Pre-symptomatic diagnosis and treatment of filovirus diseases

Abstract

Filoviruses are virulent human pathogens which cause severe illness with high case fatality rates and for which there are no available FDA-approved vaccines or therapeutics. Diagnostic tools including antibody- and molecular-based assays, mass spectrometry, and next-generation sequencing are continually under development. Assays using the polymerase chain reaction (PCR) have become the mainstay for the detection of filoviruses in outbreak settings. In many cases, real-time reverse transcriptase-PCR allows for the detection of filoviruses to be carried out with minimal manipulation and equipment and can provide results in less than 2 h. In cases of novel, highly diverse filoviruses, random-primed pyrosequencing approaches have proved useful. Ideally, diagnostic tests would allow for diagnosis of filovirus infection as early as possible after infection, either before symptoms begin, in the event of a known exposure or epidemiologic outbreak, or post-symptomatically. If tests could provide an early definitive diagnosis, then this information may be used to inform the choice of possible therapeutics. Several exciting new candidate therapeutics have been described recently; molecules that have therapeutic activity when administered to animal models of infection several days post-exposure, once signs of disease have begun. The latest data for candidate nucleoside analogs, small interfering RNA (siRNA) molecules, phosphorodiamidate (PMO) molecules, as well as antibody and blood-product therapeutics and therapeutic vaccines are discussed. For filovirus researchers and government agencies interested in making treatments available for a nation's defense as well as its general public, having the right diagnostic tools to identify filovirus infections, as well as a panel of available therapeutics for treatment when needed, is a high priority. Additional research in both areas is required for ultimate success, but significant progress is being made to reach these goals.

Keywords: Ebola; Marburg; diagnostics; therapeutics; zoonosis.

FIGURE 1

Current workflow for the detection of filoviral proteins and host response proteins in serum samples from Ebola virus-infected NHPs. The use of SDS PAGE sample buffer and boiling provides inactivation of the virus allowing downstream processing to take place in a BSL-2 environment.