Grantee Research Project Results
Final Report: The Center for Advancing Microbial Risk Assessment (CAMRA)
EPA Grant Number: R832362Center: Duke University Center for Environmental Implications of NanoTechnology
Center Director: Wiesner, Mark R.
Title: The Center for Advancing Microbial Risk Assessment (CAMRA)
Investigators: Rose, Joan B. , Gerba, Charles P. , S. Eisenberg, Joseph N. , Haas, Charles N. , Koopman, James , Gurian, Patrick , Weber, Rosina , Todd, Ewen
Institution: Michigan State University , University of Arizona , Drexel University , Northern Arizona University , University of California - Berkeley , University of Michigan
EPA Project Officer: Packard, Benjamin H
Project Period: September 1, 2005 through August 31, 2010
Project Amount: $10,000,000
RFA: DHS-EPA Cooperative Center of Excellence on the Methods and Science to Conduct Microbial Risk Assessment in Support of Homeland Security Objectives (2004) RFA Text | Recipients Lists
Research Category: Drinking Water , Human Health , Homeland Security , Water
Objective:
The Center for Advancing Microbial Risk Assessment (CAMRA) has finished its work under the EPA STAR grant funded from 2005 through March 2013. CAMRA had two missions. The first was to develop models, tools and information that will be used in a credible risk assessment framework to reduce or eliminate health impacts from deliberate use of biological agents of concern in the indoor and outdoor environment.
To accomplish this first objective, the five project teams (associated with Project I: Exposure; Project II: Infectious Disease Transmission; Project III: Dose-Response; Project IV: Risk Assessment and Analysis; and Project V: Knowledge Management and Transfer) have worked together within the Quantitative Microbial Risk Assessment (QMRA) framework, completing and publishing a total of 52 journal articles with 434 citations during the past 6 years (Figure 1 shows the key projects and number of papers and the complete list of publications is included with this report). Nineteen different pathogens have been studied and described in these publications (Figure 2). As one of the most interesting categories of pathogens to EPA and OHS, Category A agents Bacillus anthracis (B. anthracis), Yersinia pestis (Y. pestis) and Fransicella tularensis (F. tularensis), have been studied extensively in more than 10 articles. A number of agents associated with waterborne, airborne and foodborne diseases such as Cryptosporidium, E. coli, norovirus, influenza viruses and Mycobacterium tuberculosis also have received significant attention.
Figure 1. Risk assesment framework and the papers and citions by different
CAMRA projects.
Figure 2. Number of CAMRA papers with each stated pathogen or indicator (excluding review articles)
The second mission was to build a national network for microbial risk knowledge management, learning and transfer for the community of scientists and students via educational programs and community of professionals in the field and in our communities.
This has been accomplished through the QMRA summer institutes, and the final few months of the grant will focus on adding to our knowledge system, the QMRA wiki. Appendix B submitted to EPA with the progress report contained some screen shots of some of the key components of the QMRA wiki, including landing pages for Hazard ID; Dose Response; Exposure; Risk Characterization; Risk Management; and finally the QMRA calculator.
Summary/Accomplishments (Outputs/Outcomes):
CAMRA's high productivity after 6 years has now reached an exciting level of maturity in which the frameworks and assessments are being integrated into the research by all PIs and projects. The knowledge gained has been presented to the risk community this past year (2011–2012) through 23 publications and 15 presentations. The next generation of QMRA students has graduated and these individuals are entering the workforce. Dr. Jade Mitchell and Dr. Mark Weir both recently joined Michigan State University and Temple, respectively, as assistant professors.
CAMRA will finalize publications (9 in review, revision or preparation) and models as most of the outputs are in the shape of a paper in preparation or under review.
Accomplishment Type | Amount |
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Peer reviewed publications | 23 |
Peer reviewed proceedings | 2 |
Master's thesis | 1 |
Doctoral dissertations | 1 |
Conference Presentations | 15 |
Supported students | 13 |
Students graduated | 2 |
CAMRA Project I has completed work on fomite-human exposure pathways addressing the transfer efficiency of Escherichia coli, coliphage MS-2, and Bacillus thuringiensis spores on various fomite surfaces, i.e., acrylic, stainless steel, Formica, glass, ceramic tile, cotton, polyester and paper money. Project I also examined the effect of low and high relative humidity on bacterial and viral survival on several common inanimate surfaces (fomites). The data analysis and manuscript preparation for the droplet spray exposure study in Project I are completed. These data suggest that the ability to transmit infection by droplet spray exposure is highly variable across infected persons influenced by distance and force of the coughing.
Literature from published journal articles on the detection methods for influenza, norovirus, and MRSA will be reviewed. Journal articles will be collected using a number of keywords on ISI Web of Science. References will be exported into an EndNote file. A manual screening will be conducted to eliminate any references that are not expected to contain relevant data.
Digital LAMP has been investigated as a method and the environmental detection limits to address various levels of risk have been explored. The survey of environmental detection limit, published in the journal Applied and Environmental Microbiology, Implications of Limits of Detection of Various Methods for Bacillus anthracis in Computing Risks to Human Health, also highlighted the need to develop methods capable of detecting much lower concentrations of threat agents. One of the novel methods/approaches used is called digital PCR (which is akin to carrying out a most probable number analysis but in nanoliter real time PCR chambers). When combined with the method that is known for better limit of detection (isothermal amplification), such an approach has the potential to improve the environmental detection limit by at least 100-fold. The goal of this "digital LAMP" approach is to experimentally test this hypothesis.
Project I team members have used metagenomics approaches to address fomite contamination and hazard discovery for viruses, finding that a wide array of bacteriophage are likely targets for further work to improve exposure assessment. Bacterial samples collected from the fomite surfaces in dormitories at the University of Michigan will be evaluated and characterized by sequencing 16S rRNA genes using 454 FLX sequencing technology. Primers designed to target conserved regions surrounding hyper-variable regions of relevant genes will be used to amplify the 16S rRNA sequences and sequenced by high throughput sequencing. Signature sequences found with 454 Sequencing Technology will be evaluated for the presence of pathogenic and non-pathogenic organisms on the fomites.
For drinking water pathways, Project I showed the usefulness of a risk assessment simulation as a way of evaluating sensor placement and tested the axial dispersion of a sodium chloride tracer passing through a cross junction to evaluate AZRED-II in comparison to both EPANET and AZRED-I and embedded axial dispersion into the AZRED code in order to fully integrate both of the improved transport assumptions for water quality analyses.
Project II has used a deterministic differential equation based model to describe the hand and environmental mediated transmission of Methicillin-resistant Staphylococcus aureus (MRSA). Project II conducted research on modeling influenza transmission on a college campus. Local weather variables were found to be statistically significant in association with the proportion of cases that tested positive for influenza virus and the proportion of diagnosis in outpatients visiting Hong Kong influenza surveillance sites. Project II examined the successes and shortcomings of polio eradication using a transmission modeling analysis.
Project III has added to the impressive dose-response models developing models for Brucella species Leptospira bacteria, Rickettsia rickettsii, Rickettsia typhi and Avian Influenza A (HSNl) Virus. Project III has developed the first inclusion of time post inoculation into dose-response models, which allows for great advancements in understanding how the body reacts to pathogen exposure and paves the way for understanding the effect of multiple dosing of pathogens on the host. Dose Response Models incorporating Aerosol Size Dependency were developed for F. tularensis and B. anthracis. This project also addressed Francisella tularensis associated with ingestion and multiple exposures. Human health risks posed by Aspergillus fumigatus and risk mode for inhaled toxins associated with spores of Stachy are in progress.
Project IV's work on surface concentration standards for non-persistent pathogens has been a collaborative effort with Project III. Project III identified suitable dose-response models and uncertainties for the effort. In addition, a review paper on persistence of Category A pathogens developed by Project I has been a key resource for this study. A joint paper with Project III has been published in PLoS ONE and received favorable reviewer comments. Project IV researchers also performed an analysis of microbial spore recovery. The use of the wipe collection method on non-porous surfaces resulted in the highest recoveries.
Project V has investigated and implemented effective and efficient methods to enhance the understanding of microbial risk assessment (MRA) as a body of knowledge. Project V has built and maintained an online collaborative repository and collaborated with other projects working on an open repository. A major effort has been focused on development of the CAMRA Risk Wiki.
The major accomplishment of the 2011–2012 project year is the QMRA wiki, a collaborative work among all CAMRA projects (http://wiki.camra.msu.edu/index.php?title=Quantitative_Microbial_Risk_Assessment_(QMRA)_Wiki Exit).
Currently, CAMRA wiki contents include an overview of 25 different pathogens and 39 completed dose-response models (bacteria, viruses, protozoa and prion). Exposure assessment, risk characterization and risk management sections have been constructed and content is being added. Dose-Response Calculator persistent models are significant features in wiki. The dose-response models have been compiled in a dose response monograph. The final review has been undertaken and will be available for purchase by the end of the year.
Conclusions:
Many organizations are adopting wiki technology to facilitate information management and collaborations. While many studies have tried to identify factors that facilitate or impede wiki adoption, the results have been mixed. Some factors may facilitate wiki adoption in one organization, but are found to impede adoption in another organization. Through a review of existing literature, key communication scientists (Drs. Jonathan Obar and Maria Lainski working with CAMRA) argue that the mixed results may be caused by lumping wikis used for information management purposes with wikis used for collaborative communication purposes. In order to better understand how factors contribute to wiki adoption, it is vital to make the conceptual distinction between long-term information management wikis and short-term collaborative communication wikis for wiki researchers and designers. CAMRA will continue to explore how these concepts can advance QMRA knowledge, use and contributions.
Journal Articles: 56 Displayed | Download in RIS Format
Other center views: | All 101 publications | 59 publications in selected types | All 56 journal articles |
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Ahmad F, Pandey AK, Herzog AB, Rose JB, Gerba CP, Hashsham SA. Environmental applications and potential health implications of quantum dots. Journal of Nanoparticle Research 2012;14:1038. |
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Austin RG, van Bloemen Waanders B, McKenna S, Choi CY. Mixing at cross junctions in water distribution systems. II:Experimental study. Journal of Water Resources Planning and Management 2008;134(3):295-302. |
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Bartrand TA, Weir MH, Haas CN. Dose-response models for inhalation of Bacillus anthracis spores: interspecies comparisons. Risk Analysis 2008;28(4):1115-1124. |
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Boone SA, Gerba CP. Significance of fomites in the spread of respiratory and enteric viral disease. Applied and Environmental Microbiology 2007;73(6):1687-1696. |
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Casman EA, Fischhoff B. Risk communication planning for the aftermath of a plague bioattack. Risk Analysis 2008;28(5):1327-1342. |
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Corella-Barud V, Mena KD, Gibbs SG, Gurian PL, Barud A. Evaluation of neighborhood treatment systems for potable water supply. International Journal of Environmental Health Research 2009;19(1):49-58. |
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Durham DP, Casman EA. Threshold conditions for the persistence of plague transmission in urban rats. Risk Analysis 2009;29(12):1655-1663. |
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Greenberg DL, Busch JD, Keim P, Wagner DM. Identifying experimental surrogates for Bacillus anthracis spores: a review. Investigative Genetics 2010;1(1):4 (12 pp.). |
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Gunawardena S, Weber R, Agosto DE. Finding that special someone: interdisciplinary collaboration in an academic context. Journal of Education for Library and Information Science 2010;51(4):210-221. |
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Haas CN. Microbial dose response modeling: past, present, and future. Environmental Science & Technology 2015;49(3):1245-1259. |
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Hamilton MA, Hong T, Casman E, Gurian PL. Risk-based decision making for reoccupation of contaminated areas following a wide-area anthrax release. Risk Analysis 2015;35(7):1348-1363. |
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Herzog AB, McLennan SD, Pandey AK, Gerba CP, Haas CN, Rose JB, Hashsham SA. Implications of limits of detection of various methods for Bacillus anthracis in computing risks to human health. Applied and Environmental Microbiology 2009;75(19):6331-6339. |
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Herzog AB, Pandey AK, Reyes-Gastelum D, Gerba CP, Rose JB, Hashsham SA. Evaluation of sample recovery efficiency for bacteriophage P22 on fomites. Applied and Environmental Microbiology 2012;78(22):7915-7922. |
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Hong T, Gurian PL, Ward NFD. Setting risk-informed environmental standards for Bacillus anthracis spores. Risk Analysis 2010;30(10):1602-1622. |
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Hong T, Gurian PL.Characterizing bioaerosol risk from environmental sampling. Environmental Science & Technology 2012;46(12):6714-6722. |
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Hong T, Gurian PL, Huang Y, Haas CN. Prioritizing risks and uncertainties from intentional release of selected Category A pathogens. PLoS ONE 2012;7(3):e32732 (19 pp.). |
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Huang Y, Haas CN. Time-dose-response models for microbial risk assessment. Risk Analysis 2009;29(5):648-661. |
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Huang Y, Bartrand TA, Haas CN, Weir MH. Incorporating time postinoculation into a dose-response model of Yersinia pestis in mice. Journal of Applied Microbiology 2009;107(3):727-735. |
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Huang Y, Hong T, Bartrand TA, Gurian PL, Haas CN, Liu R, Tamrakar SB. How sensitive is safe? Risk-based targets or ambient monitoring of pathogens. IEEE Sensors Journal 2010;10(3):668-673. |
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Huang Y, Haas CN. Quantification of the relationship between bacterial kinetics and host response for monkeys exposed to aerosolized Francisella tularensis. Applied and Environmental Microbiology 2011;77(2):485-490. |
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Jones RM, Masago Y, Bartrand T, Haas CN, Nicas M, Rose JB. Characterizing the risk of infection from Mycobacterium tuberculosis in commercial passenger aircraft using quantitative microbial risk assessment. Risk Analysis 2009;29(3):355-365. |
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Jones R, Nicas M. Experimental determination of supermicrometer particle fate subsequent to a point release within a room under natural and forced mixing. Aerosol Science and Technology 2009;43(9):921-938. |
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Kim M, Choi CY, Gerba CP. Source tracking of microbial intrusion in water systems using artificial neural networks. Water Research 2008;42(4-5):1308-1314. |
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Kitajima M, Huang Y, Watanabe T, Katayama H, Haas CN. Dose-response time modelling for highly pathogenic avian influenza A (H5N1) virus infection. Letters in Applied Microbiology 2011;53(4):438-444. |
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Li S, Eisenberg JNS, Spicknall IH, Koopman JS. Dynamics and control of infections transmitted from person to person through the environment. American Journal of Epidemiology 2009;170(2):257-265. |
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Lopez GU, Gerba CP, Tamimi AH, Kitajima M, Maxwell SL, Rose JB. Transfer efficiency of bacteria and viruses from porous and nonporous fomites to fingers under different relative humidity conditions. Applied and Environmental Microbiology 2013;79(18):5728-5734. |
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Masago Y, Shibata T, Rose JB. Bacteriophage P22 and Staphylococcus aureus attenuation on nonporous fomites as determined by plate assay and quantitative PCR. Applied and Environmental Microbiology 2008;74(18):5838-5840. |
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Mayer BT, Koopman JS, Ionides EL, Pujol JM, Eisenberg JNS. A dynamic dose-response model to account for exposure patterns in risk assessment: a case study in inhalation anthrax. Journal of the Royal Society, Interface 2011;8(57):506-517. |
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Mayer BT, Eisenberg JNS, Henry CJ, Gomes MGM, Ionides EL, Koopman JS. Successes and shortcomings of polio eradication: a transmission modeling analysis. American Journal of Epidemiology 2013;177(11):1236-1245. |
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Milbrath MO, Spicknall IH, Zelner JL, Moe CL, Eisenberg JNS. Heterogeneity in norovirus shedding duration affects community risk. Epidemiology and Infection 2013;141(8):1572-1584. |
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Mitchell-Blackwood J, Gurian PL, O'Donnell C. Finding risk-based switchover points for response decisions for environmental exposure to Bacillus anthracis. Human and Ecological Risk Assessment 2011;17(2):489-509. |
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Mitchell-Blackwood J, Gurian PL, Lee R, Thran B. Variance in Bacillus anthracis virulence assessed through Bayesian hierarchical dose-response modelling. Journal of Applied Microbiology 2012;113(2):265-275. |
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Pujol JM, Eisenberg JE, Haas CN, Koopman JS. The effect of ongoing exposure dynamics in dose response relationships. PLoS Computational Biology 2009;5(6):e1000399. |
R832362 (2007) R832362 (Final) |
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Razzolini MTP, Weir MH, Matte MH, Matte GR, Fernandes LN, Rose JB. Risk of Giardia infection for drinking water and bathing in a peri-urban area in São Paulo, Brazil. International Journal of Environmental Health Research 2011;21(3):222-234. |
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Romero-Gomez P, Ho CK, Choi CY. Mixing at cross junctions in water distribution systems. I: Numerical study. Journal of Water Resources Planning and Management 2008;134(3):285-294. |
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Romero-Gomez P, Choi CY. Axial dispersion coefficients in laminar flows of water-distribution systems. Journal of Hydraulic Engineering 2011;137(11):1500-1508. |
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Romero-Gomez P, Lansey KE, Choi CY. Impact of an incomplete solute mixing model on sensor network design. Journal of Hydroinformatics 2011;13(4):642-651. |
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Ryan MO, Gurian PL, Haas CN, Rose JB, Duzinsk PJ. Acceptable microbial risk: cost-benefit analysis of a boil water order for Cryptosporidium. Journal American Water Works Association 2013;105(4):E189-E194. |
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Sinclair RG, Romero-Gomez P, Choi CY, Gerba CP. Assessment of MS-2 phage and salt tracers to characterize axial dispersion in water distribution systems. Journal of Environmental Science and Health, Part A:Toxic/Hazardous Substances and Environmental Engineering 2009;44(10):963-971. |
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Sinclair RG, Rose JB, Hashsham SA, Gerba CP, Haas CN. Criteria for selection of surrogates used to study the fate and control of pathogens in the environment. Applied and Environmental Microbiology 2012;78(6):1969-1977. |
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Sinclair R, Boone SA, Greenberg D, Keim P, Gerba CP. Persistence of category A select agents in the environment. Applied and Environmental Microbiology 2008;74(3):555-563. |
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Solon I, Gurian PL, Perez H. The extraction of a Bacillus anthracis surrogate from HVAC filters. Indoor and Built Environment 2012;21(4):562-567. |
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Song I, Romero-Gomez P, Choi CY. Experimental verification of incomplete solute mixing in a pressurized pipe network with multiple cross junctions. Journal of Hydraulic Engineering 2009;135(11):1005-1011. |
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Spicknall IH, Koopman JS, Nicas M, Pujol JM, Li S, Eisenberg JNS. Informing optimal environmental influenza interventions: how the host, agent, and environment alter dominant routes of transmission. PLoS Computational Biology 2010;6(10):e1000969. |
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Tamrakar SB, Haas CN. Dose-response model for Burkholderia pseudomallei (melioidosis). Journal of Applied Microbiology 2008;105(5):1361-1371. |
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Tamrakar SB, Haluska A, Haas CN, Bartrand TA. Dose-response model of Coxiella burnetii (Q fever). Risk Analysis 2011;31(1):120-128. |
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Tamrakar SB, Haas CN. Dose-response model of Rocky Mountain spotted fever (RMSF) for human. Risk Analysis 2011;31(10):1610-1621. |
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Tamrakar SB, Huang Y, Teske SS, Haas CN. Dose-response model of murine typhus (Rickettsia typhi): time post inoculation and host age dependency analysis. BMC Infectious Diseases 2012;12:77 (14 pp.). |
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Tamrakar S, Haas C. Dose-response model for Lassa virus. Human and Ecological Risk Assessment 2008;14(4):742-752. |
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Teske SS, Huang Y, Tamrakar SB, Bartrand TA, Weir MH, Haas CN. Animal and human dose-response models for Brucella species. Risk Analysis 2011;31(10):1576-1596. |
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Weber RO. Addressing failure factors in knowledge management. Electronic Journal of Knowledge Management 2007;5(3):334-347. |
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Weir MH, Haas CN. Quantification of the effects of age on the dose response of Variola major in suckling mice. Human and Ecological Risk Assessment 2009;15(6):1245-1256. |
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Weir MH, Pepe Razzolini MTP, Rose JB, Masago Y. Water reclamation redesign for reducing Cryptosporidium risks at a recreational spray park using stochastic models. Water Research 2011;45(19):6504-6514. |
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Yoon J-Y, Han J-H, Choi CY, Bui M, Sinclair RG. Real-time detection of Escherichia coli in water pipe using a microfluidic device with one-step latex immunoagglutination assay. Transactions of the ASABE 2009;52(3):1031-1039. |
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Zelner JL, King AA, Moe CL, Eisenberg JNS. How infections propagate after point-source outbreaks: an analysis of secondary norovirus transmission. Epidemiology 2010;21(5):711-718. |
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Zhao J, Eisenberg JE, Spicknall IH, Li S, Koopman JS. Model analysis of fomite mediated influenza transmission. PLoS ONE 2012;7(12):e51984 (11 pp.). |
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Supplemental Keywords:
RFA, Scientific Discipline, INTERNATIONAL COOPERATION, Water, Environmental Monitoring, Ecological Risk Assessment, Drinking Water, homeland security, microbial risk assessment, pathogens, bioterrorism, environmental awareness, biological agents of concern, biopollution, air pollution, community water system, drinking water monitoring, analytical methods, drinking water distribution system, microbial risk management, water qualityProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.