Science Needs for Microbial Forensics Developing Initial International Research Priorities (2014) / Chapter Skim
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3 Microbial Forensics and Clinical and Public Health Considerations: Commonalities and Differences
3 Microbial Forensics and Clinical and Public Health Considerations: Commonalities and Differences
Pages 59-78
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From page 59... ...
CDC outlined what public health needs to know in the event of an infectious disease outbreak due to either natural causes or a biological attack: • The identity of the agent, • Whether it has antimicrobial susceptibilities, • The method of dispersal or dissemination, • The type of preparation (was it weaponized?
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From page 60... ...
Dr. Dana Kadavy of Signature Science, LLC, noted some general differences between the procedures used for clinical diagnostics and public health versus microbial forensics: • Clinical diagnostic analyses are designed to identify rapidly the species and possibly the strain of an infectious organism to inform effective treatment strategies.
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From page 61... ...
when illness is seen in persons in close proximity who have a common ventilation system; 9. Several unusual or unexplained diseases coexisting in the same patient with out any other explanation; 10.
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From page 62... ...
In microbial forensics, samples may come not only from clinical sources, but also environmental, food, and other matrices or be a completely unexpected target, as in a hoax. Sample types range from the simple to the complex, and across a clinical, clinical/ forensic, and forensic continuum.
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From page 63... ...
Some of these are also major concerns for public health, for example, the presence of antibiotic resistance or virulence genes, which may dictate differences in treatment options. Reporting requirements for characterization also are specific for the microbial forensics space, and some of these are shared with clinical diagnostic practices and food analysis systems.
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From page 64... ...
coli O104:H4 outbreak in Germany and a Klebsiella pneumoniae outbreak in the Netherlands to illustrate the usefulness of next-generation gene sequencing (NGS) in public health responses.
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From page 65... ...
; HUS, hemolytic uremic syndrome; LT, Life Technologies Group; PGM™, Ion Torrent Personal Genome Machine™; RKI, Robert Koch Institute (Germany) ; UKM, University Hospital Muenster (Germany)
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From page 66... ...
Phylogenetic analysis based on Sanger multilocus sequence typing (MLST) showed that the closest related genome was enteroaggregative E
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From page 67... ...
They enlisted the help of the Wellcome Trust Sanger Institute in Cambridge in the United Kingdom, which was conducting a global surveillance of Klebsiella. By comparing the candidate signature sequences against Sanger's additional 200 Klebsiella genomes, they identified two candidate regions that were specific for the Dutch outbreak (Netherlands National Institute for Public Health and the Environment, 2013)
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From page 68... ...
If this is the case, stored clinical data can also be analyzed for microbial forensics purposes if mechanisms for forensic analysts to access the clinical data can be devised. Clinical microbiologists are particularly interested in global surveillance for use in detecting early outbreaks.
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From page 69... ...
Although MLST is not popular for use with monomorphic organisms owing to its limited discriminatory power, it is still useful for other organisms and is influential from an intellectual point of view. Harmsen suggests using core-genome1 MLST, or using MLST+, which enables analysis of the seven "housekeeping" genes 2 as 1 The core genome is the set of genes that are present in all members of a species, suggest ing that they are required for essential cellular functions.
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From page 70... ...
Canonical SNPs offer the same range, if not better, of discriminatory powers. Martin Maiden recently proposed a system called ribosomal MLST (rMLST)
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From page 71... ...
. GonzálezCandelas described how phylogenetic inference and coalescent theory
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From page 72... ...
They concluded that an anesthetist working at the private hospital was the likely common source. A search for other potentially infected patients revealed a sizeable outbreak of HCV that appeared to be clearly linked to this one medical professional.
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From page 73... ...
There are many populations, and the longer a person is infected the more opportunity exists for minor differences. Most differences appearing in the widely divergent clade shared by the patients in the Valencia HCV outbreak probably represented sampling from the same source at different times over 10 years.
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From page 74... ...
There were many identical sequences, which appeared to be the "smoking gun" that linked about 150 patients to the anesthetist. The scientists, however, wanted to know how they should characterize possible victims who show a single nucleotide difference between their 6 Coalescent theory and phylogenetic inference: Phylogenetic inference uses the genetic variance between members of a population to infer evolutionary relationships; at the level of specific genes, alleles are used to create trees to represent how members split into separate branches, converge, or become extinct.
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From page 75... ...
, from patients excluded (dark purple) from the outbreak, and from local controls (gray)
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From page 76... ...
The conclusion of this approach was that sequences from 274 patients were grouped with the sequences from the presumed source, while the second group included all the sequences derived from the local controls and sequences from 47 patients initially considered to belong to the outbreak. Thus the separation between the two groups became clear.
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From page 77... ...
, patients excluded from the outbreak (47 and 559, dark purple) , local controls (42 and 453, gray)
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From page 78... ...
For moving forward, González-Candelas' conclusions are 1. Molecular phylogenetics and coalescent theory are essential for microbial forensics.
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