The yellow fever virus. (Image: Science Photo Library/Getty)

An old enemy—yellow fever—is rearing its ugly head in parts of Brazil, prompting concerns that the mosquito-borne virus could spread across the Americas and into the United States. It’s a headache in the making given the severity of the disease—and the fact that vaccines are in short supply.

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In a new Perspective article published in the New England Journal of Medicine, Anthony Fauci and Catherine Paules from the National Institute of Allergy and Infectious Diseases (NIAID) warn that the current yellow fever outbreak in Brazil could start to spread in a manner similar to other mosquito-borne diseases, such as dengue and Zika. They say physicians and healthcare workers need to be on alert, especially when treating patients who have returned from Brazil. Troublingly, the virus has a chance, albeit a slim one, to spread within the United States itself. Very few people in the US—or elsewhere for that matter—are vaccinated against yellow fever, and vaccinations are in short supply, complicating matters even further.

In the Americas, four mosquito-borne diseases have either emerged or re-appeared in recent years, and they’re spreading at an alarming rate. Dengue emerged in the 1990s, followed by West Nile virus in 1999, Chikungunya in 2013, and Zika in 2015. Worryingly, there may now be a fifth in the form of yellow fever.

Image: NIAID/NEJM

Over the past several weeks, a yellow fever outbreak has broken out in the Brazilian states of Minas Gerais, Espírito Santo, and São Paulo. The vast majority of these cases are confined to rural areas, where people primarily contract the disease by coming into contact with mosquitoes. Since December 2016, there have been 234 cases and 80 confirmed deaths, signifying an alarming mortality rate. There are hundreds of cases currently under investigation. According to the NIAID, the number of cases is disproportionately high compared to previous years in these areas.

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Thankfully, and importantly, there’s no evidence that the disease is being spread from human-to-human. But the outbreak is happening close to major urban centers where yellow fever vaccine is not routinely administered. “This proximity raises concern that, for the first time in decades, urban transmission of yellow fever will occur in Brazil,” write the authors.

Yellow Fever first came to the Americas from Africa in the 1600s, and the disease claimed hundreds of thousands of lives in the 18th and 19th centuries. In 1783, an epidemic in Philadelphia killed 10 percent of the city’s population, forcing the federal government to flee the city. By the early 1900s, scientists realized the disease was being spread by mosquitoes, and insect-control measures were implemented across the United States and elsewhere. These measures, combined with a powerful vaccine developed in 1937, practically eliminated yellow fever in the Americas. The disease is still around in parts of Africa and Central and South America, claiming about 84,000 to 170,000 lives each year, according to World Health Organization.

As witnessed by other tropical diseases, mosquito-borne viruses—particularly those that hitch a ride on aegypti mosquitoes—can move like wildfire through populations that haven’t had prior exposure. Tropical diseases are spreading faster than ever before, owing to more long-distance travel, population growth and urbanization, lack of sanitation, and ineffective mosquito control. Approximately 40 percent of the world’s population live in regions where aegypti mosquitoes can be found, and this number is increasing owing to a warming climate. This is of relevance to Americans, both in terms of where they choose to travel, and the potential for yellow fever to spread locally in parts of the United States.

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“Although it is highly unlikely that we will see yellow fever outbreaks in the continental United States, where mosquito density is low and risk of exposure is limited, it is possible that travel-related cases of yellow fever could occur, with brief periods of local transmission in warmer regions such as the Gulf Coast states, where A. aegypti mosquitoes are prevalent,” write Fauci and Paules. That said, the authors believe that localized outbreaks of yellow fever aren’t out of the question—just look at the recent Zika outbreaks in Puerto Rico, Florida, and Texas.

Troublingly, it may be difficult to for physicians to detect yellow fever in patients, particularly in countries like the US where most doctors and healthcare workers have never even seen a case of the disease. After a three to six day incubation period, patients start to develop flu-like symptoms that are virtually indistinguishable from more common flus. Typically, the disease is suspected only after the onset of severe symptoms, and a diagnosis can only happen when samples are confirmed in specialized labs.

Here’s what the US Centers for Disease Control has to say about the yellow fever and its symptoms:

  • The majority of persons infected with yellow fever virus have no illness or only mild illness.
  • In persons who develop symptoms, the incubation period (time from infection until illness) is typically 3–6 days.
  • The initial symptoms include sudden onset of fever, chills, severe headache, back pain, general body aches, nausea, and vomiting, fatigue, and weakness. Most persons improve after the initial presentation.
  • After a brief remission of hours to a day, roughly 15% of cases progress to develop a more severe form of the disease. The severe form is characterized by high fever, jaundice [hence the name “yellow fever”], bleeding, and eventually shock and failure of multiple organs.

In terms of treatment, there are no antiviral medicines available for this disease, and patients should be hospitalized for observation. Most people recover after about a week or two, and become immune to subsequent infections. Among those who develop severe symptoms, however, somewhere between 20 and 60 percent may die.

If yellow fever emerges as a wider-scale epidemic in the Americas—and that’s still a big unknown—it would make Zika, with a virtually non-existent mortality rate, look like child’s play. The authors say yellow fever is “the most severe [mosquito-borne virus] ever to circulate in the Americas,” and they’re advising physicians and healthcare workers to be on alert, particularly when treating travelers returning from affected regions.

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Vaccinations are obviously an effective way to curb the spread of yellow fever, but the current stockpile is very limited, and it would take a long time to produce additional vaccines. This could make the outbreak more difficult to control.

For most Americans, this isn’t anything to worry about—at least not yet. But if you’re planning a trip to Brazil, the CDC says it’s probably a good idea to get immunized. But because of a shortage of yellow fever vaccine, you should contact your doctor well in advance of your trip.

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[NEJM]