Molecular Basis of Reduced LAIR1 Expression in Childhood Severe Malarial Anemia: Implications for Leukocyte Inhibitory Signalling

2019 ◽  
Author(s):  
Angela O. Achieng ◽  
Bernard Guyah ◽  
Qiuying Cheng ◽  
Collins Ouma ◽  
Christophe G. Lambert ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Suppression of a Novel Hematopoietic Mediator in Children with Severe Malarial Anemia

2009 ◽  
Vol 77 (9) ◽  
pp. 3864-3871 ◽  
Author(s):  
Christopher C. Keller ◽  
Collins Ouma ◽  
Yamo Ouma ◽  
Gordon A. Awandare ◽  
Gregory C. Davenport ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mononuclear Cells ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Severe Malarial Anemia ◽  
Lectin Domain ◽  
Stem Cell Growth Factor ◽  
Reticulocyte Production ◽  
Pediatric Morbidity ◽  
Malarial Anemia

ABSTRACT In areas of holoendemic Plasmodium falciparum transmission, severe malarial anemia (SMA) is a leading cause of pediatric morbidity and mortality. Although many soluble mediators regulate erythropoiesis, it is unclear how these factors contribute to development of SMA. Investigation of novel genes dysregulated in response to malarial pigment (hemozoin [PfHz]) revealed that stem cell growth factor (SCGF; also called C-type lectin domain family member 11A [CLEC11A]), a hematopoietic growth factor important for development of erythroid and myeloid progenitors, was one of the most differentially expressed genes. Additional experiments with cultured peripheral blood mononuclear cells (PBMCs) demonstrated that PfHz decreased SCGF/CLEC11A transcriptional expression in a time-dependent manner. Circulating SCGF levels were then determined for Kenyan children (n = 90; aged 3 to 36 months) presenting at a rural hospital with various severities of malarial anemia. SCGF levels in circulation (P = 0.001) and in cultured PBMCs (P = 0.004) were suppressed in children with SMA. Circulating SCGF also correlated positively with hemoglobin levels (r = 0.241; P = 0.022) and the reticulocyte production index (RPI) (r = 0.280; P = 0.029). In addition, SCGF was decreased in children with reduced erythropoiesis (RPI of <2) (P < 0.001) and in children with elevated levels of naturally acquired monocytic PfHz (P = 0.019). Thus, phagocytosis of PfHz promotes a decrease in SCGF gene products, which may contribute to reduced erythropoiesis in children with SMA.

scholarly journals Lack of mortality in 22 children with sickle cell anemia and severe malarial anemia

2017 ◽  
Vol 65 (1) ◽  
pp. e26745 ◽  
Author(s):  
Robert O. Opoka ◽  
Paul Bangirana ◽  
Richard Idro ◽  
Estela Shabani ◽  
Ruth Namazzi ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Developing a novel risk prediction model for severe malarial anemia

2017 ◽  
Vol 2 ◽  
Author(s):  
E. B. Brickley ◽  
E. Kabyemela ◽  
J. D. Kurtis ◽  
M. Fried ◽  
A. M. Wood ◽  
...  
Keyword(s):  
Prediction Model ◽  
Prediction Models ◽  
Blood Levels ◽  
Transmission Season ◽  
Severe Malarial Anemia ◽  
Screening Programs ◽  
Life Threatening ◽  
Larger Sample ◽  
Related Mortality ◽  
Malarial Anemia

AbstractAs a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002–2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as aPlasmodium falciparuminfection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70–0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54–0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.

scholarly journals Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 3016-3022 ◽  
Author(s):  
Florence Burté ◽  
Biobele J. Brown ◽  
Adebola E. Orimadegun ◽  
Wasiu A. Ajetunmobi ◽  
Nathaniel K. Afolabi ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Severe Malarial Anemia ◽  
Key Points ◽  
Mild Malaria ◽  
Anti Inflammatory ◽  
Childhood Malaria ◽  
Malarial Anemia

Key Points Hepcidin rises more dramatically in mild malaria than in severe malaria. Hepcidin levels are linked to inflammation, not anemia, in severe malarial anemia and cerebral malaria.

scholarly journals Severe Malarial Anemia: Innate Immunity and Pathogenesis

2011 ◽  
Vol 7 (9) ◽  
pp. 1427-1442 ◽  
Author(s):  
Douglas J. Perkins ◽  
Tom Were ◽  
Gregory C. Davenport ◽  
Prakasha Kempaiah ◽  
James B. Hittner ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Role of Monocyte-Acquired Hemozoin in Suppression of Macrophage Migration Inhibitory Factor in Children with Severe Malarial Anemia

2006 ◽  
Vol 75 (1) ◽  
pp. 201-210 ◽  
Author(s):  
Gordon A. Awandare ◽  
Yamo Ouma ◽  
Collins Ouma ◽  
Tom Were ◽  
Richard Otieno ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Peripheral Blood ◽  
Macrophage Migration Inhibitory Factor ◽  
Inflammatory Responses ◽  
Sub Saharan Africa ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

ABSTRACT Severe malarial anemia (SMA), caused by Plasmodium falciparum infections, is one of the leading causes of childhood mortality in sub-Saharan Africa. Although the molecular determinants of SMA are largely undefined, dysregulation in host-derived inflammatory mediators influences disease severity. Macrophage migration inhibitory factor (MIF) is an important regulator of innate inflammatory responses that has recently been shown to suppress erythropoiesis and promote pathogenesis of SMA in murine models. To examine the role of MIF in the development of childhood SMA, peripheral blood MIF production was examined in Kenyan children (aged <3 years, n = 357) with P. falciparum malarial anemia. All children in the study were free from bacteremia and human immunodeficiency virus type 1. Since deposition of malarial pigment (hemozoin [Hz]) contributes to suppression of erythropoiesis, the relationship between MIF concentrations and monocytic acquisition of Hz was also examined in vivo and in vitro. Circulating MIF concentrations declined with increasing severity of anemia and significantly correlated with peripheral blood leukocyte MIF transcripts. However, MIF concentrations in peripheral blood were not significantly associated with reticulocyte production. Multivariate regression analyses, controlling for age, gender, and parasitemia, further revealed that elevated levels of pigment-containing monocytes (PCM) was associated with SMA and decreased MIF production. In addition, PCM levels were a better predictor of hemoglobin and MIF concentrations than parasite density. Additional experiments in malaria-naive individuals demonstrated that hemozoin caused both increased and decreased MIF production in cultured peripheral blood mononuclear cells (PBMC) in a donor-specific manner, independent of apoptosis. However, PBMC MIF production in children with acute malaria progressively declined with increasing anemia severity. Results presented here demonstrate that acquisition of hemozoin by monocytes is associated with suppression of peripheral blood MIF production and enhanced severity of anemia in childhood malaria.

In-Hospital Morbidity and Mortality Due to Severe Malarial Anemia in Western Kenya

2007 ◽  
Vol 77 (6_Suppl) ◽  
pp. 23-28 ◽  
Author(s):  
Charles O. Obonyo ◽  
John Vulule ◽  
Willis S. Akhwale ◽  
Diederick E. Grobbee
Keyword(s):  
Morbidity And Mortality ◽  
Western Kenya ◽  
Severe Malarial Anemia ◽  
Hospital Morbidity ◽  
Malarial Anemia
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