Haunting Questions About a Lethal American Virus

Glowing embers cascading from Glacier Point. The ancient granite of Tuolumne Meadows. The Mist Trail leading to Vernal Falls. All these memories and more were treasured by my mom — a native Californian who loved Yosemite National Park. My mother also loved Yosemite’s canvas-covered cabins where she often stayed during childhood summers.

But now that a dozen years have passed since deceptively cute deer-mice invaded some of those cabins’ foam insulation, then shed a virus that gravely sickened eight people and killed three of them, I can’t help but wonder: decades earlier, could the same fate have befallen my mom? Similarly, did certain people in the American Southwest suffer the dire illness called hantavirus pulmonary syndrome (HPS) long before 1993, when the U.S. recorded its first official outbreak in Arizona and New Mexico? In that instance, 15 of 17 early sufferers died from inhaling an agent aerosolized from the feces, urine, or saliva of Peromyscus maniculatus mice that was later christened Sin Nombre virus (SNV) — the virus that causes HPS.

Over the next 28 years, the U.S. recorded roughly 800 laboratory-confirmed cases of HPS, of which 35% were fatal and 94% occurred west of the Mississippi River. Although New Mexico, Colorado, Arizona, California, Washington, and Texas typically lead the country in reported cases, SNV has now infected at least one person in 40 of our 48 lower states.

This brings me back to my question: Might others have been infected before the first officially recorded outbreak? Of course, SNV was present long before it made medical headlines, just like other deadly zoonotic viruses such as Ebola, Nipah, and the first SARS coronavirus. But despite their significance, SNV is especially close to my heart for reasons that will soon become clear.

Hantavirus 101

What are hantaviruses, anyway? When lecturing about rodent-borne infections, I often show a list of 24 hantaviruses that currently harm humans, each strain carried by a different rodent in a different place. Seoul, Puumala, Dobrava, Andes … and the names go on. Today’s prevailing wisdom is that these single-stranded RNA agents, which profoundly injure vascular endothelium, co-evolved with their mammalian hosts over millions of years.

Nonetheless, it was not until 1978 that the first hantavirus was isolated. Its distinctive human illness — hemorrhagic fever plus renal disease — was initially described in China in the 1930s and later sickened soldiers fighting the Korean War. This explains why CDC’s legendary virus hunter Karl Johnson, MD, named the virus after Korea’s Hantaan River. Two years earlier, Johnson also named Ebola for a waterway near a virus-ravaged village in the Democratic Republic of Congo. Sadly, America’s 1993 HPS outbreak was just as lethal.

Nick’s Story

In September 1993, a good friend with whom I had previously worked on a medical TV news show wanted to scout locations for a possible documentary. One weekend Nick decided to explore Julian — a 19th century mining town in eastern San Diego County where he entered an old, abandoned cabin that probably harbored rodents. Soon after, the same fit Nick who had recently climbed Mount Rainier returned to Los Angeles and developed unexplained fever, aches, and other worrisome symptoms that prompted immediate admission to a local hospital.

Two days later, he had progressed to full-blown shock and non-cardiogenic pulmonary edema. Even worse, while receiving multiple pressors and artificial ventilation, Nick’s oxygenation continued to drop.

Given these facts, the final hope was to use extracorporeal membrane oxygenation (ECMO) as a last-ditch measure to save Nick’s life. But, by then, he was so unstable he couldn’t be transferred to a university hospital. Surrounded by his stunned family and grief-stricken wife, he simply slipped away.

Did anyone prove that HPS killed Nick? After all, an early blood sample tested by CDC did not reveal SNV antibodies. Nonetheless, I have never doubted my friend’s diagnosis. As most doctors know, pathogen-specific antibodies can take 14 days or more to form, and Nick’s catastrophic illness lasted less than a week from start to finish.

Coda: Last month, I left a message at the office of the pulmonary and critical care specialist who had admitted my friend. Less than 5 minutes later, he and I were speaking on the phone. “Horrific” was the first word he uttered when describing Nick’s course. “Of the three most terrible cases of my career,” he then added, “I think his was the worst.”

Surveillance Meant to Save Lives

Last month, I also spoke about hantavirus with professionals at the San Diego County Health Department: one a vector-borne veterinarian, the other a seasoned public health doctor. In the early 2000s, assistant medical director Mark Beatty, MD, MPH, worked as a clinician in Crownpoint, New Mexico — the virtual epicenter of the original 1993 SNV outbreak. Even then, Beatty said, his small Navajo Nation sickbay often saw up to one or two “rule out HPS” patients every month as well as the occasional desperately ill sufferer who, like Nick, was teetering on the edge of disaster.

“We only had four emergency departments and 17 hospital beds,” Beatty added, “[so] we certainly couldn’t support serious cases. Our rule was to transport as quickly as possible to Albuquerque for ECMO, but patients often didn’t make it.”

Beatty also mentioned the link between heavy rains and the proliferation of SNV-infected mice. In New Mexico, he recalled, “it was like a 2-year lag” between a wet, El Niño season leading to expanded food sources and rodent populations followed by a rise in human cases.

On a more optimistic note, Nikos Gurfield, DVM, stressed the progress in detecting wild SNV-infected mice in higher-risk areas and increased efforts to alert humans. This is especially true in San Diego County, where surveillance is robust and 2023 saw a total of 17 hantavirus-infected mice. In 2024, the County has already confirmed 18 wild, infected mice positive for hantavirus on a quick, easy immunoassay.

“Where do you conduct your surveillance?” I asked.

“We primarily collect from areas where we anticipate that human-rodent wildlife interface,” Gurfield replied, such as “our county’s many rural parks, preserves, and campgrounds…and canyons that course through our urban areas.”

“When we do find positives,” he continued, “we like people to know about it. So you’ll periodically see press releases to remind people how to stay safe — for example, by not sweeping up rodent droppings and nests without first using a wet cleaning method. And if you enter sheds that you haven’t gone into for a long time,” he added, “make sure you get airflow, all those kinds of things. Because we’re here to protect the public.”

The communication must be working. In this century, thankfully, San Diego has seen only one human with a locally acquired hantavirus infection, and that was in 2004. If only we had known more, and informed more people, in the early 1990s. Simply writing this column has reminded me how much I still miss Nick, my close colleague and pal.

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