Researchers at the Greene Infectious Disease Laboratory at Columbia University's Mailman School of Public Health, led by Thomas Briese, associate professor of epidemiology, have developed a rapid, comprehensive diagnostic test for viral hemorrhagic fevers caused by the Ebola and Marburg viruses, as well as others. The new diagnostic tool is addressed in a paper published in the April 2006 issue of the Centers for Disease Control and Prevention's (CDC) Emerging Infectious Diseases.
Increasing international travel, trafficking in wildlife, political instability and terrorism have made emerging infectious diseases a global concern. Viral hemorrhagic fevers (VHF) are of specific concern because they are associated with high morbidity and mortality (up to 80% mortality rates), and the potential for rapid dissemination through human-to-human transmission. The term "viral hemorrhagic fever" characterizes a severe multi-system syndrome associated with fever, shock and bleeding caused by infection with one of a number of viruses, such as Ebola or Marburg.
"Currently, there is no way to treat most of these outbreaks," stated W. Ian Lipkin, director of the Jerome L. and Dawn Greene Infectious Disease Laboratory at the Mailman School, and professor of epidemiology, neurology and pathology at Columbia. He added, "The most important first step is diagnostic -- rapid identification of the exact pathogen responsible for an outbreak of disease is critical for containment and the implementation of public health measures, especially in instances where the agents are encountered out of their natural geographic context."
While other tools exist for the detection of VHF agents, none offers the sensitivity and speed of this new diagnostic screen, which incorporates MassTag PCR technology -- providing the ability to simultaneously consider multiple agents, thereby reducing the time needed for differential diagnosis. To address the need for highly sensitive diagnostics, researchers built on an established method known as polymerase chain reaction that allows amplification of genetic sequences and on a technology previously used for DNA sequencing and detection of genetic polymorphisms. Genetic probes for pathogens were coupled to markers known as mass codes. After amplification, incorporated mass codes were detected by mass spectroscopy allowing identification of the pathogen.
To facilitate rapid differential diagnosis of VHF agents, Briese and colleagues established the "Greene MassTag Panel VHF v1.0," which can screen simultaneously for Ebola Zaire, Ebola Sudan, Marburg, Lassa virus, Rift Valley fever, Crimean-Congo hemorrhagic fever, Hantaan, Seoul, yellow fever, and Kyasanur Forest disease viruses.
These results confirm earlier work in respiratory diseases indicating that MassTag PCR offers a rapid, sensitive, specific, and economic approach to differential diagnosis of infectious diseases. Small, low-cost, or mobile APCI-MS units extend the applicability of this technique beyond selected reference laboratories.
Lipkin said, "This work represents an unprecedented collaboration in the creation of diagnostics for the developing world. The contributors to this work represent laboratories devoted to strengthening global disease surveillance and outbreak response capabilities."
A vital part of the commitment includes validation of innovative, new detection tools for diagnosis of emerging and high-risk pathogens, as well as distribution of assays and reagents in global laboratory networks. The working group consisted of representatives from the following institutions:
- Jerome L. and Dawn Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, New York, USA
- Special Pathogens Unit, National Institute for Communicable Diseases, Sandringham, South Africa
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, USA
- Bernhard-Nocht-- Institute of Tropical Medicine, Hamburg, Germany
- Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, USA
- Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada
- NIH, NIAID, USA
Funding for the project was received from the National Institutes of Health / National Institute of Allergy and Infectious Diseases.