The American Plague: The Untold Story of Yellow Fever, The Epidemic That Shaped Our Nation (31 page)

HIV is a prime example of a virus’s skill at changing forms and mutating easily. Just when the body produces the right antibodies to fight a viral strain, the virus alters its outer coating just slightly. The key will no longer fit into the lock. That is why a flu vaccine, made up of several different influenza strains, is a yearly vaccine and not one that produces lifelong immunity. That is also why an influenza pandemic would prove so deadly. In the six months it would take to isolate the virus, grow it in chicken eggs and create the vaccine, the virus may have spread through the population decimating millions of people.

In spite of carrying a single, simple strand of RNA, yellow fever does not mutate easily. Instead, flaviviruses like yellow fever somehow disable the body’s immune response—a process that continues to elude science. When the body encounters the virus, it mounts a mass campaign against the foreign invader on two fronts. White blood cells known as B cells create antibodies that cleave to the virus and mark the virus for destruction. At the same time, Killer T cells search out infected cells and destroy them. During the several days it takes to organize and implement this counterattack, the virus courses through the body, taking over kidney cells, liver cells, breaking down blood vessels until the organs themselves fail, and blood flows uncontrollably. There is no way to stop it unless the body can mobilize its forces before the virus has taken hold—that is what a vaccine does. The vaccine is a milder but live form of yellow fever that activates both arms of immune response—in advance.

Max Theiler’s work in Boston caught the attention of some scientists working with the Rockefeller Foundation—one of which was Dr. Wilbur Sawyer. The Rockefeller Foundation offered Theiler double his salary at Harvard to join their yellow fever lab. Theiler accepted and began work with Sawyer on a vaccine to inoculate the doctors who worked in labs—doctors who continued to die from their work with yellow fever. Theiler himself had contracted yellow fever in the lab in 1929, but recovered, developing immunity. Recently, three other doctors had also developed yellow fever in their work in the United States and in Lagos; one had died. A vaccine would finally give the scientists trying to conquer yellow fever a fighting chance.

Sawyer and Theiler developed a makeshift vaccine combining the infected mouse-brain tissue with blood from a human immune to yellow fever. Then, they took the amalgam of virus and antibodies and injected it into a man named Bruce Wilson. Wilson, who had earned fame as a public health field director fighting against malaria, had just returned from Brazil. He was checked into a screened room at the Rockefeller Institute, where he was injected with this new vaccine. His temperature and pulse were monitored constantly, and to pass the time, Wilson taught his night nurse how to play poker. Wilson never grew ill, and instead, developed immunity to yellow fever.

They now decided to turn their attention to developing a large-scale, safe vaccine. French studies using Theiler’s mouse strain had produced some negative reactions. Even Sawyer had seen the occasional case of fatal encephalitis during his test studies on monkeys. They decided to try an entirely new vaccine using milder strains of yellow fever taken directly from monkeys, forgetting the mice all together. An extensive laboratory was set up in which thousands of flasks, a factory line of glass tubes, housed the virus—part of the Asibi strain—and reproduced it in various forms. They experimented with mouse embryos, then chicken embryos. With time, they developed what became known as the 17-D vaccine, grown in a chicken embryo and named for the seventeenth series of experiments and the type of tissue used. The only complication wasn’t really a complication at all: The virus required a little human nonimmune blood, a serum, to survive. The doctors therefore added about 10 percent human blood to the vaccine. It was cheap and safe—it seemed simple enough. But man continually underestimates nature, and as a result, nature occasionally makes folly out of man’s triumphs.

Scientists had now been working on a vaccine for nearly ten years. Throughout the 1930s, as America fell into a deep depression, the doctors locked themselves away in labs and engaged in this viral fertility study. They nurtured the yellow fever virus, disciplined it, fed it blood and grew it in the surrogate confines of a chicken egg.

By 1941, it seemed clear that America would soon be at war, and as every war in the past had taught, disease could be far more devastating than the enemy. Dr. Wilbur Sawyer worked on a mass production of the vaccine to inoculate American soldiers as they left to fight. Theiler had some reservations about the new vaccine though. He wanted to try a serum-free vaccine, one that could be used without introducing human blood into the mix. Sawyer thought it was a good idea in theory, but added that there simply wasn’t time. America was headed for war, and soldiers were headed into countries where yellow fever was rampant—particularly Africa. “You are courting disaster,” Theiler told him.

In the fall of 1941, the yellow fever vaccine was given to all troops departing for the tropics, and by 1942 seven million doses had been issued by the International Health Division to the U.S. Army, Navy and the British fighting in Africa. But, complications began to arise—infectious hepatitis was reported among soldiers. At first, it was sporadic; then, it became epidemic. The soldiers seemed jaundiced, complained of headaches, nausea and dizziness. There were a few fatalities. It did not take long for the blame to fall on the new yellow fever vaccine—the blood that fed the virus in the vaccine had been taken from several hundred volunteers. A few of those—maybe 2 percent—reported a history of jaundice. Their blood had been pooled, and roughly 400,000 doses of the vaccine had been tainted. It became known as “Rockefeller disease” and “serum hepatitis.”

In the end, there were close to 50,000 cases and 84 deaths. But there was not a single yellow fever case in an American soldier. Dr. Wilbur Sawyer took complete responsibility for the hepatitis epidemic, as well as for the notable absence of yellow fever among the troops. He would be remembered for the former, not the latter.

It was October 15, 1951, when Max Theiler received a cablegram at his lab in New York. He had been awarded the Nobel Prize in Medicine for his “discoveries concerning yellow fever and how to combat it.” When asked what he would do with his $32,000 prize money, Theiler responded: “Buy a case of Scotch and watch the Dodgers.”

Max Theiler is the only scientist ever to receive the Nobel Prize in connection with yellow fever.

History Repeats Itself

Today,
Aedes aegypti,
the striped house mosquito, is blamed for any urban outbreak of yellow fever, but several other mosquitoes are known to carry the yellow fever virus as well. Those mosquitoes play a part in what’s known as jungle yellow fever. They live in the tree canopies of Africa and South America and pass the virus back and forth through wild monkeys. When a human becomes infected it is because he, and they are usually young men, is working in the jungle clearing forests. In fact, jungle yellow fever is considered more of an occupational hazard than anything else. It survives on a continual cycle between mosquito and monkey, with the occasional human getting caught in the crossfire.

An urban epidemic of yellow fever occurs when jungle yellow fever makes the jump into a large human population. The forest-dwelling mosquitoes, perhaps an
Aedes africanus
in Africa or a
Haemagogus
in South America, fly beyond the borders of the jungle into the territory of a city-dwelling
Aedes aegypti.
The two mosquitoes share a blood meal from a monkey, and suddenly, the virus is passed from a jungle mosquito to a city mosquito that spreads the virus to a human population. In Africa, the most common type of yellow fever is the intermediate one, in which yellow fever can survive in terrains between the jungle and urban cities. Whether it starts as a jungle outbreak in South America or an intermediate one on the African savannah, the worst-case scenario is the same: The fever moves into a large city, the virus builds more strength, and it infects thousands. An outbreak of urban yellow fever is always considered an epidemic.

Because the virus is not part of an urban cycle the way it is in the jungle, the virus is unleashed on a fresh population of nonimmunes. It is much the same as it was 400 years ago when Europeans first arrived in Africa during the slave trade. They landed on the shores of West Africa armed and ready to export human labor; instead, many served as nothing more than an import of nonimmunes for the yellow fever virus.

In just the same way, the cycle happened on this side of the world. It attacked nonimmune populations that had never before seen the virus.
Aedes aegypti
mosquitoes traveled on board the ships from Africa and then proliferated, most likely spreading yellow fever to native, forest-dwelling mosquitoes in South and Central America that settled back into the jungles to begin the cycle of mosquito and monkey transmission, harboring the fever in the sultry haunt of lush tropical life.

In the United States, the cycle had taken a different turn. There were no cases of jungle yellow fever, no forest-dwelling monkeys giving refuge to the virus; it was not a yearly occurrence. Instead, there was only a series of urban epidemics when the virus exploded on a population.

The cycle would not be broken until the mosquito’s breeding places were destroyed. In Memphis and elsewhere, it happened through the invention of the sewer system and elimination of private cisterns and privies.

Massive campaigns against
Aedes aegypti
essentially wiped out the mosquito from Central and South America, and the U.S. government promised to do the same. In their book
Mosquito,
Andrew Spielman and Michael D’Antonio wrote that there was a sense of irony to the situation: “After all, America had gone to war with Spain, in part, because of the danger of yellow fever spreading from Cuba into nearby lands.” Now that Latin America had the same concerns about the United States, there was opposition to the idea. North Americans did not welcome the intrusion of government employees trampling through yards and hunting mosquito larvae. What’s more, the Environmental Protection Agency banned the use of DDT. As a result,
Aedes aegypti
never fully left the United States; if its presence today was not already known, it was brought to our attention with recent outbreaks of dengue in Texas.

Over time, mosquitoes have proven their evolutionary dexterity, adapting to insecticides and building a resistance. Once again, the striped house mosquito now flourishes in cities throughout South America, Central America and the southern United States. Its lyre-marked body and striped legs swarm around potted plants, gutters and rain-filled watering cans. A homebody, the domestic
aegypti
prefers human habitations, houses, boats and fresh water. But this was not always the case.

Hundreds of years ago,
Aedes aegypti
lived only in the jungles of Africa, where it hovered around tree trunks to lay its eggs in pools of rainwater. Its range was short; the mosquito preferred to stay in one general place, close to the trees. As man traveled into the interior of Africa, the mosquito made its evolutionary leap: It adapted to human life. Rather than tree trunks, it first sought water casks, then standing water around homes, and in modern times, oddly enough, it has adapted to tires. The dark interior and the water that clings to the inside of a tire mimic the hollows of a tree trunk. Scientists believe that the world’s mass of discarded tires in urban settings has recreated the atmosphere of those ancient jungles in Africa.

Aedes aegypti
is not the only mosquito to have made the journey from tree holes to tires. The Asian tiger mosquito,
Aedes albopictus,
is relatively new to the United States. The tiger mosquito arrived in 1983 in a shipment of tires from Asia. The large, striped mosquito is very similar in appearance to its
aegypti
cousin, but true to its name, the tiger mosquito is a more voracious feeder. As a vector the tiger mosquito has been known to carry dengue, encephalitis and yellow fever in other countries. It has yet to transmit disease in the United States. The tiger mosquito, hardy and determined, has proliferated in North America, even crowding out some of its
aegypti
neighbors. Nature has a dark sense of humor though: The first Asian tiger mosquito on this continent was found hovering in Elmwood cemetery in Memphis, Tennessee.

In recent years, vaccine usage for yellow fever has fallen off. The problem is a lack of education and funds sufficient for the dissemination of the vaccine. Surveillance is also minimal. As a result, in the 1970s, outbreaks of yellow fever began once again, creating what is known as the “yellow fever belt” in Africa. The World Health Organization described the 1980s and 1990s as an extraordinarily active period for yellow fever in Africa. But that activity continues even today, and Nigeria has reported more epidemics than any other African country.

Ninety-three percent of the countries in West Africa now have cases of yellow fever—up 30 percent just since the mid- 1990s. Yellow fever, it seems, is making a comeback; it is also spreading to areas that have never before seen the virus. Thirty-three countries in Africa and nine in South America are now known to house the virus. The number of deaths vary, but in South America, mortality rates from yellow fever have been as high as 80 percent. Two hundred thousand people worldwide are infected each year, but the number of actual cases is thought to be 10- to as much as 250-fold higher due to underreporting or misdiagnosis.

At one time in history, there were several factors in play that led to recurring, explosive epidemics of yellow fever. They were modes of transportation, populations of vulnerable hosts, warm weather cycles and the colonization of
Aedes aegypti
in urban environments. The circumstances today in Africa and parts of South America mirror those of Memphis in 1878—there is poverty, people living in shanty houses, poor sanitation, containers of water in place of plumbing, a tropical atmosphere and a high population of
Aedes aegypti
mosquitoes. As the human population increases rapidly, so does the number of nonimmune people. And just like the paddleboats and trains of the nineteenth century, we now have shipping containers and airplanes. Global warming has broadened the range of disease-carrying mosquitoes. And we have a new threat: Yellow fever is listed among the pathogens that might be used during a bioterrorist attack.