called crowd diseases.Epidemics often occur in waves and spread quickly from one person to the next until nearly everyone is exposed.In a short time,you survive or die.In the case of measles,survivors developed antibodies and remained immune for the rest of their lives. Caused by the rubeola virus,measles is the most infectious disease known to humankind,with an infection rate greater than 95 percent.In contrast,a new strain of influenza might infect from one-third to one-half of those exposed for the first time.When I worked in Africa as a student,I saw many children with measles. Typically,they had high fevers,inflamed throats,red eyes,and hacking coughs.The cough,which yielded virus-laden aerosols,was very effective in spreading the disease. Any child not previously exposed to the virus became infected immediately.After a week or so of cough and runny nose,a characteristic rash appeared at the back of the ears and then spread to the rest of the body:measles Now kids across the developed world are vaccinated,but Africa and other less- developed parts of the world have been slow in catching up.In 2011,there were 158,000 measles deaths globally,432 people,mostly kids,died from measles every day-18 deaths every hour For the measles virus to survive,it must encounter a new susceptible person every week or two.Like a Ponzi scheme,it requires new victims with startling regularity.In fact,measles can be sustained only if there is a contiguous human population of 500,000 people.In such circumstances,a 3 percent birth rate provides 15,000 newly susceptible children each year,guaranteeing measles transmission year after year.But we have had contiguous populations of 500,000 for only about 10,000 years,and thus the epidemics they enable.So measles might have jumped from animals to humans many times before in prehistory,but without sufficient population size it died out. For instance,many islands,like the Faroes in the North Atlantic,were free of measles for decades at a time.But when a ship brought in an infected person,as one did in 1846,the measles virus quickly spread from person to person. Essentially everyone got the disease.A similar outbreak occurred in Hawaii in the mid-eighteenth century,when measles was introduced by a sailor.People burning with fever went down to the ocean to cool off.But it didn't help;when the epidemic was over,one in five people had died.The virus died out,only to return by ship many years later The rise of cities brought other dilemmas.we had to store food and that attracted hungry pests and their parasites.Scavengers like rats came to visit our grain bins and trash heaps.Thus arose bubonic plague,transmitted by fleas on rats and caused by the bacterium Yersinia pestis.The so-called Black Death erupted in Europe in 1347 and within a decade wiped out a quarter to a third of the population.Once introduced,it could even spread without rats,as infected fleas hopped from person to person,and people with plague pneumonia coughed on 42
called crowd diseases. Epidemics often occur in waves and spread quickly from one person to the next until nearly everyone is exposed. In a short time, you survive or die. In the case of measles, survivors developed antibodies and remained immune for the rest of their lives. Caused by the rubeola virus, measles is the most infectious disease known to humankind, with an infection rate greater than 95 percent. In contrast, a new strain of influenza might infect from one-third to one-half of those exposed for the first time. When I worked in Africa as a student, I saw many children with measles. Typically, they had high fevers, inflamed throats, red eyes, and hacking coughs. The cough, which yielded virus-laden aerosols, was very effective in spreading the disease. Any child not previously exposed to the virus became infected immediately. After a week or so of cough and runny nose, a characteristic rash appeared at the back of the ears and then spread to the rest of the body: measles. Now kids across the developed world are vaccinated, but Africa and other lessdeveloped parts of the world have been slow in catching up. In 2011, there were 158,000 measles deaths globally; 432 people, mostly kids, died from measles every day—18 deaths every hour. For the measles virus to survive, it must encounter a new susceptible person every week or two. Like a Ponzi scheme, it requires new victims with startling regularity. In fact, measles can be sustained only if there is a contiguous human population of 500,000 people. In such circumstances, a 3 percent birth rate provides 15,000 newly susceptible children each year, guaranteeing measles transmission year after year. But we have had contiguous populations of 500,000 for only about 10,000 years, and thus the epidemics they enable. So measles might have jumped from animals to humans many times before in prehistory, but without sufficient population size it died out. For instance, many islands, like the Faroes in the North Atlantic, were free of measles for decades at a time. But when a ship brought in an infected person, as one did in 1846, the measles virus quickly spread from person to person. Essentially everyone got the disease. A similar outbreak occurred in Hawaii in the mid-eighteenth century, when measles was introduced by a sailor. People burning with fever went down to the ocean to cool off. But it didn’t help; when the epidemic was over, one in five people had died. The virus died out, only to return by ship many years later. The rise of cities brought other dilemmas. We had to store food and that attracted hungry pests and their parasites. Scavengers like rats came to visit our grain bins and trash heaps. Thus arose bubonic plague, transmitted by fleas on rats and caused by the bacterium Yersinia pestis. The so-called Black Death erupted in Europe in 1347 and within a decade wiped out a quarter to a third of the population. Once introduced, it could even spread without rats, as infected fleas hopped from person to person, and people with plague pneumonia coughed on 42
others. In 1993 plague broke out in Kinshasa,Zaire.Years of war and corruption caused the government to print money.As a result,there was hyperinflation.People bought whatever they could today,because tomorrow it would cost more.So they stored a lot of grain.This hopeful act brought rats and the plague they carried into many homes. The Industrial Revolution caused populations to balloon,and many diseases transmitted from person to person worsened.Scarlet fever caused by streptococcus, diphtheria,typhoid fever,and tuberculosis all ravaged the crowded cities.In 1900. tuberculosis was the leading cause of death in the United States.Diarrheal diseases,spread by the contamination of drinking water with sewage,sickened the growing numbers of susceptible people.Twenty percent of children did not survive to age five because of diarrheal diseases,whooping cough,diphtheria,scarlet fever,and other epidemic diseases. 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. 43
others. In 1993 plague broke out in Kinshasa, Zaire. Years of war and corruption caused the government to print money. As a result, there was hyperinflation. People bought whatever they could today, because tomorrow it would cost more. So they stored a lot of grain. This hopeful act brought rats and the plague they carried into many homes. The Industrial Revolution caused populations to balloon, and many diseases transmitted from person to person worsened. Scarlet fever caused by streptococcus, diphtheria, typhoid fever, and tuberculosis all ravaged the crowded cities. In 1900, tuberculosis was the leading cause of death in the United States. Diarrheal diseases, spread by the contamination of drinking water with sewage, sickened the growing numbers of susceptible people. Twenty percent of children did not survive to age five because of diarrheal diseases, whooping cough, diphtheria, scarlet fever, and other epidemic diseases. 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. 43
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 101F.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. 8
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. 44
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 104F.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 45
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 cotrimoxazole. 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. 45
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.“Ofcourse,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 8%
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 46