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 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. .

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.

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.

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.

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.

The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection.

Schistosomiasis is a chronic parasitic infection with over 200 million people infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get trapped in the liver, causing the formation of granulomas, which may develop into periportal fibrosis and portal hypertension, and thus severe morbidity. Eosinophil cationic protein (ECP) is a secretory protein of eosinophil granulocytes that efficiently kills the larval stage of S. mansoni, but also affects fibroblast functions. We have investigated the prevalence of the ECP gene polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area in Uganda (n=297) and from a non-endemic area in Sudan (n=78), and also compared these with a Swedish population (n=209). The genotype frequencies in the Ugandan population differed significantly from both the Sudanese and Swedish populations (P<0.001). In the Ugandan population there was a significant association between genotype and prevalence of infection (P=0.03), with lower prevalence in subjects with the GG genotype compared with GC (P=0.02) and CC (P=0.03). There was also a trend towards an association with periportal fibrosis (P=0.08) in the Ugandan population. This suggested association was confirmed when the predominant tribe (n=212) was analysed separately (P=0.004). Our results suggest that ECP may be an important protein, both in the immune response against S. mansoni and in the development of periportal fibrosis. The results also suggest genetic selection towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

Alteraciones hepáticas en la Leishmaniasis Visceral (Kalazar) en niños: revisión sistemática de la literatura / Liver injury in visceral Leishmaniasis in Children: systematic review

La Leishmaniasis Visceral o Kalazar es una infección parasitaria causada por subespecies del género Leishmania donovani y transmitida por insectos flebotomíneos. Puede evolucionar con compromiso hepático caracterizado por citólisis severa, colestasis, hipertensión portal, hepatomegalia persistente y fibrosis hepática. Estos tipos de presentaciones dificultan el diagnóstico y agravan el pronostico. Se admite que la extensión y frecuencia de este compromiso hepático han sido poco evaluados. Objetivo: Sistematizar las alteraciones hepáticas de Kalazar en la infancia descritas en relatos de casos publicados. Metodología: revisión sistemática de la literatura utilizando las bases de datos LILACS, MEDLINE y EMBASE. Se incluyeron artículos en portugués, español, inglés y francés. Se siguieron los procedimientos de revisión sistemática recomendados por el NHS Centre for Reviews and Dissemination, University of Cork. La clasificación de los artículos (relatos de casos) se basó en la cantidad de información de cada relato de caso en relación a las variables previamente sistematizadas en este estudio. Resultados: 11 (un 55%) artículos fueron incluidos abarcando 28 relatos de casos. La albúmina sérica y el tiempo de protrombina mostraron una asociación con la evolución de la enfermedad: (p = 0,05). Conclusiones: el compromiso epático, incluso grave, puede ocurrir al inicio de la enfermedad. El Kalazar debe ser considerado en el diagnóstico diferencial de hepatitis asociadas a fiebre prolongada, así como en síndromes colestásicos en la infancia en áreas endémicas para la enfermedad.

Visceral Leisshimaniosis or Kalazar is a parasitic infection caused by Leishimania Donovani subspecies. It is transmitted by phlebotomineos and may lead to liver and spleen enlargements as well as immunological impairment. Sometimes it is described liver injury simulating acute or chronic viral hepatitis and even portal hypertension. The liver injury makes difficult the diffencial diagnosis of Kalazar and other liver diseases in endemic regions. Objective: To define and clarify the liver injury spectrum described in published cases reports. Methods: Systematic revision of published data on Kalazar and liver injury, using the following databank: LILACS, MEDLINE and EMBASE. Only paper published in French, English, Portuguese and Spanish were taken into consideration. The procedures for systematic review recommended by the NHS Centre for Reviews and Dissemination, University of Cork, were adopted. The paper quality classification was based on the number of reported variables previously defined in our study. Results: Only 11/ 28 (55%) publications were includedin our analysis because they filled the minimal required data. Acute and chronic liver disease were well documented in these articles. Serum albumin and prothombine time were associated with severity of liver disease (P< .05). Conclusion: “Liver involvement, even when it is severe, may occur at tha begining of the disease. Kalazar should be considered as a differential diagnosis of cholestasis, acute and chronic liver injury, as well as portal hypertension in children.

Accelerated neutrophil apoptosis in neutropenic patients with hepatosplenic schistosomiasis is induced by serum Fas ligand.

Neutropenia in patients with hepatosplenic (HS) schistosomiasis may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from neutropenic patients with HS schistosomiasis (n = 25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n = 10), and age- and sex-matched healthy control subjects (n = 10) were examined for the degree of apoptosis after incubation with autologous sera. Neutrophil apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 time (fresh neutrophil), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Serum Fas ligand levels were assessed in sera of patient groups and healthy controls by ELISA. Compared with normal controls and HI, HS group demonstrated greater neutrophil apoptosis in the presence of autologous serum (P < 0.01, < 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates (P < 0.01). The apoptotic effect of neutropenic sera is attenuated by anti-Fas ligand. Fas expression was significantly higher in HS group as compared to both HI and normal healthy controls (P < 0.05). Serum Fas ligand levels were significantly higher among HS group as compared to both HI and control groups (P < 0.01 for both). Neutrophil apoptosis was not correlated to the size of spleen in HS group. In conclusion, the rate of neutrophil apoptosis is accelerated in neutropenic HS schistosomiasis. These findings suggest that enhanced neutrophil apoptosis demonstrated in HS patients is triggered by soluble Fas ligand, which is mostly derived from spleen.

Elevated levels of erythrocyte-conjugated dienes indicate increased lipid peroxidation in schistosomiasis mansoni patients.

Schistosoma mansoni causes liver disease by inducing granulomatous inflammation. This favors formation of reactive oxygen species, including superoxide ions, hydrogen peroxide and hydroxyl radicals all of which may induce lipid peroxidation. We have evaluated lipid peroxidation in 18 patients with hepatosplenic schistosomiasis mansoni previously treated with oxamniquine followed by splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue, by measuring levels of erythrocyte-conjugated dienes and plasma malondialdehyde (MDA). Age-matched, healthy individuals (N = 18) formed the control group. Erythrocyte-conjugated dienes were extracted with dichloromethane/methanol and quantified by UV spectrophotometry, while plasma MDA was measured by reaction with thiobarbituric acid. Patient erythrocytes contained two times more conjugated dienes than control cells (584.5 +/- 67.8 vs 271.7 +/- 20.1 micromol/l, P < 0.001), whereas the increase in plasma MDA concentration (about 10%) was not statistically significant. These elevated conjugated dienes in patients infected by S. mansoni suggest increased lipid peroxidation in cell membranes, although this was not evident when a common marker of oxidative stress, plasma MDA, was measured. Nevertheless, these two markers of lipid peroxidation, circulating MDA and erythrocyte-conjugated dienes, correlated significantly in both patient (r = 0.62; P < 0.01) and control (r = 0.57; P < 0.05) groups. Our data show that patients with schistosomiasis have abnormal lipid peroxidation, with elevated erythrocyte-conjugated dienes implying dysfunctional cell membranes, and also imply that this may be attenuated by the redox capacity of antioxidant agents, which prevent accumulation of plasma MDA.

Dexamethasone treatment improves morphological and hematological parameters in chronic experimental schistosomiasis.

Schistosomiasis, a chronic disease with considerable social impact, is an important health problem in many countries. To investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic Schistosoma mansoni infection, we evaluated the effect of dexamethasone on histological, hematological, and biochemical parameters that reflect disease severity and morbidity. Animals treated from the first day or after 35 days of infection, were analyzed. In both groups, dexamethasone: (1) induced a decrease in the number of granulomas in hepatic tissue without affecting the alanine aminotransferase profile, (2) reduced splenomegaly and hepatomegaly associated with disease, and (3) improved hemoglobin concentration, hematocrit values and reduced the percentage of reticulocytes, preventing the development of anemia that occurs in the chronic phase of infection. These data suggest that treatment with dexamethasone results in a mild course of murine schistosomiasis and point to this drug as a promising agent to complement S. mansoni specific treatment.

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hepatic dysfunction.

The aim of this study was to compare the serum cytokine profiles of Plasmodium vivax malaria patients who presented with and without hepatic dysfunction. This is a retrospective analysis of 74 consecutive cases of P. vivax malaria seen at 3 military hospitals near the Demilitarized Zone in South Korea from 1999 to 2000. All patients studied were adult active duty servicemen. On admission, the mean (+/- SEM) age of the patients who presented with (n = 36) and without hepatic dysfunction (n = 38) was 21.6 +/- 0.24 and 22.5 +/- 0.44 years, respectively (P = 0.72). On admission, there was no significant difference between the 2 patient populations in terms of mean temperature, haemoglobin level, haematocrit, total white blood cell count, platelet count, parasite index, and serum concentration of transforming growth factor-beta. Plasmodium vivax malaria patients who presented with hepatic dysfunction had significantly higher mean serum concentrations of soluble Fas ligand, interleukin (IL)-l, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma than those without hepatic dysfunction, suggesting the involvement of these cytokines in the development of hepatic dysfunction. The mean serum concentration of IL-12 was significantly lower in patients with hepatic dysfunction. The mean body temperature was not significantly different between the 2 patient populations.