Schistosomiasis japonicum diagnosed on liver biopsy in a patient with hepatitis B co-infection: a case report

Introduction Chronic hepatitis B virus and schistosomiasis are independently associated with significant mortality and morbidity worldwide. Despite much geographic overlap between these conditions and no reason why co-infection should not exist, we present what is, to the best of our knowledge, the first published report of a proven histological diagnosis of hepatic Schistosomiasis japonicum and chronic hepatitis B co-infection. A single case of hepatitis B and hepatic Schistosomiasis mansoni diagnosed by liver biopsy has previously been reported in the literature. Case presentation A 38-year-old Chinese man with known chronic hepatitis B virus infection presented with malaise, nausea and headache. Blood tests revealed increased transaminases and serology in keeping with hepatitis B virus e-antigen seroconversion. A liver biopsy was performed because some investigations, particularly transient elastography, suggested cirrhosis. Two schistosome ova were seen on liver histology, identified as S. japonicum, probably acquired in China as a youth. His peripheral eosinophil count was normal, schistosomal serology and stool microscopy for ova, cysts and parasites were negative. Conclusion Hepatic schistosomiasis co-infection should be considered in patients with hepatitis B virus infection who are from countries endemic for schistosomiasis. Screening for schistosomiasis using a peripheral eosinophil count, schistosomal serology and stool microscopy may be negative despite infection, therefore presumptive treatment could be considered. Transient elastography should not be used to assess liver fibrosis during acute flares of viral hepatitis because readings are falsely elevated. The impact of hepatic schistosomiasis on the sensitivity and specificity of transient elastography measurement for the assessment of hepatitis B is as yet unknown

Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy

Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders

Integrin Clustering Is Driven by Mechanical Resistance from the Glycocalyx and the Substrate

Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled