Hantavirus Species Research Articles

Replication reduction neutralization test, a quantitative RT-PCR-based technique for the detection of neutralizing hantavirus antibodies

Hantaviruses, which are mainly rodent-borne viruses, cause hemorrhagic fever with renal syndrome in the Old World, and hantavirus pulmonary syndrome in the New World. A neutralization test based on quantitative RT-PCR, the replication reduction neutralization test (RRNT), was developed for efficient detection of hantavirus-neutralizing antibodies. The effectiveness of the RRNT was evaluated by examining several hantaviruses and hantavirus-specific convalescent human serum samples. All convalescent serum samples tested by RRNT caused significant decreases in hantavirus genomes with only one specific hantavirus species, which allowed a straightforward identification of the related hantavirus. The results obtained by RRNT were completely comparable with the results obtained by focus reduction neutralization test (FRNT). The RRNT approach is a reliable and rapid alternative for FRNT, hitherto considered as the gold standard for hantavirus serology.

A proposal for new criteria for the classification of hantaviruses, based on S and M segment protein sequences

Hantaviruses, members of the family Bunyaviridae, are the causative agents of hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Hantaviruses are currently demarcated into species based on the guidelines provided by the International Committee on Taxonomy of Viruses (ICTV). These guidelines however, are often ignored by the descriptors of novel hantaviruses. With this study we attempted to refine the second ICTV guideline for hantavirus species demarcation by phylogenetically analyzing all in Genbank available complete sequences derived from the S, M or L segments of hantaviruses. S and M segment amino acid sequence comparison allowed clear and unequivocal distinction between different hantavirus species, and lead us to propose additional criteria for the demarcation of hantavirus species (S segment amino acid distance >10% or M segment amino acid distance >12%) and hantavirus groups (S segment amino distance >24% or M segment amino acid distance >32%). With this study, we propose to adjust the second rule of the ICTV classification guidelines (“ a 7% difference in amino acid identity when comparing the complete S segment and M segment sequences”) to a more appropriate rule, “ a 10% difference in S segment similarity and a 12% difference in M segment similarity based on complete amino acid sequences” in accordance with the current situation in the hantavirus field.

One for all? A viral protein supplants the mRNA cap-binding complex

Modulation of the host cell's translational machinery is a crucial part of viral infection strategies. Well‐characterised mechanisms that aid viruses in manipulating translational activity include, for example, internal ribosomal entry sites, which allow viral RNA translation in the absence of some or many of the canonical host translation factors. New research shows that the nucleocapsid protein from a species of Hantavirus can replace several host cell translation factors in in vitro translation reactions, suggesting that hantaviruses may have evolved a novel strategy for modulating host cell translation in the form of a multifunctional translation factor.

Epidemiological Study of Hantavirus Infection in the Samara Region of European Russia

European Russia is a highly endemic area of hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease, caused by hantaviruses. In total, 145 small mammals of four species (Myodes glareolus, Apodemus flavicollis, A. agrarius, and A. uralensis) were trapped in the Samara region of European Russia in August 2005 and examined for the presence of hantavirus (HV). Anti-HV antibodies were found in six of 68 (8.8%) M. glareolus and in one of 19 (5.3%) A. flavicollis by indirect immunofluorescent antibody assay (IFA). The Puumala virus (PUUV), which is one of the hantavirus species, was detected in the lungs of seven M. glareolus by RT-PCR. The virus S-segment was extremely similar (96.2% to 99.3%) to the sequence found in a fatal case of HFRS in the Samara region. Phylogenetic analyses of S and M segments showed that the Samara PUUVs form a cluster within the Russian Volga lineage and apparently differ from other European PUUVs. Anti-PUUV antibodies were found in blood sera from seven HFRS patients and from one undiagnosed patient from the Samara region, using IFA and an enzyme-linked immunosorbent assay (ELISA). These data suggest that the bank vole M. glareolus is a primary natural reservoir and vector for PUUV, which is the main causative agent of HFRS in humans in the Samara region.

Recent Discoveries of New Hantaviruses Widen Their Range and Question Their Origins

Hantaviruses belong to the Bunyaviridae family. While usually hosted by wild mammals, they are potentially pathogenic for humans, and several serologically distinct groups associated with different syndromes have been identified. Yet, investigations have mostly been conducted where human infections by hantaviruses constitute a real and well-identified public health problem, i.e., the holarctic and neotropical areas. Some hantaviruses have also been described from a Suncus murinus in India and a Bandicota indica in Thailand. In addition, recent investigations in Cambodia revealed new Hantavirus types. More recently, two new Hantavirus species were described: Sangassou from a Hylomyscus simus, and Tanganya from a Crocidura theresae, both from Africa (Guinea), thus strongly questioning the current views about geographic range, evolution, and epidemiology of hantaviruses. In such a framework, we have conducted a survey of Hantavirus diversity in Southeast Asia which allows us to isolate the Thailand virus and address questions about the taxonomy of their rodent hosts. Here we present a molecular analysis of representatives of all currently known Hantavirus species, thus allowing the comparison between the newly described ones with a large range sample of rodent hantaviruses. Our results clearly point to the presence of a particular lineage of hantaviruses in Southeast Asia. It also strongly suggests that new viruses, additional mammalian hosts and different related syndromes in humans are likely to be discovered in the near future, particularly in Southeast Asia and in Africa, where Muridae rodents are highly diversified. Furthermore, additional work is also urgently needed to investigate the hantaviruses associated with Crociduridae and Soricidae.

Hantaviruses: an emerging public health threat in India? A review

The emerging viral diseases haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are a cause of global concern as they are increasingly reported from newer regions of the world. The hantavirus species causing HFRS include Hantaan virus,Seoul virus, Puumala virus, and Dobrava-Belgrade virus while Sin Nombre virus was responsible for the 1993 outbreak of HCPS in the Four Corners Region of the US. Humans are accidental hosts and get infected by aerosols generated from contaminated urine,feces and saliva of infected rodents. Rodents are the natural hosts of these viruses and develop persistent infection. Human to human infections are rare and the evolution of the virus depends largely on that of the rodent host. The first hantavirus isolate to be cultured, Thottapalayam virus,is the only indigenous isolate from India,isolated from an insectivore in 1964 in Vellore, South India. Research on hantaviruses in India has been slow but steady since 2005. Serological investigation of patients with pyrexic illness revealed presence of anti-hantavirus IgM antibodies in 14.7% of them. The seropositivity of hantavirus infections in the general population is about 4% and people who live and work in close proximity with rodents have a greater risk of acquiring hantavirus infections. Molecular and serological evidence of hantavirus infections in rodents and man has also been documented in this country. The present review on hantaviruses is to increase awareness of these emerging pathogens and the threats they pose to the public health system.

Nephropathia epidemica als Folge einer Puumala-Virus-Infektion bei einer schwangeren Patientin

A 29-year-old woman in the early stage of pregnancy ( approximately 6 (th) week) presented in our hospital with influenza-like symptoms of fever, headache, aching limbs and tenderness over the costovertebral angle. Acute oliguric renal failure occurred within a few days. Ultrasonography revealed symmetrically enlarged kidneys with a small amount of perirenal fluids. The blood count showed thrombocytopenia, and viral serology verified a recent infection with Puumala virus (species of Hantavirus). Epidemic nephropathy was diagnosed. The patient underwent one session of hemodialysis and soon recovered without any residual renal damage. The pregnancy continued without any further complications. There are only few reports on infections with Puumala virus during pregnancy are. None of theses described any fetal abnormalities causes by the maternal infection, as in our patient. Hantavirus infections should be considered in differential diagnosis of acute renal failure in endemic regions.

Genetic analysis of hantaviruses carried by reed voles Microtus fortis in China

To gain more insights into the epidemiology of hantaviruses in China, the hantaviral S, M and L segment sequences were recovered from two Microtus fortis captured in Shenyang and four M. fortis trapped in Yuanjiang in China. Genetic analysis revealed that Shenyang sequences are closely related to the sequences of Fusong strains of Vladivostok virus (VLAV). Interestingly, the complete S segment and partial L segment sequences from Yuanjiang were quite distinct from those of Shenyang and Fusong strains, with up to 18% nucleotide (nt) and 5% amino acid (aa) sequence divergences. The partial M segment sequences (nt 2676–3650) from Yuanjiang were even more divergent from Shenyang and Fusong sequences (>20% and 8%, respectively). On the phylogenetic trees based on the S and partial M and L segment sequences, the Shenyang strains grouped together with Fusong strains. In contrast, four Yuanjiang sequences formed a distinct group that was a sister taxon to the Vladivostok–Fusong–Shenyang group. Our data indicated that the virus carried by M. fortis in Shenyang belong to VLAV. The newly characterized sequences from Yuanjiang might represent a novel distinct hantavirus species. Our results also demonstrated the great genetic diversity and complexity of the M. fortis-associated hantaviruses in China.

Isolation and genetic characterization of hantaviruses carried by Microtus voles in China

To gain more insights into hantavirus distribution in China, Microtus fortis were caught in Jilin province and M. maximowiczii in the Inner Mongolia Autonomous Region. Hantavirus specific RNA was detected by RT-PCR in 3 out of 26 M. fortis and 5 out of 64 M. maximowiczii. Two hantaviruses (Fusong-Mf-682 and Yakeshi-Mm-59) were isolated successfully in cell culture and their S and M segment nucleotide sequences were determined. Phylogenetic analysis of the S and M segment sequences revealed that the Mf-originated strains from Fusong were closely related to Vladivostok hantavirus (VLAV) with 99% nucleotide identity, but differed from the Yakeshi-Mm strains, with an amino acid divergence of more than 8.8% for the N protein and 11.8% for the GnGc proteins. Yakeshi-Mm strains were closely related to the Khabarovsk hantavirus (KHAV) isolated earlier from M. fortis in Khabarovsk, with an amino acid sequence identity of more than 98.4% for the S segment and 95.6% for the M segment. On phylogenetic trees, Yakeshi-Mm strains clustered together with KHAV and Topografov virus (TOPV) carried by Lemmus sibiricus. The results suggest that the hantavirus carried by M. fortis in China belongs to VLAV type and should be considered as a distinct hantavirus species. They also suggest that M. fortis is the natural host of VLAV (including Fusong-Mf strains), whereas M. maximowiczii is the natural host of KHAV including Yakeshi-Mm strains. Thus, in addition to Hantaan, Seoul, Dabieshan and Puumala-like Hokkaido viruses, at least two other hantaviruses, namely KHAV and VLAV, are circulating in China.

Emerging zoonoses: Hantavirus infections

ZusammenfassungDie weltweite Verbreitung und die jährlich steigende Zahl der Infektion mit Hantaviren lässt die Bedeutung der Hantaviren unter den „emerging viruses“ ansteigen. Die Ansteckung verläuft über das Einatmen von Staub oder Aerosolen, die mit Ausscheidungen infizierter Nagetiere kontaminiert sind. Krankheitsbild und Schwere des Verlaufs hängen vom Virustyp ab, dessen geographisch begrenztes Auftreten vom Vorkommen des virustypspezifischen Nagerreservoirs bestimmt wird. Die Infektion mit in Asien und Europa beheimateten Stämmen löst das hämorrhagische Fieber mit renalem Syndrom (HFRS) aus. Die in Deutschland vorherrschende Virusspezies Puumala löst eine mildere Verlaufsform des HFRS, die Nephropathia epidemica (NE), aus. Infektionen mit Hantavirus-Stämmen des amerikanischen Kontinents hingegen führen zu einem Krankheitsbild mit vorwiegend pulmonaler Symptomatik (hantavirales pulmonales Syndrom, HPS). Da für keinen der humanpathogenen Vertreter eine spezifische antivirale Therapie oder ein zugelassener Impfstoff zur Verfügung steht, bleibt zur Eindämmung und Vermeidung der Infektion nur die Kontrolle der Nagerpopulationen und Präventionsmaßnahmen des expositionsgefährdeten Personenkreises.

Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD(50)], approximately 100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days -1 and +5 relative to challenge were protected against intranasal challenge (21 LD(50)). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.

Detection and Typing of Human Pathogenic Hantaviruses by Real-Time Reverse Transcription-PCR and Pyrosequencing

Because the clinical course of human infections with hantaviruses can vary from subclinical to fatal, rapid and reliable detection of hantaviruses is essential. To date, the diagnosis of hantavirus infection is based mainly on serologic assays, and the detection of hantaviral RNA by the commonly used reverse transcription (RT)-PCR is difficult because of high sequence diversity of hantaviruses and low viral loads in clinical specimens. We developed 5 real-time RT-PCR assays, 3 of which are specific for the individual European hantaviruses Dobrava, Puumala, or Tula virus. Two additional assays detect the Asian species Hantaan virus together with Seoul virus and the American species Andes virus together with Sin Nombre virus. Pyrosequencing was established to provide characteristic sequence information of the amplified hantavirus for confirmation of the RT-PCR results or for a more detailed virus typing. The real-time RT-PCR assays were specific for the respective hantavirus species and optimized to run on 2 different platforms, the LightCycler and the ABI 7900/7500. Each assay showed a detection limit of 10 copies of a plasmid containing the RT-PCR target region, and pyrosequencing was possible with 10 to 100 copies per reaction. With this assay, viral genome could be detected in 16 of 552 (2.5%) specimens of suspected hantavirus infections of humans and mice. The new assays detect, differentiate, and quantify hantaviruses in clinical specimens from humans and from their natural hosts and may be useful for in vitro studies of hantaviruses.

Muju virus, a novel hantavirus harboured by the arvicolid rodent Myodes regulus in Korea

Acute-phase sera from >5 % of cases of haemorrhagic fever with renal syndrome occurring annually in Korea have been found to exhibit a fourfold or higher antibody titre to Puumala virus (PUUV) than to Hantaan virus (HTNV) by double-sandwich IgM ELISA, suggesting the existence of a PUUV-related hantavirus. Based on the phylogenetic relationships among arvicolid rodents, the royal vole (Myodes regulus) was targeted as a likely reservoir host of hantavirus. Using RT-PCR, a genetically distinct hantavirus, designated Muju virus (MUJV), was detected in lung tissue of royal voles, captured in widely separated geographical regions in Korea during 1996-2007. Pairwise analysis of the full-length S (1857 nt) and M (3634 nt) segments of MUJV indicated approximately 77 % sequence similarity with PUUV. At the amino acid level, MUJV differed from PUUV by 5.5-6.9 % (nucleocapsid) and 10.0-11.6 % (Gn and Gc envelope glycoproteins). Interstrain variation of MUJV sequences from royal voles captured in different regions suggested geographic-specific clustering. Neutralizing antibody titres against PUUV were two- to sixfold higher than to HTNV in sera of MUJV-infected Myodes regulus. Although virus isolation attempts were unsuccessful, the collective data indicate that MUJV is a distinct hantavirus species.

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.

Hantavirus in African wood mouse, Guinea.

Hantaviruses are rodentborne, emerging viruses that cause life-threatening human diseases in Eurasia and the Americas. We detected hantavirus genome sequences in an African wood mouse (Hylomyscus simus) captured in Sangassou, Guinea. Sequence and phylogenetic analyses of the genetic material demonstrate a novel hantavirus species, which we propose to name "Sangassou virus."

Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates

At least four hantavirus species cause disease with prominent renal involvement-hemorrhagic fever with renal syndrome (HFRS); and several hantavirus strains cause disease with significant pulmonary involvement-hantavirus pulmonary syndrome (HPS). The most prevalent and lethal hantaviruses associated with HFRS and HPS are Hantaan virus (HTNV) and Andes virus (ANDV), respectively. Here, we constructed a DNA vaccine plasmid (pWRG/HA-M) that contains both the HTNV and ANDV M gene segments. Rhesus macaques vaccinated with pWRG/HA-M produced antibodies that bound the M gene products (i.e., G1 and G2 glycoproteins), and neutralized both HTNV and ANDV. Neutralizing antibody titers elicited by the dual-immunogen pWRG/HA-M, or single-immunogen plasmids expressing only the HTNV or ANDV glycoproteins, increased rapidly to high levels after a booster vaccination administered 1–2 years after the initial vaccination series. Memory responses elicited by this long-range boost exhibited an increased breadth of cross-neutralizing activity relative to the primary response. This is the first time that hantavirus M gene-based DNA vaccines have been shown to elicit a potent memory response, and to elicit antibody responses that neutralize viruses that cause both HFRS and HPS.

Phylogenetic evidence for the distinction of Saaremaa and Dobrava hantaviruses

Dobrava virus (DOBV) and Saaremaa virus (SAAV) are two closely related hantaviruses carried by different rodent species. The distinction of these two viruses has been a matter of debate. While the phylogenies based on the viral M segment sequences were repeatedly showing monophyly of SAAV strains, some trees based on the S segment sequences were not, thus causing questions on the demarcation between these two viruses. In order to clarify this issue, the current collection of the virus S segment sequences was subjected to extensive phylogenetic analysis using maximum likelihood, maximum parsimony and distant matrix methods. In all inferred phylogenies, the SAAV sequences were monophyletic and separated from DOBV sequences, thus supporting the view that SAAV and DOBV are distinct hantavirus species. Since collection of the S segment sequences used in this study "obeyed" the molecular clock, calculations of the split of DOBV and SAAV were now repeated resulting in an estimation of 3.0–3.7 MYA that is very close to the values obtained earlier.

Differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses.

Hantaviruses represent important human pathogens and can induce hemorrhagic fever with renal syndrome (HFRS), which is characterized by endothelial dysfunction. Both pathogenic and nonpathogenic hantaviruses replicate without causing any apparent cytopathic effect, suggesting that immunopathological mechanisms play an important role in pathogenesis. We compared the antiviral responses triggered by Hantaan virus (HTNV), a pathogenic hantavirus associated with HFRS, and Tula virus (TULV), a rather nonpathogenic hantavirus, in human umbilical vein endothelial cells (HUVECs). Both HTNV- and TULV-infected cells showed increased levels of molecules involved in antigen presentation. However, TULV-infected HUVECs upregulated HLA class I molecules more rapidly. Interestingly, HTNV clearly induced the production of beta interferon (IFN-beta), whereas expression of this cytokine was barely detectable in the supernatant or in extracts from TULV-infected HUVECs. Nevertheless, the upregulation of HLA class I on both TULV- and HTNV-infected cells could be blocked by neutralizing anti-IFN-beta antibodies. Most strikingly, the antiviral MxA protein, which interferes with hantavirus replication, was already induced 16 h after infection with TULV. In contrast, HTNV-infected HUVECs showed no expression of MxA until 48 h postinfection. In accordance with the kinetics of MxA expression, TULV replicated only inefficiently in HUVECs, whereas HTNV-infected cells produced high titers of virus particles that decreased after 48 h postinfection. Both hantavirus species, however, could replicate equally well in Vero E6 cells, which lack an IFN-induced MxA response. Thus, delayed induction of antiviral MxA in endothelial cells after infection with HTNV could allow viral dissemination and contribute to the pathogenesis leading to HFRS.

Hantavirus infection in children.

This article focuses on recent developments in knowledge about hantavirus infections and hantavirus cardiopulmonary syndrome in children. We highlight clinical characterization, epidemiology, pathogenesis, diagnostic techniques, and current alternatives for treatment and prevention. After the first description of hantavirus pulmonary syndrome (HPS) in 1993 in the United States, new cases of HPS and new hantavirus species have been described throughout the Americas. The factors involved in the expression of hantavirus disease have, in part, been recognized, but there have been descriptions of newer viruses and newer rodent reservoirs. Several seroprevalence studies suggest that the virus-host interaction has been taking place for many years, and changes in human behavior and wild rodent ecology, sometimes secondary to industrial progress, facilitate the clinical recognition of disease. Sin nombre virus (SNV) and Andes virus (ANDV) are examples of the same disease with differences in the virus virulence and in the host response. The North American syndrome and the Southern HPS differ in epidemiologic patterns and in the spectrum of disease. Currently, no Food and Drug Administration (FDA)-approved antiviral drugs, vaccines, or immunotherapeutic agents are available for treatment of the disease, and therapy is primarily supportive. Intensive care medicine has played an outstanding role in decreasing the lethality of HPS. A ribavirin trial in the United States did not support the use of the drug in fully developed HCPS. Recently published data suggest that a strong neutralizing antibody response may be a predictor of effective clearance of and recovery from SNV infection. This has raised the possibility that passive immunotherapy may be useful in HCPS. Extensive work has been done to develop a hantavirus vaccine, but at present it seems unlikely that a vaccine will be in commercial development in the near future.

Hantavirus Cardiopulmonary Syndrome: report of four cases

Hantavirus Cardiopulmonary Syndrome was first described in southwestern USA as a condition that involves mainly the lungs, leading to a high mortality rate (over 50%), caused by a new Hantavirus species. The pathology of this disease involves the direct viral damage of lung endothelial vessel cells, leading to leaking and alveolar inundation. Huge fluid expansion may lead to deterioration of pulmonary function and increased mortality. Therefore, one has to be cautious about fluid reposition, and treatment must take into account the use of vasoactive drugs. We report four cases of such a syndrome admitted to our intensive care unit from December 2000 to March 2002. All patients came from the same county. They were rural inhabitants, living near rice and soybean storehouses that allow rodents entrance. The patients' age ranged from 31 to 57 years (median 36.5 years), and two of them were female. The initial symptoms (coughing, muscular pain, fever and dyspnea) set in from 48 to 96 hours before admission. Two patients required mechanical ventilation (and one of them also required the use of a pulmonary artery catheter). Three patients survived (intensive care unit discharge before 1 week after admission). One patient died due to pulmonary atelectasis on the seventh day after admission. Chest X-rays demonstrated in all cases mainly alveolar compromise, both bilateral and symmetrical, reminiscent of acute respiratory distress syndrome patterns in the latter stages. Blood sample serology confirmed the suspected diagnosis. Treatment consisted of general support, cautious fluid replacement and vasoactive drugs for the treatment of shock. We did not use ribavirin (although its use is well described in the literature). In conclusion, diagnosis is based on high clinical suspicion, taking into account the epidemiological aspects that are highly important in such cases. Clinical manifestation is mainly noncardiogenic pulmonary edema, due to the direct endothelial vessel cell damage, leading to leaking and alveolar inundation. Huge fluid expansion may increase mortality. Use of a pulmonary artery catheter plays an important role in selected cases, in which fluid replacement can be targeted according to the pulmonary capillary wedge pressure.