Influence of host iron status on Plasmodium falciparum infection

Clark, Martha A.; Goheen, Morgan M.; Cerami, Anthony

doi:10.3389/fphar.2014.00084

Cited by 57 publications

(57 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro studies have shown that P. falciparum is less efficient in parasitizing erythrocytes from iron‐deficient donors than from iron‐replete donors (Clark et al , 2014a,b). The same group has recently shown this to be true in Gambian children and that it applies both to laboratory and local clinical strains of P. falciparum (Goheen et al , 2016).…”

Section: Safety Of Antenatal Iron Interventions In Malaria‐endemic Sementioning

confidence: 99%

“…The same group has recently shown this to be true in Gambian children and that it applies both to laboratory and local clinical strains of P. falciparum (Goheen et al , 2016). They have further shown that young erythrocytes are more susceptible to invasion and propagation by P. falciparum merozoites than mature erythrocytes (Clark et al , 2014a,b; Goheen et al , 2016). Seven weeks of iron supplementation completely abrogated the protection offered by iron deficiency anaemia in both Gambian children (Goheen et al , 2016) and pregnant Gambian women (Drs Goheen, Bah & Cerami, MRC Unit The Gambia, Banjul, The Gambia, personal communication).…”

Section: Safety Of Antenatal Iron Interventions In Malaria‐endemic Sementioning

confidence: 99%

See 1 more Smart Citation

Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

2017

View full text Add to dashboard Cite

SummaryThe World Health Organization recommends universal iron supplementation of 30–60 mg/day in pregnancy but coverage is low in most countries. Its efficacy is uncertain, however, and there has been a vigorous debate in the last decade about its safety, particularly in areas with a high burden of malaria and other infectious diseases. We reviewed the evidence on the safety and efficacy of antenatal iron supplementation in low‐income countries. We found no evidence that daily supplementation at a dose of 60 mg leads to increased maternal Plasmodium infection risk. On the other hand, recent meta‐analyses found that antenatal iron supplementation provides benefits for maternal health (severe anaemia at postpartum, blood transfusion). For neonates, there was a reduced prematurity risk, and only a small or no effect on birth weight. A recent trial showed, however, that benefits of antenatal iron supplementation on maternal and neonatal health vary by maternal iron status, with substantial benefits in iron‐deficient women. The benefits of universal iron supplementation are likely to vary with the prevalence of iron deficiency. As a consequence, the balance between benefits and risks is probably more favourable in low‐income countries than in high‐income countries despite the higher exposure to infectious pathogens.

show abstract

Section: Safety Of Antenatal Iron Interventions In Malaria‐endemic Sementioning

confidence: 99%

Section: Safety Of Antenatal Iron Interventions In Malaria‐endemic Sementioning

confidence: 99%

Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

2017

View full text Add to dashboard Cite

show abstract

“…Iron is essential for growth, proliferation and survival of malaria parasites [16]. The parasite multiplies 8-32 times in the presence of iron during a single intra-erythrocytic lifecycle [17]. Clark, et al [15] demonstrated that host iron status and iron supplementation mediate susceptibility to erythrocytic stages of P. falciparum through elevated erythropoietic rate.…”

Section: Introductionmentioning

confidence: 99%

Iron Supplementation Alters Heme and Heme Oxygenase 1 (HO-1) Levels In Pregnant Women in Ghana

Salifu¹

2016

SOJMID

View full text Add to dashboard Cite

“…During infection, expression of the iron-regulatory hormone hepcidin increases significantly, leading to reduced dietary iron absorption and increased iron storage (9-12). The restriction of iron bioavailability may be a host defense mechanism designed to inhibit parasite access to iron, although the source of iron utilized by the parasite is still unclear (13,14). In liver-stage infection, reduced iron bioavailability brought on by previously established bloodstage infection inhibits the development of sporozoites, thereby preventing compound infections (15).…”

mentioning

confidence: 99%

Erythrocytic Iron Deficiency Enhances Susceptibility to Plasmodium chabaudi Infection in Mice Carrying a Missense Mutation in Transferrin Receptor 1

et al. 2015

View full text Add to dashboard Cite

The treatment of iron deficiency in areas of high malaria transmission is complicated by evidence which suggests that iron deficiency anemia protects against malaria, while iron supplementation increases malaria risk. Iron deficiency anemia results in an array of pathologies, including reduced systemic iron bioavailability and abnormal erythrocyte physiology; however, the mechanisms by which these pathologies influence malaria infection are not well defined. In the present study, the response to malaria infection was examined in a mutant mouse line, Tfrc MRI24910 , identified during an N-ethyl-N-nitrosourea (ENU) screen. This line carries a missense mutation in the gene for transferrin receptor 1 (TFR1). Heterozygous mice exhibited reduced erythrocyte volume and density, a phenotype consistent with dietary iron deficiency anemia. However, unlike the case in dietary deficiency, the erythrocyte half-life, mean corpuscular hemoglobin concentration, and intraerythrocytic ferritin content were unchanged. Systemic iron bioavailability was also unchanged, indicating that this mutation results in erythrocytic iron deficiency without significantly altering overall iron homeostasis. When infected with the rodent malaria parasite Plasmodium chabaudi adami, mice displayed increased parasitemia and succumbed to infection more quickly than their wild-type littermates. Transfusion of fluorescently labeled erythrocytes into malaria parasite-infected mice demonstrated an erythrocyte-autonomous enhanced survival of parasites within mutant erythrocytes. Together, these results indicate that TFR1 deficiency alters erythrocyte physiology in a way that is similar to dietary iron deficiency anemia, albeit to a lesser degree, and that this promotes intraerythrocytic parasite survival and an increased susceptibility to malaria in mice. These findings may have implications for the management of iron deficiency in the context of malaria. Iron deficiency and supplementation can influence the risk and outcome of malaria infection. Epidemiology studies have indicated that iron deficiency anemia (IDA) is associated with a reduced risk of malaria in children and pregnant women (1-5), whereas clinical trials have demonstrated that iron supplementation in the absence of adequate health care increases the risk of malaria (6, 7). While the mechanisms underlying these outcomes are not well defined, it is clear that two major factors contribute: iron bioavailability and erythrocyte physiology.Iron bioavailability and homeostasis in the host during malaria infection are complex and incompletely understood (8). During infection, expression of the iron-regulatory hormone hepcidin increases significantly, leading to reduced dietary iron absorption and increased iron storage (9-12). The restriction of iron bioavailability may be a host defense mechanism designed to inhibit parasite access to iron, although the source of iron utilized by the parasite is still unclear (13,14). In liver-stage infection, reduced iron bioavailability brought on by previously ...

show abstract

Influence of host iron status on Plasmodium falciparum infection

Cited by 57 publications

References 105 publications

Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

Iron Supplementation Alters Heme and Heme Oxygenase 1 (HO-1) Levels In Pregnant Women in Ghana

Erythrocytic Iron Deficiency Enhances Susceptibility to Plasmodium chabaudi Infection in Mice Carrying a Missense Mutation in Transferrin Receptor 1

Contact Info

Product

Resources

About