病毒性出血热新进展

病毒性出血热（viral hemorrhagie fever，VHF）是由不同类型病毒所引起，以发热、出血、休克及高病死率为特征的一组自然疫源性疾病。在当前全球紧锣密鼓反恐怖声中，生物恐怖引起了人们的极大关注，包括埃博拉出血热（Ebola hemorrhagic fever，EBHF）在内的一些易于传播的强致病性出血热病毒被利用于生物恐怖的可能性受到了国内外卫生界的高度重视。本文简单介绍VHF的新进展，着重中国没有、易于输入传播及可能被利用于生物恐怖的一些出血热病毒，包括安全防控策略问题。     

病毒性出血热研究进展

病毒性出血热（viral hemorrhagic fever,VHF）是由不同类型病毒引起,以发热、出血、休克及高病死率为特征的一组自然疫源性疾病（其临床特征见表1）。特定的脊椎动物或昆虫是这些病毒的自然宿主。     

An animal model for the tickborne flavivirus--Omsk hemorrhagic fever virus

The tickborne encephalitis (TBE) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include Omsk hemorrhagic fever virus (OHFV), a virus that is genetically related to other TBE serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. The objective of this study was to examine a potential small-animal model for OHFV and to compare the pathology of infection with that of the neurotropic tickborne flavivirus, Powassan virus (POWV). POWV-infected BALB/c mice demonstrated typical arboviral encephalitis, characterized by paresis and paralysis before death, and viral infection of the cerebrum, characterized by inflammation and necrosis. In contrast, lethal OHFV infection did not cause paralysis or significant infection of the cerebrum but showed marked involvement of the cerebellum. Distinct pathological results in the spleens suggest that the immune response in OHFV-infected mice is different from that in POWV-infected mice. This study demonstrates a clear pathological difference between OHFV-infected mice and POWV-infected mice and supports the use of the BALB/c mouse as a disease model for OHFV.     

Inhibition of Crimean-Congo hemorrhagic fever viral infectivity yields in vitro by ribavirin

Ribavirin was evaluated as a potential therapeutic for Crimean-Congo hemorrhagic fever (CCHF). Viral yields for strains of CCHF virus from Europe, Asia, and Africa in African green monkey kidney (Vero) cells were markedly reduced by this drug. Some CCHF viral strains appeared more sensitive than others, but in general, ribavirin doses as low as 5 micrograms/ml caused a transient reduction of viral yields. A further reduction in viral yields was induced by a dose of 25 micrograms/ml, and evidence of viral replication was not demonstrated in cells treated with 50 or 250 micrograms/ml. In contrast, a dose of ribavirin at least 9 times greater was required to induce a comparable inhibitory effect on the yields of Rift Valley fever virus, for which the drug has been shown to inhibit replication in monkeys and rodents.     

蓬莱市流行性出血热多脏器损害临床分析

目的分析蓬莱市流行性出血热（epidemichemorrhagicfever，EHF）多脏器损害的临床特点，为临床诊断及治疗提供依据。方法对蓬莱市人民医院1995--2006年收治的318例EHF患者的临床资料进行回顾性分析。结果302例患者合并多脏器损害，其中94．97％患者合并肝功能异常，63．84％患者肝脏声像图异常；89．31％患者合并肾功能异常，84．59％患者肾脏声像图异常；90．88％患者合并血液系统损害；35．85％患者肌酸激酶升高，77．36％患者心电图异常；12．26％患者糖代谢异常。病情越重，受累器官越多，病死率越高。EHF多脏器损害随病情好转逐渐恢复正常。结论EHF多脏器损害主要因病毒的直接作用，以及其所诱导的免疫反应损害所致。其变化与病程一致，是可逆的。     

模式识别受体在病毒性出血热中作用的研究进展北大核心CSCD

病毒性出血热(viral hemorrhagic fevers,VHFs)是一类以发热和出血为主要临床症状的急性传染病,主要由沙粒病毒科、丝状病毒科、布尼亚病毒目、黄病毒科和披膜病毒科的部分包膜RNA病毒引起。这类疾病具有许多共同的临床表现,包括发热、乏力、肌肉疼痛等,重症患者可进一步发展为低血压休克、出血和多器官功能障碍,甚至危及生命。多种病毒性出血热属人兽共患病,但在动物宿主多表现为无症状感染,可形成自然疫源地对人类活动构成威胁。固有免疫在机体识别和抵御病毒感染的过程中十分重要,其中模式识别受体又是固有免疫反应的起始环节。因此,深入研究模式识别受体在病毒性出血热感染发病中的作用,对深入探讨其发病机制、寻找治疗靶点及研发药物、疫苗均有重要意义。本文综述了近年来国内外模式识别受体在病毒性出血热中作用的研究进展,总结了研究发展趋势,可供后续研究工作参考。     

Benznidazole prevents endothelial damage in an experimental model of Chagas disease

ObjectivesTo evaluate the effect of benznidazole on endothelial activation in a murine model of Chagas disease.MethodsA low (30 mg/kg/day) and a high (100 mg/kg/day) dose of benznidazole were administered to mice infected with Trypanosoma cruzi during the early phases of the infection. The effects of the treatments were assessed at 24 and 90 days postinfection by evaluating the parasitaemia, mortality, histopathological changes and expression of ICAM in the cardiac tissue. The blood levels of thromboxane A₂, soluble ICAM and E-selectin were also measured. T. cruzi clearance was assessed by the detection of parasite DNA in the heart tissue of infected mice.ResultsBenznidazole decreased the cardiac damage induced by the parasite, and amastigote nests disappeared at 90 days postinfection. Both doses cleared the parasite from the cardiac tissue at 24 and 90 days postinfection. In addition, benznidazole decreased the thromboxane levels and normalized the plasma sICAM and sE-selectin levels by 90 days postinfection.ConclusionsEarly administration of benznidazole at a dose as low as 30 mg/kg eradicates T. cruzi from cardiac tissue. Additionally, benznidazole prevents cardiac damage and modulates endothelial activation as part of its antichagasic activity.     

Acute kidney injury in patients with hemorrhagic fever with renal syndrome caused by Hantaan virus: comparative evaluation by RIFLE and AKIN criteria

Acute kidney injury (AKI) is one of the most prominent characteristics of hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus. The present study evaluated the incidence and severity of AKI classified by both the RIFLE and AKIN criteria in 120 HFRS patients at 48 h and 1 week of the patient admission. The agreements between RIFLE and AKIN and RIFLE and AKIN defined by serum creatinine (AKINc and RIFLEc) were examined by Kappa statistics. AKI occurred in 79.2% and 82.5% at 48 h and in 84.2% and 89.2% at 1 week of admission by RIFLE and AKIN criteria, respectively. RIFLE and AKIN showed very good agreement in classifying AKI at 48 h and 1 week of admission (κ?>?0.900). RIFLE and RIFLEc and AKIN and AKINc at 48 h and 1 week of admission had almost perfect agreement (κ?>?0.900). The classifications of RIFLE and RIFLEc and AKIN and AKINc at 48 h and 1 week were in good agreement (κ?>?0.650). AKI classifications by RIFLE and AKIN were associated with mortality, occurrence of complications, and length of hospital stay. We conclude that AKI occurs in nearly 90% of HFRS patients during the disease course. RIFLE and AKIN classify AKI in HFRS with similar sensitivity. RIFLEc and AKINc may be used as alternatives of standard RIFLE and AKIN in the settings of general wards. The AKI classifications defined at 48 h of admission have predictive value for HFRS disease progression and severity.     

Antibodies against dengue viral proteins in primary and secondary dengue hemorrhagic fever

Antibodies against dengue viral proteins were demonstrated in sera from dengue-infected patients by polyacrylamide gel electrophoresis, Western blotting, and enzyme immunoassay. Primary dengue cases showed low titers of IgG class antibodies to envelope (E) proteins and two non-structural proteins, NS3 and NS5, in sera collected during the convalescent phase. Secondary dengue- infected patients always demonstrated IgG antibodies to E proteins in sera collected during the acute phase, and high titers of IgG antibodies to many other proteins, including NS1, NS3, NS5, and C proteins in sera collected during the convalescent phase. Appearance of antibodies to E, NS3, and NS5 could be detected within five days after the onset of fever. These three dengue viral proteins and their corresponding antibodies may be involved in the immunopathologic mechanism underlying this disease. For diagnostic purposes, identifying the non-structural proteins such as NS3 and NS5 may be the best means for early confirmation of the disease.     

The lack of Crimean-Congo hemorrhagic fever virus antibodies in healthcare workers in an endemic region.

We aimed to detect antibodies against Crimean-Congo hemorrhagic fever virus (CCHFV) in healthcare workers (HCWs) in an endemic region. The study was conducted in a tertiary care hospital that had cared for CCHFV infected patients in the period 2002-2003. The sera from the HCWs were collected one month after the last admitted hospital case (October 2003), and sent to the Pasteur Institute, Lyon, France to be studied for CCHF IgM and IgG by ELISA. The total number of HCWs included in the study was 75; the median age was 30, 68% of the subjects were female, and 83% of the HCWs were at risk of exposure to the body fluids of patients. Only one HCW from the group without risk of exposure was CCHF IgG positive. The adherence rate to universal precautions was high. In conclusion, a lack of CCHFV transmission from patients to HCWs was observed. This result could be related to the high rate of compliance to the universal precautions, which are sufficient to protect against CCHFV infection.