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Yellow fever is appearing in regions that haven't seen cases of the disease in years, largely as a result of climate change.
Historically, the virus ravaged cities across the Americas, Europe and Africa, until a vaccine was introduced in 1937 and its range shrunk significantly. But now, as climate change creates favorable conditions for virus-carrying mosquitoes, scientists are seeing outbreaks in unexpected areas.
"Yellow fever is a highly deadly disease," Dr. Joelle Ivy Rosser, an infectious-disease researcher at Stanford University, told Live Science, "so any environmental pressures that increase the likelihood of future yellow fever virus outbreaks … is highly concerning."
How is climate change contributing to this pattern, and could it get worse in the future?
Yellow fever is a mosquito-borne disease caused by the Orthoflavivirus flavi virus, better known as yellow fever virus (YFV). The infection causes fever, muscle aches, headaches and vomiting. About 15% of cases become severe, with patients showing jaundiced skin and eyes, bleeding from the mouth, eyes, nose and stomach, or organ failure.
Devastating yellow fever epidemics spread in the 17th to 19th centuries, before the development of a vaccine. Nowadays, an estimated 31,000 to 82,000 yellow fever deaths occur each year; severe cases have an estimated fatality rate of 20% to 50%.
Most yellow fever infections are a result of spillover from nonhuman primates; mosquitoes bite monkeys that carry the virus, such as howler monkeys, and then the infected mosquitoes bite humans. Several types of mosquitoes carry the virus, but the species Aedes aegypti is the main vector for yellow fever in cities, where high population density can make outbreaks especially severe.
Although there is an effective vaccine for yellow fever, cases have been on the rise in the past three decades. This led the World Health Organization (WHO) to set out a strategy in 2017 for eliminating yellow fever epidemics by 2026 through outbreak prevention and containment.
Climate-change-driven warming and extreme weather events may have heightened yellow fever risk over the past few decades, experts say. Rising temperatures make mosquitoes bite more because heat makes their metabolisms more active, said Dr. Seth Judson, an infectious-disease physician-scientist at UCLA. Warming also cuts down the virus's extrinsic incubation period, meaning the time it takes for the virus to replicate in a newly infected mosquito and then get passed on to another person, he told Live Science.
Changing weather patterns play a role, too. In 2017-2018, Brazil saw its first yellow fever outbreak in a city in almost a century. That outbreak, primarily in Belo Horizonte and São Paulo, was likely a result of drought, according to one study.
Extremes of weather in either direction can exacerbate mosquito-borne disease transmission
Dr. Joelle Ivy Rosser, infectious-disease researcher at Stanford University
While heavy rainfall creates a breeding ground for mosquitoes, in this case, drought pushed forest-based mosquitoes — as well as YFV carriers like marmosets and howler monkeys — closer to cities as the animals searched for water. Drier conditions can also prompt dehydrated mosquitoes to bite more as they search for fluids, study co-author Jamie Caldwell, a disease ecologist at Princeton University, told Live Science.
"Extremes of weather in either direction" — very wet or very dry — "can exacerbate mosquito-borne disease transmission," Rosser said.
Parts of Africa and South America that were considered low-risk for yellow fever have already been seeing new outbreaks, Judson said, so maps of yellow-fever-affected areas have had to be updated. In research that's been released as a preprint but not peer-reviewed yet, Judson found that yellow fever is reemerging in an area of the Colombian Andes where it hadn't been reported since 1940.
Experts are paying particular attention to the edges of cities, where urban centers meet the forest. The risk of yellow fever transmission from monkeys to humans via mosquitoes is rising at these edges due to both climate change and deforestation.
"Humans are expanding the agricultural frontier and encroaching on forests where yellow fever mosquitoes … are found," Gabriel Parra-Henao, a biologist with the WHO, told Live Science in an email. "[This] results in more people being exposed to their bites."
Similar patterns have been seen with other mosquito-borne infections, such as malaria.
Climate change is expected to bring yellow fever to new areas. One study predicts that, under the most severe climate change scenario, nearly a billion people could face their first exposure to the mosquitoes that can carry YFV in the next century. While that worst-case scenario may not be the most likely, the mosquitoes' ranges are still expected to expand under less-severe conditions.
Europe is predicted to face the largest increase in exposure to Ae. aegypti mosquitoes compared to the rest of the world, and the U.S. and Canada are predicted to see increases too. In the U.S., the mosquito species already lives in a number of states, including Florida, Mississippi, Arizona and New Mexico. However, warming would increase the chances of mosquitoes surviving in locations further north, such as Philadelphia and New York, which suffered major yellow fever outbreaks in the past. One model predicts Ae. aegypti could spread as far north as Chicago by 2050.
I think many people don't realize that we're still seeing significant yellow fever outbreaks.
Dr. Seth Judson, infectious-disease physician-scientist at UCLA
Although the mosquito lives in the U.S. already, yellow fever cases are exceedingly rare within the country because the virus is not present in local populations. That's because of an international campaign that the U.S. spearheaded in the 20th century, which involved researching YFV, eradicating mosquito breeding grounds, and vaccinating people widely.
"If yellow fever virus reestablished itself in our local Aedes aegypti population, then that would be very concerning," Rosser said.
One way yellow fever could return to the U.S. would be via people carrying the virus home with them after traveling to regions where the disease regularly circulates. Local mosquitoes could then catch the virus by biting those infected people, and then pass it on to others.
For local transmission to take hold, "there needs to be significant numbers of infections [passed to locals], and infections among travelers," Judson said. "But … it's in the realm of possibility."
With climate change driving resurgences of yellow fever in more places, and more regions of the U.S. becoming hospitable to the mosquitoes, that reintroduction scenario may become more likely. But some scientists think that even if North American cities saw yellow fever outbreaks, the outcome would likely not be devastating. Infrastructure in wealthier cities could be the difference between a disaster and a manageable health concern.
"There's access to medicines and vaccines; we pipe water to our homes, so we don't have standing water around," Caldwell said. "So it is a concern, but it's never going to be the next COVID."
Other experts noted that diligent surveillance of yellow fever infections can help public health officials prepare. In places where yellow fever is circulating in forest primates, forest conservation can limit contact among humans, wildlife and the mosquitoes that spread diseases among them. It's also crucial to make vaccines widely accessible to people who live in the virus's endemic regions and to travelers who visit those regions.
The WHO's yellow fever campaign is set to conclude at the end of this year, and its next steps are unclear. There's ongoing discussion of what comes next, Judson said, with questions about whether the control of yellow fever outbreaks will rely more on national strategies than on international coordination via the WHO.
Whatever happens, this is a time for heightened awareness of the virus, Judson said.
"We think of yellow fever as this historic disease," he said. "I think many people don't realize that we're still seeing significant yellow fever outbreaks. … It's really important to be aware of the risks and think about how we prepare for that."
This article is for informational purposes only and is not meant to offer medical advice.
Diseases that cause nerve cells in the brain to die over time are known as neurodegenerative diseases. These cells, known as neurons, are vulnerable to DNA damage because they are highly active cells that require large amounts of energy. Neural DNA damage is a normal part of aging as changes to the DNA sequence, called mutations, build up over time.
Previous scientists have shown that neurons from people with the neurodegenerative diseases Alzheimer’s disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) accumulate unusually high numbers of changes in the DNA sequence, called somatic mutations. However, researchers don’t know what causes the high number of mutations or whether the same process causes them in all 3 diseases.
To answer these questions, researchers at Boston Children’s Hospital and Harvard Medical School analyzed brain tissue from people who died with and without AD, FTD, or ALS. They compared the processes that cause DNA mutations in the 3 diseases by first accessing the DNA inside individual neurons from healthy and diseased postmortem brain tissue.
To do this, they broke apart the brain tissue and added a fluorescent marker that identified the center of each neuronal cell where DNA is housed, called its nucleus. They used a sorting machine to separate the nuclei from the rest of the cell material to access the neuron’s DNA. Using a DNA sequencing method called single-cell whole genome sequencing, the team then sequenced each neuron’s DNA to identify mutations.
They analyzed 159 neurons from people with AD, 61 neurons from people with FTD, 77 neurons from people with ALS, and 232 neurons from healthy individuals. This allowed the team to compare the number and types of DNA mutations between diseased and control (non-diseased) neurons. The researchers found that compared to the control neurons, which typically accumulate only 200 to 300 mutations over an 80-year lifespan, neurons from all 3 diseases contained an unusually high number of 2-base-pair deletions, often exceeding 1,000 mutations per cell.
When a biological process damages DNA, it leaves behind its own unique signature. By identifying these signatures, scientists can identify the biological process that likely caused the damage. Since these 2-base-pair deletions were so frequent in diseased neurons, the researchers wanted to know whether they were left behind by a biological process. The researchers used a machine learning algorithm to scan DNA sequences for recurring mutation patterns and identified a signature in neuronal DNA, which they named ID-4.
When the researchers compared the ID-4 signature with a database of previously characterized signatures, they found that it was associated with a DNA repair protein called TOP1. TOP1 temporarily cuts and rejoins DNA to relieve the tension that builds up during normal cellular activity. TOP1 typically detaches from the DNA after completing this process. However, if TOP1 fails to detach, it breaks one of the two DNA strands.
To test whether abnormal TOP1 activity was breaking the DNA, the researchers isolated DNA from control and diseased neurons. They visualized the DNA on a gel, where intact DNA forms bands while broken DNA spreads out into smears. The more fragmented the DNA is, the more intense the smear appears. Using a machine that quantified the intensity of smears, the researchers found that DNA from diseased neurons produced smears that were up to 3.2 times more intense than those from control neurons. They also found that neurons with more DNA fragmentation had more ID-4 signatures.
Based on these findings, the researchers concluded that abnormal TOP1 activity created frequent single-strand DNA breaks. They proposed that some of these breaks are repaired incorrectly, eventually leading to widespread DNA breaks in all 3 neurodegenerative diseases.
Overall, the researchers found that neurons from these 3 neurodegenerative diseases accumulated excessive DNA mutations despite differences in the disease symptoms and underlying causes. Their findings also provided evidence that abnormal TOP1 activity contributes to this mutation accumulation. Based on these findings, they stated that preventing TOP1 from becoming trapped on DNA, or improving the DNA repair process that removes trapped TOP1, could be a promising way to treat a wide range of neurodegenerative diseases.
The post Common DNA damage could cause neurodegenerative diseases appeared first on Sciworthy.
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