Which diagnostic tests (stool, serology, imaging, ERCP) are most sensitive for detecting human pancreatic trematode infections?
Executive summary
Human pancreatic trematode infections are rare and poorly studied, so diagnostic performance is inferred from data on related biliary and intestinal trematodes: molecular (PCR/qPCR) and antigen-detection assays (coproantigen/CCA-style tests) offer the highest sensitivity, especially in low-intensity or submicroscopic infections, while conventional stool microscopy (egg detection) remains the historical gold standard but is comparatively insensitive; serologic ELISAs are highly sensitive and practical for screening but can struggle to distinguish active from past exposure, and imaging/ERCP are valuable for direct visualization in established ductal disease but are not sensitive screening tools [1] [2] [3] [4] [5].
1. The messy gold standard: stool microscopy is specific but often insensitive
Parasitological detection of eggs in feces, sputum or urine has been the traditional “gold standard” for trematodiases and remains the reference in many textbooks and reviews because finding eggs is definitive evidence of infection [3] [6]. However, routine microscopy and single-sample techniques substantially underestimate prevalence in low-intensity infections and are limited by operator skill and intermittent egg shedding; concentrating methods (sedimentation, multiple samples) improve yield but do not fully close the sensitivity gap [7] [8].
2. Serology (ELISA and related antibody tests): most sensitive and practical for many trematodes
Antibody-based assays—including indirect hemagglutination, indirect immunofluorescence, and especially ELISA—are widely used for diagnosis and seroepidemiology, with ELISA described repeatedly as the most sensitive and practical serologic tool for trematode detection [2] [6]. That advantage makes serology useful for screening and in prepatent infections when eggs are absent, but antibodies may persist after cure and, as with other parasites, a positive serologic titre does not always prove active infection without corroborating evidence (analogy from serology caveats in parasitology) [2] [4].
3. Antigen detection and molecular testing: highest sensitivity for active infections, especially at low intensity
Coproantigen ELISAs and circulating antigen tests have demonstrated high sensitivity and specificity for particular trematodes (for example, an ELISA targeting an O. viverrini antigen performed well in stool) and can reflect active infection more reliably than antibody tests [2]. Molecular assays (conventional PCR and qPCR) have shown excellent sensitivity and species discrimination—some studies report detection of parasites missed by microscopy and even 100% sensitivity in validation subsets—making DNA-based tests the most sensitive tools when available and properly validated for the species in question [1] [7] [9]. Reviewers note, however, that molecular specificity can be challenged in regions with many related trematodes, so assay design and local validation are critical [5].
4. Imaging and ERCP: high specificity when positive but poor as population-level detectors
Cross-sectional imaging (ultrasound, CT, MRI) and endoscopic retrograde cholangiopancreatography (ERCP) can directly demonstrate worms, ductal dilatation, or characteristic cystic changes in biliary and pancreatic ducts, and ERCP has proven useful diagnostically and therapeutically in biliary fascioliasis [2] [4]. For pancreatic flukes specifically, definitive diagnosis has sometimes come from autopsy or direct visualization of adult worms in ducts, underscoring that imaging/ERCP detect established or heavy infections but are insensitive for early or low-burden disease and are invasive or resource-intensive [10] [4].
5. Bottom line and limits of the evidence
For detecting human pancreatic trematodes, the best available evidence—largely extrapolated from biliary/intestinal trematodes—places molecular assays (PCR/qPCR) and antigen-detection tests at the top of sensitivity for active infections, with serologic ELISAs excellent for screening and stool microscopy definitive but relatively insensitive [1] [2] [3]. Important caveats: species-specific validation is often lacking for rare pancreatic flukes, cross-reactivity and lack of a universal gold standard complicate interpretation, and imaging/ERCP are confirmatory rather than sensitive screening modalities [5] [6] [4]. The literature contains case reports (including autopsy-confirmed Eurytrema pancreaticum) but few large diagnostic accuracy studies focused solely on pancreatic trematodes, so recommendations rest on the broader trematode diagnostic literature [10] [3].