Anemia and Interleukin-10, Tumor Necrosis Factor Alpha, and Erythropoietin Levels among Children with Acute, Uncomplicated<i>Plasmodium falciparum</i>Malaria

Nussenblatt, Véronique; Mukasa, Gelasius; Metzger, Amy; Ndeezi, Grace; Garrett, Elizabeth; Semba, Richard D.

doi:10.1128/cdli.8.6.1164-1170.2001

Cited by 62 publications

(53 citation statements)

References 35 publications

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“…However, in contrast, IL-10 has been shown to downregulate the expression of TNF-a by human monocytes , an effect that might be expected to inhibit the suppression of erythropoiesis by TNF-a. Among children with acute malaria, a high ratio of IL-10 to TNF-a is associated with milder anemia (Othoro et al, 1999;Nussenblatt et al, 2001). In contrast, with the present study, which did not involve children with malaria, children with iron deficiency seemed to have a higher IL-10/TNF-a ratio than children without iron deficiency.…”

Section: Discussioncontrasting

confidence: 81%

“…A stronger association between elevated TNF-a and/or elevated AGP and anemia Vitamin A deficiency, iron deficiency, and inflammation to anemia MV Gamble et al might be found among ill children drawn from a clinic or hospital-based study, where the anemia of chronic disease would be more common. Elevations of serum TNF-a and/or AGP can occur in the presence of infection, such as malaria (Nussenblatt et al, 2001), diarrheal disease (Azim et al, 1999), or acute lower respiratory infection . This study was limited in that other acute-phase response proteins, such as C-reactive protein, were not measured, and it is possible that a combination of elevated AGP and/or elevated C-reactive protein would have detected a greater proportion of children with inflammation than AGP alone.…”

Section: Discussionmentioning

confidence: 99%

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Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands

et al. 2004

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Introduction: Although vitamin A deficiency, iron deficiency, and inflammation may contribute to anemia, their relative contribution to anemia has not been well characterized in preschool children in developing countries. Objective: To characterize the contributions of vitamin A and iron deficiencies and inflammation to anemia among preschool children in the Republic of the Marshall Islands. Subjects and methods: A community-based survey, the Republic of the Marshall Islands Vitamin A Deficiency Study, was conducted among 919 preschool children. The relationship of vitamin A and iron status and markers of inflammation, tumor necrosis factor-a, a 1 -acid glycoprotein, and interleukin-10, to anemia were studied in a subsample of 367 children. Results: Among the 367 children, the prevalence of anemia was 42.5%. The prevalence of severe vitamin A deficiency (serum vitamin A o0.35 mmol/l) and iron deficiency (serum ferritin o12 mg/dl) were 10.9 and 51.7%, respectively. The respective prevalence of iron deficiency anemia (hemoglobin o110 g/l and iron deficiency), anemia with inflammation (anemia with TNFa42 pg/ml and/or AGP 41000 mg/l), and severe vitamin A deficiency combined with anemia was 26.7, 35.6, and 7.6%. In multivariate linear regression models that adjusted for age, sex, and inflammation, both iron deficiency (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.08-2.83, P ¼ 0.023) and severe vitamin A deficiency (OR 4.85, 95% CI 2.14-10.9, Po0.0001) were significantly associated with anemia. Conclusions: Both iron and vitamin A deficiencies were independent risk factors for anemia, but inflammation was not a significant risk factor for anemia among these preschool children.

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands

et al. 2004

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“…104,105 However, several studies of malaria in African children suffering from malarial anemia have shown appropriately raised Epo concentrations. 25,[106][107][108] In fact, the Epo levels in malarial anemia are more than 3-fold higher when compared with anemic children without malaria. 72 It is possible that ineffective or inadequate Epo synthesis does contribute to malarial anemia in some settings, possibly related to age, ethnic origin, or presentation of the patient.…”

Section: Org Frommentioning

confidence: 99%

Malarial anemia: of mice and men

Lamikanra

Brown²,

Potocnik³

et al. 2007

Blood

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Severe malaria is manifest by a variety of clinical syndromes dependent on properties of both the host and the parasite. In young infants, severe malarial anemia (SMA) is the most common syndrome of severe disease and contributes substantially to the considerable mortality and morbidity from malaria. There is now growing evidence, from both human and mouse studies of malaria, to show that anemia is due not only to increased hemolysis of infected and clearance of uninfected red blood cells (RBCs) but also to an inability of the infected host to produce an adequate erythroid response. In this review, we will summarize the recent clinical and experimental studies of malaria to highlight similarities and differences in human and mouse pathology that result in anemia and so inform the use of mouse models in the study of severe malarial anemia in humans. Malaria in humansThe vast majority of morbidity and mortality from malaria is caused by infection with Plasmodium falciparum, although P vivax, P ovale, and P malariae also are responsible for human infections. The total burden of disease has recently been estimated to 515 million episodes annually and malaria is responsible for 18% of all childhood deaths in sub-Saharan Africa, equivalent to 800 000 deaths each year. 1,2 The study of malarial anemia has somewhat belatedly excited academic and professional interest. Severe malarial anemia (SMA) certainly merits concern as a major public health problem because of the very large numbers of children affected, and it is likely that these numbers may increase as drug resistance spreads. Concerns have also been raised by data from recent vaccine studies, which suggest that monkeys immunized with erythrocytic-stage antigens, and that have acquired protection from acute infection, may succumb to severe anemia during a subacute or chronic phase of infection. 3,4 Moreover, there is increasing awareness of the difficulty of satisfactory treatment by blood transfusion outside specialist centers in many endemic areas as a result of the limited availability of a rapid and safe supply of blood. 1,5 SMA is seen most frequently in areas of very high malaria transmission and most commonly in young children and pregnant women. 6 The prevalence of anemia, defined as a hematocrit (Hct) level higher than 0.33, in malaria-endemic areas of Africa, varies between 31% and 91% in children, and between 60% and 80% in pregnant women. 7,8 Given the high degree of morbidity that is associated with SMA in children, this term will be used to refer to severe anemia in this group, unless stated otherwise.It is very difficult to determine the number of cases of severe anemia attributable to malaria as the WHO definition of SMA (a hemoglobin [Hb] concentration of Ͻ 50 g/L [5 g/dL], or a Hct Ͻ 0.15, in the presence of a parasitemia Ͼ 10 000 parasites per microliter [L], and a normocytic blood film) may exclude the considerable proportion of children admitted with severe anemia that has a blood smear negative for malaria parasites but that responds to an...

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“…Previous hematological studies of individuals with malaria illustrate that bone marrow abnormalities, such as ineffective erythropoiesis, dyserythropoiesis, and reduced erythroblast proliferative rates, contribute to the development of severe anemia (1,12,42,49). Moreover, P. falciparum malaria is defined by a suboptimal reticulocyte response for the degree of anemia, even under conditions in which there are adequate levels of erythropoietin, a critical stimulus for erythropoiesis (25,32). Our previous results in western Kenya showing that children with SMA have a reduced erythropoietic response (RPI) are consistent with these findings (46).…”

Section: Figmentioning

confidence: 99%

A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

et al. 2010

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Plasmodium falciparum malaria is a leading global cause of infectious disease burden. In areas in which P. falciparum transmission is holoendemic, such as western Kenya, severe malarial anemia (SMA) results in high rates of pediatric morbidity and mortality. Although the pathophysiological basis of SMA is multifactorial, we recently discovered that suppression of unexplored hematopoietic growth factors that promote erythroid and myeloid colony development, such as stem cell growth factor (SCGF) (C-type lectin domain family member 11A [CLEC11A]), was associated with enhanced development of SMA and reduced erythropoietic responses. To extend these investigations, the relationships between a novel SCGF promoter variant (؊539C/T, rs7246355), SMA (hemoglobin [Hb] < 6.0 g/dl), and reduced erythropoietic responses (reticulocyte production index [RPI], <2.0) were investigated with Kenyan children (n ‫؍‬ 486) with falciparum malaria from western Kenya. Circulating SCGF was positively correlated with hemoglobin levels (r ‫؍‬ 0.251; P ‫؍‬ 0.022) and the reticulocyte production index (RPI) (r ‫؍‬ 0.268; P ‫؍‬ 0.025). Children with SMA also had lower SCGF levels than those in the non-SMA group (P ‫؍‬ 0.005). Multivariate logistic regression analyses controlling for covariates demonstrated that individuals with the homologous T allele were protected against SMA (odds ratio, 0.57; 95% confidence interval [95% CI] 0.34 to 0.94; P ‫؍‬ 0.027) relative to CC (wild-type) carriers. Carriers of the TT genotype also had higher SCGF levels in circulation (P ‫؍‬ 0.018) and in peripheral blood mononuclear cell culture supernatants (P ‫؍‬ 0.041), as well as an elevated RPI (P ‫؍‬ 0.005) relative to individuals with the CC genotype. The results presented here demonstrate that homozygous T at ؊539 in the SCGF promoter is associated with elevated SCGF production, enhanced erythropoiesis, and protection against the development of SMA in children with falciparum malaria.

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Anemia and Interleukin-10, Tumor Necrosis Factor Alpha, and Erythropoietin Levels among Children with Acute, UncomplicatedPlasmodium falciparumMalaria

Cited by 62 publications

References 35 publications

Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands

Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands

Malarial anemia: of mice and men

A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

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