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      Talaromyces marneffei Mp1p Antigen Detection may Play an Important Role in the Early Diagnosis of Talaromycosis in Patients with Acquired Immunodeficiency Syndrome

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          Abstract

          Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n = 93) and those without Talaromyces marneffei (non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4+ counts of < 50 cells/µL compared to those with CD4+ counts ranged from 50–100 cells/µL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4+ counts.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s11046-022-00618-9.

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          Most cited references26

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          Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects.

          Penicillium marneffei infection is an important emerging public health problem, especially among patients infected with human immunodeficiency virus in the areas of endemicity in southeast Asia, India, and China. Within these regions, P. marneffei infection is regarded as an AIDS-defining illness, and the severity of the disease depends on the immunological status of the infected individual. Early diagnosis by serologic and molecular assay-based methods have been developed and are proving to be important in diagnosing infection. The occurrence of natural reservoirs and the molecular epidemiology of P. marneffei have been studied; however, the natural history and mode of transmission of the organism remain unclear. Soil exposure, especially during the rainy season, has been suggested to be a critical risk factor. Using a highly discriminatory molecular technique, multilocus microsatellite typing, to characterize this fungus, several isolates from bamboo rats and humans were shown to share identical multilocus genotypes. These data suggest either that transmission of P. marneffei may occur from rodents to humans or that rodents and humans are coinfected from common environmental sources. These putative natural cycles of P. marneffei infection need further investigation. Studies on the fungal genetics of P. marneffei have been focused on the characterization of genetic determinants that may play important roles in asexual development, mycelial-to-yeast phase transition, and the expression of antigenic determinants. Molecular studies have identified several genes involved in germination, hyphal development, conidiogenesis, and yeast cell polarity. A number of functionally important genes, such as the malate synthase- and catalase-peroxidase protein-encoding genes, have been identified as being upregulated in the yeast phase. Future investigations pertaining to the roles of these genes in host-fungus interactions may provide the key knowledge to understanding the pathogenicity of P. marneffei.
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            Penicillium marneffei infection: an emerging disease in mainland China.

            Penicillium marneffei is an emerging pathogenic fungus that can cause a life-threatening systemic mycosis in immunocompromised hosts, especially in patients with AIDS. This infection is endemic in Southeast Asia. With the prevalence of AIDS in this area, the number of patients with systemic penicilliosis marneffei is found to be increasing rapidly in mainland China in recent years. We recently reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984 to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological and clinical features, laboratory findings, reaction to therapy and prognosis of the disease. We found that 99.4% of the cases were reported in the southern part of China; among these cases, 42.8% were from Guangxi (286 cases) and 40.6% were from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7%) of penicilliosis marneffei were reported with infection by the human immunodeficiency virus, 25 cases (3.8%) with other immunocompromised diseases, and 57 cases (8.5%) without any documented underlying diseases. Fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin lesions were the common clinical manifestations of P. marneffei infections. The 569 cases received antifungal therapy with a mortality of 24.3% (138 cases), 99 cases who had not received antifungal therapy had a mortality of 50.6%. P. marneffei was an emerging pathogenic fungus and become a medical and public health importance in mainland China. The immunocompromised patients should pay more attention to P. marneffei infection in the endemic areas.
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              Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam.

              Penicillium marneffei is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southeast Asia. The epidemiology and the predictors of penicilliosis outcome are poorly understood. We performed a retrospective study of culture-confirmed incident penicilliosis admissions during 1996-2009 at the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam. Seasonality of penicilliosis was assessed using cosinor models. Logistic regression was used to assess predictors of death or worsening disease based on 10 predefined covariates, and Cox regression was performed to model time-to-antifungal initiation. A total of 795 patients were identified; hospital charts were obtainable for 513 patients (65%). Cases increased exponentially and peaked in 2007 (156 cases), mirroring the trends in AIDS admissions during the study period. A highly significant seasonality for penicilliosis (P<.001) but not for cryptococcosis (P=.63) or AIDS admissions (P=.83) was observed, with a 27% (95% confidence interval, 14%-41%) increase in incidence during rainy months. All patients were HIV infected; the median CD4 cell count (62 patients) was 7 cells/μL (interquartile range, 4-24 cells/μL). Hospital outcome was an improvement in 347 (68%), death in 101 (20%), worsening in 42 (8%), and nonassessable in 23 (5%) cases. Injection drug use, shorter history, absence of fever or skin lesions, elevated respiratory rates, higher lymphocyte count, and lower platelet count independently predicted poor outcome in both complete-case and multiple-imputation analyses. Time-to-treatment initiation was shorter for patients with skin lesions (hazard ratio, 3.78; 95% confidence interval, 2.96-4.84; P<.001). Penicilliosis incidence correlates with the HIV/AIDS epidemic in Viet nam. The number of cases increases during rainy months. Injection drug use, shorter history, absence of fever or skin lesions, respiratory difficulty, higher lymphocyte count, and lower platelet count predict poor in-hospital outcome. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
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                Author and article information

                Contributors
                llheliza@126.com
                Journal
                Mycopathologia
                Mycopathologia
                Mycopathologia
                Springer Netherlands (Dordrecht )
                0301-486X
                1573-0832
                3 March 2022
                : 1-11
                Affiliations
                GRID grid.410737.6, ISNI 0000 0000 8653 1072, Infectious Disease Center, Guangzhou Eighth People’s Hospital, , Guangzhou Medical University, ; Guangzhou, 510060 China
                Author notes

                Handling Editor: Patrick C. Y. Woo.

                Article
                618
                10.1007/s11046-022-00618-9
                8890818
                35237935
                d42fffb3-b854-4b3c-ab16-33090efcf557
                © The Author(s), under exclusive licence to Springer Nature B.V. 2022

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 5 January 2022
                : 8 February 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82072265
                Award Recipient :
                Funded by: Guangzhou Basic Research Program on People’s Livelihood Science and Technology
                Award ID: 202002020005
                Award Recipient :
                Categories
                Original Article

                Infectious disease & Microbiology
                talaromycosis,penicilliosis,talaromyces marneffei,penicillium marneffei,mp1p

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