Hantaviruses

Unlike the ecological label “arbovirus”, hantaviruses form a true taxonomic family, the Hantaviridae, within the order Bunyavirales. The family is ancient and diverse, with members found across fish, amphibians, reptiles, mammals and even jawless vertebrates, but the species that infect humans belong exclusively to the genus Orthohantavirus.

Unusually for the order Bunyavirales, hantaviruses are not arthropod-borne. They are maintained in small mammals, and people are infected by inhaling aerosols of infected rodent excreta.

The distribution of these viruses is reservoir-restricted rather than simply geographical. Each has co-evolved with a particular small-mammal host, usually a rodent but sometimes an eulipotyphlan such as a shrew or mole, in which it establishes a lifelong, symptomless infection, so the phylogeny of the viruses largely mirrors the phylogeny of their hosts. A hantavirus is therefore found wherever its reservoir lives, and it is the host, not the map, that dictates where each disease appears.

Clinically the human pathogens are divided into haemorrhagic fever with renal syndrome (HFRS), classically an Old World disease, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. This divide is a useful first approximation rather than a strict rule: the rat-borne Seoul virus causes HFRS worldwide, and several African hantaviruses fall outside the binary. The two syndromes are best understood as a shared spectrum of profound vascular permeability, in which renal and pulmonary injury frequently overlap, rather than as wholly separate diseases.

HFRS is the common and usually survivable end of that spectrum, with tens of thousands of cases a year across Asia and Europe; HCPS is rare but highly lethal, with a case-fatality around 35 to 40%. One further feature sets a single virus apart from the rest of the group: Andes virus is the only hantavirus documented to pass from person to person.

Virology and transmission

Like all members of Bunyavirales, hantaviruses are enveloped viruses with a three-segment, negative-sense RNA genome. The large (L) segment encodes the polymerase, the medium (M) segment the envelope glycoproteins Gn and Gc, and the small (S) segment the nucleocapsid protein. They prime their messenger RNA by stealing host caps (cap-snatching) and assemble at the Golgi, the shared bunyavirus pattern.

Transmission to humans is almost always by inhalation of aerosolised rodent excreta, typically when disturbing contaminated dust in barns, storerooms or rural dwellings that rodents have colonised. Bites and contaminated food are minor routes. Infection risk therefore tracks rodent population booms, which is why HCPS outbreaks in the American southwest follow the wetter years of the El Nino Southern Oscillation: heavy rain drives a surge in deer-mouse numbers and human contact rises with them.

Humans are a dead-end host for every hantavirus but one. The virus does not normally spread between people, so a human case is a marker of rodent exposure rather than a source of onward transmission. Andes virus is the exception, below.

The New World and Old World split

Grouping the hantaviruses this way is clinically useful because, for most species, the reservoir and its geographic range predict which syndrome to expect and how severe it will be. The main exception is Seoul virus: carried worldwide by the brown rat, which has followed shipping to every continent, it causes HFRS well beyond the Old World and is the one HFRS agent an urban clinician anywhere might encounter.

Virus	Group	Syndrome	Rodent reservoir	Region	Case-fatality
Sin Nombre	New World	HCPS	Deer mouse (Peromyscus maniculatus)	North America	~35 to 40%
Andes	New World	HCPS	Long-tailed pygmy rice rat (Oligoryzomys longicaudatus)	South America	~35 to 40%
Hantaan	Old World	HFRS (severe)	Striped field mouse (Apodemus agrarius)	East Asia	~5 to 15%
Dobrava-Belgrade	Old World	HFRS (severe)	Yellow-necked mouse (Apodemus flavicollis)	The Balkans, Europe	~9 to 15%
Seoul	Old World	HFRS (moderate)	Brown rat (Rattus species)	Worldwide	~1 to 2%
Puumala	Old World	HFRS (mild)	Bank vole (Myodes glareolus)	Europe	under 1%

Two points refine the table. Puumala virus causes the mildest form of HFRS, historically called nephropathia epidemica, and accounts for most of the European caseload. And the table is not exhaustive: several African hantaviruses, such as Sangassou virus, fall outside the classic Old World and New World disease binary and are not linked to the severe syndromes at all.

Pathogenesis

Both syndromes share a mechanism that is, at first sight, surprising: the virus is not directly cytopathic. Hantaviruses infect vascular endothelial cells without destroying them, and the disease is driven instead by an immune-mediated increase in vascular permeability. Activated T cells and a surge of inflammatory cytokines loosen the junctions between endothelial cells, and plasma leaks out of the circulation.

Where that leak does its greatest damage is what distinguishes the two syndromes, though the difference is one of emphasis rather than kind. In HFRS the microvascular injury falls predominantly on the kidney, producing acute kidney injury, while in HCPS it falls predominantly on the lung, flooding the alveoli with protein-rich fluid to produce non-cardiogenic pulmonary oedema. The organs overlap in practice: HFRS, especially from Puumala virus, often causes respiratory symptoms and pulmonary oedema, and HCPS, especially from Andes virus, frequently involves the kidney.

A molecular correlate underlies the split in virulence. Pathogenic hantaviruses enter endothelial cells through beta-3 integrins, receptors that also regulate vascular permeability and platelet function, whereas non-pathogenic species use beta-1 integrins. Thrombocytopenia is near-universal in both syndromes, from platelet consumption at the damaged endothelium, and is one of the earliest laboratory clues.

Clinical syndromes

Both diseases begin after an incubation of about two to three weeks with a nonspecific febrile prodrome, then diverge.

Feature	HFRS (Old World)	HCPS (New World)
Predominant organ	Kidney	Lung
Classic phases	Febrile, hypotensive, oliguric, diuretic, convalescent	Febrile prodrome, cardiopulmonary, diuretic, convalescent
Hallmark	Acute kidney injury, haemorrhage	Non-cardiogenic pulmonary oedema, shock
Case-fatality	under 1% (Puumala) to ~15% (Hantaan, Dobrava)	~35 to 40%
Ribavirin	Benefit if given early	No proven benefit

HFRS runs through five classic phases: a febrile phase of fever, headache and the characteristic facial flushing and conjunctival haemorrhage; a hypotensive phase when vascular leak can tip into shock and disseminated intravascular coagulation; an oliguric phase of acute kidney injury that is the usual time of death; a diuretic phase of recovering urine output; and a prolonged convalescent phase. Bleeding is real but rarely the fatal event; kidney failure and shock are.

HCPS compresses into a faster, more lethal course. A febrile prodrome of a few days gives way abruptly to the cardiopulmonary phase: rapidly worsening non-cardiogenic pulmonary oedema, hypoxia and cardiogenic shock from depressed myocardial function, which can kill within a day or two of admission. Patients who survive the first 48 hours usually recover through a diuretic phase. Unlike HFRS, true haemorrhage is uncommon in HCPS despite the profound capillary leak.

The Andes virus exception

Andes virus, a South American cause of HCPS, is the only hantavirus for which person-to-person transmission is documented, and it therefore behaves unlike every other member of the group. Clusters have occurred among household contacts and healthcare workers, and the risk is highest during the patient’s viraemic late-incubation and early-symptomatic period.

The most striking recent illustration is a 2026 outbreak aboard the expedition cruise ship MV Hondius, which sailed from Ushuaia, Argentina, on a South Atlantic and Antarctic itinerary. A cluster of severe respiratory illness among passengers and crew was confirmed as Andes virus, and by mid-2026 there were 13 cases and 3 deaths, with spread aboard attributed in part to human-to-human transmission in the ship’s shared, enclosed spaces. The event drew World Health Organization (WHO) and other international attention precisely because person-to-person spread of a hantavirus is otherwise almost unknown.

This exception reshapes infection control: a suspected Andes virus case requires contact tracing and respiratory precautions of a kind that would be unnecessary for any rodent-acquired hantavirus.

Diagnosis and management

Diagnosis rests chiefly on serology, because patients usually present after the short viraemic phase, once antibody is already rising. Immunoglobulin M (IgM) is detectable at symptom onset in most cases, with a rising immunoglobulin G (IgG) titre confirming recent infection; capture enzyme-linked immunosorbent assay (ELISA) is the workhorse. Marked cross-reactivity between hantavirus species means a positive screen is often followed by a species-specific or neutralisation assay. Reverse-transcriptase polymerase chain reaction (RT-PCR) can detect and genotype the virus early in illness but is not used alone.

Management is supportive, and outcome depends heavily on recognising the syndrome early and delivering the right organ support. HFRS is managed with careful fluid balance and renal replacement therapy through the oliguric phase. HCPS is a critical-care diagnosis: meticulous fluid restriction to avoid worsening the pulmonary oedema, inotropic support, and extracorporeal membrane oxygenation (ECMO) for the most severe cardiopulmonary failure, which has improved survival in referral centres. The antiviral ribavirin has a benefit in HFRS when started early but no proven benefit in HCPS.

Prevention

There is no widely licensed hantavirus vaccine. Inactivated vaccines against Hantaan and Seoul viruses are used in parts of Asia, chiefly China and Korea, but none is available in most of the world, so prevention rests on reducing rodent contact.

The core measures are rodent control and safe cleaning of rodent-infested spaces: sealing dwellings against rodents, storing food securely, and ventilating then wetting contaminated areas before cleaning rather than sweeping or vacuuming dry, which aerosolises the virus. For the Andes virus exception, prevention additionally requires personal protective equipment and isolation precautions around a symptomatic case, as for a person-to-person respiratory pathogen.

South African context

South Africa has no documented local human hantavirus disease. The severe cardiopulmonary and renal syndromes described above are not acquired within the country.

The picture in local rodents is more nuanced. Southern African rodents do carry native, generally mild African hantaviruses, such as Sangassou virus, but not the New World species that cause hantavirus cardiopulmonary syndrome. The practical message for South African clinicians is therefore that the country’s own rodents are not a source of the severe disease, and that the realistic local risk is an imported Andes virus case in a traveller returning from South America, the very scenario that the cruise-ship outbreak brought to prominence.

Hantavirus infection is a Category 1 notifiable medical condition in South Africa, requiring notification within 24 hours. Specialised testing and outbreak support are provided by the National Institute for Communicable Diseases (NICD). Because of the Andes virus person-to-person risk, the NICD maintains a contact management protocol built around exposure risk assessment, monitoring of contacts for the length of the incubation period, and admission of suspected cases to designated isolation facilities, of which Tygerberg Hospital is one of the Western Cape sites.

References and recommended reading

• Spiropoulou CF, Bente DA. Orthohantavirus, Orthonairovirus, Orthobunyavirus, and Phlebovirus. In: Fields Virology, 7th edition, Chapter 17. Philadelphia: Wolters Kluwer; 2023. The principal source for hantavirus clinical syndromes, epidemiology and the New World and Old World split.
• Barr JN, Weber F, Schmaljohn CS. Bunyavirales: The Viruses and Their Replication. In: Fields Virology, 7th edition, Chapter 16. Philadelphia: Wolters Kluwer; 2023. The source for hantavirus genome organisation, replication and Golgi assembly.
• Mertz GJ, Ahlm C, Jonsson CB. Bunyaviridae. In: Richman DD, Whitley RJ, Hayden FG (eds.), Clinical Virology, 4th edition, Chapter 44. Washington: ASM Press; 2016. The foundational account of the HFRS and HCPS syndromes and their rodent reservoirs.
• Burrell CJ, Howard CR, Murphy FA. Bunyaviruses. In: Fenner and White’s Medical Virology, 5th edition, Chapter 29. Academic Press / Elsevier; 2017. The foundational account of hantavirus reservoir ecology and the not-arthropod- borne distinction.
• National Institute for Communicable Diseases. Hantavirus Pulmonary Syndrome: Frequently Asked Questions. NICD; 2026. The source for the South African hantavirus situation and rodent-reservoir position.
• World Health Organization. Hantavirus cluster linked to cruise ship travel, multi-country. Disease Outbreak News; 2026. The source for the 2026 Andes virus cruise-ship outbreak.