Haemostatic Changes in Five Patients Infected with Ebola Virus

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged. Collecting plasma without centrifugation only affected D-dimer values. Patients with Ebola virus disease had higher PT and APTT and D-dimer values than healthy humans with plasma collected in the same manner. Fibrinogen levels in patients with Ebola virus disease were normal or lower than values measured in healthy people. Clotting times and D-dimer levels were elevated during infection with Ebola virus but return to normal over time in patients that survived and therefore could be considered prognostic. Informative data can be obtained from plasma collected without centrifugation which could improve patient monitoring in hazardous environment

Haemostatic Changes in Five Patients Infected with Ebola Virus

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged. Collecting plasma without centrifugation only affected D-dimer values. Patients with Ebola virus disease had higher PT and APTT and D-dimer values than healthy humans with plasma collected in the same manner. Fibrinogen levels in patients with Ebola virus disease were normal or lower than values measured in healthy people. Clotting times and D-dimer levels were elevated during infection with Ebola virus but return to normal over time in patients that survived and therefore could be considered prognostic. Informative data can be obtained from plasma collected without centrifugation which could improve patient monitoring in hazardous environment

HIF1α and HIF2α independently activate SRC to promote melanoma metastases

Malignant melanoma is characterized by a propensity for early lymphatic and hematogenous spread. The hypoxia-inducible factor (HIF) family of transcription factors is upregulated in melanoma by key oncogenic drivers. HIFs promote the activation of genes involved in cancer initiation, progression, and metastases. Hypoxia has been shown to enhance the invasiveness and metastatic potential of tumor cells by regulating the genes involved in the breakdown of the ECM as well as genes that control motility and adhesion of tumor cells. Using a Pten -deficient, Braf -mutant genetically engineered mouse model of melanoma, we demonstrated that inactivation of HIF1α or HIF2α abrogates metastasis without affecting primary tumor formation. HIF1α and HIF2α drive melanoma invasion and invadopodia formation through PDGFRα and focal adhesion kinase–mediated (FAK-mediated) activation of SRC and by coordinating ECM degradation via MT1-MMP and MMP2 expression. These results establish the importance of HIFs in melanoma progression and demonstrate that HIF1α and HIF2α activate independent transcriptional programs that promote metastasis by coordinately regulating cell invasion and ECM remodeling

Effectiveness of Four Disinfectants against Ebola Virus on Different Materials

The West Africa Ebola virus (EBOV) outbreak has highlighted the need for effective disinfectants capable of reducing viral load in a range of sample types, equipment and settings. Although chlorine-based products are widely used, they can also be damaging to equipment or apparatus that needs continuous use such as aircraft use for transportation of infected people. Two aircraft cleaning solutions were assessed alongside two common laboratory disinfectants in a contact kill assay with EBOV on two aircraft relevant materials representative of a porous and non-porous surface. A decimal log reduction of viral titre of 4 is required for a disinfectant to be deemed effective and two of the disinfectants fulfilled this criteria under the conditions tested. One product, Ardrox 6092, was found to perform similarly to sodium hypochlorite, but as it does not have the corrosive properties of sodium hypochlorite, it could be an alternative disinfectant solution to be used for decontamination of EBOV on sensitive apparatus

Survival of Lassa Virus in Blood and Tissue Culture Media and in a Small Particle Aerosol

Knowledge of the survival and stability of a pathogen is important for understanding its risk, reducing its transmission, and establishing control measures. Lassa virus is endemic in West Africa, causes severe disease, and is an emerging pathogen of concern. Our study examined the survival of Lassa virus in blood and tissue culture media at two different temperatures. The stability of Lassa virus held within a small particle aerosol was also measured. In liquids, Lassa virus was found to decay more quickly at 30 °C compared to room temperature. Sealed samples protected from environmental desiccation were more stable than samples open to the environment. In a small particle aerosol, the decay rate of Lassa virus was determined at 2.69% per minute. This information can contribute to risk assessments and inform mitigation strategies in the event of an outbreak of Lassa virus

Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence

Survival and persistence of Nipah virus in blood and tissue culture media

ABSTRACTNipah virus (NiV) infection is a newly emerging zoonosis that causes severe disease in humans. Nipah virus is one of the lesser studied of the WHO emerging pathogens for which research is a priority. Survival and persistence data is important for risk management and understanding the hazard of the virus for laboratory and health care workers that may work with the virus and we present some initial findings on the survival of Nipah virus in blood and tissue culture media under different conditions. The titre of Nipah virus in blood or media at two different temperatures and exposed or sealed to the atmosphere was measured every day for three days and after a week. Nipah virus was very stable in blood in closed tubes held at room temperature with minimal decay over seven days. Decay was observed in all the other conditions tested and was more rapid in samples exposed to the atmosphere. Persistence data is useful for safety planning and risk management

Genetic Characterization of Blood Group Antigens for Polynesian Heritage Norfolk Island Residents

Improvements in blood group genotyping methods have allowed large scale population-based blood group genetics studies, facilitating the discovery of rare blood group antigens. Norfolk Island, an external and isolated territory of Australia, is one example of an underrepresented segment of the broader Australian population. Our study utilized whole genome sequencing data to characterize 43 blood group systems in 108 Norfolk Island residents. Blood group genotypes and phenotypes across the 43 systems were predicted using RBCeq. Predicted frequencies were compared to data available from the 1000G project. Additional copy number variation analysis was performed, investigating deletions outside of RHCE, RHD, and MNS systems. Examination of the ABO blood group system predicted a higher distribution of group A1 (45.37%) compared to group O (35.19%) in residents of the Norfolk Island group, similar to the distribution within European populations (42.94% and 38.97%, respectively). Examination of the Kidd blood group system demonstrated an increased prevalence of variants encoding the weakened Kidd phenotype at a combined prevalence of 12.04%, which is higher than that of the European population (5.96%) but lower than other populations in 1000G. Copy number variation analysis showed deletions within the Chido/Rodgers and ABO blood group systems. This study is the first step towards understanding blood group genotype and antigen distribution on Norfolk Island