An update on immunodiagnosis of cystic echinococcosis

doi:10.1016/S0001-706X(02)00225-5

Acta Tropica

Volume 85, Issue 2, February 2003, Pages 165-171

https://doi.org/10.1016/S0001-706X(02)00225-5 Get rights and content

Abstract

Immunological parameters are increasingly investigated as possible markers for the development of cystic echinococcosis. Among the newer immunologic tests for assessing the host–parasite relationship, assay of immunoglobulin isotypes with the use of distinct parasite antigens and detection of Th1/Th2 cytokine expression are an interesting new approach. The findings upon which we have constructed our immunological hypothesis of the host–parasite relationship are: (1) immunoglobulin isotype profiles differ in patients with distinct clinical outcomes of the disease; in particular, antigen B is the antigen of choice to detect specific IgG4, which is the immunoglobulin isotype most clearly associated with the progression of the disease; (2) the isolation and characterisation of recombinant parasite proteins that behave as molecular markers of allergic reactions associated with cystic echinococcosis; (3) Th1/Th2 cell activation is involved in the clinical outcome of Echinococcus granulosus infection and, in particular Th2 response, is associated with susceptibility to the disease, whereas a Th1 response is associated with protective immunity.

Section snippets

IgE and IgG-subclass antibody responses in the follow up of pharmacologically treated CE patients

Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is an important public health problem in many regions of the world, both in areas where the disease is endemic, and in regions where the disease is emerging or re-emerging (Schantz et al. 1995; Craig et al., 1996). Early diagnosis is important because prompt intervention can reduce morbidity. Owing to the variable signs and symptoms of the disease, the clinical diagnosis of CE is often difficult and requires physical

Recombinant allergens in the immunodiagnosis of CE

Current research involves investigation of synthetic peptides derived from sequences of antigen 5 and AgB (Leggatt and McManus, 1994; Barbieri et al., 1998) and to produce recombinant antigens with improved sensitivity and specificity as immunodiagnostic tools (Muhlschlegel et al., 1993; Ersfeld and Craig, 1995; Martin et al., 1996; Colebrook and Lightowlers, 1997).

An increased level of specific IgE antibodies is a characteristic feature of the immune response in helminth infections (Allen and

Th1/Th2 cytokine expression in CE

New interesting perspectives in the clinical follow-up of patients with CE derive from recent observations that Th1/Th2 cell activation is involved in the outcome of E. granulosus infection. A stable balance between Th1 and Th2 populations occurs through the production of regulatory cytokines, which induce reciprocal inhibition: IFN-γ and IL-12 inhibit proliferation of Th2 cells; IL-10, a polyfunctional cytokine produced by Th2 cells, macrophages/monocytes and B cells, down regulates Th1

Acknowledgements

This work was supported by Italian Ministry of Health grants (‘Surveillance project on emerging and re-emerging infectious disease’ and ‘Allergic diseases: development of diagnostic and therapeutic tools and evaluation of their suitability for the management of the allergic patient’) from the ISS (Italian Superior Institute of Health) (art. 502/12) and by grant I.S.S. n.1139/RI.

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Past and present of diagnosis of echinococcosis: A review (1999–2021)
2023, Acta Tropica
The larval forms of taeniid cestodes belonging to the genus Echinococcus are the source of the zoonotic infection known as echinococcosis. Alveolar and cystic echinococcosis are caused by Echinococcus multilocularis and Echinococcus granulosus (s. s), respectively. It is endemic in several regions of the world. In this systematic review, we describe diagnosis, and the species (human, canids, livestock, and small rodents) affected by cystic (CE) and alveolar echinococcosis (AE). From 1999 to 2021, we searched the online directory through PubMed, SCOPUS, Web of Science, and google scholar. Among the 37,700 records found in the online databases, 187 publications met our eligibility requirements. The majority of investigations employed a range of diagnostic methods, such as ELISA, imaging, copro-PCR, necropsy or arecoline hydrobromide purgation, morphological cestode confirmation, and fecal sieving/flotation to detect and confirm Echinococcus infection. ELISA was the most commonly used method followed by PCR, and imaging. The research team retrieved data describing the incidence or assessment of the diagnostic test for E. multilocularis in humans (N = 99), canids (N = 63), small ruminants (N = 13), large ruminants (N = 3), camel (N = 2), pigs (N = 2) and small mammals (N = 5). This study was conducted to explore the diagnostic tools applied to detect echinococcosis in humans as well as animals in prevalent countries, and to report the characteristic of new diagnostic tests for disease surveillance. This systematic review revealed that ELISA (alone or in combination) was the most common method used for disease diagnosis and diagnostic efficacy and prevalence rate increased when recombinant antigens were used. It is highly recommended to use combination protcols such as serological with molecular and imaging technique to diagnose disease. Our study identified scarcity of data of reporting echinococcosis in humans/ animals in low-income or developing countries particularly central Asian countries. Study reports in small rodents indicate their role in disease dissemination but real situation in these host is not reflected due to limited number of studies. Even though echinococcosis affects both public health and the domestic animal sector, therefore, it is important to devise new and strengthen implementation of the existing monitoring, judging, and control measures in this estimate.
Human cystic echinococcosis: Serological diagnosis by indirect hemagglutination test, enzyme-linked immunosorbent assay, immunoelectrophoresis, and immunoblotting in surgically confirmed patients versus cases diagnosed by imaging techniques
2020, Medecine et Maladies Infectieuses
Human cystic echinococcosis (CE) diagnosis is based on imaging findings and serology. Serology is the first-line test followed by imaging tests.
A total of 268 serum samples from CE patients were included in this study. The serodiagnosis was made simultaneously by indirect hemagglutination assay (IHA), enzyme-linked immunosorbent assay (ELISA), immunoblotting test (IB), and immunoelectrophoresis (IEP).
In serum samples belonging to surgically confirmed CE patients, we observed a percentage of positivity of 83.7% [77.2%–89.0%] and 80.7% [73.9%–86.4%] for IHA and IgG-ELISA, respectively. IgG-IB was associated with a higher positivity rate than IEP with 81.3% [74.6%–86.9%] and 62.0% [54.2%–69.5%], respectively. IHA and ELISA results were analyzed using cut-off generated by receiver operating curves. The best diagnostic performances were achieved by IHA (cut-off ≥ 1/128) and ELISA (> 1.16 index). Sensitivities reported in patients with suggestive imaging findings and positive Echinococcus IB were 86.2% [78.0%–92.2%], 72.5% [62.8%–80.9%], 49.0% [39.0%–59.1%] for IHA, IgG-ELISA, and IEP, respectively. All tests gave false negative results in the confirmed CE group. Overall, 18.6% of negative results were obtained by IgG-IB test. Cross-reactivities with non-hydatid serum samples were observed in all tests. Only one patient carrying Taenia saginata serum cross-reacted with 8/12 kDa band by IB. We observed specificity at 73% [63.2%–81.4%], 87% [78.8%–92.9%], 99% [94.6%–100.0%], and 99% [94.6%–100.0%] with IHA, IgG-ELISA, IEP, and IgG-IB, respectively. Serology was less sensitive (74%) in lung cysts. Sensitivity was better in liver cysts, especially by IgG-IB (96%).
L’immunodiagnostic de l’échinococcose kystique (EK) humaine repose sur l’imagerie et la sérologie.
Deux cent soixante-huit sérums de patients atteints d’EK ont été inclus dans cette étude. Le sérodiagnostic a été simultanément effectué par hémagglutination indirecte (HAI), méthode immuno-enzymatique Elisa, immunoempreinte (IB) et immunoélectrophorèse (IEP).
Dans le groupe des sérums de patients présentant une EK prouvée chirurgicalement, la positivité de l’HAI et de l’IgG-Elisa était de 83,7 % [77,2 %–89,0 %] et 80,7 % [73,9 %–86,4 %] respectivement alors que la positivité de l’IB était meilleure que celle de l’IEP (81,3 % [74,6 %–86,9 %] et 62,0 % [54,2 %–69,5 %] respectivement). En appliquant les seuils générés par la courbe ROC, de meilleures performances diagnostiques ont été retrouvées par HAI (≥ 1/128) et par Elisa (index > 1,16). Dans le groupe des sérums de patients diagnostiqués par imagerie et une sérologie positive par IB, les pourcentages étaient 86,2 % [78,0 %–92,4 %], 72,5 % [62,8 %–80,9 %], 49,0 % [39,0 %–59,1 %] pour l’HAI, l’IgG-Elisa et l’IEP respectivement. L’IB était négatif dans 18,6 % des cas prouvés. Un sérum de patient hébergeant Tænia saginata a réagi par IB avec la fraction antigénique 7/8 kDa. La spécificité de HAI, IgG-Elisa, IEP et IgG-IB était de 73 % [63,2 %–81,4 %], 87 % [78,8 %–92,9 %], 99 % [94,6 %–100,0 %] et 99 % [94,6 %–100,0 %] respectivement. Pour les kystes pulmonaires, la sérologie était peu performante (74 %). Elle était meilleure au niveau hépatique, notamment par IgG-IB (96 %).
Potential role of NF-κB pathway in the immuno-inflammatory responses during human cystic echinococcosis
2020, Acta Tropica
Citation Excerpt :
The established parasite modulates the immune responses by inducing a concurrent intervention of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines (Mezioug and Touil-Boukoffa, 2009; Rigano’ et al., 1995). Strong Th2 response correlates with susceptibility to progressive disease, whereas a Th1 activation is crucial for protective immunity (Mezioug and Touil-Boukoffa, 2009;Ortona et al., 2003; Rigano et al., 1995). Many studies have provided deeper insights into the essential role for Th1 cells, which secrete IFN-γ, in protective immunity through activation of macrophages to produce nitric oxide (NO) (Mezioug and Touil-Boukoffa, 2009; Touil-Boukoffa et al., 1998).
Cystic echinococcosis (CE) induces in the human host innate and adaptive immune response that plays an important role in controlling the immunopathogenesis. Due to the crucial role of nuclear factor kappa B (NF-κB) in regulating immuno-inflammatory processes, we investigated its potential contribution in systemic and local immuno-inflammatory responses in primary CE patients and relapsed patients. The expression of NF-κB and inducible nitric oxide synthase (iNOS) was analyzed in peripheral blood mononuclear cells (PBMC) as well as in pericystic layer of pulmonary hydatid cysts from Algerian primary CE patients and relapsed patients. Tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) production was evaluated in plasma samples. Our results showed high iNOS and NF-κB expression in both PBMCs and pericystic histiocytes from primary CE patients. In addition, substantial amounts of systemic NO and TNF-α were detected in the same patients. Remarkably, relapsed patients exhibited a low NF-κB and iNOS expression associated with low amounts of plasmatic TNF-α and NO. Collectively, NF-κB/iNOS pathway is involved in the host defense mechanisms at the systemic and local level during primary CE. Our results indicate that the inhibition of this pathway in relapsed patients will attenuate protective immunity and promote parasite escape. This study allowed to identify a novel predictive biomarkers of hydatidosis.
Nonthermal Ablation of Liver Lesions
2020, Image-Guided Interventions: Expert Radiology Series, Third Edition
Percutaneous image-guided chemical ablation plays a role in the management of a wide spectrum of liver lesions, ranging from simple liver cysts to multifocal primary or metastatic liver tumors. This chapter discusses the indications, contraindications, and controversies involving chemical ablation compared with surgical and other locoregional therapies in the management of liver lesions. Current literature supports the superiority of thermal ablation over chemical ablation. However, chemical ablation is a safe, simple, and effective procedure that offers many distinct advantages especially in patients who are not candidates for thermal ablation.
Hydatidosis: Preparation and evaluation of radiolabeled antigens and antibodies
2018, Experimental Parasitology
Citation Excerpt :
These serological tests are considered to be useful to confirm clinical findings, not only for the primary diagnosis but also for the follow-up of patients after surgical or pharmacological treatment (Lightowlers and Gottstein, 1995; Ortona et al., 2003). However, despite the development of sensitive and specific techniques, the immunodiagnosis of this disease remains a complex task (Ortona et al., 2003) since most tests give false negative or positive results (Fotoohi et al., 2013) and the lack of standardization of assays also contributes to discrepant results as reported by the various laboratories(Ortona et al., 2003). The surgical treatment is the only means of treatment despite advances in surgical techniques and drug therapy attempts (Anadol et al., 2001; Teggi et al., 1993).
The present preliminary study intends to evaluate the in vitro use of hydatid antigen and their antibodies once labeled with iodine 125(I¹²⁵) and characterized from viewpoint of radiochemical purity and immunoreactivity.
Radiolabelled molecules gave satisfactory purity of 94% and 96%–98%, for hydatid antigen and IgG respectively. As regards, the specific activity of these latter, varied between 4.79 and 5.97 μCi/μg.
The specificity test of radiolabelled IgG against the hydatid membranes showed a significant recognition that increased proportionally according to the contact surface. Likewise this immunoreactivity test performed with a simple binding assay, using human hydatid fluid antigen (HHF-Ag), previously fixed on a solid phase, gave satisfactory fixation rate of the order of 356 ± 48.08cpm, 2539 ± 550.12cpm and 6558 ± 712.76cpm for the concentrations of 0.1 μg/ml, 2 μg/ml and 25 μg/ml respectively.
Statistical study of 88 sera, carried out with radiolabelled antigen (¹²⁵I-HHF-Ag) in competitive radioimmunoassay test (CRIA) showed highly significant difference (p < 0.0001) in the binding capacity of antigens from patients sera with hydatid disease (65.63 ± 9.12) compared to the negative sera (19.25 ± 14.84). No cross reaction was observed using sera from patients with toxoplasmosis (33, 07 ± 13, 07) and the difference was highly significant (p < 0.0001) compared to E granulosus infected patient sera. Furthermore, this test seemed to be sensitive since among the 43 sera tested, only 37 (86%) were found to be positive by passive hemagglutination (HAP), while the totality (100%) responded positively by CRIA.
Our findings are encouraging, suggesting that these radiolabeled molecules could be useful for advancing toward new diagnostic and therapeutic modalities.
Liver hydatid disease: Still a problem
2016, Medicina Clinica

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¹: Both E. Ortona and R. Riganò contributed equally to this work.

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Review articleAn update on immunodiagnosis of cystic echinococcosis

Abstract

Section snippets

IgE and IgG-subclass antibody responses in the follow up of pharmacologically treated CE patients

Recombinant allergens in the immunodiagnosis of CE

Th1/Th2 cytokine expression in CE

Acknowledgements

Adv. Parasitol.

J. Allergy Clin. Immunol.

Mol. Biochem. Parasitol.

Mol. Biochem. Parasitol.

Curr Opin Immunol.

Mol. Biochem. Parasitol.

Acta Trop.

Immunol. Today

Ann. Allergy Asthma Immunol.

Trans. Royal Soc. Trop. Med. Hyg.

Mol. Biochem. Parasitol.

Mol. Biochem. Parasitol.

Immunology of human helminth infection

Int. Arch. Allergy Immunol.

Cyclophilins and their possible role in the stress response

Int. J. Exp. Pathol.

IgE-mediated reactions to autoantigens in allergic diseases

Int. Arch. Allergy Immunol.

Diagnostic evaluation of a synthetic peptide derived from a novel antigen B subunit as related to other available peptides and native antigens used for serology of cystic hydatidosis

Parasite Immunol.

Serological reactivity to heat shock protein 70 in patients with hydatid disease

Parasite Immunol.

Isolation, characterization, and comparison of antipeptide and antiprotein rabbit antibodies to the p-isoform of glutathione S-transferase

Z. Naturforsch.

Cloning and immunological characterization of Echinococcus granulosus ferritin

Parasitol. Res.

Molecular cloning of an Echinococcus granulosus protein expressing an immunogenic epitope of antigen 5

Mol. Biochem. Parasitol.

IgE and protective immunity to helminth infections

Parasite Immunol

Review article
An update on immunodiagnosis of cystic echinococcosis