Hepatobiliary fascioliasis: A neglected re-emerging threat, its diagnostic and management challenges

Table 1 Challenges in fascioliasis diagnostics and emerging techniques

Method		Strengths	Challenges	Emerging solutions/comments
Stool analysis		Direct detection of eggs in stool samples confirms active infection	Does not allow the differentiation between F. gigantica and F. hepatica due to morphological similarities, delay in detection (only positive 3-4 months post-infection), intermittent egg output, low or absent egg shedding in light infections, chronic cases, ectopic infections, or false positives from ingested infected liver tissue	Necessitates alternative or adjunct diagnostic methods due to limited sensitivity in early and complex cases
Serology	Serological tests using excretory/secretory Antigens[29,30]	ELISA-based tests using purified or recombinant antigens (e.g., cysteine proteinases produced in yeasts[29] or in E. coli[30]) offer high sensitivity and specificity, particularly for F. hepatica and F. gigantica	May suffer from cross-reactivity with antibodies against other helminths; delayed seroconversion in the acute phase; cannot differentiate between species in regions where both coexist	Recombinant antigens produced in yeast or E. coli have been successfully incorporated into ELISA protocols, improving diagnostic performance
	MM3 coproantigen-detection test[31]	Provides high sensitivity and specificity; suitable for large-scale screening, early detection in chronic infections, and monitoring treatment outcomes	Limited in its ability to quantify fluke burden on its own, which is crucial for determining appropriate treatment doses and assessing disease intensity	The use of a new preservative/diluent (CoproGuard™) has enhanced coproantigen extraction and antigen stability, potentially improving the test's diagnostic yield[32]
	Commercial F. hepatica IgG ELISA[26]	High sensitivity and high negative predictive value, making it useful for ruling out infection when combined with a compatible clinical history	Exhibits a low positive predictive value and lacks correlation with egg output, necessitating confirmation with additional diagnostic methods to avoid misclassification, particularly in areas with potential cross-reactive helminth infections	Considered promising for individual diagnosis and large-scale epidemiological studies, provided it is supplemented by other diagnostic tests to confirm positive results
	SeroFluke Lateral Flow Test[33]	Offers maximal specificity and sensitivity; applicable to both serum and whole-blood samples; user-friendly and suitable for point-of-care testing in both hospital settings and endemic regions	While promising, further validation is required to fully assess its performance across diverse clinical settings and to ensure its reliability in routine diagnostic practice	Represents a significant step forward in rapid, field-friendly diagnostics, potentially addressing the shortcomings of more invasive or technically demanding methods

Table 2 Summary of antiparasitic medications, including dosages and treatment regimens

Drug	Mechanism of action	Dose	Comments
Triclabendazole	Binds to β-tubulin, inhibiting microtubule formation, leading to impaired motility and disruption of vital processes in the parasite	For patients ≥ 6 years: Two doses of 10 mg/kg administered 12 hours apart (alternatively, a single 10 mg/kg dose has been used)	Taken orally with food to improve absorption. It is the drug of choice for fascioliasis, with extensive clinical experience supporting its efficacy against both immature and mature stages. FDA-approved for use in patients aged six and older. Caution is advised in patients with preexisting QTc prolongation. Resistance has been documented in some cases
Nitazoxanide	Inhibits the pyruvate: Ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction essential for anaerobic energy metabolism	For adults: 500 mg orally twice daily for 7 days	Proposed as an alternative, especially for chronic infection. However, conflicting evidence on its efficacy (ranging from as high as 94% to as low as 36%) limits its recommendation as a reliable therapeutic option
Praziquantel	Increases calcium ion permeability in parasite membranes, causing muscle contraction and paralysis	Once considered as an alternative, praziquantel is now contraindicated for fascioliasis due to insufficient efficacy against Fasciola species
Bithionol	Disrupts oxidative phosphorylation, impairing energy metabolism in parasites	A halogenated phenol formerly used as primary therapy for fascioliasis in the United States; it has been discontinued
Emetine/Dehydroemetine	Inhibits protein synthesis by interfering with the elongation step in translation	Discontinued because of inadequate efficacy and safety issues
Metronidazole	Undergoes reduction in anaerobic organisms to form reactive nitro radicals that damage DNA and other critical biomolecules
Albendazole	Binds to β-tubulin, inhibiting microtubule polymerization, leading to impaired glucose uptake and energy depletion in parasites
Niclofolan	Disrupts energy metabolism by uncoupling oxidative phosphorylation in parasite mitochondria
Chloroquine	Inhibits DNA and RNA biosynthesis and causes degradation of ribosomes in parasites
Hexachloro-para-xylol	Disrupts parasite metabolism through oxidative damage and interference with enzymatic processes
Artemisinin derivatives (artesunate/artemether)	Activated by heme iron to produce free radicals that alkylate and damage parasite proteins and membranes