AMR symposium
·
key message is that MDR is an issue with
treatment of TF with antibiotic
·
Need for close cooperation to address this
problem between clinician and laboratory experts
Genomics and host susceptibility to enteric fever and NTS
disease
·
HLA and resistance to enteric fever
o
this is beyond my understanding
o
Key messages:
§
HLA –DRB1+0405 major contributor to resistance
§
May affect antigen presentation
§
T cell response
§
Key individuals in PAHS Salmonella study – Well
Come Trust
·
Buddha Basnyat
·
Samir Koirala
·
Sabina Dongol
·
Amit Aryal
·
Abhilasha Karki
Immunity to invasive S infections: lessons from animal
models and man
·
System infection progress in distinct phases
o
Innate response
o
Adaptive response (inflammation)
o
T cell dependent acquired immunity
·
“Like a castle cards” – interesting analogy
·
Dynamics of the “in vivo” infection process,
immunity and vaccination (thru molecularly tagged or fluorescent)
·
Dispersive infections with intracellular and
extracellular phases (analogy - catch me if you can!!)
·
Lessons from Human - vaccines
o
How can we expect the infection with external
intervention?
o
Optimize antibody response: isotypes and
effector functions
o
Primed cellular response
o
Ab + Cell mediated immunity
o
Epidemiological risk factor vs. susceptibility
to disease ( innate immunity and adaptive immunity)
·
Novel insights in host response to understand
pathogenesis
o
Typhoid challenge model
o
Waddington et al., CID 2014
o
Cytokines – early response (disappears after 12
hrs)
o
Gene expression after challenge
§
Interferon
o
Cytokines – post response
Typhoid toxin (geno toxin) - Song et al, Nature (2013)
absent in non typhoidal Salmonellae
- Fundamental questions
- Cytolethal distending toxin + Pertusis toxin
o
Why it causes typhoid fever?
o
Why it only cause disease in humans?
o
a novel toxin and a novel pathway for exotoxin
delivery by an intracellular pathogen
o
Salmonella cultured does not produce it??
o
S ty[phi does not survive ……intracellular
macrophage
o
Rab 32 / 38 dependent pathway in macrophase - mechanism of restriction in mice
o
Typhoid organism must have adapted well in
humans thru certain sialic acids / glycans
o
Toxin can not affect chimpanzees
o
Deng et al, Cell (in press)
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