广东省艾滋病患者合并肺部丝状真菌感染的临床特点和病原谱分析

Clinical characteristics and pathogenic spectrum of pulmonary filamentous fungal infection in acquired immunodeficiency syndrome patients in Guangdong Province

目的分析广东省艾滋病患者合并肺部丝状真菌感染的临床特点和病原谱,为提高诊治水平提供理论依据。方法纳入2016年1月至2018年12月广州医科大学附属市八医院收治的143例艾滋病合并肺部丝状真菌感染的住院患者,对其支气管肺泡灌洗液培养的丝状真菌进行形态学和分子生物学鉴定,并分析其临床特点。统计学方法采用非参数Kruskal-Wallis H检验和χ^(2)检验。结果143例患者中,发热116例(81.1%),咳嗽104例(72.7%),咳痰83例(58.0%),气促59例(41.3%);CD4+T淋巴细胞计数为22.0(9.3,60.8)/μL,其中118例(82.5%)CD4+T淋巴细胞计数<100.0/μL;白细胞计数减少52例(36.4%),增多18例(12.6%);贫血109例(76.2%),血小板计数减少29例(20.3%);半乳甘露聚糖试验阳性64例(44.8%);胸部计算机断层成像检查表现为双肺弥漫性感染114例(79.7%),粟粒样改变12例(8.4%),胸腔积液44例(30.8%),胸腔和(或)纵隔淋巴结肿大45例(31.5%);抗真菌治疗后,治愈或好转124例(86.7%),病情恶化自动出院或死亡19例(13.3%)。143株丝状真菌中,曲霉菌属56株(39.2%,其中24株为烟曲霉),马尔尼菲篮状菌(Talaromyces marneffei,TM)37株(25.9%),青霉菌属22株(15.4%),非曲霉非青霉非篮状菌属28株(19.6%)。曲霉菌属、TM、青霉菌属和非曲霉非青霉非篮状菌属感染患者的CD4+T淋巴细胞计数中位数分别为24.5、15.0、53.5和22.0/μL,差异有统计学意义(H=11.282,P=0.010)。艾滋病患者合并不同菌属肺部丝状真菌感染时CD4+T淋巴细胞计数≤50.0/μL的占比从高到低依次为TM组[89.2%(33/37)],曲霉菌属组[67.9%(38/56)]和非曲霉非青霉非篮状菌属组[67.9%(19/28)],青霉菌属组[54.5%(12/22)],差异有统计学意义(χ^(2)=9.296,P=0.026)。结论广东省艾滋病患者肺部丝状真菌感染的临床表现无特异性,其病原谱多样化,以TM和烟曲霉为主,且病原谱可能与CD4+T淋巴细胞计数相关。

Objective To investigate the clinical characteristics and pathogen spectrum of acquired immunodeficiency syndrome(AIDS)patients complicated with pulmonary filamentous fungal infection in Guangdong Province,so as to provide evidences for improving the diagnosis and treatment.Methods A total of 143 AIDS patients with pulmonary filamentous fungal infection hospitalized in Guangzhou Eighth People′s Hospital,Guangzhou Medical University from January 2016 to December 2018 were included.The filamentous fungi cultured in bronchoalveolar lavage fluid of these patients were identified with morphological and molecular biological methods.And their clinical characteristics were analyzed.Nonparametric Kruskal-Wallis H test and chi-square test were used for statistical analysis.Results Among the 143 patients,116(81.1%)had fever,104(72.7%)had cough,83(58.0%)had expectoration,and 59(41.3%)had anhelation.The CD4+T lymphocyte count was 22.0(9.3,60.8)cells/μL and 118(82.5%)cases were below 100.0 cells/μL.The white blood cell counts decreased in 52(36.4%)cases and increased in 18(12.6%)cases,anemia was found in 109(76.2%)cases,platelet count decreased in 29(20.3%)cases.Sixty-four(44.8%)cases were positive for galactomannan test.Chest computed tomography showed diffuse infection of both lungs in 114(79.7%)cases,miliary changes in 12(8.4%)cases,pleural effusion in 44(30.8%)cases,and enlargement of pleural and(or)mediastinal lymph nodes in 45(31.5%)cases.After receiving antifungal therapy,124(86.7%)cases were cured or improved,and 19(13.3%)cases were discharged automatically or died of disease deterioration.Among the 143 strains of filamentous fungi,there were 56 strains of Aspergillus species pluralis(39.2%,including 24 strains of Aspergillus fumigatus),37 strains of Talaromyces marneffei(T.marneffei)(25.9%),22 strains of Penicilium species pluralis(15.4%),and 28 strains of other genera of filamentous fungi(19.6%).The median CD4+T lymphocyte counts in patients infected with Aspergillus species pluralis,T.marneffei,Penicilium species pluralis and other genera were 24.5,15.0,53.5 and 22.0 cells/μL,respectively,and the difference was statistically significant(H=11.282,P=0.010).The proportions of AIDS patients with different pulmonary filamentous fungal infection of CD4+T lymphocyte count≤50.0 cells/μL in descending order were T.marneffei group(89.2%(33/37)),Aspergillus species pluralis group and other genera group(67.9%(38/56),67.9%(19/28)),and Penicillium species pluralis group(54.5%(12/22)),and the difference was statistically significant(χ^(2)=9.296,P=0.026).Conclusions The clinical manifestations of pulmonary filamentous fungal infection in AIDS patients in Guangdong Province are not specific.The pathogenic spectrum contains various genera,and T.marneffei and Aspergillus fumigatus are dominant,which could be correlated with CD4+T lymphocyte count.