Jérôme Boissier

Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study

BACKGROUND Schistosomiasis is a snail-borne parasitic disease endemic in several tropical and subtropical countries. However, in the summer of 2013, an unexpected outbreak of urogenital schistosomiasis occurred in Corsica, with more than 120 local people or tourists infected. We used a multidisciplinary approach to investigate the epidemiology of urogenital schistosomiasis in Corsica, aiming to elucidate the origin of the outbreak. METHODS We did parasitological and malacological surveys at nine potential sites of infection. With the snails found, we carried out snail-parasite compatibility experiments by exposing snails to schistosome larvae recovered from the urine of a locally infected Corsican patient. Genetic analysis of both mitochondrial (cox1) and nuclear (internal transcribed spacer) DNA data from the Schistosoma eggs or miracidia recovered from the infected patients was conducted to elucidate the epidemiology of this outbreak. FINDINGS We identified two main infection foci along the Cavu River, with many Bulinus truncatus snails found in both locations. Of the 3544 snails recovered across all sites, none were naturally infected, but laboratory-based experimental infections confirmed their compatibility with the schistosomes isolated from patients. Molecular characterisation of 73 eggs or miracidia isolated from 12 patients showed infection with Schistosoma haematobium, S haematobium-Schistosoma bovis hybrids, and S bovis. Further sequence data analysis also showed that the Corsican schistosomes were closely related to those from Senegal in west Africa. INTERPRETATION The freshwater swimming pools of the Cavu River harbour many B truncatus snails, which are capable of transmitting S haematobium-group schistosomes. Our molecular data suggest that the parasites were imported into Corsica by individuals infected in west Africa, specifically Senegal. Hybridisation between S haematobium and the cattle schistosome S bovis had a putative role in this outbreak, showing how easily and rapidly urogenital schistosomiasis can be introduced and spread into novel areas where Bulinus snails are endemic, and how hybridisation could increase the colonisation potential of schistosomes. Furthermore our results show the potential risk of schistosomiasis outbreaks in other European areas, warranting close monitoring and surveillance of all potential transmission foci. FUNDING WHO, ANSES, RICET, and the Ministry of Health and Consumption.

Schistosomiasis Haematobium, Corsica, France

To the Editor: In Europe, urinary schistosomiasis (1) has previously been detected only in Portugal, where this focus disappeared during the 1950s (2). However, freshwater snails of the species Bulinus contortus, B. truncatus, and Planorbarius metidjensis, which are recognized intermediate hosts for Schistosoma haematobium trematodes, have been found in Portugal (3), Spain (4), and Corsica (5,6). This finding suggested that autochthonous schistosomiasis could re-emerge in southern Europe if these mollusks become infected. We report a probable focus for transmission of schistosomiasis haematobium in Corsica, France. In March 2014, a 4-year-old girl (index case-patient) from France was referred to the Toulouse University Hospital (Toulouse, France), with gross hematuria. Ultrasonography and cystoscopic examination of the bladder detected a polyp. Examination of the polyp for parasites identified bodies that were consistent with schistosome eggs. Parasitologic examination of urine confirmed schistosomiasis by detecting viable S. haematobium eggs. The parents of the girl (family A) did not report any stay or travel in an area to which urinary schistosomiasis was endemic; they reported summer holidays only in Mallorca in the Balearic Islands (Spain) and Corsica. However, her father reported that since 2012, he had experienced gross hematuria that had been evaluated by standard urologic investigations but not by cystoscopy; no etiology was determined. Parasitologic urinalysis in our hospital department showed numerous viable S. haematobium eggs in the father’s urine. The parents of the index case-patient also reported that an 8-year-old boy in a friend’s family (family B), who shared summer vacations with them had exhibited gross hematuria since February 2013. A third family (family C) was also investigated because they also spent holidays in Corsica with families A and B. Families B and C had also spent a summer in Mallorca, but they denied any contact with freshwater. Of 11 French native-born members of the 3 families, 6 had positive results for S. haematobium by urine examination. All case-patients had specific positive immunodiagnostic results by an ELISA that used S. mansoni extracts and by indirect hemagglutination. In addition, 2 family members who had a negative result by urine examination had a positive serologic result. Spending summer vacations in the same village in Corsica (Sainte-Lucie de Porto-Vecchio), where members of the 3 families had bathed at least once per holiday period in the Cavu River, was the epidemiologically prominent feature that linked these persons. Families A and C were in Sainte-Lucie de Porto-Vecchio in August 2011, and families A, B, and C were in the same location in August 2013. During these investigations, we were contacted by the Department of Tropical Medicine, Dusseldorf University Hospital (Dusseldorf, Germany), because a 10-year-old boy and his father had been given diagnoses of schistosomiasis haematobium on the basis of positive urinalysis results for S. haematobium eggs. Two other members of this family (5 persons) had a positive immunodiagnostic result. Locations of previous vacations for this family outside Germany included Spain (not the Balearic Islands) and Corsica, where they bathed frequently in the Cavu River. These epidemiologic findings provide strong circumstantial evidence supporting the presence of a previously unrecognized focus of urinary schistosomiasis in Corsica. We performed molecular analysis of schistosomal miracidia DNA. The second internal transcribed spacer region of the ribosomal gene complex (7,8) was amplified and sequenced. Viable eggs obtained from the patients in France were those of S. haematobium. Additional molecular investigations are being conducted to assess genetic diversity of this isolate from Corsica and the geographic origin of the introduced parasite. The malacologic situation in Sainte Lucie de Porto-Vecchio was investigated during May 12–19, 2014; three rivers (Figure) were included in the survey. Four sites were sampled in the Cavu River, and B. truncatus snails were found in 3 sites that corresponded to bathing areas (site 1: 41°43′53.57″N, 9°17′36.70″E; site 2: 41°43′22.13″N, 9°17′59.87″E; site 3: 41°42′8.40″N, 9°21′5.82″E). Snails were also found in the nearby Tarcu River (site 5) and Osu River (site 6). These findings confirmed previous data for the presence of B. truncatus snails in Corsica (5,6). Water temperature was recorded at 11:00 am at these 3 sites (range 15°C–16°C). This temperature range is not optimal for the snail intermediate host stage of the parasite life cycle (9,10). Of 148 live snails that were obtained in the Cavu River, none were infected with schistosome cercariae. Figure Corsica, France, showing malacologic survey sampling sites (oval) in 3 rivers (Tarcu, Cavu, and Osu). Bulinus truncatus snails were found at sites 1, 2, 3, 5, and 6. Data from the field survey and epidemiologic information for the cases in France and Germany, indicated transmission of schistosomiasis haematobium in the Cavu River in southeastern Corsica in 2011 and 2013. Additional supportive evidence is the fact that the father of the index case-patient had gross hematuria in 2012 and 2013. Two hypotheses are proposed to account for this situation. The first hypothesis is that the parasite (i.e., schistosome eggs) was transmitted by an infected person into the Cavu River in June or July 2011, when environmental conditions were favorable for snail infection. However, questions arise about survival of infected snails during the winter and their ability to reinfect the area during the following summers in 2012 and 2013. The second hypothesis is that schistosome eggs were spread by infected persons at the beginning of summer and caused a permanent transmission cycle in this focus. This situation would be difficult to control. Additional information should be obtained by a long-term malacologic survey to detect infected mollusks in this region.

Schistosomiasis reaches Europe

An outbreak of urogenital schistosomiasis has been detected in Europe, with patients affected in France,1,2 Germany,1,2 and Italy. The infection originated in Corsica, in a river north of Porto-Vecchio, a popular tourist destination (figure). The introduction of schistosomiasis is believed to be associated with infected people arriving from a region endemic for the exclusively African parasite, Schistosoma haematobium and disseminating parasite eggs through their urine into snail breeding sites along the river.

In Vitro Activities of Trioxaquines against Schistosoma mansoni

ABSTRACT We report the in vitro activities of trioxaquines against larval and adult-stage schistosomes at 5 and 50 μg/ml, respectively. Such activities are equivalent to that of praziquantel, the major and rather unique drug currently used for the treatment of schistosomiasis. In this range of concentrations, artemisinin derivatives (artesunate and artemether) have no activity.

Experimental observations on the sex ratio of adult Schistosoma mansoni, with comments on the natural male bias.

The sex ratio of adult worms has been observed biased towards males in Schistosoma mansoni under natural conditions. The origin of this bias is unknown. This paper determines whether males are more infective than females under controlled experimental bisexual conditions, and hence if the sex ratio is male-biased as a consequence of this. The male and female cercarial infectivities in uni- and bisexual vertebrate host infections using a range of controlled cercarial sex ratios were studied. The results showed that, in experimental unisexual infections, male cercariae were more infective than females, and that in experimental bisexual infections, male cercarial infectivity was similar to that of female, irrespective of cercarial sex ratio. Furthermore, cumulative male and female cercarial infectivity was maximal when sex ratio was equilibrated. The unbiased sex ratios obtained in our experimental bisexual infections are discussed in terms of behavioural and/or biochemical male female interaction. Alternative explanations of the natural biased sex ratio are proposed.

A review of performance and pathogenicity of male and female Schistosoma mansoni during the life-cycle

The sexual life-history traits of Schistosoma mansoni have been reviewed to compare male and female performance and pathogenicity against Biomphalaria glabrata during the life-cycle. A meta-analysis was used on pooled results from different experiments. In most cases, there was no difference between males and females but male cercariae were significantly more infectious than female cercariae. Conversely, cercarial production and cercarial life-span were significantly greater for females than for males; furthermore, females have a tendency to occur in molluscs of larger size. Each difference is discussed and interpreted when possible in terms of male and female differences in transmission strategies. The female strategy may consist of producing many long-living larvae. The male strategy may consist of producing few short-living larvae and would invest in the quality of these larvae instead of their quantity or their life-span.

Introgressive hybridizations of Schistosoma haematobium by Schistosoma bovis at the origin of the first case report of schistosomiasis in Corsica (France, Europe)

This study concerns the first urinary schistosomiasis case observed in Corsica (France, Europe) occurring in a 12-year-old German boy. The aim was to identify the relationship between this Schistosoma haematobium infection and other schistosomes of the Schistosoma group with terminal-spined ova. Morphological and molecular analyses were conducted on the ova. The results showed that the schistosome responsible for the emergence of schistosomiasis in Corsica was due to S. haematobium introgressed by genes from S. bovis.

Preliminary study on sex-related inflammatory reactions in mice infected with Schistosoma mansoni

The aim of this study was to investigate the contribution of the sex of both the parasite and the host to the inflammatory response induced in unisexual infections of Schistosoma mansoni in mice. Organ weight, cell count and the delayed type hypersensitivity reaction were used as tools in this comparative study. The inflammatory reactions differed as a function of the sex of both the host and the parasite. Female mice showed a stronger inflammatory reaction to schistosome infection than males, while male schistosomes induced a stronger inflammatory response compared to females. The host-related differences in the inflammatory reaction may reflect differences in the factors affecting the immune defence of male and female mice. The differences in the inflammatory response induced by the parasite are discussed in terms of the quantity and quality of antigens among male and female worms.

Cheap, rapid and efficient DNA extraction method to perform multilocus microsatellite genotyping on all Schistosoma mansoni stages

Schistosomes are endoparasites causing a serious human disease called schistosomiasis. The quantification of parasite genetic diversity is an essential component to understand the schistosomiasis epidemiology and disease transmission patterns. In this paper, we propose a novel assay for a rapid, low costly and efficient DNA extraction method of egg, larval and adult stages of Schistosoma mansoni. One euro makes possible to perform 60,000 DNA extraction reactions at top speed (only 15 min of incubation and 5 handling steps).

Sexual biology of Schistosomes

Schistosomes are unusual, together with some of the didymozoidae, in that they are dioecious instead of being hermaphrodite. This gonochorism is accompanied with morphological, ecological, behavioural and molecular differences between the male and the female parasites all through their life cycle. This review is an overview of the sexual biology of schistosomes and aims to provide the most recent information that may help to build future control strategies against these parasites. It proposes a new view of the life cycle of schistosomes, taking into account the sexual status of each developmental stage. It presents the relevant information available on the genetic and phenotypic sexual dimorphisms of these parasites; it proposes a comparison between the host-male parasite and the host-female parasite interactions in both the molluscan intermediate and the mammalian definitive hosts; it exposes the male-female parasite interactions that exist in both the mollusc and the mammalian hosts at the parasite individual and populational levels. This review highlights the domains of research that are still unexplored but that would be of great interest for a better knowledge of the sexual way of life of the parasites which are still responsible for one of the most important human parasitic diseases in the world.