The severity predictive index selection of severe fever with thrombocytopenia syndrome

Abstract

Objective To detect the serum viral load, lymphocyte subsets, serum enzymes and blood cell counts of severe fever with thrombocytopenia syndrome (SFTS) patients, and to use logistic regression analysis and receiver operating characteristic (ROC) curve to establish a model to analyze the severity of SFTS. Methods A case-control study of 24 SFTS cases admitted between May 2011 and July 2012 was conducted at the First Affiliated Hospital of Nanjing Medical University. All SFTS cases were defined according to Fever with Thrombocytopenia Syndrome Prevention and Control Guidelines (2010 edition) issued by the Ministry of Health of the People′s Republic of China. According to their disease severity, the patients were divided into two groups, the non-severe group (16 cases) and the severe group (8 cases). In addition, 32 healthy volunteers were also enrolled in this study. Flow cytometry was adopted to detect the CD3+, CD4+, CD8+ lymphocytes and CD3-CD16+CD56+ natural killer cells (NK cells) in the peripheral blood of SFTS patients, and cytometric beads array (CBA) was used to detect Th1/Th2/Th17 cytokines. The serum viral load in patients with severe fever with thrombocytopenia syndrome virus (SFTSV) infection was detected by fluorescent quantitative PCR technology. Besides, white blood cells, platelets and serum enzymes were measured. The multi-index conjunctive model of logistic regression analysis and receiver operating characteristics (ROC) curve were used to analyze the predictive values of indexes on severity of SFTS. Results The ROC analysis of single index found that SFTSV RNA, CD3, CD4, CD8, CD56, AST, LDH, CK, IL-6 and IL-10 have good predictability on severity of SFTS in the early course of the disease; the area under the curve (AUC) were 0.83, 0.84, 0.90, 0.75, 0.94, 0.73, 0.78, 0.87, 0.74 and 0.77 respectively, and the cut-off values of the SFTSV load, CD3+, CD4+, NK cells and CK were 6.19 log10 copies/ml, 57.51%, 19.47%, 15.71% and 696.45 U/L respectively. Using the step-by-step method logistic regression analysis to build a model and analyze the ROC curve of prediction probability, it was found that the predictability of joint indexes of SFTSV RNA/CD3/CD4/CD8/CD56, SFTSV RNA/AST/lactate dehydrogenase (LDH) /CK, or SFTSV RNA/IL-6/IL-10 increases in a certain degree. The areas under the ROC curve were 0.95 (95%CI: 0.00-1.00), 0.87 (95%CI: 0.75-0.99), and 0.83 (95%CI: 0.70-0.97), the sensitivities were 93.3%, 86.70% and 77.30%, and the specificities were 94.4%, 83.30% and 83.30% respectively. Conclusions The level of serum SFTSV is highly related to the severity of the disease. The high levels of serum SFTSV load, LDH, CK, IL-6, and IL-10, together with significant reduction of CD3+cells and CD4+ cells, may indicate poor prognosis of the SFTS patients. Based on the logistic regression model by multiple indexes, the severity of SFTS can be better predicted. (Chin J Lab Med, 2015, 38: 49-54) Key words: Runyaviridae infections; Killer cells, natural; Cytokines; Viral load; Severity of illness index; ROC curve