Isabella Oyier: Malaria and immunity
Understanding mutations in the malaria parasite gives us an insight how it escapes the immune system, as well as the mechanisms of drug resistance. This molecular work also helps find better candidates for malaria vaccines. In the long term, surveillance of markers of resistance informs national drug policy.
My name is Isabella Oyier, and I am a senior research scientist at the KEMRI Wellcome Trust Research Programme in Kilifi, working on the malaria parasite. My research involves looking to understand mutations in the malaria parasite which allow it to resist drugs, to confer resistance to antimalarial drugs and help them escape so the drugs don’t kill them.
Another set of mutations I am trying to understand is the stage of the parasite that gets into the red blood cells and causes disease, the fever and chills associated with malaria. This stage of the parasite has a set of proteins that allow it to invade red blood cells. These proteins have mutations, and we scientists are not entirely sure what those mutations are doing. Part of my work is trying to understand if these mutations allow the parasite to escape the host immune system which fights and protects us from disease, or do those mutations actually allow the parasite to invade the red blood cells better and cause disease.
One of the challenges in malaria is finding a vaccine that will work. Those challenges arise because the parasite has a lot of mutations which allow it to escape the host immune system. We need to find a way to better understand those mutations so we can produce better vaccines. For instance, one of the lead vaccine candidates at the moment is a protein called Rh5 in simplicity, it’s a protein on the stage of the malaria parasite that allows it to invade red blood cells and it has been shown to be quite important in helping the parasite do this work. My work takes place in Kilifi, in a malaria endemic population, to try and understand how many mutations we see in this protein, and if we can find a way to understand what they do, in the protein.
The current vaccine that is being rolled out in an implementation trial in western Kenya – to see how to best introduce it to the public, like a children vaccination schedule – one of its limitations is that it doesn’t provide 100% protection. That is where my work comes in, to see it we can find other potential candidates on the malaria parasite that could make that vaccine more efficacious, and if we could do a combination of different candidates so that we can improve how this vaccine would work in the field. My work is very early on in vaccine development: it’s trying to understand the biology of that molecule, at the molecular level, to better inform what these mutations are doing so we can design a vaccine to encompass all the issues that arise from understanding the protein.
In sub-Saharan Africa, in Kenya as well, it is very clear that malaria is a big public health concern. It causes a lot of illness in children under 5, in pregnant mothers, and generally being unwell is not a nice thing. The work that I do tries to find different vaccine candidates that we can put forward to make a malaria vaccine. The importance is, as shown in other diseases, if you have a vaccine against a particular organism that causes disease, a bacteria or a virus, you can prevent people from getting sick, and we are not able to do that at the moment with malaria. The purpose of my work is to understand the proteins that we could use to inform vaccine design.
What is interesting in the field at the moment is the emergence of resistance to artemisinin in Southeast Asia. This is a great concern because if that spreads globally then we will no longer have a drug we can use to treat people. The good thing that came out is a molecular marker – a gene which we know the mutation confers resistance to artemisinin – has been described. That helped the antimalarial resistance field because it means we can now study that gene in populations in Africa and understand if we have the mutations seen in Southeast Asia, in Africa; if we do that would be a cause for concern. As it stands in the field, for the studies done here in Kilifi by myself and others in other African countries, those mutations have not been identified. At the moment we are in a good place in terms of how the drugs are working in Africa, but it still means that we’ve got to maintain surveillance and monitor antimalarial resistance, particularly to artemisinin, a drug that works very well and if we lose that it would cause a problem for malaria control.
How do my work impacts on translational medicine? I work primarily in the lab, using molecular biology tools to understand mutations for instance in drug resistance. With this we’re able to inform national drug policy by saying if those mutations are present in the population and if they are that would inform a change in drug policy. Previously we were using sulfadoxine-pyrimethamine; molecular work was done to show the mutations are present in Kenya, which informed the national malaria control programme, that they need to consider changing the drug that we use. Currently what I am doing is maintaining surveillance on markers involved in artemisinin resistance that will then feed into policy in the long run as to whether we should be changing drug or not.
The roles that I play in the policy forums, to try and influence decisions made around malaria public health policy, for instance I work quite closely with the National Malaria Control Programme, in fact we are the lab that is doing the molecular work for their drug trials. The recommendation is that you have to do drug trials in children, but we need the molecular work to understand whether the drugs are working well or not. Without the molecular work we cannot say if the drugs we are using to treat malaria are working well or not. That is where our role comes in, understanding these mutations and these markers that confirm resistance to drugs.
The other way I am involved with the National Malaria Control Programme is helping them see the importance of molecular work, both generally and informing primarily drug resistance, and its utility as a good way for screening the population to understand the distribution of these mutations in Kenya. That might inform where you would target particular drugs in the event of drug resistance.
This interview was recorded in May 2019