**3.** *Schistosoma* **hybridization and risk of emerging zoonosis in Africa**

#### **3.1 Schistosoma hybridization in Africa**

Environmental and ecological changes due to natural phenomena and anthropogenic activities break species isolation barriers and increase the possibility of acquiring new infections of both human and animal origin. This can lead to the occurrence of multiple infectious species and strains within a single host [4]. Multiple infections of two or more genetically distinct agent species may permit heterospecific (between-species or between-lineage) mate pairings, resulting in the production of a new offspring (species) that can be either infertile or fertile. This process is called *hybridization* [4, 16]. During this process, unidirectional and/or bidirectional allelic exchange occurs among gene pools of the two sympatric interbreeding species to produce offspring organisms with hybrid genomes [17]. The produced hybrid offspring may introduce a single gene or chromosomal region of one of its parent species to the genome of the second (divergent) parent species through repeated backcrossing, a process known as *introgression* or *introgressive hybridization* [18, 19]. Due to the advance in diagnostic technology, there are an increasing number of reported findings of fertile hybridization and introgression events across humans, animals, and eukaryotic parasites. Hybridization and introgression among parasites, particularly those with zoonotic potential, is an emerging public and veterinary health concern at the interface of evolution, epidemiology, ecology, and control [4]. They are characterized by heterotic alterations, speciations, neo-functionalization, and adaptations, called hybrid vigor [16]. Hybrid vigor may increase parasite virulence, transmission potential, resistance, pathology, host use and can lead to the emergence of new diseases [17, 18]. Moreover, hybridization can influence parasite acquisition of novel genotypes, potentially expanding their geographical and host range and leading to novel ecological adaptations detrimental to human and animal populations [17, 20].

Trematode worms of the genus *Schistosoma* are among the parasites known to undergo hybridization and/or introgression. Hybridization and/or introgression of two or more phylogenetically related *Schistosoma* species and/or strains occur when multiple distinct species or strain and their susceptible snail hosts cohabit an area. Cohabitation may be seen as a result of selective pressure imposed by climatic changes and human activities. Activities such as hydraulic projects, road construction and the introduction of new agriculture practices create new water bodies shared by humans and livestock, increasing opportunities for mixing of and subsequent exposure to different *Schistosoma* species [21]. In addition, increases in human and livestock migration facilitate the introduction of *Schistosoma* species and strains into new areas, resulting in novel host–parasite and parasite–parasite interactions [22].

Evidence of the potential occurrence of natural hybridization within and between human and animal *Schistosoma* species was first reported in the 1940s in Zimbabwe (then known as Southern Rhodesia). The evidence was based on the suspicious morphological appearance of *Schistosoma* eggs recovered from human urine with morphological features intermediate between those of *S. haematobium* and *S. mattheei* [23]. Several other studies reported similar morphological changes in other areas; in most cases, the observations were considered, or even dismissed, as misleading identifications [18]. **Figure 2** presents examples of typical eggs of two distinctive *Schistosoma* species and those with intermediate morphological features suspected to be of hybrid schistosomes.

**Figure 2.**

*Typical morphologies of* S. haematobium *egg (a),* S. guineensis *egg (b) and intemediate morphologies of suspected*  S. hameatobium-guineensis *hybrids eggs (c1.c2 and c3). Picture adapted and modified from Moné et al. [20].*

It was not until 1980, after the invention of biochemical marker technology, that the detection of previously suspected *Schistosoma* hybrids was confirmed to be a result of hybridization between *S. haematobium* and *S. mattheei*. The study was conducted in South Africa [24]. The technology was then used to reveal other hybridizations between different *Schistosoma* species in different parts of the world, especially in Africa [18].

The number of reported *Schistosoma* hybridization and introgression events has grown significantly due to the increased use of modern molecular technology in parasitological research. The use of molecular markers (such as internal transcribed spacer [ITS 1 + 2] and mitochondrial cytochrome c oxidase subunit 1 [cox 1]) and microsatellite markers (such as ribosomal DNA and mitochondrial DNA) have confirmed that *Schistosoma* hybridization occurs in nature, in which viable, fertile hybrid offspring can be produced through first- or successive-generation backcrosses [22, 25]. In addition, these molecular markers have shown that *Schistosoma* hybridization can be either unidirectional or bidirectional. For example, a study in Kenya using microsatellite markers revealed unidirectional gene transfer between two distinct *Schistosoma* species [25], while studies conducted in Senegal, using sequence data of nuclear ITS1 + 2 and mitochondria cox1 loci, reported bidirectional hybridization between several *Schistosoma* species [22, 26].

Several *Schistosoma* species hybrids have been reported based on findings of either molecular, biochemical or morphological (phenotypic) techniques, or combinations of two or all of these techniques. The hybrids have been detected in the snail, domestic and wildlife animals, and human hosts. Moreover, these heterospecific crosses are between human schistosome species (e.g., *S. guineensis* with *S. haematobium* [20]), animal schistosome species (e.g., *S. bovis* with *S. curassoni* [12]), and, perhaps most importantly and interestingly, epidemiologically and clinically, between human schistosome species and animal schistosome species (e.g., *S. haematobium* with *S. bovis* [12]).

There is geographic overlapping between different *Schistosoma* species in different parts of the world, such as Asia (*S. japonicum* and *Schistosoma mekongi* (*S. mekongi*) [27]) and Africa (two or more of the following species: *S. bovis*, *S. curassoni*, *S. guineensis*, *S. haematobium, S. intercalatum, Schistosoma mansoni*, *Schistosoma rodhaini* (*Sirthenea rodhaini*) and *S. mattheei* [12, 20, 21, 24–26]). However, to date, no evidence of naturally occurring *Schistosoma* hybrids has been detected in Asia, although

#### Schistosoma *Hybridizations and Risk of Emerging Zoonosis in Africa: Time to Think of a One… DOI: http://dx.doi.org/10.5772/intechopen.103680*

experimental crossing of the two overlapping species has been achieved [27]. Potential natural schistosome hybrids have been reported across much of Africa, predominantly in West Africa [18]. The evidence of natural hybridization events documented in Africa between human *Schistosoma* species is for that between *S. haematobium* and *S. mansoni*, and *S. haematobium* and *S. intercalatum* or *guineensis*. *S. haematobium* and *S. mansoni* are phylogenetically distant species. However, *S. haematobium-mansoni* hybrids may be suspected if ectopic *S. haematobium* and *S. mansoni* eggs are recovered from, respectively, human stool and urine samples [16]. Elimination of ectopic *S. haematobium* and *S. mansoni* eggs has been suggested to be due to interspecific interactions and heterospecific mating between *S. haematobium* and *S. mansoni*, resulting in males of *S. haematobium* carrying *S. mansoni* females to bladder veins, where the females lay hybrid *S. mansoni* eggs that are passed in the urine. Inversely, *S. mansoni* males carry *S. haematobium* females to mesenteric veins, a process that results in hybrid *S. haematobium* eggs in the feces [28]. In Africa, ectopic *S. haematobium* and/ or *S. mansoni* eggs have been widely reported to have been found in human stool and/ or urine samples in many countries, including Senegal, Egypt, Tunisia, the Democratic Republic of Congo, Tanzania (formally Tanganyika), Zimbabwe, Sudan, Ethiopia, Côte d'Ivoire and Cameroon [28–30]. Bidirectional *S. haematobium-mansoni* hybridization has been confirmed by molecular analysis of eggs and miracidia collected from people living or traveling in coendemic areas of Senegal and Côte d'Ivoire. However, there is no evidence on whether these people were infected by hybrid cercariae or if mating of male *S. haematobium* and female *S. mansoni* and/or male *S. mansoni* and female *S. haematobium* occurred in these people's bodies [29, 30].

Natural introgressive hybridization between *S. haematobium* and the Lower Guinea strain of *S. guineensis* (which had been previously identified as *S. intercalatum*) has been recorded in Cameroon and Benin [20, 31]. Hybridization between *S. haematobium* and *S. guineensis* has been associated with the replacement of *S. guineensis* by S*. haematobium* in a *S. guineensis* hyperendemic area of Cameroon. This hybridization has been linked to the superiority of male *S. haematobium* to male *S. guineensis* in mating competitiveness [31]*.* In addition, natural hybridization was reported between *S. haematobium* and *S. intercalatum* (Zaire strain) in the Democratic Republic of Congo (formerly Zaire) resulting in the decline in the transmission of the pure *S. intercalatum* [32].

The natural hybridization events documented between animal (livestock) *Schistosoma species* in Africa are those between *S. bovis* and *S. curassoni*. The *S. boviscurassoni* hybrids have been identified in cattle, sheep and goats in Senegal [12]. Despite the demonstration that neither *S. bovis* nor *S. curassoni,* as single pure species, can fully develop in humans or nonhuman primates in the field or under experimental laboratory conditions, there is evidence that a child in Niger was infected by the hybrid of the two species [21].

The most important and interesting schistosome hybridization is that between human and animal schistosome species (e.g., *S. haematobium* with *S. bovis* or *S. curassoni* [12, 26] or *S. mattheei* [24] and *S. mansoni* with *S. rodhaini* [25]). Even though it is unable to be maintained in humans, *S. bovis* is capable of mate-pairing with *S. haematobium* in humans to produce viable hybrids. *S. haematobium-bovis* hybrids are the most frequently and widely recovered schistosome hybrids across many African countries. The majority of *S. haematobium-bovis* hybrids have been found in human and snail hosts in West Africa: in Mali, Niger (introgressive hybridization), Senegal (bidirectional hybridization), Cameroon, Benin, Nigeria and Côte d'Ivoire [7, 16]. To date, few studies have reported the presence of a *S. haematobium-bovis* hybrid parasite in a nonhuman vertebrate host (a mouse species, *Mastomys huberti* and cattle) [7, 33]. The *S. haematobium-bovis* hybrid detected in this mouse was a female found paired with a pure male *S. mansoni* [33]. Other heterospecific crosses of human and animal schistosomes detected in Africa are those due to hybridization between *S. mansoni* and *S. rodhaini* [25] and *S. haematobium* and *S. curassoni* [12] or *S. mattheei* [24]. At **Figure 3** is a map showing the distribution of different types of schistosome hybridization events reported across Africa as summarized by Panzner and Boissier [16].
