By Lauren Carruthers,
Lauren graduated with a BSc Honours in Parasitology from the University of Glasgow before undertaking two research technician positions studying drug resistance and lipid distribution in trypanosomes. She is currently a PhD student researching interactions between schistosomes, the microbiome and anti-helminthic drugs in the context of the Schisto_Persist project with the Lamberton Lab at the University of Glasgow. In her free time she enjoys participating in public engagement activities and runs the lab Twitter page which you can follow @LambertonLab.
The Lamberton Lab is a team of researchers from the University of Glasgow studying neglected tropical diseases. This story focuses on one neglected tropical disease called schistosomiasis and some of the research the team are carrying out in Uganda to understand how to improve drug treatment success and reduce disease transmission.
Chapter 1: Schistosomiasis.
In Lake Victoria, there lurks a monster but unlike Nessie, this beast is real, deadly and so small it is invisible to the human eye. This beast is a neglected tropical disease called schistosomiasis, otherwise known as bilharzia. Infection occurs when microscopic schistosome worm larvae invade unsuspecting victims venturing into the infected water. They penetrate human skin and then, over the course of about a month, migrate and mature in our bodies, finally ending up in the veins of our intestines or bladders depending on the species. Male and female worms then pair up in these veins and mate producing hundreds of thousands of eggs. The adult worms may produce gruesome connotations so you might find it surprising to learn that it is actually the eggs that cause the most damage in this infection. Eggs are excreted in the stool or urine but in chronic disease, eggs are caught in the bloodstream and travel all over the body. Along the way, they get lodged in vital organs causing damage that may be irreversible and can lead to death. Whilst there is a drug available, called praziquantel, against this disease it only kills the adult worms, the maturing larvae survive, later progressing into adulthood. The currently trapped egg burden also remains unaffected by this drug treatment. Whilst annual rounds of mass praziquantel administration to communities most at risk of the infection reduces disease burden and limits damage, this infection is ideally one of prevention rather than cure. So how do we cure, prevent or even eradicate a disease? This is where teams of researchers, such as the Lamberton Lab based at the University of Glasgow, come in.
Chapter 2: Taking the Bug out of Bugoto
The Lamberton Lab, alongside technicians from the Ugandan Ministry of Health, is studying schistosomiasis in the community of Bugoto on the shore of Lake Victoria in Uganda. Schistosomiasis has been prevalent here for many years and the number of people getting the infection appears to have increased there despite over ten years of mass drug administration in the community. Lamberton Lab thus aims to try and work out why this increase occurred by studying multiple different aspects of schistosome infection. It is hoped that this research will help scientists to understand schistosomiasis better, so that one day we can take this bug out of Bugoto!
Chapter 3: The Tale of the Snail
You’ve already learnt that the schistosome parasites burrow through the skin to invade humans and that eggs produced by adult worms are excreted in urine or stool. But how does the parasite transform from an egg to an invasive skin burrower? Well, one does not simply hatch into a human burrower. It is a bit more complicated and involves another host in the form of snails. The schistosome parasite must first hatch, infect a snail and be released from the snail before becoming infectious to humans. Unfortunately, whilst inside the snail schistosomes replicate asexually; basically making thousands of clones of themselves and turning the snails into parasite producing factories. Thus Lamberton lab aims to find snails from around Bugoto and collect the schistosome parasites released. The genetic codes, imagine lines of text in a book, of each of these collected parasites can then be read. We can then look and see which text codes help the parasites survive and track down where these parasites originated from. It is a little bit like using postcodes to work out where the schistosomes have lived and are moving to.
Chapter 4: The Faecal Matters
Poo containing schistosome eggs can also be collected for postcode analysis. Though this is a bit smellier than snails, it is safer because the schistosome hatchlings are not infective to humans at this stage. So, how do you hatch schistosomes? Fresh poo is collected, watered down, sieved through the wire mesh and then sieved again through special mesh material with specific hole sizes. Yeah, it is a bit messy at first but once you’ve poo-fected it you get on a roll. Eventually, you collect only material within egg size range and pour it into a pot. This watery material is then left in the sunshine and the eggs hatch into tiny schistosome larvae, called miracidia, that zoom around their container in the hunt for snails. One by one these tiny critters are visualised under a microscope, picked out and stored on special preservation cards so that their gene codes can be analysed. Through this work, Lamberton Lab hopes to identify who is infecting whom. These individuals can then be hopefully targeted for treatment and education to help reduce transmission of schistosomiasis. The question: ‘which came first, the schistosome adult worm or the egg?’ will probably be left unanswered.
If poo contains eggs then poo-haps you might have already guessed that poo can be used to diagnosis schistosomiasis. This technique is called the Kato-Katz method and involves a set amount of sieved poo being squished, with a special dye for visualisation, on to a glass slide. The number of eggs on this slide are then counted using a microscope. The more eggs there are the more adult worms an individual is thought to harbour. This technique is also useful as it hits more than two birds with one stone, though in this case it is parasitic worms laying the eggs, as other parasitic eggs from different species can also be detected at the same time.
Gut bacteria have also been shown to alter drug treatment success. Associations between other worm species and gut bacteria have also been documented. The interactions between schistosome worms, the gut bacteria and anti-worm drugs (praziquantel and albendazole) is, therefore, yet another focus of Lamberton Lab’s research (meaning more poo collection!). Since, as you can probably imagine, storing poo in a hot Ugandan setting poses challenges, a study looking at the best way to preserve poo for gut bacteria analysis has been undertaken. Poo has been stored in different liquids and frozen at different time points after delivery. The team also want to see if there are any associations between the composition of the gut bacteria and treatment success and if bacteria might be associated with different levels of schistosome infection intensity.
Faecal matter may also contaminate the environment with eggs, thus the team are also exploring where environmental contamination is occurring and if this contamination is contributing to infection transmission. Soil samples are being collected to see how far schistosome eggs can penetrate the soil and how far they can travel. Methods to reduce egg transmission into Lake Victoria will then be looked into.
Chapter 5: Diagnosis = Die or Notice!
Kato-Katz is not the most sensitive of techniques to diagnose schistosomiasis because it only detects schistosome worm infections that are producing eggs. Another aspect of Lamberton Lab’s research therefore aims to compare different methods of detecting schistosomiasis. Will all tests give the same results? Which one is the best and most practical? This project is incorporating a method that detects regurgitated adult worm proteins found in the urine (Yi-pee!) and the detection of specific schistosome text codes in blood and poo samples (a bit like finding a book mark in a novel to find the right page).
Chapter 6: A Bloody Nightmare
As mentioned in chapter 1, praziquantel is the drug used to treat schistosomiasis. To understand this drug better, studies into how the human body affects the drug and how the drug affects the human body are also being undertaken by the Lamberton Lab. This research involved lots of hyperactive children bouncing on beds during a sleepover party (at the health centre), held so finger prick blood samples could be collected at different time points after praziquantel treatment. These samples will help inform what happens to the drug after administration, and why the drug appears to work well in some individuals but not others. Immune response markers will also be analysed from these samples to look at how the human body tries to fight schistosomiasis infection.
Chapter 7: A Day in the Life
Aspects of daily life that may predispose an individual to schistosomiasis will also be characterised as part of a project incorporating social science. Members of Lamberton Lab have been following children over the course of a day and recording what they do. Do they enter schistosome infested Lake Victoria? How often do they do this? When do they do this? How long are they in the water for? Why are they entering the water? Social science is key to understanding the behaviour and beliefs of a community. To prevent people entering infective water we need to think about why they do it in the first place so as to come up with interventions that will be of use, will be popular with the community, and actually solve the problems. Through understanding the people, we’ll better understand the disease.
Through the projects that the Lamberton Lab is working on we hope to contribute to the control, and hopefully future eradication, of schistosomiasis. However, we still have a lot to learn and a long way to go before the book can be closed on schistosomiasis.