Iron, Infection and Anemia

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Iron deficiency is one of the most pervasive of nutritional deficiencies worldwide. Children with iron deficiency anemia have retarded brain development. Low cost iron supplements are can help to overcome iron deficiency but unfortunately recent large-scale trials have revealed extensive evidence of harm especially (but not only) in malarious areas. It is assumed that all of these adverse outcomes occur because the iron feeds bacteria and other micro-organsisms. Thus there is an urgent need: a) to understand the pathways by which iron causes disease; and b) to use this knowledge to design safer modes to give iron to pregnant mothers and their infants living in infectious environments. The discovery of a hormone called hepcidin (which acts as the master regulator of iron metabolism) offers new insights into the host-pathogen battle for iron and we are using this to develop new ways to safely administer iron.

Technical Summary

Iron deficiency (ID), leading to iron deficiency anemia (IDA) and impaired neurocognitive development, remains the most pervasive nutritional deficiency worldwide. Using currently accepted criteria the prevalence rates for IDA in mothers and young children frequently exceed 50% in low-income countries. Low cost iron supplements are efficacious in combatting IDA but recent large-scale trials have revealed extensive evidence of harm especially (but not only) in malarious areas. It is assumed that all of these adverse outcomes are attributable to host-pathogen competition for iron whereby supplemental iron has favoured pathogens more rapidly than their host; a phenomenon termed the ‘iron trap’. Thus there is an urgent need: a) to understand the pathways by which provision of iron favours pathogen virulence; and b) to use this knowledge to design safer modes for preventative and therapeutic provision of iron to pregnant mothers and their infants living in infectious environments. The discovery of hepcidin, the master regulator of iron metabolism, offers new insights into the host-pathogen battle for iron and we are using this to develop new ways to safely administer iron.

Publications

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Armitage AE (2014) Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. in Proceedings of the National Academy of Sciences of the United States of America

 
Description BMGF Discovery Expert Group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact As a member of the BMGF Discovery Expert Group I influence policy regarding global health research policies.
 
Description Chairman - Strategic Advisory Board American Society of Nutrition
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
Impact Planning the ASN's future for Vision 2028
 
Description Chairmanship of NIH/NICHD/Gates Iron Week
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description HarvestPlus
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact HarvestPlus works to introduce biofortified crops with a target of reaching 1 billion people.
URL http://www.harvestplus.org/
 
Description INSPIRE
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Description Iron and Malaria Research Review
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Description Membership of National Food Fortification TaskForce
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact The Gambian National Food Fortification TaskForce is working to encourage the production and consumption of micronutrient enriched staple foods.
 
Description NIH/NICHD/Gates Technical Working Group
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description Wellcome Trust ERG 6
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Deliberates on research funding with direct health outputs
 
Description 5 Gates Grand Challenges Explorations
Amount $100,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2012 
End 01/2013
 
Description HIGH Consortium
Amount $1,832,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2013 
End 01/2016
 
Description Healthy, Birth, Growth and Development
Amount $1,718,003 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 11/2015 
End 03/2018
 
Description Infection, inflammation and hepcidin-mediated iron deficiency anaemia in African children
Amount £851,865 (GBP)
Funding ID MR/R023360/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 09/2022
 
Description Invited submission
Amount $1,781,800 (USD)
Funding ID OPP1140952 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 08/2016 
End 09/2019
 
Description Unsolicited application
Amount $330,000 (USD)
Funding ID OPP1152353 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 11/2016 
End 10/2018
 
Title Banked DNA 
Description DNA and phenotype data from multiple cohorts in Gambia and Zanzibar. 
Type Of Material Biological samples 
Year Produced 2008 
Provided To Others? Yes  
Impact Basis of collaborations and publications 
 
Title ENID Platform 
Description The Early Nutrition and Immune Development Study recruits pregnant women throughout West Kiang. 
Type Of Material Biological samples 
Year Produced 2009 
Provided To Others? Yes  
Impact THis platform is highly productive in terms of 'add-on' studies. 
 
Title Hepcidin-based diagnostic cutoffs 
Description Development of hepcidin-based diagnostic cutoffs for pregnant woman and children to identify 'safe and ready' to receive iron. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact Publications available to all 
 
Title Keneba Biobank 
Description We are collecting DNA and biological samples from 12,000+ individuals in the West Kiang region of Gambia and banking these as the basis of numerous of our research projects 
Type Of Material Biological samples 
Year Produced 2011 
Provided To Others? Yes  
Impact The materials have already contributed to many research studies and are currently proving to be a very positive influence on drawing new collaborations and research funds to our group. 
 
Title West Kiang DSS 
Description Demographic Surveilance System for West Kiang Region 
Type Of Material Biological samples 
Year Produced 2015 
Provided To Others? Yes  
Impact Forms the platform for all studies we conduct and creates novel research findings through secondary analyses. 
 
Title Submission of epigenomic data to public databases 
Description We upload all our epigenetic analyses to public databases 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Not yet known 
 
Description Gambian National Nutrition Agency (NaNA) 
Organisation Government of The Gambia
Department National Nutrition Agency (NaNA) Gambia
Country Gambia 
Sector Public 
PI Contribution We support NaNA in numerous ways, mostly related to staff training.
Collaborator Contribution Through quarterly meetings NaNA assist us with advice about Gambian Government priorities in nutrition. They also help facilitate short-term deviations from standard government policy necessary fro certain trials.
Impact The positive and cordial relationships between MRC and NaNA over many years represent a notable output.
 
Description Genes-in-action iron 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Health Services Research and Policy
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of field samples and opportunities
Collaborator Contribution Co-supervsion of PhD student
Impact None yet.
Start Year 2016
 
Description HIGH Consortium 
Organisation Medical Research Council (MRC)
Department MRC Molecular Haematology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Partnership in successful application to Gates Foundation for $1.8m to establish HIGH Consortium
Collaborator Contribution Equal intellectual contribution to the partnership
Impact Consortium just initiated. Nutrition, haematology
Start Year 2013
 
Description KEMRI-Kilifi collaboration 
Organisation Kenyan Institute for Medical Research (KEMRI)
Country Kenya 
Sector Public 
PI Contribution Collaboration by way of pooling data and analysis on iron and genetics.
Collaborator Contribution Publications in progress.
Impact Publications in progress
Start Year 2018
 
Description MillNETi collaborators 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution We will be assessing iron bioavailability from fortified millet.
Collaborator Contribution Our partners led the funding request and lead the partnership.
Impact Collaboration recently started. Outputs pending.
Start Year 2019
 
Description NIRS assessment of brain function 
Organisation Birkbeck, University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution New NIRS systems will be piloted in MRC Keneba
Collaborator Contribution Construction and implementation of NIRS instrument
Impact None yet
Start Year 2012
 
Description NIRS assessment of brain function 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution New NIRS systems will be piloted in MRC Keneba
Collaborator Contribution Construction and implementation of NIRS instrument
Impact None yet
Start Year 2012
 
Title IHAT 
Description IHAT- a novel nano-particulate form of Iron currently in late stage of testing in an RCT in rural Gambian children. 
Type Preventative Intervention - Nutrition and Chemoprevention
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2019
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The product is licensed for possible manufacture and distribution. 
URL https://clinicaltrials.gov/show/NCT02941081
 
Title KEMRes 
Description Keneba Electronic Medical Registration System 
Type Support Tool - For Medical Intervention
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2011
Development Status Under active development/distribution
Impact KEMReS forms a vital part of our research patient selection as well as providing improved care fro our patient population. 
 
Description Government health promotion activity 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact National launch of the food fortification caravan
Year(s) Of Engagement Activity 2019
 
Description ING website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact ING now has it's own website, where key news items are posted regularly.

The website is a vital point of information to ING's research activities.
Year(s) Of Engagement Activity 2012
 
Description MRC Centenary Events @ UCL 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 500 attendees across a wide range of the public plus other academics

Wider interest and knowledge of MRC activities
Year(s) Of Engagement Activity 2013
 
Description MRC Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact MRC Festival is an Annual Showcase of MRC Unit The Gambia's activities
Year(s) Of Engagement Activity 2016
 
Description MRC UCL Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact ING participated in the UCL Centenary event, targeted at the general public but also including scientists from other MRC Units and groups in London. ING contribution included a formal lecture by Prof Prentice plus stands and exhibitions highlighting our work in Keneba.

Publicity in local London area.
Year(s) Of Engagement Activity 2013
 
Description Open Day (Gambia) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Open Day in Keneba
Year(s) Of Engagement Activity 2016
 
Description Open Days 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact OpenDays
Year(s) Of Engagement Activity 2018
 
Description Open days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Open day

Continued good relations with surrounding villagers who participate in our research
Year(s) Of Engagement Activity 2007,2008,2013,2014
 
Description Podcast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Contribution to podcast

Multiple
Year(s) Of Engagement Activity 2009,2014
 
Description Public lecture 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Open Lecture to general audience including politicians

Improved profile
Year(s) Of Engagement Activity 2008,2013
 
Description Radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact BBC World Service interview

None.
Year(s) Of Engagement Activity 2009,2014
 
Description Tama - article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Article

None known
Year(s) Of Engagement Activity 2008,2014