the top scientists are requesting it, you can imagine that it is very competitive’, Bousema continues. ‘A lot of excellent researchers who would really deserve it unfortunately fall behind the net,’ says the researcher.