Multiple Organ Dysfunction During Severe Malaria: The Role of the Inflammatory Response

Abstract

Severe malaria is a systemic illness characterized by the dysfunction of one or more peripheral organs, such as the lungs [acute respiratory distress syndrome (ARDS)] and kidneys [acute kidney injury (AKI)]. Several clinical and experimental studies suggest that features of the inflammatory response are related to the multi-organ dysfunction observed in severe malaria. Our group has been dedicated to studying the roles of proand anti-inflammatory mediators in the multi-organ dysfunction observed in experimental severe malaria, especially in the lungs, kidneys, and brain. Herein, we explore severe malaria as a pathology derived from intense inflammatory responses in different organs and further distinguish and compare these organ-specific inflammatory responses. The pathophysiological mechanism of severe malaria is not fully elucidated; however, it is important to study it as a complex inflammatory response assembled by different actors, each one orchestrating a different mechanism.

The clinical and histopathological aspect of the liver, lung, and kidney in Malaria

“…The mortality increased when the patient is in an advanced age, have hyperkalemia, jaundice, leukocytosis, oligo-anuria, and the consciousness level is altered. Early diagnosis and treatment can reduce mortality and have a better prognosis with peritoneal dialysis (da Silva et al, 2017;de Souza et al, 2016;Seilmaier et al, 2014;Kirchgatter et al, 2005).…”

“…It was hypothesized that smAKI develop secondary due to a systemic inflammatory response of the host to the parasite which causes functional and structural damage to the kidney. Some other studies suggest that the smAKI is induced locally based on the finding of intense inflammatory cell accumulation in the renal tissue (de Souza et al, 2016). The pathogenesis of smAKI where cytokines released after endothelial activation is in conjunction through either Th1 or Th2 response.…”

“…The pathogenesis is due to the deposit of the immune complex (IgG, IgM, C3, and malaria antigen) in the subendothelial as the consequence of TH2 type lymphocytes activation. The more severe form of kidney injury is the cortical necrosis and when this happen, the renal function can no longer recover and finally develop the end-stage kidney disease (da Silva et al, 2017;and de Souza et al, 2016).…”

“…Sequestration is a phenomenon where the infected erythrocyte adhere to the endothelial cell of the host vital organ's microvascular such as brain, lung, liver, and kidney (Autino et al, 2012;White, 2009). The inflammatory response also underlines the pathology of severe malaria (de Souza et al, 2016).…”

“…There are also mononuclear cells found in the peritubular capillaries, but they do not infiltrate renal tissue interstitial likely because the tight junction in renal tissue is not fully disrupted. There is also deposition of the immune complex such as immunoglobulin (Ig) isotypeG and M (da Silva et al, 2017;de Souza et al, 2016;Nguansangiam et al, 2007).…”