Key Points
- Hantaviruses spread from rodents to people. However, Andes hantavirus (ANDV) is also capable of human-to-human transmission.
- ANDV can transmit between individuals in certain close-contact conditions. Transmission is likely respiratory droplet-driven, though is less efficient than for other viruses like SARS-CoV-2.
- Compared to other RNA viruses, ANDV appears to be more stable and mutate less frequently. This may be due to viral and host factors.
- More research is needed to understand hantaviruses both in nature and in humans to develop vaccines and therapeutics to mitigate infections.
In April 2026, a passenger boarded a Dutch cruise ship in Ushuaia, Argentina after a bird-watching trip. Ten days later, he died.
The cause of his death, while initially unclear, was determined to be Andes hantavirus (ANDV), which he picked up prior to boarding the ship. His wife, sickened by the same virus, later died as well. As of this writing, there have been 10 reported cases of ANDV infection from the ship, resulting in 3 deaths.
Cruise ships may be known for viral outbreaks but, due to the virus involved, this situation was an unusual one.
Hantaviruses Spread From Rodents to People-Andes Virus is Unique
Of course, it is not unusual for a virus to spread between people. Hantaviruses, though, are different.
Rodents like mice and rats are the definitive hosts of hantaviruses. More than 40 species and strains of hantaviruses exist in nature, and over half are known to be capable of spilling over into humans. Infections can result in severe disease with high mortality rates (up to 35-40% depending on the virus and disease outcome). Symptoms take days to weeks to appear, and may include headache, fever, abdominal and back pain, vomiting and hemorrhaging.
There are currently no licensed vaccines or antivirals for hantaviruses, a family of single-stranded, negative-sense RNA viruses. Transmission usually occurs through contact with contaminated rodent saliva, feces, urine and aerosols, such as by sleeping in rodent-infested dwellings or cleaning poorly ventilated spaces. Humans are normally dead-end hosts for hantaviruses.
But ANDV is unique. It does transmit from rodents to people like other hantaviruses, and that is how most infections start. However, sporadic outbreaks over several decades-primarily in Argentina and Chile-have shown that it also has the capacity for human-to-human transmission.
For example, a 2018 outbreak in Argentina resulted in 34 confirmed cases of ANDV infection and 11 deaths. The outbreak began when someone sick with ANDV attended a birthday party with 100 people; 5 people who were seated close to the individual later developed symptoms. The chain of transmission continued from there. Overall, experts determined that "after a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events." The recent cruise ship outbreak adds to the pool of evidence.
What sets ANDV apart from its relatives? How exactly does it spread between people? Answers to these questions have implications for outbreak control and therapeutic development. They can also help experts determine what the disease landscape of the future could look like, and how to prepare for it now.
"Why are some viruses very successful at spilling over and why are some not?" asked Colleen Jonsson, Ph.D., a professor in the Department of Microbiology, Immunology & Biochemistry at The University of Tennessee Health Science Center. "We have a number of examples of viruses that have gone global and become endemic in human populations, but we know relatively little about how they began. That's where my research is focused-how the virus maintains itself in nature and what the drivers of spillover are."
How Does ANDV Spread From Person-to-Person?
Despite knowing for 3 decades that ANDV has the capacity for human-to-human transmission, scientists have not definitively determined how it happens.
Studies suggest that the virus can transmit between individuals in certain close-contact conditions, such as prolonged viral exposure in poorly ventilated or crowded settings (e.g., on a bus, airplane or, indeed, cruise ship), sleeping in the same bed or room as someone with ANDV infection or household contact or caregiving without wearing personal protective equipment.
"[Transmission] is likely respiratory droplet-driven," said David Safronetz, M.S., Ph.D., a research scientist in the Special Pathogens Unit of the Public Health Agency of Canada, National Microbiology Laboratory Branch and an adjunct professor at the Max Rady College of Medicine at the University of Manitoba. "The WHO is suggesting that it's prolonged close contact for at least 15 minutes within 2 meters or so of space. [But it] certainly doesn't seem to be as efficient as something like COVID or the common cold."
In a 2020 study, researchers used immunocytochemistry, multichannel immunofluorescence and transmission electron microscopy to examine the lung tissue and salivary glands of ANDV-infected pygmy rice rats (key primary hosts) and people who died from ANDV-induced hantavirus pulmonary syndrome (HPS), a particularly deadly outcome of hantavirus infection.
Hantavirus antigens were detected in airway-facing epithelial cells, macrophages (which could be coughed up in respiratory droplets) and secretory cells/pathways of salivary glands, in addition to endothelial cells in the lungs (hantaviruses are known to infect endothelial cells throughout the body). While the presence of ANDV antigens is not direct evidence of viral infection or replication, the results support that the virus may spread through respiratory and/or salivary pathways.
Studies have also assessed what, on a molecular level, may facilitate ANDV human transmission. Researchers identified 3 amino acid substitutions when they compared genomic sequences from ANDV clades associated with person-to-person transmission to sequences from ANDV and ANDV-like viruses not associated with that mode of spread. One mutation was present in the ANDV glycoprotein involved in host cell attachment and membrane fusion; the others were in the virus's nonstructural protein, which antagonizes host innate immune responses to facilitate infection. How these mutations specifically relate to transmission, and their functional impact, is still unclear.
Clarifying the picture is tricky, though. Apart from a Syrian hamster model that recapitulates key aspects of HPS, there are limited disease models available to study hantaviruses. Moreover, "we don't have many isolates of Andes virus," Safronetz noted. "Hantaviruses are notoriously challenging to isolate and culture, which makes the downstream analysis difficult." Due to the long incubation period of hantaviruses (1-8 weeks), HPS in humans is often recognized after the body is already making antibodies to neutralize hantaviruses, which decreases their infectivity in cell cultures. Rodents similarly produce neutralizing antibodies that can hinder isolation of culturable virus.
In light of this challenge, Jonsson emphasized the need for more high-quality genomic data from ANDV and its relatives. Those sequences, combined with epidemiological tracing, may offer some hints about the mechanisms underlying why and how ANDV spreads the way it does.
How Quickly Does ANDV Mutate?
One thing that laboratory experiments have revealed is that ANDV does not appear to be as genetically shifty as other RNA viruses that are well-adapted to humans and rapidly mutate as they spread, such as SARS-CoV-2.
For example, in vitro passage of a rodent-isolated ANDV strain 19 times led to "very few mutations"-those that developed by passage 19 resulted in significantly attenuated disease in a hamster model compared to virus from an earlier passage (p9).
In another study, Safronetz's lab passaged a human ANDV isolate in Syrian hamsters 25 times. The isolate replicates poorly in vivo and does not cause lethal disease in hamsters compared to other strains. They then infected the hamsters with virus from early, middle and late passages to identify genomic changes that influence infection outcome in the animals. The team noted a single coding mutation in the viral glycoprotein with no change in disease, suggesting minimal selective pressure in certain hosts.
It's worth noting that hamsters are similar to the virus' natural rodent reservoirs, which have co-evolved with hantaviruses for 20 million years. In more divergent hosts, the outcome may be a little different. Still, early evidence from the recent ANDV cruise ship outbreak showed the virus was closely related to sequences from the 2018-2019 outbreak in Argentina. This means that in nearly 8 years, the virus did not appear to have evolved significantly. Genomic analysis demonstrated that the virus exhibited 2 small mutations in 2 patients from the ship, with no change in its behavior.
Scientists aren't sure what explains this stability. "[Hantaviruses] replicate relatively slowly, so maybe that makes their polymerase a little bit more efficient than other RNA viruses that tend to replicate extremely quickly and introduce maybe more mutations," Safronetz postulated.
The in vivo environment plays an important role, too, as host responses can impact viral evolution. Jonsson's lab showed in a suckling mouse model that treating animals infected with Hantaan virus (another type of hantavirus) with the antiviral ribavirin reduced infectious virus levels but increased the virus's mutational frequency. The drug appears to work, in part, by inhibititing viral replication and possibly via other unknown off-target effects on the host. "[The virus underwent] purifying selection inside the animal, unless we gave it a drug. Once we gave it a drug, then it began to explore more sequence space," she said.
Could Hantaviruses Cause the Next Pandemic?
Viral stability does not equal stagnation: hantaviruses can change. Could ANDV cause a pandemic? Experts note that multiple evolutionary changes-particularly those that could help the virus transmit to and between humans more efficiently-would be required for ANDV or any recognized hantaviruses to have pandemic potential. This is possible, though unlikely, based on scientists' current understanding of hantaviruses.
Even so, proper containment and monitoring of infected or exposed individuals is important for minimizing the chances of ANDV transmitting to a larger pool of people where it could have more chances to spread and evolve.
Researchers also underscore the need to keep tabs on hantaviruses and their genetic changes in reservoir hosts, particularly as climate and environmental changes increase the risk of animal-human contact and potential spillover events.
Expanding Ecological Surveillance
For Safronetz, this focus on bolstering ecological surveillance of hantaviruses is critical. He encourages research groups to "get back out there," reflecting on how previous field studies led to the discovery of ANDV and other hantaviruses.
"I think we can get a lot more informative information if we can really understand the spillover events," he said. Studying ANDV human-to-human transmission is a critical area of investigation, "but if we can go a step backwards and figure out what the trigger is from [rodents] to humans, that would go a long way in preventing antiviral diseases in humans globally."
To that end, Jonsson's team has been working in Paraguay for more than 30 years to understand hantaviruses in nature, with the hopes of better delineating spillover dynamics. "Recently, one of the viruses that we found some time ago in Paraguay was detected in a human. So, it's just a matter of continuing surveillance in rodents," she said.
Exploring Hantavirus Vaccines and Treatments
When hantaviruses do spill over into humans-and, in the case of ANDV, have the potential to spread between them-it would be valuable to have preventive and therapeutic tools at the ready to deal with them. Right now, we don't.
"The Holy Grail is [if] we could come up with a way to treat all these viruses," Jonsson said. "And so, continuing to work on that problem, I think, is important to find small molecules, or groups of small molecules, that we can tune quickly to provide treatment."
Scientists are also working on developing vaccines and monoclonal antibodies for hantaviruses. Limitations to their ultimate production and distribution are not due to a lack of technology, but rather funding and regulatory constraints. Hantaviruses, which cause sporadic outbreaks, tend to fall under the radar compared to other more widespread public health threats. It can be challenging to secure financial support to study them.
The Need for More Research
But if the cruise ship ANDV outbreak reveals anything, it's that "we can't neglect these other pathogens that we know are present all the time globally," Safronetz said. "I think [this outbreak] just re-emphasizes the fact that research needs to still be conducted on these because during events like this, people ask the right questions: 'why is there no vaccine? Why is there no therapeutic?' And it's because [hantaviruses] have been neglected for quite some time in the research field."
The ASM Journals Hantavirus Collection provides the latest comprehensive insights into hantavirus research, covering immune responses, viral genetics, transmission and pathology, with implications for diagnostics, therapeutics and biosafety.
