Hantavirus infection causes
|
Hantavirus infection Microchapters |
|
Patient Information |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Hantavirus infection causes On the Web |
|
American Roentgen Ray Society Images of Hantavirus infection causes |
|
Directions to Hospitals Treating Hantavirus pulmonary syndrome |
|
Risk calculators and risk factors for Hantavirus infection causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Basir Gill, M.B.B.S, M.D.[2]
Overview
Hantavirus infection is caused by viruses of the genus Orthohantavirus, family Hantaviridae, class Bunyaviricetes.[1] Hantaviruses are enveloped, negative-sense, single-stranded RNA viruses with a tri-segmented genome encoding a nucleoprotein (N), a glycoprotein precursor (GPC, generating Gn and Gc), and an RNA-dependent RNA polymerase (RdRP).[2][3] Rodents are the main natural reservoir hosts, and transmission to humans occurs primarily via inhalation of aerosolized rodent excreta (urine, feces, saliva), or rarely via rodent bites.[2] Over 50 hantavirus species have been described, of which more than 24 are recognized as pathogenic to humans, causing two major clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas.[3] Approximately 150,000 to 200,000 cases of hantavirus disease are diagnosed worldwide each year.[4]
Causes
Causative Agent
Hantavirus infection is caused by viruses of the genus Orthohantavirus (formerly Hantavirus), family Hantaviridae, order Elliovirales, class Bunyaviricetes (previously order Bunyavirales).[1][5]
Viral Structure
Hantavirus virions are enveloped, pleomorphic, 80–120 nm in diameter, and contain a negative-sense, single-stranded, tri-segmented RNA genome with a total size of approximately 10.5–14.6 kb.[1][2]
The large (L) segment (~6.5 kb) encodes the RNA-dependent RNA polymerase (RdRP), which is essential for viral replication and transcription.[2][6]
The medium (M) segment (~3.6 kb) encodes the glycoprotein precursor (GPC), which is co-translationally cleaved into two surface glycoproteins, Gn and Gc. A tetrameric assembly of Gn and Gc on the virus surface constitutes the spike complex that mediates cell entry and virus assembly.[3][6]
The small (S) segment (~1.7 kb) encodes the nucleoprotein (N) and, in some hantaviruses, a non-structural protein (NSs).[3][2]
Pathogenic Hantavirus Species
All human-pathogenic hantaviruses belong to the genus Orthohantavirus within the subfamily Mammantavirinae and are maintained by rodents of the families Muridae and Cricetidae.[1][7] The distribution of each virus overlaps with the geographical distribution of its specific rodent reservoir.[2]
| Clinical Syndrome | Virus | Primary Rodent Host | Geographic Distribution | CFR |
|---|---|---|---|---|
| Hantavirus cardiopulmonary syndrome (HCPS) | Sin Nombre virus (SNV) | Peromyscus maniculatus (deer mouse) | North America (western USA, Canada) | ~36% |
| Andes virus (ANDV) | Oligoryzomys longicaudatus (long-tailed colilargo) | Argentina, Chile | 30–45% | |
| Araraquara virus (ARAV) | Necromys lasiurus | Brazil | 30–45% | |
| Juquitiba virus (JUQV) | Oligoryzomys nigripes | Brazil, Argentina | 30–45% | |
| New York virus (NYV) | Peromyscus leucopus (white-footed mouse) | North America (eastern USA) | — | |
| Monongahela virus (MGLV) | Peromyscus leucopus | North America (eastern USA) | — | |
| Bayou virus (BAYV) | Oryzomys palustris (marsh rice rat) | North America (southeastern USA) | — | |
| Black Creek Canal virus (BCCV) | Sigmodon hispidus (hispid cotton rat) | North America (southeastern USA) | — | |
| Muleshoe virus (MULEV) | Sigmodon hispidus | North America | — | |
| Choclo virus (CHOV) | Oligoryzomys fulvescens | Panama | 12–15% | |
| Laguna Negra virus (LANV) | Calomys callosus | Argentina, Paraguay, Bolivia | 12–15% | |
| Bermejo virus (BMJV) | Oligoryzomys chacoensis, O. flavescens | Bolivia, Argentina | — | |
| Lechiguanas virus (LECV) | Oligoryzomys flavescens | Argentina | — | |
| Oran virus (ORNV) | Oligoryzomys chacoensis | Argentina | — | |
| Maciel virus (MCLV) | Bolomys obscurus | Argentina | — | |
| Castelo Dos Sonhos virus (CASV) | Oligoryzomys spp. | Brazil | — | |
| Hemorrhagic fever with renal syndrome (HFRS) | Hantaan virus (HTNV) | Apodemus agrarius (striped field mouse) | China, Russia, Korea | Severe; ~1.3% (modern China) |
| Amur virus (AMRV) | Apodemus peninsulae (Korean field mouse) | China, Russia, Korea | Severe | |
| Dobrava-Belgrade virus (DOBV) | Apodemus flavicollis (yellow-necked mouse) | Balkans, southeastern Europe | Severe; CFR 10–12% | |
| Seoul virus (SEOV) | Rattus norvegicus (brown rat) | Global | Moderate; CFR 1–2% | |
| Thailand hantavirus (THAIV) | Bandicota indica | Thailand | Rare; limited data | |
| Tula virus (TULV) | Microtus arvalis (common vole) | Europe | Very rare | |
| Saaremaa virus (SAAV / DOBV-Aa) | Apodemus agrarius | Estonia, central/eastern Europe | Mild; CFR 1% | |
| Puumala virus (PUUV) | Myodes glareolus (bank vole) | Northern/western Europe, Russia | Mild; CFR 0.1–0.4% | |
| Nephropathia epidemica (NE) | Puumala virus (PUUV) | Myodes glareolus (bank vole) | Northern/western Europe, Russia, Finland | 1% |
| Saaremaa virus (SAAV / DOBV-Aa) | Apodemus agrarius | Estonia, central/eastern Europe | 1% |
Adapted from Vial et al. 2023,[2] Jiang et al. 2017,[8] and Avšič-Županc et al. 2019.[9] CFR = case fatality rate. "—" indicates insufficient data for reliable CFR estimate.
Reservoir Hosts
Rodent Reservoirs
Rodents are the main natural hosts for all human-pathogenic hantaviruses. Natural hosts are believed to be persistently infected with little biological effect.[2] Each hantavirus species shows a strong degree of host-virus specificity, with each virus typically associated with a single rodent species or closely related species complex.[3] The three principal rodent subfamilies associated with human-pathogenic hantaviruses are:
Murinae (family Muridae): Hosts for Hantaan virus, Seoul virus, and Dobrava-Belgrade virus; found in Asia and Europe. Key species include Apodemus agrarius (striped field mouse), Apodemus flavicollis (yellow-necked mouse), and Rattus norvegicus (brown rat).[2][10]
Arvicolinae (subfamily of family Cricetidae): Hosts for Puumala virus and Tula virus; found in Europe. The key species is Myodes glareolus (bank vole).[2][10]
Sigmodontinae and Neotominae (subfamilies of family Cricetidae): Hosts for Sin Nombre virus, Andes virus, and other New World hantaviruses; found in the Americas. Key species include Peromyscus maniculatus (deer mouse), Oligoryzomys longicaudatus (long-tailed colilargo), and Sigmodon hispidus (hispid cotton rat).[2][10]
Seoul virus is the only cosmopolitan hantavirus found worldwide, together with its host, the commensal brown rat (Rattus norvegicus). It is thought that SEOV originated in China and was subsequently exported to Europe and later spread through the New World following human migrations and sea trade.[11]
Non-Rodent Hosts
Although rodents are the primary reservoirs, hantaviruses have also been identified in bats, moles, shrews, reptiles, and fish.[2][1] These non-rodent-associated hantaviruses belong to other genera within the family Hantaviridae (Loanvirus, Mobatvirus, Thottimvirus) and are generally not known to cause human disease.[1]
Novel Rodent Hosts
Recent whole-genome sequencing studies have identified Sin Nombre virus in multiple rodent species not previously known to carry the virus, beyond the primary deer mouse (Peromyscus maniculatus) reservoir. These findings suggest that the host range of some hantaviruses may be broader than previously recognized and have implications for epidemiology and infection control.[12]
Modes of Transmission
Inhalation of Aerosolized Rodent Excreta (Primary Route)
The primary mode of transmission to humans is via inhalation of aerosolized viral particles shed in rodent urine, feces, and saliva.[2] Activities that disturb rodent-contaminated environments and generate aerosols are the most common source of exposure. These include cleaning previously unused homes, sweeping cellars or storage areas, demolition, construction, forestry work, agricultural work, and weeding.[2]
Environmental Viability
Data are insufficient on how long hantaviruses remain viable in the environment. Puumala virus (PUUV) remained infectious for up to 15 days in bank voles' bedding, and remained viable at room temperature after 5 days in a wet environment and 24 hours when dry. Similarly, Hantaan virus (HTNV) survived in wet conditions for 8 days at 20°C and 9 days at 37°C.[2]
Rodent Bites
Rarely, transmission can occur via direct rodent bites.[2][7]
Person-to-Person Transmission
Andes virus (ANDV) is the only hantavirus with documented person-to-person transmission.[2][13] There is no evidence for human-to-human transmission of HFRS-causing hantaviruses, although blood products drawn from infected individuals or blood transmission during medical interventions are a possible source of infection.[2]
Key findings regarding ANDV person-to-person transmission include:
A prospective study in Chile followed 476 household contacts of 76 confirmed ANDV cases for 5 weeks and found 16 additional patients, with a secondary attack rate of 3.4%. The risk of infection was 17.6% among sex partners of an index case, compared with 1.2% for other household contacts.[2]
In 2018–19, a person-to-person transmission outbreak in Epuyén, Argentina, affected 34 patients, of whom 11 died. Genomic and epidemiological analysis identified three "super-spreaders" (each generating ≥5 secondary cases) who attended crowded social gatherings while symptomatic. The outbreak's reproductive number (R) peaked at approximately 6.5 during initial super-spreading events but declined from 2.12 to 0.96 following implementation of isolation and quarantine measures.[14]
Risk factors for person-to-person transmission include being a sexual partner, tongue kissing, sleeping in the same room, and attending a social gathering with a symptomatic person, largely just before or during the febrile prodrome.[2]
ANDV is present in the blood of infected individuals for up to 2 weeks before the onset of symptoms and during symptomatic disease. A 2024 prospective study demonstrated significant viral shedding in body fluids including gingival crevicular fluid, saliva, and nasopharyngeal secretions during the acute phase (up to 16 days after onset of symptoms), with variable virus concentrations between compartments. Severity correlated with the presence of ANDV RNA in fluids besides blood.[13]
ANDV has been detected in saliva from both rodents and humans and is more resistant to inactivation by saliva than PUUV or HTNV.[2]
A 2026 update noted that ANDV possesses a unique capacity for sustained human-to-human transmission, occurring via respiratory droplets and prolonged close contact with symptomatic individuals, with a median reproductive number exceeding 2 and an incubation period ranging from 9 to 40 days.[15]
For person-to-person transmission, estimates of incubation periods range between 9 days and 40 days, with a median of 19 days and 23 days, respectively.[2]
Nosocomial Transmission
Rare nosocomial transmission of Andes virus has been reported in hospital settings.[2][13]
Blood-Borne Transmission
Although not definitively proven, blood products drawn from infected individuals or blood transmission during medical interventions are a possible source of infection for HFRS-causing hantaviruses.[2]
Risk Factors
Occupational Risk Factors
Occupational exposure to rodent-infested environments is a major risk factor for hantavirus infection. A systematic review and meta-analysis of 42 studies (total workforce of 15,043 individuals) found:[16]
Farmers: Pooled seroprevalence of 3.7% (95% CI 2.2–6.2); odds ratio (OR) 1.875 (95% CI 1.438–2.445) compared to reference population
Forestry workers: Pooled seroprevalence of 3.8% (95% CI 2.6–5.7); OR 2.892 (95% CI 2.079–4.023) compared to reference population
Other high-risk occupations include military troops (especially those with extended outdoor training), construction and demolition workers, and laboratory workers handling rodents.[2][4]
Behavioral and Environmental Risk Factors
Risk factors for hantavirus infection include:[2][4]
Forestry or agricultural work
Weeding, construction, and demolition activities
Cleaning previously unused homes, cellars, storage areas, or stables
Actions that raise dust in rodent-contaminated environments
Peridomestic rodent presence
Outdoor military training
Exposure to potentially infected dust
Smoking (reported as a risk factor for contracting Puumala virus infection and for more severe disease)[2]
Demographic Risk Factors
Sex: HCPS occurs in men in 70–80% of cases. The male-to-female ratio for HFRS cases is 2.6:1.[2]
Age: The median age for HCPS is 34 years (range 0–86 years).[2]
Setting: HCPS is acquired in rural settings by residents (80%) or visitors (20%) of endemic areas. Most HFRS cases occur in rural settings, with the exception of Seoul virus, which is mainly transmitted in urban settings where wild rats are prevalent.[2]
Genetic Susceptibility
Ethnicity has been shown to affect the clinical course of ANDV and LANV infection, suggesting that human genetic composition can influence the severity of hantavirus infections.[2] An inverse correlation of seroprevalence rates and disease severity has been observed: in the USA, Chile, and Argentina where the disease is severe, seroprevalence is low (0.1–2.2%), whereas in Paraguay and Panama, where HCPS is milder, 17–40% and 33%, respectively, are seropositive. This could be related to genetic selection of the population or more transmissible and less pathogenic viruses.[2]
Environmental and Climatic Factors
Hantavirus outbreaks are strongly influenced by ecological and climatic factors that drive rodent population dynamics and human-rodent contact.[2][10]
Climate and Rodent Population Dynamics
Temperature and rainfall are key climatic variables controlling the interannual cycles of hantavirus outbreaks. A 54-year study (1960–2013) from Central China revealed that 8-year cycles of Hantaan virus outbreaks are driven by the confluence of cyclic dynamics of striped field mouse (Apodemus agrarius) populations and climate variability. Outbreaks occur only when climatic conditions are favorable for both rodent population growth and virus transmission.[17]
In Northern Europe, 3- to 4-year cycles of Myodes glareolus (bank vole) populations drive cyclical Puumala virus epidemics. Increased tree-seed production (mast years) following warm summers and autumns leads to higher bank vole densities and subsequent hantavirus outbreaks.[18]
In the Americas, El Niño-associated increased rainfall leads to increased vegetation, higher deer mouse densities, and more frequent Sin Nombre virus transmission. Disease cases are greatest in arid states and decline exponentially with increasing precipitation.[19]
In northwestern Argentina, a significant association between HCPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months has been demonstrated.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Bradfute SB, Calisher CH, Klempa B, Klingström J, Kuhn JH, Laenen L, Maes P, Papa A, Schmaljohn CS, Tischler ND, Plyusnin A (2024). "ICTV Virus Taxonomy Profile: Hantaviridae 2024". J Gen Virol. 105 (4). doi:10.1099/jgv.0.001975. PMID 38587456 Check
|pmid=value (help). - ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 Vial PA, Ferrés M, Vial C, Klingström J, Ahlm C, López R, Le Corre N, Mertz GJ (2023). "Hantavirus in Humans: A Review of Clinical Aspects and Management". Lancet Infect Dis. 23 (9): e371–e382. doi:10.1016/S1473-3099(23)00128-7. PMID 37105214 Check
|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 Saavedra F, Díaz FE, Retamal-Díaz A, Bueno SM, Kalergis AM, Riedel CA (2021). "Immune Response During Hantavirus Diseases: Implications for Immunotherapies and Vaccine Design". Immunology. 163 (3): 262–277. doi:10.1111/imm.13322.
- ↑ 4.0 4.1 4.2 Watson DC, Sargianou M, Papa A, Chra P, Starakis I, Panos G (2014). "Epidemiology of Hantavirus Infections in Humans: A Comprehensive, Global Overview". Crit Rev Microbiol. 40 (3): 261–72. doi:10.3109/1040841X.2013.783555. PMID 23607444.
- ↑ Kuhn JH, Brown K, Adkins S, de la Torre JC, Digiaro M, Ergünay K, Forber PJ, Goldbach RW, Grybchuk D, Hughes HR, Junglen S, Klempa B, Krupovic M, Lambert AJ, Maes P, Marklewitz M, Mielke-Ehret N, Mirazimi A, Mühlbach HP, Palacios G, Pawęska JT, Peters CJ, Plyusnin A, Rubbenstroth D, Shi M, Siddell SG, Simmonds P, Sironi M, Smagghe G, Tesh RB, Turina M, Wahl V, Walker PJ, Wang L, Whitfield AE, Yeh SD, Zerbini FM, Zhang YZ (2024). "Promotion of Order Bunyavirales to Class Bunyaviricetes to Accommodate a Rapidly Increasing Number of Related Polyploviricotine Viruses". J Virol. 98 (10): e0106924. doi:10.1128/jvi.01069-24. PMID 39303014 Check
|pmid=value (help). - ↑ 6.0 6.1 Meier K, Thorkelsson SR, Quemin E, Rosenthal M (2021). "Hantavirus Replication Cycle-an Updated Structural Virology Perspective". Viruses. 13 (8): 1561. doi:10.3390/v13081561. PMID 34452426 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 7.0 7.1 Salehi-Vaziri M, Kaleji AS, Fazlalipour M, Jalali T, Shariat Bahadori M, Farahmand B, Ahmadi Vasmehjani A, Pouriayevali MH, Mostafavi E (2019). "Hantavirus Infection in Iranian Patients Suspected to Viral Hemorrhagic Fever". J Med Virol. 91 (10): 1737–1742. doi:10.1002/jmv.25522.
- ↑ Jiang H, Zheng X, Wang L, Du H, Wang P, Bai X (2017). "Hantavirus infection: a global zoonotic challenge". Virol Sin. 32 (1): 32–43. doi:10.1007/s12250-016-3899-x. PMID 28120221.
- ↑ Avšič-Županc T, Saksida A, Korva M (2019). "Hantavirus Infections". Clin Microbiol Infect. 21S: e6–e16. doi:10.1111/1469-0691.12291. PMID 24750436.
- ↑ 10.0 10.1 10.2 10.3 Tian H, Stenseth NC (2019). "The Ecological Dynamics of Hantavirus Diseases: From Environmental Variability to Disease Prevention Largely Based on Data From China". PLoS Negl Trop Dis. 13 (2): e0006901. doi:10.1371/journal.pntd.0006901. PMID 30789905.
- ↑ Ling J, Verner-Carlsson J, Eriksson P, Plyusnina A, Löhmus M, Järhult JD, van de Goot F, Plyusnin A, Lundkvist Å, Sironen T (2019). "Genetic Analyses of Seoul Hantavirus Genome Recovered From Rats (Rattus norvegicus) in the Netherlands Unveils Diverse Routes of Spread Into Europe". J Med Virol. 91 (5): 724–730. doi:10.1002/jmv.25390.
- ↑ Goodfellow SM, Nofchissey RA, Schwalm KC, Torres-Pérez F, Hjelle B (2021). "Tracing Transmission of Sin Nombre Virus and Discovery of Infection in Multiple Rodent Species". J Virol. 95 (23): e0153421. doi:10.1128/JVI.01534-21. PMID 34549977 Check
|pmid=value (help). - ↑ 13.0 13.1 13.2 Ferrés M, Martínez-Valdebenito C, Henriquez C, Travassos da Rosa E, Elkhoury MR, Vial PA (2024). "Viral Shedding and Viraemia of Andes Virus During Acute Hantavirus Infection: A Prospective Study". Lancet Infect Dis. 24 (7): 775–782. doi:10.1016/S1473-3099(24)00142-7. PMID 38582089 Check
|pmid=value (help). - ↑ Martínez VP, Di Paola N, Alonso DO, Pérez-Sautu U, Bellomo CM, Iglesias AA, Coelho RM, López B, Periolo N, Larson PA, Nagle ER, Chitty JA, Pratt CB, Díaz J, Cisterna D, Campos J, Sharma H, Dighero-Kemp B, Biondo E, Lewis L, Palacios G (2020). ""Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina". N Engl J Med. 383 (23): 2230–2241. doi:10.1056/NEJMoa2009040. PMID 32609981 Check
|pmid=value (help). - ↑ Durante-Mangoni E, Cafarella I, Mercadante S, Scarpulla N (2026). "Human Infection With Andes Hantavirus: An Update for the General Physician". Eur J Intern Med: 106946. doi:10.1016/j.ejim.2026.106946. PMID 42185150 Check
|pmid=value (help). - ↑ Riccò M, Peruzzi S, Ranzieri S, Magnavita N (2021). "Occupational Hantavirus Infections in Agricultural and Forestry Workers: A Systematic Review and Metanalysis". Viruses. 13 (11): 2150. doi:10.3390/v13112150. PMID 34834957 Check
|pmid=value (help). - ↑ Tian H, Yu P, Cazelles B, Xu L, Wang H, Wallinga J, Stenseth NC (2017). "Interannual Cycles of Hantaan Virus Outbreaks at the Human-Animal Interface in Central China Are Controlled by Temperature and Rainfall". Proc Natl Acad Sci USA. 114 (30): 8041–8046. doi:10.1073/pnas.1701777114. PMID 28696305.
- ↑ Vaheri A, Henttonen H, Voutilainen L, Mustonen J, Sironen T, Vapalahti O (2013). "Hantavirus infections in Europe and their impact on public health". Rev Med Virol. 23 (1): 35–49. doi:10.1002/rmv.1722. PMID 23280975.
- ↑ Carver S, Mills JN, Parmenter CA, Parmenter RR, Richardson KS, Harris RL, Douglass RJ, Kuenzi AJ, Luis AD (2015). "Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus". Bioscience. 65 (7): 651–666. doi:10.1093/biosci/biv047. PMID 26955081.