Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

Hookworm infections are a major cause of childhood anemia and iron deficiency. Two hookworm species exist of which Ancylostoma duodenale is the less common, yet causing more blood loss than Necator americanus. Although species differentiation and quantification are both of clinical importance, these are often not performed as the technique is complex and laborious using microscopy. Multiplex real-time PCR is a novel diagnostic tool which allows hookworm species differentiation and infection quantification. We applied this test in 830 stool samples of Malawian children with and without severe anemia. The prevalence of hookworm infections was high. A. duodenale was unexpectedly more prevalent than N. americanus. A. duodenale infections were associated with increased risk for severe anemia and iron deficiency, both of which increased with infection load. The study identifies a need for the quantitative screening of species-specific hookworm infections, which readily can be achieved by real-time-PCR. A. duodenale was independently associated with severe anemia and iron deficiency in our study population

Anaemia, iron deficiency and infections. New perceptions of the interaction between hepcidin, iron biomarkers, anaemia and inflammation in Malawian children

IJzergebrek verkleint het risico op malaria. Dit concludeert Femkje Jonker na onderzoek bij kinderen in Malawi, een land in Afrika waar ijzergebrek en malaria vaak voorkomen. Haar conclusie is dat kinderen die medicijnen krijgen voor ijzergebrek, tegelijkertijd moeten worden beschermd tegen malaria. IJzergebrek kan leiden tot bloedarmoede en een vertraagde cognitieve ontwikkeling

Anaemia, iron deficiency and susceptibility to infection in children in sub-Saharan Africa

Globally, anaemia, iron deficiency and infections are responsible for a large part of the morbidity and mortality occurring among children. As iron is essential for erythropoiesis and the human immune system as well as a crucial element for many pathogens, these three morbidities often interact. This review considers the question – have the studies conducted so far unraveled the potential complex interaction between these factors sufficiently enough to be able to develop universally applicable guidelines about iron treatment in children. It is imaginable, however, that the area is to complex and diverse, with many sub-populations, and that not universal, but tailor made guidelines are needed based on some agreed principles

Iron Status Predicts Malaria Risk in Malawian Preschool Children

Introduction Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individual's iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account. Methods and materials We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods. Results and Conclusions The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8–2.0) and 0.7 (95% CI 0.6–0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratio's 0.55 (95%-CI:0.41–0.74) and 0.49 (95%-CI:0.33–0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria

Iron deficiency in children with HIV-associated anaemia: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis to determine the prevalence of iron deficiency in HIV-infected children from high- and low-income settings and compared it with that of HIV-uninfected controls. We searched five major databases for primary studies reporting on anaemia and iron markers in HIV-infected children. A pooled analysis was done using random-effects models, with Forest plots and heterogeneity test estimates provided. Fifteen articles (2778 children) met the inclusion criteria. In the pooled analysis, mean overall prevalence of iron deficiency in HIV-infected children was 34% (95%CI 19-50%). Prevalence rates were similar in high-income (31%; 95%CI 2-61%) and low-income settings (36%; 95%CI 17-54%) (p=0.14). Studies that included a HIV-uninfected control population (n=4) were only available from low-income settings and showed less iron deficiency in HIV-infected children (28%) than in HIV-uninfected children (43%); OR 0.50 (0.27-0.94); p=0.03. The findings suggest that HIV-infected children are less likely to be iron deficient when compared with HIV-uninfected children. Possible explanations for this include HIV-induced haematosuppression and associated hypoferraemia, with adequate iron stores. Nevertheless iron deficiency is a common co-morbidity in HIV. Studies are needed to determine the role of iron deficiency in HIV-associated anaemia and the effects of iron supplementation in this population. (c) 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserve

Directed acyclic graph for the relation between iron deficiency and malaria risk.

<p>cell. immun: cellular immunity; cum exp: cumulative malaria exposure; genetic predisp: genetic predisposition; humor immun: humoral immunity; hookw: hookworm infection; hist infect: history of other infections than malaria; HIV: human immunodeficiency virus; ID: iron deficiency; Pl.f.immun: immunity for Pl.falciparum; Pl.f: Plasmodium falciparum infection; SE: socio economic score; ZD: zinc deficiency; z.h.a: z-score height for age.</p

Sensitivity analysis of the impact of unmeasured confounding on the effect of baseline iron deficiency on risk of clinical malaria.

<p>The y-axis represents the hazard ratio for malaria infection comparing iron deficiency to iron replete after adjustment for average differences in prior risk represented by α on the x-axis. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042670#pone-0042670-g002" target="_blank">Figure 2a</a> represents analyses in which net amount of confounding is specified for both iron status groups (bias parameter u = α^{(2×ID - 1)}). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042670#pone-0042670-g002" target="_blank">Figure 2b</a> represents analyses in which the amount of confounding was varied as a function of age (bias parameter u = α^{(2×ID - 1)×(1 - abs(age-36)/30}).</p

Hazard ratios (95% Cl) of iron deficiency for the risk on malaria parasitemia en clinical malaria.

<p>Iron deficiency is defined with different cut-offs for serum ferritin (SF) in ug/L, depending on presence of inflammation, defined as C-reactive protein (CRP) >10 mg/L. The marginal-structural Cox model included HIV-infection, socio economic score, age, nutrition and study site.</p