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www.ScienceTranslation
alMedicine.org 19
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sue 165 165rv13
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ssi
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Fig. 1. Remarkable fungal infections. (Top, left to right) Chronic mucocutaneous candidiasis, chromoblastomycosis, and mucicarmine-stained histological section of the cerebellum of an AIDS patient
who died from cryptococcal meningoencephalitis (demonstrating an abundance of pink-stained fungi).
(Bottom) Computed tomography (CT) scan of the lungs of a patient showing a large fungal ball
(aspergilloma, black box), which was surgically removed (right). Three smaller cavities are also visible
in the CT scan (red arrows), which is typical of chronic pulmonary aspergillosis.
rty
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Fig. 3. Diagnostic dilemma. A representative clinical scenario that demonstrates the magnitude of problems
associated with the diagnosis of fungal infections with current diagnostic tools. The figure shows the diagnostic
considerations, starting with the organ that may be involved (inner circle), the most likely diagnoses (middle
circle), and the testing required to rule in or out each of these diagnoses (outer circle). Certain features of the
illness make some diagnoses much more or less likely, in particular, the patients travel history and skin
papule, whereas other abnormalities are nonspecific. The patient is a 53-year-old man (photograph displayed
unaltered, with permission from patient) admitted after having been increasingly unwell for 10 days despite
administration of oral antibiotics. He has a previous history of pneumonia (2 years earlier), is a 30pack per
year smoker, and takes 15 mg of prednisolone (a cor-ticosteroid) and 50 mg of azathioprine (an
immunosuppressive agent) for interstitial lung disease. He has traveled extensively in the United States,
southern Europe, and the Middle East. On admission, he had a fever of 38.3C, was slightly confused but fully
conscious, had oxygen saturations of 94%, had a blood pressure of 95/60 (low), had a new nonulcerated dark
papule on his right lower arm 1 cm across, and had nonspecific general wheezing in his chest. He had a
slightly raised white blood cell count with neutro-philia, a raised serum creatinine indicative of significantly
impaired renal function, and negative blood cultures. Nine months earlier, an HIV antibody test had been
performed for employment purposes and was negative. His chest radiograph showed slightly increased
haziness bilaterally and showed no improve-ment after 36 hours of treatment with broad-spectrum antibiotics.
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1 4
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De
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c 165
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.
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s W.
t War
e noc
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t A.
s
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a
. M
p
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rh
,
.
A
.
P
f
a
l
l
e
D
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e
k
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m
a
,
4.
Pah
p issa
u;
b Bar
l cel
i ona
c Ca
ndi
h de
e mia
a Proj
l ect
t Stu
dy
of
Gro u
n isol
up,
a ate
u
r
Epi s
de t
l s
miol
u red
ogy
and
pre
dict
ors
of
mor
talit
y in
cas
es
of
Can
did
a
blo
ods
trea
m
infe
ctio
n:
Res
ults
fro
m
pop
ulati
onbas
ed
sur
veill
anc
e,
bar
celo
na,
Spa
in,
fro
m
200
e
d
,
B
.
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a
h
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n
,
8
.
2 to C
200 .
3.
J.
Clin h
.
Mic n
robi h
ol.
43, y
182 d
9
183 r
,
5
(20 M
05). .
16
. M
.
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.
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r
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n
d
r
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p
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.
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m
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a
t
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s with
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v d
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l sus
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c J.
e Clin
.
o Mic
f robi
f ol.
u 43,
n 44
g 34
e
44
m 40
i (20
a 05)
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D
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n
2.
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uu
a
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r
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k
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:
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a
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b
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l
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y
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ha
h
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g
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h
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al
t
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s
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ga
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em
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e
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m
nm
i
ark
a
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a
n
20
d
06:
Inc
n
rea
u
sin
m
g
b
inci
e
de
r
nc
s
e
m
of
fun
ga
em
ia
an
d
nu
mb
ers
of
isol
ate
s
wit
h
red
uc
ed
az
ole
sus
ce
pti
bilit
y.
Cli
n.
Mic
rob
iol.
Inf
ect
.
14,
48
7
49
4
(20
08)
.
18
. L
.
R
.
A
s
m
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n
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.
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t
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.
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r
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u
o
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.
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u
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.
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o
t
t
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o
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l
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r
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p
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m
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d
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a
:
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v
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d
e
n
ce
e2
1o
f
c
l
u
s A.
t Pfa
e ller,
r Epi
s
3.
de
mio
o
log
f
y of
can
s
did
m
emi
o
l a:
d 3e Ye
r ar
i res
n ults
g fro
m
n the
o em
s ergi
o ng
c infe
o ctio
mns
i and
a the
l epi
de
i mio
n log
f y of
e
Iow
c
a
org
t
ani
i
sm
o
s
n
stu
s
dy.
.
J.
CCli
l n.
i Mic
n robi
. ol.
40,
I 129
n 8
f 130
e2
c (20
t 02)
. .
2D
i
s
.
1
0.
4 Mor
g
7 a
, n,
e
1
7
W
.
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e
eY
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t
o
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0
0
0
i
n
a
p
o
p
u
l
a
t
i
o
n
b
a
s
e
d
a
4. c
W.
Wa
rno
ck,
Inci
de
nc
e
of
blo
od
str
ea
m
inf
ecti
on
s
du
e
to
Ca
ndi
da
sp
eci
es
an
d
in
vitr
o
sus
ce
pti
bilit
ies
of
isol
ate
s
coll
ect
ed
fro
m
19
98
t
i
v
e
s
u
r
v
e
i
l
l
a
n
c
e
p
r
o
g
r
a
m
.
J
.
C
l
i
n
.
M
i
c
r
o
b
i
o
l
.
4
2
,
1
5s
1
9
1
5
2
7
(
2
0
0
4
)
.
2
1. P
.
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a
n
d
v
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n
,
L
.
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v
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n
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r
,
A
.
D
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g
r
a
n
e
s
,
H
.
H
.
H
a
u
k
l
a
n
d
,
T
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M
a
n
n
23
.
F
.
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.
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d
d
s
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.
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,
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h
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.
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h
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.
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o
w
,
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.
L
.
o
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s
,
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e
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a
r
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t
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s
u
r
v
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y
o
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a
n
d
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d
a
b
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d
s
t
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a
m
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f
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c
t
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s
i
n
S
c
o
t
l
a
n
d
.
M /
ew
d
.
M
i
c
r
o
b
i
o
l
.
5
6
,
1
0
6
6
1
0
7
5
2
2
2
2
2
3
3
3
1
8.
(
2 H.
0 G
0 r
7 e
) e
. n
,
K
.
M
u
. t
S al
. it
h
a
& s,
D
W .
o D
e
r s
l ai
d ,
I.
P D
o .
P
p a
u v
l o
a r
t d
,
i A
o .
n J.
W
C a
l r
dl
o a
c w
k ,
s C
; .
H
.
h P
t a
t s
p hl
: e
y,
/ I
/ g
w E
w s
w e
n
. si
c ti
e z
n a
s ti
u o
n
s t
. o
2
4. U
g
o
v As
/ per
mgill
a us
i fu
n
mi
gat
us
is
ass
oci
ate
d
wit
h
red
uc
ed
lun
g
fun
ctio
n
in
ast
hm
a.
Am
. J.
Re
spi
r.
Crit
.
Ca
re
Me
d.
18
2,
13
62
13
68
(20
10)
.
33
. D
.
W
.
D
e
n
n
i
n
g
,
B
.
R
.
O
D
r
i
s
c
o
ll
,
C
.
M
.
H
o
g
a
b
o
a
m
,
P
.
B
o
w
y
e
r
,
R
.
M
.
N
i
v
e
n
,
T
h
e
l
i
n
k
b
e
t
w
e
e
n
3
3
em
ve
i
d
e
n
c
e
.
3
3
3E
u Cli
r n.
Inf
. ect
.
RDis
e.
46,
s
62
p 5
i 63
r3
. (20
08)
.
J
.
2
7
,
4
4
4 61
5
4
4
6
2
6
(
42
0
f
u
n
g
i
a
n
d
s
e
v
e
r
e
4 06
)
4.
34
4. D
5.
M
Cel
l
e Ho
n st
z Mi
i cro
a
s
t
h
m
a
:
A
s
u
m
m
a
r
y
o
f
t
h
e
be
11,
s 42
, 2
42
4
(20
. 12)
.
L
H
o
5l
5 es
,
C.
Sp
G ald
. ing
,
MH.
Z.
c
Ell
C
ou
u mi,
M.
L.
Pa
uls
on,
J.
Da
vis,
A.
Hs
u,
A.
I.
As
her
, J.
O
Sh
ea,
S.
M.
Hol
lan
d,
W.
E.
Pa
ul,
D.
C.
Do
ue
k,
Im
pai
red
T
17
cell
diff
ere
nti
ati
on
in
su
bje
cts
wit
h
aut
os
om
al
do
mina
nt
hy
per
IgE
syn
dro
me
.
Nat
ure
45
2,
77
3
77
6
(20
08)
.
REVIEW
.
F
l
a
t
o
t
,
M
.
M
i
g
a
u
d
,
M
.
C
h
r
a
b
i
e
h
,
T
.
K
o
c
h
e
t
k
o
v
,
A
.
B
o
l
z
e
,
53
. L
.
L
i
u
,
S
.
O
k
a
d
a
,
X
.
F
.
K
o
n
g
,
A
.
Y
.
K
r
e
i
n
s
,
S
.
C
y
p
o
w
y
j,
A
.
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wT
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s
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a
ti
o
n
a
Vol
4
Issu
e
165
165
rv13