A team of scientists icipe together with their collaborators in the UK recently isolated and described a  microbe, a Microsporidian, with the potential to impair transmission of Plasmodium falciparum parasites in species of Anopheles arabiensis, an important milestone in the fight against malaria. PAMCA interviewed the lead researcher, Dr Jeremy Herren to find out more about this significant development and his views about what should be done to strengthen the malaria response in Africa.

Dr Jeremy Herren is a Research Scientist at the  icipe. He has nearly 20 years of experience working in the field of vector-borne disease control, notably malaria, focusing on insect host microbial symbiont interactions. He recently led a team of researchers working on mosquito-microbial symbiont interactions which culminated in the isolation of a bacterial (Microsporidia MB) shown to be capable of stopping malaria transmission.

Could you briefly tell us what type of research is done at icipe? 

icipe is an international research institute that focuses on insect research. It’s in some way quite specific but also diverse. Any insect related research can be done at the institute, that involves a lot of agricultural pest research, research on beneficial insects including honeybee and silkworms, and also research on disease vectors. That is the area which I am specialising in and we study a number of disease vectors, but I am especially focused on the biology of malaria vectors.

Can you tell us a bit about yourself and the focus of your current research?

Originally my father is Swiss and my mother is American. They were both scientists much like I am, and they worked in Kenya. I grew up in Nairobi, I went to school here and decided to follow in their footsteps and be a scientist. My interest has always been in insect-microbe interactions and particularly the concept of symbiosis, something that I always found very fascinating. There is something about two organisms living and even working together that I find super interesting. Insects are especially commonly symbiotic partners. You get a lot of insects that rely on microbes for many aspects of their lives. Insect symbiosis is something which I specialized in quite earlier on and ultimately, I did my Ph.D on this topic in Switzerland. As I was completing my studies, endosymbionts emerged as a tool potentially to control vector-borne disease. I began to think that it could be possible to do insect symbiont research that may have real impact. It was a big shift for me, moving back to Kenya, about 6 years ago now, where I was able to work on endosymbionts on disease vectors, to see if any of them could block the transmission of diseases. That took me back to icipe where this whole project started. I decided that not enough work has been done on symbionts of mosquitoes in wild and that most of the symbionts we found in mosquitoes colonies maintained in the lab were not particularly interesting. So we went to the field and started to look what symbionts can be found in mosquitoes. We found several, but one of them, for a few reasons, seemed to be quite interesting to us. It was not previously discovered; it was quite common and when in a mosquito it was found to be in high intensity and this was a microsporidian (later named Microsporidia MB). So, we focused on Microsporidia MB and we decided quite quickly to develop an experiment to discover if it has any positive or negative impact on malaria transmission. That is basically the starting point for the paper that was published, where we showed this microsporidia can block malaria transmission.

Who are the members of your research team?

Everything we do is a massive team effort. We had a team of students at  icipe who did most of the work and the key experiments. It is three Kenyan students, notably Lilian Mbaisi, Enock Mararo and Edward E. Makhulu. They are all co-authors of the paper. They were extremely hard working and spent many months in the field collecting mosquitoes and tending to them in the laboratory. We also had international collaborators that brought in key expertise. For example, we benefited from the wealth of experience our collaborators at the Sanger Institute in the UK have on RNA/DNA sequencing and analysis. We also had collaborators from University of Glasgow who were able to do some key molecular characterization experiments. Altogether, we had very good collaboration with the different institutions. For example, Enock Mararo to spend quite some time in Glasgow and in UK and he worked closely with our collaborators there, and also some collaborators came to Kenya for part of the research. So, we were able to work in different places and together. That makes things very easy, everyone was helpful and did their part. I think it was a very smooth experience with the different collaborators.

What led you to take an interest in this specific mosquito symbionts?

The work was largely inspired by a number of projects in the last decade showing that a bacteria (Wolbachia) symbiont could block the transmission of dengue fever. Given the power of that strategy, we really wanted to develop something similar for malaria. We decided to look in malaria mosquitoes for bacteria that has similar characteristics to Wolbachia and even any other bacteria the potential to be a bit like Wolbachia (heritable and intracellular). We started looking through mosquitoes and I should be able to say we spent a year without much success. We got a lot of our assays showing high amounts of Microsporidia and we realized that this is something interesting which needed to be studied. Eventually, we pretty much shifted our entire focus to microsporidia and that is really where we started getting much more interesting results.

How did you and your colleagues get to the discovery of this new microbe in wild populations of Anopheles mosquitoes?

As I said, we were looking for other symbionts and we kept getting this Microsporidia. We thought maybe we should shift and try to see if this  Microsporidia is common and what it’s doing? At that point, we started looking in different populations and found that it was something that was present all over. We started doing microscopy so we can really see it and what tissue it infected. Finally, we started experiments to get Plasmodium infected blood and feed mosquitoes on it and see whether there was any blocking effect. Initially, we were open minded about whether the effect could be positive, negative or neutral. When we did this experiment we were very surprised that we never had a single mosquito that had a single microsporidia that was able to take up the plasmodium, so we were able to demonstrate a very strong blocking phenotype.

How efficient  Microsporidia MB is in stopping malaria transmission?

So far, there is evidence that there is very strong blocking effect. We did this experiment under very natural conditions. We were taking patient blood from malaria endemic zones, and under various circumstances we had complete blockage. Then I suspected that the blocking is not quite 100%, but it could be very close to that, which is excellent. But blocking is only one side of the coin, because we now need to find the way to increase the number of mosquitoes that have microsporidia. And if we readily get 50%+ of all mosquitoes in sample site infected with Microsporidia MB then achieving this kind of spread will be more important than the strength of blocking effect. So that is the foundation we are building on and we were trying to find ways to elevate the prevalence of the microbe in mosquito populations.

What do you think can be done to increase the proportion of mosquitoes that carry the symbiont to limit their capacity to transmit malaria?

That is going to keep us busy now and probably for the next two years. I have some speculative theories, but the truth is that we need a lot of hard work to figure out what is the best way to increase the level of this symbionts. I think we might be able to disseminate Microsporidia first in sugar baits or in larval habitat. We found that adult mosquitoes can infect other adults and we believe that it is cause by sexual transmission upon mating. We have been exploring the possibility of rearing mosquitoes and then we only release the males which are heavily infected and then these would infect wild females and of course females transmit the symbionts to their offspring. There is a number of possibilities, so we would try and explore all of them to understand what is best.

How can this research be translated into the health policies of African states?

I think we are still in the early stages of this research, and we need to get to a point where we can demonstrate that this strategy can decrease malaria burden in an area. And once we have done that, then we have a new tool which targets the malaria transmission cycle at a different point from other currently used measures (IRS, bednets). This would then be something which I hope could be integrated in other vector-control strategies and that is when we would then look at it from a policy perspective. I think at this point, it’s important that policy makers understand what we are doing and why we are doing this research so that they can also understand the result that will be coming down the pipeline. My hope is that this could be quickly adopted to really help manage the disease.

Despite progress achieved in the fight against malaria, it continues to cause thousands of deaths in Africa, particularly among children aged 0-5 years. What do you think should be done to completely eradicate this killer disease from the continent?

I think we need more investment. From an economical standpoint, we need to invest more in measures that we currently have, find more efficient ways of deployment, and build on what has been done in the last fifteen years. The other thing we need is to invest in new tools, because the tools we have today will not be sufficient to eradicate the disease. They can control the disease, but to get to that ultimate goal of eradicating malaria, I think we will still need new tools that may came out in the next five to ten years. 

 A major pandemic, COVID-19, has emerged in the global health world and in Africa and is having a major impact on malaria research. The World Health Organization (WHO) recently warned that any interruptions in malaria control efforts could increase malaria incidences and impact. Can you tell us how this health crisis poses a serious challenge to your research?

The world is being interrupted by this pandemic and presenting many challenges to our research. This pandemic is also posing a big challenge to ongoing malaria control effort, and if this is not checked, it could result to many more cases of other diseases. I think that is very concerning, and we need to react quickly but also to learn. There will be more unexpected phenomena like this, so we need our research and health systems need to be more robust. It is unlikely to be the last pandemic, there will be others and we need to make preparations and continue to do work and to control other diseases throughout these difficult times.

(Interview conducted by Junior Matock, Communications Officer, PAMCA)