̽��ֱ�� of Cambridge - ebola

Track and trace in Sierra Leone

cjb250 — Thu, 30 Sep 2021 13:17:39 +0000

Professor Ian Goodfellow played a crucial role in helping to bring the Ebola epidemic in Sierra Leone to a close in 2014. His team's work helped inform technology used today in the majority of SARS-CoV-2 sequencing, which is keeping us safe in the current pandemic.

Half of Ebola outbreaks go undetected, study finds

ta385 — Fri, 14 Jun 2019 09:00:00 +0000

̽��ֱ��research, led by Emma Glennon from Cambridge’s Department of Veterinary Medicine, is the first to estimate the number of undetected Ebola outbreaks. Although these tend to involve clusters of fewer than five people, they could represent well over one hundred patient cases in total.

̽��ֱ��study, published today in PLOS Neglected Tropical Diseases, found that the chance of detecting an isolated case of Ebola was less than 10%.

Glennon, a Gates Cambridge Scholar, says: “Most times that Ebola has jumped from wildlife to people, this spillover event hasn’t been detected. Often these initial cases don’t infect anyone else but being able to find and control them locally is crucial because you never know which of these events will grow into full outbreaks.”

"We rarely find Ebola outbreaks while they are still easy to manage. ̽��ֱ��unfolding epidemic in the DRC demonstrates how difficult it is to stop the disease once it has got out of control, even with international intervention. But if an outbreak is detected early enough, we can prevent it spreading with targeted, low-tech interventions, such as isolating infected people and their contacts.”

̽��ֱ��scientists used three independent datasets from the 2013–16 Ebola epidemic in West Africa to simulate thousands of outbreaks. From these simulations, they worked out how often they would expect a spillover event to fizzle out early versus how often they would expect to see it progress into a true outbreak. This allowed the team to draw comparisons with reported outbreak sizes and estimate detection rates of clusters of different sizes.

Glennon says: “Most doctors and public health workers have never seen a single Ebola case and severe fever can easily be misdiagnosed as the symptom of malaria, typhoid or yellow fever. To limit outbreaks at their source, we need to invest much more to increase local capacity to diagnose and contain Ebola and these more common fevers.

"We must make sure every local clinic has basic public health and infection control resources. International outbreak responses are important but they are often slow, complicated and expensive.”

Reference:

Glennon, E.E., Jephcott, F.L., Restif, O., Wood, J.L.N. ‘Estimating undetected Ebola spillovers’. PLOS Neglected Tropical Diseases (2019). DOI: 10.1371/journal.pntd.0007428

Half of Ebola outbreaks have gone undetected since the virus was discovered in 1976, scientists at the ̽��ֱ�� of Cambridge estimate. ̽��ֱ��new findings come amid rising concern about Ebola in the Democratic Republic of Congo, and highlight the need for improved detection and rapid response to avoid future epidemics.

We rarely find Ebola outbreaks while they are still easy to manage

Emma Glennon

UN Photo/Martine Perret

Burial team in Guinea carry a victim of Ebola, 2015.

Funding

Gates-Cambridge Trust (Bill & Melinda Gates Foundation [OPP1144]), the ALBORADA Trust, the Medical Research Council (MR/P025226/1).

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Ebola and Lassa fever targeted by new vaccine trial and improved surveillance

cjb250 — Tue, 25 Sep 2018 09:08:41 +0000

Researchers from the ̽��ֱ�� of Cambridge will shortly begin clinical trials of a new vaccine that builds on almost two decades of research to protect against diseases caused by RNA viruses. At the same time, they will begin studying the natural animal reservoirs of the viruses in an attempt to try and predict which strains are likely to cause future outbreaks, information that will be essential for creating effective vaccines.

Ebola, Lassa and Marburg viruses cause haemorrhagic fever, leading to severe disease, often with high mortality rates. Outbreaks can cause devastating local epidemics in the human population and to wildlife, including non-human primates. ̽��ֱ��recent Ebola epidemic in West Africa (2013–2016) killed over 11,000 people and devastated the infrastructure and economies of Liberia, Sierra Leone and Guinea.

A new approach to vaccine development

Professor Jonathan Heeney and colleagues at the Laboratory of Viral Zoonotics, ̽��ֱ�� of Cambridge, have developed and successfully tested a trivalent vaccine in guinea pigs that protects against Ebola, Lassa and Marburg viruses. As a result, Professor Heeney has been awarded a further £2 million by Innovate UK and the Department of Health and Social Care to take the vaccine to clinical trials in humans.

̽��ֱ��research takes a new approach pioneered by Professor Heeney and builds on Cambridge’s strengths in genomics, monoclonal antibody research and computational biology. It has led to the formation of DIOSynVax, a spin-out company of Cambridge Enterprise.

A virus’s genetic code is written into its ribonucleic acid (RNA), just as ours is written into our DNA, which leads to the generation of proteins. When we are infected by a virus, our immune system responds to these proteins, known as ‘antigens’, producing antibodies that can identify and try to eliminate the invading pathogen.

̽��ֱ��approach developed by Professor Heeney involves understanding how the immune system correctly identifies the virus from its proteins, and using this information to create ‘viruses’ that can generate an immune response. Using monoclonal antibodies – copies of antibodies taken from survivors of the target diseases – they can then test whether the body can effectively eliminate these fake viruses, leading to protection.

“We’ve taken fundamental science that stretches back almost two decades and developed a new approach to vaccine development,” says Professor Heeney. “This has the potential to dramatically reduce the time needed to produce new vaccines and change the way in which the industry makes them.”

With the new funding, the team hopes to scale up production while ensuring that the quality of the vaccine is maintained. They will then carry out toxicity tests in animals and human blood samples to test for potential adverse effects; if successful, they will then trial the vaccine in healthy human volunteers.

̽��ֱ��funding is part of a £5m commitment from the Department of Health and Social Care to fund five projects to develop new vaccines with a ‘One Health’ focus, considering how the environment, the health of animals and the health of humans interact. This sits within the government’s £120m UK aid commitment to develop vaccines to help tackle diseases with epidemic potential.

Predicting the next outbreak

In recent Ebola outbreaks, the approach used successfully by the World Health Organization is known as ‘ring vaccination’, focused on vaccinating and monitoring a ring of people around each infected individual. However, this approach can only be used in response to an outbreak. In order for a vaccine to be used proactively – to prevent an outbreak in the first place – it is necessary to predict which strain or strains of a virus are most likely to cause future epidemics.

“A disproportionally high number of emerging and re-emerging diseases – from Ebola and Lassa through to rabies and influenza – are caused by RNA viruses carried naturally by animals,” says Professor Heeney. “We know very little about the viral diversity within these reservoir species and what enables them to spread to humans – and hence where the likely future threats lie.”

Viral genomes are notoriously variable due to the high mutation rates that occur during replication. These accumulate over time and result in evolution of the viruses as they circulate in their natural animal reservoir populations. If some viral variants arise and are able to adapt to use human cell receptors and are then able to escape immune defences, they may become highly infectious and cause large disease outbreaks.

“Vaccines are only as good as the antigen immune targets of the virus that they are designed for,” adds Professor Heeney. “If the antigen changes, the vaccine will no longer be effective. In most cases, current vaccine candidates against RNA viruses are from past human outbreaks with little or no information of future risks from viral variants carried in animal reservoirs, especially those with the potential for animal-to-human transmission.”

Professor Heeney has also received £1.4 million from the Biotechnology and Biological Sciences Research Council (BBSRC) to lead a project that aims to predict where future outbreaks may arise from and the likely strains, and to then use this knowledge to inform vaccine design. This One Health project enlists veterinarians, clinicians, ecologists and medical and public health workers in West Africa to understand how people catch Lassa fever from rat populations. Their work will include trapping rat species that carry these viruses and placing GPS tags to monitor their movements, as well as obtaining molecular, genomic and antibody data from the animals and viral sequences from infected rats.

Professor Melanie Welham, Executive Chair of BBSRC, says: “This important research from the team at the ̽��ֱ�� of Cambridge is about providing effective treatments for some potentially deadly diseases spread by rats and bats: Lassa and Ebola respectively. Novel strategies to combat dangerous infections like these are essential and often underpin the development of much-needed next generation vaccines.

“Professor Heeney and team have already made a significant difference in this area, researching cross species transmissions of these viruses, with a view to developing vaccines for Ebola and Lassa that would be effective against multiple strains.”

In addition, the team is collaborating with Professor James Wood, Head of the Department of Veterinary Medicine at Cambridge, who is conducting a complementary study funded by the Global Challenges Research Fund to sample bat colonies in Ghana, believed to be a natural reservoir for the Ebola virus.

“Equipped with this information, we should be able to design better vaccine antigens for more effective and broadly-protective vaccines,” says Professor Heeney. “Combined with our accelerated vaccine development platform, this has the potential to have an enormous positive impact on global public health.”

Scientists hope that a new approach to vaccine development, combined with improved surveillance of potential future threats of outbreak, could help to massively reduce the impact of deadly diseases such as Ebola, Marburg and Lassa fever.

"This has the potential to have an enormous positive impact on global public health"

Jonathan Heeney

NIAID

Ebola Vaccine Study in West Africa

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Final biomedical trial on captive chimpanzees is first oral Ebola vaccine for saving wild apes

fpjl2 — Thu, 09 Mar 2017 12:06:41 +0000

̽��ֱ��results from the final biomedical research trial on captive chimpanzees for the foreseeable future have been published today in the journal Scientific Reports.

̽��ֱ��trial was of a vaccination for Ebola: the first orally administered vaccine for any disease developed specifically for the purpose of conserving wild apes.

In addition to poaching and forest loss, diseases such as Ebola and anthrax have devastated wild ape populations. Ebola alone is estimated to have killed one third of the world’s wild gorillas over the last three decades.

Now, new findings have shown an effective oral vaccine for Ebola in chimpanzees, and that the captive animals involved in the trial exhibited very few signs of stress as a result. Researchers say the work demonstrates a model that could be harnessed for other diseases and ape species in the wild.

However, after decades using chimpanzees to test vaccines destined for humans, changes in the law have seen enforced retirement of captive populations and the closing of chimpanzee research facilities in the US – the last developed country where biomedical testing on chimpanzees was legal.

In what researchers describe as a “horrible irony”, they say these reforms – a victory for long-standing campaigns by animal welfare groups – will ultimately prove detrimental to chimpanzees and gorillas in the wild, as any vaccination for wild animals must be tested in captivity first to ensure its safety.

Consequently, the promising new vaccine model may never progress to the point where it can be used to inoculate endangered wild apes, say the research team from the universities of Cambridge, UK, and Thomas Jefferson and Louisiana, US.

“In 2014 the world was gripped by fears of an Ebola virus pandemic. Yet few people realise that Ebola has already inflicted pandemic scale mortality on our closest relatives,” says lead researcher Dr Peter Walsh from the ̽��ֱ�� of Cambridge.

“African apes are also threatened by naturally occurring pathogens like anthrax, and the increasing overspill of human pathogens such as measles. A glimmer of hope lies in the fact that many of the disease threats are now vaccine preventable.

“We have developed a very promising tool for inoculating ape species against the myriad deadly diseases they face in the wild, but continued progress relies on access to a small number of captive animals.

“This may be the final vaccine trial on captive chimpanzees: a serious setback for efforts to protect our closest relatives from the pathogens that push them ever closer to extinction in the wild.”

Previous attempts to vaccinate wild apes have resorted to administering individual animals with hypodermic darts – a laborious task feasible for only a small number of apes habituated to human approach. By contrast, oral vaccines encased in appealingly edible baits could be distributed across wild ape territories to inoculate large numbers over longer periods.

Such an approach has already proved successful in other species: almost eliminating fox rabies (and the consequent need to cull foxes) across continental Europe.

̽��ֱ��latest study was carried out with ten chimpanzees in one of the last remaining chimpanzee research facilities in the US in New Iberia, Louisiana. Six received the oral vaccine, while four were injected as a control group.

All the animals displayed a robust immunity without side effects after 28 days – when the trial was terminated due to new Endangered Species Act regulations banning biomedical research on chimpanzees.

Throughout the trial, scientists closely monitored animal behaviour and physiology for signs of severe stress. Other than very minor weight loss (2% of body mass), they say that signs of trauma were “entirely absent”.

“Some pressure groups argue that all research on captive chimpanzees is tantamount to torture, not just because of procedures but also due to confinement,” says Walsh.

“Enclosures and animal care are now of a very high standard, with chimpanzees housed in large social spaces. ̽��ֱ��modest traces of stress we detected during our trial were akin to the values observed in college students anticipating exams.”

Captive chimpanzee trials are technically still legal in the US in instances that benefit the species. However, Walsh says that the limited funds available for conservation research makes it unviable for biomedical facilities to retain populations, while zoos and sanctuaries are either “ideologically opposed” or unwilling to risk any public backlash from testing.

Further work to enhance the vaccine, such as ensuring effectiveness after exposure to high tropical forest temperatures, may now never get done due to the closure of captive chimpanzee facilities.

“In an ideal world, there would be no need for captive chimpanzees,” says Walsh. “But this is not an ideal world. It is a world where diseases such as Ebola, along with rampant commercial poaching and habitat loss, are major contributors to rapidly declining wild ape populations.

“Oral vaccines offer a real opportunity to slow this decline. ̽��ֱ��major ethical debt we owe is not to a few captive animals, but to the survival of an entire species we are destroying in the wild: our closest relatives.”

Oral vaccine offers hope for ape species ravaged by Ebola and other diseases, as it can be widely dispersed to save more wild animals. However, scientists say recent law changes on captive chimpanzee testing may stop the conservation work in its tracks.

This may be the final vaccine trial on captive chimpanzees: a serious setback for efforts to protect our closest relatives from the pathogens that push them ever closer to extinction in the wild

Peter Walsh

Matthias Schnell

One of the captive chimpanzees in the research trial receiving the oral Ebola vaccination

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Call of duty: fighting Ebola in Sierra Leone

cjb250 — Fri, 13 Jan 2017 16:16:43 +0000

On the windowsill of Professor Ian Goodfellow’s office sit photographs of him with his children, and just down the corridor, his wife is carrying out research in the same department. Even at work, he is surrounded by constant reminders of the special things in his life, providing a sense of security.

His work, too – apart from the treadmill of seeking funding – is a secure, safe environment. Goodfellow is a basic scientist, carrying out lab-based studies into viruses such as norovirus, the winter vomiting virus. He doesn’t even come into contact with norovirus patients, so is at no particular risk of contracting this unpleasant, but relatively harmless, infection.

Yet in December 2014, Goodfellow chose to leave all of this security behind – for several months at a time – to join a taskforce fighting one of the most hazardous and frightening emerging infections of recent times, the Ebola outbreak in Sierra Leone. Since the epidemic began in West Africa in 2013 until it was declared over in March 2016, the virus infected more than 28,000 and killed over 11,000 people.

Goodfellow was one of over 30 people from Cambridge, coordinated by Dr Tim Brooks at Public Health England, who lent their support. Goodfellow helped set up one of the first diagnostic laboratories in an Ebola Treatment Centre near Makeni, in northern Sierra Leone, with support from the UK government. This was physically demanding and at times potentially dangerous work. “We had to move several tons of equipment and reagents by hand, in 35°C heat with over 90% humidity on a rather dangerous and very active building site,” he recalls. During their stay they encountered fires, electric shocks, and one of his own postdocs was bitten by both a spider and a snake.

Since the start of the epidemic, Goodfellow and colleagues have sequenced over 600 Ebola genomes, helping provide information about how the virus is evolving in, and how its evolution has been affected by, unprecedented levels of human– human transmission.

Towards the tail end of the epidemic, sequencing allowed researchers to trace the origin of new cases. “To end the epidemic, you need to make sure that any new cases are in transmission chains that are being monitored and are geographically contained, so you can pinpoint where this virus is coming from.”

̽��ֱ��Tonkolili District, for example, had been Ebola-free for several months when a new case occurred. “We needed to know if this new case had come from a new introduction from an animal host, from a neighbouring country, or if it was part of a chain of transmission that had been hidden from the healthcare providers.

There’s a lot of stigma around Ebola, so it was possible there was a whole cluster in a village and that no-one was reporting the cases. That would be a disaster: all of a sudden, you don’t go from one to two cases, you go from one to tens or even hundreds.”

By sequencing the virus, in a very short time they were able to trace the source back to a survivor in whom the virus had persisted, and to take appropriate measures to prevent further spread. In fact, their work showed that Ebola can persist in survivors for over 15 months after infection and be transmitted through unprotected sex, and possibly even from a mother to her child through breastmilk.

Now that the emergency has passed, the treatment centre has closed down, but its equipment is being used at the ̽��ֱ�� of Makeni Infectious Disease Research Laboratory in a building donated by the country’s president, Ernest Bai Koroma. ̽��ֱ��laboratory was kitted out with support from the Wellcome Trust and the Cambridge- Africa Programme, and now functions as a base for local and visiting scientists to carry out research. Goodfellow and his postdoc Dr Luke Meredith have helped train local technicians and researchers in some of the latest techniques in surveillance and sequencing of pathogens such as HIV and hepatitis B.

“We need to avoid ‘parachute science’, where scientists fly in, take samples and leave,” he insists. “It should be about developing sustainable partnerships, about developing local capacity. With training and support, local researchers have the ability to respond to these outbreaks; they just need the equipment and the infrastructure.”

This has already shown its value. A new case arose in January 2016 while neither Goodfellow nor any of his colleagues were in the country, but local scientists were able to use the techniques to trace the source of the infection.

Going to Sierra Leone was not an easy decision for Goodfellow, but he feels that he had a duty to respond. “ ̽��ֱ��academic virology community had a responsibility to offer support. We couldn’t just sit back and watch this massive epidemic explode in front of our eyes with the knowledge that we have skills that could be useful.”

Many of the scientists who went out have struggled to return to their normal work, he says – some even quit their jobs on returning to take up more front-line jobs or to undertake more translational research. For Goodfellow, it has certainly made him appreciate the contribution that basic science makes.

“Basic science can often feel removed from real world applications,” he says, “but the skills you gain from running a laboratory are actually very useful in these kinds of environments. ̽��ֱ��ability to think on your feet and to figure out solutions is invaluable.”

It has also given him some perspective about what he does. “ ̽��ֱ��satisfaction you get from being involved in a response like this and in capacity building is orders of magnitude better than publishing academic papers.”

Cambridge graduate Charlotte Dixon (Churchill), BA (2014) Modern and Medieval Languages, was also part of the Ebola crisis response in Sierra Leone in 2015 while working with the Department for International Development on their Graduate Scheme.

Working in a lab as a basic scientist can often seem far removed from the real world. A year since the World Health Organization declared the Ebola outbreak over, one researcher tells how the skills he learned working in a lab in Cambridge turned out to be surprisingly useful in fighting one of the most terrifying disease outbreaks of recent times.

̽��ֱ��satisfaction you get from being involved in a response like this ... is orders of magnitude better than publishing academic papers

Ian Goodfellow

Belt buckles

Dr Caroline Trotter works on an infectious disease that has killed even more than Ebola. It occurs periodically right across the ‘midriff’ of Africa from Senegal to Ethiopia, in the so-called ‘Meningitis Belt’.

In the last major meningitis outbreak, in 1996, some 250,000 were infected and 25,000 people died. It was at this point that the global health community came together to fight back.

̽��ֱ��Meningitis Vaccine Project (MVP) was launched, a partnership between international health organisation PATH and the World Health Organization (WHO). Working with the Serum Institute of India, MVP developed and rolled out the meningococcal A conjugate vaccine in just 10 years to combat the particular strain that affected the African belt. Since its introduction in 2010, 265 million people have been vaccinated. In Burkina Faso, where the vaccine was first used, a mass vaccination campaign saw 10 million people vaccinated in 10 days.

But even campaigns as huge as this aren’t enough to eliminate the infection, as Dr Caroline Trotter from the Department of Veterinary Medicine, explains: “You get a honeymoon period, but then you see a resurgence of cases.”

Trotter and her team used mathematical modelling to predict the best strategies for ensuring that this did not happen. ̽��ֱ��WHO, who funded her work, used it to shape their guidelines and ensure that the vaccine was introduced into routine vaccination programmes across sub- Saharan Africa.

She and Goodfellow were part of a Cambridge-Africa delegation to ̽��ֱ��Gambia in 2014 – a trip that inspired Goodfellow to lend support to combatting Ebola – and as a result Trotter is now working with collaborators at the Medical Research Council Unit in the country to look at the effect of the vaccine on pregnant women and their babies.

Meanwhile, she continues working with the African Meningococcal Carriage Consortium, a global research effort to study how meningococcal meningitis is spread in Africa, with the hope of gradually tightening the belt on this devastating disease.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Graduate, get a job … make a difference #2

ta385 — Fri, 13 Jan 2017 09:00:01 +0000

Charlotte Dixon (Churchill), BA (2014) Modern and Medieval Languages

Since graduating I’ve been working with the Department for International Development (DFID). I started on the one year Graduate Scheme, working in London, but in 2015 I went to Sierra Leone as part of the Ebola crisis response. My current role is Policy and Programme Manager at DFID Ethiopia.

I've only been in Ethiopia for four months, but I’m really enjoying it so far. Day-to-day life can be challenging at times but it’s definitely worth it. No day is ever the same, so I never know quite what to expect when I head to work in the morning. When I arrived, the security situation here was quite unstable, so I haven't been able to see much of the country yet, but travel restrictions have just been lifted so I’m looking forward to being able to explore a bit more.

What Cambridge did for me

I first heard about the DFID Graduate Scheme through the Cambridge Careers Service. After going along to a talk they had organised with alumni already working for DFID, I knew it was the career for me.

Studying at Cambridge has helped me because it teaches you how to think on your feet and work under pressure. I studied French, Spanish and a bit of Portuguese. I don’t use them in my day-to-day job, but the fact that I have studied languages in the past has definitely helped me to pick up Amharic (the official language of Ethiopia). There are quite a lot of opportunities to use languages in international development - I hope to work in a French-speaking part of Africa in the future.

Outside of work, learning languages has definitely enriched my life, giving me a greater understanding of other cultures and, most importantly, giving me an excuse to travel to countries like Chile, Argentina, Colombia and Guatemala.

My motivation

I always knew that I didn’t want to pursue a conventional career in the corporate world - I wanted to do something that would make a difference. I also knew I wanted a career that would allow me to travel.

Applying to Cambridge

I was lucky that quite a few people I knew from my school were also applying to Cambridge, so it didn’t feel quite so daunting, but I still remember it being a long and stressful process. ̽��ֱ��college I went to, Churchill, had a really good mix of people which made it really easy to settle in.

Cambridge graduates enter a wide range of careers but making a difference tops their career wish lists. In this series, inspiring graduates from the last three years describe Cambridge, their current work and their determination to give back

Studying at Cambridge teaches you how to think on your feet and work under pressure

Charlotte Dixon

Charlotte Dixon working in Sierra Leone

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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New model could help improve prediction of outbreaks of Ebola and Lassa fever

cjb250 — Fri, 02 Sep 2016 18:00:41 +0000

Many of the major new outbreaks of disease, particularly in Africa, are so-called zoonotic infections, diseases that are transmitted to humans from animals. ̽��ֱ��Ebola virus, for example, which recently killed over 11,000 people across Africa, was most likely transmitted to humans from fruit bats.

Modelling how outbreaks arise and whether they will take hold or quickly die out has proved challenging, with two factors in particular being difficult to quantify. ̽��ֱ��first is ‘spillover’, where the pathogen – a virus or parasite, for example – passes from an animal to a person. This can be through direct transmission, for example by being bitten or by eating ‘bush meat’ (wild animals such as fruit bats or monkeys that are caught and consumed), or indirectly, such as through contact with faeces or disease-carrying mosquitoes.

In many cases, a spillover will go no further. When a human is bitten by a rabid dog, they may become infected, but as the disease cannot transmit from human-to-human, the disease hits a dead end.

However, in some cases the infected person goes on to infect other humans. This is the case for diseases such as Ebola, Lassa fever (spread from rodents) and Crimean Congo haemorrhagic fever (spread from ticks). But in many cases, unless there are additional spillover events, the disease eventually fades out. This is referred to as a ‘stuttering chain’, and even though the disease is transmitted from human-to-human, they are still considered to be zoonotic infections.

Diseases such as HIV, however, which almost certainly began as a spillover from chimpanzees, are no longer considered to be zoonotic as the chain of transmission from humans to other humans is continuous and no longer relies on spillover to sustain transmission.

“Modelling spillovers is a real challenge,” says Dr Gianni Lo Iacono from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “We don’t have particularly good data on wildlife numbers, such as fruit bats in Sierra Leone, and only a crude idea of their geographic distribution and how many are infected. Even in the UK, we don't really know how many deer we have, which would be really useful to estimate the risk of Lyme disease.”

In addition, measuring the likelihood of contact with the infected animals is also extremely difficult as it involves understanding human and animal behaviour.

Stuttering transmission, too, can be difficult to model, says Dr Lo Iacono. “In the case of Lassa fever, people who catch the disease from animals show the same symptoms as those who get it from humans. So is this case a spillover or part of a human-to-human chain of transmission? And if members of the same family get the disease, have they caught it from a family member or from the same pot of contaminated rice?

“Sometimes you can be lucky and work this out, as we did in a previous study, but this was possible because information of outbreaks that were known to be pure human-to-human chains was, unusually, available. But we need more general methods.”

Dr Lo Iacono and colleagues have developed the most coherent and potentially most accurate mathematical model to date for zoonotic diseases, which incorporates spillover and stuttering transmission.

“ ̽��ֱ��pathogen does not care if it jumped from an animal or from another human; the only difference is that in a stuttering transmission an infected person can trigger other chains of human infections. A general, realistic model should capture this mechanism,” adds Dr Lo Iacono.

Details of the model, including a demonstration applying the framework to Lassa fever, are published today in the open access journal PLOS Neglected Tropical Diseases.

“By modelling potential outbreaks more accurately, we can help inform public health messages,” explains Professor James Wood, Head of the Department of Veterinary Medicine, and senior author. “If you know that most cases of an outbreak of Lassa fever come from spillovers, then the message might be ‘kill the rats’, but if it is now mainly spreading between humans, the messages will be around washing your hands or avoiding contact with bodily fluids.”

̽��ֱ��beauty of the model, say the researchers, is that it is simple to implement, so public health officials and non-mathematicians could easily use it. It also allows for the incorporation of data from different disciplines, factoring in socioeconomic, ecological and environmental factors, for example.

“It’s important to understand if and how these other important factors can increase the impact of stuttering chains,” says Professor Wood. “Ebola has always been a very severe disease but previously confined to small, remote regions. Then suddenly, in the last two years it exploded in West Africa. Why? Was it because social patterns changed? Our model could be used to address such questions better.”

̽��ֱ��research informing the paper was carried out as part of the Dynamic Drivers of Disease in Africa Consortium, which was funded by Ecosystem Services for Poverty Alleviation (ESPA).

Reference
Lo Iacono, G et al. A unified framework for the infection dynamics of zoonotic spillover and spread. PLOS NTD; 2 Sept 2016; DOI: 10.1371/journal.pntd.0004957

Potential outbreaks of diseases such as Ebola and Lassa fever may be more accurately predicted thanks to a new mathematical model developed by researchers at the ̽��ֱ�� of Cambridge. This could in turn help inform public health messages to prevent outbreaks spreading more widely.

If you know that most cases of an outbreak of Lassa fever come from spillovers, then the message might be ‘kill the rats’, but if it is now mainly spreading between humans, the messages will be around washing your hands or avoiding contact with bodily fluids

James Wood

Global Panorama

Ebola in West Africa

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Sexual transmission involved in tail-end of Ebola epidemic

cjb250 — Tue, 17 May 2016 23:12:14 +0000

An international team of researchers has produced a detailed picture of the latter stages of the outbreak in Sierra Leone, using real-time sequencing of Ebola virus genomes carried out in a temporary laboratory in the country.

While the study did not suggest that unconventional transmission was more common than previously thought, the authors describe several instances including a mother who may have transmitted Ebola to her baby via breastfeeding, and an Ebola survivor who passed on the virus sexually a month after being released from quarantine.

̽��ֱ��research, published today in the journal Virus Evolution, suggests that rapid sequencing of viral genomes in the midst of an epidemic could play a vital role in bringing future outbreaks under control, by allowing public health workers to quickly trace new cases back to their source.

Sierra Leone was the most widely affected of the three West African countries worst hit by the Ebola epidemic, with 14,124 cases and 3,956 deaths to date. Without effective vaccines or treatments for the infection, bringing the epidemic under control relied largely on public health measures such as the rapid identification and isolation of Ebola patients, contact tracing and quarantine, as well as encouraging safe burial practices.

By mid-2015 cases in the three most-affected countries had declined, but isolated cases of the disease continued to appear, even though all known transmission chains were thought to be extinguished.

Researchers led by the ̽��ֱ�� of Cambridge and Wellcome Trust Sanger Institute began investigating these cases in a temporary genome sequencing facility set up by Professor Ian Goodfellow. Based in a tent at the Ebola Treatment Centre in Makeni, Sierra Leone, the facility provided in-country sequencing capability to process samples from patients in Makeni and surrounding areas in real time, without the need for sample shipment out of the country.

̽��ֱ��team generated 554 complete Ebola genome sequences from samples of blood, buccal swabs, semen and breast milk collected between December 2014 and September 2015 from Ebola isolation and treatment centres in the north and west of the country. These were combined with 1019 samples sequenced by other groups to create a picture of the viral variants present in Sierra Leone.

They found that during 2015 at least nine different lineages of the virus were circulating in Sierra Leone, eight of which evolved from a single variant that introduced Ebola to the country in June 2014. ̽��ֱ��remaining viruses came from a separate, geographically distinct lineage that originated in Guinea.

Starting in mid-2015 samples from all new Sierra Leone cases were rapidly sequenced in the facility. ̽��ֱ��data, combined with the growing reference set, helped field workers locate the source of infection for some of the final Ebola cases in Sierra Leone. This work revealed that some cases were acquired through unconventional transmission chains and supports a growing body of evidence that the Ebola virus can be found in fluids such as semen or breast milk and may persist beyond the standard quarantine times.

Senior author Professor Ian Goodfellow, from the ̽��ֱ�� of Cambridge, said: “During the initial part of the Ebola epidemic several teams were sequencing samples, but the delays caused by shipping the samples out of West Africa made it difficult to use the sequence data for investigating new chains of transmission. Often by the time the data was published the samples were six months old. To be able to rapidly identify the source of new cases we need to sequence samples and release data in real-time, share samples and share data as it’s produced.”

Dr Matthew Cotten, joint senior author, from the Wellcome Trust Sanger Institute added: “During the epidemic combining our Ebola virus genome sequences with data from other groups provided insight into how the virus was evolving and contributed to an important reference for tracking the source of new cases. As the outbreak progressed, our data also show that quarantines, border control and checking methods were effective, as movement of the virus within and between countries ceased.”

̽��ֱ��sequencing facility set up by the team has now been moved to the ̽��ֱ�� of Makeni, where it forms the focal point of the new UniMak Infectious Disease Research Laboratory. ̽��ֱ��facility is providing world-class training to local students and scientists, which has proven crucial to sequencing the recent new cases of Ebola when no international staff were present.

Dr Jeremy Farrar, Director of the Wellcome Trust, said: “Close contact with an infected individual is still by far the most common way for Ebola to spread, but this study supports previous research suggesting that the virus can persist in bodily fluids for a long time after recovery. These unusual modes of transmission may have contributed to isolated flare-ups of infections towards the end of the epidemic.

“ ̽��ֱ��success of this innovative project shows how important it is to carry out genome sequencing within the affected countries, and for the data to be shared in a rapid and open way as part of the epidemic response. Strengthening laboratory and surveillance facilities where they are currently lacking will also aid early detection, making the world better prepared for infectious disease outbreaks.”

̽��ֱ��research was funded by the Wellcome Trust and is a collaboration between the ̽��ֱ�� of Cambridge and the Wellcome Trust Sanger Institute with support from the ̽��ֱ�� of Edinburgh and Public Health England. ̽��ֱ��Ion Torrent sequencing machines were supplied by Thermo Fisher Scientific.

Reference
Armando et al. Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases. Virus Evolution; 18 May 2016; DOI: 10.1093/ve/vew016

Press release from the Wellcome Trust

Some of the final cases of Ebola in Sierra Leone were transmitted via unconventional routes, such as semen and breastmilk, according to the largest analysis to date of the tail-end of the epidemic.

To be able to rapidly identify the source of new cases we need to sequence samples and release data in real-time, share samples and share data as it’s produced

Ian Goodfellow

Medici con l'Africa Cuamm

Messaggi lungo le strade della Sierra Leone

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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