25 Jun 2019

Learning with the Experts - Liverpool Neuro ID Fellowship 2019


Learning with the Experts - Liverpool Neuro ID Fellowship 2019
Sofia Valdoleiros is a Portuguese medical resident in Infectious Diseases and from January until March 2019, caried out a clinical and academical internship in Neurology, with a primary focus in Neurological Infection, with the Liverpool Brain Infections Group (LBIG), under Professor Solomon, also with Dr. Benedict Michael and Dr. Christine Burness.
The academical module took place at the Institute of Infection and Global Health (IGH), where I was so well received and involved in the activities by everyone. Along with the academical work I developed, I got to participate in the Liverpool Brain Infections Group meetings, which included the discussion of major research projects, such as Enceph-UK, and UK-ChiMES, major programmes on adult and paediatric encephalitis. I even heard from Professor Solomon himself on “How to write a winning grant”! I was given the opportunity to attend international meetings of ground-breaking multicentre projects, such as Brain Infections Global and ZikaPLAN, and what an honour it was to be able to take part in these meetings and actually meet world leaders in Neurological Infectious Diseases research!
Exciting activities seem to be always happening, such as these meetings or Neuroscience Day or open discussions about neuroscience research. I was sad my internship ended before some other events took place, such as the Big Infection Day or the Neurological Infectious Diseases Course, but these sure were “replaced” by other activities, such as the e-learning Neuro ID Course or teaching sessions with Dr. Benedict Michael, who invested a lot of time in discussing fascinating Neuro ID cases with me. 
The clinical module took place at the Walton Centre and the Royal Liverpool University Hospital. As a renowned neurosciences medical centre, at the Walton Centre it is possible to attend experts’ subspecialty Neurology Clinics, observe inpatients with neuro-infection and attend stimulating meetings, from Grand Rounds to Lectures from Neurology experts and teaching sessions, and MDT meetings such as Spinal Infection, Infection Control or Neuroradiology. At the Royal, I accompanied Dr. Burness, a Neurology consultant with a special interest in Neurological Infection, in observing referrals from the ID wards, and attended the Neuro ID Clinic, an innovative approach bringing together a Neurology consultant (specialized in Neurological Infection – Professor Solomon, Dr. Michael and Dr. Burness) and an ID consultant (Dr. Defres) in a multidisciplinary view of the patient. I was also given the opportunity to attend the Encephalitis MDT monthly meeting at the National Hospital for Neurology and Neurosurgery in London. I am so grateful for the opportunity to learn from these Neuro ID experts’ experience and for their valuable insights. It will certainly change my approach of the neuro infected patient in Portugal.
Overall, the major point I highlight is the amount of opportunities (to learn, to participate in) I was given in only 3 months. With so much and so interesting and versatile things to do, these 3 months just completely flew by. Thank you so much to everyone!

25 Apr 2019

Measles: should vaccinations be compulsory?


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Measles virus. Design_Cells/Shutterstock
Tom Solomon, University of Liverpool

Following a measles outbreak in Rockland County in New York State, authorities there have declared a state of emergency, with unvaccinated children barred from public spaces, raising important questions about the responsibilities of the state and of individuals when it comes to public health.
Measles virus is spread by people coughing and spluttering on each other. The vaccine, which is highly effective, has been given with mumps and rubella vaccines since the 1970s as part of the MMR injection. The global incidence of measles fell markedly once the vaccine became widely available. But measles control was set back considerably by the work of Andrew Wakefield, which attempted to link the MMR vaccine to autism.

There is no such link, and Wakefield was later struck off by the General Medical Council for his fraudulent work. But damage was done and has proved hard to reverse.
In 2017, the global number of measles cases spiked alarmingly because of gaps in vaccination coverage in some areas, and there were more than 80,000 cases in Europe in 2018.

Anti-vaxxer threat

The World Health Organisation has declared the anti-vaccine movement one of the top ten global health threats for 2019, and the UK government is considering new legislation forcing social media companies to remove content with false information about vaccines. The recent move by the US authorities barring unvaccinated children from public spaces is a different legal approach. They admit it will be hard to police, but say the new law is an important sign that they are taking the outbreak seriously.

Most children suffering from measles simply feel miserable, with fever, swollen glands, running eyes and nose and an itchy rash. The unlucky ones develop breathing difficulty or brain swelling (encephalitis), and one to two per thousand will die from the disease. This was the fate of Roald Dahl’s seven-year-old daughter, Olivia, who died of measles encephalitis in the 1960s before a vaccine existed.

Roald Dahl’s daughter died of measles. Carl Van Vechten/Wikimedia Commons

When measles vaccine became available, Dahl was horrified that some parents did not inoculate their children, campaigning in the 1980s and appealing to them directly through an open letter. He recognised parents were worried about the very rare risk of side effects from the jab (about one in a million), but explained that children were more likely to choke to death on a bar of chocolate than from the measles vaccine.

Dahl railed against the British authorities for not doing more to get children vaccinated and delighted in the American approach at the time: vaccination was not obligatory, but by law you had to send your child to school and they would not be allowed in unless they had been vaccinated. Indeed, one of the other new measures introduced by the New York authorities this week is to once again ban unvaccinated children from schools.

Precedents

With measles rising across America and Europe, should governments go further and make vaccination compulsory? Most would argue that this is a terrible infringement of human rights, but there are precedents. For example, proof of vaccination against yellow fever virus is required for many travellers arriving from countries in Africa and Latin America because of fears of the spread of this terrifying disease. No-one seems to object to that.

Also, on the rare occasions, when parents refuse life-saving medicine for a sick child, perhaps for religious reasons, then the courts overrule these objections through child protection laws. But what about a law mandating that vaccines should be given to protect a child?

Vaccines are seen differently because the child is not actually ill and there are occasional serious side effects. Interestingly, in America, states have the authority to require children to be vaccinated, but they tend not to enforce these laws where there are religious or “philosophical” objections.
There are curious parallels with the introduction of compulsory seat belts in cars in much of the world. In rare circumstances, a seat belt might actually cause harm by rupturing the spleen or damaging the spine. But the benefits massively outweigh the risks and there are not many campaigners who refuse to buckle up.

I have some sympathy for those anxious about vaccinations. They are bombarded daily by contradictory arguments. Unfortunately, some evidence suggests that the more the authorities try to convince people of the benefits of vaccination, the more suspicious they may become.

I remember taking one of my daughters for the MMR injection aged 12 months. As I held her tight, and the needle approached, I couldn’t help but run through the numbers in my head again, needing to convince myself that I was doing the right thing. And there is something unnatural about inflicting pain on your child through the means of a sharp jab, even if you know it is for their benefit. But if there were any lingering doubts, I just had to think of the many patients with vaccine-preventable diseases who I have looked after as part of my overseas research programme.

Working in Vietnam in the 1990s, I cared not only for measles patients but also for children with diphtheria, tetanus and polio – diseases largely confined to the history books in Western medicine. I remember showing around the hospital an English couple newly arrived in Saigon with their young family. “We don’t believe in vaccination for our kids,” they told me. “We believe in a holistic approach. It is important to let them develop their own natural immunity.” By the end of the morning, terrified by what they had seen, they had booked their children into the local clinic for their innoculations.

In Asia, where we have been rolling out programmes to vaccinate against the mosquito-borne Japanese encephalitis virus, a lethal cause of brain swelling, families queue patiently for hours in the tropical sun to get their children inoculated. For them the attitudes of the Western anti-vaccinators are perplexing. It is only in the West, where we rarely see these diseases, that parents have the luxury of whimsical pontification on the extremely small risks of vaccination; faced with the horrors of the diseases they prevent, most people would soon change their minds.


Tom Solomon is the author of:

Roald Dahl’s Marvellous Medicine.The Conversation

Liverpool University Press provides funding as a content partner of The Conversation UK

Tom Solomon, Director of the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections, and Professor of Neurology, Institute of Infection and Global Health, University of Liverpool
This article is republished from The Conversation under a Creative Commons license. Read the original article.

11 Feb 2019

International Day of Women and Girls in Science

11th February is the International Day of Women and Girls in Science. At present, less than 30 per cent of researchers worldwide are women. UNESCO and UN-Women decided to establish an annual International Day to recognize the critical role women and girls play in science and technology. In this blog we hear from Dr Ophélie Lebrasseur, a zooarchaeologist specialising in ancient and modern DNA, on what inspired her to pursue a career in science.

I’ve always wanted to be an archaeologist. Once, my grandfather took me to a dinosaur exhibit tucked away under a blue circus tent. In my 6-years-old mind, the line between archaeology and palaeontology was blurry. But I came home to my parents knowing I wanted to discover the past. There was only one main problem to deal with: What if they dig everything up before I am old enough to be an archaeologist, and I am left with nothing to find? It turns out I needn’t have worried. There will always be artefacts and bone remains waiting to be unearthed. The question is then ‘how do you use these to shed light on our past?’ And more importantly in our modern world ‘can these findings contribute to building a healthier and more secure future?’

The first step of my journey started at the University of Durham, where I studied for a Bachelor of Science (BSc) in Archaeology. My undergraduate dissertation gave me a good grasp on animal bones and how I could read them to reconstruct past human-animal relationships and economy. In other words: identifying the bone, the species, the age-at-death, the butchery marks, the palaeopathology, the list goes on. The question of health was one I was already unknowingly exploring. The site under study was a French site in Normandy which had not only been a major target during the Hundred Years War, it was also seriously hit by the Black Death. The plummeting of the population by 95% and the flooding of surrounding pastures to defend the town against attacks had caused a reduction in the natural height of domesticated animals, or so I hypothesized.

I then took my zooarchaeology skills a step further. I was, and still am, passionate about the application of scientific methods developed by biologists, chemists, physicists to ancient material and archaeological questions. And so I continued in Durham with an Master of Science (MSc) in Human Palaeoecology, learning about reconstructing the dynamics between past environments, humans and animals. What also drew me to this degree was the biomolecular component. At that point in my career, I knew I didn’t want to specialise in a particular time period or geographical region. It felt too ‘restrictive’ somehow, and I wanted to be free to explore every corner of the earth at whatever time period. My way to achieving this freedom was to become an expert in a scientific technique which stirred my curiosity and interest: ancient DNA. My dissertation took me to Dr (now Prof) Greger Larson’s lab, where I learned how to identify the origins of domesticated animals on the island of Mauritius through ancient mitochondrial DNA. Reconstructing human movement via proxies (specifically ancient animal genetics) had taken a hold of me.

It so happened that I was at the right place at the right time. Greger had just obtained a couple of grants, both of which included PhD positions. And so, with the path clear before me, I applied and was offered a Doctor of Philosophy (PhD) on the dispersal of the Lapita Cultural Complex in Oceania through modern dogs and chickens - the idea being that these animals were located on such remote islands they would most surely have retained their ancient genetic signatures. Except I couldn’t make head or tail of my results. That’s when Greger turned to me and said “I don’t think we’re asking the right question. Everyone so far has assumed you could retrace ancient dispersals and domestication using modern DNA, but it’s never been tested or proven”. And so began the last six months of my PhD, revealing that you couldn’t solely use modern DNA to directly look back into the past, because modern populations are very rarely direct representatives of past populations.

My first postdoc at the University of Oxford was a most fun project pinpointing the introduction and dispersal of chickens in this part of the world. I worked with numerous archaeologists bringing various lines of evidence to the question, including ancient genetics. But the most important outcome of this project was a follow-up side-study funded by the Global Challenge Research Fund (GCRF) looking at empowering women in Ethiopia through chicken production and cultural heritage. It was a very short project of six months, but it introduced me to the concept that archaeology could play a role in shaping our future, not only scientifically but also culturally.

I remained in Oxford until I was offered a postdoctoral position on the One Health Horn project by the University of Liverpool. Based in Addis Ababa, Ethiopia, I, along with Prof Keith Dobney back in Liverpool, are responsible for bringing the archaeological side to this One Health project. My current research aims to look at how past environments and climate affected the spread of pastoral communities and their animals in the Horn of Africa; how animals adapted to their environments genetically, and how current selection pressures affect these acquired traits. Quite novel is the integration of my archaeological results with other findings from team members of different backgrounds (epidemiology, veterinary, microbiology, disease surveillance to name but a few). I am eager to see how combining our disciplines can help in making better-informed policies.
The application of archaeogenetics to tackle global challenges is very much in its infancy. But it is burgeoning and slowly spreading. I look forward to being one of its pioneers, and seeing its growth as we collaboratively strive for a healthier future.

14 Nov 2018

Using Mini-Genomes to Study Deadly Diseases



One of the major problems faced by scientists when studying contagious diseases is the threat of scientists themselves contracting the studied disease. In some cases researchers work in specialised labs with high security and lots of personal protection equipment. However, this is not always practical option. I recently spoke to Rebekah Penrice-Randal, a 1st year PhD student in IGH, about her project on Ebola and how she is using mini-genomes to study them without the risk of infection.

First, what is Ebola? Ebola (also known as Ebola Virus Disease or Ebola Hemorrhagic Fever) is a viral disease that has been in the news in the past few years, especially 2014-16 mainly due to a major outbreak that occurred in west and central Africa. According to the World Health Organisation (WHO) there were around 28,000 cases and over 11,000 deaths and there is currently no licenced vaccine for this disease.

Patients who contract Ebola deteriorate very quickly. Within 2-21 days of becoming infected sufferers can start with symptoms including: fever; headache; muscle weakness and a sore throat. These often progress to vomiting and diarrhoea, stomach pain and unexplained bleeding (haemorrhages).
The disease is spread through direct contact: through broken skin; contaminated bodily fluids; contaminated needles. Ebola can also be contracted from infected animals such as bats, apes or monkeys. The virus often remains undetected by the immune system in certain bodily fluids e.g. semen, breast milk, ocular (eye) fluid and spinal column fluid even after someone has recovered.

So now we know what Ebola is, what are mini genomes and how do they help in the study of this disease?

Viruses have genes, some of which allow them to replicate or make more of themselves when they are within host cells. These genes have a start and stop regulatory sequence which tells the cell machinery that transcribes the genes where the gene starts and where it finishes(Transcription is the process by which the genes are converted into messenger RNA, an intermediated step which is then converted into proteins). A mini-genome is a shorter version of the Ebola genome. The regulatory sequences are kept but the viral genes in-between that make the virus ‘infective’ are removed and replaced with a reporter gene. A reporter gene is simply a gene which has easily identifiable and selectable markers, one such example is green fluorescent protein (GFP), naturally produced in jellyfish which, when expressed, fluoresces in green. The amount of fluorescence can then be easily measured.

A change in the environment can affect the regulatory sequences and in turn the amount of protein that is produced and measured. These mini genomes can be inserted into a bacterium like E. coli and when environmental conditions are changed the effects to the mini genome genes can be seen. This means you can study the transcription and replication of these genes safely and without the dangerous viral genes being produced.

Rebekah is also going to compare the transcriptomes i.e. the measure of all genes that are expressed at a particular time, both of the mini genome infected cells and the actual Ebola infected cells. This will allow her to see how representative the mini genomes are as a model. This can also show how the disease can differ depending where in the world a sample is collected and can show natural variation within the virus. Furthermore, when the environmental conditions are changed, such as by reducing the amount of oxygen, the evolution of the virus under those conditions can also be seen.

This research will contribute in the quest to understand and put an end to this deadly disease.

Eleanor Senior is a 3rd Year PhD student in IGH studying the bovine parasite Tritrichomonas foetus.

11 Oct 2018

From Snails to Sheep: The Flatworm Affecting Farms Across The UK




Farm animals are susceptible to a whole range of diseases and parasitic infections. From the commonly known and well publicised foot and mouth disease to the lesser publicly recognised bluetongue disease, farmers must deal with a wide array of viruses, bacteria and parasites that can affect their livestock. In this blog, I spoke to Bethan John, a 3rd Year PhD student in IGH about her PhD research into Liver Fluke.

Liver fluke (Fasciola hepatica) is a flatworm parasite of grazing animals such as cows and sheep. Though only the size of a 50p piece, this parasite causes weight loss and anaemia in infected animals and is estimated to cost the UK cattle industry £40.4 million per year. Therefore, it is both an animal welfare issue and an economic one. This parasite is also known to infect humans (zoonotic) when humans eat infected meat.

The liver fluke takes many forms during its life cycle. Infection occurs when the animals consume the parasite when it is in the form of a cyst attached to blades of grass. Once the cysts are in the small intestine they mature into juvenile parasites which burrow from the small intestine across the peritoneum and into the liver where they mature into adults. These adults are hermaphrodites having both male and female characteristics, and are able to reproduce both sexually (2 parents) and asexually (1 parent) resulting in the production of eggs.

These eggs are passed from the mammal via its faeces onto damp pastures where they hatch. They are then able to infect the mud snail (usually Galba truncatula) which is the intermediary host. Within the snail the parasite  is cloned into thousands of genetically identical cysts, a process known as clonal amplification. It is these genetically identical cysts  that are shed and become attached to blades of grass. This process can only occur in boggy areas where the snail can be found. The cycle is then completed when the parasite cysts are ingested by grazing animals and mature flukes develop in the liver and go on to lay eggs.

However, there has been evidence via word-of-mouth that even animals that have been housed inside and fed on silage, far away from boggy areas and snails, have still become  infected with fluke. Silage, which is grass that has been dried and fermented in airtight conditions, has also been known to transmit some bacterial diseases and other parasites. It is, therefore, thought that the fluke cysts could be transmitted from the silage to the housed animals. Moreover, it may also be the case that the eggs can survive in slurry, animal waste mixed with water and runoff, which is commonly used as a fertiliser on farms.

As part of her PhD Bethan is looking into whether the various fluke life cycle stages  can survive  under certain environmental conditions and within silage  Fluke eggs are a lot more sensitive to the environment than the cysts, they need moisture and a temperature over 10°C to hatch, whereas cysts can survive in much cooler environments; over 50% of cysts on grass can overwinter and still be infectious to grazing animals.

There is also a big issue with the use of  drugs to control fluke infections. The usual drug used, triclabendazole, is becoming less effective. If it can be shown that fluke can be passed to livestock via silage then farmers can change and improve their farming practises to reduce the incidence of fluke without the need for drugs.

Eleanor Senior is a 3rd Year PhD student in IGH studying the bovine parasite Tritrichomonas foetus.

                                          Bethan hunting for snails on a UK farm.


11 Sep 2018

The cow STI costing America over $200 million



Eleanor Senior is a 3rd Year PhD student at the Institute of Infection and Global Health. Here she shares her research investigating vaccine candidates for bovine sexually transmitted infection.

Many types of animal parasite are very well known for example, most people have heard of things like fleas, tapeworms and ticks. However,  there are many thousands of parasites that exist that you may never have heard of, but are no less important. Once such parasite is Tritrichomonas foetus.
This is a microscopic parasite that is sexually transmitted between cows and bulls causing a disease called Bovine Trichomoniasis, which is related to the human STI Trichomoniasis, caused by Trichomonas vaginalis.

T. foetus is found in many countries across the world including the USA, Brazil, France, Germany and Australia. Fortunately, this parasite does not infect cattle in the UK because of this country's strict border controls and the use of artificial insemination (AI); a procedure that allows for screening of sperm for infections prior to insemination.

So what is so bad about Bovine Trichomoniasis anyway? This parasite often doesn’t cause any symptoms in bulls in the same way that many STIs are symptomless in men. Consequently, it is difficult to detect in bulls unless there is constant sperm testing. Likewise, it is also difficult to spot in the cows.  Often it causes early stage spontaneous miscarriage which can be so early that the farmer isn't aware that the cow is pregnant in the first place. It can also cause short or long-term infertility. The first indication for the farmer that the herd is infected is that there is a decrease in the number of cows becoming pregnant or carrying to full term. Again, the best way to find out whether the parasite is present in the stock is to test all the cows. This can be pretty tricky and time consuming, particularly when there could be thousands of cows on a farm or ranch which will need to be tested at regular intervals.

The lowered calving rates and lower levels of milk production as a consequence of this parasite infection has significant economic consequences for the farmer.  Furthermore, the need for the infected cattle to be destroyed as a means for protecting the rest of the herd takes an additional financial toll.  It has been estimated that in Texas alone the losses due to this parasite can reach $195 million. Taking into account the losses from other states in America the amount is a considerably higher. So this parasite is clearly a problem both financially for the farmers and as a welfare issue for the cattle.

Although there are currently vaccines available to combat Tritrichomonas foetus, there are none as yet that prevent reinfection. Consequently available vaccines must be given at each breeding season. This again isn’t very practical when there can be thousands of cows to immunise every month or two.
My PhD is aiming to find proteins from the parasite itself that can be used as vaccine candidates. We are searching for a small group of proteins that we can further test for key vaccine qualities such as:
  • promoting an immune response
  • being found in all variants of the parasite across the globe not just in one region. This is so that one vaccine can be used against all variants rather than multiple vaccines each of which deals only with one or two specific variants
To do this I am using a reverse vaccinology approach. So what is this? Classical vaccinology is what has been used to make lots of the common vaccines available today such as the flu vaccine. In these vaccines, weakened or killed viruses or bacteria are used to promote an immune response. However, the exact protein or proteins that causes this response are often not known. Reverse vaccinology involves using computers to predict proteins that are likely to give an immune response which are then narrowed down using a variety of laboratory techniques to give a small number of candidates. Some, or all, of these candidates are then used as the starting point to produce the actual vaccine.

By the end of my PhD I hope to have come up with a list of potential proteins that can then be used to start designing a vaccine in the fight against this costly and distressing parasite.



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