Orthohantaviruses (also known as hantaviruses) are pathogens, primarily transmitted by rodents, that can cause hemorrhagic fever with renal syndrome (HFRS). In endemic regions of Kazakhstan, no confirmed HFRS cases were detected between 2020 and 2022 raising concerns about detection. Estimate antibody seroprevalence for hantaviruses and identify associated risk factors among high-risk adults in western Kazakhstan in 2023. In this cross-sectional study, adults were randomly sampled from public clinic registries in 14 villages in West Kazakhstan during June-July 2023. We interviewed 921 participants and collected serum samples which were tested for presence of hantavirus specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Socio-demographic, clinical characteristics, and residential risk-factor data were self-reported. We assessed factors associated with seropositivity using multivariable Poisson regression, adjusting for key variables such as age and gender. Among 921 participants, 63.0% were female, median age was 53 years, 72.0% resided in single houses and 38.0% reported encounters with rodents. Among 921 participants we found 3.1% (n = 28) hantavirus seroprevalence (95% confidence interval [CI]: 2.1-4.3). No seropositive participants had prior hospitalization or symptoms consistent with hantavirus. Three seronegative participants had previous hospitalization for hemorrhagic fever with renal syndrome. Over one-third (38%) of participants encountered rodents or droppings in the past year in their homes or workplaces. Higher seroprevalence was found among office occupational workers than unemployed people (prevalence ratio [PR]:7.3, 95%CI: 1.3-53.5), and among those who lived near ponds than those who did not (PR:11.5, 95%CI: 1.6-54.7). Overall, the seroprevalence was low, but indicated some risk of infection among the adult population. Our results highlight potential occupational and residential risk factors for hantavirus infection in West Kazakhstan. Relevant public health interventions should include educating the population about promoting preventive practices, workplace hygiene, rodent control measures, and enhanced case diagnosis and management. Hantavirus pulmonary syndrome (HPS) is a rare but severe pulmonary disease characterized by pulmonary edema, hypoxia, and hypotension. HPS is caused by viruses of the Orthohantavirus genus and the Hantaviridae family. Hantaviruses cause 2 main clinical presentations: Hemorrhagic fever renal syndrome is characterized by acute kidney injury, thrombocytopenia, fever, and hypotension. Found mainly in Asia, Eastern Russia, and parts of Europe, the primary causative virus species are Hantaan, Dobrava, Seoul, and Puumala. Please see our companion StatPearls article, "Hemorrhagic Fever Renal Syndrome," for further information. Fever, myalgias, and severe respiratory compromise characterize HPS. Found mainly in North and South America, the primary causative virus species are Sin Nombre in North America and Andes in South America. Clinically, patients often require mechanical ventilation, and despite appropriate care, mortality is up to 40% (compared to 1%-15% for HFRS). Both syndromes involve the primary mechanism of virus inhalation, can affect the lungs and kidneys, and involve increased microvascular permeability, consumptive platelet coagulopathy, and hyperactivity of the host immune system. Over 24 known Hantaviridae are capable of causing human disease, and the virus type varies primarily by geographic location and animal vector. All types are carried by rodents (and rarely shrews and bats) and spread to humans through inhalation of aerosolized urine, feces, or animal bites. The transmitting animals are asymptomatic carriers. There is no known cure, and treatment is supportive. The highest risk of infection is seen in those who have close contact with animal hosts, and prevention is focused on decreasing human-rodent contact. Due to a plethora of newly sequenced viral genomic data, the taxonomy classifications were updated in 2016 to include Bunyavirales as an order, and the previous genus Hantavirus became the family classification Hantaviridae. Orthohantavirus became the genus, and in this review, will be referred to as "Hantavirus."

The development and current state of hemorrhagic fever with renal syndrome (HFRS) over the past 40 years are analyzed in this study, along with explored and discovered the hotspots and frontiers in the field, which serve as the foundation for future investigation. CiteSpace and VOSviewer analysis software were used to visually analyze the literature data on HFRS from 1980 to 2022, including the annual number of publications, countries and research institutions, authors, co-cited literature and keywords. The number of pertinent papers published in the field of HFRS displayed an overall upward trend from 1980 to 2022. The United States, China, Germany, Sweden, and France are the top 5 countries in terms of publishing volume, with high intermediate centrality mainly concentrated in Europe and the United States. The top 10 co-occurring keywords were hemorrhagic fever, renal syndrome, infection, virus, epidemic, nephropathia epidemical, disease, hantavirus, outbreak, and transmission. According to keyword cluster analysis, there were 4 main research fields. In the HFRS-related study, there were mainly 21 notable keywords and "Korean hemorrhagic fever" had the highest hemorrhagic value (28.87). The United States, China, Germany, Sweden and other countries attached great importance to the HFRS-related research. Moreover, the collaboration between authors and institutions in various collaborator clusters should be strengthened. In recent decades, investigations have focused on the study of viral infection and the clinical symptoms and pathophysiology of HFRS. Future research may concentrate on factors affecting host population distribution and density, such as vaccine development and meteorological factors pertaining to virus transmission. Hemorrhagic fever with renal syndrome (HFRS) is a disease transmitted through aerosolized urine or feces of rodents (mice, rats, shrews, and voles). HFRS is the most common zoonosis in Asia and also common in parts of Europe. Various serotypes cause the disease within the Orthohantavirus genus and are endemic in parts of Asia and Eastern Russia. The most common serotypes causing HFRS are Hantaan, Dobrava, Seoul, and Puumala. Rodents are asymptomatic reservoirs of the virus, which can spread to infect humans at a rate of over 100,000 cases per year. The outcome of infection is usually self-limited, but mortality can exceed 15% with some infectious strains.  Recently, the taxonomical classification of these viruses has been updated. Due to a plethora of newly sequenced viral genomic data, classifications were expanded in 2016 to include Bunyavirales as an order, and the previous genus Hantavirus became the family classification Hantaviridae. The viruses causing hemorrhagic fever with renal syndrome are part of the Orthohantavirus genus and Hantaviridae family (previously referred to as Hantaviruses).  Two main disease processes result from Orthohantaviruses (which will be referred to as Hantaviruses from here on out): Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS). These two entities have distinct presentations and geographic predominance; the viruses causing HFRS circulate in Asia and Eastern Europe, while the viruses causing HCPS are found in the Americas. Different Hantavirus strains cause HFRS and HCPS and have different clinical pictures, but both involve increased microvascular permeability, consumptive platelet coagulopathy, and hyperactivity of the host immune system. HCPS is associated with much higher mortality.  Please see our companion StatPearls topic "Hantvirus Cardiopulmonary Syndrome," for further information. HFRS results from inhalation of Hantavirus, which spreads to other organ systems through the immune system and targets the renal vasculature. In patients who develop HFRS, a variety of clinical presentations exist, from mildly symptomatic to death. No known cure exists for Hantavirus infection other than supportive care.

Seoul orthohantavirus (SEOV) infections, uncommonly reported in the United States, often result in mild illness. We report a case of hemophagocytic lymphohistiocytosis secondary to SEOV infection that was domestically acquired in Washington, DC.

Hantaan virus (HTNV) infection of the human body causes a severe acute infectious disease known as hemorrhagic fever renal syndrome (HFRS). The aim of this study was to correlate patient cytokine profiles to HFRS severity. In this study, we discuss the clinical significance of evaluating HFRS treatment outcomes using cytokine information. The levels of 18 cytokines were quantitatively determined in three groups: 34 HTNV IgM+ cases, 63 HTNV IgM- negative cases, and 78 healthy volunteers. The level of 14 serum cytokines were higher in the patient group than that in the healthy control group. In the 34 HTNV IgM+ patient sera, a set of 27 cytokines was further assessed. The cytokines of TNF-β, IL-1ra, and IL-6 were detected at higher level in the IgM+ group than that in the IgM- group. The deterioration of HFRS was accompanied with multiple cytokines increased, such as IL-1ra, IL-12p70, IL-10, IP-10, IL-17, IL-2, and IL-6. Our data indicate that serum cytokine levels are associated with the progression of HFRS.