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Yellow Fever Resurgence

  • Writer: P.K. Peterson
    P.K. Peterson
  • May 28
  • 5 min read

“Havana, Cuba, in which city yellow fever had not failed to make its yearly appearance during the past one hundred and forty years... Havana was freed from yellow fever within ninety days.”

Walter Reed, MD,  1902

“In times of stress and danger such as come about as the result of an epidemic, many tragic and cruel phases of human nature are brought out, as well as many brave and unselfish ones.”

William Crawford Gorgas, MD, US Army physician, eradicated yellow fever in Panama

 

 

Yellow fever is a viral infection and one of the most brutal infectious diseases that profoundly shaped the early history of the Americas, including the U.S. While the last yellow fever epidemic in the U.S. occurred in New Orleans in 1905,  a rise in confirmed human cases of yellow fever in several countries, along with a change in the geographic distribution of the disease, prompted the World Health Organization (WHO) on February 2, 2025, to issue an epidemiological alert regarding yellow fever in the Americas region. The WHO’s alert prompted me to write this post.

Yellow fever; a brief history. The evolutionary origins of yellow fever most likely lie in Africa, with transmission from nonhuman primates to humans. The yellow fever virus, Orthoflavivirus flavi, as well as the mosquito vector, Aedes aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa. In any event, the first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados. (During Colonial times and the Napoleonic Wars, the West Indies was known as a particularly dangerous posting for soldiers due to yellow fever.)


Although yellow fever is most prevalent in tropical-like climates, the northern U.S. was not spared. The first yellow fever outbreak in the northern U.S. occurred in New York City in 1668 followed by outbreaks throughout the country with devastating consequences in Philadelphia, Baltimore, and southern cities such as New Orleans where the disease was referred to as “yellow jack.”


Because losses from yellow fever in the Spanish-American War in the 1890s were so high, Walter Reed and Carlos Finlay led a team of U.S. army doctors—the Yellow Fever Commission—to research the disease. Dr. Finlay hypothesized that there was a yellow fever vector, that is, mosquitoes transmitted an infectious agent that caused yellow fever to humans.  The Commission’s experiments supported Finlay’s hypothesis.  In the early 1900s, Dr. Reed showed for the first time that yellow fever was transmitted by mosquitoes. (Reed is also credited with using the first type of medical consent in an attempt to inform participants they were taking a risk by entering his studies.)


The acceptance of Finlay’s mosquito hypothesis was one of the most important and far-reaching effects of the Commission. Later, Colonel William Gorgas applied the Commission’s work in the successful control of yellow fever virus- and malaria-infected mosquitoes in the building of the Panama Canal.


Even though the yellow fever mosquito vector hypothesis was proven in the early 1900s, it wasn’t until 1927 when scientists isolated the yellow fever virus—the first human virus to be isolated. Then, in 1937, Max Theiler, a South African virologist developed a vaccine against the virus for which he received the Nobel Prize in Physiology or Medicine in 1951. Theiler’s vaccine is still in use.


What is yellow fever? The yellow fever virus (Orthoflavivirus flavi) is an enveloped RNA virus belonging to the Flaviviridae family. The virus is transmitted to humans by the bite of Aedes aegypti mosquitoes. Upon entry into the human blood stream, the virus infects monocytes, macrophages, dendritic cells, and liver cells (causing hepatitis and jaundice).


Symptoms. The incubation period for yellow fever is 3 to 6 days. Many people are asymptomatic, but when symptoms occur they include fever, muscle pain, headache, loss of appetite, nausea, or vomiting. A small percentage of patients enter a second, more toxic phase, with jaundice (yellowing of the skin and eyes—hence the name “yellow fever”), dark urine, and bleeding from the mouth, nose, eyes, or stomach. Half the patients who enter the toxic phase die within 7-10 days.

Treatment and prevention. There is no specific antiviral therapy for yellow fever. Prevention measures are aimed at mosquito control and vaccination.


The prevention of yellow fever includes all of the same behavioral interventions used to prevent other Aedes aegypti-transmitted viruses (dengue, chikungunya, and Zika virus) access to your bloodstream, that is, use of copious amounts of insect repellent, wearing long-sleeved shirts and long-legged pants, assuring proper window screens, and disposing of standing water.


Also, of great importance in prevention of yellow fever is vaccination; it is the primary means for the prevention and control of the disease. But, because this vaccine is associated with more side effects than most other vaccines, everyone who is at risk of yellow fever, that is, those residing in a yellow fever endemic country or those with plans to travel to such countries, should confer with their healthcare provider for advice regarding vaccination.


The Centers for Disease Control and Prevention (CDC) also provides an updated website to checkout before traveling. At “CDC Travelers Health,” you will find information about the risk of yellow fever by country and specific information about risks and benefits of the vaccine.


Some countries require a yellow fever vaccination certification to gain entry. The CDC also identifies where you can find such a clinic in your state. (See, CDC Search for Yellow Fever Vaccination Clinics).


Epidemiology. The WHO estimates about 600 million people live in endemic areas of yellow fever and that 200,000 cases and 30,000 deaths from yellow fever occur globally each year. As of 2023, 34 countries in Africa and 13 countries in Central and South America were endemic for yellow fever. An increase in cases outside of the Amazon basin in South America prompted the WHO’s February 2025 epidemiologic alert. As the WHO said, “The occurrence of yellow fever cases outside of the Amazon basin, combined with high fatality, varying vaccination coverage across affected countries, and a limited vaccine supply, contribute to the overall classification of yellow fever risk in the Region of the Americas, especially in endemic countries, as high.”

Could yellow fever return to the U.S.? At present, yellow fever is no longer a threat in the U.S.  By the 1930s, yellow fever had been eliminated from the U.S. and effective measures have been taken to prevent its reintroduction. But, could yellow fever return to the U.S.?

According to an article in The New England Journal of Medicine, “[T]here are renewed fears that yellow fever could return to the southern United States” and that “such an epidemic could take a greater toll than most modern outbreaks of infectious disease in the United States.” (Hotez, Peter J. and LaBeaud, Angelle Desiree, “Yellow Jack’s Potential Return to the American South,” The New England Journal of Medicine, October 14, 2023).


As the authors stated, “The combination of regular Aedes-associated arbovirus outbreaks in Florida and Texas, an expanding yellow fever risk map in the Western Hemisphere, and the potential for El Nino to exacerbate the impact of climate change and urbanization should give us pause. Our ability to respond is unclear.”  The authors believe that yellow fever “should be prioritized as part of our national pandemic preparedness.”  Whether that happens or not remains to be seen.

 

 

 
 
 

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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