Talaromyces Marneffei Infection Research Articles

Innate Immunity Acts as the Major Regulator in Talaromyces marneffei Coinfected AIDS Patients: Cytokine Profile Surveillance During Initial 6-Month Antifungal Therapy.

BackgroundTalaromycosis caused by Talaromyces marneffei infection is a fatal systemic mycosis in immunosuppressed individuals, such as patients with AIDS. Cytokines and immunocytes play a central role against fungus infection. However, how the host immune system responds to infection and treatment has not been reported to date.MethodsForty-one Talaromyces marneffei coinfected AIDS patients were followed up, their immunocytes and cytokine profiles were obtained at different antifungal treatment stages, and data on clinical features and laboratory examinations were collected. Correlation analysis was used to identify factors associated with host immunity against Talaromyces marneffei infection in AIDS patients.ResultsCommon diseases and conditions of these 41 patients were lymphadenopathy, hepatomegaly, and splenomegaly. CD4+ T cells were extremely low in all of them. Moreover, significant increases of proinflammatory cytokines (IL-12, IL-17A, TNF-α, IFN-γ, IL-18, and IL-1β), anti-inflammatory cytokines (IL-10), and chemokines (IP-10) were observed in talaromycosis before treatment (P < .05), comparing to both AIDS patients and healthy controls. The cytokines IL-6, IL-8, TNF-α, IL-18, IL-17A, IL-7, IP-10, and IL-1β reached peak levels 3 days after initial antifungal therapy, and then gradually decreased. The symptoms of the patients gradually decreased. Furthermore, patients who died showed the highest levels of IL-6, TNF-α, IL-8, IL-1β, and IP-10, which were 1.4- to 164-fold higher than in surviving patients.ConclusionsOur findings indicate that innate immune-cell-derived cytokines are critical for host defense against AIDS-associated Talaromyces marneffei infection; furthermore, excessive inflammatory cytokines are associated with poor outcomes.

Talaromyces marneffei infection in a lung cancer patient: a rare case report

BackgroundTalaromyces marneffei is an invasive, and thermal dimorphic pathogenic fungus, whose infection is life threatening in human. Although immunocompromised patients, such as patients with human immunodeficiency virus infection and recipients of organ transplant, are susceptible hosts, infections have been recently reported in people with normal immune function. Patients with cancer may also be susceptible hosts but no case of T. marneffei infection has been reported in patients with lung cancer. In this case, we describe T. marneffei infection coexisting with primary pulmonary lymphoepithelioma-like carcinoma (LELC) in an HIV-negative patient.Case presentationA 50-year-old, previously healthy female presented with a 1-month history of cough and fever. CT scans showed a mass in the left lower lung, left pleural thickening, pleural effusion, and multiple swollen lymph nodes throughout the body. Based on the pathology of the left lung lesion, she was diagnosed with left primary pulmonary LELC complicated with T. marneffei. She received both anti-tumor and anti-fungal treatments. A subsequent CT re-examination demonstrated that the mass was absorbed remarkably after treatment. Follow up showed no tumor progression and no relapse of T. marneffei infection.ConclusionThis case suggested that clinicians should pay more attention to the potential hosts of T. marneffei infection, especially those with lung cancer. Early diagnosis and treatment can improve the prognosis of T. marneffei infection coexisting with lung cancer.

Evaluation of in vitro antifungal activity of osthole against Talaromyces marneffei in yeast phase

Objective To evaluate the in vitro antifungal activity of osthole against Talaromyces marneffei (TM) in yeast phase, in order to provide an experimental reference for the clinical treatment of TM infection with Chinese medicine. Methods There were 20 TM strains, including 1 standard strain, 2 fluconazole-spontaneously resistant strains, 11 clinical isolates, and 6 isolates from wild bamboo rats. A microdilution method was used to prepare 96-well antifungal sensitivity test plates containing osthole, fluconazole, amphotericin B, itraconazole and voriconazole at different concentrations, which were incubated with (1-5) × 103 CFU/ml of tested TM strain suspensions at 37 ℃ for 48 hours. Meanwhile, TM strains cultured in the media without antifungal drugs served as positive (growth) control group, and culture media served as negative group. The minimum inhibitory concentrations (MICs) of antifungal drugs against yeasts were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M27-A2 Document) . Fluconazole MIC was defined as the lowest drug concentration that resulted in ≥ 80% growth inhibition, and MICs of other antifungal drugs were the lowest drug concentrations that resulted in 100% growth inhibition, compared with growth control wells. Results The MICs among the quality control strains were all within the reference range, and TM grew well in the positive control wells. The MIC ranges of fluconazole, amphotericin B, itraconazole and voriconazole against TM strains were 2.0-8.0 mg/L, 1.0-4.0 mg/L, 0.03-0.25 mg/L and 0.06-0.25 mg/L respectively, and the MIC of fluconazole against fluconazole-spontaneously resistant strains was 128 mg/L. The MICs of osthole against the TM standard strain (FRR2161) , fluconazole-spontaneously resistant strains and 1 isolate from wild bamboo rats were 16, 32 and 128 mg/L respectively, and the MIC range of osthole against other 16 TM strains was 16-64 mg/L. The MICs of osthole at which 90% and 50% of the TM strains were inhibited were 64 and 32 mg/L respectively. Conclusion Osthole exhibits the antifungal activity against the yeast form of TM. Key words: Talaromyces; Osthole; Microbial sensitivity tests; Talaromyces marneffei

Talaromyces marneffei Mp1 Protein, a Novel Virulence Factor, Carries Two Arachidonic Acid-Binding Domains To Suppress Inflammatory Responses in Hosts.

Talaromyces marneffei infection causes talaromycosis (previously known as penicilliosis), a very important opportunistic systematic mycosis in immunocompromised patients. Different virulence mechanisms in T. marneffei have been proposed and investigated. In the sera of patients with talaromycosis, Mp1 protein (Mp1p), a secretory galactomannoprotein antigen with two tandem ligand-binding domains (Mp1p-LBD1 and Mp1p-LBD2), was found to be abundant. Mp1p-LBD2 was reported to possess a hydrophobic cavity to bind copurified palmitic acid (PLM). It was hypothesized that capturing of lipids from human hosts by expressing a large quantity of Mp1p is a virulence mechanism of T. marneffei It was shown that expression of Mp1p enhanced the intracellular survival of T. marneffei by suppressing proinflammatory responses. Mechanistic study of Mp1p-LBD2 suggested that arachidonic acid (AA), a precursor of paracrine signaling molecules for regulation of inflammatory responses, is the major physiological target of Mp1p-LBD2. In this study, we use crystallographic and biochemical techniques to further demonstrate that Mp1p-LBD1, the previously unsolved first lipid binding domain of Mp1p, is also a strong AA-binding domain in Mp1p. These studies on Mp1p-LBD1 support the idea that the highly expressed Mp1p is an effective AA-capturing protein. Each Mp1p can bind up to 4 AA molecules. The crystal structure of Mp1p-LBD1-LBD2 has also been solved, showing that both LBDs are likely to function independently with a flexible linker between them. T. marneffei and potentially other pathogens highly expressing and secreting proteins similar to Mp1p can severely disturb host signaling cascades during proinflammatory responses by reducing the availabilities of important paracrine signaling molecules.

Effects of cotrimoxazole prophylaxis on Talaromyces marneffei infection in HIV/AIDS patients receiving antiretroviral therapy: a retrospective cohort study

ABSTRACT The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005–2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35–0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/μL, 50–99 cells/μL, 100–199 cells/μL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/μL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

Role of autophagy in regulating the immune response of dendritic cells to Talaromyces marneffei infection

Autophagy can regulate antimicrobial immunity. However, it is unknown whether autophagy mediates the immune response of dendritic cells (DCs) to Talaromyces marneffei (T. marneffei) infection. Therefore, to explore the relationship between autophagy and multiplication of T. marneffei and investigate whether ERK1/2 signaling pathway regulates activation of autophagy and TNF-α and IFN-γ secretion by intracellular signaling mechanisms during T. marneffei infection in human DCs. DCs were infected with T. marneffei for different times. First, we found that T. marneffei induced activation of autophagy and ERK1/2 in human DCs. Second, the inhibition of ERK1/2 suppressed activation of autophagy in T. marneffei-infected human DCs. Third, the suppression of ERK1/2 and autophagy decreased TNF-α and IFN-γ production and increased the proliferation of T. marneffei. These data suggest that ERK pathway plays vital regulatory roles in activation of autophagy and subsequent cytokine production during T. marneffei infection. Our data further indicate that autophagy is important in the regulation of the DC immune response to T. marneffei infection, thereby extending our understanding of host immune responses to the fungus.

An HIV-negative infant with systemic Talaromyces marneffei infection

An HIV-negative infant with systemic Talaromyces marneffei infection

‘O.I Spy’: Disseminated Talaromyces marneffei infection in an immunocompromised host

A 28-year-old Thai male was referred from Sydney international airport with acute shortness of breath requiring admission to the intensive care unit at a quaternary referral centre. Clinical examination revealed extensive lymphadenopathy, hepatomegaly and an umbilicated rash over his forehead, neck, arms and legs. Laboratory testing demonstrated deranged liver function, acute kidney injury, thrombocytopaenia and an elevated C-reactive protein. Blood cultures after 24 h incubation were positive for fungal elements. Yeast forms were visible within neutrophils on blood films, and a skin biopsy showed numerous yeast like organisms. A mould grew on solid media. This dimorphic fungus was identified as Talaromyces marneffei using molecular methods and the patient completed treatment with antifungals. HIV serology was positive with a CD4 count of 10 cells/μL, and multiple associated infections were identified and treated.

Sweet's Syndrome Associated with Talaromyces marneffei and Mycobacterium abscessus Infection Due to Anti-interferon-gamma Autoantibodies.

Sweet's Syndrome Associated with Talaromyces marneffei and Mycobacterium abscessus Infection Due to Anti-interferon-gamma Autoantibodies.

Diagnostic value of serum Mp1p antigen detection for Talaromyces marneffei infection in acquired immune deficiency syndrome patients

Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T. marneffei infection in acquired immune deficiency syndrome (AIDS) patients. Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T. marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T. marneffei infection and 29 health controls. Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T. marneffei infection in patients with AIDS were analyzed. χ2 test and t test were used for statistical analysis. Results The ratio of males to females and age of the study group were both comparable to those of the control group (χ2=0.019, P=0.889; t=1.810, P=0.07, respecitvley). The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (χ2=0.076, P=0.783). The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (χ2=0.037, P=0.847). The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (χ2=0.012, P=0.912). The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively. The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (χ2=0.049, P=0.829). The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (χ2=0.021, P=0.886). The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (χ2=0.045, P=0.832). The Kappa values were 0.83 and 0.80, respectively. Conclusion Detection of serum Mp1p antigen of T. marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T. marneffei infection in patients with AIDS. Key words: Acquired immunodeficiency syndrome; Talaromyces marneffei; Mannoprotein Mp1p; Serological diagnosis

A retrospective analysis of seven patients with acquired immunodeficiency syndrome and pharyngeal and/or laryngeal Talaromyces marneffei infection.

1.Talaromyces marneffei, formerly known as Penicillium marneffei, usually affects the monocyte-macrophage system and can cause fatal systemic mycosis in immunocompromised individuals. This retrospective study is the first to describe the clinical and endoscopic (nasal endoscopy, flexible endoscopy) features of penicilliosis with pharynx and/or larynx infection in patients with acquired immunodeficiency syndrome (AIDS). 2.During the study period, 126 patients were diagnosed with penicilliosis. Among them, only seven who presented with culture and/or histopathological evidence of pharyngeal and/or laryngeal T. marneffei infection were included; notably, all of these patients also had AIDS. 3.The most common specific pharyngeal and laryngeal features were sore throat, hoarseness, dysphagia, a pharyngeal and laryngeal mass and/or mucosal ulcerations, and enlargement of multiple cervical and axillary lymph nodes. Evaluation using nasal endoscopy and flexible endoscopy revealed pharyngeal and laryngeal ulcers and/or a mass. 4.Histopathological analysis of all pharyngeal and/or laryngeal tissue samples in our retrospective study revealed positivity for T. marneffei. The most common pathological type was non-reactive necrosis. 5.Histopathology and fungal culture of pharyngeal and laryngeal secretions and tissues are important and safe methods that allow determination of an accurate etiological basis for penicilliosis with pharyngeal and/or laryngeal infection, as well as differentiation from other diseases such as tuberculosis, lymphoma, pharyngeal cancer, and Kaposi's sarcoma. This article is protected by copyright. All rights reserved.

Serious fungal infections in Thailand.

The burden of serious fungal infection in Thailand is increasing but data regarding its incidence and prevalence are lacking. In this study we aimed to estimate the burden of serious fungal diseases in Thailand based on the size of the populations at risk and available epidemiological databases. Data derived from The Bureau of Epidemiology, Department of Disease Control, Thai Ministry of Public Health, World Health Organisation, international and local reports, and some unreported data were used. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Recurrent vulvovaginal candidiasis (>4 episodes per year) is estimated to occur in 3,310 per 100,000 population. Using a previously described rate that 14/10,000 admissions are with fungaemia and 94% of those are Candida, we estimated 8,650 patients with candidaemia. The prevalence of chronic pulmonary aspergillosis is relatively high with a total of 19,044, approximately half subsequent to pulmonary tuberculosis. Invasive aspergillosis is estimated to affect 941 patients following leukaemia therapy, transplantations, and chronic obstructive pulmonary disease, approximately 1.4/100,000. In addition, allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated at approximately 58.4/100,000 and 77/100,000, respectively. Given approximately 8,134 new cases of AIDS annually, cryptococcal meningitis, Pneumocystis pneumonia, and Talaromyces marneffei infection are estimated at 1.9/100,000, 2.6/100,000, and 0.3/100,000, respectively. The present study indicates that about 1.93% (1,254,562) of the population is affected by serious fungal infections. Owing to the lack of data, reports, and statistics, the number of patients with mycoses in Thailand can only be estimated.

Administration of Voriconazole in Disseminated Talaromyces (Penicillium) Marneffei Infection: A Retrospective Study.

Talaromyces (Penicillium) marneffei infection is a fatal disseminated mycosis caused by the dimorphic fungus Talaromyces marneffei; the therapeutic strategies for this infectious disease are limited. The aim of this retrospective study was to evaluate the efficacy and safety of voriconazole for treating patients with disseminated T. marneffei infection with or without HIV infection in a clinical setting. Patients who intravenously received voriconazole (6mg/kg q12h for the first 24h followed by 4mg/kg q12h) as the initial antifungal treatment were enrolled. The duration of the following antifungal treatment varied at the discretion of the investigators according to the patient responses. The primary global response was evaluated at Week 16 or at the end of treatment (EOT). Follow-up evaluations were performed at 6months and 1year after the EOT. Seventeen patients were enrolled in this study, but three were not evaluable because the treatment was prematurely discontinued. Among the remaining fourteen patients, ten patients had complete response and three had partial response at Week 16. Only one patient was determined to have failed response. Follow-up assessments in eleven patients showed that eight patients were cured and the remaining three patients relapsed at 6months after the EOT. These eight patients were assessed 1year later, and none of them had relapsed. No adverse events associated with voriconazole were recorded during the treatment. The results from our study suggest that voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection.

Clinical features of three patients with paradoxical immune reconstitution inflammatory syndrome associated with Talaromyces marneffei infection

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.

Disseminated Talaromyces marneffei and Mycobacterium abscessus in a Patient With Anti-Interferon-γ Autoantibodies.

Anti-interferon (IFN)-γ autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency and increased risk for infections with intracellular pathogens. We report on disseminated Talaromyces (Penicillium) marneffei and Mycobacterium abscessus infection in a 72-year-old, human immunodeficiency virus noninfected, Thai man with anti-IFN-γ autoantibody. The patient was successfully treated with antimicrobial therapy and rituximab to control B cell-derived autoantibodies.

Diffuse interstitial and multiple cavitary lung lesions due to Talaromyces marneffei infection in a non-HIV patient.

A 57-year-old man presented with unproductive cough and dyspnea for 6 months in Fujian Province, China. His misuse of a large amount of steroids (accumulated dose equivalent to 3530 mg prednisolone) resulted in Talaromyces marneffei infection. Chest computed tomographic scan revealed diffuse interstitial and multiple cavitary lung lesions. Treatment with amphotericin B combined with itraconazole resulted in total recovery, with marked regression of lung lesions.

Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatment-experienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of &lt;100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained.

Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatment-experienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of <100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained.