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Pop quiz question #1: How many clinicians can name their region's leading rickettsial threat and its arthropod vector? Globally, the small, intracellular bacteria causing spotted fevers and typhus infect humans via ticks, fleas, mites, chiggers, and lice. In Africa, China, and the U.S., Rickettsia felis can also live in , but that's a story for another day.

Here at home, our deadliest rickettsial scourge is Rocky Mountain spotted fever, which -- before treatment with chloramphenicol or tetracycline -- killed its victims. But that was then. Today, antibiotics save countless lives. However, the still-treacherous tick-borne blight has spread and can now infect people in all 48 contiguous states and parts of Canada and Latin America (the situation in northern Mexico is ). Domestically, its toll has shifted to North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri.

What about domestic flea-borne typhus (FBT) -- once another common rickettsial threat, especially in the humid American South? Thanks to DDT and modern rodenticides, FBT dramatically declined after World War II, but it still persisted in pockets of California, Texas, and Hawaii. In fact, just last month, a letter to local physicians cited Los Angeles County's count of 171 verified cases and three deaths in 2022.

A Case Study: Laurie's Story

FBT's classic clinical triad includes fever, headache, and rash, often accompanied by hepatitis and thrombocytopenia; in addition, roughly one in three patients suffer aseptic meningitis, seizures, or respiratory distress. In endemic sites, including my hometown of Pasadena and adjacent foothills, such findings should quickly trigger specific testing and empiric doxycycline. But, sadly, not every patient presents with a classic illness.

Take, for example, a previously healthy TV art-department coordinator who, in 2021, lived in a guesthouse near downtown Los Angeles. Looking back on her illness, Laurie Cooper simply remembers wracking fatigue and night sweats so severe she slept on towels. "There was so much sweat it was like I was swimming in it," she recently told me.

After doctors at her local ER threw up their hands, Cooper finally went to a university hospital where ground-glass opacities on her chest x-ray suggested sepsis. Soon, antibiotics dripped in her veins while she underwent other tests looking for cancer. But even with such focused, modern care, 3 days passed before a specialist learned that Cooper's backyard garden was a haven for urban wildlife and added doxycycline to her mix.

A final unexpected twist? Around the same time that serology and a cell-free DNA blood test proved that Cooper's true foe was Rickettsia typhi, her echocardiogram showed vegetations. One month later, the plucky TV professional had cardiac surgery to replace her damaged mitral valve, then took doxycycline for another 6 months.

Of Rats, Cats, Possums, and Fleas

Several decades ago, FBT was routinely called "murine" typhus to denote its principal reservoir in rodents and transmission via Xenopsylla cheopis, the common rat flea.

But once again, that name reflects a different reality. Today, FBT's principal hosts in suburban haunts are "Virginia opossums" (Didelphis virginiana, North America's only marsupial), and R. typhi's latest vector is , the same cat flea that commonly torments dogs and many other creatures.

Some of these flea-infested fauna were familiar to Cooper, even though she never noticed itchy bites. In her backyard garden were "possums with babies, skunks with their whole family," and plenty of feral cats, some of which occasionally lounged in her house. What she didn't know was just how many fleas opossums can carry. As cited in a brilliant of contemporary FBT, in one study of 259 opossums trapped in Orange County, California, the average flea burden was 91 -- far more than that found in rats, skunks, or raccoons.

One more feline fact? In the 1990s, a new species, Rickettsia felis, was discovered. It is now a worldwide, emerging infection largely transmitted by cat fleas, including here in the U.S.

A Perspective from Texas

Pop quiz question #2: Because FBT isn't typically reported outside California, Texas, and Hawaii, but now has a new vector, could it soon affect more humans?

For insights into FBT's future, I spoke with infectious diseases and Rickettsia expert Lucas Blanton, MD, of the University of Texas Medical Branch in Galveston. First, Blanton commented on its latest players. "The fact that cat fleas are so ubiquitous and Virginia possums are widely distributed throughout the U.S. means we shouldn't think of [FBT] as just a disease of southern California and Texas," he said.

He added that FBT in Texas "is spreading northward at a pretty rapid rate in communities that have not seen it since those DDT campaigns on rat runs following World War II." Dallas was one example he cited. Then there's Galveston, where FBT re-emerged in 2012. "There's no reason the same thing couldn't happen in New Orleans, Baton Rouge, Birmingham, Nashville, and throughout the South, at the very least."

Blanton's greatest hope for the future is a point-of-care test to prompt rapid, effective treatment in his worst-case scenario: a steadily-growing cadre of patients in new locales.

Parting Wisdom

Although fleas favor warm, humid weather, they remain active well into November or even year-round in many places. Eradicating fleas from pets that sometimes serve as bridge hosts for FBT, controlling rats, minimizing peri-domestic enticements for opossums (for starters, outdoor pet bowls and garbage) are just a few practical measures we need to promote, along with better education about FBT.

Cooper, who was diagnosed and managed by my infectious diseases colleague Ramee Younes, MD, went as far as to move to a different neighborhood. Nonetheless, her love of animals remains. Right now, however, she doesn't have pets. "But I always feed the squirrels and crows," Cooper confessed. "I just throw peanuts on the garage roof and they come and get them." Then my friends yell at me: "Stay away!" they say. "You're going to get in trouble again!"

Some habits die hard, I guess. My husband, is a lot like Cooper in his love of animals. But you can be sure our two small spaniels never miss their quarterly dose of Bravecto flea treatment.

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