Live Tweets from Applying Advanced Molecular Techniques to Healthcare Infection Day 3
26 Oct 2011Here is a crude file dump of my live tweets from the third day of the Applying Advanced Molecular Techniques to Healthcare Infection. Same caveats as before: apologies for extraneous material, but something better than nothing.
Also have created newspaper of links from the meeting here: http://paper.li/mjpallen/1319610603
#AAMTHI am signing off live tweeting and will start 3 hour drive home, skipping conference dinner; thanks for listening!
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#AAMTHI C. diff can be recovered from estuaries; same ribotypes as in human disease!
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#AAMTHI meeting closing down with last Q&A; arguing origins of Pittsburg/Montreal lineages; Lord Stan asking where C diff originated
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#AAMTHI Lawley gently dissing old-school typing methods but falling short of declaring genomic fundamentalism
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#AAMTHI in 027 lineage, 2/3 recurrences are relapses with same genotypes; 1/3 are reinfections. But even if same genotype maybe reinfection?
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#AAMTHI spread of montreal strain via Birmingham to Liverpool to Belfast incidence of 027 decreasing in Liverpool spatiotemporal clustering
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#AAMTHI phylogenomics of 027 can be reconstructed from start in Pittsburg; Montreal lineage v. spreadable; ≥4 introductions into UK
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#AAMTHI 027 strains from 19 countries sequenced pnas.org/content/107/16…
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#AAMTHI using 454 Illumina and optical mapping to do C diff genomic epidemiology via SNP trees
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#AAMTHI spores are immunogenic; spore specific abies available Wilcox report hpa.org.uk/webc/HPAwebFil…
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#AAMTHI C. diff spores very resistant and transmissible in animal house ID50 5 spores per cm2 in mice
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#AAMTHI EM images from ncbi.nlm.nih.gov/pubmed/20624955 "C. diff spores are beautiful"
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#AAMTHI Lawley now on spread of 027 strain; Canada, UK, now Australia incidence down now in UK
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#AAMTHI drinking from a fire hose? exciting stuff to come, but apparent ratio of unpublished to published work in Oxford on C. diff worrying
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#AAMTHI > 1 stool taken in 377 pts 79 cases showing mixed infections by MLST on serial samples around 20%! 2.6 new SNPs pa in trusted genome
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#AAMTHI 1500 isolates genome-sequenced good quality calls on >80% of genome error rate 1 SNP per 100 genomes
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#AAMTHI ST1 (ribotype 027) huge potential network Asked Q how many cases plausibly gained from ward contact 90% in first 2 weeks
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#AAMTHI constructed network of contacts in space/time five cases of ST63 If allow incubation period of 8 weeks get two clusters
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#AAMTHI 69 MLST types found in 984 cases at least 69 different outbreaks some rare some common clustering in time = cross infection??
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#AAMTHI 1280 C. diff cultured and MLSTed modal patients come in contact with ~300 patients within one year of C. diff
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#AAMTHI all diarrhoeal sttols tested for C diff All typed by MLST/ribotyping Research database with ethics approval 2m patients
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#AAMTHI difficult to estimate transmission parameters started with epidemiology hypothesis is that most CDI acquired by cross infection
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#AAMTHI Tim Peto on Modernising Molecular Microbiology C. difficile experience in Oxfordshire Radcliffe does tests for CDI
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#AAMTHI Atmar et al 2011 under review norovirus vaccine shows promise
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#AAMTHI ncbi.nlm.nih.gov/pubmed/21801639 Novel GII.12 norovirus strain, United States, 2009-2010
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#AAMTHI ncbi.nlm.nih.gov/pubmed/21801614 Novel surveillance network for norovirus gastroenteritis outbreaks, United States
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rnomics Fabrice Leclerc
RT @: #AAMTHI each animal has own calicivirus; reservoir for norovirus is probably... bit.ly/tZcTdE #rnomics-bioscience @MyEN
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#AAMTHI norovirus is number 1 in GI & foodborne illness 800 deaths in USA per year winter peak infectious dose 18 virions 10^10/g in stool!!
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#AAMTHI each animal has own calicivirus; reservoir for norovirus is probably humans no cell culture ~7kb +ssRNA virus
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#AAMTHI norovirus first known outbreaks probably in 1920-30s Norwalk Ohio outbreak 1972 en.wikipedia.org/wiki/Norovirus 1990 genome sequenced RT-PCR
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#AAMTHI Jan Vinje on norovirus Cruise ships ask crew to vomit over the side, not in toilets!
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#AAMTHI use SNP thresholds rather than precise numbers of SNPs Ben Cooper clearly clever enough to come work at @unibirmingham :-)
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#AAMTHI better results with sequence data; 100 SNPs; most connections make sense in light of epidemiology but some don't; need to combine
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#AAMTHI who infects who with or without sequence data ncbi.nlm.nih.gov/pubmed/18394654 Generation interval contraction and epidemic data analysis
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#AAMTHI estimates of daily per host transmission probability possible applied to WGS SNPs ! patient has cloud of strains 50 SNPs apart
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#AAMTHI ncbi.nlm.nih.gov/pubmed/21488764 Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections
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#AAMTHI ncbi.nlm.nih.gov/pubmed/21980062 Screening, isolation, decolonisation strategies in the control of MRSA in ICU: cost effectiveness evaluation
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#AAMTHI Cooper cites An augmented data method for the analysis of nosocomial infection data ncbi.nlm.nih.gov/pubmed/18635575
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#AAMTHI Ben Cooper talking about S. aureus transmission & models in Thailand cites ncbi.nlm.nih.gov/pubmed/19197054
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#AAMTHI After a morning talk about faecal microbiome transplants they serve this for lunch! twitpic.com/75lqjr
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#AAMTHI at last lunch; conclusion so far is that genomic epidemiology & culture-independent diagnosis hot topics, but lots of opportunities
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#AAMTHI mtz triggers VRE dominance; dominance in bowel microbiota predicts type of bacteraemia; VRE vs proteobacteria
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#AAMTHI aha, now some work on 16S V1-3 via 454 ncbi.nlm.nih.gov/pmc/articles/P… VRE domination of intestinal microbiota enabled by antibiotic treatment
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#AAMTHI S. viridans was problem then vanco prophylaxis led to VRE surge; surge in GNRs after quinolone prophylaxis stopped in 2010
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#AAMTHI Bactaermia common in pre-engraftment ≤10 days post-transplant; usually GI organisms VRE, Kleb, E coli, Enterobact etc VRE ++ > 2003
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#AAMTHI choice between deleting T-cells or not; if done, means less GVH, more odd opportunistic infections
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#AAMTHI now talk on allogeneic haematopoietic stem cell transplantation (allo-HSCT) and infection
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#AAMTHI ir.viropharma.com/releasedetail.… ViroPharma Initiates Phase 2 Study of VP 20621 for Prevention of Recurrence of CDI
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#AAMTHI old stuff being presented ncbi.nlm.nih.gov/pubmed/12447764 Colonization for the prevention of Clostridium difficile disease in hamsters
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#AAMTHI I find live tweeting is the only way to keep awake and alert at scientific meetings; cures ADHD and ensures CPD
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#AAMTHI ncbi.nlm.nih.gov/pubmed/19303570 New approach to the management of C. difficile infection: colonisation with non-toxigenic C. difficile...
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#AAMTHI Dale Gerding on use of non-toxigenic C diff. Looks like microbiological version of E. O. Wilson :-)
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#AAMTHI more on autism and microbiome udaan.org/drugs/vancocin… ncbi.nlm.nih.gov/pubmed/2152471… I remain skeptical...
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#AAMTHI now Louie claiming you can claiming autism by vancomycin or faecal microbiome transplant !?! Starting to get cranky!
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#AAMTHI Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients ncbi.nlm.nih.gov/pubmed/2566734 not much progress since
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#AAMTHI anecdotal stuff on which taxa change after faecal transplant; no consistent picture
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#AAMTHI 79/82 cases of CDI arrested after faecal transplant; low-level microbial ecology studies have been carried out, showing shifts
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#AAMTHI Louie explored various protocols, moved from enemas to oral capsule delivery of microbiome ncbi.nlm.nih.gov/pmc/articles/P…
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#AAMTHI The FECAL trial, Fecal therapy to Eliminate Clostridium difficile Associated Longstanding diarrhoea. trialregister.nl/trialreg/admin…
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#AAMTHI Treating Clostridium difficile Infection With Fecal Microbiota Transplantation ncbi.nlm.nih.gov/pubmed/21871249
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#AAMTHI faeces is the ultimate probiotic since 1950s known that shit stops diarrhoea 300 cases; varying metjods; enema, inoculum
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#AAMTHI revulsion common problem with this kind of research; poor legal framework; "chinese" takeaway home delivery service of human shit -)
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#AAMTHI Tom Louie on fecal microbiome transplants, i.e. eating shit coprophagy: a reboot of the microbiome common in animals
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#AAMTHI in Q&A, issue of whether metabolomics disturbance less important than disturbance of innate immunity effects from biota
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#AAMTHI Vince Young playing homage to Lord Stanley of Bitterroot alumni.stanford.edu/get/page/magaz… "It may be shit to you, but it's my bread and butter"
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#AAMTHI Young exploring probiotic potential of various spp from healthy CD-infected mice, but not naming them in this talk :-)
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#AAMTHI key paper on growing uncultured ncbi.nlm.nih.gov/pubmed/15294811 New strategies for cultivation and detection of previously uncultured microbes
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#AAMTHI need to go beyond 16S; short chain fatty acids levels go down in susceptibles
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#AAMTHI C diff becomes major component of microbiota in sick mice with CDI as measured by 16S cefaperazone model high mortality
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#AAMTHI preconditioning ABx, then clinda and C diff needed to cause colitis but lots of variability why some did not succumb?
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#AAMTHI mouse originally not good ncbi.nlm.nih.gov/pubmed/3533778 hamster popular mouse back in favour ncbi.nlm.nih.gov/pubmed?term=ke…
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#AAMTHI Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation ncbi.nlm.nih.gov/pubmed/19307217
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#AAMTHI Joke: Robert Koch one of few microbiologists not influenced by Falkow
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#AAMTHI traditional view CDI is ecological disease Koch's postulates; clindamycin colitis
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#AAMTHI dapper dresser Vincent Young takes the stage to talk about C diff and microbiota. sitemaker.umich.edu/younglab/home
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#AAMTHI Does the nose know? The odiferous diagnosis of Clostridium difficile-associated diarrhea ncbi.nlm.nih.gov/pubmed/17366472
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#AAMTHI cannot find any pubs on dogs smelling infection, but lots on cancer ncbi.nlm.nih.gov/pubmed/21790506
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#AAMTHI Beagle can sniff out smell of C. difficle; cheaper and quicker than PCR or genomics; nurses claim they can smell it
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#AAMTHI prediction of CDI recurrence possible ncbi.nlm.nih.gov/pubmed/19162027 may allow targeting of new treatments
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#AAMTHI “Archive of Live Tweets from Applying Advanced Molecular Techniques to Healthcare Infection Days 1-2 pathogenomics.bham.ac.uk/blog/2011/10/l…”
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#AAMTHI most recent study worked! Treatment with monoclonal antibodies against Clostridium difficile toxins ncbi.nlm.nih.gov/pubmed/20089970
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#AAMTHI oral and IVIG and hyperimmune Ig tried, but best is HuMab But in phase 2 HuMab antitoxin A alone failed
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#AAMTHI relations between Abies and CDI ncbi.nlm.nih.gov/pubmed/1066642… anti-toxin abies are protective against recurrence; interest in immune rx
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#AAMTHI IL-8 promoter -251 SNP ncbi.nlm.nih.gov/pubmed/21058913 African Americans get less CDI, have higher incidence of protective genotype
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#AAMTHI review from Kelly ncbi.nlm.nih.gov/pubmed/21415200 WBC counts predict bad outcome anti-CD18 ab prevents intestinal injury
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#AAMTHI Ciaran Kelly on C. difficile innate immunity colitis, pseudomembranes, PMNs, IL-8 promoter polymorphism tied to risk for CDI
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#AAMTHI storming talk just finished from Scott Hultgren too densely packed for tweeting; mannosides promising treatment ncbi.nlm.nih.gov/pubmed/20507142
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#AAMTHI more on UTI from Hultgren ncbi.nlm.nih.gov/pubmed/1809288…
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#AAMTHI complex dynamics in UTI ncbi.nlm.nih.gov/pubmed/21807904
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#AAMTHI also ncbi.nlm.nih.gov/pubmed/2129763…
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#AAMTHI talk on genetics of IBD to cut a long story short: ncbi.nlm.nih.gov/pubmed/21102463
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#AAMTHI clumping in plasma requires ClfA and coagulases; triple mutant cannot cause septic death direct thrombin inhibition delays death
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#AAMTHI two coagulases: Coa and vWBp; redundancy; double mutant delays time to death in sepsis model; coagulase gene very variable
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#AAMTHI Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses. ncbi.nlm.nih.gov/pubmed/21753082
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#AAMTHI protein A vaccine reduces load in mice and abscess numbers sepsis model is different from abscess model; far more severe
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#AAMTHI isd system involved in haem transport; IsdB vaccine has just failed in human trial :-) protein A promising candidate
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#AAMTHI sortase (strA) mutants cannot form abscesses; cleared slowly by day 15; LPXTG proteins important; 23 in genome; sdrD, isdAB, coa,cWb
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#AAMTHI small number of conserved core proteins in S. aureus; in mice bloodstream infection clears but kidney infection endures; abscesses
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#AAMTHI the legendary Olaf Schneewind takes the podium; a man who confessed yesterday that he did not know what Twitter was is being tweeted