Severe pulmonary involvement in a case attributed to domestically acquired Seoul hantavirus in the United States

Hantavirus is known to cause 2 distinct clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus is an Old World hantavirus known to cause HFRS. We report a case attributed to domestically acquired Seoul hantavirus with prominent pulmonary involvement and a fatal outcome.     

Using geographic information system-based ecologic niche models to forecast the risk of hantavirus infection in Shandong Province, China

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts.     

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%–40% for HPS. Puumala virus (PUUV) is the most common HFRS‐causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell‐mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.     

2017-2020年湖北省荆州市肾综合征出血热宿主动物监测分析北大核心CSCD

目的总结荆州市2017-2020年肾综合征出血热(HFRS)宿主动物监测结果,为该市HFRS科学防控提供依据。方法在全市8个县(市、区)开展HFRS宿主动物监测。在春季(4-5月)和秋季(9—10月)采用夹夜法分别于室内、野外布放鼠夹。室内及野外选取荆州市常见生境。对捕获鼠进行鉴定,无菌取鉴定鼠肺,利用实时荧光定量PCR(RT-PCR)检测鼠肺汉坦病毒并分型。结果 2017-2020年荆州市平均鼠密度4.83%(1 106/22 910),鼠汉坦病毒阳性率9.83%(58/590)。鼠密度居前3位的地区分别为江陵县(9.61%)、沙市区(6.44%)和石首市(4.92%)。鼠汉坦病毒阳性率由高到低依次为沙市区(17.31%,27/156)、江陵县(8.51%,16/188)、监利县(8.42%,8/95)和洪湖市(7.29%,7/96),其它地区捕获鼠未检出汉坦病毒。春季鼠密度为5.47%(578/10 566)。其中室内生境鼠密度6.15%(146/2 374),鼠汉坦病毒阳性率1.89%(1/53),阳性鼠为厨房捕获小家鼠;野外生境鼠密度5.27%(432/8 192),鼠汉坦病毒阳性率11.76%(16/136),阳性鼠以小麦田和虾稻田捕获黑线姬鼠、褐家鼠为主。秋季鼠密度为4.28%(528/12 344)。其中室内生境鼠密度6.06%(198/3 269),鼠汉坦病毒阳性率0.78%(1/129),阳性鼠为杂物间捕获黄胸鼠;野外生境鼠密度3.64%(330/9 075),鼠汉坦病毒阳性率14.71%(40/272),阳性鼠以蔬菜田、虾田、虾稻田、稻田捕获黑线姬鼠和褐家鼠为主。捕获黑线姬鼠均携带HNTV型汉坦病毒;褐家鼠、小家鼠、黄胸鼠携带SEOV型汉坦病毒。结论荆州市HFRS宿主动物以野外捕获黑线姬鼠、褐家鼠为主,分别携带HNTV型、SEOV型汉坦病毒。江陵县、沙市区鼠密度及鼠汉坦病毒阳性率均较高。     

汉坦病毒激发人胃上皮细胞病变和凋亡

目的证实人胃粘膜上皮细胞是否为汉坦病毒属(HV)汉滩病毒型(HTN)和汉城病毒型(SEO)病毒的靶细胞,病毒对其是否有致细胞病变效应(CPE)和促凋亡作用。方法建立人胃上皮细胞(HGEC)离体培养;用HVN8、76118、Z37、Seoul8039株感染HGEC,观察细胞CPE,用直接免疫荧光法(IFA)检测病毒感染细胞和感染灶;用AnnexinV FITCkit观察HV的致HGEC凋亡和坏死作用。结果HTNV和SEOV可以感染离体培养的HGEC,形成感染灶并出现CPE;与模拟感染细胞相比,N8、76118、Z37、Seoul8039株感染的HGEC凋亡和坏死细胞比例明显增高,HTNV较SEOV促凋亡和坏死作用更强。结论HGEC可作为HTNV和SEOV感染的靶细胞,致CPE并促进细胞凋亡和坏死,在急性肾综合征出血热病人胃粘膜损害机制中起重要作用。     

Hantavirus infection prevalence in wild rodents and human anti-hantavirus serological profiles from different geographic areas of South Brazil

Abstract. Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses revealed that hantaviruses from rodent samples cluster with Araucária (Juquitiba-like) or Jaborá hantavirus genotypes. The Jaborá strain was identified in Akodon serrensis and Akodon montensis, whereas the Araucária strain was detected in Oligoryzomys nigripes, Oxymycterus judex, A. montensis, and Akodon paranaensis, with the latter species being identified for the first time as a natural host. These findings expose the complex relationships between virus and reservoirs in Brazil, which could have an impact on hantavirus transmission dynamics in nature and human epidemiology.     

Dynamics of hantavirus infection in Peromyscus leucopus of central Pennsylvania

Hantaviruses are distributed throughout the United States and are the etiologic agents for hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. Hantavirus genotypes and epidemiologic patterns vary spatially across the United States. While several longitudinal studies have been performed in the western United States, little is known about the virus in the eastern United States. We undertook a longitudinal study of hantaviruses in the primary rodent reservoir host in central Pennsylvania, Peromyscus leucopus. Prevalence of hantavirus antibodies varied both by year and site, but was not correlated with host abundance. Males were significantly more likely to have antibodies to a hantavirus than females, and both antibody sero-conversion and antibody prevalence increased with mass class (indicator for age). Our findings suggest that one or more hantaviruses are present and circulating among P. leucopus of central Pennsylvania, and understanding the dynamics in this region could help prevent zoonotic transmission to humans. Our aim was to describe the differences in epizootiology of hantavirus infection in rodents from various geographical locations to enable improved analysis of the risk of rodent-to-human transmission and obtain insights that may indicate improved means of disease intervention.     

The complex ecology of hantavirus in Paraguay

Following an outbreak of hantavirus pulmonary syndrome (HPS) in the Paraguayan Chaco in 1995, Calomys laucha was identified as the rodent host for the hantavirus associated with these cases. To explore the possibility of additional hantaviruses in Paraguay, we collected 636 mammals from 10 of the 17 departments. Plasma from 27 animals in Alto Paraguay and Boquer6n in the Chaco and Neembucú and Itapúa in the eastern region had antibody to Andes virus antigens. Of these 27, five individuals (among four species) were positive for hantavirus RNA. Sera were collected from indigenous people in eastern Paraguay to ascertain whether persons were being infected with hantavirus outside of the Chaco. Seventeen percent were antibody-positive. These results suggest that several different hantaviruses are co-circulating in Paraguay, and that HPS cases occurring in eastern Paraguay may result from exposure to hantaviruses that are distinct from those in the Chaco.     

Hantavirus ecology in rodent populations in three protected areas of Argentina

In this study, we identified hantavirus genotypes and their reservoirs and evaluated the spatial and temporal distribution of the virus in rodent population in three protected areas of Argentina over 3 years (2007-2010). A total of 837 rodents were captured with an effort of 22 117 trap-nights. We detected the genotype Lechiguanas in Oligoryzomys nigripes and O. flavescens and Pergamino in Akodon azarae. There was no correlation between seroprevalence and trap success of the host. The proportion of seropositive males was significantly higher than the proportion of seropositive females. The total length of seropositives was higher than that of seronegatives in each host species. Seropositive individuals were observed in warm months and not in cold months, which suggests an infection cycle. This investigation confirms that protected areas of central east Argentina are places with a variety of sylvan rodents species associated with different hantavirus genotypes where reservoirs are numerically dominant. Although there was more than one known reservoir of hantavirus, only one species had antibodies in each area. This can be explained because the transmission of the virus does need not only the presence of a rodent species but also a threshold density. Longevity of even a small proportion of the host population in cold months may provide a trans-seasonal mechanism for virus persistence. The seroprevalence detected was higher than the one found before in rodent populations of Argentina, and this explains the appearance of human cases in two of these three areas.     

Mechanisms of shock in hantavirus pulmonary syndrome

PURPOSE OF REVIEW: Despite abundant literature on hantavirus, few reports have focused on the shock in hantavirus pulmonary syndrome. This review approaches recent advances that allow us to better understand the pathogenesis of hantavirus pulmonary syndrome shock. RECENT FINDINGS: Hantavirus pulmonary syndrome has been studied in a hamster model that mimics human shock and respiratory failure. In-vitro experiments show that pathogenic hantaviruses are able to inhibit antiviral responses, and that cytotoxicity of hantavirus-specific T cells enhances the permeability of infected endothelial cells. The idea that the primary cardiac lesion of shock is mostly functional has been shaken by the report of a typical myocarditis in hearts from human hantavirus pulmonary syndrome fatal cases. The involvement of regulatory T cells on hantavirus persistence in its rodent reservoir suggests that these cells could protect from severe hantavirus pulmonary syndrome and shock. SUMMARY: Hantavirus pulmonary syndrome shock is probably related to an exacerbated immune response of CD8+ T cells producing cytotoxicity on infected endothelial cells, presence of myocarditis and myocardial depression induced by nitric oxide. The virulence elements in G1 glycoprotein could also contribute to shock. Active suppression of immune T regulatory cells is probably involved in hantavirus pulmonary syndrome pathogenesis. These are all new aspects of hantavirus pulmonary syndrome pathogenesis that stimulate further studies to elucidate mechanisms of shock and to develop effective treatment strategies.     

肾综合征出血热抗病毒治疗及疫苗研发进展

肾综合征出血热(hemorrhagic fever with renal syndrome, HFRS)是由汉坦病毒感染引起的一种自然疫源性疾病,在世界范围内广泛流行,我国一直是流行高发区,患者占所有HFRS患者一半以上,其主要临床特征为发热、出血、低血压休克和肾脏损害,严重危害人类健康。尽管抗病毒治疗和疫苗免疫接种可以防治汉坦病毒感染,但目前尚无特效抗病毒药物。近年来,随着医学科技进步,汉坦病毒的抗病毒治疗和疫苗研发有了新的进展。本文基于近年体内外研究及临床试验结果,对HFRS抗病毒治疗和疫苗研发进展作一综述。     

Hantavirus pulmonary syndrome in northwestern Argentina: circulation of Laguna Negra virus associated with Calomys callosus

The purpose of this study was to characterize the hantaviruses circulating in northwestern Argentina. Human and rodent studies were conducted in Yuto, where most cases of hantavirus pulmonary syndrome (HPS) occur. Partial virus genome sequences were obtained from the blood of 12 cases of HPS, and from the lungs of 4 Calomys callosus and 1 Akodon simulator. Phylogenetic analysis showed that three genotypes associated with HPS circulate in Yuto. Laguna Negra (LN) virus, associated with C. laucha in Paraguay, was identified for the first time in Argentina; it was recovered from human cases and from C. callosus samples. The high sequence identity between human and rodent samples implicated C. callosus as the primary rodent reservoir for LN virus in Yuto. The genetic analysis showed that the Argentinian LN virus variant differed 16.8% at the nucleotide level and 2.9% at the protein level relative to the Paraguayan LN virus. The other two hantavirus lineages identified were the previously known Bermejo and Oran viruses.     

Hantavirus pulmonary syndrome: at the crossroads

The initial identification in 1993 of hantavirus pulmonary syndrome as a novel, highly fatal respiratory illness among American Indians in the southwestern USA in 1993 opened the window to the recognition of a well-established pan-American zoonosis with a myriad of causative viruses and rodent vectors, although all are New World hantaviruses among New World sigmodontine rodents. The clinical spectrum of symptoms has also been expanded to include asymptomatic infection through to fulminant hemorrhagic fever. Although the use of ribavirin, an antiviral drug, was disappointing in an early, open-labeled trial, early detection and supportive care is much better refined. However, much work remains in probing the pathogenesis of this syndrome to help define and explore therapeutic options and the mechanism of person-to-person transmission with Andes virus, one of the viruses that cause hantavirus pulmonary syndrome. Current remote sensing efforts and longitudinal ecologic investigations need to be expanded in order to focus prevention efforts better.     

High prevalence of hantavirus infection in a group of Chinese patients with acute hepatitis of unknown aetiology

In southwestern China, small but substantial numbers of patients with acute hepatitis were found without known hepatropic viral infections (hepatitisA, B, C, D or E, cytomegalovirus, Epstein–Barr virus) and were receiving no hepatotoxic drugs. Prevalence of antibodies, both neutralizing and specific immunoglobulin (Ig)M and IgG, to Hantaan virus were evaluated in a cohort of 136 such patients: 83 were of unknown aetiology, 53 had known viral hepatitis and 59 healthy subjects acted as controls. The results showed that the incidence of neutralizing antibody to Hantaan virus in acute hepatitis patients with non-hepatitisA–E virus infections (13 of 83) was significantly higher than in those with A–E infections (0 of 53, P <0.01). Furthermore, the incidence of specific IgM antibody to Hantaan virus in acute hepatitis patients with non-hepatitisA–E virus infections (6 of 83) was significantly higher than in those with A–E infections (0 of 53, P <0.05) and in healthy subjects (0 of 59, P <0.05). These findings suggest that Hantaan virus may be an important agent, contributing, at least in southwestern China, to a significant number of the cases of acute hepatitis of unknown aetiology. This hantavirus infection resulted in an acute hepatitis, differing from the typical diseases: haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS).     

Geographical distribution of hantaviruses in Thailand and potential human health significance of Thailand virus

Phylogenetic investigations, sequence comparisons, and antigenic cross-reactivity studies confirmed the classification of Thailand virus (THAIV) as a distinct hantavirus species. The examination of sera from 402 rodents trapped in 19 provinces of Thailand revealed that five greater bandicoot rats (Bandicota indica) and one lesser bandicoot rat (B. savilei) from four provinces were focus reduction neutralization test (FRNT) antibody-positive for THAIV. One of 260 patients from Surin province in Thailand (initially suspected of having contracted leptospirosis, but found to be negative) showed symptoms compatible with hemorrhagic fever with renal syndrome (HFRS). The serum of this patient showed high titers of hantavirus-reactive IgM and IgG. FRNT investigations confirmed virus-neutralizing antibodies against THAIV. These observations suggest that THAIV or THAI-like viruses occur throughout Indochina and may represent an additional causative agent of HFRS.     

Epidemiological investigations following an outbreak of hemorrhagic fever with renal syndrome in Greece

Epidemiological investigations were conducted following an outbreak of hemorrhagic fever with renal syndrome (HFRS) which occurred in the state of Epirus, northwestern Greece, in July and August 1983. A total of 8 patients were hospitalized during the outbreak; 3 were severely ill and 1 died. A serosurvey made in May 1984 sampled 184 of the approximately 400 residents of the village of Tsepelovo, where 4 patients resided, and found 12 (6.5%) persons, including convalescent sera from 4 patients, with antihantaviral antibody by immunofluorescent antibody (IFA) tests. Small mammal collections found house rats common in the village, but none exhibited anti-hantaviral antibody. Collections in nearby fields and mountains found Apodemus flavicollis rodents common, and 2 (6%) of 33 captured had high IFA anti-hantavirus antibody. Virus isolation attempts from rodent tissues were unsuccessful. Testing of convalescent patients' sera by IFA and plaque reduction neutralization tests indicated that the etiological agent was neither Puumala virus nor Seoul virus, but appears to be a strain of Hantaan virus or perhaps a new virus. The rodent host of this virus may be A. flavicollis, and the distribution of this species corresponds with previously reported cases of severe HFRS described elsewhere in central Europe.