Tula Virus as Causative Agent of Hantavirus Disease in Immunocompetent Person,Germany

We report molecular evidence of Tula virus infection in an immunocompetent patient from Germany who had typical signs of hantavirus disease. Accumulating evidence indicates that Tula virus infection, although often considered nonpathogenic, represents a threat to human health.     

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.     

深圳市肾综合征出血热自然疫源地调查

目的了解深圳市肾综合征出血热(HFRS)疫源地的现状,为制定防治策略提供依据。方法在我市所辖4个区设25个点采用笼日法布笼捕鼠,调查鼠类种群构成;间接免疫荧光法检验鼠血清汉坦病毒(HV)抗体;直接免疫荧光法检验鼠肺抗原。结果共捕获鼠形动物472只,捕获率为8.25%,隶属于2目2科3属4种,4种鼠形动物中,除板齿鼠外,其余3种均发现携带HV或感染,带毒鼠全部为成鼠。褐家鼠占捕获鼠形动物的87.50%,为本市优势鼠种,其HV感染率和带毒率分别为18.20%和10.97%,臭鼩鼱占4.45%,HV感染率和带毒率均为11.76%,黄胸鼠占8.05%,HV感染率和带毒率均为2.94%。鼠血清平均HV感染率为16.78%,鼠肺平均带毒率为10.38%,平均带病毒指数为0.09。福田区鼠HV感染率、带毒率最高,分别为32.41%和20.69%,带毒指数达0.14。不同生境中旧居民区、菜市场及餐饮类场所鼠带毒指数较高,分别为0.13、0.11、0.11。结论深圳市广泛存在家鼠型HFRS疫源地,呈增强趋势,主要宿主动物为褐家鼠、臭鼩鼱和黄胸鼠。     

Recent Evidence of Hantavirus Circulation in the American Tropic

Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region.     

Hantavirus disease in Germany due to infection with Dobrava-Belgrade virus genotype Kurkino

Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.     

Hantavirus and Tuberculosis Co-infection in an Indian Child

Hantaviruses are a group of antigenically distinct viruses carried out in rodents and insectivores. Humans are accidental hosts and get infected by aerosols generated from contaminated urine, faeces and saliva of infected rodents. Hantaviruses are identified as aetiological agents of two human diseases, haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Hantavirus causing pulmonary renal disease has rarely been reported in children in India. Hantavirus infection is uncommon under the age of 12 years. We report a 9-year-old girl from Mumbai, India with fever, bilateral pleural effusion, thrombocytopaenia, haemoconcentration and oliguria due to hantavirus infection. She also had associated tuberculosis.     

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B‐cell subsets circulating in Andes‐virus‐infected patients. A notable potent plasmablast (PB) response that increased 100‐fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3^neg CD19^low CD20^neg CD38^hi CD27^hi CD138^+/− IgA^+/− surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the ‘immunoblast‐like’ cells that have been previously described during blood cytology examinations of hantavirus‐infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus‐specific but we also observed a significant increase of reactivity against virus‐unrelated antigens, which suggests a possible bystander effect by polyclonal B‐cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker.     

肾综合征出血热发病机制的研究进展

肾综合征出血热(hemorrhagic fever with renal syndrome, HFRS)是由汉坦病毒感染引起的以发热、休克、出血和肾脏损害为主要特征的急性自然疫源性疾病。汉坦病毒主要感染人血管内皮细胞,引起小血管和毛细血管广泛损伤。血管通透性增加是HFRS临床表现的病理基础。国内外学者尽管在汉坦病毒致病机制方面开展了诸多研究,如病毒诱导的免疫病理反应、宿主遗传与细胞凋亡、血小板减少与功能障碍、血管内皮损伤等,但HFRS发病机制仍未完全阐明,也无特效治疗药物,深入探讨汉坦病毒致病的分子机制,寻找有效治疗药物仍是汉坦病毒/HFRS领域的研究热点。本文结合近年来国内外相关研究,阐述HFRS发病机制的研究进展。     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.