Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1β and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.
Schistosomiasis remains one of the most prevalent neglected tropical diseases especially in Nigeria which has the greatest number of infected people worldwide. A cross-sectional study was conducted among 551 participants from Kano State, North Central Nigeria. Fecal samples were examined for the presence of Schistosoma mansoni eggs using the formalin-ether sedimentation method while the urine samples were examined using the filtration technique for the presence of S. haematobium eggs. Demographic, socioeconomic and environmental information was collected using a pre-validated questionnaire. The overall prevalence of schistosomiasis was 17.8%, with 8.9% and 8.3% infected with S. mansoni and S. haematobium, respectively and 0.5% presenting co-infection with both species. The multiple logistic regression analysis revealed that age < 18 years (OR = 2.13; 95% CI; 1.34- 3.41), presence of infected family members (OR = 3.98; 95% CI; 2.13-7.46), and history of infection (OR = 2.87; 95% CI; 1.87- 4.56) were the significant risk factors associated with schistosomiasis in these communities. In conclusion, this study revealed that schistosomiasis is still prevalent among Hausa communities in Nigeria. Mass drug administration, health education and community mobilization are imperative strategies to significantly reduce the prevalence and morbidity of schistosomiasis in these communities.
Three cases of schistosomiasis in 2 Filipinos and one Chinese in Sabah are reported. Diagnosis was based on incidental histological findings of Schistosoma japonicum-like ova in the liver and rectal biopsies. As these 3 patients are immigrants to Sabah, it is assumed that they are imported cases, and that Sabah has been free of the disease from 1970 to 1977.
This study investigated the distribution of parasites as main contaminants in water environments of peninsular Malaysia (October 2011-December 2011) and the southeastern coast of Thailand (June 2012). Sixty-four water samples, 33 from Malaysia and 31 from Thailand, of various water types were examined according to U.S. Environmental Protection Agency guidelines. Drinking or household water types from both countries were free from parasitic contamination. The recreational/environmental (except a swimming pool in Malaysia) and effluent water types from these two countries were contaminated with waterborne parasites: Giardia (0.04-4 cysts/L), Cryptosporidium (0.06-2.33 oocysts/L), hookworm (6.67-350 ova/L), Ascaris (0.33-33.33 ova/L), and Schistosoma (9.25-13.33 ova/L). The most contaminated sites were recreational lake garden 3 in Malaysia and river 2 in Thailand. Higher concentrations of Giardia, Cryptosporidium, and hookworm were found in samples from Malaysia than in samples from Thailand. The presence of Giardia cysts showed a significant association with the presence of Cryptosporidium oocysts (P < 0.005).
The neglected tropical diseases, echinococcosis, schistosomiasis and toxoplasmosis are all globally widespread zoonotic diseases with potentially harmful consequences. There is very limited data available on the prevalence of these infections, except for schistosmiasis, in underdeveloped countries. This study aimed to determine the seroprevalence of Echinococcus multilocularis, Schistosoma mansoni, and Toxoplasma gondii antibodies in populations from the Monduli and Babati districts in Tanzania.
A serosurvey of various indigenous interior tribes (Orang Ulu) in upper Rejang River Basin Sarawak Malaysia, the site of a multibillion Ringgit hydroelectric power project, found 6.8% of the individual surveyed were seropositive for schistosomiasis, as determined by ELISA method using the soluble egg antigen of Schistosoma malayensis Baling strain. In all age group, the seroprevalence rate is higher (9.5%) in males than in females (4.5%) except for the 31-40 age group. Seroprevalence of schistosomiasis was found to increase with age with the above 60 age group having the highest rate followed by the 31-40 age group. Seroprevalence rate among the tribes ranges from 4.1% among the Penan to 11.6% among the Kajang. There was no seroevidence of schistosomiasis among the Ukits. A snail survey found four snail species including Brotia species, the intermediate host of the lung fluke Paragonimus westermani, however no schistosome snail host was identified. Although schistosomiasis malayensis-like infection may be endemic in the area, its public health significance remains undetermined.
For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.
Schistosomiasis is a chronic parasitic disease affecting mostly low income and resourcelimited countries. Despite the distribution of the curative medicine, praziquantel (PZQ), the frequency of re-infection is commonly reported, thus, making a difficulty to discriminate treatment failure after re-infection. Therefore, assessing Schistosoma mansoni re-infection after praziquantel administration is crucial to prove the treatment efficacy and to break the transmission of infection in endemic areas. The evolution of highly sensitive and specific diagnostic markers, reliable to detect the re-infection and to evaluate the treatment efficacy, is required to control schistosomiasis. In this study, the potential role of serpin recombinant antigen of S. mansoni as a biomarker of re-infection and chemotherapeutic efficacy has been assessed. Therefore, 20 mice were experimentally challenged and re-challenged with 50 S. mansoni cercariae and divided into 4 equal groups; the first included infected mice (control positive), the second group was twice infected with S. mansoni and left untreated, the third included mice twice infected then treated with praziquantel following the last challenge, and the forth one remained uninfected and untreated (control negative). The current findings demonstrated that high levels of IgG and IgG1 bound to serpin were detected following the re-infection and rapidly declined post treatment. In summary, S. mansoni recombinant serpin could be used as a promising marker to discriminate S. mansoni re-infection and evaluated the efficacy of treatment. The translation of such a potential tool in endemic areas will provide a significant support for the elimination and control programs against schistosomiasis.
The first living patient with a Schistosoma japonicum-type infection who presented with the nephrotic syndrome is reported in detail. It is not clear whether the nephrotic syndrome was due to the schistosome infection or to the deposition of hepatitis B antigen and antibody complexes. This is the tenth case of schistosomiasis reported from aborigines in Malaysia and a sylvatic source of infection is suggested.
Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.
Using ELISA and COPT diagnostic tests, serological evidence of Malaysian schistosomiasis was discovered among Orang Asli populations from three areas in Peninsular Malaysia. Serum samples collected in 1975 indicated an ELISA-positive prevalence of 25% and a COPT prevalence of 11% from Pos Iskandar, Pahang and an ELISA prevalence of 13% and a COPT of 4% from Bukit Lanjan, Selangor. Resurveys at these site in 1982-1984 showed a continued presence of serological positive individuals but prevalence rates were markedly lower: 7% and 1% for ELISA and 4% and 2% for COPT at Pos Iskandar and Bukit Lanjan respectively. Snail hosts were not found at either site. The source of infection for persons living in these lowland areas remains unknown. In a third area, Kuala Tahan, Pahang, located in the foothills of the central mountain range, foci of transmission have been found near to Orang Asli settlements. The serological prevalence rate among Negrito Orang Asli in that study area was 9% for ELISA and 4% for COPT. Thirty-three of 36 COPT-positive sera produced vacuolated bleb precipates and in 31 these were the only reactions seen. The high percentage of positives producing only these precipates suggests that among Orang Asli schistosomiasis patients such reactions are not an indication of recently acquired infection as has been reported for schistosomiasis patients in the Philippines.
Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca2+. All annexin members evaluated in this study were immunolocalized to the tegument, with immunoreactivity also occurring in cells and in muscle of adult parasites. All four recombinant annexins were immunoreactive and they were recognized by the sera of mice infected with S. mansoni. In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.
High-fat diet (HFD) can cause hyperlipidemia, fatty liver and cardiovascular disorders. Herein, we evaluated therapeutic effects and possible underlying mechanisms of actions of Schistosoma mansoni soluble egg antigen (SEA) against experimental HFD induced dyslipidemia, hepatic and cardiovascular pathology. Forty Swiss albino mice were divided into four groups (10 each); mice fed standard diet (SD), mice fed HFD, mice fed HFD for 8 weeks then infected by S. mansoni cercaria (HFD+I) and mice fed HFD for 8 weeks then treated with SEA (HFD+SEA), all mice were euthanized 16 weeks after starting the experiment. HFD+SEA mice showed significantly (p<0.001) reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and significantly (p<0.05) increased high-density lipoprotein cholesterol (HDL-C) comparing to HFD mice with non-significant difference with HFD+I mice group. Doppler flowmetry showed significantly (p<0.01) lower arterial resistance and significantly (p<0.05) higher blood flow velocity in HFD+SEA and HFD+I mice groups than HFD mice. HFD+SEA mice revealed improving in liver and aortic pathology and these were better than HFD+I mice group. HFD+SEA and HFD+I mice groups had less myocardium lipid deposits, but still showing some congested blood vessels. HFD myocardium revealed strong CD34+ expression on immunohistochemistry study, while that of HFD+SEA showed weak and HFD+I mice had moderate expressions. HFD+SEA mice had significantly (p<0.01) lower serum IL-1β and vascular endothelial growth factor (VEGF) and significantly (p<0.001) higher serum transforming growth factor beta 1 (TGF-β1) and IL-10 than HFD mice with non-significant difference with HFD+I mice. In conclusion, SEA lowered serum lipids, improved aortic function, decreased liver and cardiovascular pathology in HFD mice, so, it is recommended to purify active molecules from SEA to develop anti-dyslipidemic treatment.
Schistosomiasis in Southeast Asia, caused by Schistosoma japonicum, Schistosoma mekongi and Schistosoma japonicum-like, have been reported from six different countries. The S. japonicum infections are highly prevalent in the Philippines with Oncomelania hupensis quadrasi as the vector snail, and in localized areas in Indonesia with O.h. lindoensis as the snail vector. The S. mekongi infections are recent discovery in the Lower Mekong Basin in Laos and Kampuchea, with Tricula aperta as the vector snail. The S. japonicum-like infections are found as isolated cases diagnosed by the finding of S. japonicum-like eggs in the faeces, rectal biopsy, tissue biopsy or at necropsy in Thailand and Malaysia. The control measures of schistosomiasis have been implemented in the Philippines and Indonesia, while further research studies are being conducted in Thailand and Malaysia.
Authors present a case of bilharziosis incidentally diagnosed in a patient undergoing TURB for suspected bladder cancer. The patient, who in 2005 had gone to Malaysia, had been suffering from recurrent hemorrhagic cystitis since 2007, which were treated with antibiotic therapy. In November 2009 he presented to our observation for persistent hematuria, underwent ultrasound examination, fibroscopy and TURB diagnostics for suspicious lesions. The histopathology diagnosis found granulomatous lesions with typical parasites eggs due to schistosomiasis eggs. As a consequence of that, the patient underwent medical therapy. The pathologist's role becomes nullifying not only for the diagnosis of parasitic infections but also for the exclusion or evidence of urothelial squamous neoplasia. The low incidence of this rare parasitic disease in European tourists and the presence of immigrants in our country require to spread the knowledge of these parasites and the most simple tests for early detection.
The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT).