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

Linda Petrone,Saeid Najafi Fard,Mara Mariconti,Ambra Vola,Delia Goletti,Francesca Tamarozzi,Alessandra Ludovisi,Maria Angeles Gomez Morales,Enrico Brunetti,Keke C Fairfax

doi:10.1371/journal.pntd.0009648

Abstract

BackgroundCystic 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 findingsThirty 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/SignificanceWhole-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.

Highlights

Cystic echinococcosis (CE) is a parasitic zoonosis globally distributed, caused by infection with the larval stage of Echinococcus granulosus sensu lato, endemic in rural livestockraising areas, including Italy [1]
Additional studies are needed to understand whether these findings might have a clinical significance for patients’ follow-up
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 followup

Summary

Introduction

Cystic echinococcosis (CE) is a parasitic zoonosis globally distributed, caused by infection with the larval stage (cysts) of Echinococcus granulosus sensu lato, endemic in rural livestockraising areas, including Italy [1]. CE is a complex disease with clinical presentations ranging from asymptomatic infection to severe, even fatal, disease [3]. CE cysts may present in different stages, each with a peculiar morphology and different recommended clinical management approach [4]. Inaccurate diagnosis and staging contribute to the health and economic burden that CE causes on patients and health systems in endemic areas. 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

Methods

Results

Discussion

Conclusion