- Email: [email protected]
Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient
Accepted Manuscript Title: Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient Author: Hyeri Seok Jae-Hoon Ko Inseub Shin Young Hee Eun Seung-Eun Lee You-Bin Lee Kyong Ran Peck PII: DOI: Reference:
S1201-9712(15)00187-3 http://dx.doi.org/doi:10.1016/j.ijid.2015.07.020 IJID 2401
To appear in:
International Journal of Infectious Diseases
Received date: Accepted date:
16-4-2015 23-7-2015
Please cite this article as: Seok H, Ko J-H, Shin I, Eun YH, Lee S-E, Lee Y-B, Peck KR, Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient, International Journal of Infectious Diseases (2015), http://dx.doi.org/10.1016/j.ijid.2015.07.020 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-
2
infected patient
3 Hyeri Seok1*, Jae-Hoon Ko2*, Inseub Shin1, Young Hee Eun1, Seung-Eun Lee1, You-Bin Lee1, Kyong
5
Ran Peck2
ip t
4
cr
6 1
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of
8
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea
9
2
us
7
Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea
11
*These authors equally contributed to this article.
M
an
10
12
Running title: Coinfection of T. marneffei and MAC
14
Correspondence to:
15
Kyong Ran Peck, MD, PhD
16
Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan
17
University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul 135-710, Korea
te
Ac ce p
18
d
13
Tel: +82-2-3410-0329
19
Fax: +82-2-3410-0064
20
E-mail: [email protected]
21 22
Highlights
23
Talaromyces marneffei is an opportunistic pathogen in immunocompromised hosts. 1
Page 1 of 9
24
Coinfection of T. marneffei with other opportunistic pathogen is rarely reported.
25
We report the first case of T. marneffei and M. intracellulare coinfection in an AIDS patient.
ip t
26 27
cr
28
us
29 Abstract
31
A 25-year-old man with human immunodeficiency virus (HIV) infection presented with fever that
32
had lasted 1 month. The CD4+ T lymphocyte count was 7 cells/L and computed tomography
33
showed several small lung nodules, splenomegaly, and multiple lymphadenopathy. Talaromyces
34
marneffei was isolated in the initial blood cultures. As the fever persisted despite clearance of
35
fungemia and 10 days of liposomal amphotericin B treatment, cervical lymph node fine-needle
36
aspiration was performed. Mycobacterium intracellulare was isolated from sputum and neck node
37
aspiration cultures. The patient was successfully treated with liposomal amphotericin B,
38
clarithromycin, and ethambutol in addition to antiretroviral therapy. This case suggests that we
39
should consider coinfection of opportunistic pathogens in febrile immunosuppressed patients if
40
the patient does not respond properly to the initial treatment.
42
M
d
te
Ac ce p
41
an
30
43
Keywords:
44
Coinfection
45
Talaromyces
marneffei;
Mycobacterium
intracellulare;
HIV;
Lymphadenopathy;
46 47
2
Page 2 of 9
48 49
INTRODUCTION Talaromyces marneffei, previously known as Penicillium marneffei, is a facultative
51
intracellular dimorphic fungus that causes disseminated and progressive infection in
52
immunocompromised hosts, especially patients with human immunodeficiency virus (HIV)
53
infection 1,2. T. marneffei is characterized by its geographic endemism in Southeast Asia and
54
southern China, although several imported cases have been reported in non-endemic
55
countries
56
theoretically possible as most T. marneffei infection occurs in patients with an
57
immunocompromised status, reports of coinfected cases are scarce. Here we report the first
58
case of disseminated T. marneffei and Mycobacterium intracellulare infection in an HIV-
59
infected patient.
d
M
an
. Although coinfection of T. marneffei with other opportunistic infection is
Ac ce p
CASE
te
60 61
1,3
us
cr
ip t
50
62
A 25-year-old man visited our emergency room with fever and cough that had persisted for
63
a month. He was found to be infected with HIV 5 years previously, and was diagnosed with
64
AIDS 1 year ago when he was admitted to another hospital with Pneumocystis jirovecii
65
pneumonia. Although anti-retroviral therapy (ART) with emtricitabine-tenofovir and
66
ritonavir-boosted atazanavir had been started during admission, he voluntarily stopped taking
67
the ART. After his discharge he initially stayed in Guangzhou, China, but returned to Korea
68
when the fever persisted despite oral antipyretic medications. On examination, he had
69
multiple erythematous papules with central umbilication on his face, and 1- to 2-cm sized 3
Page 3 of 9
palpable lymphadenopathies on his cervical, supraclavicular, axillar, and inguinal area. He
71
had blood pressure of 119/66 mmHg, pulse rate of 133 beats/min, respiratory rate of 24
72
breaths/min, body temperature of 39.9°C, and oxygen saturation of 99%. Laboratory tests
73
showed a white blood cell count of 6,620/L with neutrophils 96.3%, hemoglobin 10.3 g/dL,
74
platelet count 162,000/L, erythrocyte sedimentation rate 84 mm/hr, and C-reactive protein
75
level 6.15 mg/dL. Peripheral CD4+ T lymphocyte count was 3 cells/L and HIV-RNA viral
76
load was 719 copies/mL. Chest and abdomen computed tomography revealed several small
77
lung nodules, splenomegaly, and multiple lymphadenopathies of cervical, supraclavicular,
78
axillary, mediastinal, mesenteric, and inguinal lymph nodes. On hospital day 2, two separate
79
pairs of blood cultures reported growth of microorganisms. As mold type fungi were seen on
80
Gram stain, treatment with amphotericin B deoxycholate was started empirically, but was
81
changed to liposomal amphotericin B because of severe shivering after infusion. On hospital
82
day 6, we observed colonies producing a red-wine colored pigment that diffused into
83
Sabouraud dextrose agar plate (Fig. 1A), and septated hyphae with phialides branching from
84
the conidiophores and chain-shaped microconidia with Lactophenol cotton blue stain (Fig.
85
1C). After sequencing of the internal transcribed spacer (ITS) rRNA gene regions, sequence
86
similarity searches using basic local alignment search tool (BLAST) revealed a complete
87
(100%) match with T. marneffei. ART with emtricitabine-tenofovir and ritonavir-boosted
88
darunavir were started on the same day. On hospital day 11, fine needle aspiration of the left
89
supraclavicular lymph node was performed because the fever persisted despite proper
90
antifungal treatment and negative conversion of fungemia. Acid fast bacilli (AFB) stain
91
revealed 1-9 AFB/10 high power fields, and Mycobacterium tuberculosis complex
92
polymerase chain reaction (PCR) was negative for both the sputum culture and lymph node
Ac ce p
te
d
M
an
us
cr
ip t
70
4
Page 4 of 9
aspiration. Ethambutol and clarithromycin were added to the treatment on suspicion of
94
disseminated Mycobacterium avium complex infection and the fever subsided 3 days later.
95
The final report of supraclavicular lymph node culture showed both T. marneffei and
96
nontuberculous mycobacteria, which was later identified as Mycobacterium intracellulare by
97
a PCR-hybridization method. The patient was discharged with oral itraconazole, ethambutol,
98
clarithromycin, and ART after 2 weeks of liposomal amphotericin therapy.
99
DISCUSSION
us
cr
ip t
93
T. marneffei, a temperature-dependent dimorphic fungus previously known as Penicillium
101
marneffei, is an important pathogen of HIV-associated opportunistic infection in endemic
102
areas 2. It was first isolated from liver of the bamboo rat (Rhizomys sinensis) in 1956, and
103
subsequently from an HIV-infected human in 1988. In endemic areas, which include
104
Southeast Asia, Southern China, Hong Kong, northeastern India, and Taiwan, T. marneffei
105
can cause fatal disseminated infection in immunocompromised hosts by inhalation of fungal
106
conidia into the lungs
107
infection in this country have been reported.
1,3
te
d
M
an
100
Ac ce p
. Korea is not an endemic area, and only three cases of T. marneffei
108
To our knowledge, this is the first report of disseminated T. marneffei and M. intracellulare
109
coinfection in an HIV-infected person. Although coinfection of T. marneffi with other
110
opportunistic pathogens is plausible as T. marneffei infection mostly occurs in
111
immunocompromised hosts 1, reports of coninfection are scarce. In a case series that
112
reviewed 24 patients with T. marneffei infection, two HIV-negative patients were coinfected
113
with disseminated M. intacellulare and M. fortuitum, respectively 4. Considering that these
114
infections are rare in healthy people, those two individuals might have other 5
Page 5 of 9
immunocompromising conditions that were not described in the report. Clinical presentation
116
of these disseminated infections may mimic each other, and a proper diagnostic approach is
117
necessary to avoid insufficient treatment. From this point of view, we think that the present
118
case is clinically informative.
ip t
115
The most common presentation of T. marneffei infection is fever and weight loss, occurring
120
in more than 75% of patients. Other manifestations are anemia, skin lesions,
121
lymphadenopathy, hepatomegaly, and pulmonary disease, in decreasing order of frequency.
122
Skin lesions are seen in 71% of patients, and include generalized papules, central umbilicated
123
papules, and acne-like lesions
124
avium complex (MAC) disease, including M. intracellulare infection, are fever, night sweats,
125
weight loss, abdominal pain, and diarrhea. Hepatosplenomegaly, lymphadenopathy,
126
pulmonary nodules, and anemia can also be observed. In the case presented here, the initial
127
presentations of fever, skin lesions, lymphadenopathy, low CD4+ lymphocyte count, and
128
hyphae on gram stain were highly suggestive of disseminated fungal infection, and empirical
129
antifungal treatment was started without delay. Although fever, several small lung nodules,
130
splenomegaly, and multiple lymphadenopathies also suggest the possibility of disseminated
131
MAC disease, a further diagnostic plan was not considered after the report of fungemia
132
because T. marneffei can also cause these manifestations. However, the fever persisted after
133
10 days of antifungal treatment and eradication of fungemia, and lymph node aspiration was
134
performed on hospital day 11. Culture of aspirated lymph node revealed growth of both T.
135
marneffei and M. intracellulare. M. intracellulare was also reported in the sputum culture.
136
The fever subsided 4 days after administration of ethambutol and clarithromycin. Without the
137
findings of lymph node aspiration, prophylactic use of low-dose azithromycin might have
us
cr
119
1,5
Ac ce p
te
d
M
an
. Clinical manifestations of disseminated Mycobacterium
6
Page 6 of 9
138
eventually resulted in induction of macrolide resistance. We report the first case of disseminated T. marneffei and M. intracellulare infection in an
140
HIV-infected patient. Features of the present case suggest that we should consider coinfection
141
of opportunistic pathogens in febrile immunosuppressed patients if the patient does not
142
respond properly to the initial treatment and emphasize the importance of appropriate
143
diagnostic approaches.
us
cr
ip t
139
144
Conflict of Interest/Funding: None
an
145
147
REFERENCES
148
1.
d
Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155
2.
te
reported cases. Clin Infect Dis 1996;23:125-30.
149 150
M
146
Samson RA, Yilmaz N, Houbraken J, Spierenburg H, Seifert KA, Peterson SW, et al. Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in
152
Penicillium subgenus Biverticillium. Stud Mycol 2011;70:159-83.
153
3. 4.
158 159
Jan IS, Chung PF, Wang JY, Weng MH, Hung CC, Lee LN. Cytological diagnosis of Penicillium marneffei infection. J Formos Med Assoc 2008;107:443-7.
156 157
Sirisanthana T, Supparatpinyo K. Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. Int J Infect Dis 1998;3:48-53.
154 155
Ac ce p
151
5.
Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 1994;344:110-3.
160 161 162 7
Page 7 of 9
163 164
FIGURE LEGENDS
ip t
165
Figure 1. (A) A colony producing a red-wine colored pigment that diffused into Sabouraud
167
dextrose agar plate, (B) Reverse side of the colony, (C) Septated hyphae with phialides
168
branching from the conidiophores and chain-shaped microconidia (Lactophenol cotton stain,
169
×400).
Ac ce p
te
d
M
an
us
cr
166
8
Page 8 of 9
d
te
Ac ce p us
an
M
cr
ip t
Figure
Page 9 of 9
S1201-9712(15)00187-3 http://dx.doi.org/doi:10.1016/j.ijid.2015.07.020 IJID 2401
To appear in:
International Journal of Infectious Diseases
Received date: Accepted date:
16-4-2015 23-7-2015
Please cite this article as: Seok H, Ko J-H, Shin I, Eun YH, Lee S-E, Lee Y-B, Peck KR, Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient, International Journal of Infectious Diseases (2015), http://dx.doi.org/10.1016/j.ijid.2015.07.020 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-
2
infected patient
3 Hyeri Seok1*, Jae-Hoon Ko2*, Inseub Shin1, Young Hee Eun1, Seung-Eun Lee1, You-Bin Lee1, Kyong
5
Ran Peck2
ip t
4
cr
6 1
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of
8
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea
9
2
us
7
Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea
11
*These authors equally contributed to this article.
M
an
10
12
Running title: Coinfection of T. marneffei and MAC
14
Correspondence to:
15
Kyong Ran Peck, MD, PhD
16
Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan
17
University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul 135-710, Korea
te
Ac ce p
18
d
13
Tel: +82-2-3410-0329
19
Fax: +82-2-3410-0064
20
E-mail: [email protected]
21 22
Highlights
23
Talaromyces marneffei is an opportunistic pathogen in immunocompromised hosts. 1
Page 1 of 9
24
Coinfection of T. marneffei with other opportunistic pathogen is rarely reported.
25
We report the first case of T. marneffei and M. intracellulare coinfection in an AIDS patient.
ip t
26 27
cr
28
us
29 Abstract
31
A 25-year-old man with human immunodeficiency virus (HIV) infection presented with fever that
32
had lasted 1 month. The CD4+ T lymphocyte count was 7 cells/L and computed tomography
33
showed several small lung nodules, splenomegaly, and multiple lymphadenopathy. Talaromyces
34
marneffei was isolated in the initial blood cultures. As the fever persisted despite clearance of
35
fungemia and 10 days of liposomal amphotericin B treatment, cervical lymph node fine-needle
36
aspiration was performed. Mycobacterium intracellulare was isolated from sputum and neck node
37
aspiration cultures. The patient was successfully treated with liposomal amphotericin B,
38
clarithromycin, and ethambutol in addition to antiretroviral therapy. This case suggests that we
39
should consider coinfection of opportunistic pathogens in febrile immunosuppressed patients if
40
the patient does not respond properly to the initial treatment.
42
M
d
te
Ac ce p
41
an
30
43
Keywords:
44
Coinfection
45
Talaromyces
marneffei;
Mycobacterium
intracellulare;
HIV;
Lymphadenopathy;
46 47
2
Page 2 of 9
48 49
INTRODUCTION Talaromyces marneffei, previously known as Penicillium marneffei, is a facultative
51
intracellular dimorphic fungus that causes disseminated and progressive infection in
52
immunocompromised hosts, especially patients with human immunodeficiency virus (HIV)
53
infection 1,2. T. marneffei is characterized by its geographic endemism in Southeast Asia and
54
southern China, although several imported cases have been reported in non-endemic
55
countries
56
theoretically possible as most T. marneffei infection occurs in patients with an
57
immunocompromised status, reports of coinfected cases are scarce. Here we report the first
58
case of disseminated T. marneffei and Mycobacterium intracellulare infection in an HIV-
59
infected patient.
d
M
an
. Although coinfection of T. marneffei with other opportunistic infection is
Ac ce p
CASE
te
60 61
1,3
us
cr
ip t
50
62
A 25-year-old man visited our emergency room with fever and cough that had persisted for
63
a month. He was found to be infected with HIV 5 years previously, and was diagnosed with
64
AIDS 1 year ago when he was admitted to another hospital with Pneumocystis jirovecii
65
pneumonia. Although anti-retroviral therapy (ART) with emtricitabine-tenofovir and
66
ritonavir-boosted atazanavir had been started during admission, he voluntarily stopped taking
67
the ART. After his discharge he initially stayed in Guangzhou, China, but returned to Korea
68
when the fever persisted despite oral antipyretic medications. On examination, he had
69
multiple erythematous papules with central umbilication on his face, and 1- to 2-cm sized 3
Page 3 of 9
palpable lymphadenopathies on his cervical, supraclavicular, axillar, and inguinal area. He
71
had blood pressure of 119/66 mmHg, pulse rate of 133 beats/min, respiratory rate of 24
72
breaths/min, body temperature of 39.9°C, and oxygen saturation of 99%. Laboratory tests
73
showed a white blood cell count of 6,620/L with neutrophils 96.3%, hemoglobin 10.3 g/dL,
74
platelet count 162,000/L, erythrocyte sedimentation rate 84 mm/hr, and C-reactive protein
75
level 6.15 mg/dL. Peripheral CD4+ T lymphocyte count was 3 cells/L and HIV-RNA viral
76
load was 719 copies/mL. Chest and abdomen computed tomography revealed several small
77
lung nodules, splenomegaly, and multiple lymphadenopathies of cervical, supraclavicular,
78
axillary, mediastinal, mesenteric, and inguinal lymph nodes. On hospital day 2, two separate
79
pairs of blood cultures reported growth of microorganisms. As mold type fungi were seen on
80
Gram stain, treatment with amphotericin B deoxycholate was started empirically, but was
81
changed to liposomal amphotericin B because of severe shivering after infusion. On hospital
82
day 6, we observed colonies producing a red-wine colored pigment that diffused into
83
Sabouraud dextrose agar plate (Fig. 1A), and septated hyphae with phialides branching from
84
the conidiophores and chain-shaped microconidia with Lactophenol cotton blue stain (Fig.
85
1C). After sequencing of the internal transcribed spacer (ITS) rRNA gene regions, sequence
86
similarity searches using basic local alignment search tool (BLAST) revealed a complete
87
(100%) match with T. marneffei. ART with emtricitabine-tenofovir and ritonavir-boosted
88
darunavir were started on the same day. On hospital day 11, fine needle aspiration of the left
89
supraclavicular lymph node was performed because the fever persisted despite proper
90
antifungal treatment and negative conversion of fungemia. Acid fast bacilli (AFB) stain
91
revealed 1-9 AFB/10 high power fields, and Mycobacterium tuberculosis complex
92
polymerase chain reaction (PCR) was negative for both the sputum culture and lymph node
Ac ce p
te
d
M
an
us
cr
ip t
70
4
Page 4 of 9
aspiration. Ethambutol and clarithromycin were added to the treatment on suspicion of
94
disseminated Mycobacterium avium complex infection and the fever subsided 3 days later.
95
The final report of supraclavicular lymph node culture showed both T. marneffei and
96
nontuberculous mycobacteria, which was later identified as Mycobacterium intracellulare by
97
a PCR-hybridization method. The patient was discharged with oral itraconazole, ethambutol,
98
clarithromycin, and ART after 2 weeks of liposomal amphotericin therapy.
99
DISCUSSION
us
cr
ip t
93
T. marneffei, a temperature-dependent dimorphic fungus previously known as Penicillium
101
marneffei, is an important pathogen of HIV-associated opportunistic infection in endemic
102
areas 2. It was first isolated from liver of the bamboo rat (Rhizomys sinensis) in 1956, and
103
subsequently from an HIV-infected human in 1988. In endemic areas, which include
104
Southeast Asia, Southern China, Hong Kong, northeastern India, and Taiwan, T. marneffei
105
can cause fatal disseminated infection in immunocompromised hosts by inhalation of fungal
106
conidia into the lungs
107
infection in this country have been reported.
1,3
te
d
M
an
100
Ac ce p
. Korea is not an endemic area, and only three cases of T. marneffei
108
To our knowledge, this is the first report of disseminated T. marneffei and M. intracellulare
109
coinfection in an HIV-infected person. Although coinfection of T. marneffi with other
110
opportunistic pathogens is plausible as T. marneffei infection mostly occurs in
111
immunocompromised hosts 1, reports of coninfection are scarce. In a case series that
112
reviewed 24 patients with T. marneffei infection, two HIV-negative patients were coinfected
113
with disseminated M. intacellulare and M. fortuitum, respectively 4. Considering that these
114
infections are rare in healthy people, those two individuals might have other 5
Page 5 of 9
immunocompromising conditions that were not described in the report. Clinical presentation
116
of these disseminated infections may mimic each other, and a proper diagnostic approach is
117
necessary to avoid insufficient treatment. From this point of view, we think that the present
118
case is clinically informative.
ip t
115
The most common presentation of T. marneffei infection is fever and weight loss, occurring
120
in more than 75% of patients. Other manifestations are anemia, skin lesions,
121
lymphadenopathy, hepatomegaly, and pulmonary disease, in decreasing order of frequency.
122
Skin lesions are seen in 71% of patients, and include generalized papules, central umbilicated
123
papules, and acne-like lesions
124
avium complex (MAC) disease, including M. intracellulare infection, are fever, night sweats,
125
weight loss, abdominal pain, and diarrhea. Hepatosplenomegaly, lymphadenopathy,
126
pulmonary nodules, and anemia can also be observed. In the case presented here, the initial
127
presentations of fever, skin lesions, lymphadenopathy, low CD4+ lymphocyte count, and
128
hyphae on gram stain were highly suggestive of disseminated fungal infection, and empirical
129
antifungal treatment was started without delay. Although fever, several small lung nodules,
130
splenomegaly, and multiple lymphadenopathies also suggest the possibility of disseminated
131
MAC disease, a further diagnostic plan was not considered after the report of fungemia
132
because T. marneffei can also cause these manifestations. However, the fever persisted after
133
10 days of antifungal treatment and eradication of fungemia, and lymph node aspiration was
134
performed on hospital day 11. Culture of aspirated lymph node revealed growth of both T.
135
marneffei and M. intracellulare. M. intracellulare was also reported in the sputum culture.
136
The fever subsided 4 days after administration of ethambutol and clarithromycin. Without the
137
findings of lymph node aspiration, prophylactic use of low-dose azithromycin might have
us
cr
119
1,5
Ac ce p
te
d
M
an
. Clinical manifestations of disseminated Mycobacterium
6
Page 6 of 9
138
eventually resulted in induction of macrolide resistance. We report the first case of disseminated T. marneffei and M. intracellulare infection in an
140
HIV-infected patient. Features of the present case suggest that we should consider coinfection
141
of opportunistic pathogens in febrile immunosuppressed patients if the patient does not
142
respond properly to the initial treatment and emphasize the importance of appropriate
143
diagnostic approaches.
us
cr
ip t
139
144
Conflict of Interest/Funding: None
an
145
147
REFERENCES
148
1.
d
Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155
2.
te
reported cases. Clin Infect Dis 1996;23:125-30.
149 150
M
146
Samson RA, Yilmaz N, Houbraken J, Spierenburg H, Seifert KA, Peterson SW, et al. Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in
152
Penicillium subgenus Biverticillium. Stud Mycol 2011;70:159-83.
153
3. 4.
158 159
Jan IS, Chung PF, Wang JY, Weng MH, Hung CC, Lee LN. Cytological diagnosis of Penicillium marneffei infection. J Formos Med Assoc 2008;107:443-7.
156 157
Sirisanthana T, Supparatpinyo K. Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. Int J Infect Dis 1998;3:48-53.
154 155
Ac ce p
151
5.
Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 1994;344:110-3.
160 161 162 7
Page 7 of 9
163 164
FIGURE LEGENDS
ip t
165
Figure 1. (A) A colony producing a red-wine colored pigment that diffused into Sabouraud
167
dextrose agar plate, (B) Reverse side of the colony, (C) Septated hyphae with phialides
168
branching from the conidiophores and chain-shaped microconidia (Lactophenol cotton stain,
169
×400).
Ac ce p
te
d
M
an
us
cr
166
8
Page 8 of 9
d
te
Ac ce p us
an
M
cr
ip t
Figure
Page 9 of 9