Dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis: data acquisition for computer modeling.

Ten adult patients with active HHV-6 variant A infections and clinical infectious mononucleosis-like disease (IM) were studied over a period of 32 weeks after onset of disease for their viral DNA load, changes in peripheral blood T-lymphocytes and subpopulations and frequency of cell death in peripheral blood cells. The data were collected as the basis for an advanced computer simulation study for which available data in the literature were too varied. Since the exact time of primary infection of the patients was not known and thus no time relationship of viral effects at cellular level were determined, we supplemented such data from separate tissue culture studies using HHV-6 alpha infection of HSB2 cells. Patients with IM demonstrate an increase in-HHV-6 DNA copies from 0 to 8.2 log 10/5 microL blood within 4 weeks return to normal by 16 weeks. Total T-lymphocytes follow infection with a 20-fold increase above normal peaking at 8-10 weeks and then return to normal by 24-28 weeks. Coincidently, less mature lymphoid cells carrying markers for stem cells, thymic cortical and medullary cells increase 8-10-fold indicating an enhanced mobilization of such cells from premature cell compartments. Cell death in peripheral mononuclear cells peaked with 30% at 8 weeks after onset of clinical disease and normalized by 24 weeks. HHV-6 replication in cell culture as determined by antigen expression, electron microscopy and harvest of infectious virus indicated a complete cycle of virus infection and replication of at least 6 days. The presented data compare well with others from the literature and will serve for testing in a computer simulation model, which is the subject of a forthcoming paper.     

不同EB病毒DNA载量的传染性单核细胞增多症患儿临床特征分析

目的:研究传染性单核细胞增多症(IM)患儿血EB病毒脱氧核糖核苷酸载量与其临床症状的关联.方法:选取28例患有传染性单核细胞增多症患儿的临床资料,根据血EB病毒(EBV)脱氧核糖核苷酸载量数据,将其分为高载量组(16例)、低载量组(12例),前者载量≥5.0×103copies/mL,后者<5.0×103 copies...     

检测传染性单核细胞增多症患者外周血单个核细胞EB病毒DNA的临床意义

目的应用荧光定量聚合酶链反应方法检测传染性单核细胞增多症患者外周血单个核细胞中的EB病毒DNA含量,探讨EB病毒感染单个核细胞的临床意义。方法应用荧光定量聚合酶链反应检测38例传染性单核细胞增多症患者发热7d内,起病1、3、6、9个月外周血单个核细胞（PBMC）及血浆中EB病毒DNA,应用酶联免疫吸附法检测血清EB病毒衣壳抗原IgM。结果38例患者在EB病毒感染发病7d内,PBMC中EB病毒DNA检出阳性34例,阳性率为89．5％（34／38）;EB病毒衣壳抗原IgM检出阳性22例,阳性率为57．9％,二者差异有统计学意义（χ^2=9．388,P〈0．05）;血浆EB病毒DNA检出阳性16例,阳性率为42．1％,与EB病毒衣壳抗原IgM比较,差异无统计学意义（χ^2=2．05,P〉0．05）;PBMC与血浆中EB病毒DNA比较,差异有统计学意义（χ^2=16．05,P〈0．05）。起病后1个月,血浆EB病毒DNA阳性2例、PBMC中EB病毒DNA阳性17例;起病后3、6、9个月血浆EB病毒DNA均为阴性,而PBMC中EB病毒DNA分别检出6例、4例、3例阳性。结论EB病毒感染初期,检测外周血单个核细胞EB病毒DNA,可作为传染性单核细胞增多症早期、快速、敏感的诊断方法;EB病毒可长期存在于单个核细胞中,荧光定量聚合酶链反应方法检测PBMC中EB病毒DNA亦可作为判断疗效及监测病情的一种有效手段。EB病毒感染患者表现出多系统损伤可能与PBMC中EB病毒感染相关。     

Clinical indications and diagnostic techniques of human herpesvirus-6 (HHV-6) infection.

The sixth member of the human herpesvirus family, HHV-6, causes early childhood infection with subsequent latency and antibody prevalence of about 60-80%. Active infection is related to a number of acute and chronic diseases such as exanthem subitum, certain cases of infectious mononucleosis and other immunoproliferative syndromes, autoimmune disorders and so-called postinfectious chronic fatigue syndrome. The clinical diagnosis of HHV-6 associated diseases requires detailed clinical differential diagnostic procedures and meticulous serological testing with exclusion of other herpesvirus infections or cross-reactivity between such infections. Diagnostic efforts, however, are warranted by certain indications for therapeutic intervention. The current review summarizes indications, techniques and limitations for the serological diagnosis of HHV-6 infection.     

Isolation of human herpesvirus-6 (HHV-6) from patients with collagen vascular diseases.

The prevalence and activity of human herpesvirus-6 in patients with collagen vascular diseases (CVD) was determined. One hundred and fifty patients with CVD (56 with systemic lupus erythematosus-SLE, 92 with rheumatoid arthritis-RA, 1 with Sharp's syndrome and 1 with atypical polyclonal lymphoproliferation-APL and rheumatoid features) were screened serologically (IFA and ELISA) for antibodies against human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Virus isolation was attempted from peripheral blood lymphocytes (PBL) of 25 persons with various disorders. PBL were grown in tissue culture and tested with standard HHV-6-positive antisera for viral antigen expression. Supernatants of the patient's lymphocyte cultures were used to infect HSB2 cells, and virus infection in these cells was proven by IFA, in situ hybridization and by electron microscopy. Fifty-five percent of the SLE patients, 6.5% of the RA patients and both patients with Sharp's syndrome or with APL had antibody titers indicative of active HHV-6 infection. Virus cultures were positive in 9 of the 25 attempts with establishment of stable virus lines. These patients were 5 with SLE or UCVD, and one each with RA, CFS, APL as well as one healthy control. Reactivated and chronic active HHV-6 infections are frequent in SLE like EBV in RA. The role of these viruses in the pathogenesis of the diseases or in their reactivation still needs further investigation.     

传染性单核细胞增多症的免疫相关性分析

目的探讨传染性单核细胞增多症（IM）患儿T细胞亚群的变化和意义。方法检测32例急性期IM患儿的T细胞亚群CD4＋、CD8＋,及CD4＋／CD8＋的比值。结果急性期IM患儿的CD8＋较儿童高（P〈0.01）,CD4--较健康儿童低（P〈0．01）。急性期IM患儿的CD4＋、CD8＋,及CD4＋／CD8＋的比值与异型淋巴细胞的比例及病程的发热时间之间无相关性。结论急性期IM患儿的CD8＋明显增高,表明细胞毒作用在急性期IM中占主要作用。     

Neurological disease in patients with human immunodeficiency virus infection.

We followed prospectively all patients with HIV infection admitted to the infectious diseases ward at Auckland Hospital over a seven month period. Neurological manifestations of HIV infection were the primary reason for admission in 18 of the 55 patients (33%). Diagnoses were usually presumptive, based on history, clinical findings, radiological appearances and response to empirical therapy. Eight patients had cerebral toxoplasmosis, three primary cerebral lymphoma, two cytomegalovirus retinitis, two HIV neuropathy, one cryptococcal meningitis, one HIV encephalopathy, and one HIV meningitis. Another patient with HIV infection was admitted to the neurology ward at Auckland Hospital with HIV myelopathy during the same seven month period. The median survival of the patients treated for presumptive toxoplasmosis was 7.5 months. Only two patients had not developed AIDS, one having HIV meningitis and the other HIV myelopathy, and in both, symptoms resolved spontaneously with no relapse at one year follow up. The spectrum of neurological manifestations of HIV infection is wide. Investigations to determine the most likely diagnosis are indicated and specific therapy may lead to both excellent palliation and prolonged survival.     

Transformation of human colostrum lymphocytes with Epstein-Barr virus.

Lymphocytes from human colostrum were transformed with EB virus to obtain immunoglobulin secreting cells. Equal proportions of IgG, IgA and IgM were detected in wells containing transformed colostrum cells. Pretreatment of colostrum cells with BCGF prior to EB virus infection reduced the transformation slightly. We discussed the possibility of establishing cell lines that produced human monoclonal antibody using colostrum cells.     

Hemorheological disorders in Epstein-Barr virus mononucleosis in children and methods of their correction

The results of observations in a group of 80 young patients aged 1-14 years with diagnosis of primary Epstein-Barr virus (EBV) infection are presented. Hemorheological disorders arising from the EBV mononucleosis were identified. The results of using reamberin in the infusion therapy for the correction of hemorheological disorders have been analyzed. It is established that reamberine infusion reduces the plasma viscosity and blood viscosity, rapidly improves the condition of children, and restores hemodynamic indices. The use of reamberine helped to reduce the duration of hospital treatment for patients with severe EBV mononucleosis.     

GB virus-C infection in patients infected with the human immunodeficiency virus.

Hepatitis virus infections are frequent in patients suffering from HIV infection due to similar transmission routes of these viruses. In addition, hepatitis virus infections lead to impaired survival in HIV positive patients. The recently discovered flavivirus GB virus C (alias Hepatitis G Virus) was initially believed to be another hepatitis virus. While there is still some minor discussion whether GB virus C (GBV-C) plays a role in fulminant hepatic failure, there is no evidence that this virus is responsible for chronic liver disease. Thus this 'orphan virus' still seeks its disease. In this review we concentrate on the published data concerning the co-infection of GBV-C and HIV. By summarizing the studies available, we show evidence for a beneficial influence of GBV-C on HIV infection. Many studies demonstrated a high prevalence of GBV-C infection in HIV positive patients due to its parenteral and sexual transmission. However, in contrast to the expectations, GBV-C does not aggravate the course of patients suffering from HIV infection. Even though not uniformly found, one often sees higher CD4 counts in patients with ongoing GBV-C viral replication. Likewise, a lower viral load appears to be accompanied by the presence of GBV-C RNA in the serum. In addition, longitudinal studies indicate that GBV-C infection slows down the progression to AIDS and eventually to death. GBV-C probably influences HIV infection associated disease by either directly inhibiting HIV replication or enhancing the immune competence to cope with HIV. Still the definitive mechanism how GBV-C could inhibit the progression to AIDS and eventually death needs to be identified.     

Active human herpesvirus-6 (HHV-6) infection associated with Kikuchi-Fujimoto disease and systemic lupus erythematosus (SLE).

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) is a well defined disorder primarily affecting young adults. The cause of this disease is still unknown. The authors report a case of a 37-yar old woman with Kikuchi-Fujimoto disease and systemic lupus erythematosus (SLE). Serologic testing for HHV-6 antibodies revealed an active infection. An excised cervical lymph node contained HHV-6 genome demonstrated by using in situ hybridization. Active HHV-6 infection should be considered in Kikuchi-Fujimoto disease.     

传染性单核细胞增多症患儿EBV-DNA检测及其意义

目的 探讨应用PCR技术检测EB病毒DNA(EBV-DNA)的临床应用价值.方法 应用PCR和荧光检测技术检测外周血EBV-DNA,对100例阳性病例的临床特点进行回顾性分析.结果:病例年龄1个月至12岁,中位年龄3岁,＜3岁65例,3～7岁25例,＞7岁10例;传染性单核细胞增多症(IM)组EBV-DNA的阳性率为84.0%(84/100),对照组阳性率为5.0%(2/40),差异有统计学意义(P＜0.01);IM患儿早期EBV的含量[(75.52±175.11)×103 copies/ml],明显高于恢复期EBV的含量[(0.67±2.27)×103 copies/ml](P＜0.01).结论 PCR法检测EBV-DNA时间短,准确性好,灵敏度高,在EB病毒感染相关疾病诊断中有一定价值.     

匹多莫德对传染性单核细胞增多症患儿T淋巴细胞亚群的影响

目的观察匹多莫德对EB病毒(EBV)相关性传染性单核细胞增多症患儿临床疗效及T淋巴细胞亚群的动态影响。方法选择2010年07月至2013年12月期间在本院接受治疗的确诊为EBV相关性传染性单核细胞增多症患儿164例,随机分为治疗组和对照组(均n=82)。对照组患儿给予对症治疗和阿昔洛韦(250 mg·m-2,iv gtt,q8h),治疗组在对照组治疗基础上加服匹多莫德(5 mg·kg-1,po,bid)。观察治疗后临床主要症状消退时间、平均住院时间,以及治疗前后实验室检测指标、T淋巴细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+等变化情况。结果治疗组发热、淋巴结肿大、异型淋巴细胞异常、咽部疼痛、肝功能异常等症状消退时间、平均住院时间较对照组显著缩短(P<0.05),临床疗效显著增高(P<0.05);咽拭子阳性率、抗EBV-CA-Ig M阳性率、抗EBV-CA-Ig G阳性率较对照组显著降低(P<0.05),抗EBV-NA-Ig G阳性率较对照组显著增高(P<0.05),治疗后第2周至第4个月CD3+较对照组显著降低(P<0.05),CD4+、CD4+/CD8+较对照组显著增高(P<0.05)。结论匹多莫德能有效改善EB病毒相关性传染性单核细胞增多症患儿的临床症状,纠正T淋巴细胞亚群失衡,缩短病程,提高临床疗效。     

Death from massive hepatic necrosis in infectious mononucleosis.

A case is reported of a 19-year-old youth who developed infectious mononucleosis and died 17 days after the onset of the illness. At autopsy massive hepatic necrosis was found, associated with enlargement of the liver.