HIV阴性儿童播散性马尔尼菲青霉病致乳糜腹水1例报告

<正>马尔尼菲青霉病(penicilliosis marneffei,PSM)是由马尔尼菲青霉菌(penicillium marneffei,,PM)引起的一种少见的机会性真菌感染。马尔尼菲青霉菌是条件致病菌,主要感染免疫功能缺陷或免疫功能抑制者,尤其是艾滋病患者。关于马尔尼菲青霉菌感染的HIV阴性患者病例报道不多,儿童更为少见。现报告1例HIV阴性儿童播散性马尔尼菲青霉病致乳糜腹水病例,并结合相关文献进行复习,以提     

HIV阴性儿童马尔尼菲青霉病并发噬血细胞综合征1例及文献复习

目的探讨HIV阴性儿童播散性马尔尼菲青霉菌病(DPSM)并发噬血细胞综合征(HPS)的临床特征。方法回顾性分析1例HIV阴性儿童DPSM并发HPS的病例资料,并复习相关文献,总结其临床特征及诊治经验。结果患儿男,2岁7个月,临床主要表现为发热、咳嗽、面色苍白、肝脾肿大,辅助检查提示全血细胞减少,低纤维蛋白原血症,转氨酶升高,铁蛋白升高,EBV-DNA载量升高,HIV抗体阴性,血液及骨髓培养检出马尔尼菲青霉菌,骨髓涂片可见噬血现象及吞噬孢子,肺部CT提示多发结节、空洞,符合噬血细胞综合征及播散性马尔尼菲青霉病诊断标准;治疗上予HLH-2004方案,同时给予伊曲康唑联合两性霉素B脂质体抗真菌及支持等综合处理,病情一度好转,但反复,最终因呼吸衰竭死亡。结论 HIV阴性儿童DPSM并发HPS,临床上少见且表现缺乏特异性,病情进展快,预后差;早期诊断,早期治疗,可能改善预后。     

儿童马尔尼菲青霉菌感染2例临床和病理分析

目的　探讨儿童马尔尼菲青霉菌感染的临床特点和病理特征。方法　通过淋巴结活检和尸体解剖的肺、肝、脾、淋巴结的病理片观察真菌的形态 ;用酶免疫法和免疫印迹法检测病例 1患儿血清人类免疫缺陷病毒 (HIV)抗体 ;用流式细胞仪检测病例 1患儿的CD3、CD4、CD8和CD1 5 5 6。结果　例 1为艾滋病合并马尔尼菲青霉菌感染 ,例 2为播散型马尔尼菲青霉菌感染。例 1的CD4显著降低 ,HIV ELISA、免疫印迹法检测阳性 ,淋巴结活检可见马尔尼菲青霉菌的腊肠状细胞和桑葚小体。对例 2进行尸体解剖 ,肝、脾、淋巴结和双肺中均发现青霉菌的典型的腊肠状细胞和桑葚小体。结论　儿童马尔尼菲青霉菌感染是机会性感染 ,主要继发于先天性免疫缺陷和艾滋病 ,早期诊断、早期治疗对预后的影响很大。     

儿童马尔尼菲青霉菌感染的诊治进展

马尔尼菲青霉菌(PM)是青霉菌中唯一的温度双相型真菌,可引起全身播散性马尔尼菲青霉菌病(PSM)。儿童PM感染多见于有免疫缺陷的宿主,由于缺乏特异性临床表现,易误诊为肺组织胞浆菌病、肺结核或侵袭肺曲霉病等。播散性的PSM进展快,并发症多,如未能及时给予有效治疗,死亡率高,故早期诊断和治疗十分重要。诊断主要包括免疫功能检...     

儿童非人类免疫缺陷病毒感染相关播散性马尔尼菲青霉菌病15例临床回顾分析

目的　总结非人类免疫缺陷病毒（HIV）感染相关儿童播散性马尔尼菲青霉菌病（penicillium marneffei,PSM）特点,提高对其的认识。 方法　回顾性分析广州医科大学附属第一医院儿科2005年1月至2016年6月诊断的15例非HIV感染相关播散性PSM患儿的临床资料、治疗方案及转归。 结果　15例患儿中,男∶女＝9∶6,中位年龄23个月（3个月至4岁10个月）。入院时均有发热、肝大,多伴有咳嗽气喘、脾大、淋巴结肿大。实验室检查红细胞沉降率升高93.3%（14/15）,真菌G试验阳性80.0%（8/10）,真菌GM试验阳性87.5%（7/8）。胸部影像学检查提示15例肺部均有累及,表现形态多样。骨髓培养和淋巴结组织活检马尔尼菲菌阳性率最高（＞90%）。预后与病程长短及抗真菌治疗疗程相关,死亡的7例患儿病程明显长于治愈的8例（P＜0.05）,抗真菌治疗时间均＜2周,主要死亡原因是感染性休克及多脏器衰竭。治愈患儿采取两性霉素B或伏立康唑静滴2～4周后改为伊曲康唑口服维持,随访半年以上无复发。结论　儿童非HIV感染相关播散性PSM好发于婴幼儿,临床及实验室诊断缺乏特异性。同时进行多部位体液培养或组织活检（尤其是骨髓培养和淋巴结活检）有助于明确诊断。病程偏长、未进行及时抗真菌治疗的患儿容易合并感染性休克及多脏器衰竭,是导致死亡的主要原因。     

非艾滋病儿童马尔尼菲青霉菌病3例报告及文献复习

目的总结非艾滋病儿童播散性马尔尼菲青霉菌病(PSM)的临床特点及治疗转归。方法回顾分析3例PSM患儿的临床资料。结果 3例患儿中女1例,男2例,发病年龄分别为5月龄、1岁5月龄、3岁2月龄,均以反复发热伴咳嗽、气促,病情进行性加重,抗感染治疗无效为主要临床特征;肺部CT均显示多发异常密度影;1例患儿处于急性淋巴细胞白血病诱导化疗期,2例为先天性胆道闭锁。2例患儿经血培养及痰培养、1例经血清及肺泡灌洗液病原微生物二代测序确诊。3例患儿经两性霉素B为主的治疗后均好转。结论 PSM可发生在非艾滋病儿童,肺部是主要靶器官;在PSM流行地区,免疫低下儿童应考虑PSM可能,尽早行病原学检查。     

儿童获得性免疫缺陷综合征临床特点

目的 探讨儿童获得性免疫缺陷综合征(AIDS)的病因、临床特征、诊治经过及预后,以提高对该病的认识.方法 对2001年以来在广西医科大学第一附属医院儿科住院的12例儿童AIDS或疑似AIDS的临床及实验室检查资料进行回顾性分析,以总结其临床特点.结果 12例患儿中男9例,女3例;年龄45 d-9岁;11例患儿父母血清均为人类免疫缺陷病毒(HIV)抗体阳性或疑似因AIDS死亡者;临床表现为生长发育迟缓并不同程度营养不良12例(100%),长期不规则发热、间断性咳嗽及肝脾大各10例(83.3%),迁延性腹泻及淋巴结大各8例(66.7%).全身性皮炎6例(50%),大脑发育不全4例(33.6%),口腔念珠菌感染3例(26.7%),中耳炎2例(16.7%);实验室检查:12例2次血清HIV抗体检测均呈阳性,CD4 T淋巴细胞的百分比均下降,CD4 /CD8 细胞比值均降低,肝功能检查转氨酶均升高,3例血清巨细胞病毒抗体阳性,4例血培养及1例骨髓培养出马尔尼菲青真菌,大便涂片及培养4例找到真菌.死亡1例,余病例对症治疗效果差.结论 儿童AIDS潜伏期相对较短,临床表现多样化,细胞免疫功能低下,对症治疗效果差.提高对该病的认识,可早期诊断、早治疗,延长患儿生命.     

X连锁高IgM血症一例并文献分析

目的探讨X连锁高IgM血症的临床表现、诊断及治疗,提高临床对本病的认识。方法回顾性分析1例基因明确诊断的X连锁高IgM血症患儿的临床资料及诊治经过。结果1例3岁9个月的男孩,因"反复口腔溃疡3个月,间断发热伴腹痛2月余"入我院消化科,完善口腔黏膜活检,胃镜、肠镜等检查,病初诊断肠白塞病、中性粒细胞缺乏,给予甲泼尼龙、英夫利昔单抗治疗后,患儿症状无好转,随即出现消化道大出血、气腹、血小板减少、马尔尼菲青霉菌真菌血症转入PICU。病程中患儿相继发生膈下脓肿、脓胸,最终经外科干预,先后两性霉素B、伏立康唑、泰能、舒普深、万古霉素、替加环素、多黏菌素等抗感染,多次丙种球蛋白输注等治疗,患儿病情好转出院。全外显子基因检测到CD40LG基因有1个半合子突变(c.707 C>A,p.S263X),来源母亲,诊断X连锁高IgM血症明确。结论X连锁高IgM血症临床罕见,发病率低,临床表现为反复感染、中性粒细胞减少,伴自身免疫性疾病,基因诊断是金标准,预后差。静脉注射免疫球蛋白可改善体液免疫缺陷造成的临床症状,减少发生危及生命的感染。     

急性白血病合并侵袭性曲霉病的临床治疗

目的探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果3例急性淋巴细胞白血病(ALL)诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2～5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35d,无霉菌复发。结论CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。     

儿童侵袭性肺真菌病9例临床分析

目的探讨儿童侵袭性肺真菌病的临床特点。方法回顾性分析2016年1月至2018年9月河北省儿童医院呼吸科确诊及临床诊断为侵袭性肺真菌病的9例患儿临床资料。结果 9例患儿确诊3例,临床诊断6例;5例念珠菌感染,2例曲霉菌感染,1例毛霉菌感染,1例新型隐球菌感染;7例存在基础疾病,8例有发热,7例咳嗽,1例咯血;5例痰真菌培养阳性,3例血真菌培养阳性,1例肺泡灌洗液镜检阳性;6例肺CT可见多发团块状或球形高密度影,1例可见晕轮征,1例呈弥漫性粟粒性结节影,1例片状磨玻璃影;分别给予氟康唑、伏立康唑、两性霉素B脂质体抗真菌治疗,6例临床痊愈,3例死亡。结论长期发热可能为侵袭性肺真菌病患儿惟一症状,胸痛、咯血对肺毛霉菌病诊断有重要参考价值;侵袭性肺真菌病CT特点不同于细菌性及病毒性肺炎,多表现为多发团块、球形结节,肺隐球菌病CT可出现类似粟粒性肺结核影。     

Disseminated fusarium infection in two neutropenic children]

Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients.Case report 1. – A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment.Case report 2. – A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence.Conclusion. – Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.     

An abdominal mass owing to Penicillium marneffei in an HIV-infected 7-year-old boy: case report

A 7-year-old boy, referred with lymphoma, presented with prolonged fever and intra-abdominal lymphadenopathy demonstrated on computed tomography (CT) of the abdomen. Blood culture isolated Penicillium marneffei. The patient was subsequently proven serologically to be positive for human immunodeficiency virus (HIV). Treatment with amphotericin B followed by itraconazole was successful. A high level of clinical suspicion and awareness is necessary for early diagnosis of penicilliosis, especially in an era of an increasing prevalence of HIV in this region.     

Chronic granulomatous disease presenting with disseminated intracranial aspergillosis

We describe an 8-year-old boy who presented with multiple unresectable aspergillus brain abscesses as the initial presentation of X-linked chronic granulomatous disease (CGD). He failed initial therapy with amphotericin B, but was subsequently salvaged with voriconazole. CGD should be considered in the differential diagnosis for all children presenting with invasive fungal infections, particularly, those involving the central nervous system (CNS). Whereas, optimal pharmacologic therapy is still unknown for CNS aspergillosis, voriconazole may have an advantage due to its ability to cross the blood brain barrier and excellent oral absorption and bioavailability.     

儿童非人类免疫缺陷病毒相关马尔尼菲篮状菌感染并噬血细胞综合征11例临床分析

目的　探讨儿童非人类免疫缺陷病毒相关马尔尼菲篮状菌感染并噬血细胞综合征的临床特征及诊治要点。方法　回顾性分析2010年1月至2020年12月广州市妇女儿童医疗中心11例非人类免疫缺陷病毒相关马尔尼菲篮状菌感染并噬血细胞综合征患儿的人口学特征、临床表现、体征、实验室检查等资料,初步探讨影响其预后的因素。结果　11例患儿中,男7例,女4例,年龄3月龄至3岁（中位年龄1岁10月龄）。最常见的临床表现及体征依次为发热（11/11,100.00%）、肝脾肿大（11/11,100.00%）和咳嗽（9/11,81.82%）。其他严重并发症包括脓毒症休克（10/11,90.91%）、急性呼吸窘迫综合征（8/11,72.73%）、多器官功能障碍综合征（8/11,72.73%）等。所有患儿均有血细胞下降,C反应蛋白升高,天冬氨酸转移酶升高。常见的外周血免疫功能异常表现为NK细胞计数下降（7/10,70.00%）,血清IgG下降（4/11,36.36%）。6例患儿行基因检测,2例患儿确诊为原发性免疫缺陷病,1例发现COPA基因突变,1例发现多个位点基因突变,2例未发现疾病相关基因突变。所有患儿通过血、骨髓等培养和（或）组织病理学阳性确诊为马尔尼菲篮状菌感染。10例患儿给予抗真菌治疗,以两性霉素B联合伊曲康唑序贯治疗最为常用。8例患儿给予高级生命支持,5例患儿给予HLH2004方案化疗,最终8例患儿死亡（8/11,72.73%）。结论　马尔尼菲篮状菌感染并噬血细胞综合征在非人类免疫缺陷病毒感染儿童临床表现无特异性,易误诊漏诊,且病情严重,病死率高。早期识别并行血、骨髓培养及组织病理活检积极寻找病原、给予抗病原和化疗治疗可能改善预后。     

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??Objective??To analyze the characteristics of disseminated penicillium marneffei??PSM?? in children and to deepen the understanding of PSM in the context of non-HIV. Methods??The clinical data??treatment program and prognosis of 15 children were retrospectively analyzed??who were diagnosed with non-HIV disseminated PSM in the First Affiliated Hospital of Guangzhou Medical University from Jan. 2005 to June 2016. Results??The 15 children??male??female??9??6?? had a median age of 23 months with a range of 3 months to 4 years and 10 months of age. All of them had clinical manifestations of fever and hepatomegaly on admission??which were often associated with cough??tachypnea??splenomegaly and lymphadenectasis. ESR was elevated by 93.3%??14/15?? in laboratory tests??80%??8/10?? was positive in fungal G tests??and 87.5%??7/8?? in fungal GM tests. Chest imaging studies revealed that the lungs were all involved and showed various forms. Bone marrow culture and lymph node biopsy showed the highest positive rate of PM??more than 90%. The prognosis was related to the duration of the disease and anti-fungal treatment. The duration of the death group??n??7?? was significantly longer than that of the cured group??n??8????P??0.05??. The duration of anti-fungal treatment for death groups was less than 2 weeks with the main death reason of septic shock and multiple organ failure. The cured group was given amphotericin B or voriconazole intravenously 2-4 weeks and later it was changed to itraconazole for oral maintenance??there was no recurrence after six months of follow-up. Conclusion??Non-HIV disseminated PSM in children occurs more often in infants under 3 years of age??and clinical and laboratory diagnosis lack specificity. Multi-site culture or biopsy??especially bone marrow culture and lymph node biopsy?? can help confirm the diagnosis. Patients with long course of disease without timely anti-fungal treatment are associated with infectious shock and multiple organ failure??which are the main cause of death.     

儿童播散性隐球菌病8例临床特征和预后

目的 探讨儿童播散性隐球菌病的临床特征和预后。方法 回顾性分析2009年5月至2013年11月复旦大学附属儿科医院感染科收治的播散性隐球菌病患儿的临床资料,总结临床特征和预后。结果 8例播散性隐球菌病连续病例进入分析,男5例,女3例,平均年龄6.1岁。血清HIV抗体均阴性,流式细胞仪检测CD4细胞计数正常。2例起病前曾口服糖皮质激素,余6例否认免疫抑制剂服用史及基础疾病史。8例患儿家长均否认鸽子或其他禽类接触史。8例患儿起病均表现为持续发热,7例有明显的肝脾肿大,4例有黄疸,2例有咳嗽等呼吸道症状,2例服用糖皮质激素患儿有皮肤损害,8例均无头痛、呕吐或意识改变等神经系统症状。8例血清隐球菌抗原滴度均>1:640,6例血培养结果示新型隐球菌阳性,4例CSF隐球菌抗原升高,5例外周血嗜酸性粒细胞计数升高。8例血清IgE均升高,平均3 896.5 KuA·L-1。3例影像学检查提示累及胆道,肝内胆管扩张,胸部CT示7例累及肺部。8例起病至确诊2～7周,均接受全身性抗真菌治疗（两性霉素B联合5-氟胞嘧啶或氟康唑）,其中1例治疗后出现隐球菌相关性免疫重建炎症综合征,8例治疗反应良好。8例诱导治疗结束后外周血嗜酸性粒细胞计数和血清IgE水平均恢复正常,停药后随访3~6个月,均无复发。结论 播散性隐球菌病可发生于无HIV感染的儿童,可累及多系统脏器,以单核-巨噬细胞系统和肺部受累多见。外周血嗜酸性粒细胞计数升高和血清IgE水平升高是本病实验室检查的显著特点。     

Salmonella-meningitis in the newborn (author's transl)]

Six children, out of twelve in a neonatal unit suffered from group D salmonellosis. Two patients presented in addition to intestinal manifestations massive extraintestinal symptoms, both with septicemia and meningitis. One patient died on the fourth day from massive disseminated intravascular coagulation and pyocephalus. The other patient had a complete recovery after an antibiotic therapy with chloramphenicol and ampicillin. As the source of infection the mother of case 1 was identified. In her stools salmonella group D were cultured. Cultures of the ward-personals, stool and the food were negative. It should be mentioned that only children fed with artificial food suffered from salmonellosis; whereas children on breastmilk had an unremarkable clinical course and consistantly negative stoolcultures.