scholarly journals Delayed iron improves iron status without altering malaria risk in severe malarial anemia

2020 ◽  
Vol 111 (5) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah E Cusick ◽  
Robert O Opoka ◽  
Andrew S Ssemata ◽  
Michael K Georgieff ◽  
Chandy C John
Keyword(s):  
Iron Deficiency ◽  
Severe Malaria ◽  
Malaria Incidence ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Malaria Risk ◽  
Antimalarial Treatment ◽  
Severe Malarial Anemia ◽  
Iron Treatment ◽  
Malarial Anemia

ABSTRACT Background WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. Objectives We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. Methods We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo–5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg–1 · d–1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. Results All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). Conclusions In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence. This trial was registered at clinicaltrials.gov as NCT01093989.

scholarly journals Malaria Incidence Does Not Differ with Immediate Compared to 28-day Delayed Iron Treatment in Children with Severe Malaria and Iron Deficiency (OR10-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Cusick ◽  
Robert Opoka ◽  
Andrew Ssemata ◽  
Michael Georgieff ◽  
Chandy John
Keyword(s):  
Iron Deficiency ◽  
Severe Malaria ◽  
Malaria Incidence ◽  
Iron Status ◽  
Iron Therapy ◽  
Zinc Protoporphyrin ◽  
Antimalarial Treatment ◽  
Group I ◽  
History Of ◽  
Malaria Episodes

Abstract Objectives We aimed to determine if delaying iron until 28 days after antimalarial treatment in children with severe malaria and iron deficiency leads to fewer subsequent clinical malaria episodes as compared to concurrent iron therapy. Methods The randomized controlled trial was conducted Ugandan children 18 mo-5 y with severe malaria [cerebral malaria (CM), n = 79; severe malarial anemia (SMA), n = 77] and healthy community children (CC, n = 83) at Mulago Hospital in Kampala, Uganda. All children with malaria received antimalarial treatment. Children with iron deficiency (defined by zinc protoporphyrin (ZPP) >= 80 µmol/mol heme) were randomized to start a 90-day course of ferrous sulfate (2 mg/kg/day) concurrently with antimalarial treatment on Day 0 (immediate group, I) or on Day 28 (delayed group, D). Incidence of malaria episodes over the 12-month follow-up period was assessed by sick-child visits to the study clinic. Malaria was defined as measured fever (T >37.5°C) plus Plasmodium falciparum on blood smear. Negative binomial regression was used to model counts of malaria episodes as a function of treatment group (I or D), controlling for age. Hazard ratios compared time to event between the I and D groups. Results All children with CM and SMA and 35 CC had high ZPP and were randomized to I or D iron. There were no differences in malaria incidence (defined with either measured fever or history of fever) with I vs. D treatment in any study group. The incidence of inpatient malaria episodes defined with history of fever was marginally statistically significant lower with D iron in the SMA group [incidence rate ratio (IRR) D/I (95% CI) = 0.38 (0.14, 1.1), P = 0.07). In the SMA group, children who received D iron tended to have a longer time to first inpatient event than children in the I group [Hazard ratio (95% CI) D/I: 0.37 (0.13, 1.1), P = 0.07]. Conclusions Delaying iron in children with severe malaria had no clear risk or benefit on subsequent malaria incidence or time-to-first episode as compared to immediate treatment. Given that previous analysis revealed that iron status was improved with delayed iron among children with SMA, the lack of difference in malaria incidence suggests that delaying iron therapy may be a safe way to improve iron status in this group. Funding Sources NIH/NICHD.

scholarly journals Prenatal Iron Deficiency and Replete Iron Status Are Associated with Adverse Birth Outcomes, but Associations Differ in Ghana and Malawi

2019 ◽  
Vol 149 (3) ◽  
pp. 513-521 ◽  
Author(s):  
Brietta M Oaks ◽  
Josh M Jorgensen ◽  
Lacey M Baldiviez ◽  
Seth Adu-Afarwuah ◽  
Ken Maleta ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Birth Outcomes ◽  
Regression Models ◽  
Iron Status ◽  
Secondary Data ◽  
Hemoglobin Concentration ◽  
Late Pregnancy ◽  
Zinc Protoporphyrin ◽  
Adverse Birth Outcomes ◽  
Soluble Transferrin Receptor

ABSTRACTBackgroundPrevious literature suggests a U-shaped relation between hemoglobin concentration and adverse birth outcomes. There is less evidence on associations between iron status and birth outcomes.ObjectiveOur objective was to determine the associations of maternal hemoglobin concentration and iron status with birth outcomes.MethodsWe conducted a secondary data analysis of data from 2 cohorts of pregnant women receiving iron-containing nutritional supplements (20–60 mg ferrous sulfate) in Ghana (n = 1137) and Malawi (n = 1243). Hemoglobin concentration and 2 markers of iron status [zinc protoporphyrin and soluble transferrin receptor (sTfR)] were measured at ≤20 weeks and 36 weeks of gestation. We used linear and Poisson regression models and birth outcomes included preterm birth (PTB), newborn stunting, low birth weight (LBW), and small-for-gestational-age.ResultsPrevalence of iron deficiency (sTfR >6.0 mg/L) at enrollment was 9% in Ghana and 20% in Malawi. In early pregnancy, iron deficiency was associated with PTB (9% compared with 17%, adjusted RR: 1.63; 95% CI: 1.14, 2.33) and stunting (15% compared with 23%, adjusted RR: 1.44; 95% CI: 1.09, 1.94) in Malawi but not Ghana, and was not associated with LBW in either country; replete iron status (sTfR <10th percentile) was associated with stunting (9% compared with 15%, adjusted RR: 1.71; 95% CI: 1.06, 2.77) in Ghana, but not PTB or LBW, and was not associated with any birth outcomes in Malawi. In late pregnancy, iron deficiency was not related to birth outcomes in either country and iron-replete status was associated with higher risk of LBW (8% compared with 16%, adjusted RR: 1.90; 95% CI: 1.17, 3.09) and stunting (6% compared with 13%, adjusted RR: 2.14; 95% CI: 1.21, 3.77) in Ghana, but was not associated with birth outcomes in Malawi.ConclusionsThe associations of low or replete iron status with birth outcomes are population specific. Research to replicate and extend these findings would be beneficial. These trials were registered at clinicaltrials.gov as NCT00970866 (Ghana) and NCT01239693 (Malawi).

scholarly journals Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 3016-3022 ◽  
Author(s):  
Florence Burté ◽  
Biobele J. Brown ◽  
Adebola E. Orimadegun ◽  
Wasiu A. Ajetunmobi ◽  
Nathaniel K. Afolabi ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Severe Malarial Anemia ◽  
Key Points ◽  
Mild Malaria ◽  
Anti Inflammatory ◽  
Childhood Malaria ◽  
Malarial Anemia

Key Points Hepcidin rises more dramatically in mild malaria than in severe malaria. Hepcidin levels are linked to inflammation, not anemia, in severe malarial anemia and cerebral malaria.

scholarly journals Effect of Maternal Iron Deficiency Anemia on the Iron Store of Newborns in Ethiopia

Anemia ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Betelihem Terefe ◽  
Asaye Birhanu ◽  
Paulos Nigussie ◽  
Aster Tsegaye
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Serum Ferritin ◽  
Complete Blood Count ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Deficiency Anemia ◽  
Iron Store ◽  
Cross Sectional ◽  
Iron Deficient

Iron deficiency anemia among pregnant women is a widespread problem in developing countries including Ethiopia, though its influence on neonatal iron status was inconsistently reported in literature. This cross-sectional study was conducted to compare hematologic profiles and iron status of newborns from mothers with different anemia status and determine correlation between maternal and neonatal hematologic profiles and iron status in Ethiopian context. We included 89 mothers and their respective newborns and performed complete blood count and assessed serum ferritin and C-reactive protein levels from blood samples collected from study participants. Maternal median hemoglobin and serum ferritin levels were 12.2 g/dL and 47.0 ng/mL, respectively. The median hemoglobin and serum ferritin levels for the newborns were 16.2 g/dL and 187.6 ng/mL, respectively. The mothers were classified into two groups based on hemoglobin and serum ferritin levels as iron deficient anemic (IDA) and nonanemic (NA) and newborns of IDA mothers had significantly lower levels of serum ferritin (P=0.017) and hemoglobin concentration (P=0.024). Besides, newborns’ ferritin and hemoglobin levels showed significant correlation with maternal hemoglobin (P=0.018;P=0.039) and ferritin (P=0.000;P=0.008) levels. We concluded that maternal IDA may have an effect on the iron stores of newborns.

scholarly journals Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia

2021 ◽  
Vol 15 ◽  
Author(s):  
Roza M. Vlasova ◽  
Qian Wang ◽  
Auriel Willette ◽  
Martin A. Styner ◽  
Gabriele R. Lubach ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Brain Development ◽  
Diffusion Tensor ◽  
Iron Status ◽  
Brain Maturation ◽  
Deficiency Anemia ◽  
Normal Brain ◽  
Brain Growth ◽  
Oxidative Energy Metabolism ◽  
Iron Treatment

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.

scholarly journals 963. Whole Blood Transcriptome Analysis Reveals Differences in Erythropoiesis and Neurologically Relevant Pathways Between Cerebral Malaria and Severe Malarial Anemia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S35-S35
Author(s):  
Srinivas Nallandhighal ◽  
Gregory Park ◽  
Yen-Yi Ho ◽  
Robert Opoka ◽  
Chandy John ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Whole Blood ◽  
Heme Oxygenase 1 ◽  
Specific Gene ◽  
Severe Malarial Anemia ◽  
Specific Gene Expression ◽  
Blood Transcriptome ◽  
Malarial Anemia

Abstract Background Plasmodium falciparum malaria can rapidly progress to severe disease that can lead to death if left untreated. Severe malaria cases commonly present as severe malarial anemia (SMA), defined in children as hemoglobin (Hb) &lt;5 g/dL with parasitemia, or as cerebral malaria (CM), which manifests as parasitemia with acute neurological deficits and has an inpatient mortality rate of ~20%. The molecular and cellular processes that lead to CM and SMA are unclear. Methods In a cross-sectional study, we compared genome-wide transcription profiles of whole blood obtained from Ugandan children with acute CM (n = 17) or SMA (n = 17) and community children without P. falciparum infection (n = 12) who were enrolled in a parent cohort study of severe malaria. We determined the relationships between gene expression, hematological indices, and plasma biomarkers, including inflammatory cytokines. Results Both CM and SMA demonstrated enrichment of dendritic cell activation, inflammatory/TLR/chemokines, monocyte, and neutrophil modules but depletion of lymphocyte modules. Neurodegenerative disease and neuroinflammation pathways were enriched in CM. Increased Nrf2 pathway gene expression corresponded with increased plasma heme oxygenase-1 and the heme catabolite bilirubin in a manner specific to children with both SMA and sickle cell disease. Reticulocyte-specific gene expression was markedly decreased in CM relative to SMA despite higher Hb levels and appropriate increases in plasma erythropoietin. Viral sensing/interferon regulatory factor (IRF) 2 module (M111) expression and plasma IP-10 levels both negatively correlated with reticulocyte-specific signatures, but only M111 expression independently predicted decreased reticulocyte-specific gene expression after controlling for leukocyte count, Hb level, parasitemia, and clinical syndrome by multiple regression. Conclusion Differences in the blood transcriptome of CM and SMA relate to neurologically relevant pathways and erythropoiesis. Erythropoietic suppression during severe malaria is more pronounced during CM versus SMA and is positively associated with IRF2 blood signatures. Future studies are needed to validate these findings. Disclosures All authors: No reported disclosures.

Iron Deficiency and Anemia: A Common Problem in Female Elite Soccer Players

2005 ◽  
Vol 15 (6) ◽  
pp. 689-694 ◽  
Author(s):  
Göran Landahl ◽  
Peter Adolfsson ◽  
Mats Börjesson ◽  
Clas Mannheimer ◽  
Stig Rödjer
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Binding Capacity ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Soccer Players ◽  
Deficiency Anemia ◽  
World Cup ◽  
National Team ◽  
Iron Binding Capacity

The objective of the study was to determine the prevalence of iron deficiency and iron deficiency anemia among elite women soccer players. Hemoglobin, serum iron, serum total iron binding capacity, and ferritin were determined in 28 female soccer players called up for the national team. Of the investigated female soccer players, 57% had iron deficiency and 29% iron deficiency anemia 6 months before the FIFA Women’s World Cup. It is concluded that iron deficiency and iron deficiency anemia is common in female soccer players at the top international level. Some might suffer from relative anemia and measurement of hemoglobin alone is not sufficient to reveal relative anemia. Regular monitoring of hemoglobin concentration and iron status is necessary to institute iron supplementation when indicated.

scholarly journals Treatment of Iron Deficiency Anemia in Orthopedic Surgery with Intravenous Iron: Efficacy and Limits

2007 ◽  
Vol 107 (6) ◽  
pp. 923-927 ◽  
Author(s):  
Oliver M. Theusinger ◽  
Pierre-François Leyvraz ◽  
Urs Schanz ◽  
Burkhardt Seifert ◽  
Donat R. Spahn
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Orthopedic Surgery ◽  
Iron Status ◽  
Intravenous Iron ◽  
Deficiency Anemia ◽  
Bonferroni Correction ◽  
Maximum Increase ◽  
Endogenous Erythropoietin ◽  
Iron Treatment

Background Preoperative anemia is frequent in patients undergoing orthopedic surgery. The purpose of this study was to assess the preoperative increase of hemoglobin in iron deficiency anemia patients treated with intravenous iron. Methods After obtaining written informed consent, 20 patients with iron deficiency anemia received 900 mg intravenous iron sucrose over 10 days starting 4 weeks before surgery. Changes of hemoglobin and iron status were measured over 4 weeks and at discharge. In the last 11 patients, endogenous erythropoietin was also measured. Data were analyzed using the Friedman test followed by pairwise Wilcoxon signed rank tests with Bonferroni correction. Results Hemoglobin increased significantly (P &lt; 0.0001) after intravenous iron treatment. Overall, the mean maximum increase was 1.0 +/- 0.6 g/dl (range, 0.2-2.2 g/dl). Ferritin increased from 78 +/- 70 to 428 +/- 191 microg/l (P = 0.0001), ferritin index decreased from 2.7 +/- 2.4 to 1.5 +/- 1.0 (P = 0.0001), and soluble transferrin receptor decreased from 4.1 +/- 2.3 mg/l to 3.7 +/- 2.3 mg/l (P = 0.049), whereas transferrin saturation (20.5 +/- 9.0 to 22.9 +/- 9.0%) and serum iron (13.3 +/- 4.6 to 13.1 +/- 4.5 microm) did not change significantly after intravenous iron treatment. Endogenous erythropoietin decreased from 261 +/- 130 pg/ml to 190 +/- 49 pg/ml 2 weeks after intravenous iron treatment (P = 0.050, not significant after Bonferroni correction). No adverse events related to intravenous iron were observed. The maximum increase of hemoglobin was observed 2 weeks after the start of intravenous iron treatment, indicating that administration of intravenous iron 2-3 weeks before surgery may be optimal. Conclusion Treatment with intravenous iron allows correcting iron deficiency anemia before elective surgery.

scholarly journals 4148 Thrombocytopenia and whole blood transfusion in children with severe falciparum malaria

2020 ◽  
Vol 4 (s1) ◽  
pp. 40-40
Author(s):  
Matthew M. Ippolito ◽  
Jean-Bertin Kabuya ◽  
Manuela Hauser ◽  
Benjamin Kussin-Shoptaw ◽  
Austin Peer ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Falciparum Malaria ◽  
Whole Blood ◽  
Hemoglobin Concentration ◽  
Rank Test ◽  
Clinical Role ◽  
Platelet Recovery ◽  
Severe Malarial Anemia ◽  
Severe Falciparum Malaria ◽  
Malarial Anemia

OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

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