An evaluation of suspected cases of Hantavirus infection admitted to a tertiary care university hospital in Düzce, Turkey, between 2012 and 2018

Background/aim: Hantavirus is a rodent borne zoonosis caused by the members of the virus family Bunyaviridae, genus Hantavirus. In this study, we aimed to determine the role of peripheral blood leukocyte ratio in differential diagnosis of Hantavirus disease. Materials and methods: The medical records of patients at the Düzce University Medical Faculty were examined retrospectively. A total of 20 patients diagnosed with hantavirus infection confirmed by serologic tests were included in the study (Group 1). The other group consisted of 30 patients suspected of hantavirus infection but found negative (Group 2). Demographic, clinical and laboratory characteristics, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte (LMR) ratios of both groups were compared. Results: As a result of the istatistics analysis, no difference was found between the groups' age, sex, and clinical complaints except lethargy-weakness (P = 0.004) and diarrhea (P < 0.001). Hemogram analysis showed a significant difference between the groups in terms of leukocyte, hemoglobin, hematocrit, platelet, mean platelet volume (P < 0.05) and PLR (P = 0.001) and LMR (P = 0.003) values from peripheral blood leukocyte ratios. Conclusion: In conclusion, NLR, PLR, and LMR ratios may be useful for clinicians in differential diagnosis of Hantavirus in patients presenting with similar symptoms of Hantavirus disease.

Tula orthohantavirus nucleocapsid protein is cleaved in infected cells and may sequester activated caspase-3 during persistent infection to suppress apoptosis.

The family Hantaviridae mostly comprises rodent-borne segmented negative-sense RNA viruses, many of which are capable of causing devastating disease in humans. In contrast, hantavirus infection of rodent hosts results in a persistent and inapparent infection through their ability to evade immune detection and inhibit apoptosis. In this study, we used Tula hantavirus (TULV) to investigate the interplay between viral and host apoptotic responses during early, peak and persistent phases of virus infection in cell culture. Examination of early-phase TULV infection revealed that infected cells were refractory to apoptosis, as evidenced by the complete lack of cleaved caspase-3 (casp-3C) staining, whereas in non-infected bystander cells casp-3C was highly abundant. Interestingly, at later time points, casp-3C was abundant in infected cells, but the cells remained viable and able to continue shedding infectious virus, and together these observations were suggestive of a TULV-associated apoptotic block. To investigate this block, we viewed TULV-infected cells using laser scanning confocal and wide-field deconvolution microscopy, which revealed that TULV nucleocapsid protein (NP) colocalized with, and sequestered, casp-3C within cytoplasmic ultrastructures. Consistent with casp-3C colocalization, we showed for the first time that TULV NP was cleaved in cells and that TULV NP and casp-3C could be co-immunoprecipitated, suggesting that this interaction was stable and thus unlikely to be solely confined to NP binding as a substrate to the casp-3C active site. To account for these findings, we propose a novel mechanism by which TULV NP inhibits apoptosis by spatially sequestering casp-3C from its downstream apoptotic targets within the cytosol.

[Pathomorphism of Hantavirus infection under prolonged heat stress]. / Patomorfoz khantavirusnoi infektsii na fone prolongirovannogo teplovogo stressa.

AIM: to provide the morphological characteristics of experimental Hantavirus infection under heat stress conditions to identify the possibilities of its modeling in resistant laboratory animals. MATERIAL AND METHODS: Experiments were carried out on outbred albino mice that were divided into 4 groups: 1) intact mice unexposed to heating; 2) those exposed to heating; 3) Hantavirus-infected animals unexposed to preheating; 4) those exposed to preheating. The animals in Groups 2-4 were long exposed to heat stress at a temperature of 30 °C for 3 hours during 3 days. Strain Aa 60343 (PM-79-95) of the Far East genovariant of Hantaan virus (the genus Hantavirus, family Bunyaviridae) from the collection of the G.P. Somov Research Institute of Epidemiology and Microbiology was used to induce infection. The animals in Groups 3 and 4 were intraperitoneally injected with 700 FFU of Hantavirus per mouse. Materials (lung, liver, kidney, and spleen) taken from Groups 2-4 animals were collected for histological examination on days 1, 3, 7 and 14 of observation. RESULTS: The intact albino mice in Group 1 showed no histopathological changes in the organs. After heat exposure, Group 2 animals were found to have an immunomorphological response in the interstitial tissues of the lung, liver and kidney in partial lymphoid hypoplasia of the spleen. There were no signs of inapparent infection in the presence of marked immunomorphological changes in the organs in Group 3 of hantavirus-infected animals unexposed to preheating. In Group 4, those exposed to preheating exhibited dystrophic and destructive changes in the target organs (lungs, kidneys) in the presence of immunodeficiency manifestations of manifestations that were more pronounced in dead animals. CONCLUSION: In an unresponsive model (adult albino mice), Hantavirus infection caused only obvious immunomorphological changes in the organs. Prolonged preheat stress in the hantavirus-infected animals promoted inapparent infection and morphological manifestations of induced secondary immunodeficiency that was responsible for the manifestation of an infectious process in some animals.

Age-related effects of chronic hantavirus infection on female host fecundity.

1. Pathogens often cause detrimental effects to their hosts and, consequently, may influence host population dynamics that may, in turn, feed back to pathogen transmission dynamics. Understanding fitness effects of pathogens upon animal host populations can help to predict the risks that zoonotic pathogens pose to humans. 2. Here we determine whether chronic infection by Puumala hantavirus (PUUV) affects important fitness-related traits, namely the probability of breeding, reproductive effort and mother and offspring condition, in the bank vole (Myodes glareolus). Using 9 years empirical data in a PUUV endemic area in Central Finland, we found differences between reproductive characteristics of PUUV-infected and uninfected female bank voles. 3. Young infected females had a significantly higher, and old individuals lower, likelihood of reproducing than uninfected animals during the middle of the breeding season. The implication is that PUUV infection may have long-term deleterious effects that are observed at old age, while in young individuals, the infection may enhance breeding probability by directing resources towards current breeding. 4. Moreover, PUUV infection was related with the mother's body condition. Infected mothers were in poorer condition than uninfected mothers in the early breeding season, but were in better condition than uninfected mothers during the middle of the breeding season. Offspring body condition was positively associated with mother's body condition, which, in turn, was related to the PUUV infection status of the mother. 5. Our findings indicate that chronic infection may affect the reproduction of female hosts, but the effect is dependent on the host age. The effect of chronic hantavirus infection was small and density-independent and hence unlikely to contribute to the cyclic population dynamics of the host. However, the effects on a female's reproductive output might affect the abundance of young susceptible individuals in the population and hence influence the transmission and persistence of the pathogen. Although experimental and long-term capture-mark-recapture studies are required to further clarify the fitness effects of hantavirus infection and their consequences for pathogen dynamics, this study shows that the infection may have complex effects that are dependent on the age of the individual and the time of the breeding season.

Sustained high level of serum VEGF at convalescent stage contributes to the renal recovery after HTNV infection in patients with hemorrhagic fever with renal syndrome.

To investigate the role of vascular endothelial growth factor (VEGF) in the increased permeability of vascular endothelial cells after Hantaan virus (HTNV) infection in humans, the concentration of VEGF in serum from HTNV infected patients was quantified with sandwich ELISA. Generally, the level of serum VEGF in patients was elevated to 607.0 (542.2-671.9) pg/mL, which was dramatically higher compared with healthy controls (P < 0.001). There was a rapid increase of the serum VEGF level in all patients from the fever onset to oliguric stage, at which the serum creatinine reached the peak level of the disease, indicating that VEGF may be involved in the pathogenesis of renal hyper-permeability. Moreover, the serum VEGF level at convalescent stage was positively correlated with the degree of the disease severity. The sustained high level of serum VEGF at convalescence was observed in critical HFRS patients, suggesting that VEGF would probably contribute to the renal recovery after the virus clearance. Taken together, our results suggested that the VEGF would be involved in the pathogenesis of renal dysfunction at the oliguric stage after HTNV infection, but may function as a recovery factor during the convalescence to help the body self-repair of the renal injury.

Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease.

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors' and decedents' cases. However, total uPA in decedents' cases was significantly higher compared to survivors'. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.

Clinical and biochemical differences between hantavirus infection and leptospirosis: a retrospective analysis of a patient series in Belgium.

Objectives: Hantavirus infection and leptospirosis are infectious diseases transmitted by rodents. The clinical picture is nonspecific, often involving the kidneys but other organs can be affected too. Clinical and biochemical clues to make a difference between these two entities will be described.Methods: A retrospective analysis was performed on a database of patients presenting between January 2012 and September 2017 at the emergency department of the university hospital Leuven, Belgium. Patients were selected on the basis of a compatible clinical picture, biochemistry, and microbiological evidence. Presenting complaints and clinical examination were compared. Blood, taken at presentation, was used for hematological and biochemical analysis.Results: Sixteen patients with hantavirus infection and eight patients with leptospirosis were identified. All patients complained about general malaise and fever. Other frequent complaints were myalgia and a headache. Patients with leptospirosis often experienced photo- or sonophobia.Looking for neck stiffness and eye lesions might help to diagnose leptospirosis.Differences in biochemistry between viral and bacterial disease could be recognized; high C-reactive protein (CRP) and leukocytosis with left shift favor leptospirosis, elevated lactate dehydrogenase (LDH) favors viral infection. Abnormal liver function with raised total bilirubin is often seen in cases with leptospirosis.Conclusion: This study demonstrates some subtle clues that may help to differentiate between hantavirus infection and leptospirosis in patients presenting to a hospital in a nonendemic region of the world. Because of small number of patients, we could not identify significant clinical or biochemical tests. Serology remains the gold standard.

An outbreak caused by hantavirus in the Black Sea region of Turkey, January-May 2009.

We present a preliminary report of 12 laboratory-confirmed cases of haemorrhagic fever with renal syndrome (HFRS) in Turkey, diagnosed between January and May 2009 according to the clinical symptoms and serological confirmation. Studies are still ongoing to better understand the dynamics of the reservoir population as well as the epidemiological characteristics and risk factors among humans.

Hemodynamic and Pulmonary Permeability Characterization of Hantavirus Cardiopulmonary Syndrome by Transpulmonary Thermodilution.

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE), and shock, which leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that have not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD: eight on MV, three required ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association with PE. The main findings were reduced stroke volume, global ejection fraction (GEF), and preload parameters associated with increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction, and increased permeability PE. Lung water correlated positively with heart rate (HR, r = 0.20) and negatively with mean arterial pressure (r = -0.27) and GEF (r = -0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r = 0.31) and negatively with cardiac index (r = -0.49), end-diastolic volume (r = -0.48), and GEF (r = -0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggest that in HCPS patients, increased permeability leads to PE, hypovolemia, and circulatory impairment.

Dendritic Cells (DCs) as "Fire Accelerants" of Hantaviral Pathogenesis.

Hantaviruses are widespread zoonotic pathogens found around the globe. Depending on their geographical location, hantaviruses can cause two human syndromes, haemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). HPS and HFRS have many commonalities amongst which excessive activation of immune cells is a prominent feature. Hantaviruses replicate in endothelial cells (ECs), the major battlefield of hantavirus-induced pathogenesis, without causing cytopathic effects. This indicates that a misdirected response of human immune cells to hantaviruses is causing damage. As dendritic cells (DCs) orchestrate antiviral immune responses, they are in the focus of research analysing hantavirus-induced immunopathogenesis. In this review, we discuss the interplay between hantaviruses and DCs and the immunological consequences thereof.

Macropinocytosis contributes to hantavirus entry into human airway epithelial cells.

Hantaviruses are emerging rodent-borne negative-strand RNA viruses associated with severe human diseases. Zoonotic transmission occurs via aerosols of contaminated rodent excreta and cells of the human respiratory epithelium represent likely early targets. Here we investigated cellular factors involved in entry of the pathogenic Old and New World hantaviruses Hantaan virus (HTNV) and Andes virus (ANDV) into human respiratory epithelial cells. Screening of a kinase inhibitor library using a biocontained recombinant vesicular stomatitis virus pseudotype platform revealed differential requirement for host kinases for HTNV and ANDV entry and provided first hints for an involvement of macropinocytosis. Examination of a selected panel of well-defined inhibitors of endocytosis confirmed that both HTNV and ANDV enter human respiratory epithelial cells via a pathway that critically depends on sodium proton exchangers and actin, hallmarks of macropinocytosis. However, HTNV and ANDV differed in their individual requirements for regulatory factors of macropinocytosis, indicating virus-specific differences.

First outbreak of Oropouche Fever reported in a non-endemic western region of the Peruvian Amazon: Molecular diagnosis and clinical characteristics.

INTRODUCTION: Oropouche fever is an under-reported and emerging infectious disease caused by Oropouche virus (OROV). Its incidence is under-estimated mainly due to clinical similarities with other endemic arboviral diseases and the lack of specific diagnostic tests. We report the first outbreak of Oropouche fever in a western region of the Peruvian Amazon in Huanuco, Peru. METHODS: A transversal study was carried out during an outbreak in the western Region of Huanuco, Peru between January and July of 2016. Blood samples of 268 patients with acute febrile syndrome were collected and analyzed for OROV via RT- PCR and genetic sequencing. RESULTS: Of all 268 patients, 46 (17%) cases tested positive for OROV. The most common symptoms reported were headache with a frequency of 87% (n = 40) followed by myalgia with 76% (n = 35), arthralgia with 65.2% (n = 30), retro-ocular pain 60.8% (n = 28) and hyporexia with 50% (n = 23). Some patients showed a clinical presentation suggestive of severe OROV infection, of which 4.3% (n = 2) had low platelet count, 8.6% (n = 4) had intense abdominal pain, and 2.1% (n = 1) had a presentation with thoracic pain. CONCLUSION: This study reports an outbreak of OROV in a region where this virus was not previously identified. The disease caused by OROV is an emerging, underdiagnosed infection that requires further research to determine its virulence, pathogenesis, host range and vectors involved in the urban and sylvatic cycles as well as identifying new genotypes to implement sensitive and specific diagnostic tools that can be applied to endemic regions.

Kidney Diseases Associated With Parvovirus B19, Hanta, Ebola, and Dengue Virus Infection: A Brief Review.

Viral infection-associated kidney diseases are an emerging public health issue in both developing and developed countries. Many new viruses have emerged with new paradigms of kidney injury, either directly through their cytopathic effect or indirectly through immune-mediated glomerulopathy, tubulointerstitial disease, and acute kidney injury as part of multiorgan failure. Herein, we will discuss Parvovirus, which causes glomerulopathy, and Hanta, Ebola, and Dengue viruses, which cause viral hemorrhagic fever and acute kidney injury. Clinical manifestations also depend on extrarenal organ systems involved. Diagnosis of these viral infections is mainly based on a high index of suspicion, serologic testing, and isolation of viral DNA/RNA. Management is largely conservative, as specific antiviral agents are unavailable.

Landscape, Climate and Hantavirus Cardiopulmonary Syndrome Outbreaks.

We performed a literature review in order to improve our understanding of how landscape and climate drivers affect HCPS outbreaks. Anthropogenic landscape changes such as forest loss, fragmentation and agricultural land uses are related with a boost in hantavirus reservoir species abundance and hantavirus prevalence in tropical areas, increasing HCPS risk. Additionally, higher precipitation, especially in arid regions, favors an increase in vegetational biomass, which augments the resources for reservoir rodents, also increasing HCPS risk. Although these relationships were observed, few studies described it so far, and the ones that did it are concentrated in few places. To guide future research on this issue, we build a conceptual model relating landscape and climate variables with HCPS outbreaks and identified research opportunities. We point out the need for studies addressing the effects of landscape configuration, temperature and the interaction between climate and landscape variables. Critical landscape thresholds are also highly relevant, once HCPS risk transmission can increase rapidly above a certain degree of landscape degradation. These studies could be relevant to implement preventive measures, creating landscapes that can mitigate disease spread risk.

[Hantavirus infections]. / Infections a hantavirus.

Hantaviruses are cosmopolite anthropozoonosis considered as an emerging disease. Four pathogenic types for humans and part of the Bunyaviridae species are hosted by rodents and have been isolated: the Sin nombre virus responsible for the severe American respiratory form; the Hantaan and Seoul viruses responsible for hemorrhagic fevers with renal syndrome (HFRS) of severe to moderate expression in Asia and also in the Balkans; the Puumala virus responsible for HFRS of moderate expression or the socalled nephropathia epidemica in Europe. The Puumala virus is responsible for a minor form of the disease that is observed in areas of the Occidental sector of the ex-URSS, in Scandinavia and in the rest of Europe, notably in the North-East of France. The epidemic episodes occur every three years. They follow the proliferation of rodents, notably russet voles, the reservoir hosts, and their degree of infection. The concept of an occupation at risk in 20 to 49 year-old men (working in forests, agriculture, living near a forest, contact with wood) in an endemic area has not always been found. Its clinical form can vary greatly in its presentation. Basically it is a severe algic influenza syndrome accompanied by acute myopia in 38% of cases, but is nearly pathognomonic in the context. Respiratory involvement is frequent but benign. The initial syndrome can suggest an abdominal or urological surgical emergency, which is source of diagnostic and therapeutic errors. Early biological examination reveals thrombopenia and proteinuria. Then more or less severe acute kidney failure appears in slightly more than 50% of cases. Although it usually regresses with symptomatic treatment, after effects remain in some patients. The environmental changes, the geographical distribution depending on the biotope, the dynamics and behaviour of rodents and the viral circulation between them and its transmission to human beings and its risk factors must continue to be studied in order to gain further knowledge on the epidemiology of this anthropozoonosis.

Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection.

INTRODUCTION: Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection. PATIENTS AND METHODS: Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped. RESULTS: The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102-1041 vs. median 175, range 51-1499 µmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3-14 vs. median 6, range 2-15 days; p = 0.032). The rare A-allele carriers (i.e. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74-170 vs.116, range 86-162 mmHg, p = 0.019, and median 68, range 40-90 vs. 72, range 48-100 mmHg; p = 0.003, respectively). CONCLUSIONS: Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection.

Lethal disease in infant and juvenile Syrian hamsters experimentally infected with Imjin virus, a newfound crocidurine shrew-borne hantavirus.

To gain insights into the pathogenicity of Imjin virus (MJNV), a newfound hantavirus isolated from the Ussuri white-toothed shrew (Crocidura lasiura), groups of Syrian hamsters (Mesocricetus auratus) of varying ages (<1, 5, 10, 14, 21, 35 and 56 days) were inoculated by the intraperitoneal route with 1000 pfu of MJNV strains 04-55 and 05-11. MJNV-infected Syrian hamsters, aged 21 days or less, exhibited reduced activity, weight loss, respiratory distress, hind-limb paralysis and seizures. Death ensued 1 to 6 days after onset of clinical disease. MJNV RNA was detected in brain and other major organs by RT-PCR and real time-PCR. Histopathological examination showed alveolar hemorrhage, interstitial pneumonia and severe pulmonary congestion; focal hepatic necrosis and portal inflammation; and acute meningoencephalitis. By immunohistochemistry, MJNV antigen was detected in pulmonary microvascular endothelial cells and glial cells. Older hamsters (35 and 56 days of age) developed subclinical infection without histopathological changes. Future studies are warranted to determine the pathophysiologic bases for the differential age susceptibility of Syrian hamsters to lethal MJNV disease.

Complete nucleotide sequence of a Chilean hantavirus.

We have determined the genomic sequence of an Andes virus (ANDV) strain isolated from an infected Oligoryzomys longicaudatus rodent trapped in Chile in 1997. This strain, for which we propose the designation Chile R123, reproduces essential attributes of hantavirus pulmonary syndrome (HPS) when injected intramuscularly into laboratory hamsters (Hooper et al., Virology 289 (2001) 6-14). The L, M, and S segment sequences of Chile R123 are 6562, 3671, and 1871 nt long, respectively, with an overall G+C content of 38.5%. These respective genome segments could encode a 247 kd RNA-dependent RNA polymerase (RdRP), 126 kd glycoprotein precursor (GPC), and 48 kd nucleocapsid (N) protein, in line with other Sigmodontine rodent-associated hantaviruses. Among hantaviruses for which complete genomic sequences are available, Chile R123 is most closely related to Sin Nombre virus (SNV) strain NM R11, with greater than 85% amino acid identity between translated L and S segments and 78% amino acid identity between translated M segments. Because Chile R123 shares essentially 100% amino acid identity in regions of overlap with partially sequenced Argentinian and Chilean ANDV strains, Syrian hamster pathogenicity and the potential for interhuman transmission are features likely common to all ANDV strains.

Hantavirus.

When hantaviruses hit the headlines with the advent in May 1993 of a new disease in the USA, and later in the New World from Canada to south Argentina, called "hantavirus pulmonary syndrome" (HPS), speculations in the lay press rose from the very beginning around the possibilities of a biological warfare (BW) weapon. Indeed, the responsible agent of HPS, hantavirus, was almost unknown at that moment in the New World, was airborne, seemed to target preferentially young adults, and induced a devastating cardio-pulmonary collapse with a high case-fatality rate (50%), often within hours. It quickly became clear, however, that the same scourge had been known for many years in the Old World under different and mostly milder presentations. With the rapidly increasing knowledge about hantaviruses, it also became clear that they lack many of the potentials of an "ideal" BW weapon, as will be explained in this paper.

Experimental infection of the Sigmodon alstoni cotton rat with Caño Delgadito virus, a South American hantavirus.

Forty-eight Sigmodon alstoni (Alston's cotton rat) were inoculated with Caño Delgadito (CDG) virus to extend our knowledge and understanding of the natural host relationships of the hantaviruses indigenous to the Americas. Infectious CDG virus was recovered from oropharyngeal secretions, urine, or solid tissues of nine of 12 animals killed on day 9 post-inoculation (PI), 14 of 24 animals killed on day 18 or 27 PI, and none of 12 animals killed on day 54 PI. In addition, virus-specific RNA was detected in the kidneys of six of the 12 animals killed on day 54 PI, and adult cotton rats inoculated with the kidneys of four animals killed on day 54 PI developed antibody to CDG virus. Collectively, the results indicate that CDG virus can establish lengthy (perhaps lifelong) infections in Alston's cotton rat and thus support the concept that S. alstoni is the principal host of CDG virus.