Isabelle Bolon

Plasminogen Mediates the Pathological Effects of Urokinase-Type Plasminogen Activator Overexpression

Increased expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is associated with different pathological conditions. Both uPAR-mediated signaling and plasmin-catalyzed extracellular proteolysis may contribute to pathogenesis. To evaluate the involvement of plasminogen in such circumstances, we have taken advantage of transgenic mouse models in which overexpression of uPA and/or uPAR in enamel epithelium, basal epidermis, and hair follicles leads to a pathological phenotype; uPA transgenic mice have chalky-white incisors and, when uPAR is co-expressed, develop extensive alopecia, epidermal thickening, and subepidermal blisters. We report here that when these transgenic mice were backcrossed into a plasminogen-deficient (Plg-/-) background, the dental and skin phenotypes appeared completely normal. Heterozygous Plg+/- transgenic mice exhibited a haplo-insufficiency, with an intermediate or normal phenotype. These results do not argue in favor of a role for uPAR-mediated signaling in our experimental model; rather, they demonstrate an essential, dose-dependent, requirement for plasminogen in uPA-mediated tissue alterations. They also support the hypothesis that plasminogen could play a part in certain skin diseases.

Precision global health in the digital age

Precision global health is an approach similar to precision medicine, which facilitates, through innovation and technology, better targeting of public health interventions on a global scale, for the purpose of maximising their effectiveness and relevance. Illustrative examples include: the use of remote sensing data to fight vector-borne diseases; large databases of genomic sequences of foodborne pathogens helping to identify origins of outbreaks; social networks and internet search engines for tracking communicable diseases; cell phone data in humanitarian actions; drones to deliver healthcare services in remote and secluded areas. Open science and data sharing platforms are proposed for fostering international research programmes under fair, ethical and respectful conditions. Innovative education, such as massive open online courses or serious games, can promote wider access to training in public health and improving health literacy. The world is moving towards learning healthcare systems. Professionals are equipped with data collection and decision support devices. They share information, which are complemented by external sources, and analysed in real time using machine learning techniques. They allow for the early detection of anomalies, and eventually guide appropriate public health interventions. This article shows how information-driven approaches, enabled by digital technologies, can help improving global health with greater equity.

Climate change and One Health

Abstract The journal The Lancet recently published a countdown on health and climate change. Attention was focused solely on humans. However, animals, including wildlife, livestock and pets, may also be impacted by climate change. Complementary to the high relevance of awareness rising for protecting humans against climate change, here we present a One Health approach, which aims at the simultaneous protection of humans, animals and the environment from climate change impacts (climate change adaptation). We postulate that integrated approaches save human and animal lives and reduce costs when compared to public and animal health sectors working separately. A One Health approach to climate change adaptation may significantly contribute to food security with emphasis on animal source foods, extensive livestock systems, particularly ruminant livestock, environmental sanitation, and steps towards regional and global integrated syndromic surveillance and response systems. The cost of outbreaks of emerging vector‐borne zoonotic pathogens may be much lower if they are detected early in the vector or in livestock rather than later in humans. Therefore, integrated community‐based surveillance of zoonoses is a promising avenue to reduce health effects of climate change.

Climate change and infectious diseases

Global changes are major determinants for infectious diseases, although attributable, part of climate change remains debatable. Vector-borne diseases are prone to be impacted by global warming, although other factors may play a substantial role, evidenced by the dramatic decrease in malaria in the last decades in places where climate change has deep and significant effects. There is now evidence that in some areas of the world, e.g. Horn of Africa, warm El Niño Southern Oscillations (ENSO), which are observed in the South Pacific Ocean, are associated with higher risk of emergence of Rift Valley fever, cholera and malaria and during cold La Niña events, dengue fever, chikungunya and yellow fever. This has been observed for these and other diseases in other parts of the world. For example, seasonal influenza outbreaks have been more intense (i.e. higher number) and more severe (i.e. higher mortality) when concomitant with La Niña events. Since climate scientists have recently observed that climate change is tied to more frequent and more intense ENSO events, we may foresee increases in frequency and severity in emerging infectious diseases in the world.

Participatory approaches and open data on venomous snakes: A neglected opportunity in the global snakebite crisis?

1 Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 2 EnviroSPACE Lab, Institute for Environmental Sciences, University of Geneva, Geneva, Switzerland, 3 Division of Tropical and Humanitarian Medicine, University Hospitals of Geneva, Geneva, Switzerland, 4 Médecins Sans Frontières, Geneva, Switzerland, 5 Citizen Cyberlab, CERN-UNITAR-University of Geneva, Geneva, Switzerland

Taking flight with Precision Global Health: a scoping review on avian influenza

Avian influenza is an infection of birds caused by the Influenza A virus, which due to crowded conditions and occupational exposure in live poultry markets, has jumped the species barrier to humans. With an estimated case fatality rate of up to 60%, it is vital to map the existing digital technologies that may be utilized to improve disease monitoring and health outcomes for avian influenza. This scoping review aimed to identify which digital technologies may improve disease prevention, detection and control, and could be used as a basis for strengthening health systems. A search was conducted on PubMed and Web of Science for studies that reported the utilization of digital technologies with specific reference to avian influenza. Search dates ranged from 2009 (January) to 2017 (July). Data was extracted into a summative table, citations managed using EndNote software and data synthesized through grouping digital technology domains, using narrative and graphical methods. The scoping review identified 111 relevant studies, and revealed data modelling (n=72) and novel technologies (n=15) referring primarily to diagnostic tools, to be the most utilized technologies in tackling avian influenza. A large portion of the data-modelling domain was compromised of computer-assisted mathematical modelling (n=42) including mathematical modelling (n=8), simulation modelling (n=14) and spatioal-temporal modelling (n=20), primarily used to estimate outbreak distribution according to migratory patterns and transmission dynamics. A major challenge reported was poor biosecurity measures of poultry markets. Digital technologies indicated potential in improving disease detection, control and prevention, particularly through the use of data modelling with meteorological data sets. However, it became evident, that to maximize potential of these digital technologies better implementation of biosecurity measures would be necessary in majorly affected regions such as Asia.