January 11, 2019

expert reaction to the sudden death of Prof. Martin Gore following a yellow fever jab

Expert reactions to the sudden death of Prof. Martin Gore following a yellow fever jab.

Commenting on the yellow fever vaccine:

Dr. Nicky Longley, Tropical Medicine consultant, Hospital for Tropical Diseases, UCLH, said:

How does the yellow fever vaccine work and why are some travelers advised to have it?

“The yellow fever vaccine is a live vaccine. It is made by modifying the yellow fever virus so that it doesn’t make people ill, but it does stimulate their immune system to make antibodies against the virus. If they are then bitten by a yellow fever-infected mosquito, their body is able to rapidly make more antibodies, so they can fight off the infection without becoming ill.

“Live vaccines are very effective vaccines, often leading to long term protection against infections.

“Travellers are advised to have the yellow fever vaccine if they are travelling to a yellow fever area. Yellow fever is a serious infection which kills up to 50% of people who develop the serious form of the disease. Recently it has spread to popular tourist destinations in South America, so the vaccine is recommended in almost all fit, healthy people under the age of 60 years travelling to yellow fever areas. Travellers are offered the vaccine if their risk of catching the infection is thought to outweigh the risks of the vaccine.”

What are the risks/benefits involved with this specific jab? How do these differ with age?

“The yellow fever vaccine is a very effective vaccine offering life-long protection against infection, with more than 98% protection after just one dose.

“There are two main types of reaction that people can suffer to this vaccine. These are yellow fever vaccine associated neurotropic disease (YEL_AND) and yellow fever vaccine-associated viscerotroptic disease (YEL-AVD). YEL-AND causes inflammation of the brain and nervous system. YEL-AVD causes infection much like yellow fever infection, with liver and kidney failure, bleeding and brain inflammation. For people between the ages of 9 months and 60 years who have no underlying health problems, these reactions are extremely rare (around 1 in a quarter of a million doses). It should be emphasized that, for most people, the risk of dying of yellow fever infection following travel is much higher than the risk of getting either of these reactions.

“For people over the age of 60 years, the risk of having one of these reactions increases around 6 fold. The decision to give the vaccine should take into consideration this increased risk of vaccine reaction, balanced against the risk of acquiring the disease during the trip abroad. The overall risk of a vaccine reaction is still low.

“There are certain other conditions that make having this type of reaction even more likely, and in these cases the vaccine is not offered to the individual at all. Examples include being on chemotherapy or other drugs that prevent the immune system from working effectively, having underlying problems with the immune system, having conditions affecting the thymus gland or being under 6 months of age.”

– Are there similar risks from other vaccines?  If not, what is different about the yellow fever vaccine?

“Live vaccines are generally not offered to individuals without a fully functioning immune system. Live vaccines replicate (grow) within the individual who has been vaccinated. This is why they are so effective at generating immunity which protects the individual against infection. However they depend on a fully functioning immune system to control their replication. If the immune system of the individual who has been vaccinated is not able to control the replication (growth) of the vaccine, the vaccine can cause disease which may be similar to the infection which the vaccine was meant to prevent. Examples include the BCG vaccine which can cause a TB-like illness in people with impaired immune systems.”

Dr. Marcus Dorner, Non-Clinical Senior Lecturer in Immunology, Imperial College London, said:

“The Yellow fever vaccine, which was first developed in 1938 and has been used in millions of people without severe complications. It completely protects from Yellow fever, which has a case fatality rate of 3% to 7.5% of infected, responsible for 5,800 deaths in 2016 alone. Since Yellow fever virus is endemic in parts of Africa and South America and is transmitted via mosquitos, the vaccine is usually recommended whenever travelling to these areas. Some countries even require proof of vaccination for entry.

“What sets it apart from other vaccines such as the tetanus vaccine is that it is a live-attenuated virus vaccine. This means it is a variant of Yellow fever virus, which does not cause disease but results in the development of immunity. In very rare cases this results in the development of severe symptoms reminiscent of Yellow fever. However, since its introduction and following vaccination of more than 600 million people, only 12 of these have been reported. It remains unclear why this is and whether genetics of the vaccinated person might play a role but it has been shown that the vaccine does not revert to the wild-type Yellow fever virus in these patients.“

Nick Phin, Deputy Director, National Infection Service, Public Health England, said:

“We are all saddened to hear about the death of Professor Martin Gore. He was one of the founding fathers of medical oncology and made a huge difference to so many people’s lives, helping them live longer and better. Our thoughts are with his family at this difficult time.

“The yellow fever vaccine is generally safe however in rare instances there can be side effects.  It is generally accepted that side effects increase with increasing age. Anyone travelling to an area where there is yellow fever should discuss their travel plans with their health professional so that a decision on having the vaccine can be made based on their age, planned activity while away and their medical history.”

Dr Louisa James, Lecturer in Immunology, Queen Mary University of London, said:

“Yellow fever is a virus spread by mosquito bites in tropical areas Africa and Latin America. Yellow fever can cause a very serious disease which can be fatal, vaccination is recommended to people travelling to countries where yellow fever exists. Similar to other vaccines such as smallpox and MMR, yellow fever vaccine contains a live-attenuated form of the virus. Yellow fever vaccine works by activating an immune response against the virus and this response can protect against infection for life. Yellow fever vaccine is highly effective and mass vaccination campaigns in the early 20th century led to a disappearance of the disease in many African countries.

“More than 600 million doses of yellow fever vaccine have been given worldwide and it is safe for the majority of individuals. Yellow fever vaccine can very rarely cause severe side effects, including life-threatening illness. People over 60 appear to have a slightly higher risk of experiencing side effects from yellow fever vaccine but the risk remains extremely low. Vaccination is an essential strategy to combat the devastating impact of yellow fever virus which killed tens of thousands of people during recent outbreaks in Africa.”

* Dr James’ comment was amended at her own request: “… this response can protect against infection for up to 10 years…” was changed to “…this response can protect against infection for life…”  (17:14, 14/01/2019).

Professor Peter Openshaw, past President of the British Society for Immunology, said:

“I was very sad to learn about the death of Professor Martin Gore.  He was a leader in the field of cancer biology and made a huge contribution to research in this area and the treatment of many thousands of patients.  My thoughts are with his family, friends and colleagues.

“Yellow fever is a serious viral disease that is found in the tropics and spread by mosquito bite. The vaccine for yellow fever has been available for many years and multiple studies have been conducted into its safety and effectiveness. While overall risk of serious side-effects remains very low (at about 1 in 100,000 of vaccine recipients), it seems that people aged over 60 have a three to four-fold increased risk of experiencing these serious effects compared with younger people. However, this estimate is based on very few reported adverse events.

“This risk has to be balanced against the risk of contracting yellow fever if you are travelling to an infected area – a nasty disease with a high mortality rate. A recent publication in The Lancet concluded that the risk of contracting yellow fever in endemic areas is higher than the risk of experiencing serious side-effects from the vaccine.  The NHS advises that all people over the age of 60 talk to their doctor before getting this vaccine, and that the best way to avoid the serious complications that may follow yellow fever infection is not to travel to parts of the world that put you at risk.

“The details of the illness that led to Professor Gore’s death have not been made public and it is important to remember that everything that happens after a vaccine is given should not be attributed to the vaccine. In the UK, the MHRA is the body charged with looking into adverse side-effects reported from vaccines. They will undoubtedly conduct a proper analysis of this case to ensure it was caused by the vaccine rather than an incidental unconnected cause, such as sepsis.”

Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“It is difficult to comment on this specific case as I don’t know the facts about his death. However, there are more general observations/statements about the YFV vaccine that can be made:

“The yellow fever vaccine, like many other vaccines that are saving thousands of lives worldwide, is based on a live, but disabled, version of the yellow fever virus. This so-called attenuated virus can infect the person it is given to but it does not cause disease. As it infects and replicates in the vaccinated individual it stimulates the immune system to produce virus-killing antibodies and cells which then protect the person if they are ever exposed to the real virus.

“Individuals are advised to have the vaccine if they are travelling to tropical and sub-tropical places in parts of Africa and the Americas, where yellow fever is known or suspected to exist. Whilst the vaccine is very safe it is known that serious side-effects can occur and the risk of these developing does seem to be greater in the over-60s and very young infants. Side effects are well-documented and that blanket vaccination shouldn’t be the norm; instead it should only be given following a proper risk assessment taking into account the likely risk of adverse effect versus the likely risk of being exposed to the virus. 

“One serious complication of yellow fever vaccination – called vaccine-associated viscerotropic disease – occurs in around 3 cases out of every 1 million doses of vaccine given, and some reports have suggested that the risk of this occurring in the over 60s increases to just around 12 cases per million vaccine doses used. This can result in multi-organ failure and around 60% of cases are fatal. It is unclear why these complication arise, but viscerotropic disease is more likely to occur in those with a disease of the thymus, a small gland in the chest that helps keep the immune system working properly.”

Dr Kevin Pollock, Senior Research Fellow, Glasgow Caledonian University, said:

“The yellow fever vaccine is a live, attenuated vaccine – consequently, it’s a bit more risky than say a subunit vaccine. Thus, the risk of side-effects is higher with this vaccine than with other vaccines, especially in those who are immunocompromised in some way e.g. it’s not advised for pregnant women. We don’t yet know whether this death was definitely due to the vaccine or not but given the short period of time after vaccination, it may have been an important precipitant. There is an increased risk of serious complications in people over 60, but it is very rare to see a fatality associated with the vaccine. Approximately 1 in a 1000 can develop severe side-effects, such as muscle pain, seizures, and unusual bleeding. However, the benefit still outweighs the risk of contracting yellow fever in countries where it is endemic. ”

Commenting on Prof. Martin Gore:

Professor Charles Swanton, Cancer Research UK’s chief clinician, said:

“I was deeply saddened to hear that Professor Martin Gore has died. Martin put patients first and he was dedicated to providing personable, high quality care. He was a towering figure in cancer research, but was always happy to roll up his sleeves.

“Against the odds, he worked tirelessly to challenge the status quo. He fought to see immunotherapy work, after many said that it couldn’t.

“He was also a great leader and mentor, who revelled in the success of others. On a personal level, I will never forget his sense of humour, which got me through some trying times. If needed, we would have walked to the North Pole and back for him. He was a remarkable man, who will be greatly missed.”

Dr Ian Hudson, Chief Executive, the Medicines and Healthcare products Regulatory Agency (MHRA), said:

“We are very sad to hear of the passing of our colleague Martin Gore. Martin was a much-valued member of the MHRA’s Commission on Human Medicines and led the oncology expert advisory group.  He provided invaluable guidance and advice to the Agency over many years. Our thoughts are with his family and friends at this time.”

Professor Charlie Swanton, Group Leader at the Francis Crick Institute and Chief Clinician at Cancer Research UK said:

“I was devastated to hear the news of Martin’s passing. Martin was a wonderful man and a world-class clinician, his death is a great loss to us all and patients most importantly. I first worked for him in 2002, in my first job in oncology as a senior house officer at the Royal Marsden. He taught me not only how to be a doctor but also a better person. He had tremendous humility, patience and humour, and was such a generous and gifted mentor. He dedicated his life and career to his patients and alleviating suffering, by demanding high standards and evidence through clinical research.

“He committed himself to his patients and his team throughout his lifetime. He was always willing to support others, and was there for his juniors when they needed advice, often decades later. He was a true pioneer, investigating new immunotherapies decades before the rest of the world became interested in the field. He was a phenomenal clinician, everybody valued his opinion on difficult cases; his gift for interacting with patients was quite remarkable.

“Most importantly, his legacy will be measured by the many UK and international oncologists who now live and practice by Martin’s example, his duty, dedication, humility and humour. His passing is a major blow to oncology and he will be greatly missed.”

Jayne Spink, Chief Executive, Genetic Alliance UK, said:

“This is such immensely sad news – Martin, who I knew best as Chair of the Gene Therapy Advisory Committee, was brilliant to work with and a truly wonderful human; supportive, empowering and generous in his leadership.  His life and work has meant so much to so many people – a force for positivity and good that will be greatly missed.” 

Cally Palmer CBE, Chief Executive, The Royal Marsden NHS Foundation Trust, said:

“Professor Martin Gore CBE was one of the world’s leading oncologists and devoted his career to improving quality of life and outcomes for all those affected by cancer.  He inspired generations of oncologists through his leadership, teaching and training.  His intellect, humour and wisdom and his impact on modern cancer care will be his legacy to patients, the NHS, and cancer research and treatment internationally.”

Prof. James Larkin, Consultant Medical Oncologist, The Royal Marsden, said: 

“I came to The Royal Marsden in 2000 as a junior doctor, uncertain about which career path to follow. That was when I met Martin and he and the Marsden inspired me to become an oncologist. I know that there are dozens of cancer specialists in the UK and around the world who would say exactly the same thing.

“He worked tirelessly to improve outcomes for patients with cancer in the UK and was never happier than when in the clinic with his team at the Marsden looking after patients.

“He was truly larger than life with his warmth, generosity, kindness and extraordinary sense of humour. Lots of people have said to me in the last 24 hours that Martin’s values were exactly the same as those of his beloved institution and that Martin really was the Marsden.

“Amongst all the tears and sadness, I feel extremely lucky and privileged to have met Martin and to have spent so many wonderful years working with him.”

Allyson Kaye MBE, President of charity Ovarian Cancer Action, said:

“Professor Gore was one of the first directors of the Ovarian Cancer Action Research Centre; he led translational research projects to provide new and better treatments for women with ovarian cancer when there was few. He was also a long-standing member of the HHMT International Forum on Ovarian Cancer, a collective accelerating research across the world. He was a giant in the field and a humorous colleague. There is no doubt that Professor Gore improved the lives of many – he will be greatly missed.”

Prof. Michel Coleman, Professor of Epidemiology and Vital Statistics, London School of Hygiene & Tropical Medicine, said:

“I knew Martin well and I am very sad to learn of his sudden death. He had so much to offer. He was a true expert, with encyclopaedic knowledge. He was a gentleman to the core, and unfailingly generous with his time and wisdom. Knowing he was always available to share his expertise was of huge reassurance. I will miss him as a colleague and a friend.”

Prof. Mel Greaves, The Institute of Cancer Research, said:

“Just the other day I had a message from Martin. It was one of many I have received recently about the news year’s honour. But it wasn’t just congratulations. Martin went to some lengths to say why he admired my research and approach to science. I don’t think I’ve ever been paid such generous compliments. I did of course let him know how appreciative I was.

“Martin was something of a force of nature, very energetic, clear thinking and compassionate. It’s a huge loss, particularly to his family and the RMT.”

Prof. Justin Stebbing, Professor of Cancer Medicine and Medical Oncology, Imperial College, said:

“I worked for him in 2000 and he was like a father figure to all the registrars – I didn’t realise until I became a consultant he was the same to them too. I remember the detail he went into with everyone and everything, and the team spirit he fostered.”

Declared interests

Dr Kevin Pollock: “I have no conflicts.”

None others received.