Schistosoma Hybridizations and Risk of Emerging Zoonosis in Africa: Time to Think of a One Health Approach for Sustainable Schistosomiasis Control and Elimination

Abstract

Current control of human schistosomiasis in Africa is based on preventive chemotherapy, whereby populations are mass-treated with an anthelminthic medication, praziquantel. The World Health Organization has set a goal of eliminating schistosomiasis as a public health problem and, ultimately, eliminating transmission in all countries where schistosomiasis is endemic by 2030. However, recurrent hybridization between Schistosoma species is an emerging public health concern that has a major impact on the distribution of the disease and ultimately may derail elimination efforts. The One Health approach recognizes interconnections between the health of humans, animals and the environment, and encourages collaborative efforts toward the best outcomes. This chapter explains how the One Health approach can accelerate the control and elimination of schistosomiasis in Africa.

1. Introduction

The World Health Organization (WHO) considers schistosomiasis the most important water-based disease in the world. The disease is caused by infection with trematodes of the genus Schistosoma species. These parasitic worms have a complicated life cycle (Figure 1). When an egg is passed in the feces or urine, it contains a fully developed miracidium. In freshwater, eggs hatch to miracidia, which swims in the water to find a suitable snail host. Upon finding a host, they penetrate its skin. The miracidia then transform into primary-stage sporocysts and migrate to the liver of the snail, where they start asexual reproduction to produce daughter sporocysts. The daughter sporocysts develop into cercariae, which are shed into the water. Then the cercariae swim until they find a susceptible vertebrate host, and penetrate its skin. Once the fluke is inside, it drops its tail, and becomes a schistomulae; upon reaching a blood vessel, the schistomulae enters and starts its journey to the lungs, becoming longer and slenderer and losing its middle spines but retaining its end spines. The parasite reaches the lungs six to eight days after infection and begins to feed. The fluke leaves the lungs through pulmonary veins to the liver. By week four, the adult fluke emerges, and it starts pairing about week five. The paired flukes migrate from the portal vein to the respective blood vessels and start to lay eggs. Using their spines, the eggs penetrate through blood vessels to the intestine or urinary bladder [1, 2].

Figure 1.

The life cycle of the most important human Schistosoma in Africa.

The damage caused by schistosomiasis results from the movement of eggs through host tissue, which triggers an inflammatory response and acute, chronic disease. Schistosomes (as members of the genus Schistosoma (S.) are commonly known) have an average lifespan of 3 to 10 years, but can live up to 40 years in their vertebrate hosts [3].

Due to increased human population growth, anthropogenic environmental changes, and global movements of humans and animals, there are increasing reports of hybridization events among Schistosoma species across Africa. Since these events involve species that infect both humans and animals (domestic and wild), researchers have raised concerns about the emergence of potential schistosomiasis zoonosis [4]. This chapter explains how the anthropocentric or disjointed sectoral approach to controlling human schistosomiasis requires a paradigm shift that entails a multisectoral (i.e., One Health) approach to preventing zoonotic transmission of schistosomiasis in Africa.

2. Burden of schistosomiasis in Africa

2.1 Human schistosomiasis in Africa

The two major Schistosoma species infecting humans in Africa are Schistosoma haematobium (S. haematobium), which causes urogenital schistosomiasis, and Schistosoma mansoni (S. mansoni), the causative agent of intestinal schistosomiasis. Schistosoma guineensis (S. guineensis) also causes intestinal schistosomiasis but is less prevalent. In Africa, S. mansoni is found in all countries while S. haematobium is found in all but four countries (Eritrea, Burundi, Mauritius, and Rwanda). The less common S. guineensis (also called Schistosoma intercalatum (S. intercalatum)) has been identified in the rain forest areas of western and central Africa. Schistosomiasis transmission has been interrupted in Equatorial Guinea, Morocco, Tunisia, Algeria, Djibouti and Lesotho [2].

The number of deaths attributable to schistosomiasis is difficult to estimate because of hidden pathologies such as liver and kidney failure, bladder cancer and ectopic pregnancies; in addition, the death rate may have decreased over the past decade due to the implementation of large-scale preventive chemotherapy campaigns [3].

The most prevalent species in Africa, S. haematobium causes approximately 112 million cases per year. It is estimated that 71 million of these infected individuals experience hematuria (blood in the urine), half of whom have dysuria, and about 18 million suffer from urinary bladder pathology. The current best estimate is that kidney failure due to S. haematobium infection is responsible for about 150,000 deaths annually in Africa. More than 54 million individuals are estimated to become infected with S. mansoni, with around 4 million people experiencing diarrhea and 8.5 million hepatomegaly; hematemesis-associated deaths are estimated to total about 130,000 annually [2].

Chronic disability is far more common than death. Intestinal schistosomiasis can result in abdominal pain, diarrhea, and blood in the stool. Liver enlargement is common in advanced cases, and is frequently associated with an accumulation of fluid in the peritoneal cavity and hypertension of the abdominal blood vessels. In such cases, there may also be enlargement of the spleen. Hematuria is the classic sign of urogenital schistosomiasis. Fibrosis of the bladder and ureter, bladder cancer, and kidney damage are sometimes diagnosed in advanced cases. In women, urogenital schistosomiasis may present with genital lesions, vaginal bleeding, pain during sexual intercourse, and nodules in the vulva. In men, urogenital schistosomiasis can induce pathology of the seminal vesicles, prostate, and other organs. This disease can also have other long-term irreversible consequences, including infertility. In children, schistosomiasis can cause anemia, stunting and a reduced ability to learn (although the effects are usually reversible with treatment). Praziquantel is the drug of choice for the treatment of schistosomiasis. The drug is recommended for the treatment of all forms of schistosomiasis. Despite that reinfection may occur after treatment, the risk of developing the severe disease is reduced after initiation of treatment [3].

The prevalence of human schistosomiasis in Africa is estimated to be 192 million, which is 93% of the total global prevalence of the disease. About 29 million people are infected by this disease in Nigeria, 19 million in Tanzania, and 15 million each in the Democratic Republic of Congo and Ghana, while Mozambique, with 13 million cases, completes the list of five countries with the greatest prevalence in Africa [5]. The heavy burden of schistosomiasis in Africa is attributed to limited access to clean water, poor sanitation and inadequate health services [2].

2.2 Animal schistosomiasis in Africa

In Africa, animal schistosomiasis is a common parasitic infection among cattle, although it rarely infects other domestic animals such as goats and sheep; nor does it appear to trouble wild rodents and primates [6]. It is estimated that 165 million domestic cattle are affected by schistosomiasis worldwide. The disease is of veterinary and economic significance [7]. In China, 1.5 million cattle suffer from schistosomiasis, and more than 5 million are at risk of infection [8]. Schistosomiasis among livestock does not show clinical effects in most cases. However, if the infection persists for a long time, it can cause enteritis and anemia, as well as emaciation leading to significantly reduced productivity and growth, and even death [9]. Schistosomiasis in animals is caused by several Schistosoma species. For example, Schistosoma japonicum (S. japonicum) (which infects human beings) has been reported to infect more than forty mammal species, including wildlife such as water buffaloes, camels and rats, and domestic animals such as cattle, sheep, pigs, dogs, donkeys, cats and goats [8, 10]. S. mansoni, which causes human intestinal schistosomiasis, has been reported to infect at least nine other members of the Primate order, such as monkeys and apes [10].

The three species with significant animal health impact in Africa are Schistosoma bovis (S. bovis), Schistosoma curassoni (S. curassoni) and Schistosoma mattheei (S. mattheei) [2, 7]. The latter two species are known solely from domestic animals [11]. S. mattheei is found in southeastern Africa, from South Africa northward to Tanzania and Zambia. S. bovis is most common in northern Zambia and northern Senegal [12, 13]. S. curassoni has been found in livestock (cattle, sheep and goats) in West African countries [2].

The distribution of Schistosoma species is governed by the intermediate host habitat—freshwater bodies such as lakes, dams and rivers. A recent study showed that S. bovis can cause high levels of infection among cattle in Côte d’Ivoire, where prevalence rates of up to 53.3% have been recorded [13]. Factors such as age and breed are significantly associated with different rates of schistosome infection. For example, cattle aged 4 years and above have higher rates of S. bovis infection than younger ones. “Zebu” and “Taurin” breeds are less likely to have S. bovis infections than “Taurin x Zebu” [13]. Livestock management systems in Tanzania have been shown to influence trematode distribution. The highest rates of trematode infection in cattle are found in traditional management systems in which animals are grazed and watered on communal land during the day and housed around the households in open bomas (livestock enclosures) at night. Rates of trematode infection are moderate in large-scale dairy systems and lowest in small-scale dairy systems [14].

Like a human, animals are treated for schistosomiasis through the administration of praziquantel. Effective treatment requires two rounds 3 to 5 weeks apart. However, unlike human schistosomiasis, which is frequently controlled by preventive praziquantel chemotherapy in areas where the infection is endemic [15], schistosomiasis in domestic animals is rarely treated in Africa, probably because little attention has been given by scientists to its zoonotic potential.

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, 25, 26]). However, to date, no evidence of naturally occurring Schistosoma hybrids has been detected in Asia, although 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, 29, 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. bovis-curassoni 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].

Figure 3.

Distribution of Schistosoma hybrids across Africa. Notes: S.h. = S. haematobium; S.m. = Schistosoma mansoni; S.g. = S. guineensis; S.i. = S. intercalatum; S.b. = S. bovis; S.c. = S. curassoni; S.r. = Sirthenea rodhaini; S.ma. = S. mattheei. Figure adapted from Panzner and Boissier [16].

3.2 Current status of Schistosoma zoonosis in Africa

Zoonotic diseases (also known as zoonoses) are those diseases caused by viruses, bacteria, fungi or parasites that are naturally transmitted between humans and other vertebrate animals [18, 34]. Currently, six main species of Schistosoma infect humans:S. mansoni, S. haematobium, S. intercalatum, S. guineensis, S. mekongi and S. japonicum.The latter two species are acknowledged zoonoses, as they are capable of naturally infecting multiple species of mammalian hosts (human, livestock and wildlife) [18]. S. japonicum and S. mekongi are the major Schistosoma species in Asia, geographically distributed across the central and middle areas of the continent. Unlike other animal schistosomes, S. japonicum and S. mekongi are unique among zoonotic helminths in that they can be transmitted between humans and other animals and maintained by all host species [35]. In Africa, only human Schistosoma species are considered to be of public health significance [9]. In addition, wild animals such as rodents are known to be the main reservoir hosts of S. mansoni in the Caribbean and South America. Even though S. mansoni is one of the two Schistosoma species of public health importance in Africa, its magnitude in animals and the contribution of animals to the perpetuation of S. mansoni transmission in the African continent is not well established [36], because very few studies have been conducted on livestock or wildlife schistosomiasis [9].

Recent studies have reported evidence of some unique schistosomiasis transmission events in Africa. It had been believed that S. haematobium as a single pure species was solely capable of infecting humans. However, a study conducted in Benin showed that pure S. haematobium may infect livestock (i.e., cattle) as well [7]. Moreover, the female S. haematobium-bovis hybrid previously detected in humans and snail hosts, though never in animal (livestock and wildlife) hosts, has been found in a pair with pure S. mansoni in a mouse [33]. In addition, S. bovis, S. curassoni and S. mattheei are known to infect a wide variety of animals including cattle, sheep and goats. Though S. mattheei has been detected at high rates of prevalence in humans in one area in South Africa [37], the other two species have never been detected in human as a single pure species. Detection of hybrids of S. haematobium with either one of these species was thought by scientists to be evidence of possible human infection with the two animal (livestock) Schistosoma species. Human infections with S. bovis and S. curassoni were suggested to occur through zoonotic spillover; hence, it was believed that the infection could not persist, as these parasites cannot be maintained in the human body [38]. However, some researchers suggest that S. haematobium-bovis hybrids could be a result of an ancient introgression event between S. haematobium and S. bovis that resulted in the introgression of some S. bovis genomic tracts into several S. haematobium lineages [39].

3.3 Risk of emerging Schistosoma zoonosis in Africa

The magnitude of Schistosoma zoonotic transmission in which both livestock and wildlife are active participants is yet to be determined in endemic countries across Africa [36]. It has been explained that natural and anthropogenic changes (Figure 4) have created opportunities for mixing of and subsequent exposure to both human and animal (livestock and wildlife) schistosomes. The coexistence of multiple Schistosoma species and their hosts—both vertebrates (human and animals) and snails—has increased the potential for the emergence and establishment of novel zoonotic Schistosoma hybrids [21]. Sporadic studies have revealed several hybrids with potential zoonotic effects that naturally infect humans and animals (livestock and wildlife) across several African countries. Examples of natural Schistosoma hybrids with potential zoonotic effects identified in Africa include S. haematobium-bovis, S. haematobium-curassoni, S. bovis-curassoni, S. haematobium-mattheei and S. mansoni-rodhaini [16].

Figure 4.

Schematic presentation of the causes and consequences of schistosome hybridization.

The ongoing emergence (or discovery) of potential zoonotic Schistosoma hybrids has caught the attention of many researchers and scientists, due to possible implications for schistosomiasis transmission and control. Zoonotic Schistosoma hybrids are thought to have a wide definitive host range and an increased range of intermediate snail hosts relative to their pure “parent” single species, which may also enable a wider geographic range for hybrid schistosome infections. In addition, zoonotic Schistosoma hybrids are capable of establishing themselves in areas where their parental single/pure species are absent (e.g., S. haematobium-bovis hybrids on the French island of Corsica). Moreover, experimental studies (on S. haematobium-bovis and S. haematobium-mattheei hybrids) have revealed that these hybrids have greater virulence than the two parental species, as well as increased adult worm fecundity and increased cercarial shedding rates in snails [9, 39]. Field research (on S. haematobium-bovis hybrids) has revealed some indicators of altered patient morbidity patterns and reduced treatment response with praziquantel [4]. Also, researchers have expressed concern that hybridization could accelerate the evolution of drug resistance by allowing drug-resistance genes to be introgressed into new populations. On the other hand, hybridization may lead to the development of refugia for drug-susceptible genotypes and thus potentially help maintain drug susceptibility [9]. Therefore, it is important to understand the transmission dynamics of potential zoonotic Schistosoma hybrids [21].

4. Schistosomiasis control and elimination in Africa

4.1 Current strategies for schistosomiasis control and elimination

Recent years have witnessed an increased interest in the control and, finally, elimination of Neglected Tropical Diseases (NTDs), and today the control of schistosomiasis has again become a priority on the agenda of many governments, donors, pharmaceutical companies and international agencies [40]. WHO has developed several road maps for NTDs, and many African countries have made significant progress by rolling out national action plans and programs targeting schistosomiasis control and elimination [41, 42]. Preventive chemotherapy is the main strategy for schistosomiasis control in Africa, supplemented with water, sanitation and hygiene (WASH) interventions in some regions [43].

4.1.1 Preventive chemotherapy

4.1.1.1 An overview of preventive chemotherapy: Praziquantel

Current control of human schistosomiasis in Africa is based on preventive chemotherapy, whereby populations are mass-treated with anthelminthic praziquantel administered in the standard single oral dose of 40 mg/kg body weight. Treatment with praziquantel is currently the strategy of choice and is endorsed by WHO [41, 43]. The ambitious goals of control and eventual elimination are underpinned by targets that require countries to reach at least 75% treatment coverage of school-age children and at-risk adults, with mass drug administration schedules and the designation of target groups depending on schistosomiasis endemicity [43]. This coverage goal is endorsed for schistosomiasis and soil-transmitted helminths in the 2012–2020 WHO road map for NTDs, in which preventive chemotherapy was identified as a key strategy for tackling NTDs [42, 44].

Over the past decade, significant progress has been made on large-scale treatments through integrated control of schistosomiasis and other NTDs. It is estimated that at least 236.6 million people required preventive treatment for schistosomiasis in 2019, of which more than 105.4 million (about 45%) were reported to have been treated [45]. In Africa, 17 countries out of the 40 that require preventive chemotherapy had not achieved the 75% treatment coverage target for school-age children during 2018, when a total of 69.1 million school-age children were treated, representing overall coverage of 62.9% [46]. In general, annual mass drug administration of preventive chemotherapy has had a significant effect on infection prevalence, intensity and associated morbidity among school-age children [47, 48, 49]. However, disease reoccurrence and persistent transmission suggest a need for more intense control measures to achieve the goal of schistosomiasis elimination.

Since the adoption of the World Health Assembly Resolution WHA 65.21 and NTDs road map 2021–2030, schistosomiasis control programs have shifted from morbidity control to disease elimination [41]. However, gaps continue to be observed in the implementation of control programs in Africa. Mass drug administration programs commonly overlook large numbers of preschool-age children, adolescents and adults, thus increasing health inequality and the risk of reinfections of previously treated groups [50]. Schistosomiasis cannot be eliminated in communities where mass drug administration is not ongoing. In the past, a key bottleneck to the implementation of preventive chemotherapy for control of schistosomiasis in Africa was the limited access to praziquantel [51]. Though there is now growing access to this medication for schistosomiasis control in Africa, it is not at the level that is projected to be necessary to reach all people who are at risk or who require treatment [52]. Analysis of data reported on treatment coverage for schistosomiasis shows that utilization of available praziquantel by NTD programs is not yet optimal in many countries [46, 52].

4.1.1.2 Strengths and weaknesses of preventive chemotherapy

Praziquantel is the drug of choice for the treatment of schistosomiasis, as it is considered cost-effective, relatively safe, inexpensive and efficacious; also, donor organizations are willing to provide the drug [53]. Despite increased efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-age children, as well as at-risk adults such as fishery workers, have not been included in many mass drug administration programs despite the evidence of schistosomiasis infection among these populations [54, 55]. This increases health inequality and the accumulation of potentially irreversible morbidities due to prolonged infection [56].

A major challenge now lies in the unavailability of a child-size formulation of praziquantel [56, 57]. The currently available formulation presents several limitations: (a) It is a large tablet, which is difficult for young children and infants to swallow and thus must be broken and crushed to allow for safe uptake. (b) It has a very bitter taste, and so is often mixed with a sweetener to make it palatable to young children. (c) The current formulation of 600 mg does not allow for flexible-dose adjustments for this age group.

4.1.2 Water, sanitation and hygiene (WASH) interventions

Clean water provision, sanitation and hygiene are critical components of the global NTD roadmap [41]. For schistosomiasis, improved sanitation across the entire community to prevent contaminated feces and urine from reaching surface water can reduce or eliminate transmission, by stopping worm eggs in feces and urine from entering water sources, which are the snail habitat [58]. The aim of United Nations Sustainable Development Goal 6 (SDG 6) is to ensure the availability and sustainable management of water and sanitation for all by 2030. WASH interventions are among the most important measures used to control water-related diseases in Africa. However, sanitation, hygienic practices, and access to clean water are inadequate in large parts of Africa where schistosomiasis is endemic [59]. According to the United Nations Children’s Fund, in 2020 more than two-thirds of the African population did not have basic sanitation services and about 18% practiced open defecation. Ethiopia, Uganda, Kenya and Tanzania had the largest numbers of people in the continent without access to basic sanitation services, while Eritrea, South Sudan and Ethiopia had the largest proportions and numbers of people practicing open defecation [60]. Furthermore, in Eastern and Southern Africa, about 50 million (over 27%) of school-age children had no access to sanitation services, while 117 million (62%) had no access to hand-washing facilities at school [60]. It has also been reported that nearly half of Africans do not have access to clean water and two-thirds lack access to sewage infrastructure [61]. A systematic review and meta-analysis of the relationship between safe water, adequate sanitation, good hygiene and schistosomiasis found that people with access to safe water were significantly less likely to acquire a Schistosoma infection than those who, while they had access to adequate sanitation, did not have safe water access [62].

4.2 A different approach to schistosomiasis control: one health

4.2.1 The concept of one health and the one health disease control approach

The Centers for Disease Control and Prevention define One Health as a collaborative, multispectral transdisciplinary approach applied at the local, regional, national and global levels, with the goal of achieving optimal health outcomes that recognize the interconnection among people, animals, plants and their shared environment [63]. The One Health approach is a collaborative effort between the human health, animal health and environmental sectors to attain optimal health for people, animals and the environment. Over 60% of emerging, re-emerging and endemic human diseases have their origins in animals [64]. Humans are at increased risk of contracting diseases of animal origin because of a wide range of interconnected variables, including mass urbanization, large-scale livestock production and increased travel [64]. Therefore, efforts to unite the sectors working to protect humans and animals and the ecosystem are of paramount significance.

4.2.2 Schistosomiasis control and elimination under the one health approach

The recurrent hybridization between Schistosoma species in nature increases the distribution of schistosomiasis and ultimately challenges current elimination efforts. Animal reservoirs can maintain transmission with zoonotic parasites even while the disease they cause in humans seems to be effectively controlled [65]. To be successful, schistosomiasis elimination programs cannot ignore the animal reservoirs of infection in Africa; this requirement demonstrates the need to consider control measures within a One Health framework [40]. The rapid occurrence of reinfection with schistosomiasis further highlights the need for a One Health approach. An anthropocentric or disjointed sectoral approach to controlling human schistosomiasis in Africa, such as the NTD intervention strategies applied alone, may be insufficient to eliminate schistosomiasis. For example, in the Mekong subregion of Southeast Asia, relying solely on deworming to prevent schistosomiasis did not prevent reinfection, but required parallel activities within the One Health framework [66]. Measures should focus on health aspects of the environment, animals and humans. They should also involve state-of-the-art approaches to schistosomiasis diagnosis and surveillance that encompass the environment (water and snails), animals (both domestic fauna and wildlife) and humans to enable an understanding of transmission ecology and the evolution of schistosomiasis across all hosts (Figure 5) [6].

Figure 5.

Schematic presentation of the proposed one health framework for controlling zoonotic schistosomiasis in Africa.

4.2.2.1 Environmental health measures

Schistosoma species depend entirely on the presence of freshwater environments harboring susceptible snails to complete their life cycle. Control measures should therefore focus on preventing excreta (fecal or urine) contamination of freshwater sources. The following control measures are ideal for preventing excreta contamination of freshwater sources:

1. Provision of improved sanitation as it has been explained above. Provision and proper use of improved sanitation facilities will prevent excreta containing Schistosoma eggs from entering freshwater sources containing snail hosts and thus will prevent subsequent snail infections [58]

2. Preventing direct contact with infested freshwater by human and animals. Prevention of direct human or animal contact will reduce the chances of excreta contamination and prevent transmission. It may be accomplished through ring-fencing of the contaminated water bodies [67].

3. Reducing snail populations. Reinforcing snail control is a part of the WHO strategic approach to eliminating schistosomiasis [68].

Snail control can be attempted through snail habitat modifications such as altering flow rate and water levels so as to disturb snail habitat and disrupt snails’ food sources. Such modifications include constructing V-shaped banks in irrigation channels, removing vegetation and draining water sources that serve no special purpose for humans, wildlife or livestock [67]. Biological control of snails using nonsusceptible competitor snails has been reported to be successful in the Caribbean region [69], although it is important not to run the risk of importing potentially invasive snails. Snail control may also be accomplished through molluscicide application; however, since molluscicides have not been notably effective in past efforts, and may cause damage to other organisms [70], the application should be targeted, and carefully monitored rather than widespread [67].

4.2.2.2 Human health measures

As part of ongoing mass drug administration campaigns, other human interventions should be considered. Therefore, WASH providers must prioritize the reduction of inequality to align with the Sustainable Development Goals agenda, as developed in the recent WASH strategy to accelerate and sustain progress on NTDs [71]. Water scarcity can result in the sharing of water sources between people and animals, which can increase the risk of zoonotic diseases. Improving access to clean water by supplying tap water or wells at homes [65], accompanied by behavioral changes such as avoiding swimming, wading, washing or bathing in contaminated ponds, rivers and lakes, would help to prevent human contact with Schistosoma-infested waters. It is safest to consider all freshwater bodies in endemic areas as potential transmission sites [67]. Furthermore, while safe water is unlikely to contain cercariae, its provision often will not prevent all human contact with infested water. In some settings, such as fishing communities, it is important to account for considerable occupational water contact that the availability of safe water supplies would not prevent [72]. Hence, periodic examination and treatment of workers and people at constant risk of infection may be the most feasible approach to controlling schistosomiasis [67]. Interventions to reduce the contamination of water bodies with Schistosoma eggs could reduce the potential for disease transmission in both humans and animals [65]. Stakeholders should scale up the provision of improved sanitation services through the construction of latrines (including aboard boats). Also, public toilets along river basins in schistosomiasis-endemic areas must be provided to stop human excrement from entering freshwater sources [67]. In addition, interventions such as the construction of big systems like sewage treatment ponds and constructed wetlands, or home-based smaller systems, would help prevent contamination of water sources. Basically, if the urine and feces of people and animals could be kept from entering water bodies, there would be no more schistosomiasis transmission. This can be seen in two highly infested bodies of water, Lake Victoria and Lake Malawi, where, thanks to local initiatives, there are actually ‘safe beaches’ with no schistosomiasis [1].

4.2.2.3 Animal health measures

The most effective way of controlling zoonotic schistosomiasis in livestock is also through keeping susceptible domestic animals from coming into contact with infested water. This can be achieved by preventing livestock grazing in infested wetlands, fencing infested water sources and supplying drinking water to the animals in troughs [73]. Apart from reducing the risk of infections to the animals, these measures will also prevent contaminated excreta from livestock from entering freshwater sources. Susceptible animals used in wetland areas for agriculture purposes should be replaced with nonsusceptible species or with farm machinery if the purpose of animals’ use is mechanical management. Periodic examination and treatment of susceptible livestock should be conducted. However, reinfection may occur quickly if the source of contamination is left uncontrolled. Regarding wild animals, high-density populations of susceptible wildlife increase the potential for disease transmission. Interaction between livestock and wildlife should be prevented wherever possible, and supplementary feeding of wild animals close to water sources should be avoided. Lastly, scientists and funders should invest in finding Schistosoma vaccines for animals and humans [67].

4.2.3 Implementation of the one health approach in Africa under current socioeconomic and political conditions

Strong social, economic and political commitments are key elements in successful schistosomiasis control, which requires persistent efforts and a systematic step-by-step approach with increasingly ambitious targets to reach elimination [35]. The disease context is complex, with the interplay of social, economic, political and cultural factors [20, 27] that may affect the attainment of the goals of the NTD 2021–2030 road map [28]. Concurrent treatment of zoonotic Schistosoma reservoirs, at least in terms of livestock hosts in Africa, is likely to be imperative for successful disruption of the transmission of human disease [15]. However, a key problem for the treatment of many zoonotic infections in livestock reservoirs is that, while the costs of treatment fall largely on the agricultural sector, the benefits of reduced transmission to humans are felt largely by the public health and medical sectors [15]. Therefore, motivating the sustainable involvement of livestock authorities and producers, who may have other disease priorities, could be difficult.

Given the potential impact of schistosomiasis on animal health and productivity, a One Health economic evaluation of extending treatment to animal hosts in Africa appears warranted, and requires data to be gathered on the costs and benefits to both the animal and human health sectors. To assess the economics of One Health interventions, the impacts on both sectors need to be integrated so that decision-makers in both sectors can assess and interpret outcomes in a way that is meaningful both to their sector and to society [74]. In light of these challenges, there is a need to revisit the current approach to schistosomiasis control among African countries irrespective of the level of endemicity.

5. Conclusion

Since the novel zoonotic Schistosoma hybrid species potentially may play a role in maintaining and exacerbating schistosome transmission in humans and animals, no single strategy will reduce transmission everywhere. What worked well in one place or time can be ineffective or inappropriate in another. The recent approach used to control schistosomiasis in Africa is designed to focus on treatment coverage, the use of vertical programs, and dependence on external supports and donors. The consequences of the approach are the predominance of preventive chemotherapy over other prevention and control strategies and the lack of cross-sector collaboration. Deploying multiple strategies across multiple sectors may help to balance the control portfolio. Therefore, control strategies may have to be adjusted within a jointed One Health framework. This could be facilitated by a successful understanding of the transmission ecology and evolution of zoonotic schistosomiasis across all hosts, both animal and human, as well as the freshwater environment.

Conflicts of interest

The authors declare that there are no conflicts of interest.