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Genomic Signature of Multi-Drug Resistant Salmonella Typhi related to a Massive Outbreak in Zambia during 2010 - 2012.
[typhoid]
Retrospectively
,
we
investigated
the
epidemiology
of
a
massive
Salmonella
enterica
serovar
Typhi
outbreak
in
Zambia
during
2010
to
2012
.
Ninety
-
four
isolates
were
susceptibility
tested
by
MIC
determinations
.
Whole
genome
sequence
typing
(
WGST
)
of
33
isolates
and
bioinformatic
analysis
identified
the
MLST
,
haplotype
,
plasmid
replicon
,
antimicrobial
resistance
genes
,
and
the
genetic
relatedness
by
Single
Nucleotide
Polymorphism
(
SNP
)
analysis
and
genomic
deletions
.
The
outbreak
affected
2
,
040
patients
with
a
fatality
rate
of
0
.
5
%
.
Most
isolates
(
83
.
0
%
)
were
multi-drug
resistant
(
MDR
)
.
The
isolates
belonged
to
MLST
ST
1
and
a
new
variant
of
the
haplotype
;
H
58
B
.
Most
isolates
contained
a
chromosomally
translocated
region
containing
seven
antimicrobial
resistance
genes
;
catA
1
,
blaTEM-
1
,
dfrA
7
,
sul
1
,
sul
2
,
strA
,
and
strB
,
fragments
of
incQ
1
plasmid
replicon
,
class
1
integron
,
and
the
mer
operon
.
The
genomic
analysis
revealed
an
overall
415
SNPs
difference
and
35
deletions
among
33
of
the
isolates
whole
genome
sequenced
.
In
comparison
with
other
genomes
of
H
58
,
the
Zambian
isolates
separated
from
genomes
from
Central
Africa
and
India
with
34
and
52
SNPs
,
respectively
.
The
phylogenetic
analysis
indicates
that
32
isolates
of
the
33
sequenced
belonged
to
a
tight
clonal
group
,
distinct
from
other
H
58
genomes
included
in
the
study
.
The
small
numbers
of
SNPs
identified
within
this
group
are
consistent
with
short
-term
transmission
that
can
be
expected
over
a
period
of
2
years
.
The
phylogenetic
analysis
and
deletions
suggest
that
a
single
MDR
clone
was
responsible
for
the
outbreak
during
which
occasional
other
S
.
Typhi
lineages
including
sensitive
ones
continued
to
co
-circulate
.
The
common
view
is
that
the
emerging
global
S
.
Typhi
haplotype
;
H
58
B
,
containing
the
MDR
incHI
1
plasmid
is
responsible
for
the
majority
of
typhoid
infections
in
Asia
and
sub-
Saharan
Africa
;
we
found
that
a
new
variant
of
the
haplotype
harbouring
a
chromosomally
translocated
region
containing
the
MDR
islands
of
incHI
1
plasmid
emerged
in
Zambia
.
This
could
chance
the
perception
of
the
term
"
classical
MDR
typhoid
"
currently
being
solely
associated
with
the
incHI
1
plasmid
.
It
might
be
more
common
than
anticipated
that
S
.
Typhi
haplotype
;
H
58
B
harbour
either
the
incHI
1
plasmid
and
/
or
a
chromosomally
translocated
MDR
region
.
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