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Photomicrograph of Penicillium marneffei (courtesy of Kornkanok Sukapan) in the skin lesion section stained with Grocott Methenamine Silver. Numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast-like organisms. The characteristic transverse septum (arrows) within the yeast cell is seen. Magnification, × 1000.
Source publication
Disseminated Penicillium marneffei infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unm...
Context in source publication
Context 1
... biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular der- mis. Tissue sections from skin biopsy stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation (Figure 3). No organism was observed in the bone marrow aspirate specimen. ...Citations
... T. marneffei-associated immune reconstitution inflammatory syndrome (IRIS) has been reported as unmasking IRIS in patients starting ART. Skin lesions can be atypical, including erythematous nodules, verrucous lesions, or erythematous plaques [63]. ...
Talaromycosis (penicilliosis) is a major fungal disease endemic across a narrow band of tropical countries of South and Southeast Asia. The etiologic agent is a thermally dimorphic fungus Talaromyces (Penicillium) marneffei, which was first isolated from a bamboo rat in Vietnam in 1956, but no formal description was published. In 1959, Professor Gabriel Segretain formally described it as a novel species Talaromyces (Penicillium) marneffei, and the human pathogenic potential of the fungus in Mycopathologia. The first natural human case of talaromycosis (penicillosis) was reported in 1973 and involved an American minister with Hodgkin’s disease who lived in Southeast Asia. Sixty years after the discovery of the pathogen, talaromycosis caused by T. marneffei is recognized as an important human disease with the potential to cause high mortality in the absence of proper diagnosis and prompt treatment. Talaromycosis remains a significant infectious complication in HIV/AIDS patients and in patients with other immune defects. The disease is being recognized with an increasing frequency well beyond the traditional endemic areas. The natural reservoirs of T. marneffei in wild rodents are well-defined, which links the ecology with the epidemiology of talaromycosis in endemic areas. There is an urgent unmet need for rapid and affordable point-of-care diagnostic tests. We also need more clinical studies to define the best therapeutic options for the management of talaromycosis patients.
... 17 To date, only four cases have been reported worldwide, of which three presented as paradoxical IRIS. 18 In 2007, Gupta et al reported a 35-year-old treatment naïve HIV-infected male from Manipur, India who presented with fever, weight loss, and heaviness in the abdomen for 2 months. His CD4 count was 4 cells/mm 3 (unknown percentage), and chest computed tomography revealed a small round opacity in the basal segment of the left lung. ...
Background
Talaromyces marneffei (T. marneffei) is an important opportunistic pathogen found in human immunodeficiency virus-positive individuals in Southeast Asia, Southern China, and Northeastern India. Patients with disseminated talaromycosis commonly develop multi-organ involvement including the skin. In this report, we describe the clinical presentation, investigation, management, and clinical outcome of an acquired immune deficiency syndrome (AIDS) patient with newly diagnosed disseminated talaromycosis without skin involvement.
Case presentation
A 27-year-old male with AIDS presented with acute onset of abdominal pain for 4 days and fever for 2 days. He had been diagnosed with AIDS, pneumocystis pneumonia, and presumptive smear-negative pulmonary tuberculosis 2 months previously. His initial CD4 count was 91 cells/mm³. After a 3-week course of trimethoprim/sulfamethoxazole and anti-tuberculosis treatment, anti-retroviral therapy was initiated. Physical examination revealed left upper quadrant tenderness but no abnormal skin lesions. On this visit, his CD4 count rose to 272 cells/mm³ (19%). Computed tomography of the abdomen showed evidence of a small hypodense lesion with a thin enhancing rim at the spleen and extensive intra-abdominal lymphadenopathy. Empirical amphotericin B deoxycholate was administered in response to positive serum galactomannan, although this was switched to intravenous liposomal amphotericin B 1 week later because of acute kidney injury. Blood and bone marrow cultures for fungus grew T. marneffei on days 9 and 12, respectively. After 21 days of treatment, oral itraconazole replaced intravenous therapy. The patient was discharged home after 29 days in the hospital and continued to improve clinically at a follow-up visit as an outpatient.
Conclusion
Talaromycosis is a fairly common opportunistic infection among AIDS patients in Thailand, despite a rise in CD4 count which may reflect a change in immune status. To a lesser extent, a systemic disease without skin involvement can be expected in real clinical practice.
... Fungi-related IRIS has also been described during infections with Talaromyces marneffei (ex-Penicillium marneffei) [47][48][49][50][51], Coccidioides spp. [52], Paracoccidioides spp. ...
... Cells of the innate immune system, such as monocytes, macrophages, and neutrophils, are of increasing interest in IRIS pathophysiology, since granuloma appears to be frequently found in IRIS lesions [19,41,47]. Indeed, granuloma is the histopathology hallmark in chronic disseminated candidiasis [19] and is commonly found in other fungi-related IRIS [37,41,48,49,56]. An extended description of granuloma in fungi-related IRIS is unavailable, and should be better studied in particular through immune staining to understand which cell types are implicated and their degree of differentiation/activation. ...
Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.
... Skin lesions can be atypical, including erythematous nodules, verrucous lesions, or erythematous plaques. 92,93 Prospective studies that define incidence, risk, and impact of talaromycosis IRIS are needed. Continuation of ART, antifungal therapy, and cautious use of non-steroidal antiinflammatory medications are the main therapeutic approaches. ...
Fungi are major contributors to the opportunistic infections that affect patients with HIV/AIDS. Systemic infections are mainly with Pneumocystis jirovecii (pneumocystosis), Cryptococcus neoformans (cryptococcosis), Histoplasma capsulatum (histoplasmosis), and Talaromyces (Penicillium) marneffei (talaromycosis). The incidence of systemic fungal infections has decreased in people with HIV in high-income countries because of the widespread availability of antiretroviral drugs and early testing for HIV. However, in many areas with high HIV prevalence, patients present to care with advanced HIV infection and with a low CD4 cell count or re-present with persistent low CD4 cell counts because of poor adherence, resistance to antiretroviral drugs, or both. Affordable, rapid point-of-care diagnostic tests (as have been developed for cryptococcosis) are urgently needed for pneumocystosis, talaromycosis, and histoplasmosis. Additionally, antifungal drugs, including amphotericin B, liposomal amphotericin B, and flucytosine, need to be much more widely available. Such measures, together with continued international efforts in education and training in the management of fungal disease, have the potential to improve patient outcomes substantially.
... Some researchers have recommended that a reduction in the number of T lymphocytes or cellular immunity is probably the most important predisposing factor to P. marneffei infection or reactivation. 14,16 Notably, all of our patients were HIV negative and had no relevant family history. Instead, two children were diagnosed with primary immunodeficiency disease, which is a common disease among pediatric patients in addition to HIV infection and secondary immunodeficiency. ...
To date, Penicillium marneffei infection has mainly been reported in adults infected with human immunodeficiency virus (HIV); only a limited number of cases have been reported in children. The aim of the article is to study the clinical and laboratory characteristics of P. marneffei in pediatric patients without HIV infection. In this study, the medical records of 10 pediatric patients with P. marneffei infection at Guangzhou Women and Children's Medical Center were evaluated from May 2011 to November 2015. The duration of symptoms before admission ranged from 8 days to 1 month. Fever was found in all 10 patients. Hepatomegaly and splenomegaly were found in 9/10 and 8/10 patients, respectively. Two patients presented with skin lesions. The main life-threatening complications during hospitalization included hemophagocytic syndrome (8/10), acute respiratory distress syndrome (8/10), disseminated intravascular coagulation (DIC) (7/10), and septic shock (6/10). Two of the 10 patients had underlying immunodefi...
... The incidence of IRIS ranges from 10% to 40% and varies by pathogen, being most commonly described in patients with infections caused by mycobacteria (particularly tuberculosis), fungi (particularly cryptococcal meningitis), and lymphotropic viruses such as JC virus (the cause of progressive multifocal leukoencephalopathy) and human herpes viruses [4,5]. To date there have been few case reports of IRIS associated with T. marneffei infection [6][7][8][9][10][11][12][13], and the incidence and risk factors have not been defined. All reported cases were classified as unmasking IRIS [7][8][9][10]12,13], except for one pediatric case from India that was classified as paradoxical IRIS [6]. ...
... To date there have been few case reports of IRIS associated with T. marneffei infection [6][7][8][9][10][11][12][13], and the incidence and risk factors have not been defined. All reported cases were classified as unmasking IRIS [7][8][9][10]12,13], except for one pediatric case from India that was classified as paradoxical IRIS [6]. Here we described three adult patients with talaromycosis-associated paradoxical IRIS at the Hospital for Tropical Diseases in Ho Chi Minh City in order to add to the currently sparse knowledge on the clinical characteristics and management of these patients. ...
... These laboratory characteristics, in addition to a rise in CD4+ T-cell counts, might aid the differentiation of patients with IRIS and those with disease relapse, as culture can be positive in both conditions. Unlike paradoxical IRIS, significant inflammation does not appear to be a prominent feature in the reported cases of unmasking IRIS in the literature, where patients tended to present with features similar to disseminated talaromycosis (skin lesions, lymphadenopathy, hepatosplenomegaly, and anemia) [7][8][9][10][11][12][13]. All three of our patients required hospitalization for exclusion of other active infections, re-treatment with high dose antifungals, and supportive care. ...
Talaromyces marneffei infection is a major cause of death in HIV-infected individuals in South and Southeast Asia. Talaromycosis immune reconstitution inflammatory syndrome has not been well described. Here we report the clinical features, management, and outcomes of three HIV-infected patients with talaromycosis-associated paradoxical immune reconstitution inflammatory syndrome in Ho Chi Minh City, Vietnam.
... Aspergillus niger also is used for enzyme and citric acid production. A. oryzae, soybean, Penicillium roqueforti, cheese and P. chrysogenum are used for penicillin production [2] . Heat resistant Byssochlamys species may produce on pasteurized fruit juices [3] . ...
ITS region which is common between fungal species can be clearly separated from other species by fungal identification.
Molecular of identification inventory in our 300 Aspergillus and Penicillium species made and Sequence information can be used
cases of 120 such sequences were compared with online gene bank with the blast of the software. As a result, Aspergillus
fumigatus (20), A. awamori (12), A. niger (9), A. tubingensis (6), A. terreus (9), A. japonicas (4), A. oryze (5), A. tamari (2), A.
versicolor (1), A. brassiliensis (1), A. flavus (1), Penicilium commune (5), P. griseofuly (1), P. chrysege (6), Penicillium
restrictcum (1) and 13 of them belong to the other fungus groups were determined. To preserve the mycelium and spores of
Aspergillus and Penicillium species also been lyophilization and labeled.
... There have been no systemic clinical nor immunological studies of talaromycosis-IRIS. The few case reports of talaromycosis-IRIS have occurred mostly as unmasking IRIS in the setting of ART and one paradoxical-IRIS (reviewed in [42]). Typically, patients present with fever, weight loss and skin lesions and may have epigastric tenderness, lymphadenopathy or tender joints [42,43]. ...
... The few case reports of talaromycosis-IRIS have occurred mostly as unmasking IRIS in the setting of ART and one paradoxical-IRIS (reviewed in [42]). Typically, patients present with fever, weight loss and skin lesions and may have epigastric tenderness, lymphadenopathy or tender joints [42,43]. Culture may reveal Talaromyces spp., and yeast cells may be seen on histopathology. ...
Invasive fungal infections (IFIs) cause significant mortality and morbidity in HIV-infected patients, patients with malignancy on chemotherapy, recipients of solid organ and haematological stem cell transplantation, patients with primary immunodeficiencies and those on immunomodulators such as steroids and tumour necrosis factor-alpha inhibitors. Immune reconstitution inflammatory syndrome (IRIS), an exaggerated, unexpected inflammatory phenomena occurring in temporal association with enhanced immune function in these conditions, is difficult to recognise and manage. Here, we detail what we have learnt from studies in cryptococcosis-associated IRIS and discuss other common fungal IRIS including histoplasmosis-IRIS, talaromycosis/penicilliosis-IRIS, pneumocystis-IRIS and a less well-recognised IRIS seen with invasive aspergillosis in the setting of neutrophil recovery. We also reflect on the enormity of what we are yet to understand about IRIS immunopathogenesis, diagnosis and management.
... Aspergillus niger also is used for enzyme and citric acid production. A. oryzae, soybean, Penicillium roqueforti, cheese and P. chrysogenum are used for penicillin production [2] . Heat resistant Byssochlamys species may produce on pasteurized fruit juices [3] . ...
... 9 P. marneffei presenting in the context of an IRIS has only been reported rarely-there has been one reported case in Europe 10 and four cases worldwide. 11 In three of the cases, presentation was dermatological, with development of papules or nodules after the start of ART. [10][11][12] Interestingly, in two of these cases the patient had skin lesions prior to the start of ART which were thought to be consistent with molluscum; the skin lesions associated with P marneffei can closely resemble those of molluscum or cryptococcal skin lesions. ...
... 11 In three of the cases, presentation was dermatological, with development of papules or nodules after the start of ART. [10][11][12] Interestingly, in two of these cases the patient had skin lesions prior to the start of ART which were thought to be consistent with molluscum; the skin lesions associated with P marneffei can closely resemble those of molluscum or cryptococcal skin lesions. In our patient's case, the skin nodules, which developed after ART, were distinct from the (subsequently histologically proven) molluscum and follicular lesions present at initial assessment. ...
A 62-year-old British man with advanced HIV was established on antiretroviral therapy and treatment for disseminated Mycobacterium avium complex and Cytomegalovirus infections. One month later he re-presented with epigastric pain, an epigastric mass and skin lesions. Abdominal imaging revealed large volume lymphadenopathy, which was not present on previous imaging. Blood cultures yielded Penicillium marneffei, a dimorphic fungus endemic to South-east Asia. The patient had spent several years travelling in Thailand prior to the diagnosis of HIV. Penicilliosis is a common AIDS-defining illness in endemic areas, but remains rare in Europe. In this case, it presented in the context of a rapidly decreasing viral load as an immune reconstitution inflammatory syndrome. The challenges of management in the context of multiple comorbidities and polypharmacy are discussed.
