Schistosomiasis Screening of Travelers from Italy with Possible Exposure in Corsica, France

To the Editor: Since 2014, many cases of urogenital schistosomiasis acquired in Corsica, France, have been described (1–4). The infections, which all occurred in persons who had bathed in the Cavu River in 2011 or 2013, represent the first cases of autochthonous Schistosoma haematobium infection acquired in Europe since the last reported case in Portugal in 1965 (5). In June 2014, France established a screening program for persons reporting exposure to the Cavu River during 2011–2013. By March 2015, a national surveillance journal had reported 110 autochthonous urogenital schistosomiasis cases in residents of France (6). 
 
We describe the diagnostic work-up for and clinical management of persons from Italy who reported bathing in the Cavu River at least once during 2011–2014. All of the patients had requested screening after learning of the risk for acquiring schistosomiasis after freshwater exposure in Corsica. Exclusion criteria for the study included residence in or travel to a country where schistosomiasis is endemic. 
 
At least 3 months after their last exposure to the Cavu River, each participant had a filtered terminal urine sample and a serum sample tested for schistosomiasis. Different commercial tests were used, depending on local availability: 3 different ELISAs and an indirect immunofluorescent antibody test (IIFAT). All serum samples were tested in parallel in a laboratory in Florence, Italy, by using 2 Western blots (WBs): a Schistosoma WB IgG kit containing antigens from adult S. mansoni worms and a second kit containing S. mansoni and S. haematobium antigens from a crude adult extract (LDBio Diagnostics, Lyon, France). 
 
Confirmed urogenital schistosomiasis was defined by confirmation of S. haematobium eggs in urine by microscopy, positive WB result, or both. Probable urogenital schistosomiasis was defined by positive serologic test results. Possible urogenital schistosomiasis was defined by signs or symptoms suggestive of schistosomiasis (i.e., urogenital symptoms), eosinophilia (>0.4 × 109 cells/L of blood), or both (7). All participants who met the case definition received 1 oral dose of praziquantel (40 mg/kg). 
 
Forty-three persons were consecutively enrolled during January 2014–January 2015; of these, 15 (34%) had confirmed (6 patients), probable (2 patients), or possible (7 patients) urogenital schistosomiasis (Table). Of these 15 patients, 7 (47%) reported repeat visits to Cavu River over a period of at least 2 years. The mean eosinophil count was 295 (range 40–1,540) cells/μL of blood; 6 (40%) patients had eosinophilia. Genitourinary symptoms were reported by 7 (47%) patients, and blood was detected by dipstick in the urine of 1 patient. Schistosoma eggs were not found in any urine samples. 
 
 
 
Table 
 
Demographic, epidemiologic, clinical, and laboratory data for 15 patients with urogenital schistosomiasis acquired after bathing in the Cavu River, Corsica, France* 
 
 
 
Schistosomiasis screening has been suggested for persons with exposure to the Cavu River (6); however, clinical history and clinical evaluation alone and eosinophilia, have low sensitivity for the diagnosis of urogenital schistosomiasis (7,8). Asymptomatic infection has been reported in 25%–36% of persons with travel-associated schistosomiasis, and eosinophilia was present in 50% of the patients (7,8). In screenings in France, only 27% of schistosomiasis-positive patients reported genitourinary symptoms (6). 
 
For the diagnosis of urogenital schistosomiasis, serologic testing is more sensitive than detection of eggs in urine, particularly in mild infections (7–9). Many asymptomatic family members of the index case-patients who acquired infection in Corsica tested positive only by serologic testing (1–4). However, commercial serologic tests for schistosomiasis have low sensitivity (9). Kinkel et al. (9) showed that sensitivity of an IIFAT and 3 ELISAs for S. haematobium ranged from 21.4% to 71.4%. In the Corsica outbreak, serologic testing may be even less sensitive because of the hybrid nature of the schistosoma (S. haematobium/S. bovis) (6). In our study, only 2 patients had positive ELISA results. Combinations of >2 serologic tests can markedly increase testing sensitivity to almost 78.6% (9). 
 
Sulahian et al. (10) found that a WB containing S. mansoni antigens had 89.5% sensitivity and 100% specificity for S. mansoni. In our study, no patients with urogenital schistosomiasis tested positive by WB containing S. mansoni antigens, but 6 patients tested positive by WB containing S. haematobium antigens. 
 
In mild infections, the absence of schistosoma antibodies cannot exclude a diagnosis of urogenital schistosomiasis (7). Therefore, we provided treatment to patients with possible urogenital schistosomiasis; our decision to treat these patients considered the tolerability of praziquantel and the possible severe genitourinary complications of untreated infections (e.g., bladder carcinoma, infertility). 
 
Our findings suggest that a sensitive screening strategy for urogenital schistosomiasis consists of a patient’s travel history (exposure in multiple years), clinical history (any new genitourinary complaints after freshwater exposure), eosinophil count, and serologic testing. Because of the failure of commercial ELISA and IIFAT methods, we emphasize that a WB containing S. haematobium antigen should also be used for screening. 
 
Of note, a confirmed urogenital schistosomiasis case acquired after a single exposure in 2014 was never reported (1–4,6). The risk for delayed diagnosis of this insidious, neglected disease, which has recently reappeared in Europe, must be reduced. To accomplish this, information regarding the risk for schistosomiasis after freshwater exposure in Corsica must be disseminated to physicians worldwide.

To the Editor: Since 2014, many cases of urogenital schistosomiasis acquired in Corsica, France, have been described (1)(2)(3)(4). The infections, which all occurred in persons who had bathed in the Cavu River in 2011 or 2013, represent the first cases of autochthonous Schistosoma haematobium infection acquired in Europe since the last reported case in Portugal in 1965 (5). In June 2014, France established a screening program for persons reporting exposure to the Cavu River during 2011-2013. By March 2015, a national surveillance journal had reported 110 autochthonous urogenital schistosomiasis cases in residents of France (6).
We describe the diagnostic work-up for and clinical management of persons from Italy who reported bathing in the Cavu River at least once during 2011-2014. All of the patients had requested screening after learning of the risk for acquiring schistosomiasis after freshwater exposure in Corsica. Exclusion criteria for the study included residence in or travel to a country where schistosomiasis is endemic.
At least 3 months after their last exposure to the Cavu River, each participant had a filtered terminal urine sample and a serum sample tested for schistosomiasis. Different commercial tests were used, depending on local availability: 3 different ELISAs and an indirect immunofluorescent antibody test (IIFAT). All serum samples were tested in parallel in a laboratory in Florence, Italy, by using 2 Western blots (WBs): a Schistosoma WB IgG kit containing antigens from adult S. mansoni worms and a second kit containing S. mansoni and S. haematobium antigens from a crude adult extract (LDBio Diagnostics, Lyon, France).
Confirmed urogenital schistosomiasis was defined by confirmation of S. haematobium eggs in urine by microscopy, positive WB result, or both. Probable urogenital schistosomiasis was defined by positive serologic test results. Possible urogenital schistosomiasis was defined by signs or symptoms suggestive of schistosomiasis (i.e., urogenital symptoms), eosinophilia (>0.4 × 10 9 cells/L of blood), or both (7). All participants who met the case definition received 1 oral dose of praziquantel (40 mg/kg).
Forty-three persons were consecutively enrolled during January 2014-January 2015; of these, 15 (34%) had confirmed (6 patients), probable (2 patients), or possible (7 patients) urogenital schistosomiasis (Table). Of these 15 patients, 7 (47%) reported repeat visits to Cavu River over a period of at least 2 years. The mean eosinophil count was 295 (range 40-1,540) cells/μL of blood; 6 (40%) patients had eosinophilia. Genitourinary symptoms were reported by 7 (47%) patients, and blood was detected by dipstick in the urine of 1 patient. Schistosoma eggs were not found in any urine samples.
Schistosomiasis screening has been suggested for persons with exposure to the Cavu River (6); however, clinical history and clinical evaluation alone and eosinophilia, have low sensitivity for the diagnosis of urogenital schistosomiasis (7,8). Asymptomatic infection has been reported in 25%-36% of persons with travel-associated schistosomiasis, and eosinophilia was present in 50% of the patients (7,8). In screenings in France, only 27% of schistosomiasis-positive patients reported genitourinary symptoms (6).
For the diagnosis of urogenital schistosomiasis, serologic testing is more sensitive than detection of eggs in urine, particularly in mild infections (7)(8)(9). Many asymptomatic family members of the index case-patients who acquired infection in Corsica tested positive only by serologic testing (1)(2)(3)(4). However, commercial serologic tests for schistosomiasis have low sensitivity (9). Kinkel et al. (9) showed that sensitivity of an IIFAT and 3 ELISAs for S. haematobium ranged from 21.4% to 71.4%. In the Corsica outbreak, serologic testing may be even less sensitive because of the hybrid  nature of the schistosoma (S. haematobium/S. bovis) (6). In our study, only 2 patients had positive ELISA results. Combinations of >2 serologic tests can markedly increase testing sensitivity to almost 78.6% (9). Sulahian et al. (10) found that a WB containing S. mansoni antigens had 89.5% sensitivity and 100% specificity for S. mansoni. In our study, no patients with urogenital schistosomiasis tested positive by WB containing S. mansoni antigens, but 6 patients tested positive by WB containing S. haematobium antigens.
In mild infections, the absence of schistosoma antibodies cannot exclude a diagnosis of urogenital schistosomiasis (7). Therefore, we provided treatment to patients with possible urogenital schistosomiasis; our decision to treat these patients considered the tolerability of praziquantel and the possible severe genitourinary complications of untreated infections (e.g., bladder carcinoma, infertility).
Our findings suggest that a sensitive screening strategy for urogenital schistosomiasis consists of a patient's travel history (exposure in multiple years), clinical history (any new genitourinary complaints after freshwater exposure), eosinophil count, and serologic testing. Because of the failure of commercial ELISA and IIFAT methods, we emphasize that a WB containing S. haematobium antigen should also be used for screening.
Of note, a confirmed urogenital schistosomiasis case acquired after a single exposure in 2014 was never reported (1)(2)(3)(4)6). The risk for delayed diagnosis of this insidious, neglected disease, which has recently reappeared in Europe, must be reduced. To accomplish this, information regarding the risk for schistosomiasis after freshwater exposure in Corsica must be disseminated to physicians worldwide.