Download Cryptococcus gattii genotype VGIIb infection in Japan

Med. Mycol. J.
Med. Mycol. J. Vol. 55（No. 3）
, 2014
Vol. 55E, E 51 − E 54, 2014
ISSN 2185 − 6486
E 51
Short Report
Cryptococcus gattii genotype VGIIb infection in Japan
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Ichiro Kawamura , Katsuhiko Kamei , Kyoko Yarita , Misako Ohkusu , Kenta Ito ,
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Mika Tsukahara , Masatake Honda , Kazuhisa Nakashima , Hiroaki Akamatsu ,
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Hanako Kurai
Division of Infectious Diseases, Shizuoka Cancer Center Hospital
Medical Mycology Research Center, Chiba University
"
Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital
'
Pathology Division, Shizuoka Cancer Center Hospital
)
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital
+
Third Department of Internal Medicine, Wakayama Medical University
ABSTRACT
This report describes a case of Cryptococcus gattii VGIIb infection of the pulmonary and central
nervous systems in an immunocompetent Japanese man with a travel history, and it hypothesizes the
place where he was infected with C. gattii using the genotype information.
Key words：cryptococcosis, Cryptococcus gattii, genotype VGIIb
Introduction
Cryptococcus gattii causes a life-threatening
infection of the pulmonary and central nervous
systems and has traditionally been considered to
be geographically restricted to the tropical and
subtropical regions of the world. However, an
outbreak in the Pacific Northwest of North
America has changed our understanding of the
1）
epidemiology of C. gattii infection . Sporadic
cases have also been documented in other
regions, including areas in Europe, Asia, Africa,
2, 3）
and South America . These reports have demonstrated a much less restrictive geographic
range for C. gattii than previously thought.
There are four genotypes of C. gattii, VGI to
VGIV, each containing subtypes as determined by
several genotyping techniques. Genotypes VGI
and VGII are prevalent worldwide, while VGIII and
3）
VGIV are less common . VG genotypes indicate
that their distribution and frequency vary among
Address for correspondence : Ichiro Kawamura
Division of Infectious Diseases, Shizuoka Cancer Center Hospital
Received : 18, April 2014. Accepted : 6, June 2014
[email protected]
different geographic regions, although further
studies are needed to explain possible connections between the distributions of various genotypes.
Since 2001, Japanese cases of C. gattii infection
4−6）
have sporadically been reported
. This report
describes a case of C. gattii VGIIb infection of the
pulmonary and central nervous systems in an
immunocompetent Japanese man with a travel
history, and it hypothesizes the place where he
was infected with C. gattii using the genotype
information.
Case
A previously healthy 41-year-old Japanese male
was referred to the Shizuoka Cancer Center for a
left lung mass. He complained of fever, cough, and
headaches for two months. Six months before his
symptoms started, he had traveled to Nanjing in
China for one week. Additional travel history
included trips to Hong Kong and Shanghai in
E 52
Medical Mycology Journal Volume 55, Number 3, 2014
Fig. 1．Contrast-enhanced chest computed tomography revealed a large consolidated mass in the left
lower lobe, accompanied by mediastinal lymphadenopathy.
Fig. 2．Axial gadolinium-enhanced FLAIR showed a
small enhancing nodule（arrow）within the temporal
lobe. FLAIR, fluid-attenuated inversion recovery.
China, as well as Hawaii in the United States
during his twenties. He was an office worker who
had not been exposed to imported timber or
animals.
Examination upon hospital admission revealed
wheezes in his left lung. Chest computed tomography revealed a large consolidated mass in the
lower left lung lobe（Fig. 1）
. Transbronchial
biopsy demonstrated numerous fungal elements
observed as encapsulated yeast with clear halos,
a characteristic of Cryptococcus spp. A Cryptococcus sp. was later cultured from bronchoalveolar lavage fluid. Magnetic resonance imaging of
the brain showed multiple small nodules throughout the cerebral parenchyma（Fig. 2）. Lumbar
puncture had a normal opening pressure at 19 cm
H2 O, and the cerebrospinal fluid contained 276
nucleated cells, 84% of which were lymphocytes;
no Cryptococcus spp. were isolated. Anti-HIV and
anti-HTLV-1 antibody tests were negative. The
cryptococcal strain isolated from the bronchoalveolar lavage was identified as C. gattii by
analyzing the sequences of the internal trans7）
cribed spacer regions . Multi-locus sequence
typing（MLST）based on the sequence analysis of
a set of polymorphic loci revealed that the isolate
8）
was molecular type VGIIb .
After eight weeks of liposomal amphotericin B
treatment, along with six weeks of flucytosine
therapy, the patient began consolidation therapy
with 800 mg of oral fluconazole daily for eight
weeks, followed by maintenance therapy with 400
mg fluconazole daily for an anticipated 16-month
9, 10）
course
. One year after the initiation of antifun-
gal therapy, the patient was asymptomatic and
appeared healthy.
Discussion
We described a case of C. gattii genotype VGIIb
infection in a Japanese male with a travel history
to several cities in China and Hawaii. In 2001,
Tsunemi et al. reported the first Japanese case in
a healthy 71-year-old physician who had traveled
4）
to Australia for one week . Okamoto et al.
reported a genotype VGIIa case in an immunocompetent 44-year-old sign painter who had
5）
traveled to Guam and Saipan . To the best of our
knowledge, genotype VGIIb was first detected in
clinical specimens from Japan.
VGII has been reported in the Western Hemisphere, Australasia, Asia, and Africa and is
reportedly the most common and virulent strain
responsible for infections in healthy and immuno3）
compromised hosts . This strain is also associated with an ongoing outbreak of C. gattii
cryptococcosis in Vancouver Island, British Col1）
umbia, Canada . These outbreak-related isolates
have been genotyped as VGIIa, the major genoty1, 11）
pe, or VGIIb, the minor genotype
. Additionally,
a unique genotype, VGIIc, was recovered in
Oregon in the United States. In this study, the
MLST analysis was performed to determine the
genetic relationship between the isolate and other
various geographic strains. Overall, the sequence
type of the isolate was ST7（sequence type 7）
based on the Fungal MLST database（http://mlst.
mycologylab. org）
; it was identical to the se-
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Med. Mycol. J. Vol. 55（No. 3）
, 2014
quence type of the Vancouver Island minor
genotype strain R272（VGIIb）
. Although a small
number of C. gattii cases have been documented
12, 13）
in Hawaii, VGIIb has not been reported there
.
However, several molecular epidemiological studies have suggested that VGI is the most common
genotype in China, with VGIIb being less common
14, 15）
among C. gattii infections there
.
Since Australian eucalypts were first reported
in 1990 as natural habitats for Cryptococcus
16）
spp. , C. gattii has been isolated from more than
50 tree species, including angiosperms and
3）
gymnosperms . C. gattii has also been associated
with native animals in Australia（koalas, echidnas）,New Zealand（kiwi）
, Africa（cheetahs）
, and
3）
Canada（squirrels） . The first reported Japanese
case had close contact with koalas when travell4）
ing to Australia . In Japan, no studies have
reported isolation of C. gattii from the environment, although koalas kept in two different zoos
17, 18）
were carriers of this pathogen
. Additionally,
there have been no reports on the epidemiology
of C. gattii genotypes in China, including their
environmental profiles.
Understanding the length of the incubation
period is critical to track the acquisition of C.
gattii. A study of seven travelers to Vancouver
Island revealed that incubation periods ranged
from two to eleven months, with a median of six to
19）
seven months . Other reports indicated a longer
incubation period of several years following likely
exposure, which suggests that C. gattii may be
20−22）
able to remain dormant
. Thus, the incubation
period of C. gattii remains uncertain and needs
more investigation.
Our patient had no exposure to imported timber
or animals while living in Japan, and there have
been only a few C. gattii clinical cases and no
isolation of C. gattii from environmental niches in
that country. Our patient had previously visited
China three times and Hawaii once, and as
previously mentioned, infections with the VGIIb C.
14, 15）
gattii genotype have been reported in China
.
Thus, the source of his infection appears to have
originated in China, although we cannot rule out
the possibility that he was infected in Japan. We
acknowledge the limitation to infer the source of
his infection from the MLST analysis because of a
lack of comprehensive environmental and clinical
surveillance samples from areas where the
patient resides or traveled. Genotype information
23）
is not essential in routine clinical practice ;
however, in terms of epidemiologic investigation,
genotyping may be helpful for estimating where a
patient was infected or for surveying which
strains are common in a region.
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