Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (8 page)

With larger and larger towns and cities and better connections established through transportation and trade, our indigenous microorganisms—those that were endemic or latent—were increasingly joined by epidemic pathogens that required large contiguous populations to sustain them, and they flourished. These were the real troublemakers, the killers and maimers, especially of children. Even tuberculosis, which had been around for a very long time, evolved strains that were selected for virulence and ease of transmission. Together, all of these pathogens thinned our human herd at enormous cost. Rich or poor, no family was immune. People could only pray for deliverance from pestilence. Not much help arrived until the late nineteenth and early twentieth centuries, when the very first advances in sanitation were made and then followed by the development of vaccines. Through concerted efforts and great international cooperation, vaccines now have eradicated smallpox from the face of the Earth, markedly reduced the reach of polio, and curtailed the measles epidemics. The other incredible advance in the fight against pathogens came when antibiotics were finally, gratefully, discovered.

5.

THE WONDER DRUGS

As I drove to work on a spring morning in 1980, the air in Atlanta held a chill. I had been away for more than two months working in the hot enclaves of Bangladesh and India and was relieved to be back at the Centers for Disease Control. The office held the usual welcomes, big piles of mail, and much to organize, but in the afternoon, I started to feel achy. Maybe it was jet lag; I had arrived the night before. But I felt lousy. My forehead was hot to the touch. After about an hour, I decided to go home. Maybe I had caught the flu on the airplane or on a prolonged stopover in England. I couldn’t remember the last time I felt too sick to work. Time to go to bed, and by the morning I would feel better.

But the next morning, I wasn’t better. My fever was up to 101°F. As an expert in infectious diseases at the CDC, I knew that malaria can begin like a case of the flu: fever, headache, achiness, sore muscles. Could I have picked up malaria? When travelers die from malaria, it’s because the diagnosis is missed and treatment is started too late. People think that they have the flu. With that in mind, I called one of my CDC colleagues in the Parasitic Diseases Branch, Dr. Isabel Guerrero. I wanted to get a blood smear taken to see if it was malaria.

“I’ll come right over,” she said.

In about thirty minutes, she was at my bedside at home, where she pricked my finger, put a spot of blood on a glass slide, and told me she would call with the results.

About an hour later, she did. “You don’t have malaria.”

Thus reassured, I was ready to wait out the flu. By then, I had developed a mild cough.

The next morning, Wednesday, I was still sick. I didn’t feel too bad, but I still had a fever. My wife convinced me to go see a specialist in infectious diseases, Dr. Carl Perlino. He examined me and, other than the fever that perversely vanished while I was in his office, I checked out fine. Even my screening blood tests were okay.

The next day, Thursday, I still had a fever and the mild cough. I was in bed all day, and that night I had a vivid nightmare. I don’t remember who was chasing me, but I woke in a cold sweat. The sheets were drenched. Even in my delirium, I knew instantly what the problem was: typhoid fever! Traveling in Bangladesh and India, where human waste often gets into food … symptoms that began about a week after I left … day after day of fever, now worsening—vague symptoms. That’s what it had to be.

By the next morning, I was very weak. My temperature had shot up to 104°F. I didn’t have the strength to button my own shirt or sit up in the car without leaning on the window. I knew that I had about a 10–20 percent chance of dying if I wasn’t treated with antibiotics. Achy, sweating, no strength, no intake of food in days but no appetite—I knew that I was acutely ill. As we drove on that exquisite spring day down a street filled with blooming magnolias, I thought that it would be a real shame to die at thirty-one.

When we got back to the doctor’s office, I was huddled and shivering. They had to put me in a wheelchair. My greatest fear was that Dr. Perlino would not understand how sick I was and would send me home. It was ironic; I knew that hospitals are dangerous places and should be avoided at all costs—people fall out of bed, they get the wrong medications, they acquire new infections—but I was desperate to be admitted, to start on treatment, not to go home.

Fortunately, he took one look at me and immediately admitted me to the hospital. Another irony is that my main job at CDC was as the
Salmonella
surveillance officer of the United States. Doctors from all over the country would call me to ask advice about patients and outbreaks of salmonella. So here, too, my doctor asked me what antibiotic I should be treated with. I knew that
Salmonella typhi
, the main cause of typhoid fever, could be treated with ampicillin, an advanced form of penicillin. Ampicillin was life-saving for millions of people. But there was a big problem: it had been used so much that by 1980 many strains of
S. typhi
had become resistant. It might be completely ineffective.

So instead I recommended a newer formulation of a sulfa drug, called
co-trimoxazole
. It combined two agents developed in the 1960s and was still widely effective against
S. typhi
(though resistance to it would later develop as well). Evidently, despite my high fever, I could still think straight. Even if I was wrong about typhoid, I was so acutely ill that the doctors had to treat me with something in case I had some other kind of bacteria spreading through my bloodstream.

Medical students came to take samples of my blood to the culture lab. If I had typhoid fever,
Salmonella typhi
would show up in the petri dishes. Then they hung a bag of fluid containing the co-trimoxazole and dripped it into my veins. I knew that the odds were turning in my favor. The chance of dying was getting smaller with each hour. That is the miracle of the antibacterial drugs that started being discovered in the 1930s.

I slept and slept. But the next morning, I wasn’t better. Still feeling achy and miserable, I asked the team, “What do the blood cultures show?”

“Nothing growing.”

Could my self-diagnosis be wrong? Was it not typhoid? But it was only twelve hours or so since the cultures had been taken, so maybe it was too early. In the odd position of both patient and specialist doctor, I recommended that we continue the course, and they agreed.

The next morning, the team came into my room. “The cultures are positive. You have
Salmonella
in your blood. The microbes are growing.”

So it was typhoid after all.

The next day there came a small surprise. It wasn’t
Salmonella typhi,
the usual cause of typhoid fever, but
Salmonella paratyphi A
, essentially the twin of
S. typhi
. But according to the textbooks, the cases are indistinguishable, and I could vouch for that.

With treatment, and a few complications, I turned the corner and started to get better every day. After a week, I was discharged from the hospital, and I spent another week at home before returning to work. A week sick at home, a week in the hospital, a week convalescing back at home—this was a serious illness. I shuddered to think what it would have been like without the co-trimoxazole.

A few years later, I was speaking with a colleague who had worked in Asia for many years. I told him that, as far as I knew, my only dietary indiscretion in the weeks before my illness was that one hot night in Mumbai, as I was walking around, I saw a street vendor who was selling slices of watermelon. His stand didn’t look that great, so I asked him to give me a slice from an unopened melon. I thought that would protect me. That was about nine days before I started to become ill, which is almost a classic incubation period.

“Of course,” my colleague said. “Of course, it was the melon.

“You see,” he told me, “in India, they sell the watermelons by weight. So the farmers inject water into them, to make them weigh more. The water comes from the rivers and streams near their fields.”

My stomach churned at the thought. The watermelon was contaminated with human waste. You get typhoid fever from ingesting food or water contaminated with the fecal waste from a person who is a carrier of the disease. I thought of the most famous carrier, Mary Mallon, better known as Typhoid Mary, the young Irish immigrant who worked as a cook for well-to-do families near New York around 1900. After an outbreak of typhoid fever in her house, she would move on to another family. And then there would be another outbreak and then another. It is not clear whether or not she understood that she was causing the outbreaks. There was plenty of typhoid around in those days; hospital wards were filled with suffering people, and at that time about a quarter of them died. A great medical detective named George Soper traced the outbreak back to Mary and made her promise to stop working as a cook. She was a typhoid carrier: she felt entirely healthy, and she
was
entirely healthy. Carriers aren’t ill; they just shed the organism.

Mary denied that she had anything to do with the prior cases, and within a short time she absconded from her parole. Eventually there was a trail of new outbreaks. Soper found her again. Here was the dilemma: Mary was perfectly well, but a menace to the community, no less than if she fired a loaded gun at random into a crowd. Typhoid was not a mild illness; people died after coming into contact with her cooking. Ultimately, a judge decided. Mary was imprisoned on North Brother Island in New York’s East River and lived the rest of her life in custody, swearing her innocence to the end. These days, we could probably cure her condition by removing her gallbladder and giving her antibiotics. And the people she infected could be treated with antibiotics, as I was.

Fast-forward twelve years from Atlanta to May 1992, when I was asked to speak at a conference highlighting advances in our understanding and treatment of infectious diseases. My topic was how our work had linked a newly discovered bacterium in the stomach,
Helicobacter pylori
, to stomach cancer, a common and difficult-to-treat malignancy. It was, we thought, a new pathogen, and people were curious to learn more.

The symposium was held at Yale specifically to mark the fiftieth anniversary of the first use of penicillin in the United States. The moderator began by recounting the case of Anne Miller, a thirty-three-year-old nurse who had suffered a miscarriage in 1942. She had been acutely ill for a month, with fevers up to 107°F, delirium, and signs of a streptococcal infection raging throughout her body. She had childbirth fever, or what doctors called
puerperal sepsis
. It was an infamous killer of young women after a miscarriage or birth of a child. Miller drifted in and out of consciousness, very near death.

By an incredible stroke of luck, her physician gained access to one of the first tiny batches of penicillin, which was not even commercially available yet. The drug was rushed via airplane and state troopers to Yale–New Haven Hospital, where it was administered to Miller on her sickbed.

Her recovery began within hours. The fever broke, the delirium ended, she could eat, and within a month she had recovered. It was the scientific equivalent of a miracle. What made the difference was 5.5 grams of penicillin, about 1 teaspoon worth, diluted into her intravenous solutions. Penicillin was in such short supply that her urine was saved so it could be shipped back to the Merck pharmaceutical company in New Jersey where the excreted penicillin was purified for use in another patient.

As the moderator recounted the details and the drama of the story, the audience was transfixed. You could hear a pin drop. And then, after a short pause, he said, “Now, will the patient please stand up.”

I turned around to look. In the third row, a small-boned, elegant, elderly woman with short white hair stood up and, with bright eyes, looked out across the room. She was Anne Miller, then in her eighties, given fifty more years of life by the miracle of penicillin. I can still picture her shy smile. She lived another seven years before her death at age ninety.

When Anne Miller’s life was saved, medical science was just beginning to learn how to defeat bacterial infections. Pneumonia, meningitis, abscesses, and infections of the urinary tract, bone, sinuses, eyes, and ears—indeed, all parts of the body—were still being treated with marginal or questionable remedies from the past. When George Washington developed a throat infection, he was bled by a surgeon. Doctors had great faith in this therapy, but it probably hastened the president’s demise. Bleeding continued as a remedy into the twentieth century.

Some treatments helped slightly but none dramatically, and the side effects of many patent medicines were worse than the diseases being treated. Some contained high levels of arsenic. Even as surgical techniques improved, infection was a constant worry and could transform a successful operation into a disaster; with bad luck, removing an ingrown toenail could lead to a foot amputation. An infected heart valve was 100 percent fatal, worse than cancer.

During the American Civil War, more soldiers died from typhoid fever and dysentery than from bullets. No one was immune. Leland Stanford Jr., the son of the governor of California and for whom the university is named, died of typhoid fever in Italy. He was fifteen. During World War I, dysentery and typhus took a greater toll than combat. In 1918 and 1919, the Great Spanish Flu spread across the globe to infect 500 million people, about a quarter of the world’s population, killing between 20 million and 40 million of them, frequently from complications due to bacterial pneumonia.

Scientists worked feverishly in the late nineteenth and early twentieth centuries to combat infectious diseases. They had one light to guide them: germ theory, the concept that many diseases are caused by the presence and action of microorganisms, especially bacteria.