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.
Organisations
- MRC Unit, The Gambia, Gambia (Lead Research Organisation)
- University College London, United Kingdom (Collaboration)
- University of Cambridge (Collaboration)
- London Sch of Hygiene and Trop Medicine, United Kingdom (Collaboration)
- Kenyan Institute for Medical Research (KEMRI) (Collaboration)
- Birkbeck, University of London (Collaboration)
- Government of The Gambia (Collaboration)
- Medical Research Council (Collaboration)
People |
ORCID iD |
| Andrew Major Prentice (Principal Investigator) |
Publications
Abuga KM
(2020)
Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.
in Wellcome open research
Armitage AE
(2019)
Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants.
in Haematologica
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
Atkinson SH
(2015)
Malaria and Age Variably but Critically Control Hepcidin Throughout Childhood in Kenya.
in EBioMedicine
Atkinson SH
(2008)
Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia in West African children.
in Blood
Bah A
(2019)
Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.
in The Lancet. Global health
Bah A
(2017)
Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.
in The Journal of nutrition
Braithwaite V
(2016)
The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism
in Bone
| 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 |