Pre-Symptomatic Diagnosis of Ebola Virus Infection

The epidemic of Ebola virus disease (EVD) that occurred in West Africa during 2013-2014 was a reminder that such outbreaks may continue indefinitely. With the aim of improving diagnosis of EVD early after possible exposure, we worked with data from studies published before the outbreak to ask if changes in the infected host might be assayable within a day of infection, well before the accumulation of viral proteins or nucleic acid which may take several days and on which all existing assays are based. We studied the changes in macaque and human peripheral blood cell gene expression after infection with Zaire Ebolavirus (ZEBOV) to identify host responses that occur before the emergence of symptoms. We identified host mRNAs that were differentially expressed at early, middle, and late times after infection. From the group of ZEBOV-specific genes, we predicted those that encoded secreted or membrane-associated proteins. We identified pairs of these host response mRNAs or proteins that are characteristic of early ZEBOV infections and other pairs that classify ZEBOV from other common pathogens (malaria, rhinovirus, influenza) that could become candidates for differential diagnosis of an early ZEBOV infection, before the emergence of conventional symptoms. Four key immune response pathways that were activated early showed profoundly decreased expression at late times, identifying key control points. We recognize the limitations of our approach which was based on in vitro and in vivo data from human cells and non-human primate infection studies. But absent stage-specific profiles of blood proteins from infected individuals, our approach shows how such data could be modeled. The need for improved diagnostics remains urgent in view of the recent findings that ZEBOV can persist in the body of a survivor for months after infection as well as the enormous mortality of health care workers in the West African outbreak.