NCOH-EID. Prophylactic and Post-exposure Vaccines (PV) Collaboration between veterinary and human health - academically, governmentally, and industrially - is extremely important for the control of infectious diseases. In-depth knowledge on antigenic make-up of pathogens, the host response to these antigens, specific approaches to modifying this response through species-specific adjuvants, and vaccine delivery are needed for development of effective vaccines. A specific target in zoonotic infections is the possibility to not only reduce disease in the reservoir hosts – if it exists – but also to reduce pathogen circulation in the reservoir host, which may be a challenge and for instance require vaccines that develop strong mucosal immunity. Ideally, vaccines are needed that induce an immune- response that can be distinguished for the response to wild-type infection. While vaccination of animals for prevention of human disease may seem a straightforward approach, acceptance of such vaccines is likely to be low if animals appear healthy (MERS Coronavirus, hepatitis E, Chlamydia etc.) unless delivery is low cost and simple. Development of vaccines requires investment in the entire chain from protective antigen discovery, vaccine production, vaccine delivery to efficacy studies requiring basic knowledge about immunity. All expertise required for the needed multidisciplinary molecular-to- population vaccine research approach is available within NCOH-EID.
NCOH-EID. Frontline Diagnostics (FD) The unpredictable nature of EID makes diagnostic preparedness challenging, as the clinical presentation of most EID do not differ from common disease syndromes. With the rapid development of molecular diagnostic methods, more generic “catch-all” culture-based or microscopy based techniques have been largely replaced in diagnostic virology, and this trend is expected to persist in the coming years. In addition, the pressures to reduce healthcare costs have impacted on the acceptance of broader diagnostic evaluation of disease syndromes, leading to significant underdiagnoses. The average time to initial laboratory confirmation of outbreaks of EID notified to WHO is a little over one month, but with substantial longer delays in many instances (Xxxx et al., 2010). Recent outbreaks in The Netherlands show similar timelines: a long delay was seen in the initial discovery of the Q fever outbreak, and the clinical syndrome that was eventually diagnosed as Schmallenberg virus. This also includes diagnosis of unusual clinical syndromes in travellers that can introduce EID8. In pursuit of improving our capability for timely detection of EID, the improvement of frontline diagnostic capabilities is therefore essential.
NCOH-EID. New (alternative) Therapeutics (NT) A specific challenge with novel EID is that - typically - the field is left empty-handed when trying to treat new viral disease outbreaks. The traditional drug discovery pipeline aiming to develop specific antivirals is long, and little emphasis has been on development of broadly-reactive antiviral drugs, unlikely the AMR field. This gap is increasingly criticized in recent high-profile EID outbreaks and has triggered studies into repurposing of commonly used and registered drugs, rapid development of antibody based treatments, and the search for novel drugs that target components of the pathogen host interaction common to multiple viruses.
NCOH-EID. Outbreak Control Strategies (OC) The control of zoonotic EID outbreaks depends on the nature of transmission, and the effectiveness of the newly introduced pathogens to spread among humans or animals. With that, the focus of intervention strategies differs: for highly transmissible EID, where outbreaks occur in human populations or animal populations following a single introduction, focus of intervention will be in the host affected by disease, as for instance was the case in Ebola. For EID of zoonotic origin in which continuous zoonotic exposure is a driver of human disease, different approaches are needed. This likely includes development of vaccines to control pathogen circulation in animals, as has been used to control the Q fever outbreak and has been suggested for MERS CoV and avian influenza, for instance. While such vaccines may not be acceptable for routine disease control, emergency vaccination strategies can be an added tool to combat an EID outbreak. This has been one of the strategies in the Castellum project.
NCOH-EID. Underpinning Research on the drivers of Emergence and Spread Changes over the past decades in population demographics, animal husbandry practices and scale of animal production, and extent and speed of global travel and trade have increased the likelihood of international spread of diseases and vectors, but also affect evolution of pathogens which as a consequence again affects their ability to spread. The mechanisms underlying these changes are complex and multifactorial, and require epidemiological and laboratory analyses to fully understand describe the patterns of disease emergence and spread. Most high impact EIDs have in common that they appear unexpectedly, have great impact, and are detected when human or animal disease starts to occur. Understanding the key properties of an EID is crucial to gauge the (human and veterinary) public health response and to come up with proportionate, effective and acceptable control measures. This can be quite challenging during early stages of an EID when little is known, media may influence the public debate, and authorities are pressed for decision making. Optimally, the NCOH will have an integrated research agenda to address key questions arising during an EID event that can support development of tools to detect and monitor the disease and provide input for modelling of disease spread and interventions. The goal of our research in this Solution Set for NCOH-EID is (1) to identify and understand the key factors that render pathogens with human pandemic potential prone to cross the species barriers, adapt to the human host and further to gain human-to-human transmissibility, and (2) to translate our increased understanding of key factors in the chain of emergence to risk assessment, and options for prevention and intervention of human pandemics emerging from such pathogens.
