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Infectious disease AND Hemorrhagic fever Hantavirus [keywords]
- Epidemiology of Hantavirus infections in humans: a comprehensive, global overview. [Journal Article]
- Crit Rev Microbiol 2014 Aug; 40(3):261-72.
Hantaviruses comprise an emerging global threat for public health, affecting about 30,000 humans annually. Infection may lead to Hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in the Europe and Asia. Humans are spillover hosts, acquiring infection primarily through the inhalation of aerosolized excreta from infected rodents and insectivores. Risk factors for infection include involvement in outdoor activities, such as rural- and forest-related activities, peridomestic rodent presence, exposure to potentially infected dust and outdoor military training; prolonged, intimate contact with infected individuals promotes transmission of Andes virus, the only Hantavirus known to be transmitted from human-to-human. The total number of Hantavirus case reports is generally on the rise, as is the number of affected countries. Knowledge of the geographical distribution, regional incidence and associated risk factors of the disease are crucial for clinicians to suspect and diagnose infected individuals early on. Climatic, ecological and environmental changes are related to fluctuations in rodent populations, and subsequently to human epidemics. Thus, prevention may be enhanced by host-reservoir control and human exposure prophylaxis interventions, which likely have led to a dramatic reduction of human cases in China over the past decades; vaccination may also play a role in the future.
- A two-tube multiplex real-time RT-PCR assay for the detection of four hemorrhagic fever viruses: severe fever with thrombocytopenia syndrome virus, Hantaan virus, Seoul virus, and dengue virus. [Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't]
- Arch Virol 2013 Sep; 158(9):1857-63.
The aim of this study was to develop and evaluate a two-tube multiplex real-time RT-PCR assay for the detection and identification of four viral hemorrhagic fever (VHF) pathogens, severe fever with thrombocytopenia syndrome virus (SFTSV), Hantaan virus (HTNV), Seoul virus (SEOV), and dengue virus (DENV), from human clinical samples. The two-tube multiplex real-time RT-PCR assay we developed has a sensitivity of 10 copies/μL for each of the targets, and the performance was linear within the range of at least 10(7) transcript copies. Moreover, we evaluated the specificity of the assay using other virus RNA as template, and found no cross-reactivity. This new assay is able to detect SFTSV, HTNV, SEOV and DENV in two reactions and brings a cost of 40 % compared to separate reactions. Evaluation of this assay with clinical serum samples from laboratory-confirmed patients and healthy donors showed 100 % clinical diagnostic sensitivity and over 99 % specificity. The assay was applied for scanning 346 clinical samples collected from patients admitted to the hospital with suspected VHF and compared with virus isolation and immunofluorescence assay (IFA). The assay indentified 59 SFTSV-, 12 HTNV-, 11 SEOV- and 9 DENV-positive samples and showed higher sensitivity. This assay thus provides a reliable and cost-effective screening tool for early clinical diagnosis of SFTSV, HTNV, SEOV and DENV in the acute phase.
- Factors driving hantavirus emergence in Europe. [Journal Article, Review]
- Curr Opin Virol 2013 Feb; 3(1):92-9.
Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe both the amplitude and the magnitude of outbreaks of HFRS have increased. The mechanisms that drive the incidences are complex and multi-factorial and only partially due to increased awareness and improved diagnostic tools. Risk determinants include reservoir ecology, virus ecology and anthropogenic factors. The dogma of one specific rodent species as primordial reservoir for a specific hantavirus is increasingly challenged. New hantaviruses have been discovered in shrews, moles and bats and increasing evidence points at host-switching events and co-circulation in multiple, sympatric reservoir species, challenging the strict rodent-virus co-evolution theory. Changing landscape attributes and climatic parameters determine fluctuations in hantavirus epidemiology, for instance through increased food availability, prolonged virus survival and decreased biodiversity.
- [Study on comprehensive monitoring of mouse and effect of hemorrhagic fever with renal syndrome vaccine in high prevalence areas of natural focus infectious disease of Zhejiang province in 1994--2010]. [English Abstract, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.]
- Zhonghua Yu Fang Yi Xue Za Zhi 2012 Oct; 46(10):908-11.
To study the comprehensive monitoring mechanism of mouse and the effect of hemorrhagic fever with renal syndrome (HFRS) vaccine in the high prevalence areas of natural focus infectious disease of Zhejiang province in 1994 - 2010.The night trapping method was used to monitor the population proportion, density and the rate of hantavirus (HV) carriers in mice in Xikou township Longyou county in August and September from 1994 to 2010. The healthy residents in Xikou township aged 16 to 60 years were recruited. The subjects were randomly selected as vaccination group and control group according to age, sex, occupational distribution (10 178 in intervention group and 16 159 in control group). Intervention group was given purified and inactivated vaccine from suckling mouse brain, while the control group received no intervention. The prevention effect was evaluated by protective rate of vaccine.The mouse population was stable in the sixteen years and the apodemus agrarius was the main type (76.5% (564/737)). The average density of mouse was 4.73% (1170/24 727). The average rate of virus carrier of mouse was 3.87% (41/1033). In 1994 - 1995, the density of mouse was 22.82% (186/815) and the rate of virus carrier was 7.0% (10/143). In 2009 - 2010, the density of mouse decreased to 2.75% (119/4330) and the rate of virus carrier was 5.5% (13/237). The average antibody positive rate of mouse from 2005 to 2010 was 4.8% (35/728) and the rate was 4.4% (6/138), 0.0% (0/113), 11.8% (16/136), 1.0% (1/104), 3.7% (4/109) and 6.3% (8/128) in each year (P < 0.01). The protective rate of HFRS vaccine was 96.2% (1 case in intervention group and 41 cases in control group).The density of mouse decreased significantly in Zhejiang province. The rate of virus carrier of mouse is stable. The vaccine is effective.
- Construction and nonclinical testing of a Puumala virus synthetic M gene-based DNA vaccine. [Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.]
- Clin Vaccine Immunol 2013 Feb; 20(2):218-26.
Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-length M segment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.
- [Characterization of S gene of a strain of hantavirus isolated from Apodemus peninsulae in Heilongjiang Province]. [English Abstract, Journal Article, Research Support, Non-U.S. Gov't]
- Bing Du Xue Bao 2012 Sep; 28(5):517-21.
In order to study the molecular characterization of the hantavirus isolated from Apodemus peninsulae in Heilongjiang Province, the S gene of a new strain NA33 was amplified, sequenced and analyzed. The results showed that the complete nucleotide sequence of the S gene of NA33 strain was composed of 1 693 nucleotides with TA-rich. The S gene contained one ORF, starting at position 37 and ending at position 1 326, encoding the N protein of 429 amino acid residues, and in line with HTN-based coding. Sequence comparison of the S genes between NA33 and reference hantavirus strains showed that NA33 was more homologous to Amur-like viruses than to the Hantaan (HTN) viruses or the other hantaviruses. Phylogenetic analysis of the amino acid sequence of N proteins showed that NA33 was clustered into the group of Amur-like viruses and was more similar to Far East Russia and Jilin strains isolated from Apodemus peninsulae. The phylogenetic tree indicated a certain degree of host-dependent characteristics and geographical aggregation characteristics of hantanviruses. Furthermore, the amino acid sequence of N protein of NA33 had the conserved amino acid sites of Amur-like viruses. In conclusion, Apodemus peninsulae carried Amur-like viruses in Heilongjiang province and was an important infectious source of hemorrhagic fever with renal syndrome (HFRS).
- Hantavirus infection: an emerging infectious disease causing acute renal failure. [Journal Article, Review]
- Kidney Int 2013 Jan; 83(1):23-7.
The function of the kidney with its highly differentiated and specialized cell types is affected by infection with several viruses. Viral infections of the kidney have a negative impact not only on patients undergoing renal transplantation and immunosuppression. Besides the increasing number of patients suffering from HIV-associated nephropathy, another group of viruses infects immunocompetent patients and induces renal failure. Hantaviruses belong nowadays to the emerging zoonoses that increase in number and geographic distribution. The viruses are distributed worldwide in endemic areas and distribution seems to expand. Together with the increase in the number of cases in the last few years, the understanding of epidemiology and pathology has deepened and some concepts had to be changed. Symptoms and mortality vary between species. The classification refers to geographical distribution: New World hantaviruses causing hantavirus cardiopulmonary syndrome (HCPS) and Old World hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). Indeed, in most HFRS cases, the kidney is mainly affected and HCPS is characterized by cardiopulmonary involvement. But the picture of strict organ tropism is changing and reports of pulmonary findings and nonrenal manifestations in infections with Old World hantaviruses are increasing. However, the overall symptoms-vascular alterations and leakage-that are responsible for organ failure are characteristic for all diseases caused by hantaviruses.
- Clinical and laboratory findings in patients with oliguric and non-oliguric hantavirus haemorrhagic fever with renal syndrome: an analysis of 128 patients. [Journal Article, Research Support, Non-U.S. Gov't]
- Clin Microbiol Infect 2013 Jul; 19(7):674-9.
Patients with haemorrhagic fever with renal syndrome (HFRS) may present without significant oliguria. We compared different initial clinical symptoms and laboratory findings in patients who developed oliguric acute renal failure (ARF) with those in patients who did not develop oliguric ARF. Overall, 128 patients with serologically confirmed HFRS were hospitalized at the University Hospital for Infectious Disease, Zagreb, Croatia between January 1999 and December 2010. Clinical signs and laboratory findings were extracted from medical charts, and were assessed for their relationship to the development of oliguric ARF. Puumala virus infection was diagnosed in 101 (79%) patients, and Dobrava-Belgrade virus infection in 27 (21%). Oliguria or anuria developed in 30% of patients. We identified the following risk factors for the development of oliguria and anuria on multivariable analysis: conjunctival hyperaemia or bleeding (relative risk (RR) 1.84, 95% CI 1.09-3.10; p 0.023), diarrhoea (RR 1.45, 95% CI 1.07-1.97; p 0.017), serum sodium of ≤133 mM (RR 2.21, 95% CI 1.34-3.64; p 0.002), and dipstick protein value of >1.5 g/L (RR 1.59, 95% CI 1.09-2.33; p 0.016), as well as hiking in the forest (RR 1.92, 95% CI 1.13-3.26; p 0.016). Our findings may help physicians in the earlier identification of patients with a more severe form of HFRS caused by Puumala and Dobrava-Belgrade viruses. Particular attention should be given to findings such as conjunctival hyperaemia or bleeding, diarrhoea, a low serum sodium level, and proteinuria.
- Dynamics of hantavirus infections in humans and animals in Wuhan city, Hubei, China. [Journal Article, Research Support, Non-U.S. Gov't]
- Infect Genet Evol 2012 Dec; 12(8):1614-21.
Hemorrhagic fever with renal syndrome (HFRS) has been a significant public problem since the first cases were reported in 1961 in Wuhan city (capital of Hubei province of China). Epidemiological surveys were carried out to better understand the dynamics of hantavirus infection in humans and animals in Wuhan. During 1961-2011, a total of 21,820 HFRS cases were registered in Wuhan. The two large epidemics had occurred during 1970-1991. They reached peaks in 1973 and 1983, respectively. There have been <10 cases since 2005. The disease occurred in the whole region including the downtown areas, but mainly in two districts. Although in 1980s and 1990s HFRS cases mainly recorded in August and winter, since 2000 the disease has mainly occurred in spring and summer. In this study, hantaviruses were identified in Apodemus mice, Rattus rats, and Mus mice by indirect immunofluorescent-assay and RT-PCR. Serological and genetic analyses showed that Hantaan virus (HTNV) and Seoul virus (SEOV) co-circulated in rodents. Phylogenetic analysis of hantaviral genome sequences revealed a novel genetic lineage of HTNV circulating in rodents in Wuhan. Another lineage of HTNV was closely related to the lineages from the provinces located in the origin and delta of Yangtze River. Remarkably, SEOV variants identified in Wuhan were more closely related to the variants found outside China. Results of the present study showed that HFRS cases in Wuhan are caused by HTNV and SEOV. Phylogenetic analysis of the hantavirus sequences revealed that a novel genetic lineage of HTNV is present in rodents in Wuhan.
- Blurred vision and myopic shift in Puumala virus infections are independent of disease severity. [Journal Article]
- Clin Microbiol Infect 2012 Oct; 18(10):E435-7.
Puumala virus infection causes epidemic nephropathia (NE), a certain type of haemorrhagic fever with renal syndrome (HFRS). Myopic shift is considered a pathognomonic sign of NE and HFRS but rates of ocular involvement vary. The aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in NE in Austria. We found that blurred vision and myopic shift are frequent in Puumala virus infections in Austria but are independent of disease severity.