The Sleeping Giant

Headache, fever, and vomiting — a simple viral infection, right?

By Tony Dajer|Tuesday, May 01, 2001
"No eating," the young woman said, pointing to her friend on the hospital bed.

"For a week."

"British?" I asked.

"Russian," she replied, trilling the r like a commissar.

The patient was lying down, facing the wall. "Nausea and vomiting the last two weeks," read the nurse's note. "Also headache and fever. Is feeling better today." Her temperature was normal.

Hello, Olga," I said, gently shaking her shoulder. "May I examine you?"

No response. Her friend whispered in her ear. Olga slowly sat up, eyes closed, black fur coat pulled tight. She was 38, with high cheekbones and blond hair. Although her chest sounds were normal, her belly seemed tender in the right upper quadrant, over the gallbladder. I tried to flex her neck.

"Ow," she cried.Her headache and fever couldn't tell me much; they're common in many diseases. Throw in neck pain, however, and you must consider meningitis. But meningitis for two weeks? With no fever now? Maybe a brain tumor. Or gallbladder disease— a common cause of recurrent vomiting.

But results from a head CAT scan and gallbladder ultrasound proved negative.

I checked Olga's neck again.

"Ow," she said, exasperated.

"Please tell her," I said to the friend, "that we need to perform a spinal tap."

The mere suspicion of meningitis— an infection of the fluid lining of the brain and spinal cord— demands immediate diagnosis and intravenous antibiotics within minutes. A relatively benign viral infection of the meninges, the membranes that encase the spinal cord and brain, seemed the best bet; virulent bacterial meningitis does not putter for two weeks. And Olga didn't seem that sick. But a spinal tap was the only way to be sure.

I slipped the long spinal needle between the vertebrae of her lower back, then removed the thin stylet. Crystal-clear cerebrospinal fluid dripped into the sample tubes.

"It's probably fine," I told Terry, the nurse who assisted me. "Let's give her a gram of Rocephin"— a dose of preemptive antibiotics.

But the microscopic analysis said she was not fine: Olga's cerebrospinal fluid contained 176 white cells per cubic milliliter instead of the normal few. Most were mononuclear cells of the class that usually fights viral, not bacterial, infection. Ominously, the protein in the fluid was three times normal, and the glucose only half. That increase argued for bacterial meningitis. Yet the spinal tap yielded no sign of bacteria. Playing it safe, the admitting team gave Olga two more broad-spectrum antibiotics.

The next day Olga ate a hearty breakfast. But at noon, the ward nurse found her nearly comatose.

It made no sense. With massive antibiotics, Olga had been improving.

Her lethargy and confusion meant the infection might have spread past the meninges and infected neurons. Certain aggressive viruses, such as West Nile, can penetrate brain cells and wreak havoc. A more common culprit is herpes simplex virus, the cause of cold sores. Fortunately, herpes yields to an antiviral called acyclovir.

The residents performed another spinal tap. The count of mononuclear white cells had jumped to 900.

"Wow," I said. "TB?"

The tuberculosis bacillus, Mycobacterium tuberculosis, shrugs off antibiotics that kill other bacteria. And, unlike its cousins, it provokes attack by mononuclear white cells.

"We've sent the samples in for culture and testing," they said.

"Are you giving antibiotics?"

"No, infectious diseases says to wait."

The tuberculosis bacillus, once called "the captain of all these men of death," can be fiendishly elusive. It always enters through the lungs, but it doesn't always stay there. In about 15 percent of cases, the first signs of disease crop up elsewhere. And in half of those cases, chest X rays are normal. To get to the brain, the TB bacilli must evade the lungs' immune defenses and slip into the bloodstream. Once the bacteria reach the space beneath the outermost membranes of the brain, where the cerebrospinal fluid flows, they form clusters. On occasion, a cluster bursts, sending new bacilli through the brain's fluid-filled passages to establish new colonies. The process can smolder for months, causing inconstant, subtle symptoms doctors often miss.

The day after getting acyclovir, Olga seemed a little better. The results of her TB skin test, in the meantime, were inconclusive. The intern and resident, for their part, kept pointing to the low glucose in the cerebrospinal fluid, a finding more typical of tuberculosis than herpes. But the infectious diseases consult did not want to commit Olga to a six-month course of four potent antituberculosis drugs without more data.

So a PCR test, which amplifies a pathogen's DNA for identification, was on the way. It takes barely a week, compared with the six weeks it takes to culture TB bacteria. And PCR is extremely accurate. It also reliably detects herpes.

On the fifth day, Olga perked up. A third spinal tap showed only 120 white cells. But the glucose was still low, and the protein count high. The next day, Olga stopped speaking and needed to be restrained from falling out of bed. On day seven, she bounced back again. But another clue surfaced: Her husband said a cousin had TB meningitis four years earlier, just before Olga left for the United States.

And then we got confirmation: The PCR was positive for Mycobacterium tuberculosis. Olga immediately got four antibiotics that target TB. Two days later, she was sitting up, smiling.

But she wasn't home free.

Over the next month, the nerve in her left eye that controls glancing sideways stopped working, making her see double whenever she looked left. Then she developed hydrocephalus— the accumulation of fluid in the brain— due to inflammation of the meninges. A combination of antibiotics and steroids kept that in check. Best of all, stroke, a dreaded complication, never struck.

A century ago, tuberculosis sickened one in five people. Today, more than 50 years after the advent of the first antibiotic against tuberculosis, the microbe still kills 2 million people around the world each year. In the United States, the prevalence of tuberculosis is low, but the global pandemic will not spare us. In 1993, foreign-born Americans accounted for 30 percent of tuberculosis cases in the United States; in 1998, the figure jumped to 41 percent.

Within a few weeks, Olga's left eye returned to normal. One month after her arrival, she was wheeled into the hospital lobby and left— wan and terribly thin— under her own steam.

"That type of infection used to be 100 percent fatal," the intern said as he watched her go. "And, boy, isn't that PCR slick?"

Sure, I mused, but an old-fashioned diagnostic guess can be even slicker.
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