Encephalitis, Tick-Borne

Researchers have come up with a new, more accurate method for detecting in ticks the emerging Powassan virus, which can cause life-threatening neuroinvasive disease, including encephalitis and meningitis. Researchers at the New England Regional Center of Vector-Borne Diseases at the University of Massachusetts Amherst have come up with a new, more accurate method for detecting in ticks the emerging Powassan virus, which can cause life-threatening neuroinvasive disease, including encephalitis and meningitis. This robust, real-time approach reduces the incidence of false positive test results, the NEWVEC researchers found. The team describes the study in a special issue of the journal Viruses, titled "Tick-borne Viruses: Transmission and Surveillance." "Powassan has been a growing concern in New England for the past several years and false positives can confound efforts to surveil," says vector-borne disease expert Stephen Rich, professor of microbiology at UMass Amherst and principal investigator and executive director of NEWVEC. "The development of sensitive detection methods for diagnostics and surveillance is critical." Named after the town in Ontario, Canada, where it was first identified in 1958 in a 5-year-old boy who died from encephalitis, Powassan virus is a flavivirus related to West Nile and other mosquito-borne viruses. Though still rare, Powassan virus is drastically increasing in incidence in the U.S., predominantly in the Northeast and Great Lakes region. More than 10% of the record 290 U.S. cases reported in 2022 (compared to only one case per year from 2004 to 2006) resulted in death, and half of the survivors suffered long-term neurological damage. The virus is transmitted to humans primarily by Ixodes scapularis, the same blood-sucking deer ticks that transmit Lyme disease, babesiosis and other tick-borne illnesses. The team at NEWVEC -- which brings together academic communities, public health practitioners and residents and visitors across the Northeast in an effort to reduce diseases spread by ticks and mosquitoes -- developed a triplex real-time PCR test for the simultaneous and quantitative detection of the Powassan virus and Powassan virus lineage II (deer tick virus) in Ixodes scapularis, or deer ticks. (The prototype Powassan virus is found mostly inIxodes cookei and Ixodes marxi ticks that feed almost exclusively on woodchucks in their burrows and rarely bite humans or human pets.) The NEWVEC team conducted a tick survey in coastal and offshore Massachusetts, focusing on 13 sites from the highly endemic regions of tick-borne diseases in Cape Cod and Martha's Vineyard. They tested the ticks for Powassan virus, comparing their new triplex PCR method to the standard, commercially available Luminex xMap technology. "The good news is that ours works as well as the other one. So, in other words, everything that the other one could detect, we could detect," Rich explains. "The great news is that we also overcame the problem of false negatives, which is what happens when a sample is not of sufficient quality that any test would ever be able to detect the virus in it." The new triplex method accomplishes a reduction in false negatives by using a "clever" quality control. Both tests seek to detect the presence of Powassan virus RNA. "But we also had a paired search for the RNA from the tick, which is present in every tick regardless of whether it has the virus or not," Rich says. "And what that tells us is, if we can amplify tick RNA, then we have some hope of being able to detect the virus RNA. If we don't detect the tick DNA, then we have no hope of being able to detect the virus RNA. "And before we developed that method, people would be left to wonder -- if they were inquisitive -- whether a negative result meant that the virus wasn't there or that the sample wasn't testable. So, we've ruled out that latter possibility. And now we know with some assurance that when a tick tests negative, it's a true negative. It's not that the sample just isn't good enough." In the areas surveyed, "We found pockets of high incidence of this virus," Rich says. Powassan virus was detected at four of six sites in Cape Code and two of seven sites in Martha's Vineyard. Of 819 ticks collected, 33 (4.03%) tested positive for Powassan virus and 752 tested as Powassan negative, using the new triplex method. Thirty-four ticks (4.15%) failed the quality control tick RNA test. That showed that the standard Luminex method underestimated the overall prevalence of Powassan virus because those 34 ticks were found Powassan negative. And only 30 ticks tested positive using the Luminex method, demonstrating that the triplex technique has a higher sensitivity to detect the virus RNA. Infection rates reached as high as 10.43% at one site in Truro on Cape Cod, and were completely absent at seven other sites. All the ticks that tested positive for the Powassan virus also were positive for the lineage II deer tick virus. The researchers say they hope this improved triplex PCR test will be useful in transmission studies and as a tool to monitor and prevent Powassan virus infections in Massachusetts and other areas where the virus has been reported. "Powassan virus is only a threat to people through the bite of tick," Rich says. "That's why these highly accurate and sensitive tests of the tick are so valuable in assessing where and when risk of exposure is highest."

The number of infections by the tick-borne TBE virus that are not detected by health services is far higher than previously assumed. This has been shown in a new study of Swedish blood donors. The number of infections by the tick-borne TBE virus that are not detected by health services is far higher than previously assumed. This has been shown in a new study of Swedish blood donors from Uppsala University and the University Hospital in Uppsala. The results have been published in the journal Eurosurveillance, which is associated with the EU's Centre for Disease Prevention and Control. "We were very surprised that such a high proportion of the blood donors showed traces of a previous TBE virus infection. This is far more than could have been suspected based on the number of reported cases," says Bo Albinsson, doctoral student at Uppsala University, one of the first authors of the article. Tick-borne encephalitis (TBE) is a very serious disease that is increasingly common in large parts of Europe. According to statistics from the Public Health Agency of Sweden, 597 cases of the disease had been reported in Sweden by November 2023, the highest number ever registered in a single year. TBE has been a notifiable disease since 2004 under the Communicable Diseases Act and all cases must therefore be reported to the regional infection control doctor and the Public Health Agency of Sweden. However, people who only develop mild symptoms or no symptoms at all are not detected by the health services and therefore do not show up in the statistics. Until now, the relationship between the number of reported cases and the proportion of people infected was unknown. Traditional methods of investigating whether someone has previously been infected by the virus are not completely reliable as individuals who have been vaccinated against TBE can also test positive. On top of this, it is not known exactly how many people have been vaccinated, since Sweden has no national vaccination register for TBE. In the new study, the result of a Swedish collaboration, the researchers have investigated blood tests from 2,700 anonymous blood donors from nine regions in Sweden. The method they used is called TBE-SMIA (suspension multiplex immunoassay) and was developed at the Zoonosis Science Center (ZSC) at Uppsala University in collaboration with the Clinical Microbiology Department at Uppsala University Hospital. It makes it possible for the first time to effectively distinguish the antibody response after TBE virus infection from the response after TBE vaccination. This has enabled the researchers to identify how many people have had the infection. They were also able to estimate the proportion of the population in each region that is vaccinated. The results showed that the proportion of blood donors with a history of TBE virus infection varied from 1 per cent to 7 per cent between the different regions. Based on the population sizes of the regions, the researchers estimated that this corresponds to a total of more than 160,000 people aged 15-65, which is significantly higher than previous estimates. The researchers also found that the proportion of blood donors vaccinated against TBE varied between 8.7 per cent and 57 per cent in the different regions. In total, this translates to over 1.6 million Swedes (aged 15-65) in the regions investigated. "It is noteworthy that the number of confirmed TBE cases is increasing despite relatively good vaccination coverage. Further research is therefore needed, for example by carefully mapping the distribution of the virus in different tick populations. Our results provide an important background for future vaccination strategies and we believe it would be well worth considering establishing a national vaccination register for TBE," says Tove Hoffman, researcher at the ZSC and the study's other first author.

Dive Brief:Bavarian Nordic will stop developing an experimental vaccine for respiratory syncytial virus, or RSV, after the shot failed to meet one of the key goals of its Phase 3 trial.Study results disclosed on Saturday showed the vaccine was only about 43% effective at preventing severe instances of respiratory disease caused by RSV, defined as including at least 3 symptoms, in adults 60 years of age or older. The vaccine was more protective against more mild cases that included at least two symptoms, but Bavarian Nordic nonetheless intends to stop development, including an ongoing partnership with Nuance Pharma.The Danish biotechnology company believes the revenue generated from a portfolio of travel vaccines it recently acquired from Emergent BioSolutionscan help offset the loss of milestone payments it couldve received from Nuance. Still, shares lost more than a quarter of their value in Monday trading, falling to their lowest levels since May 2022.Dive Insight:The bar for a successful RSV vaccine has been raised significantly in the last few months.Since May, Pfizer and GSK have both brought RSV vaccines to market, and AstraZeneca and Sanofi have followed with a protective antibody drug.Moderna has brought a shot to regulators as well, highlighting the fierce competition Bavarian Nordic has been up against. Already, one competitor, Johnson & Johnson, has bowed out despite having a vaccine in late-stage development. The Danish biotech is now following suit.Its decision comes as the result of a Phase 3 study in more than 20,000 adults at least 60 years of age, a similar group to the one now cleared to receive Pfizer and GSKs vaccines. The shot did meet one of its study goals, proving 59% effective at preventing at least two lower respiratory tract disease symptoms. But missing its other goal was unexpected, said the companys president and CEO, Paul Chaplin, in a statement.While the outcome will impact our short-term growth expectations, we continue to have a unique commercial business and given the recent strong brand and market growth, this provides a solid foundation for profitable growth in the years to come, Chaplin said.The company sells a portfolio of vaccines already, including shots for tick-borne encephalitis, smallpox and monkeypox, and acquired other products from Emergent for typhoid fever and cholera. As a result, its not expecting the study failure to have any impact on its financial projections for 2023.The company could also add to its product portfolio shortly. A vaccine for chikungunya virus recently succeeded in a late-stage study.There arent any shots or treatments available for chikungunya virus infections. '