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  Table of Contents  
Year : 2017  |  Volume : 35  |  Issue : 4  |  Page : 617-619

Diagnosis and treatment of diffusible Penicillium marneffei in human immunodeficiency virus-negative patients: A challenge for the physician

1 Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
2 Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
3 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Date of Web Publication1-Feb-2018

Correspondence Address:
Dr. Gui-Ping Li
Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_15_418

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 ~ Abstract 

Penicillium marneffei infection in human immunodeficiency virus (HIV)-negative patients is addressed far less often. In this article, a small cohort of HIV-negative patients who disseminated P. marneffei infection was included. Sites of infection were found from blood culture, as subcutaneous nodules, or from lymph node biopsy. Fever, rash, swollen lymph nodes, anaemia and weight loss were common characteristics in most infected patients. The signs and symptoms are diverse and create challenges for accurate diagnosis. This paper will assist our understanding of this disease and contribute to an appropriate regime of therapy, thus improving the health of P. marneffei-positive patients.

Keywords: Epidemiology, human immunodeficiency virus, immune dysfunction, microbiology, Penicillium marneffei

How to cite this article:
Chi XH, Xue YM, Wang QS, Li GP, Zhou HS, Qi YS. Diagnosis and treatment of diffusible Penicillium marneffei in human immunodeficiency virus-negative patients: A challenge for the physician. Indian J Med Microbiol 2017;35:617-9

How to cite this URL:
Chi XH, Xue YM, Wang QS, Li GP, Zhou HS, Qi YS. Diagnosis and treatment of diffusible Penicillium marneffei in human immunodeficiency virus-negative patients: A challenge for the physician. Indian J Med Microbiol [serial online] 2017 [cited 2021 Jan 26];35:617-9. Available from:

 ~ Introduction Top

Penicillium marneffei is a zoonotic parasitic and pathogenic dimorphic fungus endemic in bamboo rats. However, in relatively rare circumstances, this fungus can infect humans. The most significant route of transmission is through contact with P. marneffei spores in the soil during the rainy season [1],[2] or infection directly through a wound site.[3] In China, P. marneffei-infected patients were mainly located in the south, including Guangdong and Guangxi province (83.4% of patients), with most of them (87.7%) infected by human immunodeficiency virus (HIV).[4] Penicilliosis (PSM) caused by P. marneffei has become one of the three leading causes of death from opportunistic infections (including tuberculosis, pneumocystis and P. marneffei) among HIV-positive patients,[5] but how PSM occurs in patients negative for HIV is still unknown. In this paper, we retrospectively analysed five P. marneffei-infected HIV-negative patients in our hospital in the past 4 years. The study was focused on a description of the patients' symptoms, signs and treatment and reactions to treatment, with the aim of deepening our understanding of the disease in the HIV-negative setting.

 ~ Materials and Methods Top

Clinical data

P. marneffei-infected patients hospitalised in the respiratory department (two cases), intensive care centre (one case), haematology department (one case) and gastroenterology department (one case) from 2010 to 2013. All patients were HIV negative for serological detection by the Elecsys ® HIV combi PT assay.[6] Two males and three females ranged in age from 47 to 75 years. One immunocompromised patient received less than one month of hormone therapy in another hospital due to the diagnosis of eosinophilia with pneumonia.

Diagnostic criteria

All patients were diagnosed by mycological methods or histopathology of subcutaneous nodules and superficial lymph nodes.

 ~ Results Top

Clinical characteristics

All patients had underlying diseases, including multiple colorectal polyps accompanied with high fasting plasma glucose (one case), diabetes (one case), syphilis (one case), nephritis, hepatitis and tuberculosis (one case) and suspected Castleman disease with chemotherapy administered once (one case). All patients had symptoms of respiratory tract infection supported from computed tomography or chest X-ray. The most common symptoms were fever, cough, rash, chest tightness, anaemia, weight loss and swollen lymph nodes. Body temperatures ranged from 38°C to 41°C. Four patients had rash, and three out of these four had ulceration. Three patients had obvious bone destruction. The analysis of T-lymphocyte subsets showed that three patients had a normal immune function, while the remaining two patients had lowered immune function.

Treatment, outcome and reaction

Patients were generally treated with Diflucan, voriconazole or itraconazole and changed to amphotericin B when all the above treatments failed. After clinical symptoms were controlled, itraconazole was substituted by amphotericin B to consolidate the therapy. If the bone destruction was observed, suggesting a more serious infection, anti-fungal treatment was extended. All bone destruction lesions had well responded to anti-fungal therapy [Figure 1]. If patients with fungal infection also had bacterial co-infection, anti-bacterial therapy was administered when necessary.
Figure 1: (a) Bone scan showing 99Tcm-MDP abnormal activity on skull, sternum, clavicle, scapula, humerus, ribs, spine, pelvis and femur. (b) 99Tcm-MDP bone scan showed that most of the radiation-concentrated lesions disappeared after 1 year of anti-fungal treatment

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 ~ Discussion Top

Recent reports showed that most of the HIV-negative P. marneffei-infected patients present with underlying diseases and/or conditions including those caused by immunosuppressive therapy (including, but not limited to, the context of organ transplantation), connective tissue disease, tuberculosis, aplastic anaemia, diabetes, lupus erythematosus and chronic obstructive pulmonary disease treated with inhaled corticosteroids and oxygen therapy.[4],[7],[8] However, the clinical manifestations of P. marneffei infection disease lack unique descriptors. This highlights the need to find ways to distinguish this disease from other diseases. In this cohort study, we demonstrated that fever, rash, swollen lymph nodes, anaemia and weight loss were common characteristics in most infected patients.

The respiratory route is considered to be the main route of transmission.[1] Therefore, patients often have symptoms of pulmonary infection, such as fever, cough and sputum. The rash is a common sign of infection that may be manifested as subcutaneous papules with or without ulceration. Rashes often present as edematous papules with central necrosis and black callus formation in HIV-positive patients, whereas, interestingly, they present as nodules with or without ulcers and abscesses in HIV-negative patients.[9] Anaemia is a common characteristic in PSM. All cases in our study had mild-to-moderate anaemia. In the patients with decreased levels of CD4+ T cells (two patients), one died 1 month later after diagnosis of PSM; in the other patient, anti-fungal treatment was effective, but the level of CD4+ T cells showed no obvious change in the 6 months before death.

P. marneffei easily colonises in the bone marrow cavity after invading the body's protective layers.[10] In HIV-positive patients, 10.6% were found to have P. marneffei infection in the bone marrow.[11] To date, the rate of P. marneffei positivity in the bone marrow in non-HIV patients has not been reported. Until now, just one English article has reported this sign in one HIV-negative patient.[12] In our small cohort, three of the five patients had osteolytic lesions, which were distributed in the axial skeleton and accessory bone. Two of these three patients did not have bone pain during the periods of early disease and treatment. The disease of another patient relapsed after anti-fungal treatment and progressed into fungal sinusitis and fever. Significantly, he also complained of a backache. This was revealed by X-ray to be due to osteolytic lesions with a focus on the thoracic vertebrae leading to a vertebral compression fracture. Amphotericin B was given, and his temperature gradually returned to normal.

Fluconazole, voriconazole, itraconazole and amphotericin B are the most common anti-fungal drugs. Sometimes, the side effects of anti-fungal drugs or complications such as bacterial infection lead to death. Previous reports for PSM of HIV-positive patients demonstrated that anti-fungal treatment could be effectively maintained for more than 10 weeks and prolonged therapy can reduce the risk of recurrence.[13] However, PSM treatment of HIV-negative patients is still lacking in documentation. In this study, two patients underwent anti-fungal therapy for close to 1 year. The index of clinical imaging showed that infectious lesions were still present during anti-fungal therapy.

 ~ Conclusion Top

PSM in HIV-negative patients often consistently occurs with other underlying diseases, making it difficult to diagnosis. Relatively long-term anti-fungal therapy is the main way to control the disease. Diagnosis and treatment of PSM will become a new challenge for physicians in the future.


The findings and conclusions in this manuscript are those of the authors. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Financial support and sponsorship

This work was supported by the President Foundation of Nanfang Hospital Southern Medical University (No. 2013C021).

Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Vanittanakom N, Cooper CR Jr., Fisher MC, Sirisanthana T. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev 2006;19:95-110.  Back to cited text no. 1
Bulterys PL, Le T, Quang VM, Nelson KE, Lloyd-Smith JO. Environmental predictors and incubation period of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis 2013;56:1273-9.  Back to cited text no. 2
Vyawahare CR, Misra RN, Gandham NR, Angadi KM, Paul R. Pencillium keratitis in an immunocompetent patient from Pune, Maharashtra, India. J Clin Diagn Res 2014;8:D1-2.  Back to cited text no. 3
Hu Y, Zhang J, Li X, Yang Y, Zhang Y, Ma J, et al. Penicillium marneffei infection: An emerging disease in mainland China. Mycopathologia 2013;175:57-67.  Back to cited text no. 4
Feng RF, Ma Y, Liu ZF, Zhang FJ, Yang Y, Huang SB, et al. Specific causes of death among 381 AIDS patients who died in hospitals. Zhonghua Liu Xing Bing Xue Za Zhi 2013;34:1237-41.  Back to cited text no. 5
Liu Y, Li D, Wang T, Yan K, Zhu S, Yang T, et al. Clinical application evaluation of two fourth-generation human immunodeficiency virus (HIV) screening assays in West China hospital. J Clin Lab Anal 2015;29:146-52.  Back to cited text no. 6
Chen M, Houbraken J, Pan W, Zhang C, Peng H, Wu L, et al. Pulmonary fungus ball caused by Penicillium capsulatum in a patient with type 2 diabetes: A case report. BMC Infect Dis 2013;13:496.  Back to cited text no. 7
De Monte A, Risso K, Normand AC, Boyer G, L'Ollivier C, Marty P, et al. Chronic pulmonary penicilliosis due to Penicillium marneffei: Late presentation in a French traveler. J Travel Med 2014;21:292-4.  Back to cited text no. 8
Xian S, Dong-hua L, Hong L. Analysis of clinical manifestation and histopathology in skin lesions of Penicilliosis marneffei. Chin J Derm Venereol 2013;27:145-7.  Back to cited text no. 9
Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. Disseminated Penicillium marneffei infection in Southeast Asia. Lancet 1994;344:110-3.  Back to cited text no. 10
Lau SK, Tse H, Chan JS, Zhou AC, Curreem SO, Lau CC, et al. Proteome profiling of the dimorphic fungus Penicillium marneffei extracellular proteins and identification of glyceraldehyde-3-phosphate dehydrogenase as an important adhesion factor for conidial attachment. FEBS J 2013;280:6613-26.  Back to cited text no. 11
Liu GN, Huang JS, Zhong XN, Zhang JQ, Zou ZX, Yang ML, et al. Penicillium marneffei infection within an osteolytic lesion in an HIV-negative patient. Int J Infect Dis 2014;23:1-3.  Back to cited text no. 12
Yong L, Meng ZH, Su LS, Yang RY, Qin SF. A clinical study on 256 cases of AIDS complicated with Penicilliosis marneffei. Chin J Mycol 2009;4:347-50.  Back to cited text no. 13


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