Schistosoma mansoni: a diagnostic approach to detect acute schistosomiasis infection in a murine model by PCR

Schistosomiasis represents an increasing problem in non-endemic areas, due to the growing number of immigrants and to tourists contracting this disease in "off-the-beaten-track" tourism. Acute schistosomiasis is not diagnosed early due to the lack of diagnostic tools that are sufficiently sensitive enough to detect the parasite during the first weeks of infection. We have developed a diagnostic approach based on the detection of parasite DNA by polymerase chain reaction (PCR) in urine, comparing the performance of this new approach with the two currently used schistosomiasis diagnostic tools (Kato-Katz and ELISA) and the PCR in stool samples. This comparison was done in a Schistosoma mansoni murine experimental model, which permits follow up of the parasite from the acute to the chronic stage of infection. Our results suggest that this new PCR-based approach could be useful for the detection of acute schistosomiasis in easy-to-handle clinical samples such the urine.     

Neuroinflammatory implication of Schistosoma mansoni infection in the mouse

Schistosomiasis is a parasitic disease due to Schistosoma mansoni. Schistosome infection is known to induce granulomas not only in the spleen, bladder, liver and intestine but also in the brain and spinal cord resulting in severe neuropathological and psychiatric disorders though the interaction between Schistosoma mansoni infection and the nervous system has received on the whole little attention. In the present review it has been discussed recent findings from experimental Schistosoma mansoni infection in mouse nervous system. We show that brain granulomas are associated with a significant alteration in the constitutive levels of nerve growth factor (NGF), a trophic factor playing an essential role in nerve growth and differentiation and in preventing neuronal damages. Animals infected with schistosomes suffered also of increased pain sensitivity which was inhibited by TNF-alpha antibody injections and not by anti-NGF. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.     

Neuroinflammatory implications of Schistosoma mansoni infection: new information from the mouse model

Schistosoma mansoni infection is known to induce granulomas, not only in the liver and intestine, but also in the brain, resulting in neuropathological and psychiatric disorders. In the past, the interaction between Schistosoma mansoni infection and the nervous system has received little attention. Here, Luigi Aloe and Marco Fiore discuss recent findings from experimental Schistosoma mansoni infection in the mouse nervous system showing that brain granulomas are associated with a significant alteration in the constitutive expression of nerve growth factor, a neurotrophic factor that plays an essential role in growth and differentiation and in preventing neuronal damage. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.     

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection

BackgroundOne of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice.Methodology/Principal findingsTwo months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56^th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2.Conclusion/SignificanceThis study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.     

Natural infection of wild rodents by Schistosoma mansoni

In Planalto, a small locality in the interior of the Bahia state, Brazil, 47% of sylvatic rodents were found to be naturally infected with Schistosoma mansoni, whereas the prevalence of the infection in the inhabitants of the area was 3.26%. The rodents (Nectomys) live near the houses, in contact with water, passing viable schistosome eggs in the stools. Worm burden is variable amongst such rodents. Periovular granulomas are small, especially in liver and intestines, and hepatic fibrosis is mild or absent, with no morphological evidence of portal hypertension being noted. Miracidia isolated from the eggs recovered from Nectomys readly infected laboratory-raised Bahia strain of Biomphalaria glabrata. Cercariae then obtained infected Swiss mice in a similar way as the human strains of S. mansoni kept in laboratory. Also, Swiss mice left in contact with water collections in Planalto were easily infected, which proved the transmissibility potential of the area. In conclusion: sylvatic rodents found in the area of Planalto tolerate well S. mansoni infection, eliminate viable eggs in the stools, are usually infected with a strain probably of human origin and therefore may play a role in maintaining parasite cycle in the area.     

Experimental models of Schistosoma mansoni infection

Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver.     

Protein undernutrition reduces the efficacy of praziquantel in a murine model of Schistosoma mansoni infection

BackgroundUndernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel.Methodology/Principal findingsThirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36^th day post-infection. Mice were sacrificed on the 64^th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection.Conclusion/SignificanceThese results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel.     

Evaluation of urine CCA assays for detection of Schistosoma mansoni infection in Western Kenya

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests--the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections.     

Metabonomic investigation of human Schistosoma mansoni infection

Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the host-parasite interaction at the molecular level and identification of biomarkers of infection and infection-related morbidity would be of value for improved strategies for treatment and morbidity control. To this end, we conducted a nuclear magnetic resonance (NMR) based metabonomics study involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time-points, before and after (one or two times) chemotherapy with praziquantel (PZQ). Using supervised multivariate statistical analysis of the recorded one-dimensional (1D) NMR spectra, we were able to discriminate infected from uninfected individuals in two age groups (children and adults) based on differences in their urinary profiles. The potential molecular markers of S. mansoni infection were found to be primarily linked to changes in gut microflora, energy metabolism and liver function. These findings are in agreement with data from earlier studies on S. mansoni infection in experimental animals and thus provide corroborating evidence for the existence of metabolic response specific for this infection.     

Natural versus drug-induced resistance in Schistosoma mansoni infection

Rodrigo Corrêa-Oliveira, Iramaya Rodrigues Caldas and Giovanni Gazzinelli here focus on the immune response of individuals with natural resistance to schistosomiasis, which differs significantly from that of post-treatment resistant and infected individuals. They suggest that the activation of T helper type 1 (Th1) and Th2 cells is needed for the induction of natural resistance against Schistosoma mansoni infection.     

Hepatocellular carcinoma associated with chronic Schistosoma mansoni infection in a chimpanzee

Hepatocellular carcinoma associated with chronic Schistosoma mansoni infection in a chimpanzee, estimated to be a 12-year-old and born in West Africa, is reported. The hepatic tumor appeared as a solitary firm nodule, and histological examination revealed well-differentiated hepatocellular carcinoma with a trabecular pattern. Hepatitis B virus and hepatitis C virus infections were excluded by serological testing in that animal. This is the first report of hepatocellular carcinoma in the chimpanzee with schistosomiasis.     

Schistosoma mansoni: a histological study of migration in the laboratory mouse

Quantitative histological methods were applied in a study of the migratory route of schistosomula within the definitive mammal host. The observations are consistent with an entirely intravascular mode of migration in the direction of blood flow. They do not support a trans-diaphragm route. Schistosomula can be identified in low numbers in systemic organs, in the left side of the heart and in the venous compartment of the pulmonary circulation. They were not observed penetrating the diaphragm or the capsule of the liver. No histopathological evidence was found to suggest that the tissue responses of previously unexposed hosts affect migrating schistosomula at any stage during migration. These non-specific tissue responses were marked only in the skin phase of migration.     

Oxamniquine for treating Schistosoma mansoni infection in Sudan.

The efficacy and acceptability of oral oxamniquine were assessed in Sudanese patients infected with Schistosoma mansoni. Cure rates, determined by the absence of viable eggs in the stools six months after treatment, were 94.9% in patients treated with a total of 60 mg/kg, 78.8% in patients treated with 40 mg/kg, and 68.9% in patients treated with 30 mg/kg. All treatment regimens considerably reduced the egg count in those patients not cured. The drug was well tolerated and the side effects were minimal and transient, the most common being dizziness. Most of the patients noticed a reddish discoloration of their urine, which was probably caused by a metabolite of the drug. In patients who received 60 mg/kg oxamniquine there were transient rises in eosinophil counts and in serum alanine aminotransferase concentrations. Though 60 mg/kg was by far the most effective dose in terms of cure rate, egg counts were significantly reduced on all three doses. The lower doses could therefore be useful in a low-cost control programme in reducing transmission of S mansoni infection.