Pathological changes of liver in infection of Fasciola hepatica

Pathological changes of liver in infection of Fasciola hepatica. Fasciolosis caused by Fasciola hepatica is a hepatic parasitic infection that affects numerous mammal species, mainly ruminants, in several countries of Europe, Asia and America. The economic significance of fasciolosis is mainly due to direct losses caused by a decrease of weight rate, milking capacity and the confiscation of altered livers in slaughterhouse. In this review we present mechanisms of damaging of host liver during invasion of Fasciola hepatica. Parasites digest hepatic tissue and cause extensive parenchymal destruction with intensive haemorrhagic lesions and immunological reactions. Mechanical liver damage is due to migrating juvenile fluke. Macerated hepatic cells have been observed inside the oral sucker and pharynx. Moreover, the process of ulceration of liver tissue was observed in regions adjacent to the spiny body of fluke tegument. On the other hand, the injury of the liver can be induced chemically by factors produced or induced by the fluke. Probably, fluke proteases and other tissue-degrading enzymes can be responsible for negative effect on liver parenchyma. There is no evidence to link fluke-enzymes with tissue penetration. The consequences of liver damage resulting from the migrating flukes compromises liver function which is reflected in changes of plasma protein concentration (albumin, globulin). Additianally, changes of levels of hepatic enzymes released into the blood as a result of damage of liver tissue are used to monitor the progress of the infection in a variety of Fasciola hepatica hosts and as a sensitive diagnostic aid in field infection.     

Fasciola hepatica infection downregulates Th1 responses in mice

Immune responses induced with helminth parasites have been extensively studied, but there is limited information on those to Fasciola hepatica, especially on the subtype of T cell induced with this parasite. We investigated the local and systemic T cell responses of different strains of mice following oral infection with doses of metacercariae from F. hepatica. Spleen cells from BALB/c and 129Sv/Ev mice given a low-dose (5 metacercariae) infection exhibited a Th2 response, producing high levels of the cytokines IL-4 and IL-5, and low levels of IFN-gamma and IL-2. In contrast, C57BL/6 mice showed a mixed Th1/Th2 response. A more marked polarization to a Th2 response was observed in BALB/c, 129Sv/Ev exposed to a high-dose (15 metacercariae) infection and the C57BL/6 mice also exhibited a clear Th2 response. IL-4 defective (IL-4-/-) C57BL/6 mice infected with 5 metacercariae produced less IFN-gamma and more IL-5 compared to their wild-type C57BL/6 counterparts, suggesting that IL-4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN-gamma and IL-2 was completely suppressed in the high-dose infection and this was also observed in IL-4-/- mice. Thus, liver flukes may secrete molecules that downregulate Th1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nodes (HLN) were also examined since newly excysted juveniles infect through the intestinal wall of their host before migrating to the hepatic tissue. Cells from both MLN and HLN secreted higher levels of IL-4 and IL-5 compared to spleen cells. We also observed a difference in cytokine profiles secreted by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.     

Increased anti-Echinococcus granulosus antibody positivity in Fasciola hepatica infection

Background/aims: Parasitic helminths express some antigen, which often accounts for serological cross-reactions. The aim of this study was to determine the prevalence of antiEchinococcus granulosus antibody in patients with Fasciola hepatica infection using indirect immunofluorescence assay. Materials and Methods: The study population consisted of the following groups: Fasciola hepatica group (n=22), hydatid disease group (n=22) and healthy control group (n=24). Indirect immunofluorescence assay for Echinococcus granulosus was performed in all groups. Results: Indirect immunofluorescence assay was positive in all patients with hydatid disease, in 13 of 22 (59%) patients with fascioliasis and in 2 of 24 (8%) healthy subjects. The positivity rate of indirect immunofluorescence assay was significantly higher in the hydatid disease group compared to the fascioliasis group (p<0.001) and compared to the control group (p<0.001), and it was significantly higher in the fascioliasis group compared to the control group (p=0.001). Antibody titer was 1/100 in 7 patients, 1/320 in 12 patients and 1/1000 in 3 patients with hydatid disease. Indirect immunofluorescence assay was positive in 10 of 15 patients with hepatic phase and in 3 of 7 patients with biliary phase of fascioliasis. The antibody titer was 1/100 in 6 and 1/320 in 7 patients with fascioliasis. The antibody titer was 1/100 in both healthy subjects. Conclusions: Indirect immunofluorescence assay for Echinococcus granulosus may be positive in a majority of patients with Fasciola hepatica infection and in some healthy subjects.     

人胆总管肝片形吸虫病1例

患者,女,22岁,遵义人。2019年11月无明显诱因出现上腹部阵发性绞痛,偶牵涉至肩背部,可自行缓解。于2020年3月前往遵义医科大学附属医院就诊,入院查体:体温36.6℃,脉搏75次/min,呼吸16次/min,血压112/80 mmHg(1 mmHg=0.133 kPa),全身皮肤巩膜无黄染,心肺无阳性体征,腹平软,肝脾肋下未触及,全腹无压痛。实验室检查:白细胞10.32×10⁹/L,中性粒细胞百分比0.81%,淋巴细胞1.44×10⁹/L。     

Fascioliasis in relatives of patients with Fasciola hepatica infection in Peru

High prevalence rates of human fascioliasis have been described in several regions of Peru. We surveyed 20 families in an endemic area of Peru in order to determine the proportion of infection with F. hepatica in relatives of diagnosed subjects and in order to identify associated risk factors. The study included feces and blood samples of 93 subjects. Ages ranged from one to 53 (mean = 18.6; SD = 14.2). The overall prevalence of fascioliasis by fecal examinations was 33.3% (n = 83) and by serology, 51.9% (n = 86). The prevalence in age group I (< or = 19 years old) by coprological and serological tests was 61.4% and 75.9%, respectively; in group II (> 19 years old) 15.4% and 37.5%. The main associated risk factor with fascioliasis was eating salads (OR = 3.29, CI = 1.2 - 9.0, p = 0.02). In conclusion, human fascioliasis is highly prevalent in the relatives of index cases and the most significant risk factor of acquiring fascioliasis in the family is eating salads in endemic areas.     

肝片形吸虫感染宿主细胞免疫的研究进展

肝片形吸虫病是一种危害严重的人兽共患病,肝片形吸虫主要感染反刍动物及包括人类在内的哺乳动物,是一个严重威胁健康、影响经济发展的公共卫生问题。目前治疗肝片形吸虫病的药物少、疗效有限。大量研究表明,肝片形吸虫受宿主免疫应答的调控,本文对肝片形吸虫病的发病机制、肝片形吸虫主要参与诱导的几种机体细胞免疫反应及相关的研究进展进行综述.以期为肝片形吸虫病的临床治疗提供资料。     

The immune response of various species to Fasciola hepatica infection

The trematode F. hepatica is an internal parasite of many species of animals including men. In ruminants, fasciolosis is an economically important disease often resulting in a chronic and sub-clinical infection. The mechanisms of immune responses of final hosts to this infection are still poorly understood. Experimental and clinical studies reported so far suggest that both humoral and cellular effectors of the immune response are important to control the duration of F. hepatica infection. However, there are considerable variation both inter-species and between various strains of the same species in regulation of the response as well as abilities to develop resistance to subsequent infections.     

Detection of Fasciola hepatica infection in a community located in the Ecuadorian Andes

The presence of fascioliasis was assessed in four Andean communities using an enzyme-linked immunosorbent assay (ELISA) test to measure antibodies against Fasciola hepatica excretion-secretion antigens. Six percent (9 out of 150) of the individuals in one community were ELISA-positive for these antibodies. Fecal samples from two of the ELISA-positive individuals contained F. hepatica ova. All of the ELISA-positive cases, except for one, were children within the ages of 9 to 12 years.     

Fasciola hepatica: rapid switching of stage-specific antigen expression after infection

Early developmental stages of the trematode parasite Fasciola hepatica were collected from the peritoneal cavity and liver of mice during a ten day infection period. Using one dimensional SDS-PAGE, differences in protein expression profiles were observed in stages collected on the same day post-infection in different physiological locations and also in juvenile parasites collected from the same location on different days post-infection. Four rat monoclonal antibodies were raised against the parasite using lymph nodes draining infected tissues. Three monoclonal antibodies, FY3-1, FY3-2 and FY4-7, were generated using cells from the mesenteric lymph node of recently challenged immune rats, while FY1-6 was derived from hepatic lymph node cells of a chronically infected rat. The epitope recognized by FY3-2 appeared to be carbohydrate in nature and was present on the surface of newly excysted juveniles. Immunoblots revealed that the antigens recognized by FY3-1, FY3-2 and FY4-7 were only expressed for two days after infection. In contrast, FY1-6 recognized epitopes expressed across all developmental stages screened. The rapid changes in protein and antigen expression observed during the early stages of infection may assist the parasite to evade the host immune response.     

Imported Fasciola hepatica infection in the United States and treatment with triclabendazole.

Infection with Fasciola hepatica, a liver trematode, is not frequently reported in the United States. We describe 2 patients, both originally from Cape Verde, who illustrate the spectrum of clinical presentations of F. hepatica as well as the means of treating infection with this parasite. Patient 1 had extensive disease and underwent multiple diagnostic procedures before the correct diagnosis was reached. Patient 2, who had few symptoms, had fascioliasis diagnosed by a noninvasive evaluation. Both patients were treated with triclabendazole without experiencing significant side effects. Fascioliasis that has been imported to the United States may elude prompt or accurate diagnosis. Obtaining a detailed travel history and recognizing the clinical presentation early in the course of infection may permit timely and noninvasive identification of infection. Triclabendazole is now the recommended drug for treating for fascioliasis because of its efficacy, safety, and ease of use.     

Clinical presentation and management of Fasciola hepatica infection: single-center experience

AIM:To identify the characteristic clinical,laboratory and radiological findings and response to treatment in patients with fascioliasis.METHODS:Patients who were diagnosed with Fasciola hepatica infection were included in this prospective study.Initial clinical,laboratory and radiological findings were recorded.All patients were followed until a complete response was achieved or for 6 mo after treatment discontinuation.RESULTS:Fasciola hepatica infection was diagnosed in 30 patients(24 females;mean age:42....     

Praziquantel failure in the treatment of Fasciola hepatica

A case of human fascioliasis is presented in which the patient remained symptomatic after treatment with praziquantel and other agents but eventually responded to bithionol. The difficulties in finding an efficacious and tolerable drug therapy for this condition are reviewed with reference to the life cycle and pathogenesis of the parasite. It is concluded that while bithionol remains the current drug of choice, triclabendazole may play a dominant role in the near future.     

T cell subset involvement in immune responses to Fasciola hepatica infection in cattle

The lymphocyte response to F. hepatica during a primary infection in cattle was analysed to define the role of T cell subsets in the immune response. Blood lymphocytes were isolated from eight cattle infected with F. hepatica via trickle infection over a ten-day period and from two non-infected controls. CD4+, CD8+ and gamma delta + T cells were depleted from whole lymphocyte populations by magnetic bead depletion. Lymphocytes from infected animals demonstrated a transient, but marked elevation in responsiveness to F. hepatica antigen between weeks 3 and 8 post-infection. Responses were attenuated by depletion of CD4+ and CD8+ T cells during this period. Depletion of gamma delta + T cells attenuated antigen responses at one time point only, and at an earlier stage post-infection than when alpha beta + T cells were depleted. Responses to antigen correlated positively with both hepatic fluke burden and with the degree of hepatic damage. This suggests that the cellular immune response was not protective. Antigen responses in gamma delta + T cell-depleted populations were also associated with post-mortem fluke burden and with hepatic damage. This suggests that gamma delta + T cells are involved in down regulating alpha beta + lymphocytes which may have a role in a non-protective or immunopathological immune responses.     

Fasciola hepatica in the rat: immune responses associated with the development of resistance to infection

F. hepatica infections were established in rats and immune responses were monitored during primary and challenge infections. Antibody levels peaked at 3 weeks post-primary infection and at 6 days post-challenge infection. No significant correlation was found between antibody titre and number of flukes recovered at autopsy. Immunoblotting revealed a limited number of immunogenic polypeptides. When antibodies from these reactive bands were eluted and tested by IFA they all gave identical binding patterns: on juvenile fluke sections tegumental syncytium, tegumental cells and gut cells were labelled, while on adult sections the same antibodies labelled gut cells, reproductive tissue, excretory ducts and flame cells. This suggested that these tissues shared a common epitope or range of epitopes. A pronounced eosinophilia was observed throughout the infection period studied and infected liver sections showed massive cellular infiltration. Histochemical and immunocytochemical investigation of infected liver revealed the presence of large numbers of eosinophils, neutrophils, lymphocytes and phagocytes. The implications of these findings, to an understanding of concomitant immunity in the rat are discussed.     

Immunoprecipitation of Fasciola hepatica mRNA in vitro translation products using infection and hyperimmune sera

Total RNA containing messenger RNA has been isolated from adult Fasciola hepatica and translated in vitro using the rabbit reticulocyte lysate system. L-[35S]-methionine labeled translation products have been immunoprecipitated with sera collected from rabbits infected with F. hepatica, rabbits immunized with adult worm homogenate, and a rabbit and 5 calves immunized with a Fasciola/Schistosoma cross-reactive, cross-protective antigen, denoted FhSmIII(M). Precipitated antigens were analyzed by SDS-polyacrylamide gel electrophoresis. The major antigens recognized by hyperimmune sera had apparent molecular weights of 12,500, 13,500, 14,000, 26,500, and 27,000. The rabbit anti-FhSmIII(M) serum precipitated a 13,500 Mr antigen. Sera collected from calves immunized with FhSmIII(M) also precipitated a 13,500 Mr antigen together with a 26,500 Mr molecule. Antibody with specificity for F. hepatica mRNA translation products could be detected in rabbit serum 2 weeks after infection.