Degree Of Periportal Fibrosis Research Articles

Advances in the Study of Schistosomiasis: The Postgenomic Era

Schistosomiasis remains a serious public health problem in 76 countries and territories of the world, with more than 200 million individuals infected, causing annual losses of 10.4 million in DALYs (disability adjusted to life years). Although effective drugs against schistosomiasis are used in disease control programs, the prevalence of the disease remains unaltered, and new diseases foci and acute outbreaks are observed worldwide. Also, drug resistance by the parasites is a concern, and new drugs and alternative control measures need to be developed. An effective vaccine against schistosomiasis is an alternative and desirable tool to help in the disease control; however, the complex schistosome life cycle and the complexity of its interaction with the host immune system turn vaccine development into a difficult task. Neither drug development nor vaccine development is sufficient to ensure the success of schistosomiasis control programs. As a matter of fact, the combination of an effective vaccine together with chemotherapy is the strategy of choice. Many studies also demonstrate that without a more sensitive diagnosis test, able to detect individuals with low parasite burden, no control strategy will achieve the desirable result which nowadays is diseases elimination. The access to the genome from Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium recently published is expected to increase rapidly our understanding of the parasite biology and also accelerate the development of new drugs, vaccine, and diagnosis methods by helping in the identification of new targets. In this special issue, a review by C. T. Fonseca et al. gives an update on how parasite genomes together with bioinformatics tools have helped in vaccine and diagnosis development in the last few years. Since the parasite surface represents an interesting target for the host immune system, this review was focused on parasite tegument as a source of antigens. Although the genome from the three most socioeconomically important schistosome species had already been published, many questions continue to challenge researchers. The review by L. A. Nahum and coworkers discusses the advances on schistosome genomics and transcriptomics studies and point out the gaps and future directions in this research field. An example on how parasite genome database helps in understanding the parasite biology is presented in the paper by R. V. Pereira and colleagues. In their article, using in silico analysis, they identified in the S. mansoni genome orthologs of the mammalian Sentrin/SUMO-specific proteases (SENPs) 1 and 7, which are involved in many cellular processes. The S. mansoni SENPs transcriptional profile as well as its structural conservation was analyzed. Just as important as understanding the biology of the parasite is deciphering how the host immune system deals with schistosome infection and its relation to the pathogenesis of the disease. Clinically schistosomiasis is characterized by two distinct phases: the acute and the chronic phase. The acute phase is commonly observed in individuals living in nonendemic area, while chronic phase is observed in endemic-area residents. D. Silveira-Lemos et al. evaluated in their article immunological parameters in patients with acute schistosomiasis before and after praziquantel treatment. Interesting differences are demonstrated by the authors between noninfected, acute, and treated group, and a role for CD8+ T cells as a source of cytokines in acute patients is pointed by this study. The cytokine and chemokine profile observed in PBMCs from individuals infected with S. mansoni in response to specific stimulation and its correlation with different degrees of periportal fibrosis is described by R. P. de Souza and colleagues in their research article. Their results indicate potential biomarkers for the progression of liver pathology due to schistosomiasis. Many schistosome antigens have been described to modulate inflammatory diseases such as asthma. A. M. B. Bafica et al. evaluated in their article the impact of the S. mansoni antigens: Sm29, TSP-2, and PIII in PBMCs culture from cutaneous leishmaniasis patients stimulated with L. braziliensis antigen. Their results demonstrated that schistosome antigens induce a modulatory phenotype with decreased monocyte activation and increased expression of T-lymphocyte modulatory molecules. Trichobilharzia spp. infection results in bird schistosomiases, which causes severe pathogenic impact in birds and frequently results in cercarial dermatitis in humans. In their article, L. Lucie and H. Petr review the pathogenesis of bird schistosomiasis and the immune response triggered by Trichobilharzia spp. infection with emphasis on the new species T. regent. We hope you enjoy reading this special issue! Cristina Toscano Fonseca Sergio Costa Oliveira Andrea Teixeira-Carvalho Rashika El Ridi

P017 Cytokine profile expressed by monocytes of schistosomiasis patients with different degrees of periportal fibrosis

Introduction Approximately 5–10% of individuals infected with Schistosoma mansoni progress to periportal fibrosis. This pathology is predominantly caused by the host immune response to parasite egg antigens, however the mechanisms is not well understood. The aim of this study was to characterize the cytokine profile expressed by monocytes inschistosomiasis patients with different degrees of periportal fibrosis. Methods Twenty-seven patients have been enrolled in the study to date. Periportal fibrosis was classified using abdominal USG according to the WHO. Monocytes were obtained from PBMC and classified into classical (CD14 ++ CD16 − ), intermediate (CD14 ++ CD16 + ) and non-classical (CD14 + CD16 ++ ). Cytokine expression was evaluated using flow cytometry. Results In general, we observed a high frequency of classical monocytes in patients, and the expression of IL-12 was quite similar in monocytes from patients with different degrees of periportal fibrosis. However, we observed a higher expression of TNF in intermediate (mean ± SD of MIF = 269.3 ± 152.6) and non-classical (77.9 ± 28.8 MIF) monocytes from patients with moderate to severe fibrosis, compared to patients without fibrosis (84.8 ± 38.4 and 61.2 ± 33.4 MIF to intermediate and non-classical, respectively). Moreover, there was a higher expression of IL-6 from monocytes (74.3 ± 27.5 MIF in classical, 142.4 ± 63.1 in intermediate and 98.9 ± 50.4 in non-classical) of patients with moderate to severe fibrosis in comparison to those without fibrosis (15.1 ± 9.4, 21.6 ± 15.1 and 11.9 ± 9.0 MIF, in classical, intermediate and non-classical, respectively). There was also a higher expression of TGF-beta in all monocytes of patients with periportal fibrosis in relation to patients without fibrosis. Unexpectedly, the expression of IL-10 as well as of IL-10R was higher in classical (119.2 ± 15.8 MIF and 69.1 ± 15, respectively) and intermediate (170.5 ± 27.4 MIF and 134.2 ± 45.8, respectively) monocytes of patients with moderate to severe fibrosis, compared to patients without fibrosis (IL-10 = 65.4 ± 46.9 and 100 ± 72.2 MIF in classical and intermediate monocytes, respectively and IL-10R = 62.3 ± 17.9 and 111.3 ± 48.3 MIF in classical and intermediate monocytes, respectively). Conclusion In schistosomiasis patients with moderate to severe periportal fibrosis, monocytes are characterized by a high expression of proinflammatory and profibrotic cytokines such as TNF, IL-6 and TGF-beta, despite the elevated expression of the regulatory molecules IL-10 and IL-10R in these monocytes. Financial support: MCT/CNPq Universal No. 482113/2010-3.

Cytokine and Chemokine Profile in Individuals with Different Degrees of Periportal Fibrosis due toSchistosoma mansoniInfection

Periportal fibrosis in schistosomiasis has been associated to the host immune response to parasite antigens. We evaluated the immune response in S. mansoni infected individuals with different degrees of periportal fibrosis. Cytokine and chemokines were measured in serum and in supernatants of PBMC cultures stimulated with the soluble adult worm (SWAP) or egg (SEA) antigens, using a sandwich ELISA. The levels of IL-5 in response to SEA were higher in individuals with moderate to severe fibrosis (310.9 pg/mL) compared to individuals without fibrosis (36.8 pg/mL; P = 0.0418). There was also a higher production of TNF-α in cultures stimulated with SWAP in patients with insipient fibrosis (1446 pg/mL) compared to those without fibrosis (756.1 pg/mL; P = 0.0319). The serum levels of IL-13 and MIP-1α were higher in subjects without fibrosis than in those with moderate to severe fibrosis. However a positive association between serum levels of IL-13, TNF-α, MIP-1α, and RANTES and S. mansoni parasite burden was found. From these data we conclude that IL-5 and TNF-α may participate in liver pathology in schistosomiasis. The positive association between IL-13, TNF-α, MIP-1α, and RANTES with parasite burden, however, might predict the development of liver pathology.

Peso do baço como fator prognóstico do tratamento cirúrgico de pacientes portadores de esquistossomose mansônica

OBJETIVO: Analisar pré-operatoriamente o peso do baço como fator prognóstico do tratamento cirúrgico de pacientes portadores de esquistossomose mansônica. MÉTODOS: Foram analisados 114 pacientes, portadores de esquistossomose mansônica com antecedentes de hemorragia digestiva, submetidos a tratamento cirúrgico. Os pacientes foram divididos em três grupos: Grupo 1 - baço menor que 500 gramas (17); Grupo 2 - baço entre 500 e 1.000 gramas (58); Grupo 3 - baço acima de 1.000 gramas (39). RESULTADOS: No Grupo 1 a recidiva hemorrágica foi de 17,6%, trombose da veia porta de 5,9% e não houve mortalidade. A incidência de hiperesplenismo pré-operatório foi de 29,4% e o calibre da veia porta foi de 1,1cm. No Grupo 2 a recidiva hemorrágica foi de 15,5%, trombose da veia porta de 10,3% e a mortalidade de quatro pacientes (6,9%) (dois pacientes no período pós-operatório e dois no seguimento tardio, hepatocarcinoma e hemorragia digestiva). A incidência de hiperesplenismo foi de 53,4% e o calibre médio da veia porta foi de 1,4cm. No Grupo 3 a recidiva hemorrágica foi de 12,8%, trombose da veia porta de 5,1% e uma mortalidade tardia de dois pacientes (linfoma e infarto agudo do miocárdio). A incidência de hiperesplenismo foi de 76,9% e o calibre da veia porta foi de 1,5cm. CONCLUSÕES: O peso do baço apresenta relação com o hiperesplenismo pré-operatório, calibre da veia porta e permanência hospitalar pós-operatória. Não encontramos relação com a incidência de varizes de fundo gástrico, recidiva de sangramento digestivo, trombose da veia porta, grau de fibrose periportal e dados bioquímicos.

Use of ultrasound in a study of schistosomal periportal fibrosis in rural Zimbabwe

Ultrasound was used to diagnose periportal fibrosis (PPF) in a rural Zimbabwean community where Schistosoma mansoni is endemic. Ultrasound findings were compared with stool microscopy and abdominal palpation in 492 adults (305 females). 47 (9.6%) had definite PPF. The prevalence of PPF increased with age ( P<0.001), while S. mansoni egg counts decreased with age. Even within age groups, egg count did not correlate with PPF. No association was found between lifetime alcohol consumption and the presence of PPF. Splenomegaly and mid-line enlargement of the liver were specific (97% and 94%) but insensitive (21% and 28%) markers for PPF. Spleen size varied with S. mansoni egg count independently of the presence or degree of PPF. Endoscopy of 18 patients with PPF revealed oesophageal varices in two, both of whom had severe PPF.

Sonographic changes following splenectomy for portal hypertension in Schistosoma mansoni.

Eleven patients with portal hypertension due to infection with Schistosoma mansoni underwent splenectomy and devascularization operations. The patients were examined with ultrasound once preoperatively and twice postoperatively over a period of about 6 months. Following surgery there was significant and sequential reduction in the diameter of the portal vein at the hilum and the splenic vein at the pancreas. The liver lengths and index of liver size did not change significantly. No changes in the degree of periportal fibrosis could be detected.

Ultrasonographic changes of the liver in Schistosoma haematobium infection.

Abdominal ultrasonographic examination was performed in 61 hospitalized patients with chronic liver diseases and 253 school children from a village endemic for Schistosoma haematobium and were compared with 142 urban children without exposure to Schistosoma. The prevalence of ultrasound-detectable hepatomegaly and splenomegaly and the degree of periportal fibrosis was compared between those with and without S. haematobium infection. Among 13 patients with biopsy-proven schistosomal hepatic fibrosis, three with coarse changes secondary to S. mansoni infection showed grade III periportal fibrosis, while 10 patients with fine schistosomal hepatic fibrosis due to S. haematobium had borderline (two) or grade I (eight) changes. Ultrasound evidence of periportal fibrosis was not detected in patients with hepatic cirrhosis, chronic active hepatitis, or fatty infiltration. However, three of 14 patients with chronic persistent hepatitis had grade I periportal fibrosis and two had borderline changes. The frequency of ultrasound-detected hepatomegaly and splenomegaly was greater among rural S. haematobium-infected children (35.2% and 22.4%, respectively) than among noninfected rural (21.1% and 13.3%) and urban (16.9% and 4.9%) children. Also, the frequency of grade I periportal fibrosis was significantly greater (P less than 0.01) in S. haematobium-infected children (22.4%) than in noninfected rural (11.7%) and urban (0.7%) children. No patients with S. haematobium infections, either in the hospital or the village, had grade II or III periportal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of ultrasonography in assessment of portal hypertension in hepatosplenic schistosomiasis.

Ultrasonography can reveal most of the manifestations of portal hypertension complicating hepatosplenic schistosomiasis. However, direct demonstration of gastroesophageal varices by ultrasonography is still very difficult. An attempt was done to correlate sonographic features of portal hypertension with the degree of fibrosis to screen patients having varices and predicting their chance of bleeding. The results obtained were found to be consistent with the esophagogastric endoscopy and with history of hematemesis. Four parameters were used, size of spleen, degree of periportal fibrosis, presence of collaterals and portal vein diameter. A pilot field survey was also done adopting the same principle.

Paracetamol pharmacokinetics in patients with hepatosplenic schistosomiasis

Plasma concentrations and AUCs of paracetamol 1.5 g in patients with schistosomiasis and various degrees of periportal fibrosis were greater than in control subjects. As the toxic metabolite of paracetamol is a product of oxidation and as oxidative capacity is possibly reduced in patients with schistosomiasis, they may be less likely to exhibit paracetamol toxicity.

An epidemic of deaths attributed to fatty liver in Baltimore

Death rates due to cirrhosis of the liver have increased substantially in the past 20 years. Previous studies have noted that sudden deaths in which a fatty liver was the major pathological finding accounted for a large part of the increase in death rates. The current study of sudden nontraumatic deaths in Baltimore noted that 40% of the “cirrhosis” deaths were sudden. Fatty liver sudden deaths accounted for 25% of the total nontraumatic sudden deaths. Cirrhosis and fatty liver death rates were much higher in men than women and in blacks as compared to whites. Most fatty liver sudden deaths were unwitnessed. The majority of those dying did not have high blood alcohol levels. At postmortem examination, the liver was usually enlarged. Microscopic examination revealed extensive fatty change often with increased eosinophilia of hepatocytes and the presence of Mallory bodies in about 20%. In about half of the fatty liver sudden deaths there was also some degree of periportal fibrosis.