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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Basir Gill, M.B.B.S, M.D.[3]

Overview

Hantavirus infection is a zoonotic disease caused by viruses of the family Hantaviridae (formerly Bunyaviridae), transmitted primarily by rodents. The earliest clinical descriptions of hantavirus-like illness date to imperial China and medieval Europe, but the disease was first formally recognized in northeast China in 1931.[1] In 1976, Ho Wang Lee isolated the first pathogenic hantavirus along the Hantaan River in South Korea and named it the Hantaan virus (HTNV) in 1978.[1] The discovery of Sin Nombre virus during the 1993 Four Corners outbreak in the southwestern United States established hantavirus cardiopulmonary syndrome (HCPS) as a distinct clinical entity.[2] The three major clinical entities caused by hantaviruses include hantavirus cardiopulmonary syndrome (HCPS), hemorrhagic fever with renal syndrome (HFRS), and nephropathia epidemica (NE).

Historical Perspective

Early Descriptions and Pre-Modern Era

Descriptions consistent with hemorrhagic fever with renal syndrome (HFRS) appear in ancient Chinese medical texts, though definitive attribution to hantavirus is retrospective.[1]

In 1934, Swedish physicians described an epidemic condition with primarily renal involvement, later named "nephropathia epidemica" (NE) — the earliest formal European clinical description of what is now recognized as hantavirus disease caused by Puumala virus.[3][4]

Recognition of HFRS (1930s–1950s)

In 1931, HFRS was first clinically recognized in northeast China.[1]

During World War II in 1942, a large epidemic among German and Finnish soldiers in Northern Finland involved more than 1,000 patients, most probably caused by Puumala virus.[5]

During the Korean War (1951–1953), more than 3,000 cases of acute febrile illness with hemorrhagic manifestations and renal failure occurred among United Nations soldiers stationed near the Hantaan River in South Korea. The disease was termed "Korean hemorrhagic fever" and carried a case fatality rate of 5–7%.[6][1]

Discovery of Hantaan Virus (1976–1978)

In 1976, Ho Wang Lee isolated the first pathogenic hantavirus from the lungs of the striped field mouse (Apodemus agrarius) captured near the Hantaan River in South Korea.[1]

In 1978, the virus was formally named Hantaan virus (HTNV), establishing the genus Hantavirus.[1]

This landmark discovery triggered the subsequent identification of related viruses worldwide, including Seoul virus (SEOV) in Asia and Puumala virus (PUUV) in Europe.[6][4]

European Discoveries (1980s)

Puumala virus (PUUV) was first discovered in the Puumala region of Finland in the early 1980s and identified as the causative agent of nephropathia epidemica.[4]

Seoul virus (SEOV) was found to be carried by Rattus norvegicus (the brown rat) and caused laboratory outbreaks throughout Europe in the early 1980s, demonstrating the global distribution potential of hantaviruses via commensal rodents.[4]

Dobrava virus (DOBV) was identified in the late 1980s and early 1990s in the Balkans, associated with severe HFRS carried by Apodemus flavicollis (the yellow-necked mouse).[4]

Discovery of Hantavirus Cardiopulmonary Syndrome (1993)

In May 1993, an outbreak of an unexplained pulmonary illness occurred in the southwestern United States, in an area shared by Arizona, New Mexico, Colorado, and Utah known as "The Four Corners".[7]

A cluster of previously healthy young adults developed rapidly progressive noncardiogenic pulmonary edema and respiratory failure. The initial 17 patients had a mean age of 32.2 years and a case fatality rate of 76%.[2]

A novel hantavirus was rapidly identified through molecular techniques and initially named "Four Corners virus," later renamed Sin Nombre virus (SNV; Spanish for "virus without a name"). The deer mouse (Peromyscus maniculatus) was identified as the primary reservoir.[2][6]

This discovery established hantavirus cardiopulmonary syndrome (HCPS, also called hantavirus pulmonary syndrome or HPS) as a distinct clinical entity, separate from the renal-predominant HFRS of the Old World.[2]

Person-to-Person Transmission of Andes Virus (1996)

In 1996, an outbreak in El Bolsón, Argentina involving 16 epidemiologically linked cases provided the first documented evidence of person-to-person transmission of a hantavirus — Andes virus (ANDV).[8]

ANDV remains the only hantavirus with confirmed person-to-person transmission, a feature that distinguishes it from all other known hantaviruses.[8][9]

Notable Outbreaks (2012–2019)

On November 1, 2012, the National Park Service (NPS) announced a total of 10 confirmed cases of hantavirus infection in people who recently visited Yosemite National Park. Three of the 10 patients died. The cases were linked to signature tent cabins in Curry Village with evidence of rodent infestation.[10]

In 2015, eighteen hantavirus infections with four deaths were reported nationally in the United States.

In January 2017, a multi-state outbreak of Seoul virus was identified among 7 states in the United States, representing the first known transmission of SEOV from pet rats to humans in the US and Canada. The investigation ultimately identified 31 rat-breeding facilities in 11 states and 17 people with evidence of recent SEOV infection.[7]

In July 2017, 3 deaths were reported due to hantavirus infection in Washington state.

In 2018–2019, a major outbreak of ANDV-associated HCPS occurred in Epuyén, Chubut Province, Argentina, with 34 confirmed infections and 11 deaths. Genomic and epidemiological analysis identified 3 "super-spreaders" at social gatherings who drove transmission chains. The basic reproduction number (R₀) decreased from 2.12 to 0.96 after implementation of public health measures including isolation and contact tracing.[8]

Taxonomic Reclassification (2017–2024)

Prior to 2017, hantaviruses were classified within the family Bunyaviridae, genus Hantavirus.

In 2016–2017, the International Committee on Taxonomy of Viruses (ICTV) reclassified hantaviruses into the new family Hantaviridae within the order Bunyavirales, reflecting advances in molecular phylogenetics.[11]

In 2024, the ICTV further promoted the order Bunyavirales to the class Bunyaviricetes to accommodate the rapidly increasing number of related viruses identified through metagenomic surveillance.[11]

Timeline of Key Milestones

Year Milestone
1931 HFRS first clinically recognized in northeast China
1934 Nephropathia epidemica described in Sweden
1942 Large epidemic among soldiers in Northern Finland (>1,000 cases)
1951–1953 "Korean hemorrhagic fever" among >3,000 UN soldiers during the Korean War
1976 Ho Wang Lee isolates Hantaan virus from Apodemus agrarius in South Korea
1978 Hantaan virus formally named; genus Hantavirus established
Early 1980s Puumala virus discovered in Finland; Seoul virus causes laboratory outbreaks in Europe
1993 Four Corners outbreak; Sin Nombre virus identified; HCPS established as a clinical entity
1996 First documented person-to-person transmission of Andes virus in Argentina
2012 Yosemite National Park outbreak (10 cases, 3 deaths)
2017 Multi-state Seoul virus outbreak from pet rats in the United States
2017 ICTV reclassifies hantaviruses into family Hantaviridae, order Bunyavirales
2018–2019 Epuyén, Argentina ANDV outbreak (34 cases, 11 deaths); "super-spreader" transmission documented
2024 ICTV promotes order Bunyavirales to class Bunyaviricetes

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 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.
  2. 2.0 2.1 2.2 2.3 Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, Ksiazek TG, Rollin PE, Nichol S, Umland ET (1994). "Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group". N Engl J Med. 330 (14): 949–55. doi:10.1056/NEJM199404073301401. PMID 8141498.
  3. Clement J, Maes P, Van Ranst M (2014). "Hemorrhagic Fever with Renal Syndrome in the New, and Hantavirus Pulmonary Syndrome in the Old World: paradi(se)gm lost or regained?". Virus Res. 187: 55–8. doi:10.1016/j.virusres.2013.12.036. PMID 24440318.
  4. 4.0 4.1 4.2 4.3 4.4 Clement J, Heyman P, McKenna P, Colson P, Avsic-Zupanc T (1997). "The hantaviruses of Europe: from the bedside to the bench". Emerg Infect Dis. 3 (2): 205–11. doi:10.3201/eid0302.970218. PMID 9204306.
  5. Mustonen J, Henttonen H, Vaheri A (2024). "Hantavirus Infections Among Military Forces". Mil Med. 189 (3–4): 551–555. doi:10.1093/milmed/usad261. PMID 37428512 Check |pmid= value (help).
  6. 6.0 6.1 6.2 Schönrich G, Rang A, Lütteke N, Hay MJ, Hoez PJ, Krüger DH (2008). "Hantavirus-induced immunity in rodent reservoirs and humans". Immunol Rev. 225: 163–89. doi:10.1111/j.1600-065X.2008.00694.x. PMID 18785530.
  7. 7.0 7.1 "Multi-state Outbreak of Seoul Virus". Centers for Disease Control and Prevention.
  8. 8.0 8.1 8.2 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, Tattoli I, 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 32553608 Check |pmid= value (help).
  9. 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).
  10. "CDC - Outbreak of Hantavirus Infection in Yosemite National Park - Hantavirus". Centers for Disease Control and Prevention.
  11. 11.0 11.1 Kuhn JH, Brown K, Adkins S, de la Torre JC, Digiaro M, Ergünay K, Forber KM, Firth AE, Gu W, Junglen S, Klempa B, Krupovic M, Lambert AJ, Maes P, Marklewitz M, Mielke-Ehret N, Mirazimi A, Mühlbach HP, Palacios G, Pawęska JT, Radoshitzky SR, Rubbenstroth D, Shi M, Siddell SG, Simmonds P, Sironi M, Smagghe G, Song JW, Spengler JR, Stenglein MD, Tesh RB, Varsani A, Zerbini FM, Postler TS (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).

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