Species of Schistosoma worms infect hundreds of millions of people every year in tropical and subtropical areas of the world, and they are especially prevalent in sub-Saharan Africa¹.
The disease has a vast human impact, causing an estimated 140,000 cases and 11,500 deaths globally in 2019 alone². Children are particularly at risk of infection, and schistosomiasis can cause anaemia, stunted growth or development and a reduced ability to learn³. Chronic schistosomiasis in adults can cause liver and kidney damage, and debilitating long-term illness that means someone may not be able to work.
Sanger Institute scientists have led research over the last decade to decode and understand the genome and life cycle of this devastating parasite. They sequenced the genome in 2009 and since then have studied its evolution, life cycle, drug resistance and cellular biology. Their aim has been to better understand the parasite, and produce resources that can be used to develop new control strategies or treatments.
Schistosomiasis is listed by the World Health Organisation (WHO) as one of the most Neglected Tropical Diseases. The disease is widely considered to be second only to malaria as a global health problem and is an incalculable drain on the economic development of endemic countries.
Tess spoke to us about her work, and why she thinks it’s such an important disease to tackle.
Tell us about your work
I mostly do single cell analysis of Schistosoma mansoni. The worm has all these different body plans as it changes itself throughout its lifecycle. It’s also good at hiding from the immune system. I’m looking at what kind of cells are present at different stages of the life cycle, what genes are active, their quantities, and I try and do some functional analysis too. We're trying to build atlases of the animal on a single cell basis
Single cell RNA-seq is relatively new, and so it’s amazing to be able to use it to study the animal in so much detail.
How is genomics adding value to tackling schistosomiasis?
It's such a big, difficult problem to tackle, but I think genomics is part of the puzzle. Having a multi-pronged approach is really important. There are of course things like improvement of sanitation, and potentially snail control, which can target the disease4. But I think understanding the biology of the animal itself is really important. How can we develop treatments or vaccines without understanding what it is we're trying to target?
For example, if a drug treatment was trying to target a particular cell type, we need to know that the cell type is present when the worm is in its human host, and that it lasts long enough to be a good target.
How can you study the different life stages of schistosomiasis?
Dr Matt Berriman led parasite genomics work at the Sanger Institute. He has recently moved to the University of Glasgow, and he's setting up the full life cycle of the worm there – that involves keeping the parasite in tanks and snails under specific conditions that mimic their natural environment. We used to have this here at the Sanger Institute, which is how we have been able to generate much of these data. Dr Gabriel Rinaldi, who also used to be here at Sanger has moved to Aberystwyth University where they also have the life cycle. Matt is also working with partners in countries where the parasite is endemic, and trying to understand strains in the field and hybrids and things like that.
What are the challenges with genomics and neglected diseases?
There are multiple. I’d say funding is obviously one of them. It’s not flashy or exciting, and it’s not as well-funded as other diseases. As a result, things like genomes then require more resources to get good quality data, because if you're trying to say, 'Okay, what cell types do I have? What genes are being expressed?' You might be mapping to a genome that's not complete. Having more funding for annotating genomes will be a real help, because the gene models aren’t all there.
I think interest as well – it’s not something that is on our radar here in the UK. I think awareness is very important. In countries where a lot of the research funding comes from, many people won’t know what it’s like to live in a schistosomiasis endemic area.
In terms of tools, there are lots of amazing analysis tools, but much of the resources have been put into sequencing and analysing human genomes, or mice. So some of the more specific things we are trying to do won’t work and we have to try and customise those things ourselves – it isn’t something that is readily available.
Schistosoma mansoni lifecycle
Schistosoma species, also known as blood flukes, have several stages in their life cycle. Eggs survive in fresh water, where they hatch into tiny larvae, which then live in snails. They reproduce asexually in the snails, and emerge back into the water in the next larval stage. These larvae are released into ponds, rivers or lakes, where they burrow into the skin of anyone paddling, swimming, fishing, washing their clothes, or otherwise nearby in the water. Once in the human body, the worms move through the blood to the liver and bowel. After a few weeks they mature, reproduce sexually and the females lay eggs. If the eggs pass out of the body into water, they release the tiny larvae that can grow inside freshwater snails, starting the life-cycle once again.
Without treatment, the worms can colonise human blood vessels for years, laying hundreds to thousands of eggs every day. Symptoms of schistosomiasis are caused by the body’s reaction to the worms' eggs, which can become trapped in body tissues, causing progressive damage to organs.
Currently, only one drug is available to treat the disease, but there can be issues with supply, and there is evidence the parasite is becoming resistant.
Find out more about schistosomiasis at the WHO or on YourGenome
Do you think greater public awareness of genomics, as a results of COVID-19, has had any effects?
Not that I’ve seen on schistosomiasis, but there are intersections of parasites and viruses. For example, female genital schistosomiasis may increase risk of HIV5.
I recently heard about research showing that the efficacy of vaccines is less in countries where helminth infections are prevalent. A worm infection dampens the body’s immune response – and this may be a good thing in some ways – for example autoimmune disease are less prevalent. But it is a double-edged sword, as it also may mean that vaccines don’t work as well.
What drew you to this project?
I think it was this sense that we can make a resource that is going to be useful, and make it available to anyone who needs it. The Sanger Institute has the funding and resources to do single cell sequencing, so we can make the data. And once it’s there, a single cell atlas including data from all the different time points and stages in the animal's life. Then, someone can come along in a year, maybe two years’ time and reanalyse the data with some new tool and get more information out of it, whether they’re working on understanding a particular gene, or a vaccine. That’s a big benefit of working here.
Working in the area, well, in my tiny little way I feel like I'm working for something that matters. Schistosomiasis is a both a driver and a result of poverty6, so working towards reducing this burden feels important.
Plus it since being in it, I’ve found parasite genomics to be a really nice research community.
Can you describe the Sanger Institute in up to 10 words?
It's a fantastic place to work. I feel very lucky.
If you could time travel anywhere, where would you go?
Oh my gosh, I wasn’t expecting this question! I’d like to see dinos. But really, its not practical to time travel backwards is it – because you’re going to affect things too much…..
Do you have a science hero?
I think Matt [Berriman] is fantastic. Coming into his group was such a positive experience. He does excellent work, but really supports others in their work too.
More generally, all of our work is only possible because of previous scientists. None of this would be possible without lots of other scientists before me. That’s pretty amazing.
Find out more
[1] https://www.who.int/news-room/fact-sheets/detail/schistosomiasis and “Schistosomiasis. DPDx – Laboratory Identification of Parasites of Public Health Concern. Centre for Disease Control and Prevention (CDC). Available https://www.cdc.gov/dpdx/schistosomiasis/index.html [Accessed November 2021]”
[2] Global Burden of Disease Study 2019 (GBD 2019). Results [Global Burden of Disease Collaborative Network] Institute for Health Metrics and Evaluation (IHME).
[3] https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009660 and https://www.ed.ac.uk/edinburgh-infectious-diseases/news/news/urgent-action-needed-to-tackle-schistosomiasis and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766129/
[4] https://schistosomiasiscontrolinitiative.org/eliminating-ntds/wash and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575311/
[5] https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005968
[6] https://idpjournal.biomedcentral.com/articles/10.1186/s40249-021-00919-z
