The unprecedented and deadly cruise ship hantavirus outbreak, explained

An unprecedented outbreak of hantavirus has rocked a luxury cruise ship off the coast of West Africa, triggering a tsunami of news stories and a flood of post-pandemic anxiety.

So far, eight cases have been reported, including three people who have died. The Dutch-flagged ship, MV Hondius, which began its journey from Ushuaia, Argentina, on April 1, is still carrying 147 passengers and crew. To date, those remaining on board are showing no symptoms and have been asked to sequester themselves in their cabins. At the time of publication, the ship is sailing on a three- to four-day journey that began the evening of May 6 from Cape Verde to the Canary Islands, where Spanish authorities have agreed to assist the imperiled vessel.

With the ship en route, experts assembled by the World Health Organization are now racing to create a novel step-by-step procedure to allow the remaining passengers and crew on board to disembark safely. Meanwhile, authorities are tracking down and monitoring 30 former passengers who disembarked the ship onto the remote island of St. Helena on April 24—before the outbreak was identified but nearly two weeks after the first passenger had died on board on April 11. Those 30 passengers hail from at least 12 different countries, including six from the US.

“Extremely low” risk

The situation evokes chilling memories of the early days of the COVID-19 pandemic, especially the Diamond Princess nightmare, in which over 700 people were infected with the never-before-seen virus while locked down on a luxury cruise ship docked in Japan.

But in the wake of discovering the hantavirus aboard the Hondius, health officials and infectious disease experts have been quick—and virtually unanimous—in trying to quell fears. While the situation within the ship certainly is an emergency requiring careful and prompt response for those on board, the risk to the outside world is low, and the outbreak is expected to stay relatively small.

“This is not COVID. This is not influenza. It spreads very, very differently,” Maria Van Kerkhove, WHO’s acting director for epidemic and pandemic management, emphasized in a press briefing Thursday.

Given the nature of this virus and the precautions and monitoring already in place, “the risk of widespread transmission to the general public is extremely low,” Michael Marks, an infectious disease expert and professor at the London School of Hygiene & Tropical Medicine, said in a statement Thursday.

The comments echo a reassuring risk assessment on Wednesday from the European Centre for Disease Prevention and Control, which elaborated that even if there is disease spread from passengers evacuated from the ship, the virus “does not transmit easily so it is unlikely that it would cause many cases or a widespread outbreak in the community, if infection prevention and control measures are applied.”

The US Centers for Disease Control and Prevention also deemed the risk to the American public to be “extremely low” in a brief statement on Wednesday evening.

So why are infectious disease experts and health officials so confident this is not going to mushroom into another global health crisis?

Here’s what we know about this virus and the outbreak

Hantaviruses

The virus spreading on the ship is a member of the large hantavirus family, which is spread out worldwide. These are enveloped, negative-strand RNA viruses whose genomes consist of three segments.

So-called Old World hantaviruses (including Hantaan, Seoul, Puumala, and Dobrava-Belgrade) are found in Africa, Asia, and Europe, with hotspots of activity in China, Korea, Russia, and certain European countries. The first awareness of these viruses dates back to the 1950s, with disease in soldiers fighting in the Korean War. These viruses cause hemorrhagic fever with renal syndrome (HFRS), a disease marked by fever, bleeding, and kidney damage. Depending on the specific hantavirus virus involved, mortality rates are roughly between 1–15 percent.

Then there are the hantaviruses in the New World, which first came to light in 1993 amid a deadly outbreak of an unknown virus in the Four Corners region of the US. That outbreak was caused by a hantavirus now known as Sin Nombre virus. Since then, researchers have identified many other hantaviruses in North and South America, including Black Creek Canal, Bayou, New York, Juquitiba, Oran, and Andes. New World hantaviruses are associated with Hantavirus Pulmonary Syndrome (HPS).

Based on genetic testing, the hantavirus behind the cruise ship outbreak is the Andes virus, mainly found in Argentina and abbreviated ANDV.

Transmission

For both Old and New World hantaviruses, transmission to humans almost exclusively occurs from exposure to rodents—mice and rats of different species, depending on location—especially their urine, droppings, or other excretions. Rodents show no signs of infection or symptoms of illness.

In Argentina, the common rodent Oligoryzomys longicaudatus, aka the long-tailed pygmy rice rat, is a known source of the Andes virus, which was found on the Hondius.

For hantaviruses, human infections are accidental and almost always dead ends. Transmission to people generally happens when virus-laden rodent excreta gets stirred up in dust and inhaled—for example, a person sweeping out a shed or garage with a rodent infestation without a mask.

Such a scenario made headlines in the US last year when pianist Betsy Arakawa, who was married to actor Gene Hackman, was revealed to have died of hantavirus. A subsequent investigation found an extensive rodent infestation at the couple’s residence.

The one exception to this transmission route is from the Andes virus; ANDV is the only hantavirus that has been documented in rare instances to spread from person to person.

Based on that documented incidence, it is clear that person-to-person transmission requires close, prolonged contact. To date, though, it remains unclear whether breathing significant amounts of aerosolized virus from an infected person or exposure to an infected person’s respiratory droplets is behind the rare transmission.

Incubation period

Whether from rodent exposure or the ultra-rare person-to-person transmission, the incubation period for hantaviruses—the amount of time between exposure and when symptoms develop—ranges from about 7 to 42 days.

The currently recommended quarantine and/or active monitoring period for potentially exposed cases is 42 days.

Disease and symptoms

Infections with ANDV cause Hantavirus Pulmonary Syndrome (HPS), like other New World hantaviruses. This disease starts with a prodromal phase—early, nonspecific symptoms that precede full-blown disease.

In the prodromal phase, infected people have vague flu-like symptoms, often including fever, fatigue, headache, body aches, abdominal cramps, and gastrointestinal disturbances. This lasts about three to six days before the respiratory system becomes compromised in full-blown disease.

Based on information from documented person-to-person spread of ANDV, this prodromal phase is often when person-to-person transmission happens. In a 2018–2019 outbreak with 34 cases, the sole exposure for half the cases (17 people) was close contact with an infected person who was knowingly ill and experiencing their first day of fever.

After the prodromal phase, infected people begin having difficulty breathing, their lungs can fill with liquid, their blood pressure and blood oxygen levels can fall, and in the direst cases, they can go into shock and suffer cardiovascular collapse. Though some cases will only experience relatively minor respiratory compromise, for others, the onset of severe respiratory distress can be rapid, with people descending from minor breathing problems to needing intensive care in mere hours.

The estimated overall mortality rate of HPS can vary but is often reported as being between 30–40 percent. Those who develop the most severe respiratory symptoms face rates as high as 70 percent.

Treatments

There are currently no vaccines or targeted therapies against hantaviruses and their diseases. For those who fall ill, supportive care is critical.

In Chile and other places where hantaviruses are more common, a standard recommendation for patients with respiratory symptoms is to swiftly transfer them to a high-level care facility, preferably one with extracorporeal membrane oxygenation (ECMO). This is a type of life support that performs the work of the heart and lungs, pumping blood outside the body through a machine that oxygenates it using a microporous membrane that allows for gas exchange. ECMO improves survival rates of people with HPS.

Person-to-person ANDV outbreaks

Collectively, the handful of ANDV outbreaks with documented person-to-person transmission suggests this type of transmission is rare and requires close, prolonged contact with people who are knowingly or visibly ill. It’s also clear that steps like isolation measures for ill people, quarantine for high-risk contacts, and active monitoring are highly effective at limiting and ending the outbreaks.

The first evidence of person-to-person transmission came from an outbreak that occurred from 1996 to 1997, starting in the southwestern Argentine town of El Bosón. Genetic and epidemiological data made clear that there was person-to-person spread among 16 people.

“[I]t is remarkable that all 16 cases… were obviously epidemiologically linked; each patient was in close contact (household, health caring, marital contact, and/or traveling together within a car) with one or more members of this group,” the authors concluded.

Before you get concerned about the car exposure, know that it was a 20-hour-long trip with a symptomatic infected person—the housekeeper of the index case. The female exposed in the car had other exposures, as well: she stayed with her infected parents, the sister and brother-in-law of the index case.

The first ANDV person-to-person spread confirmed by whole-genome sequencing was reported in 2014 and found similar close contact between the cases. That outbreak was just three cases, including  71-year-old twin brothers who shared a bedroom. Both died from the infection. The third person was a nurse for one of the brothers, who survived.

An outbreak with superspreaders

The 2018–2019 outbreak with 34 cases in the southern Chubut province of Argentina was fueled primarily by three superspreader events. First, the index case spent 90 minutes at a birthday party while sick with a fever and fatigue. Of the approximately 100 guests at the party, the index case transmitted the viruses to five people sitting close to them.

One of those five people, a man, was the most likely source of six subsequent infections. Those six cases included the man’s spouse, while the rest were social contacts who were likely infected during crowded social encounters the man had during his prodromal phase. The man subsequently died, and his spouse attended his wake with a fever. Ten more people who attended the wake fell ill. Of the 34 cases overall, 11 people died.

Notably, investigators who meticulously examined the outbreak identified 82 healthcare workers at one hospital who were exposed to symptomatic cases. None of them fell ill. The 82 workers included 45 who worked in the intensive care unit or the emergency department. Only a small number of those 45 used personal protective equipment, such as N95 masks, goggles, or disposable lab coats, the investigators noted.

After the 18th case was identified, health authorities ordered isolations for symptomatic cases and quarantines for the exposed. After that, the median estimated R-naught value—the average number of people to which an infected person will spread a disease—fell from 2.12 to 0.96.

Overall, the investigators concluded that “high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission.”

A previous close call

While the possibility that people incubating ANDV are flying on planes may sound alarming, this would not be the first time it has happened. In 2018, CDC and state officials reported the first confirmed ANDV case in the US—a woman who had returned from a trip to Argentina and Chile and brought the virus home with her. She developed her first symptoms four days after returning, but then, three days later, she took two commercial flights while sick. She was hospitalized in Delaware three days later, where doctors identified the infection, which she survived.

CDC investigators identified 53 people across six states who had contact with her, including 28 healthcare workers, 15 airline contacts, and 10 other contacts. Investigators were able to contact and monitor 51 contacts, conducting testing on six with symptoms. All were negative, no other cases were identified over the 42-day incubation period, and the investigation was closed.

Current outbreak

Health officials are still working to understand what has happened on Hondius, amid speculation that human-to-human transmission has occurred.

Timeline

The boat left the southern tip of Argentina on April 1, with plans to stop at Antarctica and several islands in the South Atlantic.

The first case was in a man who developed symptoms on April 6. The man was traveling with his wife. Before boarding the ship, the Dutch couple had traveled through Argentina, Chile, and Uruguay on a bird-watching trip, WHO Director-General Tedros Adhanom Ghebreyesus said Thursday. The areas they visited included sites where the rat species known to carry ANDV is present.

The man died aboard the ship on April 11, and at the time, hantavirus was not suspected because his respiratory symptoms resembled those of other diseases. His wife then disembarked at St. Helena on April 24, along with her husband’s remains. She had symptoms. She deteriorated on a flight from the island to Johannesburg, South Africa. There, she collapsed at an airport and died on April 26. Test results from the wife confirmed a hantavirus infection on May 4.

Back on the ship, a third passenger developed symptoms, presenting to the ship’s doctor on April 24. He was evacuated on April 27 from the island of Ascension and traveled to South Africa, where he is now in intensive care. On Thursday, Dr. Tedros reported that the man has shown improvements.

On April 28, a fourth passenger on the ship, a woman, developed symptoms and died aboard on May 2, marking the third death in the outbreak.

Also on May 2, testing from the man in intensive care in South Africa provides the first results showing hantavirus.

The ship arrived in Cape Verde around May 4, where doctors boarded and provided care for three more symptomatic people, bringing the total number of cases from the ship to seven. Those three cases were evacuated to the Netherlands. Two are hospitalized in stable condition, and one is asymptomatic and now in Germany.

The eighth case identified was a man in Switzerland who disembarked in St. Helena on April 24. Upon notification of the outbreak from the cruise operator, he went to a hospital in Zürich and was confirmed to have a hantavirus infection. Genetic testing from this patient confirmed the virus as ANDV.

Next steps

It remains unclear whether any of the other passengers had similar travel histories to the Dutch couple or other possible hantavirus exposures prior to boarding the ship that could explain the cases. But person-to-person spread certainly seems possible given that the hantavirus involved here is the one known for such transmission, and cruise ships are notorious for providing the close, confined environments where viruses can vigorously spread—as is the case for COVID-19 or the gastrointestinal terror norovirus.

Monitoring

For now, WHO officials are working on a plan to get the remaining 147 people off the boat safely. As of May 8, the ship’s operator reports that no one on board has symptoms. However, with the possibility of person-to-person spread, an incubation period up to 42 days, and the last onboard illness onset of April 28, it will take more time before the coast is clear. Health officials will also need to identify and trace the contacts of the people who disembarked the ship amid the outbreak.

In the press briefing on Thursday, WHO officials acknowledged that 42 days is a lengthy quarantine. At this time, the United Nations’ health agency is not recommending that people stay confined for that whole period; rather, the recommendation is to do active monitoring for symptoms, such as daily temperature checks, given that person-to-person spread has only been seen from symptomatic people. Whether people are quarantined in addition to that is up to health authorities in the places with affected people.

Viral genetics

Researchers around the globe are also anxious to get the genomic data of the ANDV virus. Questions have swirled over whether the virus on the ship carries mutations or other changes that might explain the never-before-seen outbreak.

But WHO officials on Thursday were careful to note that the main differentiator of the outbreak so far is simply that it was on a ship. No other major features of the outbreak appear out of line with previously documented ANDV outbreaks involving person-to-person spread.

In the 2018–2019 outbreak, researchers noted that virus genetics didn’t seem to make a difference between an infected person who transmitted the virus to 10 people and an infected person who didn’t transmit the virus at all. The viruses looked about the same. The difference, they concluded, seemed related to individual people and their behavior.

“The absence of evidence for ANDV adaptation within or between hosts or for differences in viral diversity between spreaders and nonspreaders indicates that permissive ecology and social factors have a more substantial influence than genetic changes in sustaining person-to person transmission in human hosts,” they concluded.