Virus World

The spread of vector-borne viruses, such as CHIKV, is a significant public health concern in the Americas, with over 120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiological techniques, we characterized the ongoing large CHIKV epidemic in Paraguay.

Preprint in medRxiv (April 17, 2023):

https://doi.org/10.1101/2023.04.16.23288635 

Two human cases of West Nile virus have been reported in New York as the virus has been detected in a record number of mosquitoes in the city, health officials said Tuesday.  Across the city's five boroughs, 1,068 mosquito pools have tested positive for the virus, according to the New York City Department of Health and Mental Hygiene. The city recorded 779 positive pools at the same time last year. The two human cases were reported in Brooklyn and Queens, the health department said in a statement. The West Nile virus is most commonly spread to people through the bite of an infected mosquito, according to the US Centers for Diseases Control and Prevention. Those cases happen during mosquito season, which starts in the summer and continues through fall, the CDC said.  "We are in the height of West Nile virus season, but there are things you can do to decrease your risk of being bitten," New York City Health Commissioner Dr. Ashwin Vasan said. Using an insect repellent and wearing long sleeves and pants, especially when outside during late and early hours, may help prevent the risk of getting bit, Vasan explained. 

There is no vaccine for the virus, so preventative measures are the most effective way to avoid infection. Symptoms of West Nile infection include fatigue, fever, headache, body aches and rash. However, 80% of infected people do not display any symptoms, according to the CDC. In rare cases, the virus can also be spread through blood transfusions, organ transplants, exposure in a lab setting or from mother to infant. Less than 1% of infected people develop a serious neuroinvasive illness, such as encephalitis (inflammation of the brain) or meningitis (inflammation of the protective membranes covering the brain and spinal cord), according to the CDC. As of August 9, a total of 54 human cases of the virus disease have been reported to the CDC this year. Last year, 2,695 human cases were reported to the agency.

CNN's Aya Elamroussi contributed to this report.

A combination of the Zika virus and Chikungunya, two mosquito-borne infections, increase stroke risk, a new study reports. University of Liverpool researchers and Brazilian collaborators have been investigating the link between neurological disease and infection with the viruses Zika and chikungunya. These viruses, which mostly circulate in the tropics, cause large outbreaks of rash and fever in places like Brazil and India. Zika is widely known to cause brain damage in babies following infection in pregnancy, but the new research shows it can also cause nervous system disease in adults. The study of 201 adults with new onset neurological disease, treated in Brazil during the 2015Zika and 2016 chikungunya epidemics, is the largest of its kind to describe the neurological features of infection for several arboviruses circulating at the same time. The new research shows that each virus can cause a range of neurological problems. Zika was especially likely to cause Guillain-Barre syndrome, in which the nerves in the arms and legs are damaged. Chikungunya was more likely to cause inflammation and swelling in the brain (encephalitis) and spinal cord (myelitis). However, stroke, which could be caused by either virus alone, was more likely to occur in patients infected with the two viruses together.

Stroke occurs when one of the arteries supplying blood to the brain becomes blocked. The risk of stroke is known to be increased after some types of viral infection, like varicella zoster virus, which causes chickenpox and shingles, and HIV. Stroke is also being recognised increasingly as a complication of COVID-19. This has important implications for the investigation and management of patients with viral infection, as well as for understanding the mechanisms of disease. In total 1410 patients were screened and 201 recruited over a two-year period at Hospital da Restauração in Recife, Brazil. Comprehensive PCR and antibody testing for viruses was carried out in Fiocruz laboratories. Of the 201 patients admitted with suspected neurological disease linked to Zika, chikungunya or both, 148 had confirmation of infection on laboratory testing, around a third of whom had infection with more than one virus. The median age of patients was 48, and just over half the patients were female. Only around 10% patients had fully recovered at discharge, with many having ongoing issues like weakness, seizures, and problems in brain function. Of the stroke patients, who were aged 67 on average, around two thirds had infection with more than one virus.

Many of the people who had a stroke had other stroke risk factors, such as high blood pressure, indicating that stroke following Zika and chikungunya viral infection may most often be seen in those who are already high risk. Dr Maria Lúcia Brito Ferreira, neurologist and head of department at Hospital da Restauração, leading the Brazilian team said: “Zika infection most often causes a syndrome of rash and fever without many long-term consequences, but these neurological complications — although rare — can require intensive care support in hospital, often result in disability, and may cause death.” ..

Original Study Published in The Lancet Neurology (October 2020):

https://doi.org/10.1016/S1474-4422(20)30232-5

Mosquitoes zapped with radiation to make them sterile are set to be released into the wild in a bid to fight outbreaks of dengue fever.  The World Health Organization has announced that from next year it will start large-scale studies of what is known as the sterile insect technique. This involves irradiating male Aedes mosquitoes, the species responsible for the spread of diseases such as dengue, Zika and chikungunya. The scientists hope that the sterile males will be released in such large numbers that they will overwhelm the native male population and then go on to mate with females. But they will produce no offspring so the insect population will reduce over time, alongside the number of cases of the disease. The technique has been used for about 50 years in the management of agricultural pests, such as the Mediterranean fruit fly, and experts are confident that it poses no risk to either human health or the environment. 

WHO has been working with organisations including the International Atomic Energy Agency (IAEA) and the Food and Agriculture Organisation on preliminary studies in countries including Bangladesh, Cuba, Brazil and Mauritius. Dengue fever has become a major health threat with 110 countries around the world suffering outbreaks this year. WHO believes that as many as five million cases may be reported by the end of 2019 - up from an average of three million in previous years. Urbanisation and climate change are expected to see the mosquito responsible for transmitting the disease spread to new areas.  Raman Velayudhan, coordinator of WHO’s department of neglected tropical diseases, said there was a desperate need for new tools to control the Aedes mosquito which lives in urban areas, bites during the day and whose eggs are able to survive for long periods. 

“It’s a unique mosquito which has silently expanded and today is present in over 130 countries,” he told a press conference, where the trial was announced. Experts insist the technique is safe - the mosquitoes are not “radioactive” and there is no genetic mutation. WHO also stresses that the technique will not harm the wider eco-system. There are more than 3,500 different types of mosquito that serve as food for animals so removing one species will have little impact. The IAEA is looking at refining the technique for malaria-carrying mosquitoes, although Dr Velayudhan said there were already control tools for this mosquito, such as bed nets and indoor residual spraying. 

The MCPDH announced that they will offer free, at-home blood testing for residents after a person tested positive for dengue. The Maricopa County Department of Public Health announced on Monday that they have identified a person who recently tested positive for the mosquito-borne viral disease known as dengue. According to the MCDPH, the person who tested positive might have been exposed by an infected mosquito in Maricopa County. "Routine mosquito surveillance performed by Maricopa County Environmental Services Department (MCESD) has detected the dengue virus in a mosquito trap in one neighborhood in the county," the MCDPH said in a news release. According to Mayo Clinic, dengue is common in tropical and subtropical areas of the world with millions of cases reported each year. It is rare in the United States, however, with an average of less than 20,000 cases per year. The World Health Organization notes that while some cases are asymptomatic, symptoms from dengue fever can range from severe flu-like symptoms to severe bleeding, organ impairment, plasma leakage and death. The MCDPH has not revealed who was infected or the severity of their infection, however.

As a result of the positive test, the department announced that Public Health teams will be visiting neighborhood residents to offer free, at-home blood testing if they are interested. Those teams will also include representatives offering information for preventing bites and mosquito breeding around their homes, the MCDPH said. MCDPH did not specify which neighborhood the department would be testing in. “While previous dengue cases in Maricopa County have been related to travel to countries where dengue commonly occurs, it is important to understand if others could have been exposed or if this is an isolated incident.” said Dr. Nick Staab, MCDPH medical epidemiologist. “This is in addition to our routine investigations of anyone suspected to have dengue or other mosquito-borne diseases.” The MCDPH said that Maricopa County will field teams of staff and volunteers to conduct the free testing for residents five years and older and provide mosquito prevention kits as well. The tests will identify if any person has been infected in the last several months even if the person is asymptomatic, the MCDPH said.

“This simple test can provide information that is valuable to our residents and, on a neighborhood level, to Public Health,” Staab said. “When we look at results of this testing and mosquito testing across the county, we can determine if there is any risk to others and what Public Health, Environmental Services, and other partners can do to prevent illness.” The department said that they will send postcards to homes in the specific neighborhood to their door, to notify them about their upcoming visit before field teams go door-to-door over the next week to offer the testing, prevention kits and information on how the test results will be shared with those tested or their legal guardians.

Scientists sent mice on scented chases and swabbed the armpits of people infected with dengue to pinpoint an odor that attracts mosquitoes. Being bit by a mosquito carrying dengue or Zika virus can make you sick. The infection can also make you even more attractive for other mosquitoes, new research finds. It’s an itchy concern for anyone infected, but also poses a major risk to communities at large: Mosquitoes that aren’t already carrying the viruses could be more drawn to sick humans, become infected, and go on to infect more humans. The spread of dengue, in particular, is a threat, with about half the world’s population at risk and hundreds of millions of cases each year. Most cases are asymptomatic, but serious cases can lead to fever and vomiting, and in some instances, organ failure or death. The study, published Thursday in Cell, identifies a specific scent emitted from both Zika- and dengue-infected mice that makes them more attractive to mosquitos than those without the viruses. It also points to a potential route to neutralize the olfactory flag. “This is a highly, highly influential study,” said Nikolaos Vasilakis, a professor of pathology at the University of Texas Medical Branch in Galveston who was not involved with the research. “I’m pretty sure it’s going to foster or spin off several new lines of experimentation to get a better understanding of what’s happening in humans.” In the experiments, performed at Tsinghua University in Beijing, mosquitos in a cage could enter a chamber with virus-infected mice or one with healthy mice. The mosquitos had no preference among the mice when the experimental group was newly infected, but on days four and six of infection, around 70% of the mosquitos flew to the infected group.  “An essential scientific question is how mosquitoes effectively orient to viremic hosts with a high frequency,” lead author Gong Cheng wrote in an email. Body temperature, carbon dioxide levels, and scent are all known factors in attracting mosquitos to a host. The researchers isolated each factor in repeated experiments to systematically eliminate temperature and carbon dioxide and identify scent as the attractant.

To determine exactly what caused the change in scent, they analyzed hundreds of potential volatile compounds emitted from the sick mice and narrowed it down to one, called acetophenone. The amount of acetophenone on the infected mice was found to be 10 times higher than on the uninfected ones. “Regarding virus-induced changes in behavior, this study is like a unicorn because of how in-depth they were able to go on all these levels,” said Megan Wise de Valdez, an associate professor of biology at Texas A&M in San Antonio, who was also not involved. She said the study’s methodology was so rigorous she plans to teach it in the classroom. Still, when it comes to results, “a mouse is a mouse is a mouse is a mouse,” said Vasilakis — meaning the stronger insights come from looking at humans. So the researchers took it a step further.  They applied acetophenone to human hands and found it had a similar effect in attracting mosquitos. And after finding that dengue patients were putting out higher levels of acetophenone than healthy people, they collected odors from the armpits of both and applied the scent extracts to filter paper. The perfumed papers were stuck to a human volunteer’s hand in the trapping chambers. Those with the odors of dengue patients attracted more mosquitos. After pinpointing the cause of the increased attraction, the researchers tested a possible solution. They’d found that when viruses like Zika or dengue invade the body, they suppress a particular antimicrobial protein on the skin that controls acetophenone. Researchers were able to reactivate that protein and stop the overproduction of acetophenone by feeding the mice isotretinoin, a vitamin A derivative often used as acne medication. After that, mosquitos fed on the treated mice less than the untreated mice. “If that holds in longitudinal studies, then there is hope that this is going to be an extremely effective tool in the arsenal that we have against infectious diseases,” said Vasilakis. The researchers will focus their next studies on both the host — by testing potential treatments to suppress acetophenone in human dengue patients — and the vector, by searching for the genetic key in mosquitos that identifies and seeks the acetophenone, and attempting to remove it. In the global effort to fight the viruses, this research lays new groundwork. But it will likely take years to decades before we have a solution as simple as a pill for patients to ward off hungry mosquitos.

Research Published in Cell (June 30, 2022):

https://www.sciencedirect.com/science/article/abs/pii/S0092867422006419 

A new genetic engineering technology could help eliminate malaria and stave off extinctions — if humanity decides to unleash it. One early summer evening in 2018, the biologist Anthony James drove from his office at the University of California, Irvine, to the headquarters of the Creative Artists Agency, a sleek glass-and-steel high-rise in Los Angeles. There, roughly 200 writers, directors and producers — many of them involved in the making of science-and-technology thrillers — were gathered for an event called Science Speed Dating, where James and other scientists would explain their work. The sessions were organized, James told me, “in hopes of getting the facts at least somewhat straight.” Attendees were assigned to different groups, so each scientist had just seven minutes to describe his or her work to one group before running to the next room and starting over. “There were a lot of stairs, so I would get really out of breath,” James recalled. “I would arrive panting.” He also felt a bit overwhelmed. There were executives in expensive suits, young men and women looking unaccountably dressy in ripped jeans and, according to James, a disconcerting number of people wearing hats. Few, if any, had a deep knowledge of genetics; one participant in particular kept referring to “the dark genome,” as though that were a thing. “I had to tell him, ‘Real geneticists don’t usually talk that way,’ ” James said.

James began his presentation with a brief overview of mosquito-borne diseases like malaria and Zika. Then he turned cautiously to talking about his own area of scientific expertise: an obscure but powerful invention known as a gene drive. James began by noting that two brown-eyed human parents can sometimes produce a blue-eyed child, though only if both parents carry a copy of the recessive gene. A gene drive, he explained, was a tool that in some species could turn such events into a near certainty. For one thing, it guaranteed that a particular gene would be inherited, even if only one parent had it. And it would automatically insert the chosen gene into both copies of the offspring’s DNA, effectively turning a recessive trait into a dominant one. That alone, James explained, “lets you change the odds, so you get blue eyes 99 percent of the time.”

What made the gene drive truly strange and remarkable, though, was that it didn’t stop with one set of offspring. Generation after generation, it would relentlessly copy and paste the gene it carried, until it was present in every descendant. “For most of the people in the room, you could tell it was the first they’d heard of this,” James recalled. “You could see their eyes getting big.” This mattered, James explained, because it allowed you to change not just a single creature but — potentially — an entire population, and quickly. A few months after the technique was discovered in 2014, James engineered two mosquitoes to carry a gene drive that was tied to a gene for red fluorescent color that would target the mosquitoes’ eyes. He then put each into a box with 30 ordinary purple-eyed mosquitoes. As the mosquitoes bred, they produced offspring: roughly 3,900 after two generations. (Mosquitoes lay a lot of eggs.) Under the normal rules of inheritance, there should have been an equal number of red-eyed and purple-eyed mosquitoes. Instead, when James opened the boxes to check on the offspring, all but 25 of the 3,900 mosquitoes had red eyes....

Takeda has laid out considerable time, effort and money on its dengue vaccine program despite Sanofi's trouble with its earlier entrant. Now, the Japanese drugmaker is touting phase 3 data showing the vaccine was 80% effective at preventing dengue.

In a study called Tides, investigators tested the Takeda vaccine, TAK-003, against placebo in more than 20,000 participants aged four to 16 in dengue-endemic countries in Latin America and Asia. Twice as many participants received the vaccine as those who received placebo. In those who received both doses, the vaccine was 80.2% effective, the team reported Wednesday. Investigators tracked 61 cases of dengue in the vaccine group versus 149 in the placebo group, according to results published in The New England Journal of Medicine. 

Importantly, efficacy varied among dengue serotypes. The vaccine was 73.7% effective against dengue serotype 1, 97.7% effective against serotype 2 and 62.6% effective against serotype 3. The investigators didn't track enough serotype 4 cases to reach an efficacy determination. The shot was 95.4% effective in preventing dengue that required hospitalization; there were five hospitalizations in the vaccine group versus 53 in the placebo group. The company has said it expects phase 3 studies to form the basis for regulatory submissions. Derek Wallace, Takeda’s dengue vaccine program chief, told FiercePharma the company is “encouraged by the data” as the results demonstrate the vaccine “has a potential to have a very big impact” on the dengue burden worldwide.

Takeda is particularly pleased about the vaccine’s performance in participants who hadn't had a prior dengue infection, Wallace said. In that group, the vaccine was 74.9% effective in preventing dengue. Pharma watchers may remember that Sanofi's dengue vaccine, the world's first, tripped up because of safety problems in those who hadn't had prior infections. The French drugmaker rolled out the shot in 2016, but in late 2017, the company said a new analysis had found it could cause more serious disease in those who’d been infected before. The disclosure triggered outrage in the Philippines, where officials had started a vaccination campaign. All told, the scandal knocked Sanofi’s vaccine off its launch trajectory and the company faced numerous questions about the vaccine's safety and its rollout in the Philippines. Dengvaxia originally had blockbuster expectations, but in 2018, its sales weren’t significant enough for Sanofi to disclose. Still, Takeda isn't backing down from the dengue vaccine challenge. The company just this week opened a €130 million plant in Germany to meet global demand for the shot once it launches. The drugmaker plans to employ up to 200 workers at the plant. 

Clinical Study published in New England Journal of Medicine (November 6, 2019):

https://doi.org/10.1056/NEJMoa1903869