Characteristics and Prognosis of Talaromyces marneffei Infection in HIV-positive Children in Southern China

Knowledge about the clinical characteristics and prognostic factors of Talaromyces marneffei infection in children is limited, especially in HIV-positive children. We performed a retrospective study of all HIV-positive pediatric inpatients with T. marneffei infection in a tertiary hospital in Southern China between 2014 and 2019 and analyzed the related risk factors of poor prognosis using logistic regression. Overall, 28 cases were enrolled and the prevalence of talaromycosis in AIDS children was 15.3% (28/183). The median age of the onset was 8 years (range: 1–14 years). The typical manifestation of skin lesion with central umbilication was not common (21.4%). All the children had very low CD4⁺ cell counts (median 13.5 cells/μL, range: 3–137 cells/μL) on admission. 92.9% children were misdiagnosed and talaromycosis was only noted after positivity for HIV infection. 89.3% diagnoses of T. marneffei infections were based on positive blood cultures, with a long culture time (median 7 days, range from 3–14 days). The sensitivity of fungus 1,3-β-D-glucan assay was 63.2%. Amphotericin B was superior to itraconazole in the induction antifungal therapy of talaromycosis in HIV-positive children. A six-month follow-up revealed a 28.6% mortality. Lower ratio of CD4⁺/CD8⁺ and amphotericin B treatment not over 7 days predicted poor prognosis. Our retrospective study provided an overview and update on the current knowledge of talaromycosis in HIV-positive children. Pediatricians in endemic areas should be aware of mycoses to prevent misdiagnosis. 1,3-β-D-glucan assay did not show optimal sensitivity. Amphotericin B treatment over 7 days can improve poor prognosis.

     

播散性马尔尼菲篮状菌病1例

患者,男,32岁,反复淋巴结肿大、发热伴皮疹2年,广谱抗生素、抗结核治疗无效,肺部CT提示两肺内多发结节,血γ干扰素抗体阳性,皮肤活检组织、淋巴结组织、肺穿刺活检组织均培养出马尔尼菲篮状菌,予两性霉素B脂质体联合伏立康唑治疗效果佳。     

马尔尼菲篮状菌基因研究进展

温度依赖性双相真菌马尔尼菲篮状菌可致局限性或全身播散性感染,在东南亚以及我国南方,尤其是广西、广东有区域性流行。该菌主要感染免疫力低下的人群,是流行区艾滋病患者特征性的机会性感染。文中主要介绍马尔尼菲篮状菌的相关基础知识、基因研究历史进程以及综述马尔尼菲篮状菌在生长发育、双相转换、信号通路、细胞壁合成、细胞代谢、应激反应、热休克、色素、毒力及耐药方面的基因研究进展。     

Recurrent Talaromyces marneffei Infection Presenting with Intestinal Obstruction in a Patient with Systemic Lupus Erythematosus

Mycopathologia - Talaromyces marneffei is an important opportunistic pathogen mainly afflicting the HIV-infected patients, in rare instance, it could cause infection in non-HIV-infected...     

幼儿马尔尼菲篮状菌病2例

病例1,男,1岁6个月,咳嗽半个月、发热1周;病例2,男,11个月,反复鹅口疮3个月,咳嗽20 d。2例幼儿血培养阳性,均为马尔尼菲篮状菌,同时都存在免疫缺陷,非HIV感染,影像学提示肺部有多发小结节影,伏立康唑治疗后临床病愈出院,随访12个月无复发。     

马尔尼菲篮状菌感染动物模型的研究进展

马尔尼菲篮状菌Talaromyces marneffei是一种温度双相性致病真菌,原名马尔尼菲青霉Penicillium marneffei。马尔尼菲篮状菌病是由马尔尼菲篮状菌感染引起的一种严重的深部真菌病,主要流行于东南亚地区,在我国主要以南方地区多见,该病与HIV/AIDS的流行有高度相关性。近年来,随着艾滋病发病率的上升,马尔尼菲篮状菌病的发病率呈逐年上升趋势。该病发病隐匿,病死率高,但致病机制尚不明确。动物模型能够为疾病的发病机理和临床治疗等研究提供充分有力的证据,本文综述了马尔尼菲篮状菌感染动物模型的研究进展,对几种新型的动物模型进行了探讨。     

不同交配型马尔尼菲篮状菌的抗真菌药物敏感性

马尔尼菲篮状菌是马尔尼菲篮状菌病的致病菌,具有不同交配型,且交配型分布具有地域差异.交配型是影响某些真菌药物敏感性的因素之一,但是否影响马尔尼菲篮状菌的药物敏感性不详.为了解马尔尼菲篮状菌交配型和其药物敏感性的关系,本研究检测了不同交配型马尔尼菲篮状菌对7种抗真菌药物的敏感性.结果显示,与MAT-1型马尔尼菲篮状菌相比...     

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.     

Talaromyces marneffei Outside Endemic Areas in India: an Emerging Infection with Atypical Clinical Presentations and Review of Published Reports from India

Mycopathologia - Talaromycosis is a disseminated disease caused by Talaromyces (Penicillium) marneffei, mainly seen in acquired immunodeficiency syndrome (AIDS) patients. Its distribution is...     

Machine learning-based in-hospital mortality prediction of HIV/AIDS patients with Talaromyces marneffei infection in Guangxi,China

ObjectiveTalaromycosis is a serious regional disease endemic in Southeast Asia. In China, Talaromyces marneffei (T. marneffei) infections is mainly concentrated in the southern region, especially in Guangxi, and cause considerable in-hospital mortality in HIV-infected individuals. Currently, the factors that influence in-hospital death of HIV/AIDS patients with T. marneffei infection are not completely clear. Existing machine learning techniques can be used to develop a predictive model to identify relevant prognostic factors to predict death and appears to be essential to reducing in-hospital mortality.MethodsWe prospectively enrolled HIV/AIDS patients with talaromycosis in the Fourth People’s Hospital of Nanning, Guangxi, from January 2012 to June 2019. Clinical features were selected and used to train four different machine learning models (logistic regression, XGBoost, KNN, and SVM) to predict the treatment outcome of hospitalized patients, and 30% internal validation was used to evaluate the performance of models. Machine learning model performance was assessed according to a range of learning metrics, including area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) tool was used to explain the model.ResultsA total of 1927 HIV/AIDS patients with T. marneffei infection were included. The average in-hospital mortality rate was 13.3% (256/1927) from 2012 to 2019. The most common complications/coinfections were pneumonia (68.9%), followed by oral candida (47.5%), and tuberculosis (40.6%). Deceased patients showed higher CD4/CD8 ratios, aspartate aminotransferase (AST) levels, creatinine levels, urea levels, uric acid (UA) levels, lactate dehydrogenase (LDH) levels, total bilirubin levels, creatine kinase levels, white blood-cell counts (WBC) counts, neutrophil counts, procaicltonin levels and C-reactive protein (CRP) levels and lower CD3⁺ T-cell count, CD8⁺ T-cell count, and lymphocyte counts, platelet (PLT), high-density lipoprotein cholesterol (HDL), hemoglobin (Hb) levels than those of surviving patients. The predictive XGBoost model exhibited 0.71 sensitivity, 0.99 specificity, and 0.97 AUC in the training dataset, and our outcome prediction model provided robust discrimination in the testing dataset, showing an AUC of 0.90 with 0.69 sensitivity and 0.96 specificity. The other three models were ruled out due to poor performance. Septic shock and respiratory failure were the most important predictive features, followed by uric acid, urea, platelets, and the AST/ALT ratios.ConclusionThe XGBoost machine learning model is a good predictor in the hospitalization outcome of HIV/AIDS patients with T. marneffei infection. The model may have potential application in mortality prediction and high-risk factor identification in the talaromycosis population.     

Penicillium marneffei Infection in Immunocompromised Host

Penicillium marneffei (PM) was first described in 1973, causing human infection in a patient with Hodgkin Lymphoma. In the HIV/AIDS epidemic, it has been described as one of the important opportunistic infection following tuberculosis and cryptococcosis in endemic region of Southeast Asia and Southern China. Immunocompromised patients acquire penicilliosis through inhalation of conidia, resulting in disseminated disease characterized by prolonged fever, pancytopenia, hepatosplenomegaly, and classic cutaneous presentation of umbilicated papular eruption. Nowadays, rare manifestations such as fungemia, pneumonia, enterocolitis, genital ulcers, oral ulcer, and central nervous system infection have been reported. Over the past decade, molecular and genomic studies have revealed more knowledge of PM, and vaccines are under development. Modern era PM has become a serious threat in immunocompromised travelers, rather than HIV/AIDS patient in the endemic area, who receive an effective prophylaxis strategy along with the highly active antiretroviral therapy (HAART) initiation.     

Retrospective Analysis of 15 Cases of Penicilliosis marneffei in a Southern China Hospital

We retrospectively analyzed the medical records and clinical characteristics of 15 patients diagnosed with Penicilliosis marneffei (PSM) between January 1, 1993, and December 31, 2012, at the Third Affiliated Hospital of Sun Yat-sen University. The most common symptoms of PSM were fever (14/15, 93 %), cough (13/15, 87 %), and sputum production (6/15, 40 %), weight loss (14/15, 60 %), lymph node enlargement (9/15, 60 %), hepatosplenomegaly (7/15, 47 %), anemia (7/15, 47 %), and hemoptysis (4/15, 26 %). The most common underlying diseases in patients diagnosed with PSM were AIDS (9/15, 60 %), post-organ transplantation (3/15, 20 %), rheumatic autoimmune disease (2/15, 13 %), and hematological malignancy (1/15, 7 %). All patients, except those with AIDS, were treated with immunosuppressant drugs. White blood cell counts were increased in 10/15 (67 %) patients, while hemoglobin concentrations were decreased in 8/15 (53 %) patients. The ratios of CD4⁺/total T lymphocytes and CD4⁺/CD8⁺ T lymphocytes declined in all the 11 test cases. Nodular lesions or masses were the most common anomalies detected during computed tomography scans, but disseminated inflammation and interstitial changes were also seen. Clinical samples with positive culture results were obtained from sputum or secretions obtained by bronchoscopy, venous blood, percutaneous pulmonary puncture, bone marrow, or skin lesions. Between 1993 and 2003, only four cases of PSM, all connected with AIDS, were diagnosed, while 11 cases of PSM, with or without concurrent AIDS, were diagnosed between 2003 and 2012. Amphotericin B was used to control the disease in some cases. In conclusion, the occurrence of PSM, especially in patients without concurrent AIDS, has increased. The early culture of Penicillium marneffei from clinical samples is critical for correct diagnosis of PSM, and amphotericin B is recommended as the first choice for treatment.     

Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei

BackgroundTalaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.Conclusions/SignificanceMp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.     

非人类免疫缺陷病毒感染马尔尼菲青霉病9例临床特征分析及文献复习

为探讨和总结非人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者发生马尔尼菲青霉病的临床特点,回顾性研究复旦大学附属华山医院感染科2007年1月-2017年8月收治的9例及同期发表文献中的马尔尼菲青霉病病例,分析其临床表现、实验室检查、治疗及转归。9例马尔尼菲青霉病患者的HIV检测均为阴性,5例CD4^＋ T细胞计数正常。非HIV感染马尔尼菲青霉病的起病较缓,临床表现与经典马尔尼菲青霉病类似,真菌血症较少见,病理特点以肉芽肿改变及化脓性炎症为主,诊断方法仍以培养为主(8/9),1例通过病理及二代测序技术诊断。目前,非HIV感染马尔尼菲青霉病发病率有升高趋势,部分发生于免疫正常人群,需引起临床医师的重视。     

Detection of Talaromyces marneffei from Fresh Tissue of an Inhalational Murine Pulmonary Model Using Nested PCR

Penicilliosis marneffei, often consecutive to the aspiration of Talaromyces marneffei (Penicillium marneffei), continues to be one of the significant causes of morbidity and mortality in immunocompromised patients in endemic regions such as Southeast Asia. Improving the accuracy of diagnosing this disease would aid in reducing the mortality of associated infections. In this study, we developed a stable and reproducible murine pulmonary model that mimics human penicilliosis marneffei using a nebulizer to deliver Talaromyces marneffei (SUMS0152) conidia to the lungs of BALB/c nude mice housed in exposure chamber. Using this model, we further revealed that nested PCR was sensitive and specific for detecting Talaromyces marneffei in bronchoalveolar lavage fluid and fresh tissues. This inhalation model may provide a more representative analysis tool for studying the development of penicilliosis marneffei, in addition to revealing that nested PCR has a predictive value in reflecting pulmonary infection.     

In Vitro Susceptibility of Berberine Combined with Antifungal Agents Against the Yeast Form of Talaromyces marneffei

Mycopathologia - Talaromyces (Penicillium) marneffei can cause fatal disseminated infection in immunocompromised hosts. However, therapeutic strategies for the mycosis are limited. Reports of the...     

Infection by Intestinal Parasites,Stunting and Anemia in School-Aged Children from Southern Angola

Introduction

Intestinal parasites are responsible for morbidity in children worldwide, especially in low income countries. In the present study we determine the prevalence of intestinal parasites and explore its association with anemia and stunting in school-aged children.

Methods

A cross-sectional study was conducted from September to October 2010 enrolling 328 children attending the primary school in Lubango, the second largest city after the capital Luanda. Stool samples were collected for parasite detection through microscopy and molecular identification of Entamoeba histolytica and Entamoeba dispar. Stunting was assessed using the z-scores of height for age and hemoglobin concentration was determined using a portable hemoglobin analyzing system.

Results

The global prevalence of pathogenic intestinal parasites was 44.2%, the most common being Ascaris lumbricoides (22.0%), Giardia lamblia (20.1%) and Hymenolepis nana (8.8%). Molecular detection revealed that 13.1% of the children carried E. dispar and 0.3% were infected with E. histolytica. The prevalence of stunting (mild to severe) was 41.5%. Stunting was more frequent in older children (p = 0.006, OR = 1.886), while anemia was more frequent in younger children (p = 0.005, OR = 2.210). The prevalence of anemia was 21.6%, and we found a significant association with infection by H. nana (p = 0.031, OR = 2.449).

Conclusions

This is one of the few published studies reporting intestinal parasites infection, nutritional status and anemia in children from Angola. Furthermore, the present work highlights the importance of regular intestinal parasites screening in children.     

49例儿童暴发性心肌炎的临床特点与预后

目的:探讨儿童暴发性心肌炎的临床特点及与预后的关系。方法:回顾性分析患者病史、ECG、UCG、CMR、血清学检查资料及随访结果,得出影响预后的相关危险因素。结果:共收治49例暴发性心肌炎患者,平均年龄8.89±3.63岁。死亡9例(18.37%),平均存活时间4天,无晚期死亡。以心外表现为首发症状者占83.67%。初诊时血清CK-MB及c Tn I异常检出率分别为51.11%和81.39%,两者同时增高占47.50%。49例患者在疾病初期均存在明显的心电图异常,其中室性心律失常的发生率在恢复组与死亡组间存在明显差异(P=0.020)。恢复组与死亡组LVEF/LVFS降低的发生率分别为62.5%和100%(P=0.157),恢复组LVEF恢复正常平均时间10.22天。恢复组中10例患者在急性期行CMR检查,其中9例符合路易斯湖。所有患者均使用大剂量激素及丙种球蛋白治疗。8例患者安装临时心脏起搏器,4例接受ECOM治疗。恢复组平均随访19.28月,100%临床痊愈。多因素生存分析,最终与死亡有关的危险因素为年龄≤6岁(RR40.215,95%CI(1.285-1258.369))。结论:暴发性心肌炎起病急骤,以心外症状为首发者多见,经及时诊断、治疗的患者有望完全康复。所有患者均存在不同程度心电图异常。多因素生存分析发现年龄≤6岁为死亡的危险因素。