A major cause of respiratory failure during influenza A virus (IAV) infection is damage to the epithelial–endothelial barrier of the pulmonary alveolus. Damage to this barrier results in flooding of the alveolar lumen with proteinaceous oedema fluid, erythrocytes and inflammatory cells. To date, the exact roles of pulmonary epithelial and endothelial cells in this process remain unclear.Here, we used anin vitroco-culture model to understand how IAV damages the pulmonary epithelial–endothelial barrier. Human epithelial cells were seeded on the upper half of a transwell membrane while human endothelial cells were seeded on the lower half. These cells were then grown in co-culture and IAV was added to the upper chamber.We showed that the addition of IAV (H1N1 and H5N1 subtypes) resulted in significant barrier damage. Interestingly, we found that, while endothelial cells mounted a pro-inflammatory/pro-coagulant response to a viral infection in the adjacent epithelial cells, damage to the alveolar epithelial–endothelial barrier occurred independently of endothelial cells. Rather, barrier damage was associated with disruption of tight junctions amongst epithelial cells, and specifically with loss of tight junction protein claudin-4.Taken together, these data suggest that maintaining epithelial cell integrity is key in reducing pulmonary oedema during IAV infection.

Thrombocytopenia, which signifies a low platelet count usually below 150 × 10⁹/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, raises the suspicion of a viral infection. This phenomenon is classically attributed to platelet consumption due to inflammation-induced coagulation, sequestration from the circulation by phagocytosis and hypersplenism, and impaired platelet production due to defective megakaryopoiesis or cytokine-induced myelosuppression. All these mechanisms, while plausible and supported by substantial evidence, regard platelets as passive bystanders during viral infection. However, platelets are increasingly recognized as active players in the (antiviral) immune response and have been shown to interact with cells of the innate and adaptive immune system as well as directly with viruses. These findings can be of interest both for understanding the pathogenesis of viral infectious diseases and predicting outcome. In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.

Vaccination uptake has decreased globally in recent years, with a subsequent rise of vaccine-preventable diseases. Travellers, immunocompromised patients (ICP), and healthcare workers (HCW) are groups at increased risk for (severe) infectious diseases due to their behaviour, health, or occupation, respectively. While targeted vaccination guidelines are available, vaccination uptake seems low. In this review, we give a comprehensive overview of determinants—based on the integrated change model—predicting vaccination uptake in these groups. In travellers, low perceived risk of infection and low awareness of vaccination recommendations contributed to low uptake. Additionally, ICP were often unaware of the recommended vaccinations. A physician’s recommendation is strongly correlated with higher uptake. Furthermore, ICP appeared to be mainly concerned about the risks of vaccination and fear of deterioration of their underlying disease. For HCW, perceived risk of (the severity of) infection for themselves and for their patients together with perceived benefits of vaccination contribute most to their vaccination behaviour. As the determinants that affect uptake are numerous and diverse, we argue that future studies and interventions should be based on multifactorial health behaviour models, especially for travellers and ICP as only a limited number of such studies is available yet.

The family Flaviviridae, genus Flavivirus, holds many of the world’s most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods. We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray. Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses. Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses. The number of international travelers has increased dramatically in recent decades. This has contributed to the increase in infectious diseases in travelers which are not present in their countries of origin and so may cause a threat to the public health. Viruses transmitted by biting insects (vector-borne viruses) are an important group within these travel-related diseases. They are found across the world and can cause debilitating and life-threatening symptoms, like inflammation of the brain or excessive bleeding. Many of these diseases are difficult to distinguish from each other. They cause comparable symptoms and are genetically closely related. Testing for long lists of diseases is time consuming and expensive. Here we develop a novel testing tool that allows doctors and researchers to test for multiple viruses with just one test. The method, which uses a specific part of the virus that makes distinguishing between infections with these closely related viruses possible, requires only one drop of blood. This allows us to test for multiple viruses simultaneously with the same amount of blood previously used to test for only one virus, while distinguishing between genetically closely related viruses.