̽��ֱ�� of Cambridge - Wellcome Trust-Cambridge Centre for Global Health Research

' ̽��ֱ��Iron Lady' and the paradox of treating anaemia

lw355 — Fri, 03 Feb 2017 15:09:08 +0000

There’s a strange paradox when it comes to iron deficiency anaemia. We’ve been able to treat the condition for almost two centuries, ever since French physician Blaud of Beaucaire introduced ‘A Readily Assimilated Form of Iron for Making the Blood Red and Healthy’. And yet, in developing countries, where some of those people who are most susceptible to anaemia live, taking an iron supplement can make things worse.

Oral iron supplements contain iron in a form that dissolves quickly in the gut, passes rapidly into the bloodstream, and makes itself available for its many vital functions: carrying oxygen, building DNA and powering muscles. No wonder it’s the treatment of choice.

But, says Cambridge researcher Dr Dora Pereira, the situation is far from straightforward if the patient is not only anaemic but also carrying any one of a number of infections that are endemic in developing countries: hookworm, malaria, HIV, salmonella and amoebic dysentery, among others.

“By making iron available to the cells of the patient, you are also making it available to the cells of any pathogen they carry. ̽��ֱ��results can be far worse than the anaemia they are being treated for,” she explains.

“This is why the global burden of iron deficiency anaemia hasn’t changed in the past 20 years, particularly in children and women of reproductive age. In developing countries, taking oral iron supplements may be associated with increased infection if there is no appropriate infection control available. Unfairly, the most-deprived populations with the highest burden of disease also do worse with currently available iron supplements. So, despite considerable public health efforts, the most widespread nutritional deficiency remains without an effective cure.”

Nearly 12 years ago, while at the Medical Research Council (MRC) Human Nutrition Unit in Cambridge, Pereira and colleagues began to question whether the right type of iron was being used to treat anaemia.“If you look at our diet, we obtain iron from red meat, pulses, whole grains and leafy greens, and in all of these the iron is found in a less ‘accessible’ form than the soluble iron currently used in supplements,” says Pereira.

“ ̽��ֱ��body needs to work harder to release it, which happens within the cells that line the gut. This slows down how available it is to the body, and to pathogens. In fact, this ‘slow release’ of iron may be an innate mechanism that humans have developed throughout evolution in order to live with the many flora and fauna that colonise our guts.” They began looking for an alternative.

Iron exists in hundreds of different forms. ̽��ֱ��one we see on rusty pipes is a very crystalline and stable iron oxide; if we were to eat this we’d take in very little. At the other end of the spectrum are the soluble forms. “But the forms you find in food and those which form during digestion are not soluble forms of iron. So we decided to make a synthetic form that mimicked this more stable mineral and particulate iron structure. In a nutshell, this is a more available form of ‘rust’.”

̽��ֱ��result is IHAT (iron hydroxide adipate tartrate; the A and the T stabilise the iron and are widely used as food additives). IHAT behaves like the iron forms that are found in our diet – it doesn’t dissolve in the gut. It’s taken up whole as nanoparticles by cells in the lining of the gut and it’s broken down inside these cells – mimicking what happens with iron in the diet, and resulting in a slower release of iron into blood.

There is also another advantage. Unlike IHAT, the soluble form of iron in current supplements is what’s called ‘redox reactive’ – it can react with oxygen to produce free radicals that damage the gut lining and contribute to the side effects of taking iron supplements such as diarrhoea, constipation, abdominal pain, cramps and heartburn.

“In developed countries these may be uncomfortable, but in developing countries side effects like diarrhoea can be life-threatening, particularly in children when associated with pathogens such as Salmonella,” adds Pereira.

IHAT has already been tested in ‘first-in-man’ studies and a Phase II trial is now being conducted in 700 children in ̽��ֱ��Gambia, funded by the Bill & Melinda Gates Foundation Grand Challenges in Global Health programme. ̽��ֱ��trial is in collaboration with MRC Unit ̽��ֱ��Gambia, West Africa, and is co-led by Professor Andrew Prentice (MRC International Group and MRC Unit ̽��ֱ��Gambia), an expert at conducting oral iron intervention studies in rural Gambia.

Pereira hopes that the IHAT supplement might provide the solution to what the World Health Organization (WHO) has called ‘a public health condition of epidemic proportions’.
Lack of iron, and its associated anaemia, is the largest nutritional deficiency disorder in the world today, affecting two billion people. In developing countries, where bland diets contain too little iron and infectious diseases reduce iron absorption, at least half of all pregnant women and pre-school children are estimated to be anaemic.

Iron deficiency anaemia causes the death of around 0.8 million people each year, and many millions more are affected by an associated lowering of IQs, complications in pregnancy and unproductive working lives, all of which limit national development.

This is why in countries where more than one in five young children have anaemia, iron compounds are included in a powdered mix of vitamins and minerals made freely and widely available by UNICEF, the World Bank and NGOs.

Keeping an eye on the costs of IHAT has been crucial – if the clinical trials are successful, then the researchers need to be sure that the end product will be affordable and can be made in large quantities. Their current financial projections suggest that a month-long supply of a daily dose will cost around $1–2.

Pereira’s team has been helped with thinking ahead to the marketplace through a mentorship programme with GSK (GlaxoSmithKline), which began after IHAT won the 2014 Emerging Technologies Prize from the UK Royal Society of Chemistry.

“This has been a tremendous help,” says Pereira. “Throughout the years there were many instances where we couldn’t get funding. To many, this type of research seems more like a social enterprise than a business opportunity. But there is no reason why women and children should be dying of iron deficiency anaemia in the world today.”

“And if we are successful, then this would be a safer option with fewer side effects for anyone in the world who needs iron. If it works, it will be a very nice story of a very simple solution.”

Top inset image: Almost 200 years ago, French physician Blaud of Beaucaire introduced ‘A Readily Assimilated Form of Iron for Making the Blood Red and Healthy; image from www.mohma.org courtesy of M. Donald-Blaufox. Bottom inset image: representation of one IHAT particle by Dr Helen Chappell.

To keep up to date with the latest stories about Cambridge’s engagement with Africa, follow #CamAfrica on Twitter.

Look out for our Cambridge Science Festival 2017 event "What works for India and Africa can work for the world" on 14 March 2017 when Dr Dora Pereira and Professor Jaideep Prabhu discuss how solving medical challenges in resource-poor and pathogen-rich settings like India and sub-Saharan Africa is not just better for the people who live there but is also better for people living in other parts of the world. See website for details.

Iron deficiency can be fatal. But in countries where patients are also likely to have other serious diseases, so too can the iron supplements used to treat it. Nearly 12 years ago, Dora Pereira – sometimes referred to as ‘ ̽��ֱ��Iron Lady’ – was part of the team who had an idea for a new supplement. She now leads its clinical trial in ̽��ֱ��Gambia.

̽��ֱ��global burden of iron deficiency anaemia hasn’t changed in the past 20 years, particularly in children and women of reproductive age

Dora Pereira

Nicole Rodriguez

Check-up at MRC Unit ̽��ֱ��Gambia

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

Yes

Cambridge academics honoured in the 2015 New Year Honours List

pbh25 — Tue, 06 Jan 2015 13:25:29 +0000

Professor Sharon Peacock and Professor Graeme Barker are among those who have been given honours in this year’s New Year Honours list.

Clinical microbiologist Professor Sharon Peacock was awarded a CBE for her services to Medical Microbiology. Peacock is known for her work with the Wellcome Trust Major Overseas Programme in Thailand where for seven years she directed a wide-ranging programme of bacterial disease research. In the UK she has focused on the role of sequencing technologies in diagnostic microbiology and public health.

Peacock chairs the Cambridge Infectious Diseases Initiative and is deputy director of the Wellcome Trust Cambridge Centre for Global Health Research. She was elected to the Academy of Medical Sciences in 2013. “Delighted” to have won the award, Peacock said: “I have the privilege of working with an outstanding group of scientists at the ̽��ֱ�� of Cambridge and at the Sanger Institute, and this honour reflects their support and efforts. ̽��ֱ��award also reflects the importance of basic and applied microbiological research for individual and public health.”

Professor Graeme Barker was awarded a CBE for services to Archaeology. ̽��ֱ��former Disney Professor of Archaeology and director, McDonald Institute for Archaeological Research, is known for his research focussing on prehistoric archaeology, the relationship between landscape and people, transitions from foraging to farming, and the origins of human behaviour and migrations.

Barker has worked all over the world, including in the rainforest of Borneo, and the deserts of the Middle East and North Africa. One of his major contributions has been work showing how humans have adapted to climate change in the past, and the lessons that can be learned from this today.

Describing himself as “thrilled” to be awarded the CBE he said: “I changed to archaeology half way through my undergraduate degree at Cambridge inspired by meeting Colin Renfrew, then a research fellow, and was privileged to succeed him as Disney Professor in 2004. It has also been a privilege to work in archaeology, which has so much to tell us about what it means to be human. It is a team subject par excellence and in accepting the award I have felt very much that it celebrates the achievements of so many colleagues, and good friends from all parts of the world whose support has been so important to anything I have achieved.

Tim Oates, Group Director of Assessment Research and Development at Cambridge Assessment, was also awarded a CBE, for Services to Education.

Simon Lebus, Group Chief Executive of Cambridge Assessment said “We are all delighted that Tim has been so honoured; it is a signal recognition of the body of work he produced during his time as a Group Director at Cambridge Assessment.”

Oates, who joined Cambridge Assessment in May 2006, said “I would like to thank all those at Cambridge Assessment who enabled me to make this contribution to improving our education system.”

Trevor Llewellyn Richards, formerly Capital Project Liaison Officer at the ̽��ֱ��’s School of Clinical Medicine, was awarded a BEM for services to Biomedical Research and the Welfare of Animals in Research. Mr Richards was Director of Central Biomedical Resources from 1996 to 2012 and has been described as an “outstanding bio-facilities manager.”

Members of the ̽��ֱ�� have been recognised for their outstanding contributions to society.

̽��ֱ��text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.

Yes

Harnessing the power of research to benefit developing countries

gm349 — Thu, 25 Apr 2013 15:36:33 +0000

On Thursday 2 May, the CEO of the GAVI Alliance, Dr Seth Berkley, will discuss how to harness the power of research to expedite the development of vaccines appropriate for developing countries and improve access to them.

Dr Berkley’s talk will set out how the GAVI Alliance’s public-private partnership model brings together donors, developing countries, industry, civil society and academia to solve the challenges of reaching every child with vaccines no matter where they are born.

GAVI leverages expertise across a variety of sectors, including innovative financing for development, supply chain management, the development of mobile phone platforms for the collection of epidemiological data, mathematical modelling of infectious disease and health economics and policy.

Prior to joining GAVI in 2011, Dr Berkley was the founder, president and CEO of the International AIDS Vaccine Initiative (IAVI) for over a decade. His talk, ‘Harnessing the power of science research and the public and private sector: a 21st century model for international development’, is the Wellcome Trust-Cambridge Centre for Global Health Research’s inaugural lecture.

Dr Berkley’s talk will be followed with a presentation by the world-leading flu expert, Professor Derek Smith, Director of the WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases at the ̽��ֱ�� of Cambridge. There will be an opportunity for questions and answers after the talks.

̽��ֱ��evening begins at 5.30pm at the Howard Lecture Theatre, Downing College, Cambridge (map). If you would like to attend, please RSVP: http://wt-cghr-cambridge-gavi-lecture.eventbrite.com/

Professor David Dunne, Director of the Wellcome Trust-Cambridge Centre for Global Health Research and host of the lecture, said: “By partnering with globally important organisations such as the GAVI Alliance, Cambridge’s multi-disciplinary research and technology communities can have a more profound effect on international development, public health, and the lives of people in the developing world.”

“As an innovative public-private partnership, the GAVI Alliance works to harness the expertise and experience from a range of sectors to help us to improve access to lifesaving vaccines for children in developing countries,” said Dr Seth Berkley, CEO of the GAVI Alliance. “Our partners range from WHO and UNICEF to donors – including the UK government – implementing countries, vaccine manufacturers, civil society organisations, and academia.

“We have made great progress in the past decade, but the stark reality is that 22 million children born every year around the world don’t receive the immunisation they need against potentially fatal childhood illnesses. Supply chain management, improving the quality of vaccine coverage data and developing vaccines that remain highly effective outside of cold storage systems are just some of the challenges which, if they can be overcome, would have a huge positive impact on GAVI’s ability to reach more children.

“Cambridge ̽��ֱ�� has an outstanding reputation for academic research, coupled with its commitment to Africa, which makes it an ideal forum to set out the challenges and opportunities in improving access to immunisation in developing countries.”

̽��ֱ��GAVI Alliance is a public-private partnership which aims to immunise a quarter of a billion additional children in the developing world with life-saving vaccines by 2015. With GAVI support, countries are now introducing new vaccines against the primary causes of two of the biggest childhood killers in the world: pneumonia and severe diarrhoea. Together these diseases account for 30% of child deaths in low-income countries. It was established in 2000 by the Bill and Melinda Gates Foundation, the UK government and others to improve access to immunisation.

̽��ֱ��Wellcome Trust-Cambridge Centre for Global Health Research status was awarded to the ̽��ֱ�� of Cambridge in February of this year. ̽��ֱ��Centre plans to capture and capitalise on the extensive basic biomedical and health-related research capacity across many departments and research institutes in Cambridge. It will make this fully available for research capacity building and knowledge exchange partnerships with African universities and institutes, as a means of improving the health and welfare of those in low- and middle-income countries.

CEO of GAVI Alliance to give Wellcome Trust-Cambridge Centre for Global Health Research inaugural lecture

We have made great progress in the past decade, but the stark reality is that 22 million children born every year around the world don’t receive the immunisation they need.

Dr Seth Berkley, CEO of the GAVI Alliance

Harnessing the power of science research and the public and private sector

gavi_2012_olivier_asselin

Vaccinations in Ghana

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes