Int J Biol Sci 2011; 7(9):1427-1442. doi:10.7150/ijbs.7.1427 This issue Cite

Review

Severe Malarial Anemia: Innate Immunity and Pathogenesis

Douglas J. Perkins1, 2✉, Tom Were2,3, Gregory C. Davenport1, 2, Prakasha Kempaiah1, 2, James B. Hittner1, 4, John Michael Ong'echa2

1. Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque NM, USA
2. University of New Mexico/Kenya Medical Research Institute, Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kisumu, Kenya
3. Department of Pathology, School of Health Sciences, Kenyatta University, Nairobi, Kenya
4. Department of Psychology, College of Charleston, Charleston, SC, USA

Citation:
Perkins DJ, Were T, Davenport GC, Kempaiah P, Hittner JB, Ong'echa JM. Severe Malarial Anemia: Innate Immunity and Pathogenesis. Int J Biol Sci 2011; 7(9):1427-1442. doi:10.7150/ijbs.7.1427. https://www.ijbs.com/v07p1427.htm
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Abstract

Greater than 80% of malaria-related mortality occurs in sub-Saharan Africa due to infections with Plasmodium falciparum. The majority of P. falciparum-related mortality occurs in immune-naïve infants and young children, accounting for 18% of all deaths before five years of age. Clinical manifestations of severe falciparum malaria vary according to transmission intensity and typically present as one or more life-threatening complications, including: hyperparasitemia; hypoglycemia; cerebral malaria; severe malarial anemia (SMA); and respiratory distress. In holoendemic transmission areas, SMA is the primary clinical manifestation of severe childhood malaria, with cerebral malaria occurring only in rare cases. Mortality rates from SMA can exceed 30% in pediatric populations residing in holoendemic transmission areas. Since the vast majority of the morbidity and mortality occurs in immune-naïve African children less than five years of age, with SMA as the primary manifestation of severe disease, this review will focus primarily on the innate immune mechanisms that govern malaria pathogenesis in this group of individuals. The pathophysiological processes that contribute to SMA involve direct and indirect destruction of parasitized and non-parasitized red blood cells (RBCs), inefficient and/or suppression of erythropoiesis, and dyserythropoiesis. While all of these causal etiologies may contribute to reduced hemoglobin (Hb) concentrations in malaria-infected individuals, data from our laboratory and others suggest that SMA in immune-naïve children is characterized by a reduced erythropoietic response. One important cause of impaired erythroid responses in children with SMA is dysregulation in the innate immune response. Phagocytosis of malarial pigment hemozoin (Hz) by monocytes, macrophages, and neutrophils is a central factor for promoting dysregulation in innate inflammatory mediators. As such, the role of P. falciparum-derived Hz (PfHz) in mediating suppression of erythropoiesis through its ability to cause dysregulation in pro- and anti-inflammatory cytokines, growth factors, chemokines, and effector molecules is discussed in detail. An improved understanding of the etiological basis of suppression of erythropoietic responses in children with SMA may offer the much needed therapeutic alternatives for control of this global disease burden.

Keywords: Malarial Anemia, Innate Immunity, Pathogenesis


Citation styles

APA
Perkins, D.J., Were, T., Davenport, G.C., Kempaiah, P., Hittner, J.B., Ong'echa, J.M. (2011). Severe Malarial Anemia: Innate Immunity and Pathogenesis. International Journal of Biological Sciences, 7(9), 1427-1442. https://doi.org/10.7150/ijbs.7.1427.

ACS
Perkins, D.J.; Were, T.; Davenport, G.C.; Kempaiah, P.; Hittner, J.B.; Ong'echa, J.M. Severe Malarial Anemia: Innate Immunity and Pathogenesis. Int. J. Biol. Sci. 2011, 7 (9), 1427-1442. DOI: 10.7150/ijbs.7.1427.

NLM
Perkins DJ, Were T, Davenport GC, Kempaiah P, Hittner JB, Ong'echa JM. Severe Malarial Anemia: Innate Immunity and Pathogenesis. Int J Biol Sci 2011; 7(9):1427-1442. doi:10.7150/ijbs.7.1427. https://www.ijbs.com/v07p1427.htm

CSE
Perkins DJ, Were T, Davenport GC, Kempaiah P, Hittner JB, Ong'echa JM. 2011. Severe Malarial Anemia: Innate Immunity and Pathogenesis. Int J Biol Sci. 7(9):1427-1442.

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