<p>The interaction between nutritional status and malaria disease is complex and often controversial. Nutritional deficiencies (macro- or micro-nutrient) are thought to lead to malnutrition with subsequent susceptibility to malaria infection. On the other hand severe malaria or repeated malaria infections lead to malnutrition. While the cause and effect are difficult to attribute, micronutrient deficiencies such as iron deficiency and malaria infection often co-exist and show complex interactions leading to mutually reinforced detrimental clinical effects.</p><p>That iron deficiency has adverse effects on human health is widely recognized. Iron plays a crucial role in processes of growth and cell division and in the transport of oxygen throughout the body. It is also important for the proliferation of cells of the immune system as well as for microorganisms including the malaria parasite. Iron deficiency results in a decrease in hemoglobin concentrations and subsequent anemia. However, the etiology of anemia is multi-factorial and may be affected, in addition, by several factors including malaria and host factors, especially hemoglobinopathies such as alpha-thalassemia and sickle cell trait. These hemoglobinopathies are also common in malaria endemic areas.</p><p>In this thesis, we have investigated the relationship between nutritional status, immunity, hemoglobinopathies and <i>falciparum</i> malaria in a cohort of children less than 8 years old living on the coast of Kenya. We have found that malaria was associated with malnutrition in an age-dependent fashion. Malaria was associated with subsequent underweight or stunting in children under the age of 2 years, but this effect was not there in older children. Also, we observed that iron deficiency was associated with protection of children against clinical malaria. Children who were iron deficient had a lower incidence of malaria episodes as compared to those who were iron replete.</p><p>While studies on the effects of single micronutrient deficiencies on components of the immune system are difficult to design and interpret, there is ample evidence that micronutrient deficiencies, in general, affect all components of immunity. In line with this, we found that nutritional iron status was associated with certain malaria-specific immunoglobulins and interleukin-4 mRNA levels. Iron deficient children had lower levels of malaria-specific IgG2 and IgG4 but higher expression levels of IL-4 mRNA as compared to the iron replete children. Finally, we observed a tendency towards a higher prevalence of iron deficiency in children carrying either alpha-thalassemia or sickle cell trait.</p>

The interaction between nutritional status and malaria disease is complex and often controversial. Nutritional deficiencies (macro- or micro-nutrient) are thought to lead to malnutrition with subsequent susceptibility to malaria infection. On the other hand severe malaria or repeated malaria infections lead to malnutrition. While the cause and effect are difficult to attribute, micronutrient deficiencies such as iron deficiency and malaria infection often co-exist and show complex interactions leading to mutually reinforced detrimental clinical effects. That iron deficiency has adverse effects on human health is widely recognized. Iron plays a crucial role in processes of growth and cell division and in the transport of oxygen throughout the body. It is also important for the proliferation of cells of the immune system as well as for microorganisms including the malaria parasite. Iron deficiency results in a decrease in hemoglobin concentrations and subsequent anemia. However, the etiology of anemia is multi-factorial and may be affected, in addition, by several factors including malaria and host factors, especially hemoglobinopathies such as alpha-thalassemia and sickle cell trait. These hemoglobinopathies are also common in malaria endemic areas. In this thesis, we have investigated the relationship between nutritional status, immunity, hemoglobinopathies and falciparum malaria in a cohort of children less than 8 years old living on the coast of Kenya. We have found that malaria was associated with malnutrition in an age-dependent fashion. Malaria was associated with subsequent underweight or stunting in children under the age of 2 years, but this effect was not there in older children. Also, we observed that iron deficiency was associated with protection of children against clinical malaria. Children who were iron deficient had a lower incidence of malaria episodes as compared to those who were iron replete. While studies on the effects of single micronutrient deficiencies on components of the immune system are difficult to design and interpret, there is ample evidence that micronutrient deficiencies, in general, affect all components of immunity. In line with this, we found that nutritional iron status was associated with certain malaria-specific immunoglobulins and interleukin-4 mRNA levels. Iron deficient children had lower levels of malaria-specific IgG2 and IgG4 but higher expression levels of IL-4 mRNA as compared to the iron replete children. Finally, we observed a tendency towards a higher prevalence of iron deficiency in children carrying either alpha-thalassemia or sickle cell trait.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 69-79).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

The objectives of the present study in rural Nepali pregnant women living in the terai were: 1) to identify the risk factors of severe anemia and investigate whether risk factors for anemia without iron deficiency, iron deficiency without anemia and iron deficiency anemia (IDA) were different; 2) to examine the effect of vitamin A supplementation, alone or combined with iron, on hemoglobin (Hb) and soluble transferrin receptor (sTfR); and 3) to identify the risk factors of low birth weight (LBW) and preterm delivery, focusing on maternal Hb concentrations. The prevalence of severe anemia (Hb < 8.0 g/dl) in this population (n = 3531) was 4.2% and that of iron deficiency was 31%. Logistic regression analyses indicated that risk factors of severe anemia included hookworm infestation, impaired dark adaptation, lack of iron supplement intake, a diet low in heme iron and malnutrition manifested by thinness and short stature. These same factors differed among non-iron-deficient anemic, iron deficient non-anemic, and iron-deficient anemic pregnant women. We found a significant positive correlation between Hb and retinol concentrations (Pearson r = 0.212, P < 0.0001) and one fourth of our anemic subjects were also vitamin A deficient. There was no evidence that vitamin A alone significantly increased Hb and decreased the prevalence of anemia (n = 498). However, vitamin A, when given together with iron, had an added beneficial effect on Hb but not sTfR. In addition, women with initially compromised iron status benefited more from iron and vitamin A supplementation. The prevalence of LBW and preterm delivery was 22% and 20%, respectively (n = 915). There was an increased risk of LBW associated with short stature, thinness and impaired dark adaptation. The association between Hb measured during the second trimester and risk of LBW had a U-shaped distribution, with risk increasing significantly with Hb < 8.0 g/dl. Based on our findings, we recommend that Hb is evaluated during the second trimester as an indicator of increased LBW risk. While vitamin A supplementation to all pregnant women is recommended, routine supplementation of iron and deworming during pregnancy are essential.

The World Health Organization (WHO) states that iron deficiency (ID) is the preeminent global micronutrient deficiency. Maternal ID is linked to cardiovascular disease and hypertension in offspring, and yet the impact of ID on the kidney is not known. We characterized the impact of ID on circulating and tissue levels of iron and renal function. Seven and ten week old male and female Wistar rats were fed either control (270ppm) or low iron (3ppm) diet for ten weeks. Total, non-heme and heme iron levels in liver, kidney cortex and kidney medulla were measured following the dietary period. Hematocrit decreased most in males regardless of age (Male 7-17wk: 47%→ 31%; 10-20wk: 47%→ 33.5%; Female 7-17wk: 47%→ 34%; 10-20wk: 47%→ 39%). Dietary ID markedly decreased liver and kidney cortex non-heme iron in both males and females (Female: liver-178±25 to 21±7 ppm; kidney cortex-51±9 ppm to 10±1 ppm; Male: liver-102±18 ppm to 11±1 ppm; kidney cortex 36±14 to 15±8 ppm). In contrast, non-heme iron in the kidney medulla was not significantly decreased Secondly, in order to determine the impact of ID on renal function, blood pressure was monitored using radio-telemetry starting at six weeks of age (~175g body weight). Dietary salt challenge (5 days Low5 days HighNormal) was administered to all animals (n=16) starting at eight weeks of age. At ten weeks rats were assigned to either control (225pm) or low (3ppm) iron diet. Dietary salt challenge was repeated at 13 and 18 weeks of age respectively. Despite significant lowering of hematocrit (Control 45%  Low iron 38.6%) hemodynamic changes were minimal, in that, although blood pressure was lowered following ten weeks of dietary iron restriction, blood pressure did not change in response to dietary salt (Control MAP:105.0 ± 2.5mmHg; ID MAP:100.6 ± 3.2mmHg ). Collectively the tissue and functional analyses demonstrate that the body adapts to lowering of tissue iron supply with ID. The relative sparing of non-heme iron in the kidney medulla suggests that iron in this region of the kidney may be spared because of its importance in the systems responsible for regulating fluid and sodium balance. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2007-07-18 12:00:09.853

Maternal and fetal stressors during development can permanently alter various physiological functions and impact long-term health. These alterations are said to be programmed because they persist long after the original insult. Current evidence indicates that iron deficiency (ID) during pregnancy can induce a host of long-term programming effects, including cardiovascular complications and behavioural deficits. Despite the relevance of ID as a model of developmental programming, these effects have not been extensively studied. The purpose of the present series of experiments was to develop a model of maternal ID throughout pregnancy to study its long-term cardiovascular and behavioural consequences in neonatal and adult offspring. Female rats were fed either a low iron diet (3 mg/kg or 10 mg/kg Fe) or a control diet (> 225 mg/kg Fe) prior to and throughout gestation. At birth, all dams were fed a control diet (270 mg/kg Fe). This treatment caused altered growth trajectories which persisted in adulthood. Adult perinatal ID (PID) offspring, despite showing no signs of anemia at that time, had persistent elevations in arterial pressure (AP), as well as enhanced responsiveness of AP to high and low sodium intake. These animals also had altered responsiveness of renal medullary blood flow to changes in AP. PID offspring also had altered function of intrarenal and vascular nitric oxide signaling. Similar studies performed in acute ID animals revealed opposite trends in intrarenal and vascular NOS function, as well as in effects on the cardiovascular system. In addition to the cardiovascular effects, adult PID male offspring exhibited a number of behavioural changes, as assessed by monitoring locomotor activity in their home cages (by radiotelemetry) as well as in a novel environment. PID male offspring also performed poorly in a Morris water maze compared to controls. These differences were not observed in female PID animals. In summary, these studies provide evidence that ID during gestation has deleterious effects on various aspects of the offspring’s physiology. Given the global incidence of ID, as well as its propensity to afflict pregnant women, developmental programming from this condition could have profound implications on global health. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2009-01-22 23:32:40.931

Thesis (M.S.P.H.)--University of Michigan, 1941.

Thesis (M.Sc. (Food and Nutrition for Development))--Mahidol University, 1999.

Thesis (M.Sc. (Food and Nutrition for Nutrition for Development))--Mahidol University, 2004.