Low doses and short duration of prednisolone administration in guinea pigs experimentally infected with Schisosoma haematobium: Histopathology of liver and lungs

Schisotosomiasis is one of the most important neglected tropical diseases (NTD), endemic in 74 countries, mainly in the tropics and subtropics (Frahm et al., 2019; Farah et al., 2001). Of the three major human schistosome species, Schisosoma haematobium, causing urogenital schistosomiasis is the most prevalent species in sub-Saharan Africa, where it is responsible for substantial amount of schistosome-associated pathology (Rollinson, 2009; Botelho et al., 2010). Despite the burden of urogenital schistosomiasis, there remains scarcity of knowledge about the basic mechanism underlying the pathophysiology of this disease. This is probably because studying S. haematobium infection in the laboratory is complicated by absence of small laboratory animal model in which pathology resembles human infection with this parasite (Lewis et al., 2008; Rollinson, 2009). Historically, S. haematobium cercariae-infected hamsters and nonhuman primates are primarily the in vivo models for urogenital schistosomiasis. Although schistosome cercariae mature to adults and lay eggs in these models, use of these animals as models of humans has its limitations: 1. In Hamsters, the parasite exhibits low rates of pelvic organ infection. 2. High cost of conducting research, substantial ethical justification, and lack of species-specific tools in nonhuman primate studies (Rinaldi et al., 2015). Attempts have also been made using laboratory mice by transdermal infection with S. haematobium cercariae. The challenge of this method is the production of light infections in hepatoenteric systems and little or no oviposition in the pelvic organ (Rheinberg et al., 1998). Techniques have also been developed to administer schistosome eggs to mouse bladder wall directly. This direct injection of S. haematobium eggs into the mouse bladder, recapitulates key aspects of bladder disease in this infection. However, this technique has its own limitations. It does not permit studies of the interaction between the host, and cercariae, schistosomules, and adult worms. Other limitations of this model are that egg excretion and successful transmission may be difficult to examine; and the short life span of the mouse may make it difficult to study human carcinogenesis (Rinaldi et al., 2015).

Guinea pigs (Cavia porcellus) are proven valuable animal model to study human diseases because of the similarity of immunologic components compared to humans (Hensel and Arenas-Gamboa, 2018). In Schistosoma mansoni infection, the guinea pig was shown to be susceptible but much less so than the albino mice and hamsters, with no egg passage in faeces and very low worm return after perfusion (Martins, 1958). Reappraising the use of guinea pigs in experimental Schistosoma mansoni; Pearce and McLaren (1983) classified the susceptibility of guinea pigs to be more closely related to that of albino mice. Reasons given were that, worms of certain age in this model (guinea pig) had features identical to those exhibited by similar age mouse worms. Further, the pathology associated with cercarial invasion or egg deposition in the guinea pigs was not different to that described for other laboratory animals infected with S. mansoni. In experimental S. haematobium infection, only Meleney et al. (1953) were able to infect two of the 14 guinea pigs exposed.

Corticosteroids have been used to establish helminth parasites in hosts with little or no susceptibility. Action of corticosteroids in inducing susceptibility is attributed to its ability to reverse innate resistance (Parker, 1961; Miller, 1966; Harley and Gallicchio, 1970). Prednisolone, a glucocorticoid corticosteroid has been shown to have no cytotoxic or genotoxic effects on mitotic index and sperm head abnormality assays (Shafi, 2016). Adverse effects of prednisolone are seen when there is drug overdose and prolonged use (Fookes, 2022). In our previous study, prednisolone was administered for five consecutive days to induce susceptibility of guinea pigs to S. haematobium infection. Histological reactions to presence of worms were seen but the characteristic reactions to schistosome egg presence (granuloma) were not observed (Okeke et al., 2012). Corticosteroids suppress granuloma formation, maturation and size (Pyrrho et al., 2002), because their anti-inflammatory or therapeutic effects persist longer than their physical presence and metabolic effect (McAuley, 2013). Consequently, in the present study, the dose and duration of administration of prednisolone was reduced in order to investigate if prednisolone at reduced dose and duration is able to evoke granulomatous lesions in guinea pigs experimentally infected with S. haematobium cercariae.

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