Emerging infections: surveillance, epidemiology and pathogenesis

SUMMARY To prepare for the next emerging infection, our goal is to establish a state-of-the-art Emerging Infectious 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 emerging viruses in the past few decades. In parallel, surveillance of animal and insect vectors will be performed to identify the origins of and define transmissions patterns associated with, these novel emerging viruses. The Center includes four international surveillance sites-China, Hong Kong, Nepal and Ethiopia- which were carefully selected on the basis of having either an established history of viral emergence or high potential to capture such events. China, Hong Kong and Nepal are all situated in Southeast Asia, which has historically been a nidus for many emerging viruses such as H5N1 influenza, SARS Coronavirus, Severe Fever and Thrombocytopenia virus, and the very recently reported Alongshan virus. Ethiopia, along with Northeastern Africa, 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 their complete genomes. Subsequently, we will generate key reagents essential for establishment of diagnostic assays and the study of fundamental aspects of viral pathogenesis, epidemiology, and immune control. These include development of cell culture systems, targeted RT-PCR/PCR assays, serological assays, monoclonal antibodies for antigen detection and potential therapeutic applications, mouse models of infection, and if appropriate, ferret models of virus transmission. An additional component of the center is international capacity building. Initial efforts focus on two exemplar viruses: MERS-CoV, a recently emerged virus, and a highly variant Dengue virus, Dengue virus 5, which is has prevalence and emergence potential. MERS-CoV is a deadly zoonotic respiratory pathogen with a case fatality rate of ~35% to date. We will implement surveillance for these viruses and develop additional reagents and assays to characterize their epidemiology and pathogenic potential. These efforts will establish and validate the critical infrastructure necessary to respond to a new emerging infectious disease. In the event of a new outbreak, efforts will be reprioritized to focus on response to the new emerging threat. The priorities, in order, are: (1) Human and animal surveillance for novel/emerging viruses; (2) Assay and reagent development; (3) Define epidemiology of novel/emerging viruses; (4) Pathogenesis, immune control, transmission and treatment of novel/emerging viruses.