The regulatory roles of Fasciola hepatica GSTO1 protein in inflammatory cytokine expression and apoptosis in murine macrophages.

Fascioliasis, a global zoonotic parasitic disease, is mainly caused by Fasciola hepatica (F. hepatica) parasitizing in the livers of hosts, mainly humans and herbivores. Glutathione S-transferase (GST) is one of the important excretory- secretory products (ESPs) from F. hepatica, however, the regulatory roles of its Omega subtype in the immunomodulatory effects remain unknown. Here, we expressed F. hepatica recombinant GSTO1 protein (rGSTO1) in Pichia pastoris and analyzed its antioxidant properties. Then, the interaction between F. hepatica rGSTO1 and RAW264.7 macrophages and its effects on inflammatory responses and cell apoptosis were further explored. The results revealed that GSTO1 of F. hepatica owned the potent ability to resist oxidative stress. F. hepatica rGSTO1 could interact with RAW264.7 macrophages and inhibit its cell viability, furthermore, it may suppress the production of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α, but promote the expression of anti-inflammatory cytokine IL-10. In addition, F. hepatica rGSTO1 may down-regulate the ratio of Bcl-2/Bax, and increase the expression of pro-apoptotic protein caspase-3, thereby eliciting the apoptosis of macrophages. Notably, F. hepatica rGSTO1 inhibited the activation of nuclear factor-κB (NF-κB) and mitogen­activated protein kinases (MAPKs p38, ERK and JNK) pathways in LPS-activated RAW264.7 cells, exerting potent modulatory effects on macrophages. These findings suggested that F. hepatica GSTO1 can modulate the host immune response, which provided new insights into the immune evasion mechanism of F. hepatica infection in host.

[A case report:the progress of fascioliasis from hepatic phase to biliary phase].

This is a case report of fascioliasis that progressed from the hepatic to the biliary phases over 2 years. A woman in her late 60s ate Zingiber mioga from the field, which was followed by abdominal pain that occurred 1 month later. Although CT and MRI studies revealed an increase in blood eosinophils as well as multiple hepatic nodules, they vanished quickly. After 2 years, an MRCP study revealed multiple flat lesions, which were diagnosed as adult fascioliasis. Definitive diagnosis was provided by enzyme-labeled antibody method using fasciola-specific antigen. Triclabendazole was administered once to complete the treatment.

Prevalence and pathology of liver fluke (Fasciola hepatica) in fallow deer (Dama dama).

A survey conducted on fallow deer (n = 79) in northern New South Wales Australia, aimed to ascertain the prevalence and gross pathology of liver fluke. In total, three deer populations were assessed (1 farmed and 2 wild) across 2 sites (site A and B) by conducting total fluke counts in the liver and fluke egg counts in faecal samples. At site A, 16 of 19 farmed deer (84.2 %) and 9 of 20 wild deer (45 %) had active or resolved infections. At site B, 16 of 40 wild deer (40 %) had active or resolved infections. Deer with active infections had low fluke burdens (1-11 fluke) which were in the adult development stage, shedding eggs with faeces (0-121.7 eggs per gram). Liver pathology score did not exceed 3.5 out of 5 with gross pathomorphological lesions predominately confined to the peripheral regions of the left lobe. Farmed deer, confined within a fluky habitat, attained the highest group mean pathology score, with dense fibrosis and concomitant atrophy of the left lobe (site A: farmed - 1.8, wild- 0.6; site B: wild - 0.3). Well-defined fibrotic capsules captured and restricted fluke migration beyond the peripheral region of the left lobe of the liver. The presence of live and dead fluke within the fibrotic capsules confirms the inherent ability of fallow deer to resolve infections. This survey has highlighted the susceptibility of fallow deer to liver fluke within an endemic region. Recurrent exposure, as seen in the farmed deer confined within a fluky habitat, appears to strengthen tissue response in terms of gross pathology and may impede the release of fluke eggs from the liver. Low fluke burdens and limited lesions suggest fallow deer have a strong level of resistance to liver fluke. Nevertheless, within this endemic region, fallow deer are widespread and clearly facilitating the liver fluke life cycle. Further research is warranted to ascertain the impact of fallow deer on disease transmission in livestock production when cohabiting the grazing environment.

Early Postnatal and Preschool-Age Infection by Fasciola spp.: Report of Five Cases from Vietnam and Worldwide Review.

Fascioliasis is reported in five Vietnamese children aged 4 years or younger. A 10-month-old girl child and a 12-month-old boy child are the youngest patients ever diagnosed. Eggs in stools suggested an infection occurred at 5-6 months and 7-8 months of age, respectively. DNA sequencing and egg size indicated this to be the first report of a verified Fasciola gigantica infection in so small children. No specific diagnosis could be obtained in two 3-year-old children detected in the acute phase. A big and gravid ectopic F. gigantica-like worm was surgically found in a 4-year-old boy presenting with peritonitis. A worldwide review showed only 38 past cases in preschool children. They included 3, 7, 12, and 16 cases of 1, 2, 3, and 4 years, respectively, with a faster infection increase in males from 2 years onward. Reports were from all continents, except Oceania, including severe complications and death. The causal agent, when specifically diagnosed, was always Fasciola hepatica. Analyses include detection in hospital, surveys, and family outbreaks; infection sources; disease phases; parasite burden; ectopic cases; symptom onset; eosinophilia; biochemical markers; and clinical complications. C-reactive protein, creatinine, and γ-glutamyl transferase are the most useful biomarkers. A serological test and a coprological analysis are recommended for so small children, in which typical symptoms may be overlooked. Treatment problems were described with many drugs, except triclabendazole. Triclabendazole should be considered the drug of choice for such small children. The possibility of a very early infection by Fasciola spp. should be henceforth considered.

Fasciola hepatica coinfection modifies the morphological and immunological features of Echinococcus granulosus cysts in cattle.

Polyparasitism occurs when animals harbour multiple parasites concomitantly. It is a common occurrence but is generally understudied in wild and domestic animals. Fasciola hepatica and Echinococcus granulosus, which are helminths of ungulates, frequently coinfect cattle. The effects of this particular type of polyparasitism are not well documented. The metacestode of Echinococcus granulosus is surrounded by the adventitial layer, which constitutes the host immune response to the parasite. This layer in cattle is produced by a granulomatous reaction and is involved in echinococcal cyst (EC) fertility. Due to the systemic immune-modulating abilities of Fasciola hepatica, coinfection possibly generates a favourable environment for EC growth. A total of 203 Echinococcus granulosus sensu stricto cysts were found in 82 cattle, of which 42 ECs were found in 31 animals coinfected with Fasciola hepatica. The overall infection intensity was 3 cysts per animal. Coinfection with Fasciola hepatica decreased the mean infection intensity to 1.4 cysts per animal. Regarding EC size, coinfection resulted in smaller ECs (15.91 vs 22.09 mm), especially for infertile lung cysts. The adventitial layer of ECs in coinfected animals lacked lymphoid follicles and palisading macrophages, which are generally hallmarks of the granulomatous immune response. The ECs in coinfected animals had organized laminated layers, whereas those in animals without coinfection did not. Although coinfection was not statistically associated with EC fertility, we did not find fertile cysts in the livers of coinfected animals. We concluded that coinfection with Fasciola hepatica and Echinococcus granulosus has a detrimental effect on ECs, particularly infertile cysts.

Characterization of dendritic cells and follicular dendritic cells in the hepatic lymph nodes and liver of sheep experimentally infected with Fasciola hepatica.

Fasciola hepatica has been shown to have a high capacity for immunomodulation of the host response, making the development of protective vaccines extremely difficult. One of these immunomodulation mechanisms is the impairment of dendritic cells (DC) maturation and, therefore, suppression of antigenic presentation. The aim of this study was to evaluate the pathological changes as well as the characterization of two antigen presenting cells, DC (CD1b, CD83 and MHC-II positive) and follicular dendritic cells (FDC) (CNA.42, S100 and CD83 positive) by immunohistochemistry in the hepatic lymph nodes (HLN) and livers of sheep during the early stages of infection with F. hepatica [9 and 18 days post-infection (dpi)], compared with an uninfected group (UC) as a control. The results revealed a marked hyperplasia of HLN germinal centres at 9 and, in particular, 18 dpi, with respect to the UC group, with coincidental increased expression of CNA.42 in FDC of lymphoid follicles and CD1b in the DC of paracortical areas at 18 dpi. However, the expression of MHC-II and CD83 decreased at 9 and, particularly, at 18 dpi in HLN compared with that in the UC group. Since both markers are related to active presentation of antigens by DC and FDC, the results of the present study suggest that, despite the marked hyperplasia of HLN and increase in DC and FDC numbers during early stages of infection, the DC and FDC antigenic presentation capacity, as suggested by the expression of the markers MHC-II and CD83, is suppressed by the parasite. This suppression was not observed in the liver, probably because of the low number of DC. This is the first study of the immunophenotype of DCs and FDC in sheep infected with F. hepatica.

Case Report: Subarachnoid Hemorrhage and Eosinophilic Meningitis due to Disseminated Fascioliasis.

Human infection with the trematode Fasciola occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported. Here, we present the case of a previously healthy 31-year-old Kurdish woman, admitted to hospital with a subarachnoid hemorrhage, eosinophilic meningitis, and lung and liver disease. A diagnosis of Fasciola infection was made based on strongly positive serology in blood and cerebrospinal fluid. The patient improved following treatment with triclabendazole and prednisolone.

Fasciola hepatica seroprevalence in Northern German dairy herds and associations with milk production parameters and milk ketone bodies.

Infections with the liver fluke Fasciola hepatica remain a serious problem in dairy herds causing significant production losses. In sheep, a strong relationship between F. hepatica infections and an increase in serum ketone bodies due to reduced feed intake and liver damage was demonstrated. We hypothesized that F. hepatica infections might contribute to an increase in milk ketone bodies in dairy herds. Thus, the objective of the study was to estimate the association between F. hepatica bulk tank milk (BTM) antibodies and milk production parameters (milk yield, milk protein, fat yield), somatic cell count (SCC) and the milk ketone bodies ß-hydroxybutyrate (BHB) and acetone, inferred from Fourier transform infrared (FTIR) spectrometry, via linear mixed model analysis. A further aim was to follow up the F. hepatica seroprevalence in dairy herds in the northern German region East Frisia. We collected BTM samples between October and December from 1022 herds in 2017 and 1318 herds in 2018. Overall, 33.1 % of the herds tested positive in 2017 and 37.0 % in 2018, showing decreased F. hepatica seroprevalences compared to prior seroprevalence studies in the same region in 2010, 2008 and 2006 (> 45 % positive herds). We estimated a significant negative association (P < 0.001) between herd F. hepatica infection category and average milk yield with a loss of -1.62 kg per cow per day in strongly infected herds compared to BTM ELISA negative herds. Moreover, F. hepatica infection category had a significant effect on herd average milk protein and fat yield (P < 0.001), showing a decrease of 0.06 kg for both parameters from BTM ELISA negative herds to strongly infected herds. No significant association with milk SCC was found (P = 0.664). Regarding ketone bodies, we estimated significant higher average BHB values in strongly infected herds compared to the other three infection categories in the model analysis (P = 0.002). The association between F. hepatica infection category and acetone values was not significant (P = 0.079). Besides primary ketosis, fasciolosis should be considered as differential diagnosis in dairy herds with increased BHB values.

Lymphocyte Populations in the Adventitial Layer of Hydatid Cysts in Cattle: Relationship With Cyst Fertility Status and Fasciola Hepatica Co-Infection.

Cystic echinococcosis is a worldwide zoonosis caused by the cestode Echinococcus granulosus. Two types of hydatid cysts occur in intermediate hosts: fertile cysts that generate protoscoleces from the germinal layer of the cyst, and infertile cysts that do not produce protoscoleces and are unable to continue the life cycle of the parasite. The adventitial layer, a host-derived fibrous capsule surrounding the hydatid cyst, is suggested to play an important role in local immune regulation during infection and in fertility of the cysts. Fasciola hepatica, another important parasite of cattle, induces a characteristic Th2-like immune response that could modulate the immune response against E. granulosus. Natural co-infection of both parasites is common in cattle, but no reports describe the local immune response against E. granulosus with F. hepatica infection in the same host. This study analyzed the number and distribution of T and B cells in the adventitial layer of liver and lung cysts and the relationship with cyst fertility and F. hepatica co-infection. T lymphocytes were the predominant cell type in the adventitial layer of infertile hydatid cysts and were more numerous in infertile hydatid cysts. B lymphocyte numbers were not associated with hydatid cyst fertility. Mast cells were infrequent in the adventitial layer. The number of T and B cells was not associated with F. hepatica co-infection. The present study contributes to the understanding of local immune responses in bovine cystic echinococcosis.

Newly excysted juveniles (NEJs) of Fasciola gigantica induce mice liver fibrosis and M2 macrophage-like phenotype in vivo.

Liver flukes of animals are parasitic flatworms of major socioeconomic importance in many countries. Particularly, Fasciola gigantica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. Immune responses induced by helminth have been extensively studied, but there is limited information on this aspect by F. gigantica, especially on macrophages induced with this parasite. Studies have shown that host immune responses induced by parasitic infection is greatly correlated with the macrophage polarization axis. In the present study, we used the murine model of F. gigantica to explore the interaction of host and F. gigantica. We found F. gigantica NEJs promoted pathology and fibrosis of mice liver, and the enlargement of mice spleen. We also showed that macrophages were recruited to mice peritoneal cavity at 5 days post infection. By evaluating the expression of genetic markers of M2 macrophages such as Arg-1, Ym1 and RELMɑ, and genetic marker of M1 macrophages iNOS, we showed that M2 macrophages were induced by F. gigantica. M2 macrophages are central to the immune response during helminth infection, and our findings in this study provided insight into the immune interaction between F. gigantica and host.

Gross and histological lesions in the livers of sika deer with particular emphasis on fascioliasis.

We performed gross and histological examinations of the livers of sika deer (Cervus nippon yesoensis) in Hokkaido, Japan. Out of 1,381 deer slaughtered for venison production, thickening and dilation of the large intrahepatic bile ducts and Fasciola flukes in the duct lumens were detected in 621 deer (45.0%). Furthermore, 107 non-bile lesions (75 intrahepatic and 32 capsular lesions) were detected during gross examinations. Histologically, the bile duct lesions included chronic proliferative cholangitis, papillary hyperplasia, goblet cell and pyloric gland metaplasia, and periductal fibrosis. Many of the intrahepatic non-bile duct lesions (53/75, 71%) were considered to be Fasciola fluke migration-associated lesions, including two lesion types: necrosis, hemorrhage, and eosinophilic granuloma formation (29 lesions), and lymphoid tissue formation (24 lesions). Lymphoid tissue formation was considered to result from the persistent immune responses against dead Fasciola flukes. An epidermoid liver cyst was found incidentally, which has not been reported in the veterinary literature. In summary, this study demonstrated the predominance of fascioliasis-associated lesions in sika deer livers. The gross and histological lesions caused by Fasciola flukes in sika deer were similar to fascioliasis in other animals. Moreover, we described lymphoid tissue formation as a fascioliasis-associated lesion for the first time. The fact that bile duct lesions (45.0%) had a markedly higher prevalence than fascioliasis-associated parenchymal lesions (53/1,381, 3.8%) indicated that sika deer are a permissive host for fascioliasis. Our results provide information that will aid pathological examinations of sika deer.

Evaluation of losses in carcasses of cattle naturally infected with Fasciola hepatica: effects on weight by age range and on carcass quality parameters.

Although fasciolosis is a relatively common disease, the productive and economic losses resulting from cattle with chronic fasciolosis are unclear. This paper aims to investigate the effect of fasciolosis on the parameters of carcass quality and discuss the hypothesis that the effects on weight differ among age ranges of cattle. For this, we analysed abattoir data of 30,151 bovines, from 928 farms, slaughtered in Uruguay in 2016, of which 33.9% (95% confidence interval (CI): 27.3-41.1%) had Fasciola hepatica (liver fluke). A mixed model was built to assess whether the effect of fasciolosis on weight differs depending on the age range, using the interaction term 'age*F. hepatica'. The effect on the carcass parameters was tested using a proportional logistic regression. The interaction of age and F. hepatica was statistically significant (P < 0.001). Differences in carcass weights between infected and non-infected animals were observed mostly at younger ages (up to 30 months), with the highest difference observed in the 23-30 months age range (estimated marginal mean difference of 6.34 kg). Overall, the presence of F. hepatica was positively associated with poor conformations and lower fat scores of carcasses (P < 0.001). The carcasses of cattle infected with F. hepatica had 0.16 times greater odds of having worse conformation scores than carcasses of cattle without F. hepatica (proportional odds ratio (POR) = 1.16; 95% CI: 1.07-1.26). Similarly, carcasses of cattle with F. hepatica had 0.30 times (POR = 1.30, 95% CI: 1.23-1.39) greater odds of having poorer fat scores than carcasses of cattle without F. hepatica. Therefore, infection with F. hepatica is associated with poorer carcass quality parameters and lower weights, and the effect on weight differs across age ranges.

Bovine fasciolisis in São Paulo state, Brazil.

Fasciolosis is a zoonotic disease with a worldwide distribution caused by Fasciola hepatica, which leads to severe economic losses in cattle such as reducing meat and milk production, livers condemnation, growth retardation and increase in mortality. From October 2008 to April 2011, condemned bovine livers in slaughterhouses of different municipalities from São Paulo state, Brazil were evaluated for the presence of Fasciola hepatica. Out of 20,635 analyzed livers, 1422 were infected with F. hepatica. These cattle came from 33 municipalities, out of which 16 showed infected animals and where 7 municipalities did not show statistical difference between each month throughout the year: Tuiuti - 276/1408 (19,6%), Atibaia - 44/257 (17,1%), Joanópolis - 116/738 (15,7%), Bragança Paulista - 318/2316 (13,3%), Piracaia - 182/1442 (12,6%), Santo Antonio de Posse - 118/1005 (11,7%), Amparo 131/2003 (6,5%). The other nine municipalities, Monte Alegre do Sul, Descalvado, Campinas, Morungaba, Pedreira, Socorro, Munhoz, Jaguariúna and Itatiba showed a positive percentage varying from 5.08% to 1.46%. Our results demonstrated the presence of F. hepatica in this region was higher than official data, bringing the need for control measures. There is also an apparent increase in fasciolosis two to three months after low to medium precipitation, however high precipitation causes a decrease in fasciolosis prevalence.

Histopathological findings of Fasciola hepatica infection in non-native European hare (Lepus europaeus) in Southern Chile / Achados histopatológicos da infecção por Fasciola hepatica em lebre europeia não-nativa (Lepus europaeus) no Sul do Chile

Abstract Fasciola hepatica is a parasite introduced in America from Europe, being considered of concern for public health and animal production, especially in countries with endemic areas as occur in Chile. In this country, the research has been focused mainly in domestic ruminants, with native and introduced wildlife being largely ignored. Thus, the aim of this study was to report the infection by Fasciola hepatica in an introduced mammal, the European hare, which is distributed along a vast area of the country. One in 42 hares hunted showed histological lesions compatible with F. hepatica, and harbored a parasitic load of 6 liver flukes. This is the first report of this lagomorph acting as host of this helminth in the country and the third in South America. Yet, we found no previous reports regard the pathology of this fluke in the species. Thus, we emphasize the importance of more studies regarding introduced mammals which could be acting as reservoirs for this important fluke.

Resumo Fasciola hepatica é um parasita de origem europeia introduzido na América, de importância em saúde pública e animais de produção, especialmente em países com áreas endêmicas, como ocorre no Chile. Neste país, a pesquisa foi focada principalmente em ruminantes domésticos, com a fauna nativa e introduzida sendo amplamente ignorada. O objetivo desse trabalho é relatar a infecção por Fasciola hepatica em lebre europeia, espécie distribuída em vasta extensão do país. Uma em 42 lebres caçadas, mostrou lesões histológicas compatíveis com infestação por F. hepatica, alojando 6 vermes hepáticos. Este é o primeiro relato deste lagomorfo apresentando este tipo de parasitismo no Chile, o terceiro na América do Sul. No entanto, não encontramos relatos anteriores sobre a patologia deste acaso na espécie. Este relato salienta a importância de mais estudos considerando espécies introduzidas, as quais podem ser reservatórios desse importante parasita.

Fascioliasis: A Rare Parasitic Infection-Mimicking Tumor in the Liver: Report of Two Cases.

Fascioliasis is a rarely encountered parasitic infection in Turkey that mainly affects the liver and bile ducts. Other defined localizations of the parasite are the lungs, gastrointestinal system, and subcutaneous fatty tissue. Two cases of female patients who presented to the hospital with abdominal pain and whose physical examination and laboratory findings were normal except peripheral eosinophilia, were detected to have liver masses with necrotic areas. Segmental hepatectomies were performed in both cases with the preliminary diagnosis of liver tumors. Upon microscopic examinations of the resection materials, necrotic granulomatous inflammation with eosinophilic reaction at the periphery and the parasite (Fasciola hepatica) were seen. Both cases were reported to be fascioliasis according to these findings. Two cases of fascioliasis mimicking malignancy in the liver are presented here together with literature findings.

Histopathological findings of Fasciola hepatica infection in non-native European hare (Lepus europaeus) in Southern Chile.

Fasciola hepatica is a parasite introduced in America from Europe, being considered of concern for public health and animal production, especially in countries with endemic areas as occur in Chile. In this country, the research has been focused mainly in domestic ruminants, with native and introduced wildlife being largely ignored. Thus, the aim of this study was to report the infection by Fasciola hepatica in an introduced mammal, the European hare, which is distributed along a vast area of the country. One in 42 hares hunted showed histological lesions compatible with F. hepatica, and harbored a parasitic load of 6 liver flukes. This is the first report of this lagomorph acting as host of this helminth in the country and the third in South America. Yet, we found no previous reports regard the pathology of this fluke in the species. Thus, we emphasize the importance of more studies regarding introduced mammals which could be acting as reservoirs for this important fluke.

Epidemiological and clinical-pathological aspects of fasciolosis in livers of cattle slaughtered in southern Brazil / Aspectos epidemiológicos e clínico-patológicos de fasciolose em fígados de bovinos abatidos no sul do Brasil

Infection by Fasciola hepatica is an important cause of economic loss in cattle raised in Brazil and others countries. In slaughterhouses, the losses are mainly associated with condemnation of livers; however, it is believed that these losses can extend to diminished carcass yield and productivity throughout the life of the animals. Three slaughterhouses with a daily routine of approximately 15-20 cattle slaughters were monitored from July 2016 to November 2017. After sample collection, weighing, and liver assessment, statistical studies were conducted to determine disease prevalence and measurement of economic losses caused by fasciolosis through condemnation of the organ of choice of the parasite. Of the 210 livers assessed, 79 (37.6%) were condemned because of presence of F. hepatica, 87 (41.4%) were considered appropriate for human consumption, and 44 (20.9%) were considered inappropriate because of some other macroscopic lesions. The aim of this study was to estimate the prevalence of fasciolosis, correlate epidemiological and clinical-pathological aspects, and estimate the economic losses caused by the disease. It is estimated that the losses in southwestern Rio Grande do Sul state could reach R$ 36,943,532.60 (37.6%; 95% CI = 30,753,525.80 - 43,526,55.65) or US$ 11,437,626.20 (37.6%; 95% CI = 9,521,215.40 - 13,475,713.80) only because of condemnation of livers.(AU)

A infecção por Fasciola hepatica é uma importante causa de prejuízos econômicos para o setor pecuário no Brasil e em outros países. Em frigoríficos, as perdas estão relacionadas principalmente a condenação dos fígados, porém acredita-se que esses prejuízos possam se estender a perdas no rendimento de carcaça e durante a vida produtiva do animal. Durante o período de julho de 2016 a novembro de 2017 foram realizados acompanhamentos periódicos mensais em três frigoríficos, os quais, possuem uma rotina diária de aproximadamente 15-20 abates. Após a coleta de dados, pesagem e avaliação dos fígados foram realizados estudos estatísticos para determinação da prevalência e mensuração dos prejuízos econômicos causados por fasciolose pela condenação do órgão de eleição do parasito. Dos 210 fígados avaliados, 79 (37,6%) foram condenados devido a presença de F. hepatica, 87 (41,4%) foram considerados próprios para consumo humano e 44 (20,9%) impróprios por alguma outra alteração macroscópica. O objetivo deste estudo foi estimar a prevalência da fasciolose, e associar os aspectos epidemiológicos e clinico patológicos, além de estimar os prejuízos econômicos causados pela doença. Estima-se que as perdas na mesorregião Sudeste Rio-grandense possam chegar à R$ 36.943.532,60 (37,6%; IC.95% = 30.753.525,80-43.526.55,65) ou US$ 11.437.626,20 (37,6%; IC.95% = 9.521.215,40-13.475.713,80) somente devido a condenação de fígados.(AU)

Human case of Fasciola gigantica-like infection, review of human fascioliasis reports in Nepal, and epidemiological analysis within the South Central Asia.

The diagnosis of a 22 year-old male patient from Kerabari, Morang District, Nepal led to the review of human fascioliasis cases and analysis of the epidemiological situation in that country not included in the WHO fascioliasis map. Symptom onset one month before egg detection and normal levels of ALT and AST did not agree with the 3-4-month migratory period of fascioliasis. A shorter acute phase may happen when the main biliary duct is reached by the migratory juveniles directly from the intestinal lumen. The causal agent was ascribed to F. gigantica-like worms after considering adult fluke morphology, altitude of the patient's infection area, fasciolid characteristics in the neighbouring Bangladesh, and lymnaeid snail vector species known in Nepal and in the patient's infection area. Previous reports of human infection by Fasciola in Nepal are reviewed. The patient in question proved to be the twelfth case and the first in whom a F. gigantica-like infection is reported. In Nepal, the wide geographical distribution of livestock fascioliasis, with high prevalences in buffaloes, cattle and goats, and the reports of Fasciola-infected schoolchildren close to the capital Kathmandu, give rise to concern on the situation in remote rural areas in a country where most of the population lives in rural areas. Moreover, the climate change impact in Nepal remembers Pakistan, where human fascioliasis emergence has been related to climate change and man-made irrigation. All in all, the present analysis suggests that human infection by Fasciola may be underestimated in Nepal.

Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes.

BACKGROUND: Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection. METHODS: Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-ß, IL-1ß, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology. RESULTS: Histopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3-10 dpi) was marked by a generalized immunosuppression and elevated TGF-ß expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host's Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis. CONCLUSIONS: Our data showed distinct CD4+ T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity.