3
DISEASE DETECTIVES
Epidemiologists study the big picture: patterns of disease, how they spread, and how to stop them, whether through biomedical means or changing people’s risky behaviors. My mother often described what I do for a living by saying, “You know when they say that some disease is spreading or an epidemic is on the way? Well, my daughter is one of the ‘theys.’”
Not that I’d started out to be one of them. I’d been an undergraduate major in microbiology at the University of Toronto when Rock Hudson died in 1985 of a mysterious illness that was first referred to as “gay-related immunodeficiency”—or GRID. My professor, Stan Read, was an early leader in the field and I learned the hallmark signs of the infection—night sweats, swollen glands, and flu-like symptoms, sometimes accompanied by other infections typically seen in people whose immune systems were suppressed. The first cluster of cases of what is now called acquired immunodeficiency syndrome (AIDS) had emerged in 1981 in gay men, capturing the attention of epidemiologists at the US Centers for Disease Control (CDC), who conducted a series of outbreak investigations. As further research in North America and Europe found that hemophiliacs and injection drug users were also succumbing, it was an inspiring time to become a disease detective. Within a few years, a diagnostic test was developed based on antibodies directed against the causative virus, human immunodeficiency virus (HIV), and I’d found my calling, or so I thought.
But a few summer internships fumbling under the flow hood had convinced me that day-to-day lab work was not my forte. Then a graduate teaching assistant suggested that because of my preference for working with people rather than Petri plates, epidemiology might be a perfect fit: all the intrinsic beauty of biology, but instead of being about populations of cells, it was about populations of people. Epidemiology was the big-picture, bird’s-eye lens needed to develop strategic action to help people. When the first HIV cases appeared in my hometown of Toronto, I was moved by the drama unfolding before my eyes. I obtained my master’s degree and started my PhD. I was to become one of the few HIV epidemiologists in Canada at the time. Eager to help while still a grad student, I was one of the first group of volunteers at Casey House, which started out as one of the earliest dedicated AIDS hospices in North America. There I watched a growing number of people who had become my friends die painful, lonely deaths. In the early nineties, my doctoral supervisor, Dr. Randy Coates, and then my best friend, Michael, both of whom were stricken with HIV, died within a year of each other from opportunistic infections that they would have been able to beat if their immune systems hadn’t been annihilated. I was devastated. And that was it: I became committed to studying this pandemic and finding ways to stop it. That was the first time my personal life and my professional life had collided, but it wouldn’t be the last.
During that same period, I learned how, even as scientists, our intuitions can help us. When I was working on my master’s degree, I’d worked part-time as a research interviewer for an HIV study on people who inject drugs and sell sex. The participants with the highest-risk behaviors often confided that they had been victims of child sexual abuse, even though that wasn’t an interview question. I told the principal investigator about it, but at that point she couldn’t change the study questionnaire, which meant that we couldn’t study it. But I never forgot about those stories. Years later, when I was directing studies of people who inject drugs and young gay men in Vancouver, I included questions on childhood sexual abuse and discovered that it was strongly predictive of HIV risk behaviors in both populations. My finding became part of a budding body of research that showed that social determinants—including the driving forces in our economics, politics, and laws—helped explain the marginalization and stigma in these key populations, increasing their vulnerability to HIV. I received a Young Investigators Award at the 1996 International AIDS Conference for that research, and that early insight inspired my career path to shift away from a focus on individual behavior change to change the conditions that put people at risk in the first place. Beyond that recognition was the power of the lesson I’d learned as a young scientist and practiced ever since: listen to your intuitive hunches, don’t let the unknowns limit your search, and approach all possibilities with an open mind and rigorous research.
At the moment, my intuitive antenna wasn’t picking up much from the bathroom, where Tom hunched in pain. Then the Red Pyramid guard’s ominous warning about the “poisonous gases” in the tomb echoed in my mind. Until the end of the nineteenth century, most people, including scientists and physicians, embraced miasma theory, the belief that “bad air” was the cause of diseases we now know to be caused by bacteria, like bubonic plague, cholera, and syphilis. Their opponents who supported germ theory were outnumbered and sometimes even outcast. That is, until John Snow, a medical doctor who would later be known as the father of epidemiology, conducted his famous investigation into the London cholera epidemic. That story had drawn me to the field of epidemiology and was later the subject of one of my favorite books, The Ghost Map, which laid out his meticulous detective work.
After studying the first cholera pandemics that occurred earlier in the nineteenth century, Snow observed that they tended to follow trade and military routes. He hypothesized that those afflicted might have been exposed to water that was contaminated with some sort of microorganism. But his 1849 article on the subject was criticized because he had no proof. With the London outbreak, he got his chance. London had burgeoned into a megacity without a sewer system for handling the tons of excrement generated from two million people and their animals. The city’s poop was collected by so-called night soil men, who carted it off to cesspools in the boonies that stank to high heaven. The public health commissioner, a fervent believer in the miasma theory, was intent on creating a sanitation system to rid the city of its smelly cesspools, which now numbered about three hundred thousand. There was one problem. He was focused on cleaning the air, not the water. His solution was to eliminate the cesspools and dump the masses of poop into the Thames River, which turned it into a polluted mess that inadvertently contributed to cholera outbreaks that would kill thousands.
The 1854 outbreak began quietly but ferociously in London’s Soho district, which was one of the city’s poorest. Within days, hundreds then thousands of people were overcome with terrible stomach pains, explosive greenish diarrhea, and extreme dehydration that more often than not quickly led to their deaths. John Snow, who lived in a neighboring district, took it upon himself to investigate, putting himself at considerable risk due to the neighborhood’s high crime rate, in addition to the risk of acquiring the infection himself.
Suspecting that a water source was the culprit, he sampled water from the closest pump on Broad Street to inspect under a light microscope. But microscopy at that time fell short of what Snow needed to find conclusive evidence. The offending bacterium, Vibrio cholerae, was actually isolated that same year by Italian scientist Filippo Pacini, but it would take decades before its significance was recognized. Meanwhile, the cause of the Soho cholera outbreak remained elusive until Snow literally took a broader view. He knocked on doors to survey people about where they drew their water, tracked which pumps were linked to the city’s sewer system, and then which of those drew water from the Thames. Comparing his data and death statistics from adjacent neighborhoods, he showed that cholera death rates differed dramatically based on their water source. With that evidence, he convinced the Board of Health that the Broad Street pump was the point source of the outbreak. In a symbolic gesture that would become a critical moment in medical history, the Broad Street pump handle was removed, ushering in a new era in which the miasma theory was eventually abandoned in favor of germ theory. The field of epidemiology was born.
Whether you’re tracking the cause of cholera, HIV, or some other outbreak of disease, the big breakthroughs often come from simple, dogged detective work—what a professor friend once called “gumshoe epidemiology.” In the middle
of the night, in bed on a cruise ship overlooking the Nile, simple was the only kind of microbial detective work possible. My undergrad years in microbiology gave me a place to start.
First, I considered what we had eaten: fish, clams, prawns, and mussels. Shellfish are often contaminated with fecal coliforms, which are bacteria found in human and animal poop. So we could be looking at a virulent strain of Escherichia coli or any number of Shigella, Salmonella, or Vibrio species. On my smartphone, I googled a few of the more exotic bugs and added Listeria and Clostridium.
Next, I did a simple calculation to take into account that bacteria have different incubation periods depending on the time of exposure. When had we eaten relative to Tom’s first onset of symptoms? It was past midnight now, which meant about five hours since dinner. But the culprit in food poisoning may be something you ate anywhere from an hour to two weeks or more before, depending on the organism. I googled the CDC website that tabulated incubation periods for foodborne pathogens. Scanning the list, I excluded some bugs with longer periods, like Campylobacter jejuni and Vibrio cholerae, but that still left a slew of nasties.
Tom crawled out of the bathroom, but before he could even get to the bed to rest, he turned in his tracks and stumbled back, retching.
Although I couldn’t diagnose what he had, I jumped out of bed and rummaged through our suitcase for that don’t-leave-home-without-it Cipro. It was usually a universal lifesaver, clearing up most cases of vomiting or the trots within hours. The problem was, Tom couldn’t keep anything down. Not dinner. Not the mild broth that the ship’s chef had sent, not hot tea, not even a sip of water. I watched as our only dose of Cipro was flushed down the toilet. An assortment of small dishes and cups, their contents untouched, sat like sacred offerings on the bedside table.
Could Tom have acquired a viral or parasitic infection from what we ate? We had both been vaccinated against hepatitis A, so I crossed that one off the list. Most parasitic infections would have taken longer to make him sick, so I discounted them too, at least for now. Of the possible viruses, norovirus came to mind, since it causes stomach pain and vomiting, and was the cause of most outbreaks of foodborne illnesses on cruise ships. But we were the only passengers on the ship, and neither Khalid, myself, nor any of the crew were sick.
Tom had such a cavalier attitude about food and drink on our travels that he might have picked something up anywhere in the past few days. He was no stranger to dysentery, having pushed through some pretty impressive bouts of it, so I confess I’d become a bit jaded to even that prospect. He liked to boast of the time in his younger adventuring days when he and a friend had gone off-road camping the length of Baja California, a thousand miles with no paved roads. After an initial bout of Montezuma’s revenge, he figured he’d bested any bugs in the water and it wouldn’t hurt to drink the water anywhere they found it. His dysentery landed him in the hospital, where the doctors identified four different pathogens. That was the bad news, but the good news was that he’d lived to tell the tale, as always. The chorus in my head was always: By this time tomorrow, he’ll be laughing at me for being a worrywart.
Dawn came, and with it my hope that this would resolve itself. But things didn’t get better. Tom still couldn’t keep anything down and was growing weaker and more dehydrated by the hour.
4
FIRST RESPONDERS
I didn’t want to flat-out overrule Tom on calling a doctor—even in this state he would be furious. So I did the next best thing. I texted our friend and colleague, Dr. Robert “Chip” Schooley, chief of infectious diseases back home at our institution, UC San Diego. Chip and I were both division chiefs and saw each other frequently for work purposes—sometimes socially, too, so he and Tom were well acquainted. They shared a mutually wry sense of humor, and enjoyed swapping stories from their travels. As a physician and a scientist, Chip was laser sharp and serious—qualities that distinguished him as an international leader in the field of infectious disease. At the same time, he possessed a natural warmth and wit.
Chip had come to our rescue once before, after Tom and I contracted a strange skin infection on another Thanksgiving trip we took in 2008 to Goa, in western India. By the time we arrived home, both of us had several boils on our arms and legs that started out looking like giant zits before turning into big balls of pus, throbbing and pulsing with a life of their own. None of them responded to antibiotic cream, and I immediately became alarmed.
“I bet this is MRSA,” I’d told Tom. “If it is, we need to see a doctor ASAP.” Tom scoffed at me.
“Isn’t that just a type of Staph?” he’d replied as he peered at the greenish boil on his forearm. “Can’t you get a stronger ointment?”
MRSA is a form of Staph, all right, but it’s resistant to the antibiotic that used to be used to treat it: methicillin. Which is why it’s called MRSA—methicillin resistant Staphylococcus aureus. It was the first of the antibiotic-resistant “superbugs” identified in the UK in the early 1960s, and since then it had quickly spread worldwide. It was a good bet that we’d gotten it when we took that swim in the Arabian Sea. In retrospect, we’d noted, no one else had been swimming, which should have been a tip-off.
The hotel in Goa was adjacent to a large slum, and in the distance, we could see several large oil tankers that had probably been emptying their bilges into the ocean. We hadn’t given it much thought at the time. It’s the ocean, right? A habitat for thriving thousands of species of sea creatures, flora and fauna. Who knew that there are 100 million times as many bacteria in the oceans as there are stars in the universe? I should have known that sea water is often contaminated with some of the gnarliest bacteria around.
MRSA had been all over the news at the time, due to a few high-profile cases that implicated this and other antibiotic-resistant bacteria in flesh-eating disease; some people died or had limbs amputated. Tom thought I was being histrionic, but with the Thanksgiving holiday around the corner, I convinced him that I should contact Chip for advice, and he had paid us a house call that afternoon. Chip looked a bit like an aging Alfred E. Neuman, the cover boy of Mad magazine, sans the protruding ears but with a generally jovial expression that put you at ease. I hadn’t often seen him without his lab coat. Chip had just returned from a trip to Mozambique, where he had established a new medical education program, and that day he was in shorts and a T-shirt, and his freckled face took on the sheen of burnished copper.
He reached into his pocket to pull on some gloves while I pulled up the hem of my dress to show him the boil on my leg.
“Whoa, that’s MRSA all right,” Chip chortled. “I don’t need to come any closer. Of course, to properly diagnose it, we would need to culture it. But that would take a few days, and you need some antibiotics right away. I’m betting this dip you took in the Arabian Sea gave you a superbug souvenir. The good news is that MRSA from natural environments like this is usually still sensitive to oral antibiotics. The trickier ones to treat are strains of MRSA and other multi-drug-resistant bacteria that are acquired in hospitals, because they’ve grown in what amounts to a hothouse for developing antibiotic resistance.”
We were lucky. After two weeks of oral antibiotics, our boils dried up, although we missed Thanksgiving dinner that year because we didn’t want to pass on our infection to anyone else. Within six months, our immune systems cleared the bug and we had forgotten all about it. Except when we went to the dentist, where I routinely reminded the hygienist that we had been MRSA carriers; it was a sure-fire way to avoid a deep clean.
Fast-forward seven years, and Chip was playing first responder once again. He was en route to his project in Mozambique again and the cell phone reception wasn’t great, but I got the gist from our brief conversation: call a doctor. He thought my gumshoe detective work that pointed at food poisoning sounded reasonable, but at the very least, Tom would need IV fluids. Against Tom’s continued protests, I happily blamed Chip and asked Khalid to summon a doctor to the ship.
Dr. Busiri
arrived within an hour in the early afternoon carrying a classic black leather medical bag and wearing a pristine white doctor’s coat over a dark green button-down shirt tucked into pressed dress pants. He was tall, thin, and clean-shaven, with an air of efficiency. He’d had to make his way across the three docked ships and up a narrow three-level winding staircase to reach our room, but he didn’t complain. He shook my hand and smiled warmly, then turned to Tom, who was pale and sweating in the bed. He took Tom’s vitals calmly and quickly—temperature, heart rate, blood pressure—then pulled out a notepad and began to ask questions about Tom’s medical history.
History of heart problems? Diabetes? No heart issues, and although Tom had borderline diabetes, nothing would suggest a tie-in with this gut attack.
“He needs IV fluid,” Dr. Busiri concluded, removing the stethoscope from his ears, and reaching for a collapsible IV pole he had brought along. “I suspect food poisoning, so I will prescribe some gentamycin. That always works.” He tied a rubber tourniquet around Tom’s arm, flicked a syringe to expel any air bubbles, and swabbed the vein inside the crook of Tom’s elbow. Tom winced as Dr. Busiri inserted the needle. “The fluid will make him feel much better,” Dr. Busiri said as he attached the IV bag to the pole. “I expect him to be up and around before dinnertime.”
I sighed with relief. Dr. Busiri stayed nearly an hour, until the last drip of saline and antibiotics had drained into Tom’s arm. “If he is not better, call me,” he said, as I walked him to the door, paid him, and thanked him again.
The Perfect Predator Page 3
