When news broke of a deadly outbreak of a rodent-borne hantavirus aboard the cruise ship MV Hondius last month, it took only hours for wild conspiracy theories to start to circulate about how it might have started. Was this a side effect of COVID-19 vaccines? Did the virus leak from a lab in Australia?
A more prosaic and plausible origin story also took hold quickly: The first patient, a 70-year-old Dutch man who died on board the ship on 11 April, could have come into contact with rodents carrying hantavirus while he and his wife were birdwatching at a landfill in Ushuaia, the city on Argentina’s southern tip where the cruise started on 1 April. (His wife died 2 weeks later on her way back to the Netherlands.)
But even that story “never made much sense,” says Gustavo Palacios, a virologist at the Icahn School of Medicine at Mount Sinai. No hantaviruses have ever been reported around Ushuaia, and the region has never seen cases of the disease they cause, hantavirus pulmonary syndrome. Palacios and a large group of other researchers are now investigating several other possible scenarios, including some that would revise scientists’ knowledge of where the virus circulates or its incubation period.
The investigation promises fresh insights into the little-studied Andes virus, the species that caused this outbreak and the only hantavirus documented to transmit from person to person. (Other strains infect people only through contact with rodents, such as breathing in dried rodent feces or being bitten.) “We don’t yet understand whether this virus is more transmissible in some regions than in others” because of genetic differences between strains, says Nicole Tischler, a virologist at the Science and Life Foundation and San Sebastián University. Finding out where different Andes strains circulate, under which circumstances they jump to humans, and how easily they spread is key to “strengthening surveillance, prevention, and response strategies for similar future events,” Argentina’s minister of health, Mario Lugones, wrote in a statement to Science.
The Dutch couple, both retired ornithologists, took a 4-month road trip through Argentina, Chile, and Uruguay before boarding the ship. Researchers have pieced together their itinerary through geolocation data from bird photos they posted on a website called eBird and records of their border crossings. Strangely, they do not appear to have traveled through areas where Andes virus is known to circulate, or where human cases of disease have appeared, during the virus’ known incubation period. Estimates vary, but the Pan American Health Organization puts that period at 7 to 39 days.
Although researchers were skeptical of the link to Ushuaia from the start, it has only become more unlikely as they have gathered evidence. The Dutch passengers arrived in Ushuaia on 29 March, and the man is now understood to have developed a fever just 5 days later, on 3 April. (Earlier reports had pinpointed 6 April.) Such a short incubation period is “not impossible, but it seems very unlikely,” says Valeria Martinez, a virologist at Argentina’s National Institute of Infectious Diseases and a collaborator on the investigation. And trapping efforts by an Argentine team at the Ushuaia landfill turned up no long-tailed pygmy rice rats, the rodents that carry Andes virus, Martinez adds.
Genomic evidence points to a different region. When researchers compared the viral sequences recovered from passengers on the MV Hondius with Andes virus sequences from other patients, they found the closest matches dated to 2018. They were taken from two brothers who fell ill in Villa Meliquina in Neuquén province, more than 2000 kilometers north of Ushuaia and bordering Chile. After discovering the match, Argentine researchers sequenced samples from more recent cases in that area and found that these, too, were very similar to the virus isolated from cruise ship passengers. “So we know that these viruses are still circulating in that area,” Palacios says. Their itinerary shows the couple passed through Neuquén in their motor home before the cruise. But that was in the first days of February, which would mean an unprecedentedly long incubation period of 60 days.
Evidence from animals bolsters the connection between the outbreak and this region. Lissette Ulloa-Zepeda, a Ph.D. student at the University of Development who has been setting up genetic surveillance of Andes virus in rodents, published sequences online in May that are even more closely related to the outbreak strain. They come from long-tailed pygmy rice rats caught in 2013 in Toltén in Araucania, the region that borders Neuquén on the Chilean side, and through which the Dutch couple passed on their way to Argentina. “The genomic data points to that region in Chile and Argentina,” says Ulloa-Zepeda. But fewer than 100 full genomes of Andes virus have ever been published, leaving large gaps in researchers’ knowledge. “We need more sequences to say anything more precise,” Ulloa-Zepeda says. For now, the closest sequences from both rodents and humans come from areas the couple passed through outside of the known incubation period, Palacios notes.
There are other possibilities. One is that the Dutch man was not the first case in the infectious chain but was infected by another human while traveling. But the most likely scenario for now, Martinez says, is that a rodent snuck into the couple’s mobile home and infected the man at some later point during the trip. “This is pretty common in the area when winter comes,” she says. “The rodents invade the cars looking for food and shelter.” However, she adds, “We are still learning about this virus, so I can’t rule out any hypothesis.”
Researchers and public health authorities in Uruguay have located the couple’s motor home, which had been parked there since they joined the cruise. “We didn’t find feces or any obvious remnants of rodents in the van,” says Adriana Delfraro, a virologist at the University of the Republic. The researchers have taken swabs from the van to look for evidence of the virus or its rodent host. “It’s gonna be hard” given how much time has elapsed, Delfraro says. “But let’s see what we can find.”
If the 60-day incubation period is correct, that would call into question the 42-day quarantine the World Health Organization (WHO) has recommended for healthy passengers who have left the MV Hondius, which most countries are following. But even in that case, 60 days is likely an outlier, says Thomas Ksiazek, a researcher at the University of Texas Medical Branch who was not involved in the investigation: “The probability of it being that long is still not very high.” And patients only become infectious around the time they start to have symptoms, he notes, meaning monitoring former passengers for symptoms might be enough.
In fact, even 42 days is a long quarantine. Argentina, which first quarantined contacts of Andes virus cases during an outbreak in 2018, has become more flexible as it faced more outbreaks, shortening requirements from 40 days to 30 days for high-risk contacts and 21 for low-risk contacts, Martinez notes. WHO’s more cautious response to this one-off outbreak is “maybe a little exaggerated,” she says, “but that’s OK when it’s only one time.”
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