An Observational Study Designed to Elucidate the Pathways by Which Inflammation Contributes to Anaemia in Sick Rural African Children From 6 Months to 36 Months

Overview

The Investigator have previously shown that hepcidin is up-regulated even by low levels of inflammation and, according to our prior stable isotope studies, is predicted to block iron absorption. In this follow-up observational study, the investigator aim to characterise the relationship between infections, acute inflammation, hepcidin and iron iron deficiency anaemia in rural African children. The Investigator will study 200 sick children (6-36 months of age) living in the rural region of West Kiang. The Investigator will: 1. Recruit 50 sick febrile children in each of 4 categories; Upper Respiratory tract infections, Lower respiratory tract infections (pneumonia), Urinary tract infections, gastroenteritis. 2. Assess iron absorption and its relationship to iron and anaemia status, inflammation, EPO, erythroferrone and hepcidin.

Aim 1: To test whether non-malarial infections increase hepcidin levels and for how long in sick children (note that the investigator exclude malaria because the investigator and others have previously examined the effect of malaria). Hypothesis 1: On day 0, 3 and 7 of acute illness, hepcidin will be higher when compared to levels in well children. On Day 14 iron absorption and hepcidin levels will have returned to baseline. Research Question 1: What affect do non-malarial infections (upper respiratory tract infections, lower respiratory tract infections, urinary tract infections and gastroenteritis) have on hepcidin levels and how long does this effect last? Aim 2: To retest our existing hepcidin threshold for discriminating iron absorbers from non-absorbers by repeating our prior ROC analysis based on a much larger sample. Hypothesis: On day 0, 3 and 7 of acute illness, iron absorption will be lower. On Day 14, iron absorption will be equivalent to iron absorption in well children. Note that the Hepcidin levels and iron absorption data obtained in this study will be compared with the results obtained from similarly aged children in IDeA Study 1 (SCC 1664). Also note that The investigator anticipate that most of the children enrolled in this study will have a base-line level of anaemia (eg Hgb\<11g/dL). Research Question: What is the relationship between hepcidin and oral iron absorption in acute illness and convalescence and how does this differ from the relationship in well children? Aim 3: To examine EPO synthesis and EPO resistance in children with acute non-malarial infections? Hypotheses: 1. Children with acute non-malaria infections will have both acute and chronic anaemia of inflammation. 2. EPO is increased during acute infection. Research Question: Is there decreased EPO synthesis and/or increased EPO resistance in children with acute non-malarial infections living in rural Gambia? Aim 4: To examine erythroferrone in children with acute non-malarial infections leaving in rural Gambia. Hypothesis: First The investigator will conduct a hypothesis-free exploratory analysis to assess whether erythroferrone behaves as predicted based upon mouse models (ie up-regulated by stress erythropoiesis and inversely related to hepcidin). The investigator additionally hypothesize that there may be a vicious cycle initiated by inflammation and then perpetuated by the consequent low levels of (iron-restricted) erythropoiesis, leading to low erythroferrone and loss of hepcidin suppression. Research Question: What is the relationship between erythroferrone, iron status, inflammation, hepcidin, EPO and CRP in anaemic and non-anaemic children living in rural Gambia? This is an observational study of 200 sick children who will be recruited at the Keneba clinic. Each child will be seen four times (at day 0, 3, 7 14). 200 subjects aged 6 -36m brought to Keneba clinic with an acute illness. 50 patients from each category: Upper respiratory tract infections (including ear, nose and throat infections), Lower respiratory tract infections, urinary tract infections and gastroenteritis.