Parasitological and histological aspects of Holochilus sciureus naturally infected by Schistosoma mansoni / Aspectos parasitológicos e histológicos de Holochilus sciureus naturalmente infectados por Schistosoma mansoni

Abstract Schistosomiasis is a neglected disease that affects millions of people around the world, being common in the state of Maranhão. A total of 225 rodents of the Holochilus sciureus species from the Western Lowland Maranhão were studied, of which 144 animals (64%) exhibited Schistosoma eggs in their feces samples. Macroscopic lesions characterized as well-defined whitish areas on the liver and spleen surfaces were observed. Histopathological examination revealed multifocal granulomas in the esophagus, liver, spleen, pancreas and duodenum, with structures compatible with Schistosoma mansoni eggs, as well as severe hepatic micro-vacuolar degeneration, multifocal and coalescent, with proliferation of random bile ducts and associated epithelial hyperplasia to areas of fibrosis. Adult forms of the parasite were observed in the blood vessels of the portal space. The lungs exhibited moderate and diffuse interstitial pneumonia with intralesional S. mansoni eggs. In the kidneys, hyaline cylinders were observed in the pelvis and diffuse hemorrhage. In conclusion, H. sciureus displays a pathological picture similar to human being. This rodent plays a role as sentinel in Baixada Maranhense.

Resumo A esquistossomose é uma doença negligenciada que afeta milhões de pessoas em todo o mundo, sendo comum no estado do Maranhão. Um total de 225 roedores da espécie Holochilus sciureus da Planície Ocidental do Maranhão foram estudados, dos quais 144 animais (64%) apresentaram ovos de Schistosoma em suas fezes. Lesões macroscópicas caracterizadas como áreas esbranquiçadas bem definidas nas superfícies do fígado e baço foram observadas. O exame histopatológico revelou granulomas multifocais no esôfago, fígado, baço, pâncreas e duodeno, com estruturas compatíveis com ovos de Schistosoma mansoni, degeneração micro-vacuolar hepática grave, multifocal e coalescente, com proliferação de ductos biliares aleatórios e hiperplasia epitelial associada a áreas de fibrose. Formas adultas do parasito foram observadas nos vasos sanguíneos do espaço portal. Os pulmões exibiram pneumonia intersticial moderada e difusa com ovos de S. mansoni intralesionais. Nos rins, foram observados cilindros hialinos na pelve e hemorragia difusa. Em conclusão, H. sciureus apresenta um quadro patológico semelhante ao ser humano. Este roedor desempenha um papel de sentinela na Baixada Maranhense.

Evaluation of the efficacy of pediatric suspension of praziquantel against schistosoma mansoni in experimental animals

Background: Schistosomiasis is one of the neglected tropical diseases with recent evidences about the high prevalence among preschool-age children. The pediatric formulation of Praziquantel [PZQ] has to be assessed for the efficacy as it gave controversial results in several countries

Objective[s]: The current study aimed at evaluating the efficacy of the pediatric suspension of PZQ against Schistosoma mansoni Egyptian strain in the experimental animals

Methods: 150 Swiss albino mice infected with Schistosoma mansoni were divided into three groups, the first group was treated with 600 mg/kg body weight of PZQ pediatric suspension, the second group was treated with 600 mg/kg PZQ tablets and the third one received no treatment as a control. The efficacy of the pediatric formulation was experimentally evaluated in comparison with the tablet formulation as a benchmark on the basis of the following specific parasitological parameters [worm burden, tissue egg load, and oogram pattern i.e. percentage of dead, live or immature eggs shown in the stool sample]

Results: The comparison between the mean egg count per gram stool in the two groups pediatric suspension of PZQ [Epiquantel] and adult tablets of PZQ [Distocide], and the control group by applying one way ANOVA revealed a statistically significant difference [p<0.05] between the mean egg count in both treated groups [Epiquantel and Distocide] and their control group. The reduction of the total worm burden caused by Epiquantel[registered] was 96.9%, while that of Distocide[registered] was 86.7%, they were found to be statistically significant[p<0.05] in comparison with the control group. Epiquantel[registered] reduced the male worms by 100% and the females were reduced by 94.1%. Distocide showed a similar effect, it reduced the worms by 88.4% and 85.1% for males and females respectively. The administration of a single oral dose of both Epiquantel[registered] and Distocide[registered] resulted in a statistically significant reduction [p<0.05] in the mean egg count per gram tissue either the liver or the wall of small intestine when compared to their infected untreated control group. Complete absence of immature egg stages, high reduction in the mature eggs, and the increase in the dead eggs were observed in both Epiquantel[registered] and Distocide[registered] groups when compared to the control group

Conclusion: The results prescribed that the pediatric suspension formula of PZQ is as efficient as the tablet formula against Schistosoma mansoni [Egyptian CD strain] in the mouse model. It could be recommended for pediatric treatment

Biochemical and histological changes in liver of Nectomys squamipes naturally infected by Schistosoma mansoni / Alterações na bioquímica e histologia do fígado de Nectomys squamipes naturalmente infectado por Schistosoma mansoni

The South American water rat Nectomys squamipes is a wild mammal reservoir of Schistosoma mansoni in Brazil. In the present study, wild rodents were collected in the field and categorized into two groups: infected and uninfected by S. mansoni. Blood was collected to analyze changes in the serum glucose level (mg/dL) and liver fragments were used to determine the hepatic glycogen content (mg of glucose/g tissue). The histological examination showed inflammatory granulomatous lesions in different phases of development in the liver of rodents naturally infected with S. mansoni, in some cases with total or partial occlusion of the vascular lumen. Early lesions were characterized by the presence of inflammatory infiltrate around morphologically intact recently deposited eggs. Despite the significance of these histological lesions, the biochemical changes differed in extent. N. squamipes naturally infected by S. mansoni showed no variation in hepatic glycogen reserves. These findings were accompanied by a significant increase in plasma glucose contents, probably as a consequence of amino acids deamination, which are degraded, resulting in the formation of intermediates used as precursors for the glucose formation, without compromising the reserves of liver glycogen. In the wild, naturally infected N. squamipes can maintain S. mansoni infections without undergoing alterations in its carbohydrate metabolism, which minimizes the deleterious effects of S. mansoni.

Nectomys squamipes é um mamífero silvestre reservatório de Schistosoma mansoni no Brasil. No presente estudo, os roedores silvestres, colhidos no campo, foram classificados em dois grupos: infectado e não infectado por S. mansoni. O sangue foi colhido para análise da alteração no nível de glicose sérico (mg/dL) e fragmentos de fígado foram usados para determinar o conteúdo de glicogênio hepático (mg de glicose/g tecido). A análise histológica demonstrou lesões granulomatosas em diferentes fases de desenvolvimento no tecido hepático dos roedores naturalmente infectados com S. mansoni, localizados principalmente na região periportal, com total ou parcial oclusão do lúmen vascular. As lesões foram caracterizadas por presença de infiltrado inflamatório ao redor de ovos morfologicamente intactos recentemente depositados. Apesar da grande significância das lesões histológicas, as alterações bioquímicas não diferiram no mesmo grau. N. squamipes naturalmente por S. mansoni não apresentaram variação na reserva de glicogênio hepático. Esses achados foram acompanhados pelo aumento significativo nos conteúdos de glicose plasmática, provavelmente como consequência ao processo desaminativo de aminoácidos, que passam a ser degradados notadamente para a formação de glucose, sem contudo comprometer a reserva de glicogênio hepático. Em condições naturais a infecção de S. mansoni pode ser mantida usando N. squamipes como hospedeiro definitivo, sem alterações significativas nos conteúdos de glicogênio hepático, minimizando os efeitos deletérios causados por S. mansoni nos roedores N. squamipes naturalmente infectados.

potential use of n, diethyl-m-toluamide [deet] as a prophylactic agent in the control of schistosomiasis

This work studied the effect of [N, N-diethyl-m-toluamide] DEET on Schistosoma mansoni cercariae viability [in vitro] and skin penetration and migration [in vivo]. DEET concentrations of 30%, 15% and 7.5% were highly efficient in killing all cercariae in vitro within 30, 60 and 240 minutes, respectively. Two concentrations of DEET [15% and 7.5%] were tested separately for their antipenetrant and protective effects in mice by immersing their tails in the drug and then exposed to cercariae, 30 minutes later. It was concluded that DEET [cutaneous application] can be potentially used in the prophylaxis against S. mansoni. The cercaricidal, antipenetrant and protective effects were maximal at a concentration of 15% and resulted in complete protection from infection, which was difficult to achieve with helminthic vaccines. Single application of DEET could effectively protect against schistosomal infection for up to three days and even after two hours water wash. It is recommended to use OFF spray for its dual benefits. The topical use of DEET for protection against schistosomal infection might not be practical for large scale application

Effects of schistosomal mansoni infection on Calomys callosus coelom-associated lymphomyeloid tissue (milky spots)

Calomys callosus Rengger, 1830 (Rodentia: Cricetidae) is a mouse-like South American wild rodent, which is permissive to Schistosoma mansoni infection. In this paper we studied the effect of schistosomal infection in C. callosus mesenteric and omental milky spots (MS), subsidiary foci of coelom-associated lymphomyeloid tissue (CALT), during the acute, transitional (acute to chronic), and chronic phases of the infection. MS were morphologically analyzed by historical methods, using brightfield and confocal laser scanning microscopies. The MS of infected animals were mainly of lymphomyelocytic (42 to 90 days) and lymphoplasmacytic (160 days of infection) types and showed frequent presence of lymphoid follicles with germinal centers, plasmacytogenesis and plasmacytosis, mastocytosis, megakaryopoiesis, erythropoiesis and less pronounced eosinopoiesis. These results indicate that MS are a preferencial site of germinal-center-dependent and independent plasmacytogenesis, and a bone narrow-like organ, committed with various cellular lineages. The consequence of a C. callosus MS reactivity for schistosomal infection is still unknown and is under investigation.

Role of cytokines in the formation and downregulation of hepatic circumodal granulomas and hepatic fibrosis in Schistosoma mansoni-infected mice

Schistosoma mansoni infections are associated with a strong Th2 cytokine response. Treatment of mice with IL-12 or anti-IL-2 or anti-IL-4 before i.v. injection of eggs increased IFN-gamma production and downregulated Th2 responses and pulmonary granuloma size. Conversely, anti-IFN-gamma antibody treatment increased Th2 responses and granoloma size. Similar manipulation produced less dramatic results in infected mice. However, sensitization of mice with eggs + IL-12 before infection augmented the Th1 response and decreased Th2 cytokines, granoloma size and fibrosis. Antisera to IFN-gamma, TNF-alpha or IL-12 during IL-12-egg immunization partly restored granuloma size and fibrosis following infection. Variations in the size of granulomas in acute (8 weeks) infections may be influenced primarily by the number and state of activation of T cells. In chronic (12-16 week) infections immunologic downmodulation proceed normally in mice without functional CD8 + cells and in IFN-gamma KO mice but not in B cell KO (µMT) mice or in mice deficient in FcR expression in spite of the fact that these mice downregulated their T cell and cytokine responses. It is evident that the participation of cytokines in granuloma formation and regulation is complicated and that the mechanisms controlling both these phenomena are likely to involve both T cells and antibody/FcR interactions.

Immunological pattern in Syrian golden hamsters experimentally infected with schistosoma mansoni and Leishmania D. infantum

The immunoglobulins [IgG, IgM, IgE and IgA] and the complements [C3 and C4] were studied in hamsters as result of a single infection [S. mansoni or L. D. infantum] and as concomitant infection [L. D. infantum on top of S. mansoni]. The immunological pattern showed profound IgG and IgA increase in the concomitant group than either infection alone. Also, concomitant infection induced more IgE increase than either infection alone. On the other hand, C3 and C4 showed more decrease in concomitant infection. The whole results were discussed

Assessment of the therapeutic efficacy of praziquantel on the colonic lesion in experimentally infected mice with schistosoma mansoni

Therapeutic efficacy of praziquantel on colonic schistosomiasis was assessed in this study. Sixty swiss albino mice were infected by 80-100 Schistosoma mansoni cercariae and classified into four groups these first group received a single oral dose of 6.24 mg praziquantel/mouse, the second group was treated by the same dose daily in two successive days, the third group was treated also by the same dose in three successive days and the fourth group was left untreated as a control group. It was found that the third group which was treated by the triple doses give a higher cure rate [98%] than the other two treated groups [64.7% and 82.7% respectively]. Histopathological examination of the colon showed no definite pathological changes in the third group in comparison with the other groups. These data indicate that treatment by the triple doses of praziquantel on three successive days gives a high cure rate of the patients with less side effects

Effect of schistosoma mansoni infection on kidney sodium potassium adenosine triphosphatase activity in experimental

Schistosoma mansoni is a common parasite in Egypt. Disturbance in renal function is a striking complication of bilharzial infection. ATPase enzyme is considered to be responsible for the generation of energy supply for the extrusion of Na[+] exchange for K[+] and maintence of water and electrolyte balance. In this study Na [+] K[+] ATPase activities have been assayed in kindeys of healthy and Schistosoma mansoni - infected mice before and after treatment with praziquantel. Schistosoma mansoni infection caused significant decrease of the kidney Na[+] - K[+] ATPase activities which were reversed by treatment of mice with praziquantel [200 mg/kg B. Wt. for three doses in 24 hours]. Possible explanations of these findings are clarified

Evidence for a relationship between the expression of dominant idiotypes in the offspring's of schistosoma mansoni infected rats and the immunopathology of the disease

In Schistosomiasis, there is increasing evidence, in both human and murine models, that there is association between the idiotypic regultion and the immunopathology of the disease. The presence of dominant shared idiotypes across species had been described by both our laboratory and others. It is not clear, if this dominant idiotypes is a consequence of the immunopathology of egg deposition, or the presence of such dominant idiotypes direct the immunopathology, and consequently the morbidity of the disease. In this study, the presence of dominant idiotypes in the offsprings of S. mansoni-infected rats and their effects on the morbidity in subsequent infections have been evaluated. In the offsprings, the idiotypes levels were found to be in three levels; high, intermediate and low levels in comparison to the maternal and control level. All the groups were infected with 100 cercaria. The infection were confirmed by the presence of ova in stool examination after 8 weeks of infections. After 11 weeks of infections, rats stopped passing ova in their stools. Four weeks later, the rats were sacrificed and examined for pathology. Our data indicated that rat offsprings with high level of idiotypes showed maximum granulomatous reaction and egg deposition, while rat offsprings with low level of idiotypes showed minimum granulomatous reaction and egg deposition. Significance of our studies in the predicion of the prognosis of human schistosoma infection will be discussed. Supported by USAID/MOH Egypt, 263-0140.2 Project, SRP grant No 01-03-34

Experimental association of infection by salmonella and schistosoma mansoni in Swiss Albino mice

Sixty swiss males albino mice from the same breed, were used in this study. They were classified into four groups [I] normal non-infected control group [10 mice][II] control group infected by Salmonella typimurium organism [10 mice][III] control group infested by Sch. mansoni [20 mice] and [IV] a study group infected by both Sch. mansoni and Salmonella typimurium [20 mice] The relation between schistosomiasis and salmonella organism was evaluated by egg-count per gram stool and per gram liver tissue and by studying the worm load by worm perfusion method. The relation was also evaluated by a histopathological study for the liver, spleen and intestine and by a bacteriological study including culture of the perfused worms, liver and spleen. The study demonstrated: 0.99% reduction of egg-count per gram stool and 0.61% reduction of egg-count per gram liver tissue in the group [IV] compared to the third one. Histo pathological study revealed reduction of bilharzial granulomas in the liver of group [IV] compared to the third group. Regarding the bacteriological study, the most important result was the presence of salmonella growth in 60% of cultures of perfused worms from group [IV]