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Clinical data were retrospectively reviewed for one case of penicillium marneffei infection after renal transplantation (RT) to explore a proper management of peniciliosis marneffei (PSM)transplantation.This case had a history of pulmonary tuberculosis and underwent RT due to uremia.After discharging, postoperative recovery was excellent.Recurrent cough occurred at Month 7 post-operation.Fiberoptic bronchoscopy and pulmonary CT indicated a possibility of pulmonary tuberculosis.However, a definite diagnosis of PSM was confirmed by next generation sequencing (NGS) and pathogenic bacteria culture of alveolar lavage fluid.After adjusting immunosuppressive agents and regular antifungal treatment with voriconazole, respiratory symptoms improved and pulmonary CT hinted at a resorption of lesion.Features of pulmonary CT and bronchoscopic examination were nearly similar to those of tuberculosis.Thus early bacterium culture and NGS may aid an definite diagnosis.Voriconazole is an effective treatment of the disease.
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Penicillium marneffei (PM) is the only thermally dimorphic species as a Penicillium that causes the transmitted penicilliosis marneffei (PSM). PM infection is more common in immunodeficient children.Due to the lack of specific clinical manifestations, PSM is easily misdiagnosed as pulmonary plasmacycosis, tuberculosis or pulmonary aspergillosis.Because of the rapid progress and multiple complications of transmitted PSM, its mortality remains high without timely and effective treatment.Therefore, early diagnosis and treatment are of great significance, and the diagnosis of PSM mainly relies on the immune function examination, measurement of serum markers, pathogen detection and imaging examinations.There is no standard antifungal regimen, and Amphoterus B and Itraconazole are used as the first-line treatment.This study aims to review the progress of diagnosis and treatment of PM infection in children.
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Introduction: Invasive fungal infections other than theCandida species and Aspergillus species are becomingcommon in the nosocomial setting particularly among theimmunocompromised patients but there is a hinderance intheir accurate diagnosis. Aim of our study was to know theprevalence of rare fungal species and to know the patientsoutcome in our region. Aim of our study is to know theprevalence of rare fungal species and to know the patientsoutcome in our region.Material amd Methods: The present study was carried outon the patients attending outpatient department and inpatientdepartment of T.B. and Respiratory Diseases, along with thoseattending antiretroviral treatment clinic and ICTC (Departmentof Microbiology), in J. N. Medical College, AMU during theperiod of January 2015 to October 2016.Results: Majority of the cases i.e., 47 (31.3%) were between31-40 years with a mean age of 32.5 years. Of 65 isolates,Cryptococcus neoformans and Pneumocystis jiroveciirepresented 2 (6.1%) isolates each, all of which were foundin HIV positive cases. 1 (3.1%) isolate of Mucor from adiabetic patient and 1 (3.1%) isolate of Penicillium marneffeifrom an HIV positive patient as detected. Cryptococcus andPneumocystis jirovecii were isolated from both patients withCD4 count< 200. and 114(+19.9) respectively.Conclusions: Invasive fungal infections other than thecandidia species and aspergillus species are becoming verycommon now a days.
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Penicilliosis is a rare opportunistic fungal infection caused by Talaromyces marneffei, especially in the HIV-infected patients. The untreated disease is highly fatal. The infection is endemic in Southeast Asia and Northeast India. The present case is the first case of disseminated penicilliosis from North India and Delhi in a 31-year-old male, recently diagnosed with HIV. This case highlights the importance of considering an unusual organism as the cause of disseminated disease in the nonendemic area.
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Objective To investigate the autophagy level of Ana-1 cells after ingesting melanized Penicillium marneffei (PM),and to explore the feasibility of rapamycin in killing the bacteria by inducing macrophages autophagy.Methods Melanized PM was cultivated and isolated from the medium containing dopamine.The expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) in Ana-1 cells stimulated by conventional or melanized PM was detected by western blot.The expression levels of LC3 Ⅱ protein in Ana-1 cells treated with rapamycin and incubated with melanized PM was detected.Then,the localization of LC3 Ⅱ in Ana-1 cells which contained melanized PM was observed by immunofluorescence staining.Finally,the direct sterilization effect of rapamycin on melanized PM were detected,and the sterilization effect of Ana-1 cells treated with or without rapamycin on melanized PM was measured.Results No significant change was found in the LC3 Ⅱ level of Ana-1 cells after ingesting melanized PM (P＞0.05),while LC3 Ⅱ level in Ana-1 cells treated with rapamycin which contained melanized PM was significantly increased (P=0.009).The colocalization of LC3 Ⅱ with melanized PM in cytoplasm of Ana-1 cells was observed.For Ana-1 cells treated with rapamycin,3 h and 6 h after incubated with melanized PM,the survival rates of melanized PM both were significantly reduced (P=0.026,0.014).No significant sterilization effect of Ana-1 cells or rapamycin was observed under the same conditions.Conclusion Melanized PM can suppress the activation of macrophage autophagy,and rapamycin can improve sterilization effect of Ana-1 cells by inducing the activation of autophagy.
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Penicillium marneffei is a dimorphic fungus causing infection mainly in immunocompromised individuals, especially those with HIV infection. Penicillium marneffei is an important opportunistic pathogen of HIV infection in South East Asia including Manipur. Common clinical manifestations are fever, cough, weight loss, generalised lymphadenopathy, and papulonodular eruptions. We report an unusual case of HIV patient with Penicillium marneffei infection presenting as hoarseness
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In order to increase awareness of infection of Penicillium marneffei combined with Pneumocystis carinii pneu monia,we analysed and discussed the diagnosis and treatment of a P.marneffei combined with Pneumocystis carinii pneumonia and reviewed relevant literaure.Pharynx and larynx P.marneffei infection uozhes logy and molecullar was confirmed by physical examination,sputum culture and biopsy.Pneumocystis carinii pneumonia was diagnosed by CT findings and tested positive by PCR for P.carinii (PC).After antifungal treatment,the patient's symptoms and signs showed significant im provement.In conclusion,to achieve early diagnosis and appropriate treatment,sputum culture,biopsy and chest radiograph are suggested for pharynx and larynx recurrent ulcer which is difficult to heal.
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Objective:To investigate the thoughts and methods of clinical pharmacists involving in the treatment of 2 cases of atyp-ical pathogen infection. Methods:The consultation cases of 2 patients with atypical pathogens infection were analyzed,and the consul-tation experience was summarized. Results: After the consultation, the treatment efficacy of the patients was obvious. Conclusion:Clinical pharmacists can assist doctors in improving the efficacy and safety of drug treatment.
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ObjectiveTo understand the clinical and microbiological characteristics of AIDS-associated bloodstream infection (BSI).MethodsThe clinical and laboratory ifndings of 143 cases of BSI in AIDS patients who were hospitalized during the period from 2013 to 2014 were retrospectively analyzed.ResultsThe prevalence of BSI in AIDS patients was 22.1%. The 143 patients were divided into two groups in terms of fungal or bacterial infection. The incidence of speciifc skin rashes, anemia, hepatosplenomegaly and lymph node enlargement in fungal infection group was higher than those in bacterial infection group (allP<0.05). CD4+ cell count, WBC, neutrophils, RBC, hemoglobin, and platelet count in fungal infection group were lower than those in bacterial infection group, while AST and Cr were the opposite (allP<0.05).Penicillium marneffei(84/143, 58.7%) was the most common pathogen isolated from AIDS-associated BSI, followed byEscherichia coli (10/143, 7.0%),Cryptococcus neoformans (9/143, 6.3%),Klebsiella pneumoniae (7/143, 4.9%),Salmonella (6/143, 4.2%),Candida albicans(3/143, 2.1%), andAeromonas (3/143, 2.1%). Most strains were still susceptible to the commonly used antibiotics.ConclusionsThe prevalence of BSI is high in AIDS patients. Fungal BSI is more likely to have skin rash, anemia, hepatosplenomegaly and lymphadenopathy, hematologic abnormalities, liver and renal function impairment. Fungi, especiallyPenicillium marneffei, are the main pathogen of AIDS-associated BSI. Most strains are susceptible to the commonly used antibiotics.
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Objective To investigate the effect of levodopa on melanogenesis in Penicillium mameffei (PM),and to determine if melanization affects the antifungal drug susceptibility of PM.Methods A clinical isolate of PM,GXMU121011,was inoculated onto Sabouraud's dextrose agar (SDA) containing different concentrations (0.1-10 mmol/L) of levodopa at an inoculum density of 1.0 × 106 cfu/ml,or onto SDA containing 1 mmol/L levodopa at three inoculum densities (1.0 × 105,1.0 × 106,1.0 × 107 cfu/ml),and cultured at 37 ℃ for 7 days.Subsequently,melanization of PM colonies was observed.The paper-disk method was used for antifungal susceptibility testing,and the diameter of inhibition zones of itraconazole,fluconazole and amphotericin B against 8 clinical strains of PM was determined on SDA with or without levodopa.Results The melanization of PM colonies increased when the concentration of levodopa increased from 0.1 to 1.0 mmol/L,peaked when that reached 1.0 and 3.0 mmol/L,but mildly decreased when that continuously increased beyond 3.0 mmol/L,and a slight shrinkage was observed in PM colonies when that was 10.0 mmol/L.The color of colonies deepened along with the increase in inoculum density of PM.The average diameters of inhibition zones of itraconazole,fluconazole and amphotericin B against PM were all significantly lower on SDA with levodopa than on SDA without levodopa (all P ＜ 0.05).Conclusions Levodopa concentration and inoculum density both affect melanogenesis in PM.Melanization may decrease the susceptibility of PM in yeast phase to itraconazole,fluconazole and amphotericin B in vitro.
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Objective To observe ultrastructural changes in a clinical isolate of Penicillium marneffei(PM) before and after treatment with amphotericin B or voriconazole by using scanning electron microscopy (SEM)and transmission electron microscopy (TEM). Methods A microdilution method was performed to determine the minimum inhibitory concentration (MIC)of amphotericin B and voriconazole against a clinical isolate of PM. Then, the PM isolate was treated with amphotericin B or voriconazole at their MICs and 10-fold MICs for 24, 48 and 72 hours. The ultrastructural changes in this isolate before and after the treatment were observed by using SEM and TEM. Results After the treatment with amphotericin B, SEM showed that the conidia or yeast cells of the PM isolate were gradually damaged, and their outer layers experienced detachment, shrinkage, breakage and adhesion with the increase in treatment duration and concentrations of amphotericin B; TEM also showed degenerated mitochondria, broken nuclei and cell walls, and shrunken cytoplasmic membrane with disappearance of cytoplasmic organelles. Similarly, the damage, shrinkage, shriveling and collapse of PM cells were seen by using SEM, and TEM showed many high-density electron-dense granules in cytoplasm, degeneration of mitochondria, roughening of cell wall surface, damage and shrinkage of cytoplasmic membrane, and disappearance of cytoplasmic organelles after voriconazole treatment. Conclusions Amphotericin B and voriconazole both had a strong antifungal effect on PM, and could induce evident ultrastructural changes, which were positively associated with treatment duration and concentrations. Moreover, amphotericin B caused more severe damage to PM compared with voriconazole.
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Objective To investigate the ultrasonographic and pathological changes of peripheral pulmonary lesions in acquired immunodeficiency syndrome (AIDS) complicated with Penicillium marneffei pneumonia (PMP) and their clinical significance.Methods The ultrasonographic and pathological data of peripheral pulmonary lesions in 31 cases of AIDS complicated with PMP who were diagnosed in Fourth People's Hospital of Nanning were retrospectively reviewed.Results Among 31 cases of PMP,20 cases (64.5％) showed star-like diffuse sonogram,7 cases (22.6％) low solid echo and 4 cases (12.9 ％) black hole-like sonogram in ultrasonographic changes of peripheral pulmonary lesions.In pathological examination,Penicillium marneffei were seen in all samples:periodic acid-Schiff stain (PAS) and periodic acid-Schiff diastase stain (PAS-D) were all positive.Twenty four cases (77.4％) mainly showed infiltration of inflammatory cells,and 7 cases (22.6 ％) mainly showed necrosis and fibrous hyperplasia.Among 20 patients with star like diffuse sonogram,19 were mainly infiltration of inflammatory cells in pathological changes,and 19 were CD4+ T lymphocyte counts of 100-200/μL.Among 4 patients with black hole-like sonogram,all were necrosis in the central and hyperplasia in the peripheral in pathological changes,and CD4-T lymohocyte counts were all＜50/μL.Conclusions In AIDS patients complicated with PMP,ultrasonographic features were probably correlated with pathological changes in biopsy tissues and CD4-T lymphocyte counts.
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Objective To observe the ultrastructure of dimorphic Penicillium marneffeiisolates from wild bamboo rats (Rhizomys pruinosus) in Guangxi region as well as from a patient with penieilliosis marneffei,and to compare their biological characteristics and anti-oxidative mechanisms.Methods Two Penicillium marneffei strains,including one isolated from wild bamboo rats (Rhizomys pruinosus) in Guangxi region and one from a patient with penicilliosis marneffei,were cultured with or without the presence of 2.0 mmol/L hydrogen peroxide in potato dextrose agar (PDA) at 25 ℃ and in brain-heart infusion (BHI) broth at 37℃ for seven days.The shape of colony and growth of both strains were observed.Light microscopy was carried out to study the morphology,and transmission electron microscopy to observe the ultrastructure,of both isolates.Results Ater incubation with hydrogen peroxide,there was a slowdown in the growth of both Penicillium marneffei isolates at both mycelial phase and yeast phase,with an increase in the production of pigment at mycelial phase at 25℃.No obvious changes were observed at 37 ℃ in the morphology of either the clinical isolate or the bamboo rat isolate when cultured with hydrogen peroxide compared with those cultured without hydrogen peroxide.Light microscopy showed attenuated spore formation by the clinical isolate when cultured at 25 ℃ with hydrogen peroxide,crenation of both isolates when cultured at 37 ℃ with hydrogen peroxide.Under a transmission electron microscope,the mycelial cells of both isolates exhibited smooth cell walls,intact cell membranes,with nuclei,mitochondria,endoplasmic reticulum,lipid body,vacuoles of various sizes in the cytoplasm at 25 ℃,and even microbodies at 37 ℃,when cultured without the presence of hydrogen peroxide.After incubation with hydrogen peroxide,the cell wall of both isolates became incomplete with defects in some areas and uneven thickness,the cell membrane discontinuous with shrinkages and projections,and the cytoplasm was inhomogeneous with obvious phagocytosis and numerous phagocytic vacuoles.Conclusions The clinical and bamboo rat isolates of Penicillium marneffei experience different biological and morphological changes under oxidative stress,hinting differences in antioxidative mechanism between them.
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Objective To evaluate the role of complement receptor 3 (CR3) on murine macrophages in the recognition of Penicillium marneffei.Methods RAW264.7 murine macrophage cells were cultured in vitro,and divided into four groups to be cocultured with inactivated and live Penicillium mameffei yeast cells as well as inactivated and live Penicillium marneffei conidia respectively at 37 ℃ in 5％ CO2 for one hour.The RAW264.7 cells incubated with phosphate-buffered saline (PBS) served as the blank control group.Then,reverse transcription-PCR was conducted to detect CR3 mRNA expression,Western blot to measure CR3 protein expression,flow cytometry to determine phagocytosis rate,enzyme-linked immunosorbent assay (ELISA) to quantify cytokine levels in culture supernatant.Some RAW264.7 macrophages were transfected with a specific siRNA targeting CR3 gene and cocultured with inactivated Penicillium marneffei conidia,subsequently,phagocytosis rate and supematant cytokine levels were determined.Data were processed by the SPSS 16.0 software,and one-way analysis of variance (ANOVA) was conducted for inter-group comparisons of these parameters.Results No significant differences were observed in the mRNA or protein expressions of CR3 among the four groups of RAW264.7 cells cocuhured with different forms of Penicillium marneffei (both P ＞ 0.05).The phagocytosis rate was 95.14％,89.56％,91.03％ and 90.78％ in RAW264.7 cells cocultured with inactivated conidia and yeast cells,as well as live conidia and yeast cells of Penicillium marneffei,respectively (P ＞ 0.05).The levels of interleukin (IL)-2,interferon (IFN)-γ,IL-4 and IL-10 in culture supernatant were increased at different degrees after one-hour coculture in the four coculture groups compared with the blank control group,but no statistical difference was noted among the four coculture groups in the supernatant levels of these cytokines (all P ＞ 0.05).After coculture with inactivated Penicillium marneffei conidia,the siRNA-transfected RAW264.7 cells showed a statistical decrease in phagocytosis rate (10.89％ vs.92.78％,P ＜ 0.05) and supernatant levels of IL-2,IFN-γ IL-4 and IL-10 compared with untransfected RAW264.7 cells.Conclusions In early stage of innate immunity,CR3 on macrophages may be one of the pattern recognition receptors participating in the recognition and mediation of phagocytosis of Penicillium marneffei.It's possible that both Thl-and Th2-type cytokines,such as IL-2,IFN-γ,IL-4 and IL-10,are involved in the immune response of macrophages against Penicillium marneffei.
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Objective To isolate and purify melanin from yeast cells of Penicillium mameffei (PM) and to analyze its physicochemical features.Methods PM yeast cells were cultured in minimal medium containing levodopa (L-dopa) with continuous shaking at 37 ℃.Melanin was isolated from the yeast cells of PM by cell walllysing enzyme,denaturant,concentrated hot acid,and purified by sodium hydroxide and concentrated hydrochloric acid.The physicochemical properties of isolated melanin were assessed on the basis of combined chemical analysis and spectroscopic methods including ultraviolet-visible (UV-vis),Fourier transform infrared (FT-IR) and electronparamagnetic resonance (EPR).Results Similar to synthetic dopa-melanin,the isolated melanin from PM was alkali soluble,acid-resistant,insoluble in water and most organic solvents,precipitated at or below PH 3,and could be bleached by hydrogen peroxide.UV-vis spectrophotometric analysis showed that the PM-derived melanin had a typical absorption peak at 205 nm and the absorbance decreased with the increase of wavelength.FT-IR spectroscopy displayed two absorption peaks at about 3 μm and 6 μm,which was characteristic of classic melanin.EPR spectroscopy revealed that the isolated melanin contained stable free radicals.Conclusion Yeast cells of PM can use exogenous L-dopa to synthesize dopa-melanin.
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Objective To discuss the clinical features of immunocompetent patients with Penicilliosis marneffei.Methods To analyze and summarize the clinical data of 4 immunocompetent patients with Penicilliosis marneffei.Results Clinical manifestation of patients centered on intermittent slight or mild fever,lymphadenectasis,skin eruptions,osteolytic destruction,anaemia,and leukocytosis.The cultural Penicillium marneffei in specimen such as blood,pus showed a higher positive rate.Amphotericin B and itraconazole was available in treatment.Conclusion Immunocompetent people can be infected by Penicillium marneffei,and they appear nonspecific in clinical manifestation after infection.A timely and effective antifungal therapy can improve the prognosis of patients.
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Penicillium marneffei may cause life-threatening systemic fungal infection in immune-compromised patients and it is endemic in Southeast Asia. A 39-yr-old HIV-infected male, living in Laos, presented with fever, cough, and facial vesiculopapular lesions, which had been apparent for two weeks. CT scans showed bilateral micronodules on both lungs; Pneumocystis jirovecii was identified by bronchoscopic biopsy. Despite trimethoprim-sulfamethoxazole and anti-tuberculosis medications, the lung lesions progressed and the facial lesions revealed central umbilications. Biopsy of the skin lesions confirmed disseminated penicilliosis, with the culture showing P. marneffei hyphae and spores. The P. marneffei was identified by rRNA PCR. A review of the bronchoscopic biopsy indicated penicilliosis. The patient completely recovered after being prescribed amphotericin-B and receiving antiretroviral therapy. This is the first case of penicilliosis in a Korean HIV-infected patient. It is necessary to consider P. marneffei when immunocompromised patients, with a history of visits to endemic areas, reveal respiratory disease.
Subject(s)
Adult , Humans , Male , Amphotericin B/therapeutic use , Anti-HIV Agents/therapeutic use , Antifungal Agents/therapeutic use , Bronchoscopy , Dermatomycoses/drug therapy , HIV Infections/diagnosis , Immunocompromised Host , Laos , Lung Diseases/drug therapy , Penicillium/genetics , Pneumocystis carinii/isolation & purification , Tomography, X-Ray ComputedABSTRACT
Se presenta el primer caso humano de peniciliosis por Penicillium marneffei observado en la República Argentina. El paciente era un joven de 16 años, HIV-positivo, procedente de un área rural del sur de China. El paciente fue internado en el Hospital "F. J. Muñiz" por padecer una neumonía grave con insufciencia respiratoria aguda. El agente causal fue aislado de un lavado broncoalveolar y se lo observó en un citodiagnóstico de piel. La identifcación de P. marneffei fue confrmada por las características fenotípicas del aislamiento y la amplifcación del ADNr. El enfermo padecía una infección muy avanzada por HIV que condujo a la aparición simultánea de infecciones por citomegalovirus, Pneumocystis jirovecii y procesos bacterianos nosocomiales. Este complejo cuadro derivó en una evolución fatal.
The frst case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identifcation was confrmed by rRNA amplifcation and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.
Subject(s)
Adolescent , Humans , Male , AIDS-Related Opportunistic Infections/microbiology , Dermatomycoses/microbiology , HIV-1 , HIV-2 , Lung Diseases, Fungal/microbiology , Penicillium/isolation & purification , AIDS-Related Opportunistic Infections/epidemiology , Argentina/epidemiology , Bronchoalveolar Lavage Fluid/microbiology , China/ethnology , Cytomegalovirus Infections/complications , Diagnosis, Differential , DNA, Fungal/analysis , Dermatomycoses/epidemiology , Fatal Outcome , Histoplasmosis/diagnosis , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/epidemiology , Pneumocystis carinii , Polymerase Chain Reaction , Penicillium/classification , Pneumonia, Pneumocystis/complications , RibotypingABSTRACT
Objective To discover the clinic presentation and therapy of disseminated Penicillium marneffei infection in children.Methods We reported the clinic presenation,pathology and therapy of the disseminated Penicillium marneffei in children.Results Case one,l-year-old boy presented with fever and cough for one month.Penicillium marneffei was cultured from bone marrow and blood.Case two,8-year-old girl presented with delirium.Penicillium marneffei was cultured from blood.Treatment with voriconazole solely was successful in the first case.Conclusion Central nervous system could been infected by Penicillium marneffei.Treatment with voriconazole solely could be effective in children.