Accuracy of an experimental whole-blood test for detecting reactivation of echinococcal cysts

Background Cystic echinococcosis (CE) is a complex disease for which clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. We evaluated the accuracy of a whole-blood stimulation test based on Interleukin (IL)-4 detection in response to Antigen B (AgB) of Echinococcus granulosus sensu lato to discriminate cyst viability and detect cyst reactivation in patients with hepatic CE. Methodology/Principal findings Thirty patients with CE3b cysts and 37 patients with spontaneously-inactivated CE4-CE5 cysts were recruited (T0). After enrollment, 5 patients with CE3b cysts received albendazole, resulting in cyst solidification (CE4) in 4/5. Within a two-year follow-up, the whole-blood test was repeated at two time-points, in >= 14 (T1) and in >= 4 (T2) patients per group. IL-4 and a panel of other soluble factors were measured in the stimulated plasma. Baseline IL-4 levels were significantly higher in patients with CE3b compared to those with CE4 cysts (p = 0.006). Test accuracy for CE3b diagnosis had a sensitivity of 33-60% and a specificity of 76-95%, depending on the cut-off applied. Overall, IL-4 levels did not change significantly over time in either group; however, patients within the CE3b group showed a significant decrease of IL-1ra, IL-6, IL-8, G-CSF, IFN-gamma, IP-10, MCP-1, MIP-1 alpha, FGF at T1 compared to T0 (p <= 0.042). Conclusions/Significance Whole-blood IL-4-response to AgB is significantly higher in patients with active compared to inactive CE but apparently not modulated over time after treatment. On the contrary, the levels of IL-1ra, IL-6, IL-8, G-CSF, IFN-gamma, IP-10, MCP-1, MIP-1 alpha, FGF significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients' follow-up. Author summary Cystic echinococcosis (CE) is a complex disease for which a clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. The development of a laboratory test able to assess CE cyst viability and reactivation over time would facilitate the classification of patients and cysts, their rational assignment to a clinical management option and the implementation of a regular follow-up. Here, we evaluated the accuracy of a cytokine-based whole-blood test to detect the reactivation and the viability of hepatic CE cysts. The results showed that IL-4-response to AgB is not modulated over-time after treatment, while, IL-1ra, IL-6, IL-8, G-CSF, IFN-gamma, IP-10, MCP-1, MIP-1 alpha, FGF levels significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients' follow-up.