Our results show that, as a population, male long-term migrants from sub-Saharan African areas with a high endemicity of schistosomiasis tend to have a history of unexplained genitourinary signs and symptoms, which are significantly associated with having positive Schistosoma serology test results, even though urine exams fail to detect evidence of parasites. In most of the cases studied here, despite many previous contacts with the health care system in the receiving country during which no definitive diagnosis for those clinical signs or symptoms had been given, schistosomiasis had not been considered. In fact, only 11 over 399 (2.8%) individuals initially screened had received praziquantel in the past and were consequently excluded from this study. These data suggest that untreated long-lasting chronic infection with S. haematobium can be associated in males with a considerable burden of urogenital involvement and may be largely underestimated. A review of the literature found that all studies that focused exclusively on MGS were performed in endemic countries or only included recently arrived migrants [12]. In these studies symptoms associated with MGS were frequent (i.e. haematospermia and genital or coital pain), as was the observation of eggs in urine and/or semen [13, 19] or prostate biopsy [20]. However, studies were found that focused specifically on male MGS among long-term residents in non-endemic countries.

Whether these signs and symptoms correspond to low-grade persistent active infection or alternatively to post-infection chronic sequelae is currently unknown. The diagnosis of active schistosomiasis in people exposed so many years before is extremely difficult. The diagnostic yield of urine exams is low and urine antigen or even PCR tests have not been validated for chronic infections, nor are they routinely available in non–endemic countries. We found significantly higher rates of up to 8 key genitourinary clinical signs or symptoms in these untreated male sub-Saharan African migrants. These signs and symptoms included, in decreasing order of prevalence: haematuria, dysuria, pelvic pain, infertility, orchitis, dyspareunia, erectile dysfunction, and unspecific syndromic STI, all them without isolation of the causal agent. These conditions may have led to frequent consultations with the health care system and even misguided treatments for certain interrelated conditions.

According to our network analysis, male genitourinary signs and symptoms tend to present as clusters in any one individual rather than as a single clinical finding in isolation. Furthermore, the manifestations of chronic urogenital involvement of schistosomiasis may have different features compared to those seen in acute infection in recently exposed individuals. Our analysis indicates that the optimal definition of a potential MGS case is when at least 3 clinical signs or symptoms are present, for all parameters measured, followed by dysuria and pain on ejaculation. This suggests that these latter two are key symptoms of genitourinary schistosomiasis. We also found that pain on ejaculation, dyspareunia, and haematospermia tend to present together in individuals. By the same token, dysuria, haematuria, urethral discharge and UTI also tend to appear in clusters. In contrast, infertility, pelvic pain, and erectile dysfunction tend not to be clustered with other signs or symptoms.

The relationship to MGS of one characteristic condition, male infertility, has already been described in the context of endemic countries [12, 21]. There are different causal pathways underpinning infertility in schistosomiasis, including inflammation, mechanical blockage, the destruction of anatomical structures [21, 22], or hormonal disruption [23]. The prevalence of female infertility associated with S. haematobium infection in endemic countries seems to parallel the male infertility found in this study [24].

Overall, the weak ability of gold standard tests (i.e. direct urine or tissue microbiology determination of schistosomiasis) to confirm active disease among long-term migrants and the limited specificity and sensitivity of serologic methods [25, 26] accentuate the need for a set of clinical criteria to expedite screening for MGS in exposed migrants. It is important to also consider the linguistic and cultural factors that can impede access to health care in this migrant population [27, 28]. Directed questionnaires to identify occult genitourinary symptoms could be of help in this difficult scenario. In our study, the structured directed questionnaire identified a significantly higher prevalence of all occult genitourinary signs and symptoms (but not urinary tract infections) when actively sought than did clinical history records (Additional file 1: Table S2). This points to the sensitivity of structured questionnaires as a screening tool for chronic genitourinary schistosomiasis-associated signs and symptoms.

In contrast with the existing reported series, our study sample corresponded to individuals with long-lasting residence (median of 17 years) in a non-endemic European country, who had not been previously screened or were unaware of having been treated for schistosomiasis. While some endemic countries in sub-Saharan Africa have advanced schistosomiasis control or elimination programmes, others have yet to start programmes using the recommended strategies.

An earlier diagnosis would most likely have averted genitourinary involvement and chronic lesions in at least some of the cases studied here. Therefore, diagnostic delay is a matter of concern. The possible reasons for such delays include not only difficulties in accessing health care among migrant populations but also a lack of awareness among healthcare professionals about imported schistosomiasis and specifically the possibility of long-lasting urogenital disease associated with schistosomiasis. Importantly, the stigma surrounding male sexual and reproductive health among these communities deters many migrants from seeking care earlier for some of these symptoms. Additionally, the presence of non-genital manifestations of schistosomiasis, which are often more severe, may overshadow genital involvement in males, leading to underdiagnoses of MGS [12, 29]. The fact that the direct questionnaire employed in our study captured significantly more frequently nearly all items asked about indicates that this sort of instrument has the potential to prevent underdiagnoses or delayed diagnosis of this condition.

An additional consideration is the association reported between MGS and an increased susceptibility to HIV infection [30,31,32]. This is due to both overall immunological effects and local genital tract involvement with a friable epithelium and increased bleeding. Additionally, both diseases principally affect impoverished populations. In our study we identified a trend towards increased HIV incidence in men with a positive Schistosoma serology test (P = 0.07) and even diagnosed two new HIV cases. Screening for HIV should be considered for all potential long-term MGS patients.

Based on our results, it is clear that there are sufficient grounds to include schistosomiasis in the differential diagnosis of male African migrants with genitourinary signs and symptoms. A final question remains, however, Should empiric praziquantel treatment be automatically provided to individuals with suspected chronic genitourinary schistosomiasis? Considering the shortness of the two-dose treatment and its low toxicity and high efficacy in acute/recent infection, systematic praziquantel treatment might be advisable even when it is impossible to confirm the presence of active infection microbiologically. Given that an estimated 24% sub-Saharan Africans living in Europe (a population numbering around 4 million) [33] are thought to be schistosomiasis-positive [34], the benefits of such a strategy could be substantial, assuming that the treatment confirms its efficacy in controlled clinical trials. In this regard, a recent study highlighted that presumptive praziquantel treatment of all immigrants from endemic countries was an effective alternative in terms of costs, survival, and sequelae [35, 36]. However, the efficacy of praziquantel in chronic schistosomiasis with fibrotic lesions is uncertain [37,38,39]. MGS treatment studies with praziquantel have only been carried out in endemic countries, and in acute infections [22, 40, 41]. In addition, there is currently no high-grade evidence coming from randomized controlled trials comparing different treatment strategies for long-term schistosomiasis. The time elapsed since first infection, subsequent reinfections, age, and clinical presentation might all have a bearing on the most appropriate therapeutic approach as well. Given the potential severity of some of the genitourinary conditions—including severe and life-threatening complications like kidney insufficiency or bladder carcinoma—the administration of a standard two-dose praziquantel treatment should be explored as a potential strategy in suspected chronic MGS, once alternative diagnoses have been excluded and provided that the patient has tested positive for Schistosoma and comes from a high-endemic country.

Our study has certain limitations. As we have noted, there is a lack of a true gold standard to diagnose active infection in chronic MGS. Therefore, we cannot be categorically certain that all our participants had chronic active infection. Secondly, participants with more prominent symptoms or higher health-care awareness could well have been overrepresented in our series, while hard-to-reach populations might have been underrepresented due to the fact that inclusion in the study was voluntary. We also cannot exclude the possibility that some participants had received praziquantel many years ago in the context of mass drug distribution campaigns in their country of origin, something which they no longer recall or whose relevance to the present study participants did not recognize. However, given the long-term residence of most of them in Spain, the scope of such campaigns (if they took place) was likely too small to have affected them. An additional consideration is that serology-based testing cannot distinguish between S. mansoni and S. haematobium infection, whose respective geographical areas of distribution largely overlap in sub-Saharan Africa [16]. The ELISA test is reported to be less sensitive to S. haematobium [25], yet S. haematobium is by far the more frequent causative agent of MGS in African migrants. This may have diluted the associations we observed.