[Clinical characteristics and distribution of peripheral T lymphocyte subsets in patients with schistosomal hepatic diseases in Suzhou City].

OBJECTIVE: To investigate the clinical characteristics and the distribution of peripheral blood T lymphocyte sub-sets in patients with schistosomal hepatic cirrhosis in Suzhou City. METHODS: A total of 32 inpatients with liver diseases due to advanced schistosomiasis at the Department of Infectious Diseases, The First Affiliated Hospital of Soochow University from January 2016 to January 2018 were recruited and assigned into the infection and non-infection groups according to presence of co-infections, and 20 old healthy volunteers served as controls. Venous blood samples were collected on the day of admission, and the proportions of CD4+ T cells, CD8+ T cells, regulatory T (Treg) cells and Th17 cells were detected in peripheral blood using flow cytometry. RESULTS: Most patients with liver disorders due to advanced schistosomiasis were admitted to hospital in Suzhou City because of portal hypertension-associated complications, with a high prevalence of co-infections (59.38%, 19/32). The proportions of peripheral CD4+ and CD8+ T cells and Th17 cells were all significantly lower in patients with liver disorders due to advanced schistosomiasis than in controls (t = -5.111, -4.470 and -2.749, all P < 0.05), and a higher proportion of Treg cells was detected in patients than in controls (t = 5.628, P < 0.05). In addition, there were significant differences among the infection group, non-infection group and controls in terms of the percentage of CD4+ T cells, CD8+ T cells, Th17 cells and Treg cells (F = 15.837, 16.594, 9.290 and 27.866, all P < 0.05). CONCLUSIONS: Portal hypertension-associated complications are predominantly seen in patients with liver diseases due to advanced schistosomiasis at admission in Suzhou City, and co-infections are common. Imbalance of peripheral T cell subsets is detected in patients with liver diseases due to advanced schistosomiasis in Suzhou City.

Clinical and laboratory characterizations of hepatic capillariasis.

Hepatic capillariasis is a rare and neglected parasitic disease caused by infection with Capillaria hepatica in human liver. The disease is not well described and the information for the disease's clinical manifestation, laboratory findings and disease management strategy is not well reported. The limited information for this neglected infection often results in the delay of diagnosis or misdiagnosed to other diseases, therefore the real prevalence or severity of the infection may be underestimated. More case report with systemic analysis and features summary of this disease is needed to better understand the serious zoonotic disease. This study included systemic analysis of 16 patients infected with hepatic capillariasis in China between 2011-2017, including clinical manifestations, laboratory/radiative image findings and treatment results. Clinical manifestation included sustained fever (56.25%), respiratory disorder (37.5%), abdominal pain (37.5%), diarrhea (25%), leukocytosis (93.75%) and eosinophilia (100%). No egg was detected in feces of all patients. Over 60% patients showed elevated level of hepatic enzymes and proteins related to liver fibrosis in sera. Ultrasound and MRI examinations displayed scattered parasitic granuloma leisure in affected liver. Liver biopsy revealed parasite eggs, necrotized parasitic granulomas and septal fibrosis. Treatment with albendazole combined with corticoids for several treatment courses cured all patients with capillariasis. The difficulty of diagnosis, apparent damage of liver functions and potential fibrosis make the disease's prevalence and severity underestimated.

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.

Correlation between platelet count and both liver fibrosis and spleen diameter in patients with schistosomiasis mansoni.

CONTEXT: Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. OBJECTIVES: Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. METHODS: Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. RESULTS: One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. CONCLUSIONS: Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter.

Correlation beteeen platelet count and both livr fibrosis and spleen diameter in patients with schistosomiasis mansnni / Correlação entre o número de plaquetas e o grau de fibrose hepática e o tamanho do baço em pacientes com Esquistossomose mansoni

Context Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. Objectives Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. Methods Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. Results One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. Conclusions Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter. .

Contexto Estudos vem descrevendo correlação entre o número de plaquetas e o grau de fibrose hepática na hepatite viral crônica, mas poucas publicações estudaram esta correlação em pacientes com Esquistossomose mansoni. Objetivos Correlacionar a contagem de plaquetas com o padrão de fibrose periportal e com o diâmetro do baço, avaliados pela ultrassonografia em pacientes com Esquistossomose mansoni. Métodos Os pacientes com Esquistossomose mansoni foram avaliados pela ultrassonografia abdominal, por um único examinador, para determinação do padrão de fibrose periportal (classificação de Niamey) e do diâmetro do baço. A contagem de plaquetas foi realizada em contador automatizado. Resultados Cento e oitenta e sete pacientes com Esquistossomose mansoni com média de idade de 50,2 anos foram incluídos no estudo, 114 (61%) dos quais eram mulheres. De acordo com a classificação de Niamey, a ultrassonografia revelou que 37, 64, 64 e 22 pacientes exibiam padrões C, D, E e F, respectivamente. Nestes quatro grupos, o número médio de plaquetas foi 264, 196, 127 e 103 x 109/L, respectivamente, e o diâmetro médio do baço foi 9,2, 11,9, 14,9 e 16,2 centímetros, respectivamente. Observou-se, portanto, redução significativa na contagem de plaquetas associada à progressão da fibrose periportal e ao aumento do tamanho do baço. Conclusões Neste estudo verificou-se que a contagem de plaquetas foi inversamente correlacionada com o padrão de fibrose periportal, como também com o diâmetro do baço nos pacientes com Esquistossomose mansoni. .

Brain MR imaging changes in patients with hepatic schistosomiasis japonicum without liver dysfunction.

BACKGROUND: The hyperintense signal on T1-weighted magnetic resonance (MR) images in the globus pallidus and substantia nigra of the brain can be found in patients with liver cirrhosis. The abnormality has been considered resulting from the manganese (Mn) deposition caused by liver failure and portal-systemic shunting. However, similar finding may also be found in hepatic schistosomiasis patients, who lack the biochemical evidence of liver dysfunction. OBJECTIVES: To describe the brain MR imaging findings in patients with hepatic schistosomiasis japonicum (HSJ) without liver dysfunction. METHODS: Brain MR and CT images of 18 patients with HSJ without liver dysfunction and 9 healthy volunteers were reviewed by two radiologists in consensus. The signal index (SI) in globus pallidus was obtained on T1-weighted images. Whole blood Mn, serum iron, serum calcium, and other laboratory tests of liver function were investigated. RESULTS: Symmetric hyperintense signal in the globus pallidus and substantia nigra was observed in 15 of 18 HSJ patients (83.3%) and in none of controls on T1 weighted imaging. No abnormal CT findings were seen in both groups. Blood Mn level in patients was significantly higher than controls (p<0.05). Significant correlations were demonstrated between blood Mn and SI (p<0.05). No significantly abnormal results of serum iron, serum calcium and other laboratory tests were shown (p>0.05). CONCLUSION: The portal-systemic shunting leading to Mn deposition may be the main cause of the basal ganglia hyperintense signal on T1-weighted MR imaging, which is a frequent finding in patients with HSJ without liver dysfunction.

Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection.

Hepcidin is one of the regulators of iron metabolism. The expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. Recent studies have indicated that serum hepcidin level is also increased in human subjects infected with Plasmodium falciparum. The mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. In this study, we determined the expression of hepcidin in livers of mice infected with Plasmodium berghei. The expression of hepcidin in the liver was upregulated and downregulated during the early and late stages of malaria infection, respectively. Inflammation and erythropoietin, rather than the iron-sensing pathway, are involved in the regulation of hepcidin expression in livers of infected mice. Meanwhile, we investigated the effect of hepcidin on the survival of mice infected with P. berghei. Treatment of malaria-infected mice with anti-hepcidin neutralizing Abs promoted the rates of parasitemia and mortality. In contrast, lentiviral vector-mediated overexpression of hepcidin improved the outcome of P. berghei infection in mice. Our data demonstrate an important role of hepcidin in modulating the course and outcome of blood-stage malaria.

Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 µg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

HBV and HCV serological markers in patients with the hepatosplenic form of mansonic schistosomiasis.

CONTEXT: Blood transfusion is one of the major risk factors for the transmission of the hepatitis B (HBV) and C (HCV) viruses. However, there are no reports describing the endoscopic transmission of these viruses in patients with the hepatosplenic form of schistosomiasis. OBJECTIVE: To estimate the prevalence of serological markers of HBV and HCV in patients with the hepatosplenic form of schistosomiasis and evaluate the possible risk factors associated with these infections. METHODS: A cross-sectional study was conducted on 230 patients with hepatosplenic form of schistosomiasis who attended a university hospital in Recife, Northeastern Brazil, from February to August 2008. The patients answered a standardized questionnaire about risk factors. Serum samples were analyzed for anti-HBc total, anti-HBs, HBsAg, and anti-HCV using enzyme-linked immunosorbent assays. Univariate analysis and multiple logistic regression were performed. RESULTS: The prevalence was 30% for anti-HBc total and/or HBsAg and 7.4% for anti-HCV. There was a higher frequency of the serological markers in females and in patients aged .50 years. A significant association was detected between the presence of anti-HCV and the receipt of six or more blood transfusions. There was no association of history and number of digestive endoscopies with the serological markers analyzed. CONCLUSIONS: We observed a higher prevalence of serological markers for HBV and a lower prevalence of anti-HCV. Our results indicate that females and patients of an advanced age are the most affected categories and that patients that received multiple transfusions are at a higher probability of HCV infection.

HBV and HCV serological markers in patients with the hepatosplenic form of mansonic schistosomiasis / Marcadores sorológicos do VHB e VHC em pacientes com esquistossomose mansônica na forma hepatoesplênica

CONTEXT: Blood transfusion is one of the major risk factors for the transmission of the hepatitis B (HBV) and C (HCV) viruses. However, there are no reports describing the endoscopic transmission of these viruses in patients with the hepatosplenic form of schistosomiasis. OBJECTIVE: To estimate the prevalence of serological markers of HBV and HCV in patients with the hepatosplenic form of schistosomiasis and evaluate the possible risk factors associated with these infections. METHODS: A cross-sectional study was conducted on 230 patients with hepatosplenic form of schistosomiasis who attended a university hospital in Recife, Northeastern Brazil, from February to August 2008. The patients answered a standardized questionnaire about risk factors. Serum samples were analyzed for anti-HBc total, anti-HBs, HBsAg, and anti-HCV using enzyme-linked immunosorbent assays. Univariate analysis and multiple logistic regression were performed. RESULTS: The prevalence was 30 percent for anti-HBc total and/or HBsAg and 7.4 percent for anti-HCV. There was a higher frequency of the serological markers in females and in patients aged .50 years. A significant association was detected between the presence of anti-HCV and the receipt of six or more blood transfusions. There was no association of history and number of digestive endoscopies with the serological markers analyzed. CONCLUSIONS: We observed a higher prevalence of serological markers for HBV and a lower prevalence of anti-HCV. Our results indicate that females and patients of an advanced age are the most affected categories and that patients that received multiple transfusions are at a higher probability of HCV infection.

CONTEXTO: A transfusão sanguínea destaca-se entre os fatores de risco implicados na transmissão dos vírus das hepatites B (VHB) e C (VHC); entretanto não há relatos da transmissão endoscópica destes vírus em pacientes com esquistossomose na forma hepatoesplênica. OBJETIVO: Estimar a prevalência dos marcadores sorológicos do VHB e VHC em pacientes com esquistossomose hepatoesplênica e avaliar os possíveis fatores de risco associados a essas infecções. MÉTODOS: Estudo do tipo transversal, com 230 pacientes com esquistossomose hepatoesplênica atendidos em um Hospital Universitário de Recife, PE, Brasil, no período de fevereiro a agosto de 2008. Os pacientes responderam a um questionário padronizado sobre os fatores de risco. Nas amostras de soro foram pesquisados o anti-HBc total, o anti-HBs, o HBsAg e o anti-VHC por ensaio imunoenzimático. As análises estatísticas utilizadas foram a univariada e a regressão logística múltipla. RESULTADOS: Encontrou-se prevalencia de 30 por cento para anti-HBc total e/ou HBsAg e 7,4 por cento para o anti-VHC. Houve maior frequencia de pacientes positivos do sexo feminino e idade .50 anos para os marcadores analisados. Verificou-se associação significativa entre a presenca do anti-HCV e a categoria de seis ou mais transfusões. Nao foi constatada associação do antecedente e numero de endoscopias digestivas com os marcadores sorologicos analisados. CONCLUSÕES: Constatou-se maior prevalência de marcadores sorológicos do VHB e menor prevalência para o anti-VHC. Evidenciou-se o sexo feminino e paciente de idade avançada como as categorias mais atingidas e maior probabilidade da infecção pelo VHC em pacientes politransfundidos.

Evaluation of the cytokines IL-10 and IL-13 as mediators in the progression of Symmers fibrosis in patients with hepatosplenic schistosomiasis mansoni.

OBJECTIVE: To investigate the serum levels of IL-10 and IL-13 in patients with hepatosplenic schistosomiasis mansoni (HSM), evaluating the role of these cytokines in the development of hepatic fibrosis. METHODS: The study was prospective and analytical, developed at the Department of Surgery, Federal University of Pernambuco, Keizo Asami Laboratory of Immunology. We studied three groups: Group I - 25 patients with hepatosplenic schistosomiasis mansoni who were not submitted to surgery; Group II - 30 individuals who underwent splenectomy and ligature of left gastric vein; Group III - 33 subjects without hepatosplenic schistosomiasis mansoni or any other disease or condition that could compromise the hepatic functional reserve. Serum concentrations of IL-10 and IL-13 were obtained through ELISA. Considering their non-parametric nature, all concentrations were analyzed by Kruskal-Wallis test, with p<0.05 used to reject the null hypothesis. RESULTS: The mean concentrations of IL-10 in ng/mL in serum were GI: 50.0 ± 59.0; GII: 38.0 ± 270; GIII: 38.0 ± 20.0. Concentrations of IL-13 in ng/mL in the serum of patients were respectively: 41.0 ± 93.0 in GI, 16.0 ± 17.0 in GII and 18.0 ± 34.0 in GIII. There was no significant difference between the mean concentrations of IL-10 and IL-13 between the study groups (p> 0.05). CONCLUSION: The mean serum concentrations of IL-10 and IL-13 were similar in all three groups, indicating that possibly the presence of these cytokines in serum is not associated with different degrees of Symmers fibrosis in patients with hepatosplenic schistosomiasis mansoni.

Avaliação das citocinas IL-10 e IL-13 como mediadores na progressão da fibrose de Symmers em portadores de esquistossomose mansônica na forma hepatoesplênica / Evaluation of the cytokines IL-10 and IL-13 as mediators in the progression of symmers fibrosis in patients with hepatosplenic schistosomiasis mansoni

OBJETIVO: Investigar os níveis de IL-10 e IL-13 no soro de portadores da esquistossomose mansônica na forma hepatoesplênica (EHE), avaliando o papel destas citocinas no desenvolvimento da fibrose hepática. MÉTODOS: O estudo foi prospectivo e analítico, desenvolvido no Departamento de Cirurgia da Universidade Federal de Pernambuco, Laboratório de Imunologia Keizo Asami. Foram estudados três grupos: Grupo I - 25 portadores de esquistossomose mansônica na forma hepatoesplênica e não submetidos a tratamento cirúrgico; Grupo II - 30 submetidos à esplenectomia e ligadura da veia gástrica esquerda; Grupo III - 33 indivíduos sem esquistossomose mansônica na forma hepatoesplênica ou qualquer outra doença ou agravo que comprometesse a reserva funcional hepática. As concentrações séricas de IL-10 e IL-13 foram obtidas pelo método ELISA. Considerando-se a natureza não paramétrica, todas as concentrações foram analisadas pelo teste de Kruskal-Wallis. p<0,05 foi usado para rejeição da hipótese de nulidade. RESULTADOS: As médias das concentrações de IL-10, em ng/mL, no soro foram: GI 50,0 ± 59,0; GII 38,0 ± 270; GIII 38,0 ± 20,0. As concentrações de IL-13, em ng/mL, no soro dos pacientes foram respectivamente: GI 41,0 ± 93,0; GII 16,0 ± 17,0; GIII 18,0 ± 34,0. Não se observou diferença significante entre as médias das concentrações de IL-10 e IL-13 entre os grupos de estudo (p>0,05). CONCLUSÃO: As médias das concentrações séricas de IL-10 e IL-13 foram similares nos três grupos estudados, indicando que, possivelmente, estas citocinas no soro não estejam associadas aos diferentes graus de fibrose de Symmers nos pacientes.

OBJECTIVE: To investigate the serum levels of IL-10 and IL-13 in patients with hepatosplenic schistosomiasis mansoni (HSM), evaluating the role of these cytokines in the development of hepatic fibrosis. METHODS: The study was prospective and analytical, developed at the Department of Surgery, Federal University of Pernambuco, Keizo Asami Laboratory of Immunology. We studied three groups: Group I - 25 patients with hepatosplenic schistosomiasis mansoni who were not submitted to surgery; Group II - 30 individuals who underwent splenectomy and ligature of left gastric vein; Group III - 33 subjects without hepatosplenic schistosomiasis mansoni or any other disease or condition that could compromise the hepatic functional reserve. Serum concentrations of IL-10 and IL-13 were obtained through ELISA. Considering their non-parametric nature, all concentrations were analyzed by Kruskal-Wallis test, with p<0.05 used to reject the null hypothesis. RESULTS: The mean concentrations of IL-10 in ng/mL in serum were GI: 50.0 ± 59.0; GII: 38.0 ± 270; GIII: 38.0 ± 20.0. Concentrations of IL-13 in ng/mL in the serum of patients were respectively: 41.0 ± 93.0 in GI, 16.0 ± 17.0 in GII and 18.0 ± 34.0 in GIII. There was no significant difference between the mean concentrations of IL-10 and IL-13 between the study groups (p> 0.05). CONCLUSION: The mean serum concentrations of IL-10 and IL-13 were similar in all three groups, indicating that possibly the presence of these cytokines in serum is not associated with different degrees of Symmers fibrosis in patients with hepatosplenic schistosomiasis mansoni.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients.

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-ã, TNF-á and TGF-â, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, ã-glutamil transferase (ã-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-á (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), ã-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

[Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis]. / Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61%). Ten patients (24%) from 41 showed serum globulins levels raised and 21 (51%) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0.047), as well as those who showed standards D and E as compared to C (P = 0.011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica / Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

CONTEXTO: Tem sido descrita correlação entre os níveis séricos de globulinas e o grau de fibrose hepática nas hepatites crônicas, mas não se encontram relatos na esquistossomose mansônica. OBJETIVO: Avaliar os níveis séricos de globulinas e de IgG, e a intensidade da fibrose periportal mensurada pela ultrassonografia em pacientes com esquistossomose mansônica. MÉTODOS: Entre novembro de 2006 e fevereiro de 2007, foram estudados 41 pacientes que preencheram ficha clínica e realizaram dosagens de IgG por imunoturbidimetria e de globulinas indiretamente pelo método do biureto. A ultrassonografia foi realizada por um único pesquisador, seguindo os protocolos do Cairo e de Niamey. RESULTADOS: A média de idade foi 41 anos, sendo 25 pacientes (61 por cento) do sexo feminino. Dez dos 41 pacientes (24 por cento) apresentaram elevação dos níveis séricos de globulinas e 21 (51 por cento) dos de IgG. Conforme a classificação do Cairo, 21 pacientes apresentaram grau I de fibrose, 18 grau II e 2 grau III, e pela classificação de Niamey 8 apresentavam padrão C, 20 D e 13 E. Aqueles com graus II ou III de fibrose tiveram maiores níveis de IgG do que os de grau I (P = 0,047), assim como aqueles que apresentaram padrões D e E em relação ao C (P = 0,011). Não houve associação entre os níveis de globulinas e o grau ou padrão de fibrose. CONCLUSÃO: Em pacientes com esquistossomose mansônica, observou-se elevação dos níveis séricos de IgG de acordo com a progressão do grau e do padrão de fibrose periportal, mas o mesmo não se observou com os níveis de globulinas.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61 percent). Ten patients (24 percent) from 41 showed serum globulins levels raised and 21 (51 percent) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0,047), as well as those who showed standards D and E as compared to C (P = 0,011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Platelet function and the von Willebrand factor antigen in the hepatosplenic form of schistosomiasis mansoni.

Forty-five individuals with hepatosplenic schistosomiasis mansoni were studied with the aim of measuring levels of von Willebrand factor antigen (vWF:Ag), detecting abnormalities in platelet morphology and aggregation, and identifying changes to surface antigens. Haemograms, platelet aggregation tests, flow cytometry investigations of CD41/CD42b antibody and vWF:Ag assays were performed. Mean platelet counts were low (77,522/mm3) and 82.2% of patients presented thrombocytopenia. An inverse relationship between spleen size and platelet count was seen. Macroplatelets were found in 57.1% of patients, indicating good bone-marrow response, but were insufficient to compensate for the decrease in platelets due to splenomegaly. Decreased or absent platelet aggregation was seen in 50% of patients, probably due to low platelet counts. Markers for GPIIb/IIIa were normal in more than 90% of patients, not supporting the increased capture and destruction of platelets in the spleen that is hypothesized to occur with cirrhosis. Similar to cirrhosis, vWF:Ag levels were high or very high in 70.5% of patients. High levels of vWF:Ag were associated with platelet counts <100,000/mm3, larger spleen diameter and oesophageal varices. In conclusion, hepatosplenic schistosomiasis leads to a lower platelet count due to pooling in the spleen and, consequently, impaired aggregation, but not to increased capture and destruction of platelets in the spleen. High vWF:Ag levels probably promote stabilization of platelet microaggregates and prevent minor manifestations of thrombocytopenia such as petechiae, ecchymosis and gingival bleeding.

[Haptoglobin, serum amyloid-a and ceruloplasmin concentrations in goats with mixed helminth infection]. / Miks Helmint Enfeksiyonlu Keçilerde Haptoglobin, Serum Amiloid-A ve Seruloplazmin Konsantrasyonlari.

In this study, the concentrations of haptoglobin, serum amyloid A and ceruloplasmin were measured in goats with mixed gastrointestinal infections of nematodes and liver trematodes. Twelve patients who were diagnosed as having mixed helminth infection after detection of Trichuris spp., Trichostrongylidae spp. and Fasciola spp. and six healthy controls participated in the study. The concentrations of the acute phase proteins (haptoglobin p< or =0.001; serum amyloid-A p< or =0.05) were significantly higher in the goats with mixed gastrointestinal infection with nematodes and liver trematodes than the control goats. As a result of this study, we determined that the concentrations of haptoglobin and serum amyloid-A increased in goats with mixed helminth infection but further studies of the clinical importance of those increases in relation to prognosis and monitoring therapy of helminthic infections in goats should be made.

Protective effect and granuloma down-modulation promoted by RP44 antigen a fructose 1,6 bisphosphate aldolase of Schistosoma mansoni.

A Schistosoma mansoni adult worm cDNA expression library was screened using rabbit IgG against PIII, an adult worm protein fraction, already known to possess protective and immunomodulating effects to a challenge infection in mice. A positive cDNA clone was selected and characterized. The cDNA screened encodes a protein (P44) with an ORF of 1089 bp and an amino acid sequence of 363 residues with a predictable molecular weight of 44 kDa. The P44 amino acid sequence exhibits 100% identity to the fructose 1,6 bisphosphate aldolase of S. mansoni, 66% to Homo sapiens and 66% to Mus musculus. The cDNA was cloned into a pGEX-4T-3 vector and expressed in Escherichia coli as a fusion protein (GST/P44). Mice vaccinated with recombinant P44 were able to develop high levels of IgG or IgG1 and displayed low levels of IgG2a isotype. Moreover, immunization of mice with this antigen induced a significant protection of 57% against a challenge infection and significant decrease in hepatic granuloma formation. Our results demonstrate that granuloma modulation can be targeted for pathology elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.