# African zoonotic schistosomiasis: a paradigm shift

Boris Savassi, Julien Kincaid-Smith, David Courtin, Moudachirou Ibikounlé, Eve Toulza, Richard Galinier, Jacqueline Milet, Laure Gineau, André Garcia, Roch Appolinaire Houngnihin, et al.

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## To cite this version:

Boris Savassi, Julien Kincaid-Smith, David Courtin, Moudachirou Ibikounlé, Eve Toulza, et al. African zoonotic schistosomiasis: a paradigm shift. Philosophical Transactions of the Royal Society B: Biological Sciences, 2026, 381 (1941), pp.20240522. 10.1098/rstb.2024.0522. hal-05469106

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## PHILOSOPHICAL TRANSACTIONS B

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**Cite this article:** Savassi *B et al*. 2026 African zoonotic schistosomiasis: a paradigm shift. *Phil. Trans. R. Soc. B* **381**: 20240522.

https://doi.org/10.1098/rstb.2024.0522

Received: 19 March 2025

Accepted: 12 May 2025

One contribution of 14 to the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.

**Subject Areas:**

health and disease and epidemiology, ecology, evolution, genetics

**Keywords:**

schistosomiasis, animal reservoir, hybrids

**Author for correspondence:**

Jerome Boissier

e-mail: boissier@univ-perp.fr

## African zoonotic schistosomiasis: a paradigm shift

Boris Savassi<fnref n="1" />, Julien Kincaid-Smith<fnref n="2" />, David Courtin<fnref n="3" />, Moudachirou Ibikounle<fnref n="4" />,<fnref n="5" />, Eve Toulza<fnref n="1" />, Richard Galinier<fnref n="1" />, Jacqueline Milet<fnref n="6" />, Laure Gineau<fnref n="6" />, Andre Garcia<fnref n="6" />, Roch Houngnihin<fnref n="7" />, Manon Blin<fnref n="8" />, Carine Brouat<fnref n="2" />, Song Liang<fnref n="9" /> and Jerome Boissier<fnref n="1" />

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In Asia, *Schistosoma japonicum* infects humans and many animal species, making it a zoonotic disease. In Africa, the two major species infecting humans are *Schistosoma mansoni* and *Schistosoma haematobium*, which cause mesenteric and urogenital schistosomiasis, respectively. Despite the significance of these parasitic infections for human health, few studies have examined the zoonotic aspects of these parasites. In the initial section of this article, we examine the advancements made in analysing the zoonotic characteristics of *S. japonicum*, with a particular emphasis on the diverse scenarios observed in the field. We also review the role of rodents and non-human primates in transmitting *S. mansoni* and the emerging importance of cattle and rodents in hybrid schistosomiasis involving *S. haematobium* and *Schistosoma bovis* (a livestock and rodent parasite). Second, we examine the genetic diversity of these hybrid forms across their distribution in West Africa. Hybrid forms exhibit considerable diversity across all spatial levels, ranging from the transmission site to the national scale. Ultimately, we aim to explore the implications of zoonotic urogenital schistosomiasis in relation to the role of each host in its transmission, together with parasite gene flow, parasite diversity and parasite virulence.

This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.

### 1. Introduction

Zoonotic pathogens are either bacteria, fungi, viruses or metazoan parasites that are transmitted between vertebrate animals and humans. Most human infectious diseases are zoonotic. Approximately 1500 referenced human pathogens and approximately 200 emerging or re-emerging agents, 58% and 73%, respectively, are zoonotic [1]. Among the human infectious diseases, the World Health Organization (WHO) currently recognizes 20 diseases as neglected tropical diseases [2], with schistosomiasis being the most significant in terms of prevalence, morbidity and socio-economic impact [3]. It is estimated that schistosomiasis infects over 250 million people, of whom

© 2026 The Author(s). Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

<footnote n="1">¹IHPE, University of Montpellier, CNRS, Ifremer, University of Perpignan Via Domitia, Perpignan, France</footnote>

<footnote n="2">²CBGP, IRD, CIRAD, INRAE, Institut Agro Montpellier, University of Montpellier, Montferrier-sur-Lez, France</footnote>

<footnote n="3">³Intertryp, Institut de Recherche pour le Développement, CIRAD, University of Montpellier, Montpellier, France</footnote>

<footnote n="4">⁴Centre de Recherche pour la lutte contre les Maladies Infectieuses Tropicales (CReMIT/TIDRC), Université d'Abomey-Calavi, Abomey-Calavi, Benin</footnote>

<footnote n="5">⁵Institut de Recherche Clinique du Bénin (IRCB), Abomey-Calavi, Benin</footnote>

<footnote n="6">⁶Université Paris Cité, IRD, Inserm, MERIT, 75006 Paris, France</footnote>

<footnote n="7">⁷Laboratoire d'Anthropologie Médicale Appliquée (LAMA), Université d'Abomey-Calavi, Abomey-Calavi, Benin</footnote>

<footnote n="8">⁸SAS ParaDev®, 66 860, Perpignan, France</footnote>

<footnote n="9">⁹Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA</footnote>

<footnote>BS, 0000-0003-3536-160X; ET, 0000-0003-2049-2279; JB, 0000-0002-0793-3108</footnote>
90% live in sub-Saharan Africa [4]. The etiological agents of schistosomiasis are trematode helminths from the *Schistosoma* genus. *Schistosoma haematobium* (endemic in Africa, the Arabic Peninsula and Europe), *Schistosoma mansoni* (endemic in Africa and South America) and *Schistosoma japonicum* (endemic in Asia) are the major species responsible for human disease burdens recorded worldwide [5]. From an evolutionary perspective, all human-infecting schistosome species are zoonotic, because they supposedly originated from ancestral vertebrate parasites of animals [6]. The jump from an animal host to a human host has occurred three times in the course of evolution. From an epidemiological point of view, however, except for *S. japonicum* in Asia, schistosomes are generally not recognized as zoonotic parasites and the role of vertebrate hosts (i.e. reservoirs) other than humans has been largely overlooked in control strategies. However, this perspective is based on limited understanding and does not fully account for the potential role of non-human vertebrate hosts in sustaining transmission, particularly in low-transmission settings where extensive control efforts are in place and the goal is elimination of the diseases as a public health problem [7].

The mere presence of the same parasite species in both human and animal hosts does not necessarily indicate zoonotic transmission [8]. A parasitic life cycle can function independently in humans and animals without the two encountering. For zoonotic transmission to occur, both the encounter filter (spatial and temporal overlap) and the compatibility filter (the parasite must be able to successfully infect the host and evade its defence) must be open [9]. In the case of schistosomes, the encounter filter may be closed if humans and animals are exposed to infection in different water bodies or at different times, even when they share the same environment. This independent evolution of the schistosome life cycle in distinct host species can be observed in certain features of the parasite's life history traits, such as the cercarial chronotype. For instance, studies on *S. mansoni* have demonstrated a diurnal cercarial chronotype in humans and a nocturnal chronotype in rodents, reflecting the selection pressures imposed by their respective definitive host behaviour [10]. Although the differential pattern of cercarial release may favour the infection of different hosts, there is no reproductive barrier when both chronotypes co-infect an experimental host mouse. If the encounter filter is open, the compatibility filter may still prevent zoonotic transmission. This host-parasite compatibility can be tested throughout experimental exposure of vertebrate hosts to assess the ability of a schistosome to infect an animal. In the *S. mansoni* pathosystem, for example, several non-human primates, including green monkeys (*Chlorocebus aethiops*), chimpanzees (*Pan troglodytes*), vervet monkeys (*Cercopithecus aethiops*) and patas monkeys (*Erythrocebus patas*), can be experimentally infected by the same strain and are also found naturally infected in the natural environment [11]. However, successful experimental infection does not necessarily imply that these species act as reservoir hosts in the field. A prime example is the mouse, which is commonly used in laboratory settings to maintain *S. mansoni* or *S. japonicum* strains (*S. haematobium* is typically maintained in gerbils or hamsters). Despite this, mice generally avoid water and are never found to be infected in the field. Finally, the only way to conclusively affirm that transmission is zoonotic in the field is by using genetic and genomic tools to confirm circulation of the parasite populations between different host species [12].

In the first part of this article, we provide an overview of the current understanding of the zoonotic potential of *S. japonicum* and *S. mansoni*. Building on existing knowledge of the zoonotic potential of these non-hybrid species, we then review the emerging insights into *Schistosoma bovis* × *S. haematobium* hybrids. *S. bovis* is a livestock and rodent-infecting parasite [13]. Hybridization adds complexity to the schistosome transmission system, as it brings together two species, introducing original genetic features and characteristics, in contrast to *S. japonicum* and *S. mansoni*. In the second part, we will examine the genetic diversity of these *Sh* ×*Sb* hybrid forms and explore the potential links to the zoonotic capacity of these hybrids. In the final section, we discuss the anticipated epidemiological consequences of zoonotic urogenital schistosomiasis.

## 2. Species and putative hybrids of anthroponotic and zoonotic schistosomes

*Schistosoma japonicum* has been recognized as a zoonotic parasite for decades. Several studies have been carried out, ranging from genetic evidence of zoonotic transmission to the integration of the reservoir hosts in control strategies. Approximately 46 mammalian species have been suspected as potential reservoir hosts for *S. japonicum*, and genetic evidence of zoonotic transmission has been documented for water buffalo, cattle, pigs, dogs, rats and cats [14–18]. Interestingly, the zoonotic transmission patterns of *S. japonicum* vary regionally. In the marshland region of Anhui province (China), water buffalo and cattle appear to play a more significant role as reservoirs than other domestic animals [17]. However, in the hilly region of the same area, rodents and dogs are found to be the primary reservoirs [15], whereas in the province of Samar, the Philippines, dogs have been found to play a dominant role in *S. japonicum* transmission [14]. Considering that the transmission of schistosomes is highly focal, these regional differences likely result from a specific selection of a given reservoir host (e.g. dogs, water buffaloes or rodents), resulting in genetic adaptation of the parasite to a given host in specific areas. This high adaptability has led some researchers to suggest that *S. japonicum* may represent a complex of species that could have different reservoirs depending on the epidemiological situation [19]. Because animals have been shown to actively contribute to the transmission of *S. japonicum*, they are now often integrated into control strategies [20]. This includes the development of vaccines targeting animal reservoirs [21], improved animal diagnostics [22] and targeted treatment for livestock and other domestic animals [23]. Additionally, mathematical modelling is used to assess transmission dynamics in animal reservoirs and evaluate the potential impact of various control measures [24].

The definitive host spectrum of *S. mansoni* has recently been synthesized [10]. This study references 56 host species naturally infected by *S. mansoni*, including 31 rodent and 14 primate species. It has therefore been suggested that rodents in Africa [25] or in Brazil [26], and non-human primates in Africa [27,28], could serve as reservoir hosts for human schistosomiasis. Many studies on rodent hosts (*Rattus rattus*) have been carried out in Guadeloupe [29–32]. These studies have shown that the definitive host species has an influence on the cercarial emission pattern. At sites where rats were the only hosts, the chronobiology of
cercariae was late; at sites where only humans were present, the chronobiology was early; and when both host species were present simultaneously, the emission pattern was intermediate [33]. In the Guadeloupe system, parasite genetics studies focused on rodent parasites and not on human parasites. The same is true in Africa, where it has been shown that *Mastomys huberti* and *Arvicantis niloticus* hosted *S. mansoni*, *S. bovis* and *Sh × Sb* hybrids in Senegal [34]. In the same area, subsequent research using similar markers characterized schistosomes from molluscs (*Biomphalaria pfeifferi*), humans and rodents (*M. huberti* and *A. niloticus*), and confirmed the presence of multiple *S. mansoni* lineages that could infect both rodents and humans [35]. This study marked a pivotal first step towards a paradigm shift, suggesting that African *Schistosoma* species and their hybrids may be true multi-host pathogens. More recently, in the same area of Guiers Lake, Senegal, another study confirmed the infection of *M. huberti* and *A. niloticus*, observing spatio-temporal variations in infection patterns. Transmission was highly focal with most infected rodents found during or just after the rainy season, a period when older individuals dominate rodent populations [36]. Interestingly, although the last study mainly found *S. mansoni* over time and across space, they also identified sporadic cases of infection with *S. bovis* and, for the first time, with adult and miracidia of *S. haematobium* in *M. huberti*. Given that all schistosomes exhibit a strong affinity for rodents (all schistosome species are maintained in rodents in the laboratory), some authors have proposed that they could act as biotic hubs, serving as hosts where hybridization phenomena may occur [34,37]. These latter studies strongly suggest a role for rodents in *S. mansoni* transmission; however, the genetic markers employed were primarily designed for phylogeographic analysis rather than for epidemiological investigations. Rodents can serve as hosts that are occasionally infected by the schistosome but do not maintain a parasite cycle (spill-over hosts), hosts that can sustain a cycle (reservoir hosts), or hosts that are crucial for maintaining the parasite cycle (key hosts) [6]. To specify the role of rodents in *S. mansoni* transmission, more appropriate markers, such as microsatellites or single nucleotide polymorphisms (SNPs) or whole-genome sequencing data, should be employed. Additionally, these three last field studies were all conducted in the same region in northern Senegal, highlighting the need to carry out surveys followed by molecular studies in other areas to broaden our understanding. Similarly, several studies have been carried out in non-human primates to identify the presence of *S. mansoni*, either through parasitological or serological diagnostic tests or after necropsy [11]. Primates of the genera *Cercopithecus*, *Papio*, *Gorilla*, *Erythrocebus* and *Pan* have been found naturally infected with *S. mansoni* across six different West and East African countries [11]. Once again, molecular epidemiological studies are very rare: only one study using microsatellite markers provided evidence that *Chlorocebus aethiops* (vervet monkeys) and *Papio anubis* (baboons) share the same parasite population as human hosts in Ethiopia, demonstrating the role of these animals as reservoirs for *S. mansoni* [38].

Until recent discoveries, urogenital schistosomiasis caused by *S. haematobium* was considered exclusive to humans [13]. However, in 2009, the first doubts arose after the discovery of a hybrid of *S. haematobium* and an animal parasite (*S. bovis*) infecting humans in Senegal [39]. The introgression of genes from an animal-infecting parasite raised concerns about the potential zoonotic capacity of this newly identified pathogen. In 2013, a putative *Sh × Sb* parasite emerged in Corsica, France [40,41]. Given that it had previously only been detected in Senegal, and that genetic analysis traced the strain responsible for the Corsican outbreak back to Senegal [32], an important question arose: did its emergence result from its hybrid status, or can similar hybrids be found in other regions of West Africa? After extensive epidemiological studies, the question is whether there is a hybrid-free zone in West Africa. Indeed, so far *Sh × Sb* hybrids have been found in humans in many sub-Saharan African countries, including Mali, the Ivory Coast, Senegal, Cameroon, Nigeria, Niger and Benin [42], with reported frequencies ranging from 11% in Cameroon [43] to 100% in Benin [44,45]. Despite being recognized for 15 years [39], few field studies have been conducted to identify these hybrids in animals. While *Sh × Sb* hybrids have not been identified in cattle in Senegal [46,47] or Cameroon [48], they have been identified in Benin, infecting both cattle and rodents [44,45], and in Senegal, where they have been found in rodents [34]. Very few experimental studies have been carried out on these hybrids. One study using hamsters (*Mesocricetus auratus*), a non-natural host, found that the infection intensity of the Corsican strain was similar to that of pure *S. bovis* or *S. haematobium* [49]. Alternatively, laboratory rats (*Rattus norvegicus*) exposed to the hybrid strain that emerged in Corsica revealed very low compatibility [50]. Finally, a more recent study produced parasite lines with varying degrees and directions of introgression between the two species, and then exposed sheep to infection [51]. The study showed that: (i) while *S. haematobium* alone does not infect sheep, all hybrid forms, whether F1 or back-crossed with either *S. bovis* or *S. haematobium*, were able to infect this *S. bovis* natural animal host; (ii) no parasites were found in the veins surrounding the bladder, and the parasite's tropism varied depending on its genetic background (pure *S. bovis* strain or hybrid): while *S. bovis* parasites were found in the veins surrounding the small intestine, hybrid parasites were detected in the veins throughout the entire digestive tract, from the small intestine to the rectum; (iii) the ability of parasites to infect sheep depended on the direction and the level of introgression (i.e. hybrids back-crossed with *S. bovis* showed higher infection success compared with those back-crossed with *S. haematobium*), suggesting that the zoonotic capacity may be linked to the relative genomic assemblage of the two species. While hybrids between *S. bovis* and *S. haematobium* have been identified in West and Central Africa, hybrids between *S. mattheei* and *S. haematobium* have been identified in South-East Africa. Less work has been done on these hybrids than on *Sh × Sb* hybrids [52]. *S. mattheei* × *S. haematobium* hybrids have been identified in the excreta or semen of humans [53–56] but also in cattle faeces [57].

### 3. *Schistosoma bovis* × *Schistosoma haematobium* hybrid diversity

Most studies that have identified putative *Schistosoma* hybrids have used a multi-locus genotyping approach. The first genotyping method relies on the mitochondrial gene coding for cytochrome oxidase subunit 1 (COI) genetic marker, which makes it possible to attribute to which species the maternally inherited mitochondria belong. This mitochondrial genotype is typically obtained by rapid diagnostic PCR (RD-PCR) [58] or through Sanger sequencing. It is important to note that RD-PCR is limited
<figure><img src="image_7.png" /><figcaption>**Figure 1.** Distribution of the different genotypes between *S. haematobium* (*Sh*) and *S. bovis* (*Sb*) obtained after genotyping of mitochondrial haplotypes (by COI) and nuclear alleles (by ITS). Code: COI(haplotype)_ITS(allele 1) ITS(allele 2).</figcaption></figure>

to distinguishing *S. bovis*, *S. mansoni* and *S. haematobium* and cannot distinguish *S. bovis* from *S. curassoni* (a goat parasite) or *S. guineensis* (a human parasite), while sequencing can differentiate all *Schistosoma* species. The second genotyping method targets a biparentally inherited nuclear marker, typically the internal transcribed spacer region (ITS), which has the advantage of containing five species-specific SNPs distinguishing *S. bovis* from *S. haematobium*. This allows for obtaining three possible genotypes: *ShSh*, *SbSh* or *SbSb*. This last nuclear genotyping is performed using PCR-restriction fragment length polymorphism (PCR-RFLP), Sanger sequencing or, more recently, allele-specific tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) [59]. To fully differentiate all species in the *S. haematobium* group (including *S. haematobium*, *S. bovis* and *S. curassoni*), sequencing of the 18S gene or the use of T-ARMS PCR is required. More recently, a two-tube high-resolution melt assay has been developed, targeting one mitochondrial and one nuclear gene capable of differentiating the species-parentage of schistosomes from a possible range of six schistosome species (*S. mattheei*, *S. curassoni*, *S. bovis*, *S. haematobium*, *S. mansoni* and *S. margrebowiei*) [60]. By combining these double genotyping methods, six different genotypes can be identified (COI_ITS/ITS: *Sh_ShSh*, *Sb_ShSh*, *Sh_ShSb*, *Sb_SbSb*, *Sh_SbSb* or *Sb_SbSh*. We are referring to different genotypes, not pure or hybrid parasites involving whole genome analysis. The presence of a single *S. bovis* gene in humans indicates a hybrid parasite, as pure *S. bovis* cannot infect humans. Figure 1 illustrates the distribution of these six genotypes collected in humans across various studies carried out in West and Central Africa [39,40,43–47,61–65]. In Senegal, Corsica, Mali and Cameroon, the predominant genotype is *Sh_ShSh*. In the Ivory Coast, both *Sh_ShSh* and *Sb_ShSh* are prevalent, whereas in Benin, the *Sh_ShSh* genotype is totally absent, with *S. bovis* genes/alleles being more dominant, including a non-negligible presence of the *Sb_SbSb* genotype. This suggests that the distribution of genotypes differs from one country to another, with different studies within the same country showing a certain degree of reproducibility (figure 1). This pattern of diversity has also been observed in genomic studies [42,43]. A pan-African genomic analysis revealed significant variations in the distribution of *S. bovis* and *S. haematobium* alleles across different samples [43], as well as differences in the estimated number of generations since introgression with *S. bovis* [42]. This genetic diversity echoes the situation observed for *S. japonicum*, for which some authors consider a species complex [19]. The selective pressures imposed by a specific host species (dog, human, rodent or cattle) within distinct epidemiological contexts could explain this genetic structuring in *S. japonicum*. Although we observe genetic heterogeneity within *Sh × Sb* hybrids, there is currently no clear evidence linking this heterogeneity to the definitive host spectrum, as has been suggested for *S. japonicum*.

Figure 2 shows the relative frequencies of COI *S. bovis* versus *S. haematobium* haplotypes, ITS *S. bovis* versus *S. haematobium* alleles and the frequency of hybrids across various studies. *S. bovis* COI haplotype frequencies ranged from 4% in Cameroon to 100% in Benin. Notably, the frequency of *S. bovis* COI haplotypes correlates strongly with the frequency of *S. bovis* alleles within the ITS (Pearson correlation *r* = 0.71, *p* = 0.01). Consequently, the frequency of hybrids follows the same trend, ranging from 11% in Cameroon to 100% in Benin. These findings suggest that the introgression process is dynamic and that hybridization patterns may differ between countries. Interestingly, the country showing the highest frequency of *S. bovis* genes (Benin) is also the only country where *Sh × Sb* hybrids have been detected in both cattle and rodents [45]. These findings align with experimental studies in animals, which show that zoonotic capacity is linked to the level of *S. bovis* introgression into *S. haematobium* [51]. At the transmission site level, a study carried out in Cameroon showed considerable variability in the frequency of hybrids, ranging from 2.6% to 21.2% [43]. This inter-site variation had previously been observed in Senegal [66]. The study carried out in Cameroon further demonstrated that the percentages of these hybrids are correlated with the genetic diversity of the parasite, as measured by microsatellite markers, highlighting that hybridization is a key biological process shaping the local
<figure><img src="image_8.png" /><figcaption>**Figure 2.** Relative frequency of (A) mitochondrial haplotypes on the COI mitochondrial marker, (B) nuclear alleles on the ITS marker and (C) hybrids between *S. haematobium* and *S. bovis* in the various studies reported in the literature.</figcaption></figure>

<table><caption>**Table 1.** Rodent, cattle and human life history traits may have consequences on schistosome transmission.</caption><thead><tr><td>trait</td><td>rodent</td><td>cattle</td><td>human</td></tr></thead><tbody><tr><td>activity pattern</td><td>late diurnal/nocturnal</td><td>early diurnal</td><td>diurnal</td></tr><tr><td>body size</td><td>small</td><td>extra large</td><td>large</td></tr><tr><td>life span</td><td>short</td><td>long</td><td>very long</td></tr><tr><td>territory</td><td>small</td><td>large</td><td>very large</td></tr><tr><td>movement range</td><td>very short distance</td><td>long distance</td><td>long/very long distance</td></tr><tr><td>reproductive rate</td><td>high</td><td>moderate</td><td>low</td></tr><tr><td>population density</td><td>low to very high</td><td>low/medium</td><td>very high</td></tr><tr><td>population dynamics</td><td>seasonal/constant according to the species and the habitat</td><td>constant</td><td>constant</td></tr><tr><td>expected transmission index</td><td>medium</td><td>high</td><td>very high</td></tr></tbody></table>

genetic diversity of *S. haematobium*. Additionally, the study highlights the dynamic nature of hybridization patterns at the scale of transmission sites.

The genomic patterns observed at the continental scale [67–69] appear to contradict the population genetic patterns described at regional scales [43]. While whole-genome sequencing studies of hybrid parasites have found no evidence of recent introgression [67–69], population genetic studies suggest that introgression may be an ongoing and dynamic process. One possible explanation is that hybridization events are relatively rare and may be difficult to capture in genomic studies, which typically analyse a limited number of individuals due to cost constraints. If we consider the *Sb_SbSb* genotype, based on previous studies showing the frequency of this genotype (0.04%, 0.69% and 8.51%), we would need to sample 7488, 433 or 34 parasites in Senegal, the Ivory Coast and Benin, respectively, to have a 95% probability of detecting it. In contrast, genomic studies often analyse only a single parasite per site [69] or less than 30 individuals overall [67,68], with most samples originating from human hosts. To bridge this gap, applying population genomics tools in a large number of parasites, such as RADseq, which has already been successfully used for *S. japonicum* [70], could provide deeper insights into hybridization dynamics.

## 4. Potential consequences of zoonotic urogenital schistosomiasis

In the case of zoonotic transmission, the role of animals needs to be considered not only as reservoir hosts influencing human transmission dynamics but also as potential ‘biotic hubs’ facilitating parasite gene flow, with some putative consequences on both morbidity and epidemiology.

### (a) Assessing the role of each host in the zoonotic transmission of urogenital schistosomiasis

The contribution of different hosts to transmission depends on the species involved and their respective life history traits. Table 1 summarizes key traits of rodents, cattle and humans that may have consequences on schistosome transmission.

Host behaviour in relation to frequency and/or timing of water contact can shape schistosome cercarial emergence patterns [33]. Analysing this life history trait referred to as ‘activity pattern’ in table 1 is important for assessing the role of a given animal species in schistosome transmission [71]. For instance, in the case of *S. japonicum*, late afternoon emergence occurs when rodents are the reservoir host, while morning emergence is observed when cattle are the reservoir host [72]. These distinct
phenotypic patterns are associated with genetic clustering, supporting the hypothesis that *S. japonicum* may represent a complex of parasite strains rather than a single homogeneous species [72]. In Benin, *Sh* × *Sb* hybrid parasites exhibit a less contrasted emergence pattern compared with *S. japonicum*, with multiple peaks observed over a 24 h period [44,45]. This polymorphism may stem from the complexity of the pathosystem, which involves several hosts involved in transmission (human, rodent and cattle) and the intricate genetic background of *Sh* × *Sb* hybrids. We propose that the activity pattern is more diurnal than nocturnal for humans. This may be qualified by certain human activities such as hunting or fishing, which may be carried out at night, mainly by males. Cattle and humans, due to their larger size and longer lifespan, are likely to host a greater effective population size and higher genetic diversity of parasites compared with rodents. Additionally, as cattle and humans are more mobile and use a larger territory than rodents, they are expected to acquire and disperse more parasites from diverse geographic locations, further contributing to a greater diversity of parasites. In contrast, rodents, with their smaller geographical ranges, may maintain a more localized schistosome population. However, it should be noted that commensal rodents can travel several hundred kilometres, transported by human activities. Another important point is that rodent population dynamics generally exhibit strong seasonality, linked to local climatic or environmental conditions, which influence food availability [73,74], unlike cattle or humans. In the *S. japonicum* pathosystem, young rats are typically not found to be infected, with prevalence increasing progressively with age [75]. A similar pattern has been observed in Senegal, where schistosomes are found mostly, if not exclusively, in adult rodent individuals [36]. The development from larvae to mature adult worms that produce eggs and contribute to transmission takes several weeks (approx. 5–7 weeks post-exposure). When reproduction is seasonal, infection rates in a rodent population may thus periodically decrease when the older rodents die, although there is generally an overlap between the older generation and the new generation that is starting to get infected. Therefore, rodent infection and their contribution to transmission are potentially lower at each new generation in the following season. This can be nuanced for rodents living as commensals where seasonality is much less pronounced. Finally, host density likely also plays a crucial role in transmission, as parasites are likely to favour the most abundant hosts [76]. Ultimately, the importance of each host in transmission can be assessed using a transmission index that considers the number of eggs released per host per day, the number of hosts and the prevalence [18,77,78]. In the *Sh* × *Sb* transmission system, we assume a medium, high and very high transmission index for rodents, cattle and humans, respectively (table 1). Mathematical models provide a powerful framework for quantifying these host-specific contributions to *Sh* × *Sb* transmission. By integrating host-specific parameters such as infection prevalence, parasite burden, egg output, water contact rates, host lifespan, movement patterns and seasonal fluctuations, models can offer quantitative insights into the relative roles of different host species.

## (b) Parasite gene flow and parasite diversity in the zoonotic transmission of urogenital schistosomiasis

An expected consequence of pathosystem complexity is an increase in parasite gene flow between different hosts [79]. Several factors, such as the animal species involved, their diversities, sizes, densities and behaviours may influence this transmission. This increase in gene flow is likely to enhance the genetic diversity of the parasites. It has been shown that hosts exposed to different genotypes have a greater susceptibility compared with those infected with parasite clones [80,81]. This phenomenon is likely the result of concomitant immunity, which recognizes genotypes during primary infections and allows subsequent infections with different genotypes to succeed during reinfections [80]. The immune system appears to be ‘trapped’, favouring the diversity of parasite infrapopulations. As a consequence, the genetic structure of the schistosome infrapopulation is often described as a ‘genetic mixing bowl’ [82]. Indeed, after several successive light infections, the long-lived, mobile vertebrate definitive host gradually acquires genotypes produced by the short-lived, less mobile mollusc intermediate host. In addition to parasite gene flow, hybridization introduces new alleles through genetic introgression, further increasing the diversity within the mixing bowl. This latter point has been demonstrated in Cameroon, where the higher the frequency of hybrid schistosomes at a given site, the greater the genetic diversity of the parasite population [43]. This increase in genetic diversity within the parasite population should promote the establishment of the parasite in both intermediate and definitive hosts. Regarding the mollusc intermediate host, the matching phenotype model [83] suggests that the more diverse the miracidium population, the greater likelihood of compatibility between a miracidium and a mollusc host.

## (c) Parasite virulence in the zoonotic transmission of urogenital schistosomiasis

An increase in parasite burden, genetic diversity or hybridization between human- and animal-infecting parasites could ultimately have consequences for both human and animal morbidity. Quantitatively, a higher worm burden leads to increased egg production, exacerbating disease severity. Qualitatively, greater genetic diversity within the parasite infrapopulation is expected to enhance virulence [84]. A link between genetic diversity and virulence has already been observed in various host-parasite systems, including protozoan (e.g. *Plasmodium chadaudi/Anopheles stephensi* [85]) and metazoan (e.g. *Diplostomum pseudopathaceum/Oncorhynchus mykiss* [86]). Additionally, the introgression of *S. bovis* genetic material into *S. haematobium* may also modify the risk of infection and the virulence of the parasite through hybrid vigour [69]. The role of schistosome genetic diversity on human disease severity remains an understudied area [79,87]. Regarding *S. mansoni* infections, two studies sought to address potential links between the parasite's genetic diversity and the prevalence/intensity of infection [88,89]. Using microsatellite markers, Barbosa *et al.* [88] failed to find a link between parasite genetic diversity and epidemiological characteristics. However, a more recent study has shown an association between a specific microsatellite allele and infection intensity or morbidity level [89]. This allele is located near the cGMP-dependent protein kinase gene, which is expressed in reproductive organs of adult schistosome worms and appears to be linked to egg production [89]. Concerning *S. haematobium*
infections, earlier studies using low-polymorphic genetic markers (RAPD) failed to establish a link between the parasite's genetic diversity and the severity of the infection [90]. However, a more recent study evidenced an increase in hepatic morbidity (hepatomegaly) and a decrease in urogenital morbidity in *Sh* × *Sb* hybrid infections compared with non-hybrid infections [91]. The relationship between parasite diversity and morbidity remains an area that requires further investigation in the human-schistosome interaction. Finally, as with many infectious diseases [92], it is well established that schistosome transmission is also strongly influenced by several factors related to the definitive host, such as gender, age, genetic background, behaviour, etc. [93]. These co-factors must also be integrated into a 'One Health' approach in order to fully assess the impact of zoonotic transmission on human morbidity.

## 5. Conclusion

Schistosomiasis remains a significant public health issue in Africa, with efforts primarily focused on human transmission, often overlooking the impact of animals. It is essential that current initiatives to decrease the prevalence of this disease consider the role animals may play in its transmission and in animal health without impeding these efforts. Decades of research on *S. japonicum* have established methodologies for an in-depth analysis of the role of animals in the transmission of schistosomiasis. Since animals are known to be crucial in transmitting *S. japonicum*, studies have focused on treatment protocols, vaccine trials and diagnostic tools. We need to draw inspiration from this work to develop similar tools for African schistosomiasis. Building on previous research, it is essential to examine the role of rodents and primates in the transmission of *S. mansoni*, as well as the role of rodents and ruminants in the spread of hybrid urogenital schistosomiasis. This includes studying hybrids between *S. bovis* and *S. haematobium* in West Africa, and hybrids between *S. haematobium* and *S. mattheei* in South-East Africa. As far as ruminants are concerned, studies have focused on livestock, mainly cows, sheep and goats, but it would also be interesting to look at the presence of these hybrids in wild animals.

The majority of genetics studies aimed at analysing the role of animals in the transmission of African schistosomiasis used markers that are not very discriminating. Some studies, however, have used whole-genome sequencing approaches [67–69], providing complementary and sometimes contradictory information to the population genetics studies. Population genomics tools, such as RADseq, already used for *S. japonicum* [70], can also be used for *S. mansoni* or *S. haematobium* infections. The same applies to the genetic identification of hybrids, which is based on a two-loci system. More global approaches will provide a new perspective on hybrids, their evolutionary history and their diversity.

Finally, it seems that there are major disparities in the type and frequency of hybrids across all the scales considered. The optimal scale for operations is at the transmission site level, as each location may possess unique epidemiological characteristics (e.g. presence of livestock, large rodent population, human migration, etc.) and its own history, such as treatment history that could have implications in hybrid frequency. Current projects, such as the HUGS and SCHIS-CAM projects in Malawi and Cameroon, funded by the Wellcome Trust Foundation, and the AFZOONS project in Benin, funded by the French national research agency, consider a site-based approach. These initiatives aim to provide detailed insights into the role of animals in different transmission sites under various contexts in the coming years.

**Ethics.** This work did not require ethical approval from a human subject or animal welfare committee.

**Data accessibility.** This article has no additional data.

**Declaration of AI use.** We have not used AI-assisted technologies in creating this article.

**Authors' contributions.** B.S.: conceptualization, writing—original draft; J.K.-S.: conceptualization, project administration, writing—original draft; D.C.: conceptualization, project administration, writing—review and editing; M.I.: conceptualization, project administration, writing—review and editing; E.T.: conceptualization, writing—review and editing; R.G.: conceptualization, project administration, writing—review and editing; J.M.: conceptualization, writing—review and editing; L.G.: conceptualization, writing—review and editing; A.G.: conceptualization, writing—review and editing; R.H.: conceptualization, writing—review and editing; M.B.: conceptualization, writing—review and editing; C.B.: conceptualization, writing—review and editing; S.L.: conceptualization, project administration, writing—review and editing; J.B.: conceptualization, project administration, supervision, writing—original draft.

All authors gave final approval for publication and agreed to be held accountable for the work performed therein.

**Conflict of interest declaration.** We declare we have no competing interests.

**Funding.** This research was supported by the programme AFZOONS (ANR-CE35-6032) from the French Research National Agency and ACTS from University of Montpellier. This study is set within the framework of the 'Laboratoires d'Excellence (LABEX)' TULIP (ANR-10-LABX-41).

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