Reduced S1P tied to anaemia, thrombocytopenia in malaria
Malaria patients infected with Plasmodium falciparum and Plasmodium vivax have reduced serum concentrations of sphingosine 1-phosphate (S1P), reveals a new study. S1P levels are also correlated with anaemia and thrombocytopenia in P. falciparum malaria.
“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,” researchers said.
“These findings can be a proof of concept to support that S1P may represent a novel drug target for adjuvant treatment for severe malaria,” they added.
Compared with healthy controls (n=18), patients with P.vivax (n=29), uncomplicated P. falciparum (n=30) and complicated P. falciparum (n=13) infections all had significantly lower serum S1P concentrations (p<0.05 for all) on admission. [PLoS One 2017;doi:10.1371/journal.pone.0180631]
With a mean concentration of 0.26±0.04 µM, S1P levels in the complicated P. falciparum infection were the lowest and showed significant differences compared with those observed in uncomplicated P. falciparum (1.00±0.07µM; p<0.001), P. vivax (0.87±0.10 µM; p<0.001) and healthy control (1.47±0.09 µM; p<0.001) groups.
At day 7 post-treatment, serum S1P showed significant increases from baseline in all infection groups. Notably, S1P levels in the P. vivax group had returned to normal levels (p>0.05 compared to controls) while those in the uncomplicated (1.17±0.04 µM; p<0.001) and complicated (0.53±0.07 µM; p<0.001) P. falciparum groups were still significantly lower than normal.
Both at admission and post-treatment, there were no significant associations between S1P and parasitaemia (p=0.275 and p=0.00 [r=0.00], respectively), haemoglobin (Hb; p=0.727, p=0.127), haematocrit (Hct; p=0.189, p=0.853) and platelet count (p=0.717, p=0.920) observed in the P. vivax group.
On the other hand, Hb (p=0.020, p<0.001) and Hct (p=0.018, p=0.002) levels post-treatment were significantly positively associated with uncomplicated and complicated P. falciparum infections, respectively.
“A reduction in Hb and Hct levels was found particularly in complicated P. falciparum which indicates the decrease in RBC volume or anaemia,” researchers explained.
“Anaemia in malaria can be caused by a variety of pathophysiologic mechanisms. It involves direct invasion of malaria parasites into the RBCs, as well as decreased production of RBCs in the bone marrow,” which, in turn, could have resulted in the reduced S1P production, they continued. [Hematology Am Soc Hematol Educ Program 2009;2009:87-93; Parasitol Res 2007;101:1463-1469]
Malaria patients, diagnosed through microscopic examinations, were recruited from the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahindol University in Thailand. Whole blood samples were then collected for serum marker measurements. Cases with hyperparasitaemia, severe anaemia or elevated serum creatinine were defined as complicated malaria cases.
“Whether a reduction in the serum S1P concentration in malaria might be a simple result of the disease complications or might possibly contribute to malaria severity should be further evaluated,” researchers recommended.
“It is also of interest to determine whether the serum S1P concentration would be useful as a novel marker of malaria severity,” they said.