Shao Ping HUANG,*^ Yu Jie ZHAO,* Shui Hua LU,# Ji Lin CHENG,* Yan Ling FENG$*Gastroenterology Section, #Tuberculosis Section, $Pathology Department, Shanghai Public Health Clinical Center Affiliated to Fudan University, ^Endoscopy Research Institute Fudan University, Shanghai, ChinaCorrespondence to: Shui Hua LU, Shanghai Public Health Clinical Center Affiliated to Fudan University, Jinshan District, Shanghai, China. Email: tubercle@shaphc.orgAbstractTuberculosis is the most common opportunistic infectious disease in HIV-infected subjects, and HIV infection is a high risk factor for tuberculosis, the convergence of HIV and tuberculosis is a disaster practically unequalled in medical history. This is a rare case report on the topic of pulmonary miliary tuberculosis and intestinal tuberculosis with AIDS. In this case, one month after the patient treated with HAART and anti-tuberculosis treatment, the number of CD4+ cell count increased and the symptoms improved, but the local intestinal lesion aggravated, which is commonly seen in IRIS. AIDS with intestinal tuberculosis locally aggravated is rare, and should be paid more attention.Key Words:intestinal tuberculosis;HIVPeople infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis accounts for a number of 25 million worldwide. Tuberculosis is the most common opportunistic infectious disease in HIV-infected subjects, and HIV infection is a high risk factor for tuberculosis, the convergence of HIV and tuberculosis is a disaster practically unequalled in medical history(1). This is a rare case report on the topic of pulmonary miliary tuberculosis and intestinal tuberculosis with AIDS. Cast reportA 38-year-old male was admitted on October 5, 2007 with a two-month history of intermittent abdominal pain, and had been treated with spasmolytic drugs without effect. A colonoscopy showed an annular bulging with about 1.0 × 1.6 cm ulcers, 40cm from the anus. The colonic lumen was narrowed and the histopathology indicated chronic inflammation with necrosis and granulation tissue. He had several sex partners, was found to have syphilis in May 2006, and had been treated for 15 days only. on September 12, 2007 he was known to have HIV infection and had been treated with antiviral drugs. On admission, vital signs were: T 37.6℃, P 86 / min, R 18 / min, BP 110/60mmHg (1 mmHg = 0.133kPa), being mentally clear, lymph nodes were not enlarged but with decreased breath sound over both lungs. His heart was normal and abdomen soft but with tenderness over left lower quadrant; liver and spleen were not palpate. Muscle strength, tendon reflexes were all normal. The Laboratory tests results Hb 110 g/L, PLT 77.30 × 109/L, RBC 3.70 × 1012/L, WBC 5.33 × 109/L. C-reactive protein 87.00 mg/L; IgA 1.97 g/L; IgG 30.30 g/L; serum albumin 32.3 g/L, ALT 60 U/L, AST 67 U/L; BUN 4.51 mmol/L, Cr 49.7 mmol/L; Cell-mediated immunity: CD4+ cell count 85 cell/μl; CD8+ cell count 591 cell/μl. B-ultrasound examination: hepatomegaly, splenomegaly and celiac lymphadenectasis, were present. Chest CT: bilateral pulmonary miliary tuberculosis. Abdominal CT: Lymphadenectasis was shown at porta hepatis. Colonoscopy displayed an ulcerative-proliferative mass at splenic flexure, adjacent to the mass involving the intestinal wall, was a 1.0×0.6 cm ulcer (Figure 1). Biopsy showed: chronic inflammation with atypical hyperplasia. Based on the clinical, laboratory and the histopathologic findings, a diagnosis of AIDS with pulmonary military tuberculosis and intestinal tuberculosis was made. HAART therapy and anti-tuberculosis treatment (isoniazid, rifampicin, Pyrazinamide and ethambutol) were given, one month afterwards, the patient’s general condition improved, fever subsided, part of pulmonary lesion absorbed, and CD4+ cell count increased up to 165 cell/μl, but abdominal pain became aggravated. A second colonoscopy showed the colonic lumen much narrowed and left hemicolon resection was performed. Typical tuberculous granuloma with caseous necrosis was shown in histopathology (shown in Figures 2, 3), and tissue culture showed the presence of tuberculosis. HAART therapy and anti-tuberculosis treatment had continued since then all symptoms improved after combination with anti-tuberculosis treatment. However, Since then the patient’s symptoms were gradually disappeared, and one month later, the patient was discharged without abdominal pain and other symptoms.DiscussionActive tuberculosis can be triggered by weakened immune function of the patient, it has become the second most common killer of patients with HIV/AIDS worldwide. The incidence of tuberculosis can be very high in Africa (356/100 000 population) and mortality (81/100 000), but being lower in America (incidence: 41/100 000, mortality: 5.9/100 000)(2). HIV is the highest single risk factor to boost tuberculosis disease in adults, and tuberculosis is able to occur early in the course of HIV infection. The clinical presentation of tuberculosis can be modified by immune suppression, which has a real influence on the prognosis of HIV infection (3). AIDS patients with secondary intestinal tuberculosis are rarely reported. Most of the intestinal tuberculous lesions are in ileocecum accounting for 80%, the remaining lie in ileum or colon which are mostly secondary to pulmonary tuberculosis, and will cause narrowing or obstruction in advanced stage, some of them can even result in adhesive ileus because of the complication of tuberculous peritonitis (4). The reason of intestinal tuberculosis being easy to be misdiagnosed in our patient was that both clinical and endoscopic features were atypical. The abdominal pain became aggravated but the patient’s general symptoms were improved after the combined treatment of HAART and anti-tuberculosis therapy. Intestinal tuberculosis mimics many other conditions such as Crohn’s disease, malignancy, and infectious diarrhea, and is often difficult to diagnose. Only when the biopsy found caseous necrosis or acid-fast bacilli at microscopy that precise diagnosis can be established. The increased prevalence of extra-pulmonary tuberculosis in HIV patients presents a particular diagnostic challenge, the major factor hampering our ability to diagnose tuberculosis in HIV patients is lack of a sensitive, specific and rapid diagnostic test. The World Health Organization (WHO) Directly Observed Therapy Short Course (DOTS) Program relies on the microscopic identification of Mycobacterium tuberculosis. However, due to alteration of the normal host immune response to Mycobacterium tuberculosis in HIV patients, cavitation and transfer of Mycobacterium tuberculosis into respiratory secretions are markedly reduced. Indeed, smear-negative tuberculosis has been linked to poor treatment outcome, the increased prevalence of extra-pulmonary forms of tuberculosis in HIV-infected patients is a further challenge to the management of tuberculosis in resource-poor settings, where access to histopathology and advanced imaging tests are limited or absent. The lack of a reliable, rapid test for smear-negative tuberculosis not only means that we often miss the correct diagnosis, but also that patients often started on anti-tuberculosis therapy erroneously on the basis of clinical presentation alone (5). WHO has updated the guidelines for management of smear-negative and extra-pulmonary tuberculosis, and has provided algorithms for the management of smear-negative pulmonary and extra-pulmonary tuberculosis in HIV-prevalent communities. They highlight the need for HIV testing of all tuberculosis suspects rather than only confirmed tuberculosis cases. Furthermore, the diagnostic algorithms used for management of extrapulmonary tuberculosis are much clearer, providing more detailed advice on which tests to employ and improve the definitions of common extrapulmonary forms of the disease to aid the clinicians (6). Patients co-infected with HIV and Mycobacterium tuberculosis have a greatly increased risk of developing active tuberculosis (5). In the course of anti-tuberculosis therapy, the abdominal pain of our patient became aggravated, the possible reason can be: ①emergence of complication; ②existence of drug-resistant tuberculosis (7); ③HAART treatment-related immune reconstitution inflammatory syndrome (IRIS). During the course of treatment, the CD4+ cell count increased from 85 cell/μl up to 165 cell/μl, this hints that IRIS may be the most possible cause. As we know, potent antiretroviral therapy can substantially reduce the likelihood of both opportunistic infections and progression of HIV infection to AIDS. Shortly after starting HAART, as many as 25% of the patients experience clinical worsening because of subclinical opportunistic pathogens or recurrence of previously disease. This phenomenon is commonly known as IRIS. One study has indicated that initiation of HAART therapy at 4-12 weeks of tuberculosis treatment in advanced AIDS may be safe and effective.(8). In this case, one month after the patient treated with HAART and anti-tuberculosis treatment, the number of CD4+ cell count increased and the symptoms improved, but the local intestinal lesion aggravated, which is commonly seen in IRIS. AIDS with intestinal tuberculosis locally aggravated is rare, and should be paid more attention.References 1. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.Arch Intern Med 2003;163:1009–21.2. Nissapatorn V. Lessons learned about opportunistic infections in southeast Asia. Southeast Asian J Trop Med Public Health. 2008,39:625-641.3. Dye, C. . Global epidemiology of tuberculosis. Lancet. 2006, 367,938–940.4. Ramesh J, Banait GS, Ormerod LP. Abdominal tuberculosis in a district general hospital: a retrospective review of 86 cases. QJM,2008,101:189 - 195.5. World Health Organisation, Global tuberculosis control: surveillance, planning, financing. WHO Report 2005. Geneva, 2006.6. World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents: recommendations for HIV-prevalent and resource-constrained settings. Geneva, Switzerland: World Health Organization.2006.7. French CE, Glynn JR, Kruijshaar ME, et al. The association between HIV and antituberculosis drug resistance. Eur Respir J, 2008,32:718-7258. Sungkanuparph S, Manosuthi W, Kiertiburanakul S, et al. Initiation of antiretroviral therapy in advanced AIDS with active tuberculosis: clinical experiences from Thailand. J Infect,2006;52:1-7Figure 1. First colonoscopy shows an ulcerative proliferative mass 40 cm from the anus.Figure 2. Tuberculous granuloma shown in the excised colon.Figure 3. Caseous necrosis in the excised specimen.
【摘要】 目的 探讨上海地区今年甲型H1N1流感确诊病例的临床特点。 方法分析2009年5月24日~2009年7月1日上海市(复旦大学附属)公共卫生临床中心收治的甲型H1N1流感68例确诊病例的流行病学及临床资料。结果 68例甲型H1N1流感确诊病例的临床特点:①不同性别和各年龄段均可感染和发病,但主要见于青少年,女性患者偏多。②首发症状多为发热,大多数为中低热,发热持续时间为1-4天;主要症状包括发热(98.5%)、咳嗽(83.8%)、咽痛(52.9%);主要体征为咽部充血(95.6%)、扁桃体肿大(54.4%);少数患者可出现病毒性肺炎。③血清C反应蛋白升高和前白蛋白下降比较常见。④在奥司他韦治疗的前提下,病人病毒转阴时间1~7天,中位时间4天。结论 此次甲型H1N1流感病毒具有很强的传染性,能在人与人之间传播,并能在不同国家扩散。该次流行期间的感染者大多表现出轻微的症状,病很快痊愈。【关键词】 新型甲型H1N1流感;临床特征Clinical Features of 68 Cases of Novel Influenza A (H1N1) in ShanghaiHUANG Shao-ping, ZHANG Zhan-qing,LU Hong-zhou,HU Yun-wen,ZHOU Zhi-tong,YUAN Zheng-hong※【Abstract】 Objective To analyze characteristics of novel influenza A (H1N1) in Shanghai. Methods Analysis of epidemiology and clinical datas of 68 confirmed cases with novel influenza A (H1N1) From May 24th to July 1st, 2009. Results clinical features of 68 cases of novel influenza A (H1N1): ① People among different genders and ages can be infected and fall ill,mainly young people.②the first symptoms are fever, mostly low-grade fever, which last for 1-4 days; main symptoms include fever(98.5%), cough(83.8%), pharyngodynia(52.9%),; the main signs of congestive heart for the pharynx(95.6%), swollen tonsils(54.4%); a small number of patients with viral pneumonia can occur. ③elevated serum C-reactive protein and decreased prealbumin is more common. ④oseltamivir in treatment under the premise of H1N1 negative patients from 1 to 7 days, with a median time of 4 days. Conclusion novel influenza A (H1N1) is highly contagious and can spread from person to person, and proliferation in different countries. The prevalence of the infection period showed a slight majority of the symptoms, patients recovered quickly. 【Key words】Novel Influenza A (H1N1); Clinical Feature2009年4月初,世界卫生组织宣布出现了新型甲型H1N1流感疫情。在全球化时代,新型甲型 H1N1流感飞速传播,2009年5月24日上海确诊了首例新型甲型H1N1流感病例,本文对上海68例新型甲型H1N1流感患者进行回顾性分析。1 对象与方法1.1 研究对象 2009年5月24日至2009年7月1日上海市公共卫生临床中心收治的68例新型甲型H1N1流感确诊病例,所有患者的诊断符合卫生部颁布的《甲型H1N1流感诊疗方案(2009年试行版第一版)》的标准。其中男性29例,女性39例;年龄4~75岁。1.2 研究内容 流行病学资料包括性别、年龄、种族、感染地区、接触史、发病日期、抵沪日期,临床资料包括症状、体征、并发症、病情转归,实验室资料包括外周血细胞检查、肝功能、肾功能、细胞免疫、体液免疫、影像学检查等。2 结 果2.1 人口特征 68例患者中,男︰女比例=1︰1.34,平均年龄26.1岁。黄种人61例,白种人患病7例。见表1。表1 68例新型甲型H1N1流感患者的人口特征年龄(岁) 病例数(构成比)黄种人︰白种人比例≤10 2(2.9%)2︰011~20 28(41.2%)27︰121~30 23(33.8%)21︰231~40 4(5.9%)3︰1>40 11(16.2%)8︰3合计68(100%)61︰72.2 感染地区及接触史 68例患者中,有1例为国内二代病例,为确诊新型甲型H1N1流感患者的密切接触者;67例为归国人员、属于输入性病例,64例来自澳大利亚、美国、加拿大等疫区城市。感染地区见表2。有明确接触史者12例,接触到发病时间分别为2~6天,中位时间为3天,潜伏期均在6天或以内。有同架飞机多人发病,或有接受医学观察人员中多人或家庭成员(夫妻或母女)相继发病的情况。表2 67例新型甲型H1N1流感患者的感染地区国家城市病例数(构成比)澳大利亚37(54.4%)墨尔本27(73%)悉尼10(27%)美国19(27.9%)纽约8(42.1%)芝加哥4(21.1%)旧金山2(10.5%)洛杉矶2(10.5%)波士顿1(5.3%)底特律1(5.3%)盐湖城1(5.3%)加拿大8(11.8%)多伦多5(62.5%)温哥华2(25%)埃德蒙特1(12.5%)新加坡2(3.0%)菲律宾马尼拉1(1.5%)中国上海1(1.5%)合计68(100%)68(100%)2.3 临床表现2.3.1 起病特点 发病到住院时间为1~4天,中位时间为2天。2.3.2 症状与体征 68例患者中,首发症状为发热者55例(80.9%),咽痛者8例(11.8%),咳嗽者3例(4.4%)。最高体温(腋温)波动于37.2~39.7℃之间,最高体温37~38℃ 33例(48.5%)、38~39℃ 26例(38.2%)、大于39℃ 7例(10.3%)。症状持续时间为1~7天。体温升高持续时间为1~4天。主要症状和体征的构成见表3。表3 68例新型甲型H1N1流感患者的临床症状和体征主要症状与体征病例数(构成比)发热67(98.5%)咳嗽57(83.8%)咽痛36(52.9%)咯痰19(27.9%)流涕16(23.5%)鼻塞13(19.1%)肌肉酸痛13(19.1%)腹泻1(1.5%)咽部充血65(95.6%) 扁桃体肿大37(54.4%)浅表淋巴结肿大25(36.8%)2.4 并发症 68例患者中,发生鼻炎16例(23.5%)、鼻出血2例(3.6%),腹泻1例(1.8%)、病毒性肺炎13例(19.1%)。 2.5 实验室检查2.5.1 外周血细胞检查 68例患者入院当天均进行了外周血细胞检查,其中白细胞和中性粒细胞绝对计数超过正常参考值上限者分别为4例(5.9%)和2例(2.9%);低于正常参考值下限者分别为13例(19.1%)和10例(14.7%)。2.5.2 体液和细胞免疫 68例患者中,41例进行了体液和细胞免疫检查,其中C反应蛋白超过正常参考值上限者28例(68.3%);CD8+低于正常参考值下限者7例(17.1%);CD4+低于正常参考值下限者18例(43.9%)。2.5.3 肝功能与肾功能 68例患者均进行了肝肾功能检查,其中丙氨酸转氨酶超过正常参考值上限者3例(4.4%);前白蛋白低于正常参考值下限者31例(45.6%)。尿素和肌酐均在正常参考值范围。2.5.4 胸部χ线检查 68例患者均进行了胸部CT检查,其中13例(19.1%)患者胸部CT发现有异常改变,表现为肺小叶渗出性炎症、一侧或两侧胸膜少许炎症分别为8例(11.8%)、5例(7.4%)。纵隔淋巴结肿大5例(7.4%),腋下淋巴结肿大4例(5.9%)。2.5.5 病毒转阴时间 68例患者中,41例每日送检咽拭子标本检测甲型H1N1流感病毒核酸,病毒核酸转阴时间在1~7天,中位时间为4天。患者发病天数与甲型H1N1流感病毒转阴例数分布见图1。图1 患者发病天数与甲型H1N1流感病毒转阴例数分布2.6 治疗及转归 所有患者均予以奥司他韦75mg,每日二次,口服治疗,有扁桃体肿大或中性粒细胞升高者同时加用阿奇霉素治疗。68例患者症状消失时间1~7天。以症状消失3天及病毒转阴2天为出院标准,68例患者住院1~9天。3 讨 论今年新型甲型 H1N1流感正在全球蔓延。根据美国CDC的初步调查,新型甲型 H1N1流感主要通过飞沫和接触传播,主要表现为咳嗽、发热,头痛,咽痛,流涕,肌肉酸痛等症状;少数患者可出现病毒性肺炎,病情较重者可因呼吸衰竭和多脏器功能损伤导致死亡[1,2]。对642例患者的研究指出,新型甲型H1N1流感主要见于青少年,年龄低于18岁的患者占60%;主要症状出现的频率:发热、咳嗽、咽痛、腹泻分别占94%、92%、66%、25%[3]。根据本文资料,新型甲型 H1N1流感有以下特点:①不同性别和各年龄段均可感染和发病,但主要见于青少年,女性患者偏多。②患者来自不同国家和地区,包括热带国家,说明甲型H1N1流感病毒有较强的环境抗力。③接触传播为主,飞沫传播为辅,提示新发甲型H1N1流感病毒有很强的感染力和传染性,人群对该病毒普遍易感[4]。④接触到发病时间为2~6天,中位时间为3天,潜伏期均在6天或以内。⑤发病到住院时间为1~4天,中位时间为2天。⑥首发症状多为发热,大多数为中低热,发热持续时间为1-4天;主要症状包括发热、咳嗽、咽痛,分别占98.5%、83.8%、52.9%;主要体征为咽部充血、扁桃体肿大,分别占95.6%、54.4%;少数患者可出现病毒性肺炎。⑦中性粒细胞绝对计数低于正常参考值范围的比例大于高于正常参考值范围的比例,提示有一定程度的中性粒细胞减少。⑧血清C反应蛋白升高和前白蛋白下降比较常见。⑨在奥司他韦治疗的前提下,病人病毒转阴时间为1~7天,中位时间为4天;推测自然转阴的中位时间为5天;⑩预后良好,该组病例全部好转出院。 4 参考文献[1] Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team.Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 May 7;doi:10.1056/NEJMoa0903810[2] US Centers for Disease Control and PreventionC. Swine-origin influenza A (H1N1) virus infections in a school—New York City,April 2009. MMWR 2009,58 (Dispatch):1–3[3] Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360:2605-2615 [4] Sherif Beniameen Mossad, MD. The resurgence of swine-origin influenza A (H1N1). Cleveland Clinic Journal of Medicine. 2009,76:337-343
黄绍萍王介非 程计林 赵玉洁 史佩炯 马学东 【摘要】目的 探讨聚乙二醇干扰素α-2a治疗慢性乙肝发生HBsAg转阴病例的临床及实验室指标的特点,探索影响HBsAg转阴的相关因素。方法 收集4年时间我院所有确诊的慢性乙肝经聚乙二醇干扰素α-2a治疗的患者共61例,建立病史资料库,并按人口学特征、患病情况、实验室指标、病毒学指标及免疫状态及相关影响因素等多项指标分别进行统计学处理。结果 61例经聚乙二醇干扰素α-2a治疗的慢性乙肝患者中,HBsAg转阴患者有5例,56例未发现HBsAg转阴。通过多因素logistic回归分析得出:病毒基因型、年龄、病程、HBV DNA滴度成为最有可能的相关影响因素。结论 聚乙二醇干扰素α-2a的抗病毒治疗能够使HBsAg转阴;治疗前根据相关因素进行疗效评估有一定的参考意义。【关键词】 慢性乙肝;聚乙二醇干扰素α-2a;基因型;HBsAg;HBV DNA;乙型肝炎病毒Case analysis of antigenic diversion of HBsAg in the patients treated with Pegylated interferon α-2a 【Abstract】Objective To investigate the clinical and laboratory characteristics in the chronic hepatitis B cases whose HBsAg diverted negative after pegylated interferon α-2a treatment, and to explore the related factors of HBsAg negative.Methods All the chronic hepatitis B with pegylated interferon α-2a from my hospital for 4 years were collected, altogether 61 patients, put their history information to the database, and analyze in statistics the indexes of demography features, pathogenetic conditions, laboratory data, virology data and the immune status and related factors. Results In all the 61 cases who were treated with pegylated interferon α-2a, 5 cases’HBsAg turned negative at last , 56 cases didn’t turn negative.Through the multifactorial logistic regression analyze: virus Genotype, age, course of disease, HBV DNA titer turned to be the most probable related factors. Conclusion Pegylated interferon α-2a can turn the HBsAg negative of Chronic hepatitis B.When patients were reasonable chosen,you would get a higher conversion rate of HBsAg.【Key words】Chronic hepatitis B; Pegylated interferon α-2a; Genotype;HBsAg; HBV DNA;HBV慢性感染乙型肝炎病毒( HBV )是一个重大的全球性的健康问题[1]。现有的抗HBV药物治疗HBsAg的转阴率均不高,本文通过使用聚乙二醇干扰素α-2a对慢性乙肝进行治疗,观察HBsAg转阴病例的临床特点,并就影响HBsAg转阴的相关因素进行分析。资料与方法 一、研究对象本组研究对象为我院2005年1月-2008 年12 月期间所有住院经聚乙二醇干扰素α-2a(180ug,一次/每周)抗病毒治疗的慢性乙肝患者共计84例,诊断均符合2005年12月修订的《慢性乙型肝炎防治指南》,经过调查整理,删除治疗丢失或不完整以及依从性差的患者,最终共计61例患者入资料库,抗病毒疗程均为1年,其中发生HBsAg转阴5例(8.2%),未发生HBsAg转阴56例。二.研究方法(一)采用含有30条项目的自制调查表。调查表包含临床症状(乏力、纳差等)、影响因素(包含年龄、性别、家族史、抗病毒史、HBsAg阳性病史、肝功能异常史等)、实验室指标情况(HBVM滴度、HBV DNA滴度、CD4、CD4/CD8等)、治疗情况(剂量、疗程、临床及实验室转归等)四个方面,临床使用中具较好的实用性及可操作性。(二)血清肝炎病毒标志物采用微粒体酶免疫分析法检测(美国雅培公司提供Abbott 试剂); HBV DNA定量检测采用荧光定量-聚合酶链反应(罗氏公司提供试剂)检测病毒定量,根据外参照标准曲线判断结果, < 103 拷贝/ ml 判为阴性结果,采用求对数平均值的方法计算HBV DNA 的平均拷贝数(copies/ml) ;HBV基因分型PCR微板核酸杂交ELISA试剂盒,检测方法按说明书进行,CD4计数用FACS Calibur型流式细胞仪,采用Mutiset自动软件进行结果分析。三、随访和统计 入选的61例慢性乙肝患者的资料输入Excel库,包括性别、年龄、职业、家庭住址、联系电话等人口学资料和临床表现、诊断及治疗等。逐个随访,了解患者治疗前后的HBVM滴度、HBV DNA滴度、CD4,CD8绝对计数、抗病毒治疗的副作用情况、病情转归等。随访得出补充资料,完善Excel资料库。录入数据至SPSS 11.5统计分析软件进行统计分析。计数资料组间比较采用卡方检验,多因素相关分析采用Logistic回归。 结果一、性别比和年龄构成HBsAg转阴组患者男女之比为1.5:1, HBsAg未转阴组患者男女之比为1.57:1;两组性别构成比无显著差异(P>0.05)。HBsAg转阴组的最大年龄为32岁,最小14岁,平均年龄为25.5岁(25.5±7.5岁)。HBsAg未转阴组的最大年龄为47岁,最小为20岁,平均年龄为35.7岁(35.7±8.3岁),HBsAg转阴组与HBsAg未转阴组患者年龄比较结果P<0.05,差别有显著性,故认为HBsAg转阴组年龄较HBsAg未转阴组年轻。二、HBV基因型与聚乙二醇干扰素α-2a治疗发生HBsAg转阴的关系 将转阴组5个病例及抽取未转阴组20个病例的预留血清行HBV基因型检测,见表1。表1 基因型与HBsAg转阴的关系基因分型N平均年龄(岁)病毒载量(copies/ml)转阴未转阴转阴率B1429.2±5. 0 5.7±2.1×1055935.7%C1138.5±6.24.2±1.1×1070110转阴率:B型与C型比较, P < 0.05平均年龄:B型与C型比较, P < 0.05病毒载量: B型与C型比较, P < 0.05故认为:B基因型比C基因型容易发生HBsAg转阴;感染B基因型的患者较C基因型年龄轻, 感染B基因型的患者较C基因型病毒量低。三、常见影响因素及HBsAg转阴之间关系将常见影响因素(包括饮酒、年龄、性别、家族史、抗病毒史、HBsAg阳性病史、病程、病毒基因型、HBsAg滴度、HBeAg滴度、HBV DNA滴度、CD4、CD4/CD8、治疗剂量、疗程等)通过单因素logistic分析,筛选出“病毒基因型”、“年龄”、“病程”、“HBsAg滴度”、“HBV DNA滴度”、“ALT水平”为可能的影响因素,病毒基因型为B型、年龄小、病程短、HBV DNA滴度低的患者发生HBsAg转阴的几率较高,其OR值分别为18.143(1.024-321.384),31.750(1.670-603.640),1.123(1.022-1.233),30.750(1.570-601.540)。本研究将这些因素作为自变量,而以HBsAg作为因变量,进行Logistic多元逐步回归分析,据此来筛选出那些可能对慢性乙肝患者发生HBsAg转阴产生影响的最为主要的因素。最后结果显示:“HBV基因型为B型、年龄小、病程短、HBV DNA滴度低”入选,成为最具可能性的影响因素,方程分类能力达到92.6%。方程有效性经卡方检验,χ2=23.347, P=0.00。 讨论慢性乙肝的自然病程取决于宿主免疫反应与病毒复制状态的相互作用,慢性HBV感染的自然史分为4个阶段:免疫耐受,免疫清除,非活动的HBsAg携带状态和恢复期。在免疫耐受和非活动的HBsAg携带状态,不需要治疗。患者在免疫清除期或恢复期是最佳的抗病毒治疗时机[2]。在过去的十年中,治疗慢性乙肝的方法已大大改善[3]。现有数据表明,干扰素比核苷类似物有较高的持续应答率和HBsAg的转阴率。Ⅱ期临床试验表明,在HBeAg阳性慢性乙肝的治疗中聚乙二醇干扰素α-2a优于常规干扰素 [4]。Chan HL等的研究[5]显示聚乙二醇干扰素α-2a治疗慢性乙肝中有5 %(2/40)的患者HBsAg转阴。本组病例治疗后HBsAg转阴率为8.2%(5/61),与文献报道一致。本组研究显示年龄小的患者HBsAg容易清除,B基因型比C基因型容易发生HBsAg转阴;感染B基因型的患者较C基因型年龄轻, 感染B基因型的患者较C基因型病毒量低。Orito E 等研究认为C基因型比B基因型在年龄偏大患者时( > 35 岁)有更高的病毒载量[6]。Morillo Verdugo R等[7]的研究发现乙肝患者的ALT水平高,低复制的HBV DNA和基因型A和B显示干扰素的疗效最佳。另有文献报道,基因C和D型对干扰素治疗反应要比基因A和B差[8]。国内外研究表明HBV基因型可能与疾病进程、感染后临床表现、预后与抗病毒治疗应答等密切相关[9] 。故在临床治疗上,了解患者的HBV基因型对乙肝的治疗选择和疗效评估可提供一定的临床依据。 本研究进行Logistic多元逐步回归分析,据此来筛选出那些可能对慢性乙肝患者发生HBsAg转阴产生影响的最为主要的因素。最后结果显示:“HBV基因型为B型、年龄小、病程短、HBV DNA滴度低”为最具可能性的影响因素。有文献资料显示病毒载量低和血清谷丙转氨酶在 2-5倍的正常上限,是聚乙二醇干扰素α-2a治疗的最佳时机[10]。聚乙二醇干扰素a-2a是有效的治疗慢性乙肝、抗病毒治疗的药物;合理选择病例,监测HBsAg滴度变化,治疗前根据相关因素给病人进行疗效评估,可以增加患者的HBsAg的转阴率。参考文献1 Lai CL, Ratziu V, Yuen MF, et al. 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黄绍萍王介非 谢德胜【提要】 近十多年来,肾综合征出血热发病率明显减少,不少低年资医师对此病不熟悉,特别是对缺少五期典型经过的不典型肾综合征出血热病例缺少认识,容易误诊漏诊,为减少误诊、提高对本病的早期诊断水平,本文介绍2例一家庭两成员共患的不典型肾综合征出血热患者的诊治经过及文献复习。【关键词】 肾综合征出血热The Diagnosis and treatment of two members from the same family suffering from hemorrhagic fever with renal syndrome HUANG Shao-ping WANG Jie-fei XIE De-sheng【Abstract】 Over the last decade,the incidence of hemorrhagic fever with renal syndrome was significantly reduced.Many young physicians are not familiar with this disease. Especially, the cases without typical five courses hemorrhagic fever with renal syndrome are easily misdiagnosed. In order to reduce the misdiagnosis and improve the level of early diagnosis,we reported two atypical cases from the same family suffering from hemorrhagic fever with renal syndrome.In this paper, we made an analysis of atypical clinical symptoms of hemorrhagic fever with renal syndrome and a review of the literatures.【Key Words】Hemorrhagic fever with renal syndrome近十多年来,肾综合征出血热(hemorrhagic fever with renal syndrome,HFRS)发病率明显减少,不少低年资医师对此病不熟悉[1]。为减少误诊、提高对本病的早期诊断水平,本文介绍2例不典型HFRS患者的诊治及文献复习。一、临床资料例1 女性,35岁。因发热、肝功能异常于2009年3月6日收入复旦大学附属第五人民医院。4 d前患者出现高热,最高体温达40.2℃,伴有畏寒,头痛,腰痛。1 d前门诊查肝功能:ALT 215 U/L,AST 165 U/L,总胆红素 18.5 μmol/L,拟诊急性肝炎收入院。既往无肝炎病史。入院查体:体温40℃,脉搏110次/min,呼吸20次/min,血压110/65 mm Hg(1 mm Hg=0.133 kPa)。急性病容,皮膜黏膜未见黄染和出血点,球结膜轻度充血水肿。腹平坦,无压痛及反跳痛,肝脾肋下未触及,移动性浊音阴性,双肾区无叩击痛。血白细胞11.2×109/L,分类中性粒细胞0.70,血红蛋白108 g/L ,血小板计数123×1012/L,未见异型淋巴细胞,血尿素氮4.7 mmol/L,血肌酐65.7 μmol/L, ALT195 U/L,AST 143 U/L, 总胆红素 16.2 μmol/L。尿蛋白( + )。诊断为“急性肝炎”,给予保肝降酶、对症等治疗,2 d后体温恢复正常,头痛、腰痛症状消失,7 d后肝功能恢复正常,血白细胞6.7×109/L,分类中性粒细胞 0.62,血红蛋白106 g/L,血小板计数126×1012/L,尿蛋白( - ),肾功能及其他指标均未发现异常,球结膜水肿消退,但监测尿量发现每日尿量>2500 ml。例2 男性,38岁,为例1患者的丈夫。因发热、肝功能异常于2009年3月11日收入复旦大学附属第五人民医院。3 d前患者出现高热,最高体温达40.3℃,伴有畏寒、头痛、腰痛,门诊查肝功能异常拟“急性肝炎”收入病房。既往无肝炎病史。入院查体:体温40.2℃,脉搏112次/min,呼吸21次/min,血压120/85 mm Hg。急性病容,皮肤充血,以颜面、颈部明显,球结膜中度充血水肿。腹平坦,无压痛及反跳痛,肝脾肋下未触及,移动性浊音阴性,双肾区无叩击痛。血白细胞13.4×109/L,分类中性粒细胞 0.69,血红蛋白108 g/L ,血小板计数147×1012/L,未见异型淋巴细胞,血尿素氮5.1 mmol/L,血肌酐66 μmol/L, ALT 257 U/L,AST 164 U/L, 总胆红素 15.2 μmol/L。尿蛋白( + ),尿隐血(+)。追问病史,夫妇是来沪打工者,在奉贤农村居住已半年,家里养猪,猪圈里有很多大老鼠寄居,喂猪时经常看到老鼠并且有驱赶老鼠的经历。最初住院时两患者均未监测尿量,监测尿量后发现每日尿量>2500 ml。3月14日夫妻血液标本送至上海市疾病控制中心行免疫荧光素标记肾综合征出血热病毒IgM抗体检测,均为阳性,明确诊断为HFRS。二、讨论HFRS是由汉坦病毒引起的急性传染病,是一种自然疫源性疾病,鼠为其主要传染源。主要临床表现是发热、出血和肾损害,典型临床经过有发热期、低血压休克期、少尿期、多尿期和恢复期。发热期时多数有“三痛征”和“酒醉貌”[1]。HFRS典型患者应具备五期临床经过,非典型患者注意有无多尿期(尿量>3000 ml/d)。对于轻症或非典型病例的诊断常需借助于实验室病毒学检查[2-3]。本病流行于世界许多国家,我国是高疫区。本病病情严重而复杂,一直是我国重点防治的传染病之一,近年来疫区不断扩大,可能因人体免疫力增强、侵犯人体病毒量少、预防接种等原因轻型病例明显增多,表现不典型[4]。只有少数病人发病凶险,发热期、低血压休克期、少尿期3期重叠, 病情危重。进入21世纪以来,本病在国内发病率已明显下降,传统的高发疫区发病率也明显降低,有些大城市反而出现了新的疫情,其主要发病患者群多居住在劳动场所卫生条件较差、且鼠害相对较重的城市郊区、施工工地。第五人民医院感染科的前身是闵行区传染病医院,处在上海市、属城乡交界部,周围居住的农村居民、外来打工人群居多,麻疹、水痘等急性传染病人数均较多,但近5年来第五人民医院感染科从未诊治过HFRS患者;此2例HFRS患者的发现,为我市、我区传染病的防疫提供了第一手资料,为我们临床医生能更全面地诊治发热性疾病提供参考。此2例HFRS患者传报后,上海疾病控制中心人员及时派专人前往该区进行消毒灭鼠及指导预防,对患者其他家庭成员给予注射疫苗,故未再发现有其他HFRS病例。HFRS早期诊断主要是指发热期患者的诊断,应熟悉发热期的各种临床表现,如急起的高、中度发热,明显头痛,面、颈、上胸部皮肤充血潮红,双侧腋下皮肤出血点及软腭黏膜出血点,眼球结膜水肿等;球结膜中度或重度水肿是本病早期最具特征或独有的临床表现。患者病后3~5病日外周血象和尿常规已出现明显的变化,如早期血液常规化验出现“三高一低”(即外周血白细胞增高,分类中性粒细胞百分率增高,异型淋巴细胞比率增高和血小板计数减低),且尿蛋白“++”以上,结合临床和流行病学资料可以拟诊本病;确诊有赖于特异性抗体检测。HFRS常伴有肝功能损害[5-6],ALT、AST多在疾病早期升高[7]。本组患者虽有发热,头痛、腰痛,球结膜水肿,血白细胞增高,肝功能异常等的变化,却无HFRS的发热期、低血压休克期、少尿期、多尿期和恢复期典型经过,故今后对发热、肝功能异常的农村患者,要注意询问接触史,不要忽视球结膜水肿及早期血尿常规的变化,进一步鉴别诊断,以防漏诊或误诊。本例误诊原因: ①发现肝功能异常,传染科医生先入为主诊断为急性肝炎,忽略与其他发热疾病鉴别;②经验不足, 对早期表现或非典型表现、早期血尿常规的变化缺乏认识;③因本病在我市一直呈散发状态,很多年轻医师对本病已经淡忘,诊断思维局限,缺乏全面分析。参考文献[1]梁万年.法定传染病识别与处理.北京:中国协和医科大学出版社,2005:69.[2]张建傲,罗端德,曾令兰,等.免疫酶斑点法检测汉坦病毒抗原的研究.中华实验和临床病毒学杂志,2004,18(1):88-90.[3]王卫华,王峰,陈洁,等.流式细胞术检测汉坦病毒抗原血症的临床应用.中国病毒学,2006,21(3):298-300. [4]蒋银香.流行性出血热72 例临床分析.四川省卫生管理干部学院学报,2005,24(1):35-36[5]赵洪全,姚智慧,付春生,等.肾综合证出血热病毒致肝脏损害的临床与实验室研究.中国实用内科杂志,1997,17:147.[6]唐正运,叶晓光,廖云珍,等.103例流行性出血热并发多器官功能障碍的临床分析.热带医学杂志,2005,2:174-175.[7]Puljiz I,Kuzman I,Turcinov D,et al.Laboratory findings in patients with hemorrhagic fever with renal syndrome.Acta Med Croatica,2005,59:105-111.(收稿日期:2009-04-30)(本文编辑:邵隽一)
上海地区215例成人麻疹患者的临床分析黄绍萍1,2王介非1,2,谢德胜2作者单位:黄绍萍,王介非,谢德胜,1、201508 上海市(复旦大学附属)公共卫生临床中心;2、200240,上海市(复旦大学附属)第五人民医院摘要: 目的 分析成人麻疹患者的流行病学及临床特征,总结成人麻疹的特点。方法 回顾性分析近3年收治的215例成人麻疹患者的流行病学及临床资料。结果(1)麻疹发病年龄主要在18-35岁之间。(2)未接种过麻疹疫苗的患者有67.9%。(3)主要并发症有肝功能异常183/215(85.1%),结膜炎82/215(38.1%),腹泻49/215(22.8%),肺部感染41/215(19.1%)等。结论 成人麻疹的并发症以肝功能异常最多见。成人麻疹发病率高与未进行麻疹疫苗接种;麻疹疫苗接种时间太长,抗体滴度降低;流动人群发病率高有关。关键词: 成人麻疹;临床分析;麻疹疫苗;并发症 Clinical analysis of 215 cases with adult measles patientsHUANG Shao-ping,WANG Jie-fei,XIE De-shengHUANG Shao-ping,WANG Jie-fei,Shanghai Public Health Clinical Center Affiliated to Fudan University,Jinshan, Shanghai, P.R.China,201508;Xie De-sheng,Copyright by The Fifth People's Hospital of Shanghai,Fudan University,200240Abstract: Objective To analyze the epidemiology and clinical characteristics of adult measles patients,and to summarize characteristics of adult measles.Methods Retrospective salysis epidemiology and clinical datas of 215 cases with adult measleses patients in our hospital at 2005-2008.Results (1)The episode age was at 18-35 years old.(2)Haven’t been vaccinated(67.9%).(3)The main complications were hepatitis (85.1%),conjunctivitis(38.1%),diarrhea(22.8%), pneumonia (19.1%) etc.. Conclusion The most common complication of adult measles patients is abnormal of liver function.The reason of the high rate of adult measles:(1)Don’t be vaccinated measles vaccine.(2)Antibody concentration lowered in the person vaccinated.(3)Incidence of the floating population is high.Key words:adult measles;clinical analysis;measles vaccine;complications麻疹系冬春季常见的急性呼吸道传染病,其发病率高,人类易感性强,故极易引起流行。近年来,随着麻疹疫苗的广泛接种,麻疹的发病率显著下降,特别是幼儿及青少年的发病率明显降低。但值得注意的是成人麻疹的发病增多,成人麻疹所占比例相对增加。近年来关于成人麻疹的发病报告明显增加,现将我院05-08年收治的215例成人麻疹患者进行回顾性分析,现将结果报告如下。1 材料与方法1.1 研究对象 研究对象为05-08年上海市(复旦大学附属)第五人民医院收治的215例成人麻疹病例,诊断标准参照文献[1]。其中男性121例,女性94例,年龄18-51岁,平均年龄32.2±8.1岁。1.2 调查内容 年龄,性别,籍贯,病情转归,住院天数。麻疹接触史,麻疹疫苗接种史。临床症状及体征,并发症,辅助检查等。1.3 麻疹IgM的检测 病人血清均送上海市闵行区疾病控制中心,用酶联免疫吸附试验(ELISA)检测血清麻疹抗体。2 结果2.1 一般情况调查 麻疹患者发病年龄,麻疹疫苗接种与否及是否外来人员情况见表1。表1 麻疹患者发病年龄、接种麻疹疫苗及外来人员情况年龄N未接种麻疹疫苗外地来沪人员18—35岁160(74.4%)91(56.9%)115(71.9%)>35岁55(25.6%)55(100%)45(81.8%)总数215146(67.9%)160(74.4%)我院05-08年收治成人麻疹病例215人,其中188例(87.4%)麻疹IgM(+),有5例病人初次查为阴性,1周后抽血复测为阳性,其余患者均检测一次。97位患者有明确的麻疹接触史。全年均可发病,麻疹流行季节为3、4、5三月。其中有在校学生患病54例(25.1%),医院里的医务人员患病19例(8.3%)。本组中有五位患者为第二次发病。患者中有3例孕妇,一例孕6周,入院前就已经发生难免流产;一例孕30周,好转出院;一例湖南来沪妇女产后1天确诊患麻疹。2.2 临床症状及体征 患者的临床症状体征见表2。表2 麻疹患者的临床症状体征症状及体征例数(%)发热215(100)典型皮疹192(89.3)麻疹粘膜斑137(63.7)流涕、咳嗽、咽痛86(40)流泪、畏光、结膜充血82(38.1)恶心、腹泻49(22.8)浅表淋巴结肿大29(13.5)声嘶16(7.4) 2.3 常见的并发症 并发症有肝功能异常183/215(85.1%),结膜炎82/215(38.1% ),腹泻49/215(22.8% ),肺部感染41/215(19.1%),喉炎16/215(7.4%),脑炎3/215(1.4%)。2.4 辅助检查 血WBC<4.0×109 /L有135(62.7%)例患者,WBC>1.0×109 /L有23例患者。WBC平均4.5±0.5×109/L,中性粒细胞平均为71.2±12.7%,淋巴细胞平均为18.1±9.8%。本组患者肝损伤程度均较轻,主要表现为ALT(<330U/L)和AST(<240U/L)升高,无一例出现胆红素升高,LDH在伴或不伴肝损的患者中均明显升高,异常率达95.4%,平均为446.6±105.6U/L。2.5 转归 经积极的对症支持及防治并发症等治疗后,全部临床症状改善出院。平均住院天数为6.3±2.1天,最长为15天。3 讨论据世界卫生组织(WHO)估计,全球每年仍有约3500万麻疹病例,在疫苗可预防的病毒性疾病中,麻疹仍是死亡例数最多的[2]。而本组患者中全部好转出院,预后良好。既往麻疹主要在儿童中流行,目前随着麻疹疫苗的接种,儿童发病率下降,成人麻疹发病率则逐渐增高[3,4],老年人中发病也屡见不鲜[5]。学校常为麻疹流行的场所,本组在校生占25.1%。医院是传染病隔离的场所,医务人员要做好自身的消毒隔离,本组医院里的医务人员患病19例,故要加强医务人员的防护[6],上岗前需注射疫苗保护。麻疹全年均有发病,流行季节为3、4、5三月。本研究显示,麻疹好发年龄段为18—35岁,67.9%患者未接种麻疹疫苗,外地来沪人员占74.4%。我国于1965年开始对麻疹易感儿实行麻疹疫苗接种至今,随着时间的推移,抗体水平逐渐下降,有一部分人失去了麻疹抗体,导致易感性增加。另一方面,由于当时疫苗处于问世初期,无效接种和漏种的较多,也是造成成人发病率增加的原因。40岁以上的人发病相对较少,可能与幼儿曾患过麻疹有关。孕妇患麻疹后在孕早期易引起自然流产和死胎,应引起临床重视。本组患者中有1例孕妇患麻疹导致流产、死胎。有学者报道,成人麻疹并发肝损伤普遍,重者可导致腹水[7]。麻疹病毒侵入人体后经过2次病毒血症, 病毒在侵入脏器的细胞内增殖, 破坏细胞引起炎症。国外学者在麻疹伴肝功能损害患者的肝脏组织检查中,发现肝细胞有轻度坏死, 通过PCR法在肝细胞内检测到麻疹病毒的RNA , 因此认为麻疹病毒对肝细胞的损害是直接作用造成的。本组肝损伤患者为183例,占85.1%;肝损伤程度均较轻,主要表现为ALT和AST升高,无一例出现胆红素升高,肝功能随着麻疹的好转也随之好转,无慢性化趋势。LDH异常率达95.4%,原因可能与患者发热引起的中毒症状有关。本组成人麻疹临床表现大多不典型,病情较重,全身中毒症状较小儿明显,部分病例体温超过40℃,发热持续时间长,出疹、退疹迟缓,这可能与成人的机体反应较强有关。皮疹发生率高,仍以典型斑丘疹为多,且皮疹较儿童麻疹重,出疹顺序及疹形仍较典型,出疹时间推迟较明显,卡他症状与出疹程度成正比。麻疹粘膜斑出现比例较高(63.7%),且持续时间长。本组成人麻疹发病与下列因素有关:(1)未接种疫苗者,特别是外地来沪人员。(2)接种过疫苗的患者随着年龄增长,免疫效价降低,体内抵抗麻疹的能力降低。(3)本组有5例患者第二次患病推测与麻疹病毒变异有关。有文献报道麻疹病毒抗原性是稳定的,只有一个血清型,患病后可获得持久免疫力,很少第2次患病。朱建琼[8]等报道,尽管麻疹病毒被认为是单血清型别,但是序列分析表明,存在着截然不同的麻疹野病毒基因型,并可共同在人类中传播。故加强麻疹疫苗的覆盖面,特别是外地来沪人员,确保麻疹疫苗的接种率;在易感人群中可进行麻疹疫苗的补种复种;进一步研究麻疹病毒的基因分型并研制开发新疫苗;加强人们的防病意识,从而减少流行季节麻疹的发病。 【参考文献】[1]杨绍基. 传染病学. 北京: 人民卫生出版社,2005:57-58.[2]World Health Organization. Nomenclature for describing the geneticcharacteristics of wide-type measle viruses(update).Wkly EpideMoil Rec,2001,76(2):241-247[3]梁晓岳,向华,周加新.224 例成人麻疹临床分析.中华实验和病毒学杂志, 2005,19(1):99.[4]朱菊珍.以腹泻为主要表现的成人麻疹21 例. 中华传染病杂志,2005,23 (2) : 140-141.[5]陈艳,文进.重庆市涪陵区免疫后麻疹的流行特征分析.中华流行病学杂志,2001,22:110.[6] Torner N, Martinez A, Costa J, et al.Measles outbreak in the Barcelona Region of Catalonia, Spain, October 2006 to February 2007. Euro Surveill. 2007;12(8):3144.[7]刘刚,袁正宏,谢德胜,等.上海地区成人麻疹170例[J].中华传染病杂志, 2006,24:4152417.[8]朱建琼,彭志强,雷满根,等.2000年东莞市麻疹病毒流行株基因分析[J].中华流行病学杂志,2001,25(5):355-358.
非HIV儿童马尔尼菲青霉病的肺部感染特点及文献复习黄绍萍,吴文娟Characteristics of Penicilliosis Marneffei with pulmonary infection in a non-HIV-infected child:a case report and review of the literatureShao-Ping Huang, Wen-Juan Wu, Shanghai Public Health Clinical Center Affiliated to Fudan University摘要:本文报道一例非HIV的儿童马尔尼菲青霉菌肺炎病例,该患儿为8岁;因反复发热、咳嗽、咳痰1年,加重3周入我院,患儿以肺部感染起病,经多种抗菌素反复治疗后未见好转,入我院时发展为重症肺炎,考虑侵袭性真菌病,立即给予伏立康唑经验性抗真菌治疗,但患儿迅速发展为MODS死亡。先前所送痰培养、骨髓培养均找到马尔尼菲青霉菌。本文对马尔尼菲青霉菌肺炎的临床表现进行分析,并对儿童马尔尼菲青霉病的相关文献进行复习,探讨如何早期诊治,减少病患死亡。关键词: 马尔尼菲青霉菌;马尔尼菲青霉病;肺部感染;儿童Abstract: In this case,we report a 8-year-old child of Penicilliosis marneffei pneumonia with non-HIV-infected who was admitted to hospital because of repeated fever、cough and expectoration for 1 year and getting worse for 3 weeks. She was treated with a variety of antibiotics as soon as the pulmonary infection,but finally died with MODS before culture of Sputum and bone marrow turned positive of Penicillium marneffei.In this paper, we explore the characteristics of Penicilliosis Marneffei with pulmonary infection in a non-HIV-infected child and review related literature in order to get early diagnosis and decrease the mortality.Key Words: penicillium marneffei; penicilliosis marneffei; pulmonary infection;child马尔尼菲青霉菌(Penicillium Marneffei,PM)是迄今发现少数能使人类致病的青霉菌之一,为条件致病菌,可寄生于细胞内,是青霉菌中唯一的温度双相型真菌;主要感染免疫功能缺陷人群,尤其是艾滋病(AIDS)病人,引起马尔尼菲青霉病(Penicilliosis Marneffei ,PSM);常成为AIDS患者的死因原因之一。PSM在免疫功能正常人群患病报道较少,在免疫功能正常的儿童中感染更加少见,故往往造成对儿童PSM缺少认识,导致延误诊断,儿童感染死亡率相对更高[1]。本文报道一例少见的非HIV儿童马尔尼菲青霉菌肺炎死亡病例并结合肺部感染特征的临床资料及文献复习,以探讨提高马尔尼菲青霉菌肺炎的早期诊断及鉴别诊断。 临床资料患儿,女,8岁,温州人。因“反复咳嗽、咳痰1年,加重伴发热3周”入院。发病初期表现为发热,咳嗽、咳痰,痰为黄色粘痰,量较多。间断性发热,体温在37.5℃左右,无明显规律性。当地医院查肺部阴影,拟“肺部感染”给予多种抗生素(青霉素、阿莫西林、头孢曲松等)反复抗感染治疗近10个月,未见好转,复查胸部CT:两肺散在分布团块状阴影,考虑结核可能,转入我院。体格检查:T:37.5℃,P:144次/分,R:20次/分,BP:100/72mmHg。贫血貌,全身皮肤粘膜无黄染、无瘀点瘀斑、无皮疹。全身浅表淋巴结未触及肿大。两肺呼吸音稍粗,未闻及干、湿啰音。心率144次/分,律齐未闻及病理性杂音。腹平软,全腹无压痛及反跳痛,肝肋下1cm,剑下2cm,质软,无触痛;脾肋下可扪及1cm,质中,移动性浊音(±)。辅助检查:肝功能ALT 108U/L,AST 141U/L,A 30.8g/L;血常规:Hb 83.7g/L,N7 3.9%,PLT 122.0×109/L,RBC 4.11×1012/L,WBC 7.19×109/L;凝血指标:PT15.8s;HIV阴性;血沉、结核菌涂片、结核抗体、细胞免疫、血隐球菌培养未见明显异常。真菌D葡聚糖177.6pg/ml。腹部CT:肝脾肿大,腹腔及后腹膜多发淋巴结肿大,少量腹水。头颅MR:左侧基底节区及左侧额叶大脑镰旁异常信号。结果患儿入院后查胸部CT:右侧肺门呈大片状实变影,两肺多发小片状高密度影,两上肺病灶内可见小空洞影;伴胸腔积液、肺不张(见图1)。考虑“重症肺炎,侵袭性真菌病可能”给予伏立康唑治疗5天后病情迅速恶化,呼吸加快;胸部CT示病灶增多,肝、脾肿大明显,肝功能异常,血细胞三系水平急速下降,行骨穿检查见大量噬血细胞;PT由18.3s延长至38.7s。复查血常规:Hb63.70g/L,N27.6%,PLT56.90×109/L,RBC3.35×1012/L,WBC3.42×109/L;PT由38.7s延长至58.4s(仅1d);遂转至ICU治疗,但是患儿病情进展迅速,很快发展为MODS,转ICU3天后抢救无效死亡。死后第2天痰培养及骨髓培养结果回报为PM(图2,3)。图1胸部CT示两肺多发小片状高密度影伴小空洞影 图2 真菌培养:双相性生长, 在25℃成霉菌型生长, 见特征性的酒红色色素产生 图3 真菌培养:镜检示帚状枝菌丝讨论近几年播散性PSM的发病率逐年上升,PM已从AIDS人群向一般人群扩散。我国最早于1985年广西报道该病1例,以后报道逐渐增加,以华南地区特别是广西、广东两省为最多;随着病例增多呈现由南向北扩展趋势, 据统计我国公开报道的病例接近200例[2],这只是冰山一角,还有不少未发表的病例及未被确诊的病例。上海曾有1例HIV感染PM的报道,但尚无儿童非HIV患者感染PM的报道。本病的传染途径还不明确,Hamilton等发现吸入马尔尼菲青霉的分生孢子可能是最主要的传播途径。直接接触竹鼠或竹鼠的排泄物、食用竹鼠或马尔尼菲青霉污染甘蔗的传染方式尚待进一步证明[3]。PM通常是经肺侵入人体, 进入人体后,真菌会变为酵母型并通过网状内皮系统播散,早期肺炎时不易想到该病。个别病例病变局限于肺部,大部分病例发展为播散性感染;其中肺常常是全身性播散性感染的首要器官,PM肺部感染的临床表现缺乏明显特征性,病例大多通过行纤支镜检查取盥洗液培养或肺活检获得确诊,痰培养阳性率不高[4]。莫让辉等报道PSM经常以发热、干咳为首发症状,呼吸道症状与体征多数轻微,胸部影像学异常多见,肺部多表现为呼吸音增粗,无明显干湿性啰音。胸部X线表现双肺呈间质性改变, 呈弥漫性、粟粒状真菌性肺炎;片状渗出性改变;胸腔少量积液;纵隔淋巴结肿大等易误诊为肺结核及其他机会性感染[5]。本患儿是上海发现的罕见的非HIV儿童播散性PSM,首发症状表现为发热,咳嗽,胸片提示肺部阴影,考虑肺部感染经多种抗菌素治疗未见好转,多次痰培养未发现致病菌,从温州到上海来看病,故此例为上海PSM输入性病例。患儿来我院后考虑“重症肺炎”,侵袭性真菌病可能,给予伏立康唑抗真菌治疗5天后发生MODS死亡,死亡后痰培养及骨髓培养回报找到PM,确诊为播散性PSM。在患儿拟不明原因肺炎反复治疗10个月期间,因未对其进一步行肺穿、纤支镜取标本,延误了明确病原的时间,故对反复发作的难治性儿童肺部感染,要想到真菌感染的可能,及早寻找病原,一旦发生播散性PSM,病死率极高;血或分泌物培养要等21天才做出阴性结果的判断,PM阳性培养结果也一般在14天左右,故对早期不明原因肺部感染寻找病原、明确病原显得极为重要。本患儿的胸部CT表现为:①肺部片状实变影;②双肺弥漫性小片状高密度影,大小不等粟粒状结节影;③纵隔、肺门淋巴结肿大;④胸腔积液、肺不张;⑤病灶内可见小空洞影。该患儿的胸部CT改变与文献报道基本一致[6],较为典型。因为对本病的早期肺部感染的影像学改变不熟悉,亦是造成此患儿没有早期确诊的原因。PSM病情发展快,病死率高,但若能及早诊断并应用有效抗真菌药物,通常可收到较好疗效[5]。曾有人采用E-test法做PM的抗真菌药敏试验,证实了两性霉素B和伊曲康唑是较敏感的药物,可控制症状和临床治愈。国外报道应用两性霉素B初始治疗2周,剂量为0.6 mg/( kg·d) ,然后伊曲康唑400mg/d治疗10周,对大多数病例都是有效的。此患儿虽考虑真菌感染使用伏立康唑抗真菌治疗,但因病情发展很快,终因MODS死亡;故早期诊断、早期明确肺部感染的病原对降低病患死亡尤为重要。参考文献:1 张小玲,刘跃梅,黄俊云,等.儿童马尔尼菲青霉菌病2例报道并文献复习.新医学,2008,39(10):646-6472 赵国庆,冉玉平,向耘.中国大陆马尔尼菲青霉病的临床表现及流行病学特征的系统评价.中国真菌学杂志,2007,2(2):68-723 Vanittanakom N, Cooper CJ, Fisher MC, et al. Penicilliummarneffei infection and recent advances in the ep idemiology and molecular biology aspects. ClinMicro Rev, 2006, 19: 95-1104 邓西龙,陈万山.艾滋病合并肺部马尔尼菲青霉菌病临床分析.热带医学杂志,2006,6(7):782-7845 莫让辉,唐小平,蔡卫平,等.艾滋病合并播散性马尔尼菲青霉菌病41例临床分析.中国实用内科杂志,2006,26(24):1953-19556 余卫业,陆普选,朱文科,等.艾滋病合并播散性马尔尼菲青霉菌感染的临床与影像学特点.中国临床医学影像杂志,2007,18(6):434-437
黄绍萍,卢洪洲 上海市(复旦大学附属)公共卫生临床中心摘要: 目的 探讨上海地区今年甲型H1N1流感确诊病例的临床特点。 方法 2009年5月24日~2009年6月15日上海市(复旦大学附属)公共卫生临床中心收治的甲型H1N1流感最初10例确诊病例的流行病学及临床资料。结果 甲型H1N1流感病例的临床特点:①10例患者平均年龄为30.1岁(18~47岁);全部为输入性病例,感染地区为美国(70%),澳大利亚(30%)。②起病急、发病到住院时间平均为2.7天;潜伏期平均为4.3天;首发症状多为发热(70%),大多数为中低热、持续1~4天。主要症状和体征为发热(100%)、咳嗽(80%)、咽痛(50%),咽部充血(100%)和扁桃体肿大(50%)等,症状持续时间为1-7天。少数患者可出现病毒性肺炎(20%),无重症病例。③WBC多数正常,没有显著的中性粒细胞和淋巴细胞计数上升或下降;C反应蛋白升高和CD4+下降比较常见。④全部病例给予奥司他韦治疗,流感病毒转阴时间1-6天,中位时间4天。 结论 上海出现的甲型H1N1流感能在人与人之间传播,感染者大多表现出轻微的症状,病很快痊愈。关键词: 新型甲型H1N1流感;发病年龄;流行病学;临床特征Clinical features of new influenza A(H1N1)2009 in shanghai: the first ten adult imported casesShao-Ping HUANG,Hong-Zhou LU, Shanghai Public Health Clinical Center Affiliated to Fudan UniversityAbstract: Objective To summarize the epidemiology and clinical features of new l influenza A (H1N1),and to analyze characteristics of the first ten adult cases in Shanghai. Methods Retrospective analysis epidemiology and clinical datas of 10 cases with new influenza A (H1N1) From May 24 to June 15, 2009. Results clinical features of 10 cases of new influenza A (H1N1): ①Mean age was 30.1(range 18~47) years;All were travellers for United States (70%), Australia (30%);②acute onset, They developed symptoms within a mean of 2.7 days of arrival in hospital;incubation period of 4.3days(2 to 6 days); the first symptoms were fever (70%), mostly in low-heat, last for 1 to 4 days. The main symptoms and signs are fever (100%), cough (80%), pharyngodynia (50%), pharyngeal hyperemia (100% ), tonsillar swelling(50%); a small number of patients may be with viral pneumonia(20%), non-severe cases. ③WBC were more normal, no significant neutrophil and lymphocyte count upward or downward, elevated serum C-reactive protein and decreased CD4 is more common; ④oseltamivir in treatment under the premise of H1N1 negative patients from 1 to 6 days, with a median time of 4 days. Conclusion New Influenza A (H1N1) can spread from person to person, The prevalence of the infection period showed a slight majority of the symptoms, patients recovered quickly in Shanghai. Key words:New Influenza A (H1N1);Episode Age;Epidemiology;Clinical Feature2009年3月墨西哥暴发“人感染猪流感”疫情[1],造成人员死亡,随即在多国暴发了甲型 H1N1流感病毒疫情[2]。2009年5月24日上海也发现了新型甲型H1N1流感病例。为了给进一步的甲型H1N1流感诊治提供参考,现将上海最初10例新型甲型H1N1流感确诊病例临床特点进行报道。资料与方法一、研究对象 2009年5月24日至2009年6月15日上海市(复旦大学附属)公共卫生临床中心收治的上海最初10例新型甲型H1N1流感确诊病例,所有患者的诊断符合卫生部颁布的《甲型H1N1流感诊疗方案(2009年试行版第一版)》的标准。其中男性3例,女性7例;年龄18~47岁。二、研究内容 流行病学资料包括性别、年龄、种族、感染地区、接触史、发病日期、抵沪日期,临床资料包括症状、体征、并发症、病情转归,实验室资料包括外周血细胞检查、肝功能、肾功能、细胞免疫、体液免疫、影像学检查等。三、病毒检测 患者入院后即刻采集咽拭子标本,送上海市(复旦大学附属)公共卫生临床中心生物安全三级实验室,采用反转录聚合酶链反应(RT-PCR)法检测新型甲型H1N1流感病毒核酸。检测方法参照卫生部颁布的《甲型H1N1流感监测方案(第一版)》。四、研究方法 对患者的流行病学资料、临床资料和实验室资料进行描述性分析。结 果一、人口特征 10例患者中,男︰女比例=1︰2.33,平均年龄30.1岁。黄种人9例,白种人患病1例。二、感染地区及接触史 10例均为归国人员、属于输入性病例,其中有3例上飞机前已经发病,7例在抵沪后1~5天内发病。感染地区有7例来自美国(70%)、,其中5例来自纽约,l例芝加哥,1例波士顿;3例来自澳大利亚墨尔本(30%)。有明确接触史者3例,接触到发病时间平均4.3天。发病到住院时间为2.7天。见表1表1:上海发现的前10例甲型H1N1流感患者临床资料病例性别年龄感染地区抵沪日期发病日期住院日期转阴日期接触史首发症状最高体温(℃)1男30澳大利亚墨尔本20090523200905212009052420090527无流涕39.22女25美国芝加哥20090523200905262009052720090527无发热383男22澳大利亚墨尔本20090523200905252009052820090530有咽痛37.74女33澳大利亚墨尔本20090523200905282009052820090530有发热37.35女23美国纽约20090528200905292009053120090602无发热38.26女61美国纽约20090529200905312009060120090604无发热38.47女18美国纽约20090530200905302009060220090604无咽痛37.78女18美国纽约20090604200906022009060520090607无发热389女47美国纽约20090604200906062009060620090610有发热37.410男24美国波士顿20090606200906052009060720090611无发热38.3三、症状与体征 10例患者中,首发症状为发热者7例,咽痛者2例,流涕者1例。主要症状分别为发热(100%)、咳嗽(80%)、咽痛(50%)、咯痰(白色或黄色黏痰)(20%)、肌肉酸痛(20%)、流涕(20%)、鼻塞(20%)等,其中最高体温(腋温)波动于37.3~39.2℃之间。症状持续时间为1-7天。体温升高持续时间为1~4天;主要体征分别为咽部充血(100%)和扁桃体肿大(50%)。四、并发症 10例患者中,发生病毒性肺炎2例(20%);没有鼻窦炎、中耳炎等并发症。 五、外周血细胞检查 10例患者入院当天均进行了外周血细胞检查,其中白细胞绝对计数1.95~10.5×109/L,平均为5.37×109/L;低于正常值下限3例(30%),中性粒细胞绝对计数0.69~6.47×109/L,平均为3.4×109/L,低于正常值下限2例(20%);淋巴细胞绝对计数0.68~1.92×109/L,平均为1.23×109/L,低于正常值下限4例(40%)。六、辅助化验 10例患者均进行了体液和细胞免疫检测,其中C反应蛋白2.65~71.1mg/L,超过正常参考值上限的病例数为8例(80%),C反应蛋白平均值20.25mg/L;类风湿因子范围20~32IU/mL,超过正常参考值上限的病例数为5例(50%),类风湿因子平均值22.91IU/mL;CD3范围568~1351×106/L,低于正常参考值下限的病例数为3例(30%),CD3平均值848.5×106/L; CD8范围181~591×106/L,低于正常参考值下限的病例数为2例(17.1%),CD8平均值327×106/L; CD4范围216~747×106/L,低于正常参考值下限的病例数为4例(40%),CD4平均值488.6×106/L。10例患者均进行了肝肾功能检查无异常。七、胸部CT检查 10例患者均进行了胸部CT检查,其中4例患者胸部CT发现有异常改变,部分肺小叶渗出性炎症4例次,一侧或两侧胸膜少许炎症2例次,肺节段肺不张1例次。八、病毒转阴时间 10例患者每日送检咽拭子标本检测甲型H1N1流感病毒核酸,病毒核酸转阴时间在1~6天,中位时间为4天。九、治疗方案及转归 所有患者均予以奥司他韦75mg,每日二次,口服治疗,有扁桃体肿大或中性粒细胞升高者同时加用阿奇霉素治疗。10例患者症状消失时间为1-6天,中位时间为4天。以症状消失3天及病毒转阴2天为出院标准,10例患者住院平均时间为8天。讨论流感病毒感染是危害人类健康的顽症之一。2009年3月墨西哥暴发“人感染猪流感”疫情,造成人员死亡,随即在多国暴发了甲型 H1N1流感病毒疫情,此前曾被人们称之为猪流感,世界卫生组织2009年5月1日宣布停止使用“猪流感”一说,以避免由此引发的混乱。研究发现,此次疫情的病原为变异后的新型甲型H1N1流感病毒,该毒株包含有猪流感、禽流感和人流感三种流感病毒的基因片段,可以在人间传播。甲型流感病毒H1N1亚型(A(H1N1)或H1N1),也称H1N1病毒,是甲型流感病毒的一种,也是人类最常感染的流感病毒之一。1918年的流感大流行就是由H1N1病毒株引起的[3]。目前新型甲型 H1N1流感的流行和临床特点以及防治规律是各国传染病临床研究的一个重点内容。此次变异后的新型甲型H1N1流感病毒所引起的急性呼吸道传染病,是通过飞沫、气溶胶、直接接触或间接接触传播,临床主要表现为咳嗽、咳痰,发热,头痛,咽痛,流涕,肌肉酸痛等流感样症状,少数病例病情重,进展迅速,可出现病毒性肺炎,合并呼吸衰竭、多脏器功能损伤,严重者可以导致死亡[4,5]。1918年由H1N1病毒株引起的流感大流行主要死亡原因是细菌性肺炎[6]。在全球化时代,甲型 H1N1流感飞速传播,任何国家都不可能是一座孤岛。香港5月1日确认了首例甲型H1N1流感患者,5月11日我国内地诊治了首例甲型H1N1流感病例。5月份上海也不可避免的出现输入性病例,本组10例甲型H1N1流感病例,均经国家疾病预防控制中心或上海市疾病预防控制中心咽拭子甲型流感病毒核酸检测阳性,主要特点有①平均年龄为30.1岁(18~47岁);全部为输入性病例,感染地区为美国(70%),澳大利亚(30%);有3例病例有明确的接触史,证实甲型H1N1流感具有高度的传染性,可以在人-人之间传播[7]。目前在美国流行的H1N1流感主要影响的是年轻人,60%是影响18岁的青年或更年轻的人[4,5]。②起病急、发病到住院时间平均为2.7天;潜伏期平均为4.3天;首发症状多为发热(70%),大多数为中低热、持续1~4天。主要症状和体征为发热(100%)、咳嗽(80%)、咽痛(50%)、咯痰(20%)、肌肉酸痛(20%)、流涕(20%)、鼻塞(20%),咽部充血(100%)和扁桃体肿大(50%)等,症状持续时间为1-7天。少数患者可出现病毒性肺炎(20%),无重症病例。③WBC多数正常,没有显著的中性粒细胞和淋巴细胞计数上升或下降,无肝肾功能损害。C反应蛋白升高和CD4下降比较常见。④目前通过试验对H1N1流感病毒敏感的神经氨酸酶抑制剂是奥司他韦和扎那米韦[8]。本组全部病例给予奥司他韦治疗,流感病毒转阴时间1-6天,中位时间4天;患者均为轻型病例,预后良好,全部好转出院。此次全球爆发的大流感疫情,在今后数月内,目前还不清楚这种流行病的发展方向,我国各地5月份相继出现输入性甲型H1N1流感病例,传2代病例已经发现,这给我国传染病防治提出了新的要求,早期发现、早期隔离,增强市民的防病意识,治愈患者,争取早日战胜这次全球性的甲型H1N1流感流行。参考文献1. New influenza A (H1N1) virus infections: global surveillance summary, May 2009. World Health Organisation. Weekly Epidemiological Record 2009; 84:173-84. Available at: www.who.int/wer/2009/wer8420/en/index.html. Accessed June 5,2009.2. Epidemic and pandemic alert and response (EPR). Influenza A(H1N1), update 48. World Health Organisation. Available at:www.who.int/csr/don/2009_06_12/en/index.html. Accessed June 15, 2009.3 Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solórzano A, Swayne DE,et al.Characterization of the reconstructed 1918 Spanish pandemic influenza virus.Science 2005;310(5745):77–80.4 Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team.Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 May 7;doi:10.1056/NEJMoa0903810.5 US Centers for Disease Control and PreventionC. Swine-origin influenza A (H1N1) virus infections in a school—New York City,April 2009. MMWR 2009; 58 (Dispatch):1–3.6 Morens DM, Taubenberger JK, Fauci AS. 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临床资料患者,女性,23岁,因“发热伴咳嗽、咳痰2天”于2009年5月30日入院。患者5月28日从美国乘飞机抵达上海。5月29日出现发热伴咳嗽、咳痰,体温37.5℃,无咽痛,无鼻塞流涕。自服双黄连口服液及利君沙治疗后症状未改善。5月30日于松江区第一人民医院就诊,测体温38.2℃。5月31日上海市CDC:咽拭子甲型H1N1流感病毒特异性核酸阳性,拟诊甲型H1N1流感疑似病例转至我院隔离病房。体格检查:T:36.3℃,P:84次/分,R:20次/分,BP:105 / 63 mmHg。神志清晰,咽部充血,双侧扁桃体无肿大,两肺呼吸音清,未闻及干、湿啰音,未闻及胸膜摩擦音。心率84次/分,律齐,各瓣膜听诊区均未闻及病理性杂音,腹平软,全腹无压痛及反跳痛,肝脾肋下未扪及,移动性浊音阴性。辅助检查:5月30日松江区第一人民医院血常规:WBC 4.0×109/L,N 0.486,L 0.415,5月31日上海市CDC报告:甲型H1N1流感病毒特异性核酸阳性。患者31日入我院隔离病房后,经市级专家组会诊明确诊断为:甲型H1N1流感确诊病例。5月31日给予奥司他韦胶囊75mg Q12H口服治疗,6月1日查血常规:WBC 1.95×109/L,N 0.353,L 0.471,Hb 138g/L,PLT 160×1012/L。肝肾功能、电解质均正常。给予重组人粒细胞集落刺激因子(惠尔血)75ug皮下注射后,6月2日血常规:WBC 11.1×109/L,N 0.844,L0.1,Hb129g/l,PLT 142×1012/L。6月3日血常规:WBC 6.53×109/L,N 0.633,L0.257,Hb 123g/L,PLT 158×1012/L。6月5日血常规:WBC 4.86×109/L,N 0.573,L0.321,Hb 136g/L,PLT 164×1012/L。讨论 2009年3月-5月多国暴发了流感疫情,5月份上海也出现了输入性病例。我院作为上海市唯一一家成人甲型H1N1流感病例定点收治医院,从2009年5月24日起开始收治了甲型H1N1流感病例,截止6月10日共收治了11例输入性甲型H1N1流感患者,该11例患者均给予达菲75mg Q12H 口服。其中有一例患者服用一粒达菲后出现白细胞下降,考虑药物引起的白细胞下降,给予重组人粒细胞集落刺激因子(惠尔血)75ug皮下注射后WBC升为11.1×109/L。达菲( tamiflu)是磷酸奥司他韦(oseltamivir, OS)胶囊的商品名,由瑞士罗氏公司研制生产,美国食品药品管理局(FDA)于1999年批准上市,WHO批准为抗禽流感的首选药物。达菲适用于成人和1岁及1岁以上儿童的甲型和乙型流感治疗;或者适用于成人和13岁及13岁以上青少年的甲型和乙型流感的预防。在成人流感治疗的III期临床试验中,报告的不良事件中发生率最高的是恶心和呕吐。儿童流感治疗的III期临床试验中,报告发生率最高的不良事件是呕吐,其他比较常见的不良事件是腹痛、鼻衄、耳痛和结膜炎。2007年6月13日国食药监注[2007]330号发布了国家食品药品监督管理局关于修订磷酸奥司他韦胶囊说明书的通知,在磷酸奥司他韦胶囊说明书中提到磷酸奥司他韦胶囊上市后经验:有个案报道出现了胰腺炎、血管性水肿、喉部水肿、支气管痉挛、面部水肿、嗜酸粒细胞升高、白细胞下降和血尿。国外已经有白细胞下降的报道,故国内在使用奥司他韦时要严密监测血常规情况,注意白细胞下降引起的不良后果。