Pathophysiology of Anemia in HIV-Infected Children Exposed to Malaria.

Anemia is a common condition in HIV-infected children; however, its pathophysiology and the contribution of frequent causes of anemia such as iron deficiency (ID) and malaria are poorly understood. We carried out an ancillary study on the effect of HIV on anemia as part of a case-control study on risk factors of anemia among Mozambican children aged 1-59 months with documented HIV status. Of them, 390 children were admitted to the hospital with anemia (hemoglobin [Hb] < 11 g/dL), whereas 272 children without anemia (Hb ≥ 11 g/dL) were recruited in the community. We assessed differences by HIV status in the presentation of anemia etiological factors and the effect of HIV infection on the association of each factor with anemia. Among the 99 HIV-infected and 563 uninfected children included, HIV-infected anemic children had an increased risk of undernutrition (P < 0.0001), Epstein-Barr virus infection (P < 0.0001), bacteremia (P = 0.0060), a decreased risk of malaria (P < 0.0001), and a similar risk of ID (P = 0.7371) compared with anemic-uninfected children. HIV-infected children were significantly less likely to have anemia associated with Plasmodium falciparum hyperparasitemia (P = 0.0444) and had a lower prevalence of parasitemia in the bone marrow (BM) (P < 0.0001) than anemic-uninfected children. Levels of BM erythropoiesis and dyserythropoiesis were comparable between groups. These findings suggest that the pathophysiology of anemia among HIV-infected malaria-exposed children is not related to HIV-specific effects. For unclear reasons, HIV-infected children had reduced risk of malaria infection, whereas ID prevalence was comparable in HIV-infected and uninfected children, suggesting that iron supplementation recommendations should not be different in HIV-infected children.

Anaemia in hospitalised preschool children from a rural area in Mozambique: a case control study in search for aetiological agents.

BACKGROUND: Young children bear the world's highest prevalence of anaemia, the majority of which is of multifactorial aetiology, which in turn hampers its successful prevention. Even moderate degrees of anaemia are associated with increased mortality and morbidity. Despite this evidence, there is a lack of effective preventive programs and absence of consensus in the safety of iron supplementation in malaria areas, which reflects the poor understanding of the contribution of different aetiologies to anaemia. In order to reduce the anaemia burden in the most vulnerable population, a study to determine the aetiology of anaemia among pre-school Mozambican children was performed. METHODS: We undertook a case-control study of 443 preschool hospitalized children with anaemia (haemoglobin concentration <11 g/dl) and 289 community controls without anaemia. Inclusion criteria were: age 1-59 months, no blood transfusion in the previous month, residence in the study area and signed informed consent. Both univariable and multivariable logistic regression analyses were performed to identify factors associated with anaemia and adjusted attributable fractions (AAF) were estimated when appropriate. RESULTS: Malaria (adjusted odds ratio (AOR) = 8.39, p < 0.0001; AAF = 37%), underweight (AOR = 8.10, p < 0.0001; AAF = 43%), prealbumin deficiency (AOR = 7.11, p < 0.0001; AAF = 77%), albumin deficiency (AOR = 4.29, p = 0.0012; AAF = 30%), HIV (AOR = 5.73, p = 0.0060; AAF = 18%), and iron deficiency (AOR = 4.05, p < 0.0001; AAF = 53%) were associated with anaemia. Vitamin A deficiency and α-thalassaemia were frequent (69% and 64%, respectively in cases) but not independently related to anaemia. Bacteraemia (odds ratio (OR) = 8.49, p = 0.004), Parvovirus-B19 (OR = 6.05, p = 0.017) and Epstein-Barr virus (OR = 2.10, p = 0.0015) infections were related to anaemia only in the unadjusted analysis. Neither vitamin B12 deficiency nor intestinal parasites were associated with anaemia. Folate deficiency was not observed. CONCLUSIONS: Undernutrition, iron deficiency, malaria, and HIV are main factors related to anaemia in hospitalised Mozambican preschool children. Effective programs and strategies for the prevention and management of these conditions need to be reinforced. Specifically, prevention of iron deficiency that accounted in this study for more than half of anaemia cases would have a high impact in reducing the burden of anaemia in children living under similar conditions. However this deficiency, a common preventable and treatable condition, remains neglected by the international public health community.

Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections.

BACKGROUND: While WHO guidelines recommend iron supplements to only iron-deficient children in high infection pressure areas, these are rarely implemented. One of the reasons for this is the commonly held view that iron supplementation increases the susceptibility to some infectious diseases including malaria. Secondly, currently used markers to diagnose iron deficiency are also modified by infections. With the objective of improving iron deficiency diagnosis and thus, its management, we evaluated the performance of iron markers in children exposed to high infection pressure. METHODOLOGY/PRINCIPAL FINDINGS: Iron markers were compared to bone marrow findings in 180 anaemic children attending a rural hospital in southern Mozambique. Eighty percent (144/180) of the children had iron deficiency by bone marrow examination, 88% (155/176) had an inflammatory process, 66% (119/180) had moderate anaemia, 25% (45/180) severe anaemia and 9% (16/180) very severe anaemia. Mean cell haemoglobin concentration had a sensitivity of 51% and specificity of 71% for detecting iron deficiency. Soluble transferrin receptor (sTfR) and soluble transferrin receptor/log ferritin (TfR-F) index (adjusted by C reactive protein) showed the highest areas under the ROC curve (AUC(ROC)) (0.75 and 0.76, respectively), and were the most sensitive markers in detecting iron deficiency (83% and 75%, respectively), but with moderate specificities (50% and 56%, respectively). CONCLUSIONS/SIGNIFICANCE: Iron deficiency by bone marrow examination was extremely frequent in these children exposed to high prevalence of infections. However, even the best markers of bone marrow iron deficiency did not identify around a quarter of iron-deficient children. Tough not directly extrapolated to the community, these findings urge for more reliable, affordable and easy to measure iron indicators to reduce the burden of iron deficiency anaemia in resource-poor settings where it is most prevalent.

The effects of short-term iron supplementation on iron status in infants in malaria-endemic areas.

Iron deficiency and Plasmodium falciparum malaria are the two main causes of anemia in young children in region endemic for this disease. The impact on iron status of prophylactic oral iron supplementation (2 mg/kg/day from two to six months of age) and the duration of this effect were assessed in a group of 832 Tanzanian infants exposed to P. falciparum malaria. Iron parameters and red blood cell indices were assessed at 2, 5, 8, and 12 months of age. Infants who received iron supplements had a significantly lower prevalence of iron deficiency (P < 0.01 at 5 months and P < 0.001 at 8 and 12 months). Red blood cell indices (mean corpuscular volume, mean cell hemoglobin, and mean cell hemoglobin concentration) were increased in children receiving iron supplementation and they did not differ between those protected and unprotected against malaria. The prevalence of ferropenia was similar in children protected against malaria and in those who were not protected and did not receive iron supplements (34.7% versus 37.3% at 12 months of age). We concluded that iron supplementation between the ages of 2-6 months improves iron status at least up to 12 months of age. Malaria infection does not contribute to iron deficiency.

Malaria infection does not appear to modify the risk of bronchiolitis early in life.

BACKGROUND: The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown. METHODS: To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants. RESULTS: The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48% vs. 55%, P = 0.05). CONCLUSIONS: This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life.

Malaria infection does not appear to modify the risk of bronchiolitis early in life

Background: The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown. Methods: To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants. Results: The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48% vs. 55%, P = 0.05). Conclusions: This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life