From Exploration to Eradication: The Story of Yellow Fever in American History

The Age of Exploration, initiated by Columbus’ discovery of the New World, spurred a wave of global exploration as Europeans sought wealth and resources. This drive led to increased interactions among continents, culminating in the establishment of the triangular trade system. This network facilitated extensive contact between the Americas, Western Europe, and Western Africa, promoting the exchange of goods, resources, and human labor. However, this era of burgeoning trade and exploration also allowed for the intercontinental spread of diseases, as these interactions were not limited to commodities but extended to pathogens that accompanied traders and goods across the oceans. Consequently, the movement of people and products during the Age of Exploration became a vector for disease transmission, impacting populations on a global scale. One significant disease that traversed these new paths was yellow fever, which, like many commodities, found its way across the Atlantic, deeply affecting the populations it reached. Its introduction had a profound impact on North America, with outbreaks significantly affecting the population and shaping the nation’s public health history. 

Yellow fever (YF) is a zoonotic arbovirosis, caused by the leading virus in the Flavivirus genus, part of the Flaviviridae family, which comprises about 70 RNA viruses with a single, positive-strand. The virus primarily spreads from bites of mosquitoes, notably from the Aedes (Stegomyia) aegypti (Linnaeus) which originated in Africa. Yellow fever typically starts with high fever, body aches, and nausea, and can escalate to jaundice, abdominal pain, and bloody vomiting. Severe cases might lead to organ failure and can be fatal, while recovery from mild cases usually leaves no lasting effects (Monath, p.1-4). The first reliably documented Yellow Fever outbreak in North America occurred in 1693 in New England. It was brought by an English fleet carrying the disease, leading to several fatal cases among the local population. Following the initial outbreak, North America witnessed a rise in yellow fever incidents, with the disease intermittently ascending the Mississippi River during the 19th century. Cities such as New Orleans, Mobile, Savannah, and Charleston were frequently afflicted, resulting in approximately 100,000 to 150,000 deaths (Carter, p. 187-198). 

The initial emergence of yellow fever in the United States was marked by extensive mortality and suffering, as exemplified by the severe outbreaks in the Philadelphia port and New Orleans. However, significant medical advances, including the identification of the mosquito as the disease’s vector and the development of the 17D vaccine, have dramatically reduced the fatality rates. This notable decrease in deaths not only underscores the remarkable progress in the United States’ medical and public health improvements to yellow fever but also sets a precedent for future healthcare advancements. 

In the early stages of its spread, yellow fever initially struck port cities, as they were the primary points of entry for the disease that originated from Africa via the maritime trade routes. The contagion, primarily transferred by sea, initially impacted these coastal areas. As the years progressed, up to the mid-19th century, the intensity of the outbreaks in these ports escalated, resulting in mortality rates that frequently reached 5% to 10% of the population in the affected cities (Bryan, p.280-281). 

The Philadelphia port in 1793 became infamous for a severe yellow fever epidemic that began in July and escalated through early October. At the time, as the nation’s capital and most diverse city, Philadelphia was home to a community of 2,000 free Black individuals and numerous French-speaking whites who had fled the slave uprisings in Santo Domingo during the Haitian Revolution. The city, which housed several notable figures from the American Revolution, saw a mass exodus as the epidemic worsened, described by Thomas Jefferson in a letter to James Madison noting the widespread flight. The impact was devastating, with 5,000 deaths from a population of 45,000 and estimates suggesting an additional 17,000 people left the city, as recorded by chronicler Mathew Carey (Rush, p.3-28). During this epidemic, around 10% of the city’s residents perished, and numerous others, including a sick Alexander Hamilton and his spouse, evacuated the area. Dr. Benjamin Rush, who remained, published recommendations on how to prevent infection and was instrumental in establishing a hospital specifically for those suffering from the fever. However, it wasn’t just the fatalities that affected North America; the outbreak also enhanced medical protocols for epidemics. It revealed that infection spread through long exposure in small, stuffy rooms and direct contact with the unventilated belongings of the sick. Adequate ventilation, exercise, balanced eating, and moderate alcohol use emerged as key preventive measures, while excessive drinking and superstitious practices proved to be unhelpful, often exacerbating fear (Currie, p. 9-15). 

Additionally, New Orleans saw a considerable proliferation of yellow fever cases. The epidemic of New Orleans 1847 was marked by the high number of fatalities and widespread illness, with reported cases beginning with intermittent fevers in the spring and escalating to a full-blown epidemic by July. Initially traced back to Vera Cruz, the disease spread rapidly, highlighted by a notable case involving a man from Vera Cruz who died in June at a New Orleans hotel, subsequently infecting others. Despite frequent yellow fever cases, it was only when the number of sick individuals surged in July that the situation was officially recognized as an epidemic (Fenner, p.190-191). Following the initial case report, yellow fever cases escalated after the first case report of patients, culminating in 2,306 deaths in 1847—a stark surge compared to 83 in 1844, 2 in 1845, and 146 in 1846. This marked a significant spike in the incidence of the disease. Over the long term, from 1817 to 1905, New Orleans experienced over 41,000 fatalities due to the fever, with some years recording no deaths and nine years seeing the death toll rise above a thousand (New Orleans Public Library). 

Enduring years of recurring yellow fever outbreaks, the United States began to innovate solutions to combat the disease. The initial strides in successfully eradicating yellow fever in Havana came from collaborative efforts between American and Cuban medical professionals. Cuban physician Carlos Finlay, who formulated the theory that mosquitoes transmit yellow fever in 1881, shared his insights and publications, as well as mosquito egg specimens, with the U.S. Army Yellow Fever Commission (Chaves-Carballo, p.881-884). The United States Army Yellow Fever Commission, established in 1900 and led by Walter Reed, confirmed Carlos Finlay’s earlier hypothesis that the Aedes aegypti mosquito was the vector for yellow fever. Through their work, which included human volunteers undergoing experimental infection, it was determined that the mosquito must harbor the virus for about 12 days before it can transmit the disease. This groundbreaking research, which indicated the virus was too small to be seen with a microscope, laid the groundwork for controlling yellow fever. By 1901, William Crawford Gorgas had successfully implemented mosquito control measures in Havana, eradicating the disease. This strategy was later applied in Panama by Gorgas and in Rio de Janeiro by Oswaldo Cruz. Consequently, control measures against Aedes aegypti became standard in tropical ports, significantly reducing the spread of yellow fever and ensuring that the overwhelming infestations of the past were unlikely to occur again (Downs, p. 721-726).

Following the discovery that mosquitoes transmit yellow fever, Max Theiler made a significant advancement in the fight against the disease. He discovered that cultivating the yellow fever virus in different tissues altered its potency. Growth in mouse embryo tissues mildly decreased its severity, avoiding lethal outcomes in monkeys. The virus became considerably less potent in chick embryo tissues, causing only mild effects in monkeys and extended the incubation period in mice without inducing severe brain disease. Similarly, testicular tissue cultures lessened the virus’s virulence but still resulted in fatal outcomes when introduced directly into the brains of monkeys. This research led to Theiler’s creation of the 17D vaccine strain, which has been instrumental in saving countless lives globally (Theiler, p.767-786). In 1951, Max Theiler of the Rockefeller Foundation received the Nobel Prize in Physiology or Medicine for his discovery of an effective vaccine against yellow fever—a discovery first reported in the JEM 70 years ago. This was the first, and so far the only, Nobel Prize given for the development of a virus vaccine (Norrby, p.2779-2783). 

In conclusion, the saga of yellow fever in the United States, concluding with the last epidemic in New Orleans in 1905, exemplifies a significant evolution in public health and medical science (Carrigan, p. 19-28). From its introduction during the Age of Exploration to devastating outbreaks in cities like Philadelphia and New Orleans, yellow fever shaped the nation’s public health response. The collaborative efforts between American and Cuban doctors, particularly the work of Carlos Finlay, Walter Reed, and Max Theiler, were instrumental in understanding and combating the disease. The identification of the mosquito as the vector and the development of the 17D vaccine represent milestones in medical science. Today, yellow fever remains endemic only in South America and Africa, a testament to the significant strides made in understanding and managing this once-devastating disease (Jentes, p. 622-632). This story of overcoming yellow fever underscores the resilience and innovation in the face of public health challenges, marking a significant chapter in both U.S. history and medical advancements.

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By. Sungju Park