Research Training Fellowship: Dr Manish Sadarangani
First published on 27 May 2007
Updated on 24 March 2014
What did the project achieve?
“My work has increased understanding of immune defences against a bacterium called Neisseria meningitidis,” says Dr Manish Sadarangani, of the University of Oxford. “This dangerous bacterium causes meningitis and septicaemia, killing one in 10 of those affected.1 My findings could help in the design of better vaccines to protect babies and children from these devastating infections in the future.”
Both meningitis and septicaemia (a form of blood poisoning) can kill with alarming speed – within just hours.2 Those who survive can experience permanent consequences, including deafness, epilepsy and learning difficulties. Some need to have fingers, toes, or even an arm or a leg amputated.
Neisseria meningitidis bacteria are masters of disguise and their ability to change the appearance of their outer surface complicates vaccination efforts. They also exist in many different forms. Vaccines are already available to protect against some of these bacteria but they don’t work against all of them.
“The MenB form of the Neisseria meningitidis bacterium remains a serious threat, killing more children under five than any other infectious disease in the UK,” says Dr Sadarangani.3 “My work could eventually help add to our armoury against these dangerous bacteria, broadening protection and sparing more children from the terrible experience of developing meningitis or septicaemia.”
1. Public Health England. Meningococcal infection factsheet. http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1195733822509 Website accessed 18 February 2014.
2. Meningitis Research Foundation home page. http://www.meningitis.org/ Website accessed 20 March 2014.
3. Meningitis Research Foundation. MenB vaccine to be available in the UK privately. http://www.meningitis.org/news-media/bexsero Website accessed 11 December 2013.
This research was completed on 2 September 2010
Protecting children from meningitis and septicaemia
Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research. Dr Sadarangani’s grant of £161,296 will fund his three-year evaluation of a possible new vaccine for meningitis and septicaemia.
Dr Manish Sadarangani is one of our brightest young doctors, with degrees from the Universities of both Oxford and Cambridge. After demonstrating an exceptional talent for research while volunteering to help sick children at a district hospital in Kenya, he is determined to find new ways to combat infectious disease.
In this Fellowship, Dr Sadarangani is focussing his attention on a dangerous bacterium, called Neisseria meningitidis, which causes meningitis and septicaemia, killing around one in ten of those it infects.1 Dr Sadarangani is evaluating the potential of a possible new vaccine.
"I am very excited about being given this opportunity to fight meningitis and septicaemia. Action Medical Research has an extensive portfolio of research in childhood disease and disability, and vaccine development, making it an ideal charity to fund my project," he said.
Meningitis and septicaemia strike fear in the hearts of parents
Those who have heard of the bacterium Neisseria meningitidis know only too well the devastation it can cause – 1,500 to 2,500 cases of septicaemia and meningitis each year in the UK,2 half a million cases worldwide.3 One in ten of those infected die.1 Most are children.2,4 ‘Meningitis and septicaemia are feared by parents and healthcare professionals alike. Both illnesses can kill within a matter of just a few hours. Both can result in devastating disability,’ explains Dr Sadarangani.
Neisseria meningitidis kills more children in the UK than any other infection.4 Survivors can be left with permanent complications, like deafness, epilepsy and learning disabilities. Some have to have fingers, toes, or even more of their limbs, amputated. As the majority of cases occur in childhood, these complications can cause lifelong handicap.
‘Although we have an effective vaccine against some types of Neisseria meningitidis, we still do not have a vaccine against serogroup B, which causes most of the cases of meningitis in developed countries,’ says Dr Sadarangani. ‘The thought of being able to make a difference to so many people’s lives, by working towards a vaccine that could perhaps be offered to all our children, is very exciting and is a great motivation.’
Is a new vaccine feasible?
‘In this Fellowship, I am evaluating a possible new type of vaccine for meningitis and septicaemia, which targets one of the most important bugs that causes these illnesses – serogroup B Neisseria meningitidis,’ explains Dr Sadarangani. ‘I am also increasing our understanding of the bacterium.’
Neisseria meningitidis has a molecule on its surface, called Opa, which helps it to stick to human cells, including cells of the immune system, during the infection process. Recent work suggests that Opa is a candidate for incorporation into a possible future vaccine, but we don’t know exactly how it influences the behaviour of the immune system. So Dr Sadarangani is investigating what Opa does to several key immune cells and is assessing the practicalities of including it in a vaccine.
|Project Leader||Dr M Sadarangani|
|Location||Department of Paediatrics, University of Oxford|
|Grant awarded||27 February 2007|
|Start date||3 September 2007|
|End date||2 September 2010|
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Important steps towards eradicating two dangerous diseases
Dr Sadarangani’s work will improve our understanding of serogroup B Neisseria meningitidis, the bacterium that is responsible for so many cases of meningitis and septicaemia, mostly in children. These terrible illnesses are traumatic in the extreme, even for children who survive unharmed.
Our improved understanding could, in turn, help in the design of future new treatments for meningitis and septicaemia. Perhaps even more importantly, it may also take us one step further towards the ultimate goal of eradicating these dreadful diseases, by helping in the design of an effective and safe new vaccine.
At the beginning of a promising career
For Dr Sadarangani, this Fellowship is a vital springboard in his ambition to dedicate his entire career to fighting infectious diseases in children. ‘Unfortunately only a minority of research is carried out in the field of Paediatrics,’ says Dr Sadarangani. ‘Yet infectious diseases constitute a significant burden of childhood illness.
Research in this area is extremely important.’ The training that Dr Sadarangani receives in this Fellowship should continue to pay dividends over many years to come. This outstanding young researcher is determined to keep on pushing the boundaries, both by increasing our understanding of exactly how infectious organisms make us ill, and by striving for new ways to prevent and treat disease.
Dr Sadarangani is an extremely committed, caring and intelligent clinician and researcher. But, sadly, this isn’t always enough to help his young patients. ‘By the time that some children arrive at hospital with meningitis, or septicaemia, they are so sick that there is nothing we can do to help. It’s heartbreaking. It highlights the limitations of medical treatment, even in the 21st century, and certainly emphasises the old saying that “prevention is better than cure”.’
Dr Sadarangani hopes his work will ultimately help in both prevention and treatment of meningitis and septicaemia. He is studying how infection with Neisseria meningitidis causes disease, on a molecular level. His laboratory studies are focusing on the role of a protein, called Opa, which is found on the surface of the bacterium. He is studying how Opa interacts with immune cells and influences the development of immunity to the bacterium, and whether it might work in a similar way in a vaccine.
The research will take place at the prestigious Centre for Clinical Vaccinology and Tropical Medicine, part of the University of Oxford’s Department of Paediatrics. The Professors who are supervising Dr Sadarangani have excellent credentials and their laboratory’s track record in researching Neisseria meningitidis is world class. Dr Sadarangani sees this Fellowship from Action Medical Research as a wonderful opportunity in the battle to prevent meningitis and septicaemia.
I am delighted that this Fellowship is allowing me to get down to some vital research towards a new vaccine.Dr Manish Sadarangani
- Trotter C, Samuelsson S, Perrocheau A, de Greeff S, de Melker H, Heuberger S, Ramsay M. Ascertainment of meningococcal disease in Europe. Euro Surveill. 2005 Dec;10(12):247-50.
- Meningococcal Reference Unit; Gray SJ, Trotter CL, Ramsay ME, Guiver M, Fox AJ, Borrow R, Mallard RH, Kaczmarski EB. Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the Meningococcal Reference Unit. J Med Microbiol. 2006 Jul;55(Pt 7):887-96.
- Tzeng YL, Stephens DS. Epidemiology and pathogenesis of Neisseria meningitidis. Microbes Infect 2000; 2:687-700.
- Office for National Statistics. 2004. Mortality Statistics (Series DH2, No. 31). Office for National Satatistics.