Yellow Fever: A Transcontinental Threat?

Researchers are seeing red over yellow fever.

In a pair of submissions published in the April 13, 2017 issue of The New England Journal of Medicine, 2 separate teams describe concerns regarding potential yellow fever outbreaks in very different parts of the world—namely, Africa and the Americas.

As noted in the first, a commentary authored by Catherine I. Paules, MD, and Anthony S. Fauci, MD, of the US National Institutes of Health (NIH), yellow fever has become the fifth arthropod-borne virus—after dengue, West Nile, chikungunya, and Zika—to emerge or reemerge in the latter region, “spreading rapidly through populations that had not previously been exposed to them.” It is the most severe of these viruses, with the highest morbidity and mortality rates.

Indeed, yellow fever, Drs. Paules and Fauci wrote, has “broken out” in Brazil (ground zero for the Zika virus since 2014), striking primarily rural areas of the country, with humans serving as only “incidental hosts” in so-called sylvatic (or “jungle”) cases transmitted between mosquitoes and nonhuman primates. In March, Brazil’s Health Ministry reported that there had been hundreds of confirmed cases, with more than 200 fatalities.

“The high number of cases is out of proportion to the number reported in a typical year in these areas,” Drs. Paules and Fauci continue. “Although there is currently no evidence that human-to-human transmission through Aedes aegypti mosquitoes has occurred, the outbreak is affecting areas in close proximity to major urban centers where yellow fever vaccine is not routinely administered.”

Although the authors are not particularly concerned about the possibility of yellow fever outbreaks in the continental United States, they noted 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 Aedes aegypti mosquitoes are prevalent.” In addition, US territories such as Puerto Rico, which has been significantly impacted by the Zika virus, remain vulnerable to local transmission of yellow fever.

“To prevent a similar occurrence in Brazil or in future yellow fever outbreaks [elsewhere], early identification of cases and rapid implementation of public health management and prevention strategies, such as mosquito control and appropriate vaccination, are critical,” they wrote. “Early recognition may be difficult in countries such as the United States, where most physicians have never seen a case of yellow fever and know little about the clinical manifestations.”

Meanwhile, in a correspondence, researchers from the Institut Pasteur and the World Health Organization (WHO) describe a particularly vexing—and dangerous—manifestation of yellow fever: coinfection with Japanese encephalitis virus. As the authors note, although yellow fever and Japanese encephalitis are both flavirviruses, they are endemic to distinct regions and are transmitted via different mosquito vectors. However, they describe the case of coinfection, which occurred in March 2016, during the yellow fever outbreak in Angola, in a 19-year-old man with no history of travel.

The patient presented with a 5-day history of fever, headache, and jaundice. He had been working in Angola’s capital, Luanda, at the onset of disease. Clinicians obtained a blood sample, which tested positive for yellow fever. The sample was then processed for high-throughput RNA sequencing, which “revealed a Japanese encephalitis virus genome (GenBank accession number, KX945367) in addition to the expected yellow fever virus genome (GenBank accession number, KX982182),” the authors wrote.

“Phylogenetic analysis revealed that this Japanese encephalitis virus variant belongs to genotype III, clustering closely with variants sampled in Asia,” they continued. “The yellow fever virus sequence was closely related to both a sequence from the 1971 yellow fever virus outbreak in Angola and the recently reported yellow fever virus sequence detected in a sample from a Chinese traveler returning from Angola.”

The authors of the correspondence believe the “likelihood of sample contamination is small,” and note that “none of the 15 additional RNA samples from patients with yellow fever virus who were treated at the same time provided sequence reads that corresponded to Japanese encephalitis virus.” They added that because Angola has suitable vectors and hosts for Japanese encephalitis, increased “serosurveillance” is advisable.

“Increased levels of population movement between Asia and Africa may provide opportunities for pathogens to expand their geographic range,” they concluded.

Brian P. Duleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.