Application of Urine and Copro Antigen Assays after Primary Infection and Drug Treatment in an Experimental Opisthorchiasis Animal Model

Abstract

Infection by Opisthorchis viverrini causes significant health problems, including cholangiocarcinoma (CCA); thus control and elimination of this trematode is an important strategy for the reduction of CCA. Currently, urine and copro antigen detection is more sensitive than parasitological examination of the feces for the diagnosis of opisthorchiasis. Given limitations in human studies, we used an animal model to quantify the parasite antigen profiles in urine and feces in O. viverrine–infected hamsters, and postdrug treatment. The positive detections of O. viverrini antigen began from week 1 in urine and week 2 in feces after infection until week 28 of the study. The recoveries of O. viverrini worms were detected starting from week 1 and eggs of O. viverrini were detected in feces from week 3 after infection and remained detectable throughout the study period. There was a significant positive correlation of urine and copro antigen levels with the number of fecal egg counts (P < 0.01) and worm recovery (P < 0.01). In the drug-treatment experiment, treatment of infected hamsters with praziquantel significantly reduced worm burden, fecal egg output, and antigen in urine and feces compared with the untreated controls (P < 0.001). At 4 weeks posttreatment, the egg and worm reduction rates were 100% and 95.5%, respectively. The positive antigen detections in urine and feces corresponded with partial worm clearance from praziquantel treatment. This study demonstrated a direct link of urine and copro antigen tests with worms infecting the liver thereby reaffirming the reliability of urine and copro antigen assay in opisthorchiasis diagnosis.

Long-term Persistence of Opisthorchis viverrini Antigen in Urine: A Prospective Study in Northeast Thailand

“…Antigen detection in urine samples provides advantages not only for diagnosis of light infection but also early stage (prepatent) infections where the worms are still in the immature stage and have not reached full reproductive age. 10 Our study supports this possibility because five of 42 individuals (11.9%) had six to 18 eggs per gram of O. viverrini on day 30 of the study. Possible explanations included low worm burden or a small number of very old, degenerating worms.…”

“…Evidence from animal models also indicates that the antigen detected in urine is directly linked to the presence of adult worms in the liver. 10 Therefore, human and animal studies support the reliability of urine antigen detection to indicate active or current opisthorchiasis.…”

Effects of day-to-day variation of Opisthorchis viverrini antigen in urine on the accuracy of diagnosing opisthorchiasis in Northeast Thailand

“…Lastly, an animal model study showed that the antigen detected in urine as well as in feces corresponded to the presence of worms in the liver of the O . viverrini -infected hamsters [ 25 ]. Moreover, after adult worms were killed by praziquantel treatment, the antigen test became negative in hamsters with complete worm clearance and the antigen test remained positive in hamsters with incomplete worm clearance.…”

“…In addition to adult worms, O . viverrini antigen in urine and feces may originate from juvenile worms as early as one week after infection in an opisthorchiasis-animal model [ 25 ]. Further investigation is needed to determine whether a single-worm infection can be detected using urine ELISA, as has been reported in schistosomiasis [ 30 ], since this is a critical threshold to assess the impact of parasite control and elimination programs.…”

Accuracy of a new rapid diagnostic test for urinary antigen detection and assessment of drug treatment in opisthorchiasis

“…A long-standing mass drug administration has resulted in most people still having light O. viverrini infection, but fecal examination methods have low diagnostic sensitivity [13]. Moreover, fecal egg examination is not able to detect prepatent infection, obstruction of eggs in the biliary tract due to chronic brosis, or blockage by adult worms following recent anthelmintic treatment [12][13][14]. Repeated stool examination is recommended to increase the reliability of faecal examination [15,16], but this further increases logistical complexity during population screening.…”