Introduction
Schistosomiasis is a parasitic disease caused by digenean trematodes of the genus Schistosoma. Schistosomiasis is of considerable medical and veterinary importance in tropical and subtropical regions. It is estimated that nearly 779 million people live in endemic areas (Panzner & Boissier, Reference Panzner and Boissier2021) and, as of 2019, approximately 236.6 million people were in need of preventive chemotherapy in 78 countries (Ossai et al., Reference Ossai, Dankoli, Nwodo, Tukur, Nsubuga, Ogbuabor and Eze2014; WHO 2022). Sub-Saharan Africa alone accounts for 90% of infected cases (Dawet et al., Reference Dawet, Yakubu, Longmut, Benjamin, Nannim and Daburum2012). Schistosoma infections in domestic livestock, such as cattle, sheep, and goats, are also widespread and commonly occur in Africa, the Middle East, Asia, and in several countries bordering the Mediterranean (Boissier et al., Reference Boissier, Kincaid-smith, Berry, Allienne, Fillaux, Toulza and Fillaux2016; De Bont & Vercruysse, Reference De Bont and Vercruysse1998). Epidemiological statistics for livestock schistosomiasis are certainly underestimated, but the number of infected animals worldwide has been estimated at 165 million (De Bont & Vercruysse, Reference De Bont and Vercruysse1998). Among the 23 known species of Schistosoma, there are currently six major species of Schistosoma that infect humans: Schistosoma mansoni (S.m), S. haematobium (S.h), S. intercalatum (S.i), S. guineensis (S.g), S. mekongi (S.me), and S. japonicum (S.j). The two latter species are recognized as zoonoses, capable of infecting a wide range of livestock and wildlife but are not currently present in Africa. Concerning animal infecting parasites, 19 species are reported to naturally infect animals (Rey et al., Reference Rey, Webster, Huyse, Rollinson, Van den Broeck, Kincaid-Smith and Boissier2021; Webster & Littlewood, Reference Webster and Littlewood2012), for which nine of these species (Schistosoma mattheei [S.ma], S.b, S.c, S. spindale [S.sp], S. indicum [S.ind], S. nasale [S.n], S. incognitum [S.inc], S. margrebowiei [S.mar], and S.j) have received special attention (Léger & Webster, Reference Léger and Webster2017), mainly because of their veterinary importance concerning ruminants in Asian and African countries. Of these, two species (S.b and S.c) are found in West Africa, and the other seven are narrowly distributed in central and eastern Africa (Mouchet & Bremond Reference Mouchet and Bremond1989; Ndifon, Betterton & Rollinson, Reference Ndifon, Betterton and Rollinson1988; Rollinson et al., Reference Rollinson, Southgate, Vercruysse and Moore1990; Vera et al., Reference Vera, Mouchet, Bremond, Sidiki, Sellin and Sellin1992; Vercruysse, Southgate & Rollinson, Reference Vercruysse, Southgate and Rollinson1984). The S.h species group consists of nine sister species subdivided into two: S.i and S.g, which cause human schistosomiasis, and S.b, S.ma, S.mar, S.leiperi (S.l), S.c, and S. kisumuensis (S.k), which infect a variety of wild, ruminant, and livestock.
All species of the haematobium group are transmitted by snails of the family of Planorbidae and the subfamily of Bulininae. Because of the host/parasite specificity, the distribution of the disease is determined by that of the specific snail host in response to its ability to adapt to environmental conditions (pollution, drought, rainfall, etc.). Overall, the species involved in schistosomiasis transmission varies from one geographic area to another and even within the same micro-geographical area.
The schistosome transmission cycle involves two hosts, a vertebrate host where sexual reproduction occurs, and a freshwater snail host where asexual reproduction occurs. The sexual stage of these parasites promotes interactions between male and female worms inside the definitive host, whereas the asexual stage gives rise to clonal larvae that facilitates exposure and potential infection of mammals in contact with cercarial-infested water. In the field, the sharing of the same water bodies by animals and humans promotes interspecies Schistosoma spp interaction within the same definitive vertebrate hosts. Consequently, coinfections can allow for heterospecific mate pairings, resulting in parthenogenesis, introgression, or whole-genome admixture through hybridization (Detwiler & Criscione, Reference Detwiler and Criscione2010; King et al., Reference King, Stelkens, Webster, Smith and Brockhurst2015). In endemic areas, it is assumed that the limited distribution of schistosome species and their hosts (intermediate and/or definitive) limits the hybridization phenomenon. However, according to Platt et al. (Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019), barriers that prevent the unspecific host/parasite couple from forming are now breaking down because of increasing economic development, human migration, global trade, and climate change. Several crosses between schistosome species have been demonstrated in the laboratory and in the field (Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013, Léger et al., Reference Léger, Garba, Hamidou, Webster, Pennance, Rollinson and Webster2016; Wright et al., Reference Wright, Southgate, Van Wijk and Moore1974). The most frequent hybrids are found within the haematobium group, most notably between S.h and both (S.b or S.c) livestock parasites.
The purpose of this review was to describe the presence of schistosome hybrids of the haematobium group in West and Central Africa from a cartographic perspective. We analyzed the presence of these hybrids with respect to the general distribution of S.h in the different countries of sub-Saharan Africa, with a brief description of the situation in the other regions of Africa. Using a cartographic approach to represent the well-known distribution of S.h. will enable information gaps in the distribution Schistosoma hybrids to be identified at multiple scales, whether at the regional scale, country scale, or at the scale of the African continent.
Method
Search strategy and article selection
We searched the PubMed and Google Scholar public online databases for relevant publications on human or animal schistosome hybrids by applying the following keywords: ‘schistosomiasis and hybrids’, ‘Schistosoma’, ‘haematobium’ ‘bilharzia’, ‘Hybridization’, ‘introgression’, ‘schistosome’, and ‘Africa’. To limit the scope of the search, we included these search terms related to Africa or to specific regions where hybrids have been reported. Publications that identified hybrids with molecular methods (e.g., using a gene of mitochondrial cytochrome oxidase and/or nuclear ribosomal internal transcribed spacer) were the most focused, followed by other methods (e.g. enzymatic, morphological). The species S.i, as reported in West African countries, will be considered as S.g, because S.i is only present in the Democratic Republic of Congo (Pagès et al., Reference Pagès, Jourdane, Southgate, Tchuem Tchuenté, Combes and Jourdane2003).
Among the 216 articles selected and imported into Mendeley software, duplicates and publications for which full texts were not available were eliminated. Subsequently, 113 articles were retained for this manuscript. The final searches were performed on 15 April 2023. For each country, the review is presented in chronological order of recorded reports. All maps produced in this review are based on bibliographical reports.
Mapping
Geographical coordinates of survey locations, as reported in publications or reports from the Ministry of Health in each country, were extracted. Distribution maps of urogenital schistosomiasis and hybrids were then produced using QGIS Remote Sensing mapping software version 2.18.4 (Figs. 1–10).
Figure 1. Distribution of S.h and hybrids in Niger.
S.c-S.b hybrid found in Niamey
Distribution of S.h (Mouchet et al., Reference Mouchet, Develoux and Magasa1988; Mouchet et al., Reference Mouchet, Labo, Develoux and Sellin1987; Vera et al., Reference Vera, Mouchet, Bremond, Sidiki, Sellin and Sellin1992, Ministère de la Santé, Reference de la Santé2017 )
Distribution of Schistosoma hybrids (Brémond et al., Reference Brémond, Mouchet, Chevallier, Sellin, Vera and Sellin1990; Mouchet et al., Reference Mouchet, Theron, Brémond, Sellin and Sellin1992; Pennance et al., Reference Pennance, Allan, Emery, Rabone, Cable, Garba and Webster2020; Platt et al., Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019)
Results
In Niger
The presence of eggs of typical S.b in the stool of 17 individuals in Niakoye in the Gaya region in the southern part of Nigeria (Fig. 1) strongly indicates that this region is a strong candidate for a possible hybridization between S.b species and S.h. (Mouchet et al.,1988). In 1990, Bremond et al., demonstrated (using isoelectofocusing in gel) the existence of gene flow between S.b and S.c in Zinder (Niger) (Brémond et al., Reference Brémond, Mouchet, Chevallier, Sellin, Vera and Sellin1990), and in 1993 the intermediate egg forms and allozyme phenotypes were observed between S.b and S.h or S.c in children from eastern Niger. These findings suggested a natural interaction between S.h and S.b (Bremond et al., Reference Bremond, Sellin, Sellin, Nameoua, Labbo and Theron1993). Although allozyme profiles strongly indicated a hybrid origin, the exact role of S.c could not be established because the allozyme markers did not distinguish between S.h and S.c. The authors proposed that S.c might also be involved through hybridization with S.b (Bremond et al., Reference Bremond, Sellin, Sellin, Nameoua, Labbo and Theron1993). Beyond the possibility of a two-species hybridization, a study by Léger et al., demonstrated (using cox1 and ITS1 +2 DNA region) an interaction between three species (S.b × S.h × S.c) in the Tillabéri region (Léger et al., Reference Léger, Garba, Hamidou, Webster, Pennance, Rollinson and Webster2016) (Fig 1).
An interesting genome-wide study of S.h miracidia exomes collected along the Niger River in northeastern Niger (Niamey) showed (through sequencing) that 3.3% to 8.2% of the nuclear genomes were derived from S.b (Platt et al., Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019). The authors concluded that hybridization between S.h and S.b species is an ancient phenomenon and dates back from 108 to 613 generations.
The more recent molecular study (Cox1, 18S, and ITS1 + 2 DNA regions) of cercariae excreted by naturally infected Bulinus spp. in the Niamey district showed that of S.b × S.h and S.b × S.h × S.c hybrids are transmitted to humans through? Bulinus truncatus (Pennance et al., Reference Pennance, Allan, Emery, Rabone, Cable, Garba and Webster2020).
In Mali
Only the southern region in Mali is affected by schistosomiasis because the north is predominantly characterized by desert conditions. With the exception of reports of interactions between S.c and S.b in livestock (using isoelectofocusing in gel) in the Bamako and Mopti regions (Rollinson et al., Reference Rollinson, Southgate, Vercruysse and Moore1990), there are limited data on schistosome hybridization, despite the utilization of all existing water points by people and animals in these Sahelian regions. The study of Rollinson et al. (Reference Rollinson, Southgate, Vercruysse and Moore1990) was the first to focus on hybridization in Mali, revealing evidence of interactions between S.b and S.c as observed in cattle from Bamako (prevalence = 28.6%) and Mopti (prevalence = 12.5%). Observations were made on egg morphology, surface structure and enzyme profiles of S.c and S.b from Mopti and monospecific infection with S.b was found in 10 animals, whereas 24 animals were found to harbor only S.c (Rollinson et al., Reference Rollinson, Southgate, Vercruysse and Moore1990). In 2016, 10 Belgian travelers returned from Mali with an S.h-S.b hybrid infection, confirmed by DNA sequencing from eggs. Even if clinical symptoms and laboratory findings resembled those of classic acute schistosomiasis, the detected eggs were morphologically unusual (Soentjens et al., Reference Soentjens, Cnops, Huyse, Yansouni, De Vos, De Bottieau and Van Esbroeck2016). However, to date, no reports of infection in local people from hybrids of the haematobium group, have yet been reported. Results of a genomic analysis (presence of invadolysin gene) of cercariae released from infected snails that were collected in 1994 led to the hypothesis that an ancient hybridization between S.h and S.b existed in Mali (Rey et al., Reference Rey, Webster, Huyse, Rollinson, Van den Broeck, Kincaid-Smith and Boissier2021). Following surveys carried out on Dogon Country (Mopti district) data based on egg morphology and Ziehl Neelsen staining of egg shells, a possible occurrence of S.h-S.g hybrids was detected (De Clercq et al., Reference De Clercq, Rollinson, Diarra, Sacko, Coulibaly, Landouré and Vercruysse1994) (Fig 2).
Figure 2. Distribution of Schistosoma hybrids in Mali.
S.c-S.b hybrid found in Bamako and Mopti. S.h-S.b hybrid found only in Bandiagara.
Distribution of S.h (Dabo et al., Reference Dabo, Durand, Morand, Diakite, Langand, Imbert-Establet and Jourdane1997, Reference Dabo, Mahamat Badawi, Bary and Doumbo2011, Reference Dabo, Bary, Kouriba, Sankaré and Doumbo2013, Reference Dabo, Diarra, Machault, Touré, Niambélé, Kanté and Doumbo2015; Kouriba et al., Reference Kouriba, Traoré, Dabo, Sangaré, Guindo, Keita and Dessein2005; Lyke et al., Reference Lyke, Dabo, Sangare, Arama, Daou, Diarra and Sztein2006; Clements et al., Reference Clements, Bosqué-Oliva, Sacko, Landouré and Dembélé2009; Sangho et al., Reference Sangho, Dabo, Sidibé, Dembélé, Diawara, Diallo and Konaté2009; Sissoko et al., Reference Sissoko, Dabo, Traoré, Diallo, Traoré, Konaté and Doumbo2009; Lyke et al., Reference Lyke, Dabo, Arama, Daou, Diarra, Wang and Sztein2012a;Niangaly et al., Reference Niangaly, Djimde, Traore, Sangare, Guindo, Konate and Doumbo2012).
Distribution of Schistosoma hybrids (Rollinson et al., Reference Rollinson, Southgate, Vercruysse and Moore1990; Soentjens et al., Reference Soentjens, Cnops, Huyse, Yansouni, De Vos, De Bottieau and Van Esbroeck2016).
In Senegal
In Senegal, in addition to the studies conducted by Rollinson et al. (Reference Rollinson, Southgate, Vercruysse and Moore1990) on S.b and S.c in West Africa, many other studies have been conducted, particularly since the construction of the Diama Dam in 1985. The habitats found in the Senegal River Basin (SRB) changed dramatically with the construction of this dam, which was intended to prevent saltwater intrusion from the sea, and thus facilitated rice and sugarcane agriculture. These new aquatic habitats allowed for the spread of Biomphalaria pfeifferi, the intermediate host of S.m, and various Bulinus species responsible for the transmission of S.h and S.b and S.c. There are now several sympatric zones between these schistosomes, and many children are found co-infected with human (urogenital and intestinal) and animal schistosomiasis. This means that with the construction of the Diama Dam, the SRB represents a hot spot of human and animal schistosomiasis transmission dynamics with the proliferation of hybridization zones (Léger et al., Reference Léger, Borlase, Fall, Diouf, Diop, Yasenev, Catalano, Thiam, Ndiaye, Emery, Morrell, Rabone, Ndao, Faye, Rollinson, Rudge, Sène and Webster2020; Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013; Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018).
The first cases of hybridization between schistosome species under natural conditions in humans were identified in Senegal (SRB) through the work of Huyse et al. (Reference Huyse, Webster, Geldof, Stothard, Diaw and Rollinson2009). Hybrid schistosomes recovered from the urine and feces of children and intermediate snail hosts (B. truncatus and B. globosus), had a nuclear ITS rRNA sequence identical to S.h, whereas the partial mitochondrial sequence cox1 was identified as S.b (Huyse et al., Reference Huyse, Webster, Geldof, Stothard, Diaw and Rollinson2009). This study provided the first insights into the subtleties between a human and a bovine schistosome species.
In 2013, authors observed (Cox1 and ITS 1 +2 DNA region) hybrid crosses between S.h and S.c in children residing in Tambacounda and the Ferlo Valley but not in the SRB (Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013). These findings lend support to the hypothesis that the emergence of schistosome hybrids in humans may be linked to the presence of bovine species in cattle within the same region.
Boon et al. (Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018) conducted a study to determine and understand the spatiotemporal distribution of S.h-S.b hybrids in the SRB. Using 10 villages, distributed over the four main watersheds, the author genotyped miracidia and/or schistosome eggs collected from human urine samples using a partial mitochondrial Cox1 and nuclear ITS1 + 2 DNA region. Results showed that hybrid schistosomes were unevenly distributed, with significantly higher numbers in villages bordering Lake Guiers than in villages located at the Lampsar River and Senegal River valley (Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018). Surprisingly, the frequency of hybrids per village was not related to the prevalence of urinary schistosomiasis in that village, which is one of the most common schistosome species (S.h) in this region (Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018). To explain the geographic heterogeneity of hybrids in the SRB, the authors first supported the hypothesis that in regions with high hybrid frequency, local conditions may facilitate hybridization between S.h and S.b (currently or in the past) more than in other regions. As shown in studies on other organisms, in regions with higher hybrid frequency, introgression of S.b mtDNA (or nuclear DNA) may be more adaptive and under positive selection (Irwin, Reference Irwin2002; Toews and Brelsford, Reference Toews and Brelsford2012). The link between hybrid distribution and schistosomiasis prevalence has raised more questions than expected. One possible explanation for this link was that active immune suppression by another species (S.m) could make a person more susceptible to infection by schistosome species that typically are unable to infect humans (e.g., S.b, hybrid species), though this did not explain why S.h and S.b hybrids were not positively associated with S.h endemic areas (McSorley and Maizels, Reference McSorley and Maizels2012). We agree with Boon et al. (Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018), who suggested that individual-level studies linking within-host hybrids to intensity of single Schistosoma infection and co-infection with S.m, coupled with host-related factors (e.g., host immunology, ethnicity, water contact behavior) could improve our understanding of this hybrid heterogeneity.
Several studies (Léger et al., Reference Léger, Borlase, Fall, Diouf, Diop, Yasenev, Catalano, Thiam, Ndiaye, Emery, Morrell, Rabone, Ndao, Faye, Rollinson, Rudge, Sène and Webster2020; Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013) have shown that large-scale multiloci molecular analyses of parasite samples collected from children and domestic livestock across Senegal revealed introgressive interactions between the three closely related species of the S.h group ([i] S.h, which causes urogenital schistosomiasis in humans, and [ii] S.b and S.c, agents responsible for intestinal schistosomiasis in cows, sheep, and goats). Evidence of hybridization between S.h-S.c and S.h-S.b was commonly found throughout Senegal with an estimated 88% of children suspected of excreting hybrid schistosome eggs. These results would be the first conclusive evidence of natural hybridization between S.h and S.c. According to Boon et al. (Reference Boon, Mbow, Paredis, Moris, Sy, Maes and Huyse2019), 25.6% of the parasites had a S.b cox 1 profile, whereas 74.4% had a S.h cox 1 profile in the same area. In the most recent study, approximately 63% to 72% of infected children carried S.h-S.b hybrids. In Richard Toll and Guiers Lake, 18.88% of infected urine samples contained S.h-S.b hybrids. In Barkedji and Linguère (Louga district), 9% to 11% of miracidia from samples tested in children were S.h-S.b hybrids compared to 10% in adults (Léger et al., Reference Léger, Borlase, Fall, Diouf, Diop, Yasenev, Catalano, Thiam, Ndiaye, Emery, Morrell, Rabone, Ndao, Faye, Rollinson, Rudge, Sène and Webster2020). No hybrids formed with human schistosome species (i.e., S.h-S.b) were found in cattle. According to data recorded in Richard Toll and Guiers Lake, 35% of infected intermediate hosts of the genus Bulinus spp. were found to excrete cercariae of S.h-S.b hybrid profiles, compared to excretion rates of 68% and 17% for S.h and S.b profiles, respectively (Léger et al., Reference Léger, Borlase, Fall, Diouf, Diop, Yasenev, Catalano, Thiam, Ndiaye, Emery, Morrell, Rabone, Ndao, Faye, Rollinson, Rudge, Sène and Webster2020).
Numerous studies suggest that hybridization can result in phenotypic changes that can significantly influence disease dynamics and parasite evolution (Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018; Irwin, Reference Irwin2002; Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013). Increasing the host range of hybrid parasites and changes in host distribution can directly impact the transmission of these schistosomes. Focusing on epidemiological parameters, globally, the habitat of SRB has changed significantly over the past 30 years because of the construction of the Diama (1985) and Manantali (1988) dams in Senegal and Mali, respectively. These artificial water resources have not only helped to prevent saltwater intrusion from the sea and to stabilize water flow, they have also facilitated new forms of agriculture. The successive migration of first human populations, followed by animals and snails to these resources, created areas where humans and domestic livestock were near to one another, thereby facilitating interactions between the schistosome species they carry. Very recently, authors identified hybrid cercariae (S.h-S.b) excreted by infected snails collected in the Fatick in Senegal, using cox1, nuclear ITS1 + 2, and partial 18S rDNA regions (Senghor et al., Reference Senghor, Webster, Pennance, Sène, Doucouré, Sow and Sokhna2023) (Fig 3).
Figure 3. Distribution of Schistosoma hybrids in Senegal.
Distribution of S.h (Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018; Briand et al., Reference Briand, Watier, Le Hesran, Garcia and Cot2005; De Clercq et al., Reference De Clercq, Vercruysse, Picquet, Shaw, Diop, Ly and Gryseels1999; Ten Hove et al., Reference Ten Hove, Verweij, Vereecken, Polman, Dieye and van Lieshout2008; Meurs et al., Reference Meurs, Mbow, Boon, Van Den Broeck, Vereecken, Ndiaye Diè Ye and Polman2013; Sene-wade et al., Reference Sene-wade, Marchand, Rollinson and Webster2018; Senghor et al., Reference Senghor, Diallo, Sylla, Doucoure, Ndiath, Gaayeb and Ba2014; Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013 ; Ministère de la santé, Reference de la Santé2021)
Distribution of Schistosoma hybrids (Boon et al., Reference Boon, Mbow, Paredis, Moris, Sy, Maes and Huyse2019; Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018; Rollinson et al., Reference Rollinson, Southgate, Vercruysse and Moore1990; Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013; Senghor et al., Reference Senghor, Webster, Pennance, Sène, Doucouré, Sow and Sokhna2023)
In Côte d’Ivoire
In a molecular study on cercariae shed by naturally infected snails, Tian-Bi et al. (Reference Tian-Bi, Konan, Sangaré, Ortega-Abboud, Utzinger, N’Goran and Jarne2019a) reported (using Cox1 and ITS2 DNA region analysis) transmission of S.h-S.b hybrids from the northern and central parts of Côte d’Ivoire with an average prevalence of 0.4% of 75 discriminated cercariae. The same survey technique yielded an average prevalence of 12.5% S.h-S.b hybrids in the districts of Dix-huit Montagnes, Agnéby, and Lagunes (Angora et al., 2019). This technique should be considered when investigating the elimination of ectopic schistosome eggs in future studies. The LAMP test has made it possible to identify not only pure schistosome species, but also S.h-S.b hybrids in a urine sample (Crego-Vicente et al., Reference Crego-Vicente, Fernández-Soto, Febrer-Sendra, Diego, Boissier, Angora and Muro2021) (Fig 4).
Figure 4. Distribution of Schistosoma hybrids in Côte d’Ivoire.
S.h-S.b hybrid found in Dekoué, Adzopé, Agboville.
Distribution of S.h (Coulibaly et al., Reference Coulibaly, N’Gbesso, Knopp, Keiser, N’Goran and Utzinger2012; Chammartin et al., Reference Chammartin, Houngbedji, Hürlimann, Yapi, Silué, Soro, Kouamé, N’Goran, Utzinger, Raso and Vounatsou2014; Angora et al., Reference Angora, Boissier, Menan, Rey, Tuo, Touré and Balmer2019a, Ministère de la Santé, Reference de la Santé2016)
Distribution of Schistosoma hybrids (Angora et al., Reference Angora, Allienne, Rey, Menan, Touré, Coulibaly and Boissier2019b, Reference Angora, Vangraefschepe, Allienne, Menan, Coulibaly, Meïté and Boissier2022; Tian-Bi et al., Reference Tian-Bi, Webster, Konan, Allan, Diakité, Ouattara, Salia, Koné, Kakou, Rabone, Coulibaly, Knopp, Meité, Utzinger, N’Goran and Rollinson2019b).
S.h interacts with S.b in the northern, southern, and western regions of Côte d’Ivoire to produce hybrids that infect humans. To identify and quantify S.h-S.b hybrids among schoolchildren in four sites across the Côte d’Ivoire, individual miracidia hatched from urine samples were molecularly characterized through an analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions (Angora et al., Reference Angora, Vangraefschepe, Allienne, Menan, Coulibaly, Meïté and Boissier2022) (Fig 4). In this study, pure S.b was found in some children, which indicates proof of a potential zoonotic infestation by S.b.
In Benin
The first study that molecularly characterized (ITS2 rDNA high-resolution melting and Cox1 sequences) Schistosoma from humans in Benin showed S.h-S.g hybrids in Dangbo, Ouemé district and Doh village, and Atacora district (Moné et al., Reference Moné, Minguez, Ibikounlé, Allienne, Massougbodji and Mouahid2012) (Fig 5).
Figure 5. Distribution of Schistosoma hybrids in Benin.
S.h-S.b hybrid found Kessounou and Sô-tchanhoué
Distribution of S.h (Onzo-Aboki et al., Reference Onzo-Aboki, Ibikounlé, Boko, Savassi, Doritchamou, Siko and Kaboré2019).
Distribution of Schistosoma hybrids (Moné et al., Reference Moné, Minguez, Ibikounlé, Allienne, Massougbodji and Mouahid2012; Reference Moné, Holtfreter, Allienne, Mintsa-nguéma, Ibikounlé and Boissier2015; Savassi et al., Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021).
However, the authors did not identify a pure strain of S.g. Further studies by Moné et al. (Reference Moné, Holtfreter, Allienne, Mintsa-nguéma, Ibikounlé and Boissier2015) revealed (Cox1 and ITS2) the presence of another schistosome hybrid in additional villages in Benin (Sô-Ava and Pahoue, Atlantic District). A molecular analysis of two adult worms (one from Sô-Tchanhoué and the other from Toho) confirmed hybrids of S.h-S.b. More extensive molecular epidemiological studies carried out by Savassi et al. in Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020 and Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021 further showed that the S.h-S.b hybrid is most prevalent in the Ouémé and Atlantic districts (Savassi et al., Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021). Although no hybrids have yet to be identified in livestock in other West African countries, zoonotic transmission has been established in Benin because Savassi et al. (Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021) revealed that cows and rodents were infected with the same strain of hybrid found in infected humans. Although this study revealed both genetic evidence for the endemicity of S.h and the presence of the S.h-S.b hybrid, this was not the case for S.g and the S.h-S.g hybrid (Fig 5). These observations allowed us to qualify S.g and its hybrid as a rare schistosome species in Benin. Another of the most parsimonious hypothesis would be the replacement (Webster et al., Reference Webster, Tchuem Tchuenté, Jourdane and Southgate2005) of the latter by S.h-S.b hybrids. Additional research is required to test these hypotheses.
In Nigeria
There is only one major molecular epidemiology study on schistosomes in Nigeria. It was performed on miracidia Schistosoma collected in urine from schoolchildren (Onyekwere et al., Reference Onyekwere, Rey, Allienne, Nwanchor, Alo, Uwa and Boissier2022a). Molecular characterization by rapid diagnostic multiplex polymerase chain reaction targeting mtDNA (mtDNA Cox1) genes showed the S.b Cox1 profile in the sample from districts of Plateau, Benue, Enugu, Ebonyi, Anambra, Ondo, and Osun, suggesting hybridization between S.h and S.b (Onyekwere et al., Reference Onyekwere, Rey, Allienne, Nwanchor, Alo, Uwa and Boissier2022a) (Fig 6). This study provides new insights into hybridization and population genetic structure of S.h in Nigeria.
Figure 6. Distribution of Schistosoma hybrids in Nigeria.
S.h-S.b hybrid found in Ondo, Osun, Ebonyi, Enugu, Anambra, Benue, and Plateau.
Distribution of S.h (Agi & Okafor, Reference Agi and Okafor2005; Biu & Agbadu, Reference Biu, Kolo and Agbadu2009; Dawet et al., Reference Dawet, Yakubu, Longmut, Benjamin, Nannim and Daburum2012; Ekpo et al., Reference Ekpo, Hürlimann, Schur, Oluwole, Abe, Mafe and Vounatsou2013; Ivoke et al., Reference Ivoke, Ivoke, Nwani, Ekeh, Asogwa, Atama and Eyo2014; Lai et al., Reference Lai, Biedermann, Ekpo, Garba, Mathieu, Midzi and Vounatsou2015; Abdulkadir et al., Reference Abdulkadir, Ahmed, Abubakar, Suleiman, Yusuf, Imam and Musa2017 ; Ezeh et al., Reference Ezeh, Chibuike Onyekwelu, Phebian Akinwale, Shan and Wei2019; Onyekwere et al., Reference Onyekwere, Rey, Nwanchor, Alo, Angora, Allienne and Boissier2022b).
Distribution of Schistosoma hybrids (Onyekwere et al., Reference Onyekwere, Rey, Nwanchor, Alo, Angora, Allienne and Boissier2022b).
The phenomenon of hybridization within the haematobium group has also been studied in Central Africa, such as Cameroon, Gabon, and Democratic Republic of Congo.
In Cameroun
Two hybrid profiles have been reported in the literature. The first, S.h-S.g, was reported initially on the morphological basis of eggs passed with human feces (Southgate, van Wijk & Wright, Reference Southgate, van Wijk and Wright1976; Tchuem Tchuenté et al., Reference Tchuem Tchuenté, Southgate, Njiokou, Njine, Kouemeni and Jourdane1997; Wright et al., Reference Wright, Southgate, Van Wijk and Moore1974) and confirmed by biochemical and molecular analyses (Ndifon et al., Reference Ndifon, Betterton and Rollinson1988; Rollinson and Southgate, Reference Rollinson, Southgate, Rollinson and Anderson1985; Webster et al. Reference Webster, Tchuem Tchuenté, Jourdane and Southgate2005; Webster, Southgate, and Tchuem Tchuenté, Reference Webster, Southgate and Tchuem Tchuenté2003). This hybrid pattern has remained local within in the village of Loum, Littoral district (Rollinson and Southgate, Reference Rollinson, Southgate, Rollinson and Anderson1985; Southgate et al., Reference Southgate, van Wijk and Wright1976; Tchuem Tchuenté et al., Reference Tchuem Tchuenté, Southgate, Njiokou, Njine, Kouemeni and Jourdane1997; Webster et al., Reference Webster, Tchuem Tchuenté, Jourdane and Southgate2005, Reference Webster, Southgate and Tchuem Tchuenté2003; Wright et al., Reference Wright, Southgate, Van Wijk and Moore1974). The second hybrid profile, S.h-S.b, was recently reported (Cox1 and ITS) (Teukeng et al., Reference Teukeng, Blin, Bech, Gomez, Zein-Eddine, Simo, Allienne, Tchuem-Tchuenté and Boissier2022) and seems to have a wider distribution than the S.h-S.g hybrid (Fig 7). The presence of this hybrid in all schistosomiasis-endemic regions of Cameroon should be considered because its presence was recorded in all of the areas surveyed (Teukeng et al., Reference Teukeng, Blin, Bech, Gomez, Zein-Eddine, Simo, Allienne, Tchuem-Tchuenté and Boissier2022) (Fig. 7).
Figure 7. Distribution of Schistosoma hybrids in Cameroun.
S.h-S.g hybrid found in Kumba, Loum, Barombi Mbo, and Barombi Kotto. S.h-S.b hybrid found in Gazawa Bizili, Guereme, Mokolo and Mourtouwa, Bessoum, Djiporde, Gounougou and Ouroudoukoudje, Matta Barrage, and Loum.
Distribution of S.h (Ministry of Public Health of Cameroun, 2019).
Distribution of Schistosoma hybrids (Teukeng et al., Reference Teukeng, Blin, Bech, Gomez, Zein-Eddine, Simo, Allienne, Tchuem-Tchuenté and Boissier2022; Webster et al., Reference Webster, Southgate and Tchuem Tchuenté2003).
In Gabon
Speculation about the existence of eggs that appear to be morphological hybrids resulting from the crossing of S.g and S.h. in Lambaréné dates to 1985 (Burchard & Kern, Reference Burchard and Kern1985). Subsequently, in 2010, the presence of hybrids between S.h and S.g was detected in Estuaire Province (western Gabon). Egg morphology showed three morphotypes: S.h, S.g, and intermediate morphotypes, using single-strand conformational polymorphism analysis on adult worms (Nguema et al., Reference Nguema, Milama, Kombila, Richard-Lenoble, Tisseyre, Ibikounlé and Mouahid2010) (Fig. 8).
Figure 8. Distribution of Schistosoma hybrids in Gabon.
S.h-S.g hybrid found in Lambaréné.
Distribution of S.h (Dejon-Agobé et al., Reference Dejon-Agobé, Edoa, Adegnika and Grobusch2022; Mintsa Nguema et al., Reference Mintsa Nguema, Mavoungou, Mengue Me Ngou-Milama, Mabicka Mamfoumbi, Koumba, Sani Lamine, Diarra and Bouyou Akotet2018).
Distribution of Schistosoma hybrids (Burchard & Kern, Reference Burchard and Kern1985).
In Democratic Republic of Congo
Tchuenm Tchuenté et al. (1994) showed the existence of a natural hybrid species between S.i and S.h in Kinshasa. These isolates were obtained by exposing Bulinus wrighti to miracidia from eggs collected from two infected children and identified by biochemical (phosphoglucomutase isoenzymes), molecular (restriction fragment length polymorphism and randomly amplified polymorphic deoxyribonucleic acid analysis), and morphological (egg measurements) techniques (Tchuenté et al., Reference Tchuenté, Southgate, Vercruysse, Kaukas, Kane, Mulumba and Jourdane1997) (Fig. 9).
Figure 9. Distribution of Schistosoma hybrids in Democratic Republic of Congo.
S.h-S.i hybrid found in Kinshasa.
Distribution of S.h (Madinga et al., Reference Madinga, Linsuke, Mpabanzi, Meurs, Kanobana, Speybroeck and Polman2015).
Distribution Schistosoma hybrids (Tchuenté et al., Reference Tchuenté, Southgate, Vercruysse, Kaukas, Kane, Mulumba and Jourdane1997).
Table 1 summarizes the distribution of different cases of hybridization between Schistosoma spp. with those of S.h depending on molecular or enzymatic techniques used in Africa.
Table 1. Details on detected natural hybridization between Schistosoma spp. with S.h in Africa
Discussion
Figure 10 summarizes the presence of hybrids within the haematobium group at the scale of the African continent. The figure also includes information about the presence of hybrids in other parts of Africa not considered in this review (Chiti et al., Reference Chiti, De Bont, Fransen, Kane, Mwase, Southgate and Vercruysse2000; Cnops et al., Reference Cnops, Huyse, Maniewski, Soentjens, Bottieau, Van Esbroeck and Clerinx2021; De Bont et al., Reference De Bont, Vercruysse, Southgate, Rollinson and Kaukas1994; Kruger & Hamilton-Attwell, Reference Kruger and Hamilton-Attwell1988; Pitchford RJ, Reference Pitchford1961; Webster et al., Reference Webster, Alharbi, Kayuni, Makaula, Halstead, Christiansen and Stothard2019; Wright & Ross, Reference Wright and Ross1980; Zwingenberger et al., Reference Zwingenberger, Feldmeier, Bienzle and Steiner1990). This review shows that hybrids within the haematobium group are particularly common in West and Central Africa. In Africa, hybrids have been detected in a few countries where S.h is known to be endemic, including Senegal, Mali, Niger, Nigeria, Benin, Côte d’Ivoire, Cameroon, Tanzania, Zambia, Malawi, South Africa, Zimbabwe, Gabon, and Democratic Republic of Congo. For the remaining countries endemic to Africa (Aula et al., Reference Aula, McManus, Jones and Gordon2021), it is therefore not possible to know whether hybrids are absent from these countries or whether they have simply not been identified. Given the current state of knowledge, discovering an area where no hybrids are found would be an exception or, perhaps, an area for further study to better understand why no hybrids are present. It is important to continue to map hybrids at different scales, whether at the country, region, or transmission site scales.
Figure 10. Distribution of schistosome hybrids of the haematobium group in Africa.
This review also highlights that S.h seems to be involved in most cases of hybridization. That this parasite is a human-infecting parasite certainly introduces a bias because it attracts more scientific attention than animal-infecting parasites. It is also easier to collect parasites in the urine of human patients than in animal stool or urine. It is also surprising to note that the one species (S.h) that lives in the veins of the perivesical plexus easily hybridizes with a variety of species that live in mesenteric veins. Where these parasites, which have very different tropisms, meet, is still unknown. It is less surprising to find hybrids that share both the same host and the same tropism, as in the case of hybrids between S.c and S.b. Historically, only limited data existed on hybrids, but over the past few decades this phenomenon has received a renewed interest. Even today, animal bilharziasis remains largely neglected when compared to human bilharziasis. These hybrids are of particular concern because they may be at the root of the tri-specific hybrids (S.h-S.b-S.c) already observed in Mali and Niger. Efforts must be made to characterize hybrids in humans as well as in animals. Today, S.b × S.h hybrids have been found in rodents in Senegal (Catalano et al., Reference Catalano, Sène, Diouf and Fall2018) as well as rodents and cows in Benin (Savassi et al., Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021). Identifying hybrids in animals does not guarantee that they are zoonotic. To determine this, it is necessary to check that the same hybrids circulate in both humans and animals. This requires the use of molecular markers that are sufficiently polymorphic. A study carried out in Senegal (Boon et al., Reference Boon, Mbow, Paredis, Moris, Sy, Maes and Huyse2019) that used microsatellite markers to genotype parasites from humans and cattle showed that the animal parasites were genetically different from the human parasites, suggesting the absence of a zoonotic transmission. It is important to notice that S.h × S.b hybrids have never been identified in cows in Senegal. This kind of population genetic analysis needs to be performed in areas where hybrids have been identified in both human and in either rodents (Senegal and Benin) or cows (Benin). Today, the zoonotic nature of S.h × S.b crosses has not been confirmed. In this cross, it seems clear that humans are the key host and that the role of animals as reservoirs or as spillover hosts needs to be addressed (Webster et al., Reference Webster, Gower, Knowles, Molyneux and Fenton2016).
Hybridization must also be analyzed in terms of transmission typology. In the Sahelian region (Burkina Faso, Niger, Mali, Senegal), all of the temporary or permanent water points attract both humans and animals (cattle, sheep, and goats) for multiple needs (drinking water for animals, and drinking water, laundry, fishing, recreational activities, and agriculture for humans). Therefore, depending on the region, there’s a big difference in the type and frequency of water sources used by definitive hosts. In West Africa, it is common practice for farmers to bathe daily the local ponds. In another example, for many parts of the world, cattle may have free access to water bodies while grazing or might be led two to three times per day to a river or canal (early morning, midday, and/or afternoon). In most areas, cattle are only in contact with water for drinking. This suggests that the type of water contact plays an important role in the transmission of schistosomiasis. It also means that within the same herd, the number of times that an animal comes into contact with water is unlikely to change with age. According to Stothard et al. (2020), details of the dynamics of these interactions and hybridization events in different contexts are certainly warranted, as differences are likely to occur at both micro and macro geographical scales (Stothard et al., 2020).
It is also important to note that within one type of cross, there are several types of hybrids. This is particularly visible in S.h-S.b hybrids, which have been studied extensively. Hybrids are classically detected by mitochondrial typing, offering two possibilities (S.b or S.h), and nuclear typing, offering three possibilities (S.bS.b, S.bS.h, and S.hS.h). There are therefore six possible hybrid categories. Nuclear alleles based on ITS2 are derived predominantly from Sh. Most studies show S.h ITS2 in excess of 75% (Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013; Teukeng et al., Reference Teukeng, Blin, Bech, Gomez, Zein-Eddine, Simo, Allienne, Tchuem-Tchuenté and Boissier2022; Angora et al., Reference Angora, Vangraefschepe, Allienne, Menan, Coulibaly, Meïté and Boissier2022; Savassi et al., Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Reference Savassi, Dobigny, Etougbétché, Avocegan, Quinsou, Gauthier and Mouahid2021). Nigeria, with only 49% S.h ITS2, seems to stand out. Specific variations in mitochondria are the most important. Variations in S.b mitochondria can range between 11% (Nigeria) and 95% (Senegal). The reasons for this variation in diversity and the expansion dynamics of these hybrids are not known. Exome capture analysis of miracidia from Niger and Zanzibar showed that hybridization is an ancient event dating back 240 years (Platt et al., Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019). No first-generation hybrids were observed among the 48 miracidia of Nigerian origin. These authors concluded that if interbreeding continues to exist (e.g., the presence of F1 miracidia), it is most likely rare. In fact, some studies based on less resolutive approaches have shown that the frequency of first-generation ITS S.b × S.c heterozygotes can be low. In Senegal, this frequency can vary between 0.6% (Boon et al., Reference Boon, Van Den Broeck, Faye, Volckaert, Mboup, Polman and Huyse2018) and 9% (Webster et al., Reference Webster, Diaw, Seye, Webster and Rollinson2013). On a country scale, these variations can be significant (ratio of 15), making it difficult to generalize. This is also observable on a larger scale because the frequencies of ITS S.b × S.c heterozygotes are 7.5%, 18.8%, 29.8%, and 41.3%, in Cameroon, Cote d’Ivoire, Benin, and Nigeria, respectively (Angora et al., Reference Angora, Allienne, Rey, Menan, Touré, Coulibaly and Boissier2020; Onyekwere et al., Reference Onyekwere, Rey, Allienne, Nwanchor, Alo, Uwa and Boissier2022a; Savassi et al., Reference Savassi, Mouahid, Lasica, Mahaman, Garcia, Courtin and Moné2020; Teukeng et al., Reference Teukeng, Blin, Bech, Gomez, Zein-Eddine, Simo, Allienne, Tchuem-Tchuenté and Boissier2022). As first reported in a pioneering study by Platt et al. (Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019), who used high-throughput sequencing, it is now essential to study these hybrids at wider spatial and temporal scales, with more markers and at a higher resolution. Finally, it is important to note that hybrid identification is mainly based on molecular analyses of mitochondrial-nuclear discordance or targeting just a few single nucleotide polymorphisms. Recently, a molecular method for differentiating S.b, S.c, and S.h has made it possible to identify hybrids between these three species in a single polymerase chain reaction (Blin et al., Reference Blin, Dametto, Agniwo, Webster and Angora2023). However, it would be misleading to think that the genome can be simplified to a single single nucleotide polymorphism, as this method doesn’t identify backcrossing events that can mask hybridization events. The use of NSG (Next Generation Sequencing) methods has clearly shown that the frequency of hybrids is largely underestimated (Platt et al., Reference Platt, McDew-White, Le Clec’H, Chevalier, Allan, Emery and Shapiro2019). This underestimation is due to the fact that backcrossing can lead to hybrid parasites being diagnosed as pure. It is therefore important to develop more powerful tools to better characterize hybrids and to characterize the level of genetic introgression between the species concerned.
Conclusion
In conclusion, this literature review centered on the various schistosome hybridizations within the haematobium group shows that interactions between species continue in West and Central Africa, and involve migratory phenomena, climatic changes, and host/parasite compatibility. In the past, few studies focused on this phenomenon, but now there is a strong increase in such studies in many parasitic species, especially in schistosomes. Because of increased human population growth, anthropogenic environmental changes, and global movements of humans and animals, hybridization is a growing field of interest within the research community because of the many questions it raises, particularly in Africa. This review gives us a global idea about the foci of hybridization of urinary schistosomiasis in West and Central Africa and requires a paradigm shift that entails a multisectoral (e.g. One Health) approach to preventing zoonotic transmission of schistosomiasis.
Author contributions
P.A: Methodology, Writing-Original Draft Preparation, Writing – Review & Editing; B.A.E.S: Produced all the maps, Writing – Review & Editing; M.D and M.I: Writing – Review & Editing; A.D. and J.B: Conceptualization, Methodology Supervision, Writing – Review & Editing.
Acknowledgements
Not applicable.
Financial support
This study has not received any funding.
Competing interest
The authors declare that they have no competing interests.
Ethical standard
Not applicable. All authors have given their consent for publication of this article.
