Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis.

Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosoma mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.

[Mechanisms for the formation of a combination of the natural foci of trematodiases and tularemia in the floodplain-river ecosystem of the Konda River in different periods of epizootic activity of an infection focus].

The basis of the mechanism responsible for the formation of a combination of the natural foci of trematodiases and tularemia in the infection foci in the interepizootic periods is their association with the morphological structure of the floodplain-river landscape of the Konda River. The landscape's facias and holes, which are common to the foci, are integrated, by predetermining the territorial combination. The formation of a closed trinomial Francisella tularensis parasite system integrating these foci serves as a basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia on transition of the latter from the interepizootic state to epizooty. The absence of host populations linking the foci of methorchiasis (M. xanthosomus), bilharziasis, and tularemia determines their combination both in the interepizootic periods and at the level of the landscape morphological structure. The basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia in the periods of diffuse epizooties in the infection foci is the formation of an open binomial F. tularensis parasite system and the infestation of the co-members of F. tularensis trematode parasite systems. By penetrating into them, the pathogen forces the F. tularensis parasite system to enter the trematode parasite systems, causing their complete (opisthorchiases, methorchiases) or partial (bilharziasis) coincidence. Thus, these foci are combined at the level of parasitocenoses of the parasite systems of infections and infestations, by giving rise to pseudosystem combined foci. The natural foci of B. polonica and F. tularensis are combined at the level of parasitocenosis of the coacting hemipopulation of trematode parthenitas, F. tularensis subpopulations and intermediate host population, by forming an autoecious population-combination bilharziasis-tularemia focus. The formation of territorial-combination, autoecious population-combination, and pseudosystem-combination foci of trematodiases and tularemia in different periods of the epizootic activity of an infection focus is determined by the functional organization of the parasite system of a tularemia focus and the biocenotic (functional) structure of natural foci of infestations.

Acute- phase response and iron status markers among pulmonary tuberculosis patients: a cross-sectional study in Mwanza, Tanzania.

Fe status is difficult to assess in the presence of infections. To assess the role of the acute- phase response (APR) and other predictors of serum ferritin and transferrin receptor, we conducted a cross-sectional study among pulmonary tuberculosis (PTB) patients in Mwanza, Tanzania. The acute- (serum ferritin) phase protein, serum alpha1-antichymotrypsin (ACT) and serum ferritin and serum soluble transferrin receptor (sTfR) were measured, and data on smoking, soil and alcohol intake, and infection status were collected. Linear regression analysis was used to assess the role of elevated serum ACT and other predictors of serum ferritin and serum sTfR. Of 655 patients, 81.2 % were sputum positive (PTB+) and 47.2 % HIV+. Mean serum ACT was 0.72 g/l, with 91.1 % above 0.4 g/l. Among females and males, respectively, geometric mean serum ferritin was 140.9 and 269.1 microg/l (P < 0.001), and mean serum sTfR 4.3 and 3.8 mg/l (P < 0.001). Serum sTfR was increased 0.5 mg/l and log serum ferritin increased linearly with serum ACT >0.4 g/l. PTB+ and HIV infection, alcohol drinking and smoking were the positive predictors of serum ferritin, and female sex, soil eating, Schistosoma mansoni and hookworm infection were the negative predictors. Similarly, smoking and HIV infection were the negative predictors of serum sTfR, and female sex, soil eating and PTB+ were the positive predictors. Serum ferritin and serum sTfR are affected by the APR, but may still provide information about Fe status. It may be possible to develop algorithms, based on the markers of the APR and Fe status, to assess the Fe status among the patients with tuberculosis or other infections eliciting an APR.

Vesicle-based secretion in schistosomes: Analysis of protein and microRNA (miRNA) content of exosome-like vesicles derived from Schistosoma mansoni.

Exosomes are small vesicles of endocytic origin, which are released into the extracellular environment and mediate a variety of physiological and pathological conditions. Here we show that Schistosoma mansoni releases exosome-like vesicles in vitro. Vesicles were purified from culture medium by sucrose gradient fractionation and fractions containing vesicles verified by western blot analyses and electron microscopy. Proteomic analyses of exosomal contents unveiled 130 schistosome proteins. Among these proteins are common exosomal markers such as heat shock proteins, energy-generating enzymes, cytoskeletal proteins, and others. In addition, the schistosome extracellular vesicles contain proteins of potential importance for host-parasite interaction, notably peptidases, signaling proteins, cell adhesion proteins (e.g., integrins) and previously described vaccine candidates, including glutathione-S-transferase (GST), tetraspanin (TSP-2) and calpain. S. mansoni exosomes also contain 143 microRNAs (miRNA), of which 25 are present at high levels, including miRNAs detected in sera of infected hosts. Quantitative PCR analysis confirmed the presence of schistosome-derived miRNAs in exosomes purified from infected mouse sera. The results provide evidence of vesicle-mediated secretion in these parasites and suggest that schistosome-derived exosomes could play important roles in host-parasite interactions and could be a useful tool in the development of vaccines and therapeutics.

Schistosomiasis among obstetric fistula patients in Lilongwe, Malawi.

BACKGROUND: Schistosoma haematobium infection has been documented as an uncommon cause of vesicovaginal fistula (VVF) and can result in impaired wound healing of urogenital tissues. For these reasons, it could potentially be linked to an increased rate of obstetric fistula among women who experience obstructed labor and/or in a higher failure rate of fistula repair. Therefore, the primary objective of our study was to determine the prevalence of S. haematobium infection among women undergoing obstetric VVF repair in Lilongwe, Malawi. Our secondary objectives were to assess if S. haematobium infection could be a risk factor for obstetric fistula development or unsuccessful VVF repair in our patient population. METHODS: From July to October 2013, we conducted S. haematobium testing via urine microscopy on 96 patients undergoing obstetric VVF repair surgery at the Fistula Care Centre in Lilongwe, Malawi. RESULTS: The prevalence of S. haematobium infection among women undergoing obstetric VVF repair was 2% (n=2). Both women with S. haematobium had successful VVF repairs. CONCLUSIONS: Although S. haematobium has the potential to be a risk factor for obstetric VVF formation or unsuccessful VVF repair, it was uncommon among the women in our clinic with obstetric VVF.

Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.

Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196), P < 0.01. The rise in sCD14 was lower (P < 0.01) in the rifaximin group (median rise 122 ng/mL, IQR-184, 783) than in the non-rifaximin group (median rise 832 ng/mL, IQR 530, 967). TNFR1 decreased (P < 0.01) in the rifaximin group (median -39 ng/mL IQR-306, 563) but increased in the non-rifaximin group (median 166 ng/mL, IQR 3, 337). Other markers remained unaffected. Rifaximin led to a reduction of inflammatory markers and bacterial 16S rRNA which may implicate BT in the inflammation in HSS.

Bacteriuria in urinary schistosomiasis in Egypt a prevalence survey.

An epidemiologic survey to assess the prevalence of bacteriuria in urinary schistosomiasis was carried out in a region endemic for urinary schistosomiasis in Egypt. Twenty of 390 (5.1%) school boys aged 5--16 years were bacteriuric. This prevalence rate is more than 10 times greater than that found in comparable surveys in areas non-endemic for urinary schistosomiasis. In this endemic population bacteriuria was found in 6.5% of active egg excreters and 2.3% of non-egg excreters.

Distribution and extent of schistosomiasis in female pelvic organs, with special reference to the genital tract, as determined at autopsy.

PIP: Tissue samples were taken in a series of 64 consecutive autopsies of African women aged 16-70 years. These were block-dissected and studied to determine the frequency of schistosome eggs in tissues of the uterus, and its adnexa, and in the vagina, as well as to determine the numbers of eggs in these tissues. In addition, by histological examination, it was hoped that the frequency and degree of inflammation accompanying the eggs' presence could be learned. 37 of 64 autopsy specimens showed evidence of schistosomiasis. In terms of the mean number of eggs per gram of tissue, the heaviest deposition of eggs was in the bladder. The cervix, uteri, fallopian tubes, and ovaries had eggs to much the same degree, leaving the myometrium and parametrium with the fewest eggs resident. Rectal tissue was relatively clean, surprizingly. Tissues of pelvic organs were positive for schistosome eggs in a total of 37: 33 by digestion technique, 24 by histology, and 20 by both. Inflammatory changes associated with schistosome eggs were found in 12 of 24 infections discovered histologically. Inflammation in the gential tract was only found in 3 cervixes and 2 vaginal walls; in bladders for example, infectious inflammation was seen in 7. Eggs of S. haematobium were identified in 19 of 24 histologically discovered infections. Eggs of S. haematobium were found in all 33 instances identified by the digestion technique, and in 9 of these instances, eggs of S. mansoni were also found. 7 of 9 infections with S. mansoni were of the rectum and 2 were of the bladder.^ieng

Infarction of testicle and Schistosoma mansoni.

The first case of clinical involvement and infarction of the testes caused the Schistosoma mansoni is reported. Although a rare rhenomenon, one must consider this in the differential diagnosis of testicular disease in patients who have resided in endemic areas of S. mansoni.

Imported schistosomiasis in Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas. METHOD: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty-three reports of schistosomiasis were analyzed for epidemiologic and clinical features. RESULTS: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schistosoma haematobium, 130 to Schistosoma mansoni, and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded. CONCLUSION: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe.

Hepatitis B virus markers in patients with schistosomiasis, liver cirrhosis and hepatocellular carcinoma in Khartoum, Sudan.

Markers of hepatitis A and B virus were tested in 88 adult Sudanese subjects in Khartoum, Sudan. The subjects consisted of 25 control hospitalized patients, 21 volunteer blood donors, 23 patients with hepatosplenic schistosomiasis, 13 patients with liver cirrhosis and 6 patients with hepatocellular carcinoma (HCC). Antibody to hepatitis A virus was detected in 96% of the total. Hepatitis B surface antigen (HBsAg) was positive in 4, 24, 22, 31, and 67% of the subject groups, respectively. Antibody against hepatitis B core antigen (HBcAb) of undiluted serum was positive in 60, 57, 65, 77 and 83%, and there was no difference in incidence among the groups. It was positive in 200X diluted serum in 4, 24, 17, 23 and 60%. HBsAg and HBcAb (200X) were detected more often in HCC patients than in the control subjects (p less than 0.01). Hepatitis B virus is an important factor in the etiology of HCC in the Sudan.

A study on the etiological factors of bilharzial bladder cancer in Egypt. 6. The possible role of urinary bacteria.

A correlation was obtained between a positive nitrite test in urine and the severity of urinary bacterial infection. Bacteria isolated from the urine of bilharzial or bladder cancer patients were found to be rich in nitrate reductase activity. "Escherichia coli" was the most common microorganism isolated from these specimens. Urine and several urinary constituents activate bacterial nitrate reductase. beta-Glucuronidase activity in the urine of patients with chronic "Schistosoma haematobium" infection and bladder cancer was measured and shown to be significantly greater than that of urine of normal control subjects. Urinary bacterial infection was shown to be the source of the increased urinary level of enzyme activity at pH 7.0.

[Health assessment on safe treatment of night-soil on schistosomiasis endemic areas].

The family size biogas tanks were built in the study site. Their effects were monitored. Faecal coliform and parasite eggs were examined before and after biogas digestion. The results of whole-year operation indicate that faecal coliform and parasite eggs can be reduced by 99.7% and 99.8%, respectively. The schistosome eggs survival experiment showed that the eggs all died off in 100 days of retention in biogas tanks. Therefore, the appropriate technology of nightsoil treatment can effectively interrupt the life cycle of schistosome.

Human schistosomiasis is associated with endotoxemia and Toll-like receptor 2- and 4-bearing B cells.

Schistosomiasis is caused by parasitic trematodes. Individuals can accumulate hundreds of intravascular worms, which secrete a myriad of antigenic molecules into the bloodstream. Some of these molecules suppress immunity to microbial Toll-like receptor (TLR) ligands, such as lipopolysaccharides, which may increase host susceptibility to coinfecting pathogens. We show that schistosomiasis is associated with extremely high levels of endotoxemia as well as high mobility group 1, an endogenous inflammatory TLR ligand, in the absence of other coinfected pathogens. Circulating B cells express surface TLR2 and TLR4, reflecting systemic exposure to microbial ligands. Bacterial translocation may occur with schistosomal egg movement from the vascular to the gut and other routes, such as the skin during infection. Our report suggests that immunosuppressive schistosome antigens may have evolved to curb inflammatory responses to the high antigenic burden of translocated bacteria products and endogenous TLR ligands that arise during parasite exposure and inflammation.