Impact/Purpose:

Explore and support the best approaches for determining how, when, and for what pathogens, VFAR concepts can be used to identify pathogens that are hazardous to humans, in order to identify pathogens to nominate for the CCL process.

Description:

The Board on Environmental Studies and Toxicology (BEST) of the National Research Council (NRC) recently published recommendations on "Classifying Drinking Water Contaminants for Regulatory Consideration" (2001). In that report, (see http://books.nap.edu/books/0309074088/html/143.html#pagetop) the NRC proposed that virulence factor activity relationships (VFARs) of pathogenic microorganisms may be analogous to the structural activity relationships (SARs) that are used to predict the physical/chemical properties of chemicals. To the extent that this analogy is valid, VFARs should be useful in predicting the pathogenicity of microorganisms in specific cases. The Office of Ground Water and Drinking Water (OGWDW) would like to know how, and under what circumstances, VFARs can be used to identify microorganisms that need regulatory attention. While offering great potential for identifying potentially hazardous pathogens, the use of VFARs also faces several technical challenges, including: (1) the entire array of factors needed to cause disease is not known for any pathogen; so the presence of the DNA coding for one or several virulence factors in a single organism does not necessarily mean that organism is capable of causing illness, (2) some organisms carry virulence genes but don't express them, and (3) some of the analytical techniques to identify the genetic markers, like polymerase chain reaction (PCR) and microarray analyses, do not distinguish between live or dead microorganisms. In spite of these and other challenges, it may be possible to incorporate VFARs, along with other factors, in the process of evaluating the pathogenic potential of CCL-1 microorganisms as well as microorganisms to be considered for the third Contaminant Candidate List (CCL-3). The National Exposure Research Laboratory (NERL) will solicit proposals for research to help us identify factors that promote virulence in bacteria, viruses and protozoan parasites, identify factors that distinguish pathogens that infect humans from those that only infect non-human species or enable us to determine the extent to which structural similarities of virulence factors carry over across species, genus or even family lines. The solicitation will be prepared using the expert advice that will be provided in a workshop to be held in Baltimore MD, October 28 and 29, 2004.

Record Details:

Record Type:PROJECT

Start Date:05/01/2003

Projected Completion Date:09/01/2007

OMB Category:Other

Record ID: 56118

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Project Information:

Progress :This is one of five tasks in MCEARD for understanding and characterizing the use of virulence factors to predict the hazard that microorganisms may pose to humans. A steering committee, consisting of participants from NERL and The Office of Ground Water and Drinking Water, was formed and the design of the workshop was completed. The workshop was held in October2004 using the World health Organization (WHO) format. A suumary report will be completed iby January 2005 and a book consisting of chapters based on the workshop presentations will be published in 2005. The majority of participants believe that the ultimate goal of analyzing water samples with microarrays containing probes for virulence genes is not achievable in the near future, but there were many examples cited of the use of factors like VFARS to describe virulence in specific instances. The workshop participants suggested that pilot studies should be developed to allow EPA to incorporate the VFARs concept into evaluating current CCL organisms and determining the next CCL, where applicable. The information from the report will be used in developing a request for proposals.

Relevance :The NRC subcommittee has suggested that VFARs may provide a more rapid means of identifying waterborne pathogens than the current process that relies on exposure and health effects as the two primary categories for screening potential microbial drinking water contaminants. If VFARs can fulfill their potential, then the current approach, which enables us to address only one or two microorganisms for unregulated contaminant monitoring every five to ten years, would be considerably faster. This in turn would speed up the entire regulatory process for microbial contaminants.

Project IDs:

ID Code :15585

Project type :OMIS