Charles Agoti: Using genomics to understand diarrhoea epidemiology
Vaccines against rotavirus, the most common cause of diarrhoea globally, don’t work well in LMICs populations that need them the most. Co-infections might influence vaccine immunity. Genomics and epidemiology help us improve diagnostics, and find out whether some additional strains need to be included in future vaccines.
My name is Dr Charles Agoti. I work on rotavirus, the leading cause of diarrhoea globally.
We do have vaccines against the rotavirus, but they do not work optimally in the populations that need them the most, in low and middle income settings. My interest is why these vaccines do not work optimally. I use a variety of tools including genomics, molecular diagnostics and epidemiology to try and understand why these rotavirus vaccines are suboptimal in our setting.
Diarrhoea is an important public health problem in the tropics, and my research focusing on the viral infection that we have a vaccine on but is suboptimal, is contributing to fighting illnesses in the tropics. In particular, I am interested to know where the strains in the post-vaccine era originated from. I am using tools which are now readily available including genomics to try and answer that very important question. The other thing which we know about pathogens which we are fighting at the moment, especially viruses, is that they change rapidly, and once you have a vaccine in place, there is potential that the virus will evolve and have another type that is not included by the vaccine.
What we are doing is characterising these strains and trying to look at the vaccine to understand whether there is vaccine escape, and that is going to point towards whether we need to rethink our vaccine strains included in this vaccine. That is how I am trying to provide information from the best science I am doing, so that that it can go to the vaccine developers.
The other thing which I might add is that the diagnostics are really important. Diarrhoea is caused by a variety of pathogens, and in particular we have up to 30 agents. By involving my work which looks at how molecular tools can address that, I am able to tell you whether an infection is not from rotavirus, and that can stop for instance giving unnecessary antibiotics, or if the infection is from a parasite. It helps the clinician know when a child is coming in with an infection whether they need to give them a set of treatment or preventative measures, which is important in addressing problems in the tropics.
Some very important lines of research have been developed in the last couple of years. For instance, understanding on how co-infections influence vaccine immunity. When a child receives that vaccine, what other infections they have in the gut, and how that influences how they are going to respond to the vaccine. When you are seeing a child in the hospital and you find them with rotavirus, what other infections do they have? It could just actually be rota. Things to do with re-infections: there are children who become repeatedly infected with this virus, for instance, which is really important to understand.
Genomics is another area which has developed in the last couple of years, so how can we use it, and what’s coming through genomics to help us understand infections in the tropics. We are trying to understand genomics variation to help us understand vaccine escape in mutants to help us develop diagnostics. Those are the new lines of research which are now developing.
It is really important for us to invest in understanding, for instance, why vaccines are suboptimal in populations that need them the most, especially in low and middle income countries. For every vaccine improvement, effectiveness increases; you are saving lives.
My research fits into translational medicine indirectly; as I stated I am at a more basic science level, but this is part of the continuum, how you get understanding of a pathogen in the lab, to how you get a product in the end. By understanding what characteristics we have in the viruses we see in children who come to hospital that will inform how we constitute the vaccine for instance.
Understanding which strains are still in circulation and understanding where they come from, even when you are vaccinated, is going to help us point where we need to focus our intervention mechanisms. We are producing information at the best level, for instance how many co-infections are occurring, which is going to help public health experts know what else they need to do in the community to prevent children from carrying these types of infections that we find as co-infections in diarrhoea cases at the hospital.
This interview was recorded in May 2019