Addressing the Challenges of Anaemia in the Andean Region

Online 20-21 January 2021 The Academy of Medical Sciences is the independent body in the UK representing the diversity of medical science. Our mission is to promote medical science and its translation into benefits for society. The Academy’s elected Fellows are the United Kingdom’s leading medical scientists from hospitals, academia, industry and the public service. We work with them to promote excellence, influence policy to improve health and wealth, nurture the next generation of medical researchers, link academia, industry and the NHS, seize international opportunities and encourage dialogue about the medical sciences.

This workshop is funded by the Academy, through the Global Challenges Research Fund (GCRF). Meeting Background

Low and middle income countries (LMICs) account for 89% of all anaemia-related disability. However, despite several interventions, the number of people diagnosed as anaemic rose from 25% of the world’s population between 1993-2005 to 27% by 2013.1,2 In Africa 37% of children aged between 6-14 years are anaemic largely due to 3 malnutrition and parasitic infections. Despite a high prevalence of anaemia also in Meeting Background Latin America there is little understanding of the main cause in this region.

A particular consideration regarding anaemia should be given to the Andean region. The Andean region constitutes a complex geographical area with coast, mountain and jungle and includes different countries whose capitals or important cities are located in highland settings, as Quito (Ecuador), Bogota (Colombia), San Jose (Costa Rica), Mexico DF (Mexico) among others. In Peru and Bolivia, a high proportion of the whole population lives over 3000m altitude.

Anaemia persists in the Andean region despite governmental effort to reduce the burden. Worryingly, anaemia rates have not decreased since the early 2010’s. Children living at high altitude are at a particular risk of anaemia. In Bolivia for example, despite iron supplementation over an 18-year period, the prevalence of anaemia on the whole remained unchanged whereas it increased in children living at high altitude. Iron deficiency appears to explain only a small proportion of childhood anaemia and there is an urgent need to better understand its other causes to develop appropriate and effective interventions.4

Anaemia is not only a question of iron deficiency. Haemoglobin measurements continue to be used to diagnose anaemia despite this being an unreliable marker as haemoglobin levels vary substantially with age, sex, smoking and altitude. Much of the Andean region is located over 2500 metres above sea level and rates of anaemia increase after adjustment of haemoglobin by altitude. The World Health Organization (WHO) recommends adjustment of Haemoglobin by altitude from 1000m.5 There is an on-going debate of whether or not the altitude-adjustment, recommended by the WHO, is appropriate since it has been found to overestimate anaemia rates.6,7 Despite major breakthroughs in iron metabolism, guidelines established in the late 1950s have not been updated to reflect this increase in understanding.

1. Kassebaum NJ & GBD 2013 Anemia Collaborators (2016). The Global Burden of Anemia. Hematol Oncol Clin North Am 30(2), 247-308. 2. De Benoist B et al (2008). Worldwide prevalence of anaemia 1993-2005. WHO Global database on anaemia 2008. 3. Tariku EZ et al (2019). Anemia and its associated factors among school-age children living in different climatic zones of Arba Minch Zuria 4. District, Southern Ethiopia. BMC Hematol 19:6. 4. Cordero D et al. (2019). Anemia in Bolivian children: a comparative analysis among three regions of different altitudes. Ann N Y Acad Sci 1450(1), 281–290. 5. World Health Organization (2011). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral

Nutrition Information System. 6. Sarna K, et al (2018). WHO hemoglobin thresholds for altitude increase the prevalence of anemia among Ethiopian highlanders. Am J Hematol 93(9), E229–E231.

7. Gonzales GF, Begazo J, & Alarcón-Yaquetto D (2019). Suitability of hemoglobin adjustment to define anaemia at high altitudes. Acta Hematol 19, 1-2. Meeting Background (contd.)

Increasing evidence points to intestine-microbiota metabolic crosstalk that is important for systemic iron homeostasis.8 Iron supplementation in toddlers may generate an imbalance between commensal and enteropathogenic bacteria and lead to the development of local and systematic inflammatory processes. Both of which will have 9 consequences in the development of anaemia. Furthermore, most cases of anaemia Meeting Background are mild yet it is not well understood how and whether mild anaemia affects health. Indeed, several studies have demonstrated that haemoglobin values associated with mild anaemia result in better reproductive outcomes for mother and child and improved growth in pre-school children.10

Many research questions and knowledge gaps remain to be addressed to understand the complex association/interaction between anaemia and high altitude. As evidence mounts that iron supplementation may be counterproductive, we should tread carefully in recommending a supplementation in children diagnosed with anaemia despite a lack of stunting and clinical signs of anaemia. As we now better understand anaemia it may be time to update the way anaemia is diagnosed using direct iron status marker measurements instead of indirect markers such as haemoglobin. However, research is needed to understand how feasible it is to use new measures to solve the current anaemia problem. More research is needed to establish the main cause of anaemia in the Andean region in order to tackle the problem effectively.

10. Gonzales GF, et al (2018). Correcting the cut-off point of hemoglobin at high altitude favors misclassification of anemia, erythrocytosis and excessive erythrocytosis. Am J Hematol 93(1), E12-E16. Meeting Background (Español)

Los países de bajos y medianos ingresos (LMIC) representan el 89 % de toda la discapacidad relacionada con la anemia. No obstante, a pesar de diversas intervenciones, la cantidad de personas diagnosticadas con anemia aumentó del 25 % en la población mundial entre 1993 y 2005 al 27 % para 2013.1,2, En África, el 37 % de los niños de entre 6 y 14 años tienen anemia debido, en gran parte, a desnutrición e 3

infecciones parasitarias. A pesar de una gran prevalencia de la anemia también Meeting Background presente en América Latina, no se conoce en profundidad la razón principal de su presencia en esta región.

Debe tenerse en cuenta un aspecto particular de la anemia en relación con la región Andina. La región Andina abarca un área geográfica compleja que incluye costas, montañas y selvas, y diferentes países cuyas capitales o ciudades importantes se ubican en tierras elevadas, como Quito (Ecuador), Bogotá (Colombia), San José (Costa Rica), Ciudad de México (México), entre otras. En Perú y Bolivia, una gran parte de toda la población vive por encima de los 3000 m de altitud.

La anemia persiste en la región Andina a pesar de los esfuerzos gubernamentales por reducirla. Es preocupante que los índices de anemia no hayan disminuido desde comienzos de la década de 2010. Los niños que viven en altitudes elevadas se enfrentan a un mayor riesgo de tener anemia. En Bolivia, por ejemplo, a pesar de la complementación con hierro durante un período de 18 años, la prevalencia general de la anemia se mantuvo sin cambios, aunque aumentó en los niños que viven en altitudes elevadas. La deficiencia de hierro pareciera explicar únicamente una pequeña proporción de la anemia infantil, y existe una urgente necesidad de comprender mejor sus otras causas para desarrollar intervenciones apropiadas y eficaces.4

La anemia no se trata únicamente de la deficiencia de hierro. Las mediciones de hemoglobina siguen utilizándose para diagnosticar la anemia, a pesar de ser un marcador poco confiable, dado que los niveles de hemoglobina varían sustancialmente según la edad, el género, la altitud, y en función de si la persona es o no fumadora. Gran parte de la región Andina se ubica por encima de los 2500 metros sobre el nivel del mar, y los índices de anemia aumentan luego de ajustar la hemoglobina según la altitud. La Organización Mundial de la Salud (OMS) recomienda ajustar la hemoglobina según la altitud a partir de los 1000 m.5 Existe un debate continuo sobre si el ajuste según la altitud recomendado por la OMS es apropiado, dado que se ha demostrado que sobrevolara los índices de anemia.6,7 A pesar de los grandes descubrimientos en términos del metabolismo del hierro, los lineamientos establecidos a fines de la década de 1950 no han sido actualizados para reflejar este aumento en el conocimiento.

3. Tariku EZ et al (2019). Anemia and its associated factors among school-age children living in different climatic zones of Arba Minch Zuria 4. District, Southern Ethiopia. BMC Hematol 19:6. 4. Cordero D et al. (2019). Anemia in Bolivian children: a comparative analysis among three regions of different altitudes. Ann N Y Acad Sci

1450(1), 281–290. 5. World Health Organization (2011). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. 6. Sarna K, et al (2018). WHO hemoglobin thresholds for altitude increase the prevalence of anemia among Ethiopian highlanders. Am J Hematol 93(9), E229–E231. 7. Gonzales GF, Begazo J, & Alarcón-Yaquetto D (2019). Suitability of hemoglobin adjustment to define anaemia at high altitudes. Acta Hematol 19, 1-2. Meeting Background (Español)

Una mayor cantidad de evidencia apunta a una interferencia metabólica entre el intestino y la microbiota que es importante para la homeostasis sistémica del hierro.8 La complementación con hierro en niños pequeños podría generar un desequilibrio entre las bacterias comensales y enteropatógenas, y llevar al desarrollo de procesos

inflamatorios locales y sistemáticos, que tienen consecuencias para el desarrollo de la Meeting Background anemia.9 Asimismo, la mayoría de los casos de anemia es leve, pero no se termina de comprender de qué forma, o si la anemia leve afecta la salud. De hecho, en diversos estudios se ha demostrado que los valores de hemoglobina asociados con la anemia leve dan como resultado mejores resultados reproductivos para la madre y el hijo, y mejoraron el crecimiento en niños en edad preescolar.10

Siguen sin abordarse muchas preguntas de investigación y brechas en el conocimiento para comprender la compleja relación/interacción entre la anemia y la altitud elevada. Mientras se sigue apilando evidencia de que la complementación con hierro podría ser contraproducente, deberíamos recomendar con cautela la complementación en niños diagnosticados con anemia, a pesar de una falta de signos clínicos y de retraso de la anemia. Dado que ahora comprendemos mejor la anemia, podría ser momento de actualizar la forma en que se la diagnostica mediante mediciones de marcadores directos de la condición del hierro, en vez de marcadores indirectos, como la hemoglobina. No obstante, se requieren más investigaciones para comprender cuán probable es usar nuevas mediciones para resolver el problema actual de la anemia. Asimismo, se requieren más investigaciones para establecer una causa principal de la anemia en la región Andina a fin de abordar el problema de forma eficaz.

8. Das NK, et al (2020). Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis. Cell Metab 31(1), 115–130.e6. 9. Verma S & Cherayil BJ (2017). Iron and inflammation–the gut reaction. Metallomics 9(2), 101-111. 10. Gonzales GF, et al (2018). Correcting the cut-off point of hemoglobin at high altitude favors misclassification of anemia, erythrocytosis and excessive erythrocytosis. Am J Hematol 93(1), E12-E16.

Aims of the meeting Meeting Meeting aims The main objective of this workshop is to establish an understanding of research priorities of anaemia in the Andean region and consider the role that research can play in improving this in the region. The workshop will take a particular focus on the impact of altitude on the prevalence of anaemia. In addition, the workshop will provide a platform for countries to share knowledge of what hasn’t worked and of successful approaches, which have led to an improvement. To achieve this, our aims are as follows:

• Bring together evidence from all countries in the Andean region on the current state of play on anaemia including suitability of haemoglobin adjustment, iron and gut microbiota and iron status as indicator of anaemia

• Identify country/region specific and shared research challenges and barriers to managing the issues identified.

• Provide a platform for different countries and sectors to share their research experiences, challenges and successes to allow countries to learn from one another.

• Agree on a list of research priorities and solutions to overcome the identified barriers, which can be addressed on a regional level.

El objetivo principal de este taller es comprender las prioridades de investigación sobre la anemia en la región Andina y analizar el papel que puede desempeñar la investigación en la mejora de esta en la región. El taller pondrá el foco especialmente en el impacto que tiene la altitud sobre la prevalencia de la anemia. Además, en el taller se brindará una plataforma para que los países compartan conocimiento sobre lo que no ha funcionado y sobre enfoques exitosos que han generado una mejora. Para lograrlo, nuestros objetivos son los siguientes:

• Recopilar pruebas de todos los países de la región Andina sobre el estado actual de la anemia, incluida la conveniencia del ajuste de la hemoglobina, el hierro y la microbiota intestinal, y el estado del hierro como indicador de anemia.

• Identificar barreras y desafíos de investigación específicos de la región/del país y compartidos para tratar los problemas identificados.

• Brindar una plataforma en la que diferentes países y sectores compartan sus experiencias, desafíos y éxitos de investigación para permitir que los países aprendan los unos de los otros.

• Acordar una lista de prioridades y soluciones de investigación para superar las barreras identificadas, que pueden abordarse a nivel regional. Steering committee

Co-chairs

Dr Gustavo F. Gonzales, President of National Academy of Sciences, Peru committee Steering

Professor Lucilla Poston FMedSci, Head of the Division of Women’s Health and Director of Maternal and Fetal Research Unit, School of Medicine, Kings College London, UK

Members

Dr Claudio F Lanata, Senior Researcher, National Academy of Medicine, Lima, Peru

Dr Roberto Accinelli, Director High Altitude Research Institute, Peru

Dr Cynthia Beall, Case Western Reserve University, USA

Dr Cynthia Gonzales-Castañeda, Universidad Peruana Cayetano Heredia, Peru

Cinthya Vásquez-Velasquez, National Academy of Science, Peru

Professor Dino Giussani, Professor of Developmental Cardiovascular Physiology & Medicine, University of Cambridge, UK

Dr Sophie Moore, Reader in Global Women & Children’s Health, Department of Women & Children’s Health, King’s College London, London, UK

Dr Andrew Armitage, Senior Postdoctoral Scientist, MRC Human Immunology Unit (HIU), MRC Weatherall Institute of Molecular Medicine, University of Oxford, UK

Speakers Speakers Dr Andrew Armitage, Senior Postdoctoral Scientist, MRC Human Immunology Unit (HIU), MRC Weatherall Institute of Molecular Medicine, University of Oxford, UK

Cinthya Vásquez-Velasquez, National Academy of Science, Peru

Dr Roberto Accinelli, Director High Altitude Research Institute, Peru

Dr Nicole Stoffel, Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Laboratory of Human Nutrition, ETH Zurich, Zurich, Switzerland

Professor Parmi Suchdev, Associate Director, Emory Global Health Institute Professor of Pediatrics and Global Health, Emory University

Dra Maria Elena Ugaz, UNICEF, Peru

Dr Ana Maria Aguilar Liendo, Instituto de Investigaci´on en Salud y Desarrollo, Universidad Mayor de SanAndres, La Paz, Bolivia

Day One Day Day one Participants check-in Please note all timings are given in UTC-5

09.00-09.10 Welcome and introductions

09.10-09.20 Aims, objectives and format of the Workshop Meeting co-chairs: Dr Gustavo F. Gonzales and Professor Lucilla Poston FMedSci

09.20-10.20 Keynote Session: Context setting Chair: Professor Lucilla Poston FMedSci

This session will aim to introduce the current situation for anaemia in Latin America and in particular the Andean Region. It will also provide context for the following sessions over the course of the workshop.

Each talk will be 15 mins and there will be 15 minutes after all speakers have presented for questions.

Speakers:  Mechanisms of anaemia and current understanding of iron metabolism Dr Andrew Armitage  Regional perspective: Misclassification of anaemia on High Altitude Dr Gustavo F. Gonzales and Cinthya Vásquez-Velasquez  Haemoglobin thresholds for anaemia and iron deficiency Dr Roberto Accinelli 10:20-10:30 Break

10:30-12:10 Breakout sessions

Breakout groups During this session, participants will be divided into breakout groups (4 breakout rooms of 15 participants each) and share evidence and examples on anaemia research in their respective countries with a specific focus on high altitude and Amazonian populations. This will include identifying what is known about research on anaemia, about barriers and challenges to tackle the increased prevalence of anaemia in the Andean Region.

The four breakout groups: 1) Aetiology and diagnosis of anaemia

2) Is iron supplementation an effective treatment?

3) Haemoglobin cut-off to define anaemia

4) High altitude physiology and adaptation: impact on haemoglobin

Day One Day Day one 10.30-10.45 Group Introductions Participants will each have one minute to introduce themselves and their expertise and experience.

10.45-12.05 1) Breakout group one: Aetiology and diagnosis of anaemia and iron deficiency Moderator: Dr. Andrew Armitage

Summary: Anaemia is frequently considered an iron deficiency condition, and iron interventions are typically central to anaemia control strategies. However, there are multiple causes of anaemia and not all anaemia is iron-responsive. Moreover, diagnosis of iron deficiency (ID) itself is challenging in the presence of inflammation and infection. Anaemia diagnosis is basically defined according to haemoglobin concentration, yet understanding anaemia aetiology requires interpretation of a broader array parameters. In 2016, the WHO recommended the application of the hemogram in vulnerable populations for comprehensive assessment of the haematological status of patients. The session aims to discuss the causes of both anaemia and altered iron status, and to consider approaches and challenges in diagnosis.

• What are the potential causes of anaemia, and how might these be differentiated diagnostically? • What are current challenges associated with assessment of iron status? • How can recent insights into iron biology influence approaches to anaemia control strategies?

2) Breakout group two: Is iron supplementation a safe and effective treatment in this population? Moderator: Dr. Claudio Lanata

Summary: Iron supplementation is the universal treatment for the condition of anaemia. This metal is indispensable for the development and biological functionality of cells and tissues. However, it has been discussed that this element has a high inflammatory and oxidizing power, which would generate various side effects. In the case of the gut microbiome, recent studies show that it can present a deregulation of the same or that it interacts negatively with pharmacological treatments. The objective of this session is to discuss the application of this measure as a universal treatment, and to correlate its cost-benefit on different populations.

• Is providing non hem-iron a risky intervention to children<2 years of age? • What is the effect of non-hem or hem-iron on gut microbiota? • Trade off between hem vs non-hem iron supplementation in young children: absorption vs potential side effects in non-malaria endemic regions. • Safe and effective iron supplementation schemes in young children in LMIC.

Day One Day Day one 11.00-12.05 3) Breakout group three: Haemoglobin cut-off to define anaemia in low and high altitude countries Moderator: Professor Max Gassmann

Summary: The cut-off points and thresholds for the diagnosis of anaemia have long been arbitrarily set. These points have not been reformulated with the new scientific knowledge about iron homeostasis and iron fine-tuning. The goal of this session will be to reformulate knowledge to help understand these thresholds and consider whether they are applied correctly.

• What is the biological/physiological explanation of the current haemoglobin threshold for anaemia diagnosis? • What would be the pros and cons of changing the current haemoglobin threshold for anaemia diagnosis, including the impact on the governmental policies and strategies to fight anaemia? • What new biomarkers would be suitable for a better anaemia diagnosis?

4) Breakout group four: High altitude physiology and adaptation: impact on haemoglobin Moderator: Dr. Cynthia Beall

The oxygen and iron homeostasis pathways respond to the stress of acute or chronic high-altitude hypoxia in ways that facilitate a marked increase in hemoglobin concentration in visitors and in indigenous populations in some parts of the world, but, not all. The indigenous populations of the Andean, Asian, and East African plateaus have adapted successfully over thousands of years, yet the outcomes with respect to hemoglobin concentration and iron metabolism are different. How can we compare and contrast the genomes and responses of acutely exposed individuals with those of the three highland populations to inform our understanding of anemia and nutritional status at high altitudes.

• The physiology of the oxygen homeostasis and iron homeostasis pathways relevant to the healthy concentration of hemoglobin concentration. • What do we know about the relationship between hemoglobin concentration and indicators of good health and function at high altitude? • What do we need to learn to understand the How and Why of the differences in oxygen and iron homeostasis among the various highland populations?

12.05-12.10 Presentation Development

12.10-12.20 Daily wrap up Meeting co-chairs: Professor Lucilla Poston FMedSci, Dr Gustavo F. Gonzales

Day Two Day Day two 09.00-09.05 Participants check-in Please note all timings are given in UTC-5

09.05-10.05 Breakout Group Presentations and group discussion Session Chair: Professor Dino Giussani

Speakers: Group 1: Aetiology and diagnosis of anaemia and iron deficiency (10 mins) 5 min discussions

Group 2: Is iron supplementation a safe and effective treatment in this population? (10 mins) 5 min discussions

Group 3: Haemoglobin cut-off to define anaemia in low and high altitude countries (10 mins) 5 min discussions

Group 4: High altitude physiology and adaptation: impact on haemoglobin (10 mins) 5 min discussions

10.05-10.45 Moving forward to identify appropriate markers and treatments Session Chair: Dr. Roberto Accinelli

The panellists will give short talks (10 mins) on examples of research, which is addressing anaemia in the Andean region/high altitude.

They will cover the problem that the research sought to address, what has worked, what have been the challenges, methods for achieving impact, and any follow up activities.

• Professor Parmi Suchdev, Emory Global Health Institute • o Practical Actions to Improve Anemia Assessment in the Andean Region • Dr Nicole Stoffel, ETH Zurich • Dr Ana Maria Aguilar, Universidad Mayor de San Andrés • Dr Maria Elena Ugaz, UNICEF

10.45-11.05 Q&A/panel discussion

11.05-11.15 Break

Day Two Day Day two

11.15-11.55 Group discussion (40 mins) Chaired by: Dr Gustavo F. Gonzales

Following the morning’s presentations, participants will have the opportunity to discuss all of the evidence, challenges and opportunities highlighted, including priorities and next steps. This includes:

 Actions achievable in the short term (3-12 months) to address the identified challenges or barriers to tackling the high prevalence of anaemia in the Andean region  Actions achievable in the longer term (1-3 years)  Collaboration opportunities locally, regionally and internationally to put these actions into practice

Session Outcome The output from this session will be up to seven common research areas

11.55-12.10 Conclusions and Wrap Up Dr Gustavo F. Gonzales and Professor Dino Giussani Co-chair biographies

Dr Gustavo F. Gonzales chair chair biographies

President of National Academy of Sciences, Peru - Co

Biography

Dr. Gustavo F. Gonzales is Professor of the Faculty of Sciences and Philosophy of the Universidad Peruana Cayetano Heredia with a wide and recognized scientific career nationally and internationally since 1977 to the present day. Physician and biologist by profession is the first Doctor of Sciences of the Peruvian University Cayetano Heredia (1985) and also holds a Doctor degree in Medicine (1999) with a post-doctorate at Monash University in Melbourne, Australia and is a Member of two Academies in Peru, the National Academy of Medicine and the National Academy of Sciences. During his 40 years of scientific life, he has devoted to the research in reproductive endocrinology in the populations living at high altitudes- In Peru, 30% of the population resides at altitudes over 2000 m achieving great contributions to society. His studies on maternal and child health have allowed to know the negative effect of elevated levels of maternal hemoglobin on perinatal and maternal health. This elevated level of hemoglobin affects negatively the birthweight. Tis negative effect is potentiated when mothers are using kitchens with biomass fuel for cooking. Their studies also demonstrate that the threshold of hemoglobin to define anemia should not be adjusted in populations living at high altitude. He demonstrates that Hb adjustment increase anaemia prevalence in populations living at high altitude but they are iron sufficient. In the field of adaptation to high altitude (hypoxia), he has developed a new theory to explain the lack of adaptation to high altitude and that involves the endocrine system and that has been corroborated with the genome studies of the native at high-altitude.

He is currently Treasurer of the National Academy of Medicine, and is President of the National Academy of Sciences. He is an Honorary Doctorate from the Universidad Privada Los Andes, in Huancayo and Ricardo Palma University and is Honorary Professor at Antenor Orrego University in Trujillo at the North of Peru. He is also Honorary Professor at the Universidad Nacional del Altiplano (Puno, Peru) in the Southern Highlands. He was during 20 years coordinator in Peru of the Collaborative Center of the Human Reproduction Program of the World Health Organization (WHO). He is also a principal investigator in Peru of the Training Program and Research in Environmental and Occupational Health (ITREOH) (NIH Research Grant #5-D43TW005746-04). Currently is principal investigator of the GEOHealth (Global Environmental and Occupational Health) hub grant centered in Peru and supported by the NIH, USA

Dr. Gonzales is author of 349 scientific publications including 12 books and 23 book chapters. He has received 75 awards/recognitions between nationals and internationals during his scientific career, including the Esteban Campodónico Prize in 2002, which supports the worth of his research work for the benefit of society. He is a referee of 50 international journals and has been an international master's and doctoral thesis jury in Colombia, Mexico and South Africa. He has advised more than 36 bachelor's theses, 21 master's theses and 8 doctoral theses underpinned and approved. Co-chair biographies

Professor Lucilla Poston FMedSci chair chair biographies Head of the Division of Women’s Health and Director of -

Maternal and Fetal Research Unit, School of Medicine, Kings Co College London, UK

Biography

Professor Poston graduated in Physiology from University College London, and undertook her PhD at King’s College London. She was appointed to her present position as Tommy’s the Baby Charity Chair of Maternal and Fetal Health in 2005. Her particular research interests include nutrition in pregnancy, pre-eclampsia and developmental origins of disease. Professor Poston is an honorary Fellow of the Royal College of Obstetricians and Gynaecologists, an NIHR Senior Investigator (UK) and Fellow of the Academy of Medical Sciences (UK). She has published more than 250 original research papers. Steering Committee biographies

Cinthya Vásquez-Velasquez

National Academy of Science, Peru Steering Committee Committee Steering biographies Biography

Biologist, with finished studies of Master of Science with a major in Physiology. Researcher of the Laboratory of Endocrinology and Reproduction at Universidad Peruana Cayetano Heredia. Member of the High Altitude Research Institute. I have participated and coordinated different studies with aim in haemathology at sea level and high altitude, and Public and Environmental Health, jointly with Peruvian universities as Universidad Nacional de San Antonio Abad del Cusco, and internationally with Tulane and Emory University. I have published several papers that address the evaluation of haemoglobin and anemia diagnosis in adults and vulnerable groups as children and pregnant women.

Professor Dino Giussani

Professor of Developmental Cardiovascular Physiology & Medicine, University of Cambridge, UK

Biography

Dino is The Professor of Developmental Cardiovascular Physiology & Medicine at the University of Cambridge. He also holds a Professorial Fellowship at Gonville & Caius College in Cambridge, where he is Director of Studies in Medicine. His current programmes of research use an integrative approach at the whole animal, isolated organ, cellular and molecular levels to determine the role of fetal oxygenation and reactive oxygen species in cardiovascular development, and in setting an increased risk of cardiovascular disease in later life and across generations. Professor Giussani is the current President of The Fetal & Neonatal Physiological Society. He has secured over £17 M in grant funding, published over to 210 full papers and his research has won 35 international prizes including: The Lister Institute Prize, The Royal Society Wolfson Research Merit Award, the Nick Hales Award from the International DoHAD Society and the GL Brown Prize Lecture from The UK Physiological Society. He has served as Reviewing Editor for The Journal of Physiology, Section Editor for Pediatric Research and for the American Journal of Physiology. In 2017 and 2018, respectively, he was awarded honorary Fellowships by distinction from The Royal College of Obstetrics & Gynaecology (FRCOG) and the Academy of Sciences of Latin America (ACAL) in recognition of the contribution of his research to the wellbeing of women and their children. Steering Committee biographies

Dr Claudio F Lanata

Senior Researcher, National Academy of Medicine, Lima,

Peru Steering Committee Committee Steering biographies Biography

I have a large experience in conducting many clinical trials in vaccines in Peru, in a continuous way since 1984. During my fellowship I started the first large typhoid vaccine trial in school children in Santiago, Chile, enrolling 80,000 subjects. The trials done in Peru has ranged from few hundred subjects to a large cholera vaccine trial which was terminated because absence of disease after immunization in the south of Peru, where 92,000 children and adults were randomized in a double-blind, placebo-controlled trial, and given two oral vaccine doses in a two months’ window. As part of the multicentre trial of the GSK rotavirus vaccine, I was the principal investigator coordinating 16 study clinics covering most of peri-urban Lima where 12,000 infants were enrolled in a 5 months’ period at 2 months of age. I successfully meet all enrolment requirements in all my trials, even facing harsh media conditions. I have had several audit visits by sponsors and Peruvian regulatory agency and one by the European Medicines Agency, all with excellent results (compliance award by GSK, EMA inspection with only one minor observation). We are now committed to help the development of safe and effective vaccines for SARS-CoV-2, seriously affecting Peru and the world.

Dr Roberto Accinelli

Director High Altitude Research Institute, Peru

Biography Steering Committee biographies

Dr Cynthia Beall

Case Western Reserve University, USA Steering Committee Committee Steering biographies Biography

Dr. Beall is a biological anthropologist whose research focuses on human adaptation to high- altitude hypoxia, particularly the different patterns of adaptation exhibited by Andean, Tibetan and East African highlanders. Her current research deals with the genetics of adaptive traits and evidence for natural selection, with the role of nitric oxide in oxygen delivery at high altitude. Dr. Beall is a member of the U.S. National Academy of Sciences, American Philosophical Society, and the American Academy of Arts and Sciences.

Dr Cynthia Gonzales-Castañeda

Universidad Peruana Cayetano Heredia, Peru

Biography

Cynthia Gonzales, Ph.D., is a post-doctoral fellow at Universidad Peruana Cayetano Heredia. She was granted her Ph.D. from Monash University, in Australia in 2014, and her M.Sc. from Universidad Peruana Cayetano Heredia in 2009, where she specialised in the area of human physiology. A research scientist, Dr. Gonzales has worked for more than 15 years in the areas of endocrinology and human physiology, working on the impact of environmental health factors on human wellbeing leading to the publication of 16 scientific articles and several book chapters, four awards and an honorary mention. She has trained graduate and undergraduate students in the development of their research proposals and experimental designs, and has supervised several thesis projects in the areas of human reproduction and endocrinology. As an academic lecturer, she has worked with students from the School of Medicine and from the Faculty of Science and Philosophy, where she has developed, created and delivered lectures, mainly in the area of human physiology. Steering Committee biographies

Dr Sophie Moore

Reader in Global Women & Children’s Health, Department of Women & Children’s Health, King’s College London,

London, UK Steering Committee Committee Steering biographies Biography

Sophie Moore is a Reader in Global Women and Children's Health in the Department of Women & Children's Health, an Honorary Associate Professor at the London School of Hygiene and Tropical Medicine (LSHTM) and an Honorary Senior Research Fellow at the MRC Unit The Gambia (MRCG). Her research focuses on the nutritional regulation of ‘healthy’ fetal and infant growth, incorporating infant immune and brain development as outcomes, and on the mechanisms through which maternal, infant and childhood nutrition may influence development and later health. Much of her current research is based at MRCG, but with implications for nutritional vulnerabilities globally. Sophie has recently been awarded a Wellcome Trust Senior Research Fellowship to investigate micronutrient interventions to improve infant neurocognitive development and growth in early infancy.

Dr Andrew Armitage

Senior Postdoctoral Scientist, MRC Human Immunology Unit (HIU), MRC Weatherall Institute of Molecular Medicine, University of Oxford, UK

Biography

Dr. Andrew Armitage is a Senior Postdoctoral Scientist from the MRC Human Immunology Unit (HIU) at the MRC Weatherall Institute of Molecular Medicine, University of Oxford. After completing an undergraduate degree in Biochemistry in Oxford, he carried out his DPhil (2004- 2008) with Dr. Astrid Iversen and Prof. Sir Andrew McMichael investigating the involvement of APOBEC3 antiviral restriction factors in HIV pathogenesis. Since 2008, he has worked with Prof. Hal Drakesmith on control of systemic iron homeostasis and its implications, particularly in a global health context. This has included several projects carried out in collaboration with the group of Prof. Andrew Prentice (MRC The Gambia Unit at LSHTM). His research centres around understanding the regulation of the iron regulatory hormone hepcidin, and its relationships with anaemias, infection pathogenesis and immune function. Through collaboration with Dr. Sant- Rayn Pasricha (WEHI, Melbourne, Australia) and Dr. Jena Hamadani (icddr,b. Dhaka, Bangladesh), he is currently investigating how nutritional iron interventions influence immune development and vaccine responses in infants participants of the BRISC iron intervention trial in Bangladesh. Breakout group chairs

Max Gassmann

Institute of Veterinary Physiology and Zurich Center for

Integrative Human Physiology (ZIHP), University of Zurich, Breakout group chairs group Breakout Switzerland

Biography

Max Gassmann is a trained Swiss veterinarian with Peruvian roots. He is full professor of Veterinary Physiology and director of the institute, as well as chairman of the Zurich Center of Integrative Human Physiology (ZIHP), both institutions located at the University of Zurich. He graduated in Zurich before moving as a postdoctoral fellow to Stanford University Medical School were he joint the team of Prof. Paul Berg (Nobel Prize Laureate) for three years. Back in Zurich he first was lecturer at the Institute of Human Physiology before heading the one in the Veterinary Faculty. Prof. Gassmann work focuses mainly on hypoxia and erythropoietin (Epo) in men since 1992. He is member of the Leopoldina National Academy of Science, Faculty of 1000 (F1000), Founding Member and Member of the Editorial Board of the newly established Journal “HYPOXIA” and has a standing visiting professorship at the Medical Faculty of the Universidad Peruana Cayetano Heredia (UPCH) in Lima, Peru. Moreover, he is corresponding member of the National Academy of Sciences of Peru and Bolivia as well as member of the Swiss Academy of Medical Sciences. Speaker biographies

Dr Nicole Stoffel

Department of Health Sciences and Technology, Institute of

Food, Nutrition and Health, Laboratory of Human Nutrition, Speaker biographies Speaker ETH Zurich, Zurich, Switzerland

Biography

Dr. Nicole Stoffel received her BSc and MSc degrees in Pharmaceutical Sciences from ETH Zurich, Switzerland and completed her PhD in the Laboratory of Human Nutrition at ETH Zurich. She is currently a Postdoctoral Fellow at the Laboratory of Human Nutrition at ETH Zurich. Dr. Stoffel was awarded the Swiss Foundation for Nutrition Research 2020 for her landmark publications on oral iron supplementation in Lancet Hematology 2017 and in Haematologica 2019. She received the ETH Medal for her outstanding Doctoral thesis in 2018. Her current research interests are optimizing oral iron supplementation regimens in pregnant women and in young infants, the effects of obesity on iron metabolism and investigating the effects of iron deficiency anemia on vaccine response.

Parmi S. Suchdev, MD, MPH

Associate Director, Emory Global Health Institute Professor of Pediatrics and Global Health, Emory University

Biography

Dr. Suchdev is Associate Director of the Emory Global Health Institute and holds faculty appointments in the Department of Pediatrics, Hubert Department of Global Health, and Laney Graduate School. Dr. Suchdev completed the CDC Epidemic Intelligence Service fellowship before joining Emory faculty in 2007. He is a practicing Pediatrician and cares for hospitalized patients at Children's Healthcare of Atlanta.

Dr. Suchdev’s research focuses on micronutrient malnutrition, in particular the safety and effectiveness of home fortification programs, as well as the effects of infection/inflammation on nutrition biomarkers. He has written over 100 papers on this topic, which have contributed to the formulation of global nutrition policy. Dr. Suchdev also has a passion for global health education and has established curricula that have been implemented at multiple training programs across the U.S. He is immediate past-Chair of the American Academy of Pediatrics Section on Global Health. Speaker biographies

Dra Maria Elena Ugaz

UNICEF, Peru Speaker biographies Speaker

Biography

Ana Maria Aguilar Liendo

Docente investigadora del Instituto de Investigación en Salud y Desarrollo - Facultad de Medicina . Universidad Mayor de San Andrés Member of the Academia Boliviana de Medicina

Biography Breakout group 1: Aetiology and diagnosis

of anaemia Breakout Groups Breakout

Chair: Dr. Andrew Secretariat: Fern Brookes Facilitator: Kate Clare Professor Parmi Suchdev Armitage International Policy Officer, Vivari Communications, UK Emory Global Health University of Oxford, Academy of Medical Institute, US UK Sciences, UK

Amy Anderson Dr Angela Flynn Prof Mairead Kiely Professor Sarah Atkinson Department of Anthropology, Department of Women and School of Food and KEMRI-Wellcome Trust University of California Santa Children’s Health, King’s Nutritional Sciences, Research Programme and Barbara, US College London, UK University College Cork Department of Paediatrics, University of Oxford, UK

Dr Yibby Forero Torres Dr César V. Munayco Professor Manuel Dr Elaine McCarthy Coordinadora de Nutrición General Directorate of Olivares Lecturer in Nutrition, School del Instituto Nacional de Epidemiology, Ministry of Institute of Nutrition and of Food and Nutritional Salud de Colombia, Colombia Health. Lima Peru Food Technology (Retired in Sciences, University College 2017), Chile Cork, Ireland Independent consultant

Professor Carlos Alberto Dra Alejandra Nunez de la Dr. Dante Chumacero Del Dr Diego Gaitán Delgado Bocanegra Mora Castillo Colombia Associate Professor of Universidad Veracruzana, Bolivia Paediatrics, Universidad México Nacional Mayor de San Marcos (UNMSM) and Instituto Nacional de Salud del Niño (INSN), Lima Breakout group 2: Is iron supplementation an

effective treatment? Breakout groups Breakout

Chair: Dr. Claudio Lanata Secretariat: Claire Gorby Facilitator: Marsha Dr Sophie Moore National Academy of Policy Intern, Raynes Kings College London, UK Medicine, Peru Academy of Medical Vivari Communications Sciences, UK

Dr Nicole Stoffel Dra Maria Elena Ugaz Dr Ana Maria Aguilar Lidia Sofía Caballero Department of Health UNICEF, Peru Liendo Universidad Nacional del Sciences and Technology, Instituto de Investigaci´on Altiplano Puno Institute of Food, Nutrition en Salud y Desarrollo, E.P. Nutrición Humana and Health, Laboratory of Universidad Mayor de Dpto. Básicas Human Nutrition, ETH SanAndres, La Paz, Bolivia Fisiología de la Nutrición Zurich, Zurich, Switzerland

Hilary Creed-Kanashiro, Dr Nelly Zavaleta Professor Gustavo Cediel Professor Mary E. Penny MPhil Instituto de Investigación University of Antioquia | Instituto de Investigación Nutritionist, Senior Nutricional, Peru UdeA · Escuela de Nutrición Nutricional Av La Molina Researcher, Instituto de y Dietética, Colombia 1885, La Molina, Lima 12, Investigación Nutricional, Peru Peru

Dr Rosario Bartolini Dr Achsah Dorsey Dr. Ricardo Amaru Lucana Dr Wilma B Freire Instituto de Investigación Assistant Professor, Bolivia Universidad San Francisco de Nutricional | IIN · Aspectos Department of Quito, Quito, Ecuador sociales y culturales Anthropology,University of vinculados a nutrición, Peru Massachusetts, Amherst, US Breakout group 3: Haemoglobin cut-off to define

anaemia in low and high altitude countries Breakout Groups Breakout

Chair: Professor Max Secretariat: Alex Hulme Facilitator: Hayley Kane Professor Dino Giussani Gassmann Head of International, Vivari Communications, UK Professor of Developmental Institute of Veterinary Academy of Medical Cardiovascular Physiology & Physiology and Zurich Center Sciences, UK Medicine, University of for Integrative Human Cambridge, UK Physiology, University of Zurich, Switzerland

Dr William Checkley Wilfredo Villamonte Jose Begazo Dr Miguel Dávila Director of a Five City Project Calanche Dr. En Ciencias de la Salud, Organización Panamericana on Health in Peru Centro Multidisciplinario de Magister en Ciencias de la de la Salud, Lima, Investigación en Medicina Nutrición, Licenciado en Perú/PAHO Peru Materno Perinatal de Altura Nutrición Humana, Peru Universidad Andina del Cusco

Juan Pablo Aparco Balboa Dr Virginia Abello Polo Professor Francisco Dr Jose L San Miguel Centro Nacional de Facultad de Medicina, Mardones Instituto Boliviano de Alimentación y Nutrición, Fundación Universitaria de retired full professor of Public Biología de Altura, Facultad Instituto Nacional de Salud, Ciencias de la Salud, Bogotá, Health at the Pontificia de Medicina, Universidad Lima, Perú. Fundación Universitaria de Universidad Católica de Chlle Mayor de San Andrés, P.O. Ciencias de la Salud, Bogotá Box 641 La Paz, Bolivia.

Andrea Sosa Moreno University of Michigan Breakout group 4: High altitude physiology

and adaptation: impact on haemoglobin Breakout Groups Breakout

Chair: Dr. Cynthia Beall Secretariat: Hayley Carr Facilitator: Jack Clare Dr Roberto Accinelli Case Western Reserve Policy Intern, Vivari Communications Director, High Altitude University, USA Academy of Medical Research Institute, Peru Sciences, UK

Dr Cynthia Gonzales- Cinthya Vásquez- Dr Samuel Verges Dr Tatum Simonson Castañeda Velasquez Hypoxia Physiopathology Assistant Professor, John B. Universidad Peruana National Academy of laboratory, INSERM, West Endowed Chair in Cayetano Heredia, Peru Science, Peru Grenoble Alpes University, Respiratory Physiology Grenoble, France Division of Pulmonary, University of California, San Diego, USA

Dr Martina Muckenthaler Professor Miguel Angel Professor Heimo Germany Méndez Silva Mairbäurl Universidad San Francisco de Translational Lung Research Quito Center Heidelberg, German Center for Lung Research, University Hospital Heidelberg Academy of Medical Sciences 41 Portland Place London W1B 1QH

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