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.

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.

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.

Esquistosomiasis como causa de hematuria macroscópica / Schistosomiasis as a cause of gross hematuria

La esquistosomiasis (o bilarzhiasis) es una enfermedad parasitaria muy extendida en el mundo, que deberemos considerar en el diagnóstico diferencial de diversas entidades, predominantemente la hematuria, ante población inmigrante procedente de áreas endémicas. Presentamos el caso de un varón de 11 años original de Gambia con hematuria macroscópica de larga evolución por esquistosomiasis vesical. El estudio microbiológico de orina demostró huevos de Schistosoma haematobium(AU)

Bilarzhia is one of the most prevalent parasitic diseases in the world, that we should consider in the differential diagnosis of different entities, such as hematuria, most of it occurs in immigrant population coming from endemic areas. We present a case report of a child eleven years old original from Gambia, with gross hematuria due to vesical esquistosomiasis. The urinary microbiology study showed Schistosoma haematobium eggs(AU)

[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.

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.

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.

Esquistosomiasis: una parasitosis urinaria cada vez más frecuente / Schistosomiasis: not an uncommon parasitosis in Europe

Las parasitosis urinarias, muy infrecuentes hasta la fecha en nuestro medio, están siendo diagnosticadas cada vez con mayor frecuencia debido a los fenómenos migratorios. Presentamos un nuevo caso de esquistosomiasis urinaria y realizamos una revisión de la literatura en relación a su diagnóstico y tratamiento. Paciente subsahariano de 28 años que consulta por hematuria y síndrome miccional de 1 año de evolución. La cistoscopia muestra características granulaciones blanquecinas pequeñas en la mucosa vesical y el estudio anatomopatológico de la biopsia fría de la mucosa vesical confirma la existencia de huevos y parásitos adultos. A pesar de la infrecuencia de la esquistosomiasis en nuestro medio y en relación al aumento de los fenómenos migatrorios poblacionales, debemos incluir esta afectación urinaria en el diagnostico diferencial de la hematuria monosintomática

Despite the fact that urinary parasitosis are very unusual diseases in our place, their frequency is growing up because of migration movements. Clinical case: A 28 years old subsaharian patient presented with haematuria and low urinary symptoms. The cystoscopic shows small white round granulate in bladder mucosa and anatomopathologic study informed about eggs an adult parasites on bladder biopsy. Despite of the infrequency of schistosomiasis in our country and because of migration movements we must include this disorder in monosimptomatic haematuria differential diagnosis

Diagnóstico da infecção por trematódeos em moluscos através de Multiplex-PCR

A Fasciola hepatica têm despertado interesse médico e veterinário nos últimos anos, uma vez que, os casos de fasciolose humana e animal se tornam cada vez mais freqüentes em todo o mundo. Da mesma forma, o S. mansoni continua sendo estudado em decorrência de seu grande impacto sócio-econômico e na saúde pública. O diagnóstico clássico da infecção de S. mansoni em Biomphalaria bem como de F. hepatica em limneídeos é feito rotineiramente em laboratório através de exames dos moluscos após estímulo luminoso (exposição à luz artificial) para observação de cercárias, e/ou dissecando ou esmagando os moluscos, onde além de se observar cercárias também observa-se a presença de rédias (no caso de F. hepatica) e esporocistos, principalmente se estes estiverem localizados na glândula digestiva. Entretanto o encontro de larvas de helmintos em moluscos quase sempre traz resultados inconclusivos, uma vez que existe uma grande semelhança morfológica entre formas intramolusco de trematódeos. No presente trabalho, foi desenvolvido um diagnóstico molecular rápido e eficaz capaz de detectar F. hepatica e S. mansoni em seus hospedeiros intermediários

Com o intuito de detectar a infecção de S. mansoni e, simultaneamente identificar a espécie de Biomphalaria, utilizamos a Multiplex-PCR para amplificar a região ITS2 dos caramujos e a região do DNAmt desse trematódeo, utilizando simultanemente 6 iniciadores. Esse procedimento permitiu diagnosticar a infecção pelo S. mansoni e realizar a identificação espécie-específica do molusco parasitado, em uma única reação (artigo 1). Para a detectar a infecção de limneídeos por F. hepatica realizamos a Multiplex-PCR, utilizando 4 iniciadores em uma única reação, sob condições de alta estringência, permitindo a amplificação específica do DNA do trematódeo e do molusco (artigo 2). Este método foi altamente sensível, detectando a infecção por até um miracídio de F. hepatica no período pré-patente da infecção, não amplificando DNA de outros trematódeos. Além da especificidade, a Multiplex-PCR também permite o uso de um eficiente controle interno da reação pela amplificação do DNA do molusco. A via migratória e as alterações histopatológicas causadas por helmintos em moluscos têm sido estudadas através de técnicas histológicas

Diante das dificuldades encontradas em se identificar especificamente a presença de trematódeos em limneídeos através apenas da análise de cortes histológicos sob microscópio de campo claro, padronizamos um método sensível capaz de extrair DNA de cortes histológicos em lâminas que foram previamente fixados em formalina, embebidos em parafina e corados com HE (artigo 3). Essa metodologia permitiu detectar a presença de F. hepatica em L. viatrix através da Multiplex-PCR, que mostrou ser um método rápido, seguro e específico, altamente sensível capaz de amplificar DNA de tecidos fixados, a despeito da baixa quantidade de DNA e da degradação causada pelo processo de fixação, possibilitando detecção da presença da F. hepatica mesmo em lâminas onde não era possível observar estágios larvais desse trematódeo através da análise sob microscópio óptico. Dessa forma, as metodologias moleculares, propostas no presente trabalho, para identificação de trematódeos em seus hospedeiros intermediários contribuirão para um avanço em estudos epidemiológicos e de controle da fasciolose e da esquistossomose

Diagnóstico da infecção por trematódeos em moluscos através de Multiplex-PCR / Diagnosis of infection by trematodes in snails by Multiplex-PCR

A Fasciola hepatica têm despertado interesse médico e veterinário nos últimos anos, uma vez que, os casos de fasciolose humana e animal se tornam cada vez mais freqüentes em todo o mundo. Da mesma forma, o S. mansoni continua sendo estudado em decorrência de seu grande impacto sócio-econômico e na saúde pública. O diagnóstico clássico da infecção de S. mansoni em Biomphalaria bem como de F. hepatica em limneídeos é feito rotineiramente em laboratório através de exames dos moluscos após estímulo luminoso (exposição à luz artificial) para observação de cercárias, e/ou dissecando ou esmagando os moluscos, onde além de se observar cercárias também observa-se a presença de rédias (no caso de F. hepatica) e esporocistos, principalmente se estes estiverem localizados na glândula digestiva. Entretanto o encontro de larvas de helmintos em moluscos quase sempre traz resultados inconclusivos, uma vez que existe uma grande semelhança morfológica entre formas intramolusco de trematódeos. No presente trabalho, foi desenvolvido um diagnóstico molecular rápido e eficaz capaz de detectar F. hepatica e S. mansoni em seus hospedeiros intermediários.

Com o intuito de detectar a infecção de S. mansoni e, simultaneamente identificar a espécie de Biomphalaria, utilizamos a Multiplex-PCR para amplificar a região ITS2 dos caramujos e a região do DNAmt desse trematódeo, utilizando simultanemente 6 iniciadores. Esse procedimento permitiu diagnosticar a infecção pelo S. mansoni e realizar a identificação espécie-específica do molusco parasitado, em uma única reação (artigo 1). Para a detectar a infecção de limneídeos por F. hepatica realizamos a Multiplex-PCR, utilizando 4 iniciadores em uma única reação, sob condições de alta estringência, permitindo a amplificação específica do DNA do trematódeo e do molusco (artigo 2). Este método foi altamente sensível, detectando a infecção por até um miracídio de F. hepatica no período pré-patente da infecção, não amplificando DNA de outros trematódeos. Além da especificidade, a Multiplex-PCR também permite o uso de um eficiente controle interno da reação pela amplificação do DNA do molusco. A via migratória e as alterações histopatológicas causadas por helmintos em moluscos têm sido estudadas através de técnicas histológicas.

Diante das dificuldades encontradas em se identificar especificamente a presença de trematódeos em limneídeos através apenas da análise de cortes histológicos sob microscópio de campo claro, padronizamos um método sensível capaz de extrair DNA de cortes histológicos em lâminas que foram previamente fixados em formalina, embebidos em parafina e corados com HE (artigo 3). Essa metodologia permitiu detectar a presença de F. hepatica em L. viatrix através da Multiplex-PCR, que mostrou ser um método rápido, seguro e específico, altamente sensível capaz de amplificar DNA de tecidos fixados, a despeito da baixa quantidade de DNA e da degradação causada pelo processo de fixação, possibilitando detecção da presença da F. hepatica mesmo em lâminas onde não era possível observar estágios larvais desse trematódeo através da análise sob microscópio óptico. Dessa forma, as metodologias moleculares, propostas no presente trabalho, para identificação de trematódeos em seus hospedeiros intermediários contribuirão para um avanço em estudos epidemiológicos e de controle da fasciolose e da esquistossomose.

Multiple microembolic borderzone brain infarctions and endomyocardial fibrosis in idiopathic hypereosinophilic syndrome and in Schistosoma mansoni infestation.

We report two cases of multiple distal borderzone ischaemic strokes associated with hypereosinophilia due to idiopathic hypereosinophilic syndrome in one patient and to acute Schistosoma mansoni infestation in the other. Endomyocardial fibrosis (EMF) was documented pathologically, in one case at autopsy and in the other after cardiac surgery; and by cardiac CT, with initially negative echocardiography, in one patient. These observations suggest that so called borderzone infarcts may be due to microembolisms and that, in the context of hypereosinophilia, EMF diagnosis warrants complete cardiac investigation including cardiac CT and repeat echocardiography.

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.

[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.

Studies on gastric bacterial growth and gastric PH in endemic schistosomal hepatosplenomegaly.

Acid content and bacterial flora were studied in the gastric juice of 30 patients with endemic hepatosplenomegaly and 10 normal controls. The acid content in the gastric juice was significantly low in the group of patients. Also the bacterial flora were present in larger number of patients (80%) opposite to (30%) in normal control group.

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.