Parasitemia, Anemia, and Malarial Anemia in Infants and Young Children in a Rural Holoendemic Plasmodium Falciparum Transmission Area

Ong’echa, John Michael; Keller, Christopher; Were, Tom; Ouma, Collins; Otieno, RO; Landis-Lewis, Zachary; Ochiel, Daniel; Slingluff, Jamie L.; Mogere, Stephen; Ogonji, George A.; Orago, Alloys S. S.; Vulule, John; Kaplan, Sandra S.; Day, Richard; Perkins, Douglas J

doi:10.4269/ajtmh.2006.74.376

Cited by 88 publications

(139 citation statements)

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“…These results suggest that the pattern of IL-23, IL-12, and IL-10 production observed in children with malarial anemia in the current study were significantly influenced by the strong relationship between parasite density and production of these cytokines. It is also important to point out that in this population of children, we have consistently observed that parasitemia is not strongly associated with malarial anemia severity [29,35,38]. This could explain, at least in part, our observation that the absolute levels of these cytokines were comparable between the MlMA and SMA groups.…”

Section: Discussionmentioning

confidence: 71%

“…SMA is the primary clinical manifestation of severe malaria in children under the age of 5 years in this region, with the peak incidence of malarial anemia occurring in children 7-24 months of age [5,34]. A detailed description of the study area and the hematological manifestations of pediatric malarial anemia (MA) in the study population can be found in our recent publication [35].…”

Section: Study Areamentioning

confidence: 99%

“…Children (n=69; age 0-3 years) presenting with acute P. falciparum malaria were recruited from an on-going hospital-based longitudinal study at the SDH, western Kenya [35]. Children with P. falciparum parasitemia (any density) were stratified according to Hb levels into the following categories: mild malarial anemia (MlMA, n=25; Hb 8.0-10.9 g/dL and free from the symptoms of severe malaria such as hypoglycemia); and SMA (n=25; Hb<6.0 g/dL and free from the symptoms of severe malaria such as hypoglycemia).…”

Section: Study Populationmentioning

confidence: 99%

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Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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Severe malarial anemia (SMA) is a leading cause of mortality among children in sub-Saharan Africa. Although the novel cytokine, interleukin (IL)-23, promotes anemia in chronic inflammatory diseases, the role of IL-23 in SMA remains undefined. Since IL-23 and IL-12 share the IL-12p40 subunit and IL-12Rβ1 receptor, and are down-regulated by IL-10, relationships among these cytokines were explored in Kenyan children with varying severities of malarial anemia. Children with malarial anemia had increased circulating IL-23 and IL-10, and decreased IL-12 relative to healthy controls. Enhanced anemia severity and elevated parasitemia were associated with increased IL-10 relative to IL-23 and IL-12. Further exploration of the relationships among the cytokines using an in vitro model in which peripheral blood mononuclear cells were treated with synthetic hemozoin (sHz, malarial pigment) revealed that IL-12p35 and IL-23p19 transcripts had a sustained induction over 72 hrs, while IL-12p40 and IL-10 message peaked at 24 hrs, and rapidly declined thereafter. Taken together, results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria.

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Section: Discussionmentioning

confidence: 71%

Section: Study Areamentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Ong’echa

Remo

Kristoff

et al. 2008

Clinical Immunology

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“…20 records met our inclusion criteria (table), [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and of these 15 contained the necessary data for inclusion in the quantitative analysis (meta-analysis). Five records were excluded from the quantitative analysis either because Bayesian credible intervals were reported (n=2) or because ORs could not be calculated from the available data (n=3)[A: sentence correct as edited?].…”

Section: Resultsmentioning

confidence: 99%

Socioeconomic development as an intervention against malaria: a systematic review and meta-analysis

et al. 2013

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Official URL: http://dx.doi.org/10.1016/S0140-6736(13)60851-X More details/abstract: Background: Future progress in tacking malaria mortality will probably be hampered by the development of resistance to drugs and insecticides and by the contraction of aid budgets. Historically, control was often achieved without malaria specific interventions. Our aim was to assess whether socioeconomic development can contribute to malaria control. Methods: We did a systematic review and meta-analysis to assess whether the risk of malaria in children aged 0-15 years is associated with socioeconomic status. We searched Medline, Web of Science, Embase, the Cochrane Database of Systematic Reviews, the Campbell Library, the Centre for Reviews and Dissemination, Health Systems Evidence, and the Evidence for Policy and Practice Information and Co-ordinating Centre evidence library for studies published in English between Jan 1, 1980, and July 12, 2011, that measured socioeconomic status and parasitologically confirmed malaria or clinical malaria in children. Unadjusted and adjusted effect estimates were combined in fixed effects and random-effects meta-analyses, with a subgroup analysis for different measures of socioeconomic status. We used funnel plots and Egger's linear regression to test for publication bias. Findings: Of 4696 studies reviewed, 20 met the criteria for inclusion in the qualitative analysis, and 15 of these reported the necessary data for inclusion in the meta-analysis. The odds of malaria infection were higher in the poorest children than in the least poor children (unadjusted odds ratio [OR] 1•66, 95% CI 1•35-2•05, p<0•001, I²=68%; adjusted OR 2•06, 1•42-2•97, p<0•001, I²=63%), an effect that was consistent across subgroups. Interpretation: Although we would not recommend discontinuation of existing malaria control efforts, we believe that increased investment in interventions to support socioeconomic development is warranted, since such interventions could prove highly effective and sustainable against malaria in the long term. Version: Accepted Author ManuscriptTerms of use: This work has been licensed by the copyright holder for distribution in electronic format via any medium for the lifetime of the OpenDocs repository for the purpose of free access without charge. NOTICE: this is the author's version of a work that was accepted for publication in The Lancet. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Lancet 382.9896 (2013) SummaryBackground Future progress in tacking malaria mortality will probably be hampered by the development of resistance to drugs and insecticides and by the contraction of aid budgets. Historically, control was often achieved without malariaspecific interventions. Our aim was to assess whether socioeconomic de...

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“…[1][2][3][4] In addition to destruction of infected and uninfected red blood cells, insufficient erythropoiesis, due to either ineffective erythropoiesis and/or dyserythropoiesis, plays a key role in malarial anemia. 5,6 Deficient erythropoietin (EPO) production does not appear to provide an explanation for malarial anemia since most studies indicate that EPO production is adequately increased in response to the level of anemia.…”

Section: Introductionmentioning

confidence: 99%

STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia

Thawani¹,

Tam²,

Stevenson³

2008

Haematologica

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The online version of this article contains a supplementary appendix. BackgroundThe contribution of pro-inflammatory cytokines to the pathogenesis of malarial anemia has been studied extensively but the roles of Th2 cytokines remain unknown. Here, we investigated the role of signal transducer and activator of transcription (STAT)6-mediated responses in erythropoietic suppression during acute malaria infection in mice. Design and MethodsNaïve and/or erythropoietin-treated wild-type and STAT6 -/-mice were infected with Plasmodium chabaudi AS (P. chabaudi), and the effects on parasitemia, hematologic parameters, erythropoietin receptor, TER119, and CD71 expression, in vitro erythropoietin-stimulated proliferation of splenic erythroid precursors, and serum cytokine levels were analyzed. To explore the role of interleukin-4 in STAT6-dependent erythropoietic suppression, mice were treated in vivo with a monoclonal antibody to interleukin-4 and the effects on parasitemia, hematologic parameters, and cytokine levels were analyzed. Results Infected STAT6-/-mice developed enhanced reticulocytosis compared to wild-type mice despite higher parasitemia and a similar course of anemia. Enhanced reticulocytosis in infected STAT6 -/-mice was associated with an increased frequency of late-stage erythroblasts, fewer leukocytes expressing CD71, and increased erythropoietin-stimulated proliferation of splenocytes compared to infected wild-type mice. Interleukin-4-depleted wildtype mice had increased levels of parasitemia and a course of reticulocytosis similar to responses observed in infected STAT6 -/-mice. Determination of serum cytokine levels in STAT6 -/-and wild-type mice depleted of interleukin-4 by treatment with mAb revealed significantly lower levels of interferon-γ compared to control wild-type mice during infection. ConclusionsTogether, these findings provide evidence for a STAT6-dependent mechanism in mediating erythropoietic suppression during acute blood-stage malaria and indicate a role for interleukin-4 and possibly interferon-γ in STAT6-induced erythropoietic suppression.Key words: malaria, anemia, erythropoiesis, STAT6, interleukin-4, interferon-γ.Citation: Thawani N, Tam M, and Stevenson MM. STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia. Haematologica 2009; 94:195-204. doi:10.3324/haematol.13422 ©2009 Ferrata Storti Foundation. This is an open-access paper. STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n N. Thawani et al.

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Parasitemia, Anemia, and Malarial Anemia in Infants and Young Children in a Rural Holoendemic Plasmodium Falciparum Transmission Area

Cited by 88 publications

References 35 publications

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

Socioeconomic development as an intervention against malaria: a systematic review and meta-analysis

STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia

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