Critical care management of hantavirus cardiopulmonary syndrome. A narrative review.

Hantaviruses, members of the Bunyaviridae family, can cause two patterns of disease in humans, hantavirus hemorrhagic fever with renal syndrome (HFRS) and cardiopulmonary syndrome (HCPS), being the latter hegemonic on the American continent. Andesvirus is one of the strains that can cause HCPS and is endemic in Chile. Its transmission occurs through direct or indirect contact with infected rodents' urine, saliva, or feces and inhalation of aerosol particles containing the virus. HCPS rapidly evolves into acute but reversible multiorgan dysfunction. The hemodynamic pattern of HCPS is not identical to that of cardiogenic or septic shock, being characterized by hypovolemia, systolic dysfunction, and pulmonary edema secondary to increased permeability. Given the lack of specific effective therapies to treat this viral infection, the focus of treatment lies in the timely provision of intensive care, specifically hemodynamic and respiratory support, which often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This narrative review aims to provide insights into specific ICU management of HCPS based on the available evidence and gathered experience in Chile and South America including perspectives of pathophysiology, organ dysfunction kinetics, timely life support provision, safe patient transportation, and key challenges for the future.

Orthohantaviruses in Misiones Province, Northeastern Argentina.

Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.

Preventive Practices of Hantavirus in a Rural Community in Panama: An Explanatory Sequential Mixed Methods Study.

INTRODUCTION: Preventive care practices are a challenge in community care. This study examined hantavirus preventive practices and their relationship with personal and social factors, lifestyle, and cultural beliefs. METHOD: An explanatory sequential mixed methods design, guided by Leininger's Theory of Culture Care Diversity and Universality, was used in two phases: (a) a cross-sectional relational design (n = 109) and (b) ethnonursing research (n = 30), in an endemic community in Panama. Univariate and bivariate analyses were used to analyze the quantitative data, whereas the Leininger's analysis model was used to analyze the qualitative data. RESULTS: In the quantitative phase, the most frequent preventive practice was household hygiene, and the least frequent was vector control. Two of the eight preventive practices were associated with personal factors and two were associated with social factors. In the qualitative phase, lifestyle, beliefs, and context were found to influence the adoption of hantavirus preventive practices and help explain the quantitative findings. DISCUSSION: Knowledge and understanding of the social and cultural contexts are essential for hantavirus prevention.

Hantavirus infection in central Sri Lanka - an unusual clinical presentation: a case report.

Hantavirus infections are emerging zoonoses. In Asia, the hantavirus commonly manifests as haemorrhagic fever with renal syndrome (HFRS), apparent with fever, thrombocytopenia and acute kidney injury. There are a few cases with the atypical clinical course with cardiopulmonary symptoms in Asia including Sri Lanka. Here, we report a case of hantavirus infection with an atypical cardiopulmonary syndrome-like illness with serological evidence of the Puumala/Puumala-like virus.

Xiaoer-Feire-Qing granules alleviate pyretic pulmonary syndrome induced by Streptococcus pneumoniae in young rats by affecting the lungs and intestines: An in vivo study based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. PURPOSE: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. METHODS: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1ß, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. RESULTS: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. CONCLUSION: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application.

Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study.

BACKGROUND: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated. METHODS: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). RESULTS: While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197. CONCLUSIONS: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107.

Trans-catheter closure of an unusual type of Abernethy malformation in a child presenting with severe pulmonary hypertension.

Abernethy malformation is a congenital extra-hepatic porto-systemic shunt. This malformation is characterized by an abnormal connection between the portal vein or its branches and one of the systemic veins. Though rare, this anomaly can lead to pulmonary hypertension. Drainage of Abernethy malformation into coronary sinus is extremely rare. We describe a child with Abernethy malformation with unusual drainage into coronary sinus. The abnormal channel was successfully closed by trans-catheter technique with normalisation of pulmonary arterial pressures.

Filling the gaps in the Argentinian distribution of orthohantavirus: First finding of Lechiguanas virus in rodents from Corrientes, Argentina.

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease caused by orthohantaviruses in the Americas. In Argentina, since 1995, several reservoirs and virus variants have been described, but the northeastern and central endemic zones in the country include an area without human or rodent infections, despite sharing rodent species with areas with that disease. The aim of this study was to search for orthohantavirus in rodent communities that inhabit this area, which borders two endemic areas of HPS. Small rodents were captured in June of 2022 through a total effort of 644 trap nights distributed in five grids located in the Iberá National Park, Corrientes, Northeastern Argentina. All rodents were sexed, weighed, and the species was recorded. Blood samples were extracted to detect ANDV-specific immunoglobulin G (IgG), and to extract the RNA virus. Trimmed sequences were mapped against reference sequences from GenBank. We captured a total of 36 Oligoryzomys flavescens and 15 Oxymycterus rufus. We detected the O. flavescens species infected with Lechiguanas orthohantavirus in the camping area of the National Park. A nucleotide comparison with previously published sequences shows a 98.34% similarity to the virus obtained from a human case of HPS reported in the adjacent Misiones province. This study demonstrated, for the first time, that O. flavescens is a host of the Lechiguanas orthohantavirus in this zone and contributes to closing information gaps on the distribution of orthohantavirus in Argentina. Additionally, the high similarity with the hantavirus found in the human case of Misiones suggests that the reservoir in that province would also be O. flavescens (not previously confirmed). This information permits us to focus on the preventive measurements to protect the human population.

Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus-A Case Report and Literature Review.

In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24-73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Novel Ozark Orthohantavirus in Hispid Cotton Rats (Sigmodon hispidus), Arkansas, USA.

We report a novel orthohantavirus, putatively named Ozark orthohantavirus, in hispid cotton rats captured within the Ozark Plateau in Arkansas, USA. This virus phylogenetically clusters with other orthohantaviruses that cause severe human disease. Continued orthohantavirus surveillance and virus sequencing are needed to address the potential public health threat of this virus.

Detection of Hantavirus during the COVID-19 Pandemic, Arizona, USA, 2020.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

A Brief History of Bunyaviral Family Hantaviridae.

The discovery of Hantaan virus as an etiologic agent of hemorrhagic fever with renal syndrome in South Korea in 1978 led to identification of related pathogenic and nonpathogenic rodent-borne viruses in Asia and Europe. Their global distribution was recognized in 1993 after connecting newly discovered relatives of these viruses to hantavirus pulmonary syndrome in the Americas. The 1971 description of the shrew-infecting Hantaan-virus-like Thottapalayam virus was long considered an anomaly. Today, this virus and many others that infect eulipotyphlans, bats, fish, rodents, and reptiles are classified among several genera in the continuously expanding family Hantaviridae.

Electrocardiogram, Echocardiogram and NT-proBNP in Screening for Thromboembolism Pulmonary Hypertension in Patients after Pulmonary Embolism.

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation, the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive tests providing diagnostic clues to CTEPH, or ascertaining this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations are caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of this study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: Out of the total number of patients (n = 261, male n = 123) after PE who were included in the study, in the group of 155 patients (59.4%) with reported functional impairment, 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4.5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD also had higher levels of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/mL did not differentiate patients with CTEPH/CTEPD (p > 0.05). Additionally, the proportion of patients with right bundle brunch block registered in ECG was higher in the CTEPH/CTED group (23.5% vs. 5.8%, p = 0.034) but there were no differences between the other ECG characteristics of right ventricle overload. Conclusions: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to the pre PE period. It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED predominantly had abnormalities indicating chronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor.

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hantavirus infection, and they also indicate the need for further research in vivo.

Acute Hantavirus Infection Presenting With Fever and Altered Mentation in the Absence of Pulmonary or Renal Manifestations.

Illness caused by hantaviruses is often severe and is typically characterized by diffuse pulmonary disease or renal insufficiency depending on the type of hantavirus. Here we report 2 cases of hantavirus infection that resulted in severe cognitive impairment but did not have any pulmonary or renal manifestations. These 2 cases may be indicative of previously underreported symptoms of hantavirus infection and might represent examples of hantavirus-related encephalopathy.

Pulmonary complications of portal hypertension: The overlooked decompensation.

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.

Factores pronósticos de síndrome cardio-pulmonar y muerte por hantavirus Andes Sur: estudio de cohorte en San Carlos de Bariloche y su zona de influencia sanitaria / Prognostic factors for cardio-pulmonary syndrome and death by hantavirus Andes Sur: cohort study in San Carlos de Bariloche and health influence área

Resumen Las infecciones por hantavirus, ocurren a través de la inhalación de aerosoles provenientes de excretas de roedores infectados. Estos virus causan síndrome cardiopulmonar en el caso de la variante Andes Sur, con una mortalidad que puede alcanzar el 50%. Se presenta como casos esporádicos o en pequeños conglomerados, en los que predomina el contagio interhumano. En este estudio observacional de tipo cohorte histórica, en personas infectadas con hantavirus Andes Sur durante los años 2009 a 2019 que fueron asistidas en el subsector público de salud de San Carlos de Bariloche(Argentina), se buscó identificar factores que pudieran predecir mala evolución (síndrome cardiopulmonar y muerte). Para ello se caracterizó el riesgo para cada una de las variables y, para obtener información clave sobre las relaciones entre las mismas, se aplicó además un análisis de correspondencias múltiples. Durante el período de estudio, 38 personas fueron incluidas. La edad media fue de 35 años. Se sospechó contagio de persona a persona en 10/38 (26.8%) casos. El 21.1% (8/28) tuvo al momento del diagnóstico un síndrome pulmonar por hantavirus. Mientras que, 55.3% (21/38) lo desarrolló durante su evolución y 44.7% (17/38) de los infectados fallecieron durante la internación. La edad mayor a 15 años y la plaquetopenia, se asociaron con un mayor riesgo de progresión clínica, mientras que las formas de leves o las personas asintomáticas, el contagio persona a persona o durante un brote epidemiológico, se asociaron con un menor riesgo de muerte.

Abstract Hantavirus infections occur through the inhalation of aerosols from the excreta of infected rodents. These viruses cause a cardiopulmonary syn drome in the case of the Andes Sur variant, with a mortality that can reach 50%. It occurs in sporadic cases or in small clusters, in which interhuman contagion predominates. In this historical cohort-type observational study, in people infected with Andes Sur hantavirus during the years 2009 to 2019 who was assisted in the public health subsector of San Carlos de Bariloche (Argentina), it was sought to identify factors that could predict poor evolution (cardiopulmonary syndrome and death). For this, the risk for each of the variables was characterized and, to obtain key information about the relationships between them, a multiple correspondence analysis was also applied. During the study period, 38 people were included. The mean age was 35 years. Person-to-person contagion was suspected in 10/38 (26.8%) cases. 21.1% (8/28) presented a hantavirus pulmonary syndrome at the time of diagnosis, while 55.3% (21/38) developed it during their evolution, and 44.7% (17/38) of those infected died during hospitalization. Age over 15 years and thrombocytopenia were associated with a higher risk of clinical progression, while mild forms or asymptomatic people, person-to-person transmission, or during an epidemiological outbreak, were associated with a lower risk of death.