Date Published: June 30, 2017
Publisher: Public Library of Science
Author(s): Chuchard Punsawad, Parnpen Viriyavejakul, Laurent Rénia.
Sphingosine 1-phosphate (S1P) is a lipid mediator formed by the metabolism of sphingomyelin which is involved in the endothelial permeability and inflammation. Although the plasma S1P concentration is reportedly decreased in patients with cerebral malaria, the role of S1P in malaria is still unclear. The purpose of this study was to examine the impact of malaria on circulating S1P concentration and its relationship with clinical data in malaria patients. Serum S1P levels were measured in 29 patients with P. vivax, 30 patients with uncomplicated P. falciparum, and 13 patients with complicated P. falciparum malaria on admission and on day 7, compared with healthy subjects (n = 18) as control group. The lowest level of serum S1P concentration was found in the complicated P. falciparum malaria group, compared with P. vivax, uncomplicated P. falciparum patients and healthy controls (all p < 0.001). In addition, serum S1P level was positively correlated with platelet count, hemoglobin and hematocrit levels in malaria patients. In conclusions, low levels of S1P are associated with the severity of malaria, and are correlated with thrombocytopenia and anemia. These findings highlight a role of S1P in the severity of malaria and support the use of S1P and its analogue as a novel adjuvant therapy for malaria complications.
It was estimated that 3.2 billion people still remain at risk of malaria in 2015. According to the latest reports, 214 million cases of malaria occurred globally with estimated mortality of 438,000 deaths . Malaria in humans is caused by 5 plasmodium species, namely Plasmodium falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. Most of the fatal cases, which predominantly occur in P. falciparum infection, are due to cerebral malaria or severe anemia, but different clinical complications such as acute kidney injury, pulmonary edema, metabolic acidosis and thrombocytopenia also exist and vary in severity and outcome, depending on the parasite species, the organ involved and the access to care [2, 3].
The main findings of our study indicated that patients with complicated P. falciparum malaria had reduced levels of serum S1P on admission and day 7 post-treatment. A decrease in S1P level had previously been documented in acute dengue infection , sepsis , chronic hepatitis C infection  and obesity . In contrast, elevated serum level of S1P has been previously reported in autoimmune and inflammatory diseases, including juvenile-onset systemic lupus erythematosus  and systemic sclerosis . In human malaria, S1P levels have been showed to decrease significantly in Ugandan children with cerebral malaria . The current work confirms the finding in complicated P. falciparum malaria. Nevertheless, limitations in this study include (1) lack of confirmation for mixed infection of P. falciparum and P. vivax, (2) lack of kinetics of S1P levels in all patient groups, and (3) only pertinent clinical and laboratory findings were used to find correlation with S1P, other malaria severity parameters such as cerebral malaria, pulmonary edema, acidosis, hyperbilirubinemia were not available for analysis.
Serum S1P concentration is decreased in malaria patient infected with P. vivax and P. falciparum, suggesting that S1P signaling cascade is implicated in the severity of malaria. Decreased serum S1P concentration is associated with thrombocytopenia and anemia in P. falciparum malaria as well as malaria severity. These findings can be a proof of concept to support that S1P may represent a novel drug target for adjuvant treatment for severe malaria.