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

PLoS Negl Trop Dis. 2021 Aug 20;15(8):e0009648. doi: 10.1371/journal.pntd.0009648. eCollection 2021 Aug.

Abstract

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-γ, IP-10, MCP-1, MIP-1α, 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-γ, IP-10, MCP-1, MIP-1α, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albendazole / therapeutic use
  • Animals
  • Cysts / immunology*
  • Cytokines / blood
  • Echinococcosis / blood*
  • Echinococcosis / drug therapy
  • Echinococcus granulosus / immunology*
  • Female
  • Hematologic Tests
  • Humans
  • Interleukin-4 / blood*
  • Life Cycle Stages / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome

Substances

  • Cytokines
  • Interleukin-4
  • Albendazole

Grants and funding

This work was supported by grants from the Italian Ministry of Health Linea 1-Ricerca Corrente and Ricerca Finalizzata-Giovani Ricercatori “New diagnostic approaches for cystic echinococcosis through antigen discovery and detection of immune responses” [grant number GR-2016-02361497, Principal Investigator: LP]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.