The message was brief but urgent: "Honeymooner arriving tonight from Tahiti. Has fever, headache, hemorrhagic rash. Will take ambulance to our emergency room. Can you meet her there?"
That year, I took care of three returning newlyweds with the same tropical woe—but none as sick as Susie Gold.
Susie and her fiancé, Jeff, had resolved to have a one-of-a-kind wedding in the South Pacific, where they would exchange vows under a cabana of palm fronds. Everything went off without a hitch, but five days later Susie developed teeth-chattering chills. Her muscles felt sore and bruised. At first she downplayed her symptoms, figuring she was wiped out from the wedding or fighting a bug she had picked up on the plane. It would pass.
Sure enough, a day later, she was better. She and Jeff resumed snorkeling and strolling along the beach, their happiness marred only by sunburned noses and mosquito bites.
The next morning Susie's head and eyeballs ached furiously, her brow was hot, and her legs sported a rash that looked like purple shooting stars. Her biggest scare came after flossing her teeth. She tasted salt, looked in the mirror, and saw bright red blood.
Jeff called Susie's dad, a psychiatrist. He listened to Susie's symptoms, then rang off to consult with the family internist. Thirty minutes later he was back on the line.
"Jeff, you've got to bring Susie back. Don't worry; I've arranged everything. Once you land in Los Angeles, an ambulance will take her straight to the university hospital."
If Dr. Gold had actually spoken to me before Susie boarded her plane, I probably would have vetoed the daylong wait before she was seen by a doctor. To an infectious-diseases specialist, her constellation of fever, headache, and pinpoint bleeding in the skin indicates meningococcemia until proven otherwise. Meningococci are bacteria that invade the blood and the meninges that line the brain. A 12-hour delay in receiving antibiotics can be the difference between life and death.
But deep in my gut, I worried that Susie might have another misery that can mimic meningococcemia. Starting in the 1980s, dengue—a mosquito-borne virus that dogged Allied and Japanese troops during World War II—made a stunning comeback in the Pacific, Southeast Asia, and the Caribbean. Like meningococcal infection, dengue also causes fever, headache, and hemorrhagic rash.
A small, black-and-white mosquito, Aedes aegypti, is dengue's main vector. It loves to breed in water-filled crockery, cisterns, trash containers, and spare tires that surround human habitation in the tropics. That's a lucky coincidence for an insect whose survival depends upon blood meals. In turn, the blood-borne dengue virus profits from its vector's feeding habits. With the slightest provocation, the female Aedes stops her blood meal, only moments later to resume probing and siphoning the same or another nearby victim. Thus, a lone mosquito carrying dengue from a previous host can spread the virus to multiple recipients.
After an Aedes loaded with dengue inoculates its victim, illness begins within seven days. Although symptoms range widely, fever, chills, and headache often herald the attack, along with facial flushing, swollen glands, and a mild sore throat. Then comes a deceptive lull before dengue's encore fever arrives. This later stage features an array of skin rashes as well as dengue's famous aches, otherwise known as breakbone fever.
Dengue's most dreaded complications are hemorrhage and shock, which typically strike children and adolescents battling the infection for a second time. During a second bout of dengue, old antibodies are thought to bind to the new virus, but they fail to clear it because of changes in the new infecting virus. Instead, antibody-virus complexes are engulfed by watchdog cells called macrophages. During severe infections, macrophages can release chemical signals that cause capillaries to leak, which results in bleeding and, at times, drastic depletion of plasma volume.
Still, Susie's case didn't stack up perfectly for dengue because her bleeding didn't fit with a first-time infection. A true diagnosis would be tricky: There's no easy test for dengue.
Eight hours later I got a call on my pager from our emergency room. Susie had arrived.
I hurried to the cubicle where she lay pale and sweaty but lucid. Her blood pressure was low and her pulse was high. She had bleeding gums and a sprinkling of hemorrhagic dots on all four extremities, just as she had described. Otherwise, the physical exam revealed only a few lentil-size lymph nodes and a tender liver edge below the right rib cage.
"She didn't eat a thing on the plane," Jeff said, his voice tinged with worry, "and when she stood up at the end of the flight, she nearly fainted."
Drip, drip, drip: An intravenous set was running saline into Susie's vein at the fastest rate the tubing would allow. Adding fluid would help bring up her blood pressure and prevent her from going into shock.
"Her vascular volume is low," I replied, avoiding the term "shocky," which the ER resident had used to describe the washed-out bride. "Right now she needs lots of fluid. We'll deal with food later."
I turned to Susie. "Don't worry. It will be rough, but you'll pull through."
At that point I left to review lab tests. Just as expected in a major viral assault, Susie's leukocytes and platelets were low. That meant she was depleted of cells that counter infection and bleeding. At the same time, her liver enzymes were elevated three- to fourfold, corresponding to the swollen, tender edge I felt on exam. Everything fit with dengue, yet nothing was truly diagnostic. Meanwhile, it would take 48 hours before blood cultures were known to be negative for meningococcus.
Sometimes being a purist is a mistake in medicine. Although I was confident that Susie had dengue, a disease for which antibiotics are ineffective, I asked myself: In her shoes, would I want antibiotic treatment until a serious bacterial infection was 100 percent excluded? My answer was yes.
"Let's start ampicillin and ceftriaxone for now," I said to the resident, "but don't forget to order an antibody test for dengue fever. It may take a long time to get the result, but it could be our only proof."
My next stop was the library. All day a vague memory had nagged me. Hadn't I seen a case report describing hemorrhage and shock in first-time dengue? Or was my mind playing tricks on me?
The American Journal of Tropical Medicine and Hygiene came through: "Dengue shock syndrome in an American traveler with primary dengue 3 infection" (March 1987). In the 15 years since that report, with the blossoming of dengue and exotic overseas travel, such cases in tourists are no longer rare. For reasons that are unclear, even these first-time infections can occasionally lead to bleeding and shock.
As for Susie, she spent the next few days in the hospital while her plasma volume restored, her bleeding stopped, her skin hemorrhages cleared, and her lab tests normalized. As expected, her blood cultures remained negative, so we finally shut off her antibiotics 48 hours after admission. Three days later, when she and Jeff were ready to return to the East Coast, the only remnant of her ordeal was depression. Post-dengue blahs, sometimes referred to as neurasthenia, were well known to British colonials. I reassured Susie that her mood was normal and would gradually improve on its own. The following week her dengue antibody sent from the emergency room finally came back positive.