Emerging infections: surveillance, epidemiology and pathogenesis

To prepare for the next emerging infection, our goal is to establish a state-of-the-art EmergingInfectious Diseases Research Center with surveillance for the key disease syndromes - respiratory disease,encephalitis and fever of unknown origin- that have been observed most frequently associated with emergingviruses in the past few decades. In parallel, surveillance of animal and insect vectors will be performed toidentify the origins of and define transmissions patterns associated with, these novel emerging viruses. TheCenter includes four international surveillance sites-China, Hong Kong, Nepal and Ethiopia- which werecarefully selected on the basis of having either an established history of viral emergence or high potential tocapture such events. China, Hong Kong and Nepal are all situated in Southeast Asia, which has historicallybeen a nidus for many emerging viruses such as H5N1 influenza, SARS Coronavirus, Severe Fever andThrombocytopenia virus, and the very recently reported Alongshan virus. Ethiopia, along with NortheasternAfrica, is at high risk for emergence of MERS Coronavirus (MERS-CoV) due to endemicity of MERS in camels,a key reservoir in the region. To identify novel or emerging viruses, we will use complementary virus family-specific consensus PCR and unbiased next generation sequencing approaches and then sequence theircomplete genomes. Subsequently, we will generate key reagents essential for establishment of diagnosticassays and the study of fundamental aspects of viral pathogenesis, epidemiology, and immune control. Theseinclude development of cell culture systems, targeted RT-PCR/PCR assays, serological assays, monoclonalantibodies for antigen detection and potential therapeutic applications, mouse models of infection, and ifappropriate, ferret models of virus transmission. An additional component of the center is international capacitybuilding. Initial efforts focus on two exemplar viruses: MERS-CoV, a recently emerged virus, and a highlyvariant Dengue virus, Dengue virus 5, which is has prevalence and emergence potential. MERS-CoV is adeadly zoonotic respiratory pathogen with a case fatality rate of ~35% to date. We will implement surveillancefor these viruses and develop additional reagents and assays to characterize their epidemiology andpathogenic potential. These efforts will establish and validate the critical infrastructure necessary to respond toa new emerging infectious disease. In the event of a new outbreak, efforts will be reprioritized to focus onresponse to the new emerging threat. The priorities, in order, are: (1) Human and animal surveillance fornovel/emerging viruses; (2) Assay and reagent development; (3) Define epidemiology of novel/emergingviruses; (4) Pathogenesis, immune control, transmission and treatment of novel/emerging viruses.