Hepatobiliary Ascariasis in a Piglet.

PURPOSE: Ascariasis caused by the helminth Ascaris suum is the most common parasitosis of swine worldwide and it may involve all age categories of pigs. The present study reports an unusual localization of A. suum worms in the biliary system of a piglet slaughtered for human consumption. METHODS: The liver was subjected to ultrasound scan and pathological examination. The isolated worms were morphologically examined and the DNA was extracted for the molecular identification of the species involved. RESULTS: A total of 43 preadult nematodes were found within the gallbladder and the bile ducts. Parasites were morphologically identified as belonging to the genus Ascaris and molecularly as A. suum. At gross examination, the liver was moderately enlarged, with the bile ducts severely dilated. A chronic inflammatory infiltrate was noted, often centered around ectatic bile ducts (up to 5 mm in diameter), lined by hyperplastic epithelium and filled with sections of nematodes. The worm sections showed smooth cuticle, coelomyarian musculature, and an intestinal tract lined by columnar, uninucleated cells within a pseudocoelom. The ex vivo ultrasonographic examination of the liver allowed the visualization of several nematodes in the bile duct lumen and could be suggested for in vivo diagnosis. Unfortunately, the absence of the intestine did not allow to define the pathogenesis of the infection. CONCLUSION: Although, given the unusual nature of this finding, it is difficult to identify predisposing factors for this A. suum localization, it suggests that ascariasis should be considered in the differential diagnosis of pigs with hepatobiliary disease.

Hepatic Capillaria hepatica (Bancroft, 1893) infection in cat (Felis catus)-histopathological findings and first report from Iran.

Capillaria hepatica (syn. Calodium hepaticum) is a globally distributed nematode with a high affinity to the liver of a wide range of mammalian hosts, including humans. Documented reports of the nematode in cats and associated histopathology are rare. Here, we describe a case of C. hepatica infection in a 5-year-old male stray cat from Iran. At post-car accident necropsy, all body parts appeared normal except for the liver, in which a few yellowish-white granulomatous nodules were observed through the capsule and in the organ. Histopathological examination of the tissue revealed a large number of clustered parasite eggs in the parenchyma. The barrel-shaped, un-embryonated eggs (55.19 × 28.37 µm), with inconspicuous caps at both ends, were covered with striated shells. The presence of ova in the liver tissue had resulted in the development of hepatic inflammation with hepatocellular necrosis associated with the development of multifocal granulomas. As predators of small rodents, the cats might have a significant role in the epidemiology of C. hepatica. Infection of hosts through ingestion of embryonated eggs in contaminated water, food, or soil is of major importance in the epidemiology of C. hepatica. Since the rare reports of feline infection have come mainly from accidental detection of the parasite, any hepatic disease presenting difficulties to find an etiological agent may virtually be associated with the infection with this little-known nematode.

γδ T cells in malaria: a double-edged sword.

Malaria remains a devastating global health problem, resulting in many annual deaths due to the complications of severe malaria. However, in endemic regions, individuals can acquire 'clinical immunity' to malaria, characterized by a decrease in severe malaria episodes and an increase of asymptomatic Plasmodium falciparum infections. Recently, it has been reported that tolerance to 'clinical malaria' and reduced disease severity correlates with a decrease in the numbers of circulating Vγ9Vδ2 T cells, the major subset of γδ T cells in the human peripheral blood. This is particularly interesting as this population typically undergoes dramatic expansions during acute Plasmodium infections and was previously shown to play antiparasitic functions. Thus, regulated γδ T-cell responses may be critical to balance immune protection with severe pathology, particularly as both seem to rely on the same pro-inflammatory cytokines, most notably TNF and IFN-γ. This has been clearly demonstrated in mouse models of experimental cerebral malaria (ECM) based on Plasmodium berghei ANKA infection. Furthermore, our recent studies suggest that the natural course of Plasmodium infection, mimicked in mice through mosquito bite or sporozoite inoculation, includes a major pathogenic component in ECM that depends on γδ T cells and IFN-γ production in the asymptomatic liver stage, where parasite virulence is seemingly set and determines pathology in the subsequent blood stage. Here, we discuss these and other recent advances in our understanding of the complex-protective versus pathogenic-functions of γδ T cells in malaria.

Positive consequences of splenectomy for patients with schistosomiasis-induced variceal bleeding.

BACKGROUND: Patients with hepatic schistosomiasis are at high risk of gastroesophageal variceal bleeding, which is highly torrential and life threatening. This study aimed to assess the effects of splenectomy on patients with schistosomiasis-induced variceal bleeding, especially those influences related to overall survival (OS) rate. METHODS: From January 2005 to December 2018, 112 patients with schistosomiasis-induced varices were enrolled. In that period, all the patients with hepatic schistosomiasis who received endoscopic treatment for primary and secondary prophylaxis of gastroesophageal variceal bleeding were found eligible. The patients were divided into splenectomized group (n = 44, 39.3%) and control group (n = 68, 60.7%). RESULTS: Multivariate regression analysis of OS showed that splenectomy, hepatic carcinoma, and times of endoscopic treatment were independent prognostic factors for OS. Kaplan-Meier analysis revealed that the 5-year OS rate was 82.7% in splenectomized group versus 53.2% in control group (P = 0.037). The rate of no recurrence of variceal bleeding during 5-year (56.8% vs. 47.7%, P = 0.449) indicated that there was no significant difference between the two groups. Patients who received splenectomy had increased risk of portal vein thrombosis (52.3% vs. 29.4%, P = 0.012) and decreased proportion of severe ascites (20.5% vs 50.0%, P = 0.002). CONCLUSION: Splenectomy prior to endoscopic treatment provides a superior long-term survival for patients with schistosomiasis-induced variceal bleeding.

Fungal and Parasitic Infections of the Liver.

Hepatosplenic candidiasis and other fungal infections of the liver are uncommon in healthy individuals; however, high index of suspicion is essential in immunocompromised patients with prolonged fever. Parasitic infections are protozoan or helminthic; their distribution and epidemiology are variable among different world regions. Clonorchiasis, opisthorchiasis, fascioliasis, and ascariasis are helminthic infections that commonly involve the biliary systems. Signs and symptoms of cholangitis require prompt management to relieve biliary obstruction; addition of antihelminthic agents is essential. Parasitic infections are mostly transmitted to humans by fecally contaminated food and water. Proper hand and food sanitation measures are essential in preventing disease transmission.

Lipophosphoglycan-3 recombinant protein vaccine controls hepatic parasitism and prevents tissue damage in mice infected by Leishmania infantum chagasi.

AIMS: In this work, we aimed to evaluate the effects of the Leishmania infantum chagasi infection on the liver of vaccinated mice, considering parameters of tissue damage and the inflammatory response elicited by vaccination. MAIN METHODS: We used recombinant LPG3 protein (rLPG3) as immunogen in BALB/c mice before challenge with promastigote forms of L. infantum chagasi. The animals were separated into five groups: NI: non-infected animals; NV: non-vaccinated; SAP: treated with saponin; rLPG3: immunized with rLPG3; rLPG3 + SAP: immunized with rLPG3 plus SAP. The experiment was conducted in replicate, and the vaccination protocol consisted of three subcutaneous doses of rLPG3 (40 µg + two boosters of 20 µg). The mice were challenged two weeks after the last immunization. KEY FINDINGS: Our results showed that rLPG3 + SAP immunization decreased the parasite burden in 99 %, conferring immunological protection in the liver of the infected animals. Moreover, the immunization improved the antioxidant defenses, increasing CAT and GST activity, while reducing the levels of oxidative stress markers, such as H2O2 and NO3/NO2, and carbonyl protein in the organ. As a consequence, rLPG3 + SAP immunization preserved tissue integrity and reduced the granuloma formation, inflammatory infiltrate and serum levels of AST, ALT, and ALP. SIGNIFICANCE: Taken together, these results showed that rLPG3 vaccine confers liver protection against L. infantum chagasi in mice, while maintaining the liver tissue protected against the harmful inflammatory effects caused by the vaccine followed by the infection.

Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates.

BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model.

The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species.

Infection by Platynosomum illiciens (= P. fastosum) in domestic cats of Araguaína, Tocantins, northern Brazil / Infecção por Platynosomum illiciens (= P. fastosum) em gatos domésticos de Araguaína, Tocantins, Norte do Brasil

Abstract Platynosomiasis is a hepatopathy caused by Platynosomum illiciens(= P. fastosum) (Trematoda: Dicrocoelidae), which occurs mainly in domestic and wild cats in tropical and subtropical areas. The objective of this study was to verify the occurrence of P. illiciens infection in domestic cats in the city of Araguaína, Tocantins, Brazil, using necropsy and coproparasitological tests. Additionally, we aimed to evaluate the use of two different techniques to diagnose P. illiciens infection in domestic cats and verify whether this parasitism was associated with individual feline characteristics. For this, 54 cats of different ages were analyzed. The percentage of infection was 33.3% (CI = 21.1-47.5%), parasite load was 9-509, mean intensity was 151.7, and mean abundance was 50.5 trematodes per animal. The risk of infection was higher for females than for males (OR = 5.00; P = 0.017). The spontaneous sedimentation coproparasitological test demonstrated the greatest sensitivity and specificity in diagnosing P. illiciens. This study is the first to report the occurrence of P. illiciens in cats in the state of Tocantins, northern Brazil.

Resumo A platinosomose é uma hepatopatia causada por Platynosomum illiciens(= P. fastosum) (Trematoda: Dicrocoelidae), que ocorre principalmente em felinos domésticos e selvagens de áreas tropicais e subtropicais. O objetivo deste trabalho foi verificar a ocorrência de P. illiciens em gatos domésticos do município de Araguaína, Tocantins, Brasil, por meio de necrópsia e exames coproparasitológicos, bem como avaliar o uso de diferentes técnicas no diagnóstico de P. illiciens em gatos domésticos e verificar a associação da parasitose com características individuais dos felinos. O estudo foi realizado em 54 gatos com diferentes idades, machos e fêmeas. O percentual de infecção foi de 33,3% (IC= 21,1% - 47,5%), a carga parasitária observada foi de 09-509, a intensidade média de 151,7 e a abundância média de 50,5 trematódeos por animal. As fêmeas apresentaram maior chance de infecção do que os machos (OR=5,00; P=0,017). O teste coproparasitológico que demonstrou maior sensibilidade e especificidade foi o de sedimentação espontânea. O presente estudo faz o primeiro relato da ocorrência de P. illiciens em gatos no estado do Tocantins, região Norte do Brasil.

Infection by Platynosomum illiciens (= P. fastosum) in domestic cats of Araguaína, Tocantins, northern Brazil.

Platynosomiasis is a hepatopathy caused by Platynosomum illiciens(= P. fastosum) (Trematoda: Dicrocoelidae), which occurs mainly in domestic and wild cats in tropical and subtropical areas. The objective of this study was to verify the occurrence of P. illiciens infection in domestic cats in the city of Araguaína, Tocantins, Brazil, using necropsy and coproparasitological tests. Additionally, we aimed to evaluate the use of two different techniques to diagnose P. illiciens infection in domestic cats and verify whether this parasitism was associated with individual feline characteristics. For this, 54 cats of different ages were analyzed. The percentage of infection was 33.3% (CI = 21.1-47.5%), parasite load was 9-509, mean intensity was 151.7, and mean abundance was 50.5 trematodes per animal. The risk of infection was higher for females than for males (OR = 5.00; P = 0.017). The spontaneous sedimentation coproparasitological test demonstrated the greatest sensitivity and specificity in diagnosing P. illiciens. This study is the first to report the occurrence of P. illiciens in cats in the state of Tocantins, northern Brazil.

Assessment of histological liver alterations in dogs naturally infected with Leishmania infantum.

BACKGROUND: The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no differences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with differing clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil. METHODS: We examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way. RESULTS: Our results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this inflammatory response and parasite load in the animals' spleens. It is important to note that while hepatic alterations, such as portal and perivascular inflammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal inflammatory cell aggregates and Kupffer cell hypertrophy. CONCLUSIONS: Our findings suggest that the presence of mononuclear inflammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a first line of defense mechanism in the control of parasite infection, which could be related to the presence of inflammatory cells and Kupffer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of inflammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.

Flexible 3D Cell-Based Platforms for the Discovery and Profiling of Novel Drugs Targeting Plasmodium Hepatic Infection.

The restricted pipeline of drugs targeting the liver stage of Plasmodium infection reflects the scarcity of cell models that mimic the human hepatic phenotype and drug metabolism, as well as Plasmodium hepatic infection. Using stirred-tank culture systems, spheroids of human hepatic cell lines were generated, sustaining a stable hepatic phenotype over 4 weeks of culture. Spheroids were employed in the establishment of 3D Plasmodium berghei infection platforms that relied on static or dynamic culture conditions. P. berghei invasion and development were recapitulated in the hepatic spheroids, yielding blood-infective merozoites. The translational potential of the 3D platforms was demonstrated by comparing the in vitro minimum inhibitory concentration of M5717, a compound under clinical development, with in vivo plasma concentrations that clear liver stage P. berghei in mice. Our results show that the 3D platforms are flexible and scalable and can predict the efficacy of antiplasmodial therapies, constituting a powerful tool for integration in drug discovery programs.

In vitro anthelmintic effect of biologically synthesized silver nanoparticles on liver amphistome, Gigantocotyle explanatum.

In order to ensure global food security a rationale approach is required to control all those factors which directly or indirectly affect the food productivity. The neglected helminthic diseases alone are responsible for huge economic losses to the agrarian stakeholders. The problem is further compounded by the emerging drug resistance in flukes against the commonly used anthelmintics like triclabendazole. Therefore, the search for alternatives including the nano-based approaches has become a necessity to develop future control strategies. In the present study the effect of biologically synthesized silver nanoparticles (AgNPs) was investigated on an economically important amphistome parasite, Gigantocotyle explanatum, obtained from the infected liver of the Indian water buffaloes, Bubalus bubalis. In vitro treatment of the adult worms with different doses of AgNPs severely affected the worm motility and caused ROS mediated damages in the treated flukes. The antioxidant system and the detoxification ability of the worms appeared to be disrupted along with pronounced DNA damage in the treated worms as compared to the controls. Following the treatment of worms with different concentrations of AgNPs there was a significant (p < 0.05) increase in lipid peroxidation and protein carbonylation levels which are the key oxidative stress markers. The tegumental surface which is metabolically active, was severely damaged as evident from the loss of papillae, severe blebbing, shearing and erosion of the surface structures. Such topographical disruptions would facilitate the penetration of the nanoparticles deep within the tissues that might greatly reduce the invasive potential of the flukes as evident from the decreased motility. Taken together our findings suggest that the AgNPs posses great anthelmintic potential and could be further exploited for the development of anthelmintic formulations which may be tested in vivo.

Case Report: Hepatic Fascioliasis in a Young Afghani Woman with Severe Wheezing, High-Grade Peripheral Eosinophilia, and Liver Lesions: A Brief Literature Review.

A 23-year-old recent emigrant from Afghanistan presented in August 2017 with severe wheezing and dyspnea that required hospital admission. Her illness was associated with marked peripheral blood eosinophilia (9,900-15,600/µL; 45.2-68%), as well as mild nausea, epigastric pain, and decreased appetite. She had lived until 3 months earlier in close proximity to cattle in her home in Kabul and did not recall eating watercress or other leafy plants associated with Fasciola hepatica transmission. Computerized tomography scanning showed bilateral ground-glass lung consolidations and multiple distinctive hypo-attenuating linear, tubuliform, and nodular liver lesions, including a large subcapsular hematoma. Numerous tests for rheumatological and malignant disorders were negative. Fasciola hepatica infestation was suspected on epidemiological, clinical, and radiographic grounds, and was confirmed by immunoblotting at the Centers for Disease Control (CDC). Multiple stool ova and parasite examinations were negative and endoscopic retrograde cholangiopancreatography did not identify trematodes. Her acute respiratory illness resolved with asthma-targeted therapies and her eosinophilia resolved with triclabendazole, which was obtained from CDC via an FDA Investigational New Drug application. Fascioliasis is uncommon in the United States, but the prolonged warfare and civil strife in Afghanistan and adjacent areas may lead to increased incidence outside the endemic region. Her case also demonstrates how hepatic imaging features of fascioliasis can be pathognomonic in clinical scenarios with eosinophilia and appropriate epidemiology and clinical features. We also highlight her relatively unusual presentation with symptoms of Loeffler-like syndrome alone.

The polysaccharide from Inonotus obliquus protects mice from Toxoplasma gondii-induced liver injury.

The study aimed to explore the protective effects and mechanism of Inonotus obliquus polysaccharide (IOP) on liver injury caused by Toxoplasma gondii (T. gondii) infection in mice. The results showed that treatment with IOP significantly decreased the liver coefficient, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and nitric oxide (NO), and increased the contents of antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH). IOP effectively decreased the expression of serum tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ) and interluekin-4 (IL-4) in T. gondii-infected mice. In agreement with these observations, IOP also alleviated hepatic pathological damages caused by T. gondii. Furthermore, we found that IOP down-regulated the levels of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), phosphorylations of nuclear factor-κappaB (NF-κB) p65 and inhibitor kappaBα (IκBα), whereas up-regulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). These findings suggest that IOP possesses hepatoprotective effects against T. gondii-induced liver injury in mice, and such protection is at least in part due to its anti-inflammatory effects through inhibiting the TLRs/NF-κB signaling axis and the activation of an antioxidant response by inducing the Nrf2/HO-1 signaling.

Small Molecules Effective Against Liver and Blood Stage Malarial Infection.

Malaria is a lethal disease causing devastating global impact by killing more than 8,00,000 individuals yearly. A noticeable decline in malaria related deaths can be attributed to the most reliable treatment, ACTs against P. falciparum. However, the cumulative resistance of the malaria parasite against ACTs is a global threat to control the disease and, therefore the new effective therapeutics are urgently needed, including new treatment approaches. Majority of the antimalarial drugs target BS malarial infection. Currently, scientists are eager to explore the drugs with potency against not only BS but other life stages such as sexual and asexual stages of the malaria parasite. Liver Stage is considered as one of the important drug targets as it always leads to BS and the infection can be cured at this stage before it enters into the Blood Stage. However, a limited number of compounds are reported effective against LS malaria infection probably due to scarcity of in vitro LS culture methods and clinical possibilities. This mini review covers a range of chemical compounds showing efficacy against BS and LS of the malaria parasite's life cycle collectively (i.e. dual stage activity). These scaffolds targeting dual stages are essential for the eradication of malaria and to evade resistance.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.