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Background: The point-of-care circulating cathodic antigen (POC-CCA) test is increasingly used as a rapid diagnostic method for Schistosoma mansoni infection.The test has good sensitivity,although false positive results have been reported among pregnant women and patients with urine infections and hematuria.We validated the POC-CCA test’s ability to diagnose Schistosoma mekongi infection in Lao People’s Democratic Republic (Lao PDR),where S.mekongi is endemic.Of particular interest was the test’s specificity and possible cross-reactivity with other helminth infections.Methods: We conducted a cross-sectional study of children and adults in the provinces of Champasack (Schistosoma mekongi and Opisthorchis viverrini endemic),Savannakhet (O.viverrini endemic) and Luang Prabang (soil-transmitted helminths endemic) between October 2018 and April 2019.POC-CCA and urine dipstick tests were administered to all study participants,while an additional pregnancy test was offered to women.Two stool samples were collected from participants and examined with a Kato-Katz test (two smears per stool).Logistic regression was used to associate potential confounding factors (predictors) with POC-CCA test results (outcome).Results: In S.mekongi-endemic Champasack,11.5％ (n =366) and 0.5％ (n =2) of study participants had positive POC-CCA and Kato-Katz test results,respectively.Only one of the two Kato-Katz positive patients was also POC-CCA positive.In Champasack and Luang Prabang,where Sekongi is not endemic,the POC-CCA test yielded (presumably) false positive results for 6.0％ (n =22) and 2.5％ (n =9) of study participants,respectively,while all of the Kato-Katz tests were negative.POC-CCA positive test results were significantly associated with O.viverrini infection (1.69,95％ confidence interval (CI): 1.02-2.77,P=0.042),increased leukocytes (adjusted Odds Ratio (aOR)=1.58,95％ CI: 1.15-2.17,P =0.005) and hematuria (aOR =1.50,95％ CI: 1.07-2.10,P =0.019) if the observed trace was counted as a positive test result.Two pregnant women from Champasack province had POC-CCA positive tests.Conclusions: We observed a cross-reaction between the POC-CCA test and O.viverrini infection.To some extent,we can confirm previous observations asserting that POC-CCA provides false positive results among patients with urinary tract infections and hematuria.In S.mekongi-endemic areas,POC-CCA can be applied cautiously for surveillance purposes,keeping in mind the considerable risk of false positive results and its unknown sensitivity.