The use of Circulating Cathodic Antigen rapid test and serology for diagnosis of active Schistosoma mansoni infection in asymptomatic migrants in Italy

Objectives: Diagnosis of schistosomiasis in migrants coming from endemic areas can be difficult, especially in asymptomatic subjects. Light-intensity disease may be missed due to the low sensitivity of the stool microscopy and serologic testing cannot distinguish between a resolved infection and an active infection in patients who have been infected and treated in the past, because specific antibodies can persist despite cure.
Materials and Methods: This is a cross-sectional study on asymptomatic migrants, living in Italy and coming from Egypt, who participated to a survey for the assessment of schistosomiasis at the outclinic of Tropical Medicine of the Infectious Diseases Department, San Raffaele Hospital, since February 2014 to January 2016. Patients were tested for Schistosoma mansoni on single blood [anti-schistosome antibodies, total IgE] and urine [point-of-care (POC) circulating-cathodic-antigen (CCA) test] samples.
POC-CCA test was also evaluated in 5 healthy volunteer subjects never exposed to Schistosoma and in 10 symptomatic patients with an active schistosomiasis diagnosed in Saint Michel Centre (Central African Republic) by microscopic stool analysis. Healthy subjects and patients with active S. mansoni infections were assessed by anti-schistosome antibodies, and POC-CCA test as negative and positive controls.
Results: Overall 82 migrants were evaluated, patients characteristics according to serology for Schistosoma spp are shown in Table 1.
Two male subjects (2.4%) without urinary symptoms had an active infection; 66 subjects (81%) had a past S. mansoni infection, while 14 people had neither an active nor a past infection.
None of the patients with an active infection and 55/66 patients with a past infection had been treated for schistosomiasis in the past; the median time since the last previous treatment was of 31.2 (16.6-65.1) months.
Elevated total IgE were observed in one out of 2 patients with an active S. mansoni infection as well as in 41/66 (62%) patients with a past infection.
The 2 patients with an active infection were subsequently treated with praziquantel (40 mg/kg/day in two doses for three days); they were re-assessed after three months from the end of the treatment and a negative POC-CCA test was observed in both cases.
Discussion: Findings of this study seem to suggest that a positive POC-CCA test is likely associated with the presence of an active infection in patients with a positive serology, no previous treatment for schistosomiasis and regardless of total IgE values. In addition, a negative single POC-CCA test, regardless of total IgE values, may represent a sign of previous S. mansoni infection if associated with a positive serology (immunological memory) or a previous treatment.
Migration from Africa into Europe has greatly increased in recent years and European countries have to face with imported infectious diseases not typically present in Europe. Serologic testing for anti-schistosome antibodies is indicated for diagnosis of travelers or immigrants from endemic areas who have not been treated for schistosomiasis in the past. In patients who have been infected and treated in the past, serologic testing cannot distinguish resolved infection from active infection because specific antibodies can persist despite cure. The antigen test can detect active infection and its validity is supported by findings of previous studies showing that the positive and negative predictive values of a single POC-CCA test are 77% and 72-89%, respectively, if compared to multiple Kato-Katz thick smears as diagnostic reference standard.
As a strength of the study, we highlight that, to our knowledge, this is the first study assessing a sample of patients (although limited in number) living in non-endemic countries tested for schistosomiasis because of their origin instead of symptoms. Among the study limitations, we mention the small number of considered patients, for this reason, our findings may not be intended as confirmatory but rather exploratory. Another limitation is that no stool samples were available in the study patients, impairing the assessment of POC-CCA performance as compared to microscopy, still representing the reference standard for schistosomiasis diagnosis. Further studies including this comparative assessment would be of great value.
Epidemiological surveys in large population of migrants to be tested with POC-CCA are warranted in order to prevent S. mansoni infection long-term complications and to reduce health care costs avoiding useless treatments in case of past Schistosoma infection.
Conclusions: In conclusion, the reported data seem to suggest that the use of POC-CCA urine test may be a simple, non-invasive test to differentiate active from past S. mansoni infection and therefore rapidly guide treatment initiation in migrants from endemic areas and living in non-endemic countries. Further, larger studies, also providing a comparative assessment with stool microscopy, would certainly be of value in elucidating the potential usefulness and cost-effectiveness of POC-CCA test as a screening diagnostic tool also in asymptomatic migrants living in non-endemic high-income countries.

Stefania Chiappetta
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