Announcing a new article publication for Zoonoses journal. The COVID-19 pandemic threatens public health systems worldwide, both in developed and developing countries.
The authors of this article discuss various effects of the pandemic on the status of neglected tropical diseases (NTDs). COVID-19 will be a public health issue for an extended period. COVID-19 presented several challenges and opportunities for NTD prevention and control. Significant alterations include impact of the pandemic on preventive/control measures and poverty-related plans, service failures and injury to health workers, delayed treatment of NTDs, health service funding, and worsening poverty in marginalized societies.
Additionally, the COVID-19 pandemic necessitated school and university closures on public education and research institutes. Furthermore, the COVID-19 pandemic has also provided opportunities, such as improving health literacy, changing approaches to NTD treatments, restructuring the health system and emergency responses, and enhancing science communication.
Source:
Journal reference:
Zarandi, M. B., et al. (2023) Pandemic COVID-19 and Endemic Neglected Tropical Diseases: Friends or Foes?. Zoonoses. doi.org/10.15212/ZOONOSES-2023-0024.
BOSTON - A new study finds some patients who have a persistent loss of smell after COVID-19 may benefit from an experimental treatment.
Loss of smell has been a common symptom of COVID-19, especially with earlier variants.
While most patients recover their sense of smell within a few weeks, for some, it has lasted months or even years, negatively impacting their taste, appetite, and quality of life.
However, Jefferson Health in Philadelphia researchers have found that a nerve block could help bring it back.
They took patients who had lost their ability to smell normally for at least six months post-COVID and injected both an anesthetic and a steroid into a group of nerves at the base of the neck.
They found that nearly 60% of them reported significant improvement in their symptoms one week later.
Of those, more than 80% reported even greater improvement at one month.
While the nerve block didn't work for everyone, they say at least this treatment is showing promise where many others have failed.
Mallika Marshall, MD is an Emmy-award-winning journalist and physician who has served as the HealthWatch Reporter for CBS Boston/WBZ-TV for over 20 years. A practicing physician Board Certified in both Internal Medicine and Pediatrics, Dr. Marshall serves on staff at Harvard Medical School and practices at Massachusetts General Hospital at the MGH Chelsea Urgent Care and the MGH Revere Health Center, where she is currently working on the frontlines caring for patients with COVID-19. She is also a host and contributing editor for Harvard Health Publications (HHP), the publishing division of Harvard Medical School.
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With an eighth wave of coronavirus circulating in Western Australia in recent weeks, many people are being infected with the virus again.
Unlike in years gone by when WA was in "state of emergency" mode, the rules surrounding the virus are less hard and fast and more reliant on people doing the right thing and "considering others".
So, if you find yourself feeling sick, what should you do?
That is the clear official health advice if you test positive for COVID-19.
The Health Department says you should stay home from work and events "until your symptoms have resolved" which could take up to 10 days or more, but "a minimum of five days is a good guide".
The Chief Health Officer, Dr Andy Robertson, issued a reminder last week that the virus is well and truly still around.
"Even if you're feeling better towards the end of end of it, it takes generally four or five days before you've cleared the virus and become less of an infectious risk," he said.
As well as avoiding close contact with anyone while infectious, people who test positive for COVID are also urged to inform anyone they have had close contact with recently.
Someone with the virus is most infectious during the two days before symptoms begin.
Anyone who has tested positive or who has been a close contact should avoid high-risk and healthcare settings including hospitals and care facilities for disability, mental health, and aged care for seven days.
In fact, masks are now a requirement for anyone entering a high-risk area of a hospital.
If you need to visit hospital or another health service for urgent medical care, COVID patients and close contacts are asked to inform the facility ahead of time.
Those employed in such facilities should tell their employer and check the rules for their workplace.
Select"Western AustraliaTop Stories"from either the ABC News homepage or the settings menu in the app.
Outside of those settings, taking work off for COVID-19 now generally carries the same protections for employees as any other sick leave they might or might not be entitled to.
But the Director General of WA Health, Dr David Russell-Weisz, urged anyone facing pushback from an employer to have a conversation about it.
"I think most employers are going to be pretty reasonable, and certainly not want you back at work and potentially taking out more staff with COVID," he said.
"And obviously, we all have a duty of care to elderly people, to people with chronic medical conditions, to make sure we don't put them at risk."
For some employers time-off for COVID-19 related illness may now require a medical certificate or statutory declaration as proof.
While you have COVID-19, WA Health encourages people to manage their symptoms with "rest" and "pain relief".
People can also make inquires as to whether anti-viral treatments are available or suitable for them.
And if symptoms become severe people should contact a GP or in an emergency ring Triple-0.
After recovering, most people should be okay within a few weeks' time but may feel more tired and have trouble concentrating for a period.
If you develop new symptoms 35 days after recovery, the chances are you have a new infection and should get tested again and go back to step 1.
Some people can also remain unwell and develop long COVID.
No.
The Chief Health Officer said there were no plans to reintroduce any mask mandates or restrictions in the broader community.
The requirement for people to wear masks in some hospital wards, which came into effect yesterday, was the first public health measure introduced since WA's 'state of emergency' mode ended in October 2022.
But unless cases surge dramatically and the health system becomes overwhelmed, compulsory masks wearing is off the table.
The Health Minister, Amber-Jade Sanderson, has renewed her call for anyone eligible to consider getting a COVID booster or vaccine to protect themselves and those around them.
Ms Sanderson said people should get a booster as soon as it is due, rather than necessarily waiting for the newest boosters which will cover more recent variants.
"I think early December is around when pharmacists and GPs will be able to access the new variant," she said.
"But if you're due for your booster, get your booster."
People are also urged to have some supplies ready at home in case they catch the virus and need to spend time isolating and resting.
Vancouver --News Direct-- Tonix Pharmaceuticals
Tonix Pharmaceuticals CEO Dr Seth Lederman recently joined Steve Darling from Proactive to share exciting news about their COVID vaccine, TNX-1800, selected for testing in Project Next Gen, a White House initiative managed by the Department of Health and Human Services, NIH, and NIAID.
The vaccine is based on a live virus platform, providing a unique approach to waking up the immune system. Live virus vaccines, like TNX-1800, offer more durable immunity that lasts a long time and can potentially block virus transmission, addressing limitations seen in mRNA vaccines.
This choice of TNX-1800 is a testament to Tonix's nearly decade-long dedication to vaccine development. The technology platform can also be adapted to protect against other infectious diseases, such as monkeypox, smallpox, and tuberculosis, making it a versatile solution for future pandemics.
This development highlights the significance of vaccine platforms for tackling various infectious threats. Tonix's approach promises to offer more robust, long-lasting immunity and potential transmission prevention, which could revolutionize our approach to infectious disease control. The platform's adaptability positions it as a valuable tool for future vaccine strategies.
Proactive Studio
+1 347-449-0879
na-editorial@proactiveinvestors.com
View source version on newsdirect.com: https://newsdirect.com/news/tonix-pharmaceuticals-ceo-reveals-next-generation-covid-vaccine-technology-chosen-for-key-program-673655021
At the beginning of this year, the global alarm caused by monkeypox in 2022 had practically vanished. Although the virus was still being closely monitored by public health services, and the World Health Organization (WHO) still considered it a health emergency of international importance (it did not declare the end until May), after 85,000 cases and 89 deaths worldwide, there were three causes for optimism. The first was that the number of new cases had been dropping for months, from the thousand a day reached in August to just a few dozen. The second was its low mortality rate, which was far from the initial forecasts that spoke about 10% of those infected. And finally, the certainty that the virus was inefficiently transmitted outside of the risk behaviors associated with group sexual relations, which ruled out an increase in cases among other population groups.
February was an important moment for decision-making regarding the first global outbreak of monkeypox (which was renamed mpox at the end of 2022). The WHO advocated for a global strategy to control and eliminate the disease, but the European countries had assumed just the opposite: that the virus was here to stay and that trying to get rid of it was not only going to be very difficult, but it would also be too costly and even counterproductive due to the need to apply strict public health measures, which could be met with some social opposition, as was the case at some point of the fight against Covid-19.
This information is revealed by the minutes of the meeting of the Advisory Forum of the European Centre for Disease Prevention and Control (ECDC), held at the organizations headquarters in Stockholm, Sweden, on February 21 and 22 of this year. At the meeting, the Danish representative of the Forum stated that it was important to prepare for long-term work on this issue, because the underlying drivers of the outbreak had not disappeared, and there would be a new young, unvaccinated, sexually active cohort, so there could be a new outbreak. For this reason, complete elimination might not be feasible. By continuing to vaccinate, test and advise the high-risk population, it will be possible to keep the outbreak under control, and monkeypox will be just another sexually transmitted disease. The ECDC Advisory Forum, made up of officials from the organization and the different countries public health guardians, sets the guidelines of the European public health agency.
Mike Catchpole, ECDC chief scientist, added that the cost benefit argument for elimination did not appear to be compelling. This is a reflection of the dilemma that everyone present were facing: continue doing things as before or impose surveillance measures with more or less force, with mandatoriness as a last resort to identify suspected cases, carry out diagnostic tests, comply with quarantines and vaccinate the at-risk population. Measures that should be followed until the virus is eradicated from Europe, and then repeated every time an outbreak caused by an imported case occurs, something that is quite likely considering that the pathogen continues to circulate in other continents such as America and Africa.
The Slovenian representative, on her part, pointed out that as long as monkeypox is perceived as a non-serious disease, it will be very difficult to eliminate, and enforcing these measures will not be an easy task.
As for the vaccines highly sought-after in the early stages of the epidemic the representative of France wondered if there is still interest in them, because HERA (the health emergency preparedness and response department of the EU) had just delivered the second batch of vaccination, but there was little demand for it, unlike last July when there was a shortage. She agreed about not striving for elimination but asked whether countries were confident that they could procure vaccinations, undertake testing and have a long-term strategy for the disease.
The representative of the Netherlands shared the results of the models on the evolution of the disease that were developed in that country, which discourage the adoption of more drastic measures: If the 0.7% of the population who were highly active became infected, a herd immunity threshold was achieved that actually caused the outbreak to wane, as had been observed last summer. Therefore, monkeypox appeared to be less infectious than had been assumed and the highest risk group would have already had the infection, he emphasized.
However, this does not mean that future risks should be ruled out. The outbreak, he said, highlighted the fact that this type of disease could be globally active if introduced into a certain group, and it is important to communicate this fact. The problem, he continued, is that even in a country like the Netherlands, where there is little stigma around this group (men who have relations with multiple same-sex partners), this population segment is hard to reach.
The part of the meeting dedicated to mpox was closed by Vicky Lefevre, head of the Public Health Functions Unit of the ECDC, who stated that the agency would continue to cover ways to reach out and protect this group, in addition to monitoring, testing, raising awareness and offering the vaccination to high-risk groups. As a finishing remark, she mentioned that she was glad to hear that everyone appeared to be in agreement on the elimination issue.
The final stance of the ECDC was made official in a document published two months later describing in detail the recommendations to continue dealing with the mpox outbreak, which do not introduce any major changes to the strategy developed since the summer of 2022. Notably, the word elimination is not mentioned once in the 28 pages of the text.
The meetings of the Advisory Forum are of a technical-scientific nature and all points of view are addressed with the aim of gathering, among all members, the best evidence available for decision-making. In this sense, the Forum would have failed in its functions and its mission if the difficulties involved in any initiative to eliminate a disease and the advisability or not of developing it had not been raised and discussed, states a spokesperson for the Spanish Ministry of Health.
Carlos Maluquer de Motes, professor of molecular virology at the University of Surrey (UK) and expert in smallpox viruses, explains: As a virologist, and taking into account that this virus is similar to that of [traditional] smallpox [already eradicated], I think it is always less risky to opt for a strategy of elimination instead of one of containment, which in the long run gives the pathogen time to continue adapting to humans and reach other population groups.
However, he admits that there are other relevant factors that public health experts take into account in their decision-making. The strategy that eradicated smallpox almost half a century ago included mandatory vaccination, something that is not in line with the current criteria, which are based on voluntary participation and face challenges such as anti-vaccine movements. This requires adapting the response in a way that takes into account the natural immunity of those who have already had the disease, which in this case is favored by the low mortality of mpox. In any case, allowing the virus to continue circulating requires close monitoring and considering measures to adapt the response, if necessary, he continues.
In recent months, there has been a slight increase in mpox cases, something that the WHO and those responsible for public health already feared, given the proliferation of summer festivals in which risky practices are common. According to the latest WHO report, published on October 20 with data from late September, diagnosed cases exceeded 91,000 worldwide, with 157 deaths, most of them in the American continent. In Europe, 229 cases were diagnosed in September, seven times more than in August, although still far from the 2022 figures of several hundred a day.
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Many adults erroneously believe that immunizations are only for kids. However, that is simply not true. There are several vaccines that are recommended in adulthood, some which require more than one.
Many vaccines start in infancy and occur at regular intervals for the first 5 years of life. After childhood, several other immunizations are also recommended. With that being said, vaccine maintenance should be a major component of the yearly physical.
The COVID-19 pandemic should have been an excellent lesson in what can happen when there is widespread infection in our community. It is a known fact that vaccines help prevent disease. Vaccines should be a normal part of any annual wellness exam.
Fall is a great time to review recommended adult vaccines since most providers are discussing the importance of the yearly flu shot anyway. Vaccines help to prevent certain illnesses. They work by introducing your body to an antigen, which pretends to be an illness. Your bodys immune system reacts, and this response will help your body fight certain disease-causing pathogens in the future. So, what are the recommended vaccines for adults?
COVID-19: The COVID-19 virus is constantly changing. If you have been up to date with recommendations thus far, you should be on your 5th COVID-19 vaccine. Per the CDC, vaccination remains the best protection against COVID-19 related hospitalizations and deaths.
HPV: HPV is the human papillomavirus which causes cervical, throat, and anal cancer. The HPV vaccine is recommended as a 2-dose series from ages 9-14 and a 3-dose series from ages 15-45 if you were previously unvaccinated. Unfortunately, only 24.7% of Black people are vaccinated against HPV.
Influenza: The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccines for everyone 6 months and older. It is estimated that from 2019-2020, there were approximately 25,000 deaths and 390,000 hospitalizations related to influenza illnesses.
Mpox (formerly known as monkeypox): Mpox is caused by a virus that is like the virus that causes smallpox. The CDC recommends vaccination against Mpox for certain populations only. For more information, go to CDC.gov.
Pneumococcal: Pneumococcal infections are caused by streptococcus bacteria and can range from ear and sinus infections to serious infections in the blood. The two distinct types of vaccines available protect against many of the pneumococcal bacteria. Pneumococcal vaccination is recommended for all children younger than 5 years old, people 5 through 64 years old who are at increased risk for pneumococcal disease, and adults 65 years and older.
RSV: Recently the FDA approvedthe first of two vaccines for preventing RSV lower respiratory tract disease for adults at least 60 years old. This vaccine is recommended for individuals who are at increased risk. The decision to vaccinate should be discussed with your provider.
Shingrix (Shingles): Adults at least 50 years old should receive 2 doses of Shingrix, separated 2-6 months apart. Adults 19 years old or older with a weakened immune system should also receive 2 doses of Shingrix. Post-herpetic pain (PHN) is a complication of shingles, and the shingles vaccine is the only preventable treatment. Shingrix is more than 90% effective in preventing shingles and PHN.
Tdap: The Tdap vaccine protects against diphtheria, tetanus, and pertussis (whooping cough). Adults should receive the vaccine every 10 years. The vaccine is also important if adults will be around babies.
The COVID-19 pandemic should have been an excellent lesson in what can happen when there is widespread infection in our community. It is a known fact that vaccines help prevent disease. Vaccines should be a normal part of any annual wellness exam. We ALL have a responsibility to maintain the health and wellness of our community. Please do your part and make sure you are up to date on your immunizations!
Denise Hooks-Anderson, MD, FAAFP can be reached atyourhealthmatters@stlamerican.com.
With Thanksgiving less than a week away, we want to get you the latest COVID-19 data, starting with an update on vaccinations in Minnesota.
As of Nov. 13, roughly 720,000 doses of the recently available updated COVID-19 vaccine have been administered in Minnesota, accounting for just over 13 percent of the population.
In other vaccine news, a recent study from the State Health Access Data Assistance Center sheds new light on Minnesotas initial efforts to vaccinate its population against COVID-19, through 2022.
Notably, disparities existed across age, race and ethnicity in both the overall vaccination rates of population subgroups and how quickly they reached a threshold of 50 percent fully vaccinated.
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Due to public health policy prioritizing vaccination for older populations, Minnesotans over the age of 65 had higher rates of vaccination by the end of 2022 (98 percent) compared to younger populations in the state.
And they reached a 50 percent threshold of vaccination in only three months; it took younger adults eight months to reach that halfway threshold.
Clear disparities existed when looking at vaccine data by race and ethnicity. Because Minnesotas white population skews older, prioritizing older populations meant that white Minnesotans reached 50 percent fully vaccinated in six months, earlier than other racial and ethnic groups except Asian and Native Hawaiian or Pacific Islander Minnesotans, who also reached the 50 percent threshold in six months.
It took Black and Latino Minnesotans twice as long to reach 50 percent fully vaccinated, and Minnesotas American Indian and Alaska Native population took 15 months to reach that threshold.
Among young adults, Minnesotas American Indian population had not achieved the 50 percent threshold by the end of 2022, taking more than 24 months to reach that mark.
Asian young adults in Minnesota were fully vaccinated the fastest with half vaccinated after only five months. Black, white and Latino young adults took nine, 10 and 11 months, respectively.
A new Kaiser Family Foundation survey found that nationally half of all adults will likely get the updated COVID-19 vaccine, but the survey also reveals racial disparities when it comes to those who plan on getting vaccinated in this case, however, the disparities are reversed, with fewer white Americans indicating they will pursue getting vaccinated than either Black or Latino Americans.
Majorities of Black adults, 59 percent, and Hispanic or Latino adults, 60 percent, have been vaccinated or plan to be.
Less than half of white adults, 42 percent, indicated they have been vaccinated or plan to be. Just twenty percent of white Republican adults plan to get the vaccine.
If youre looking to get vaccinated, use this finder to locate services near you.
The latest data on the three primary respiratory viruses COVID-19, influenza and RSV (respiratory syncytial virus) in Twin Cities Metro shows that all three continue to track well below the levels seen at this time last year, at least in terms of hospitalizations.
Looking at flu in other recent years, however, shows just how much earlier last years flu season was in comparison. So, while flu is well below where it was last year, its ramping up earlier than the last pre-COVID fall flu season (2019-2020). And, just because it isnt as high as this time last year, doesnt mean it will necessarily be a milder flu season.
This year's flu season is off to slower start than last year, but is taking off earlier than the 2019-2020 season. MMWR Week indicates the week number starting from the first of the calendar and equates roughly to early October.
Focusing on COVID-19, preliminary data through Nov. 7 shows hospitalizations ticking up again, following a drop in the prior week.
(This graph uses a Department of Health dataset that is statewide and has slightly more recent data available than in the Twin Cities three-viruses graph above.)
Since May, COVID deaths have stayed below the weekly averages of last year except for a brief stint in mid-October, which was after several months of increasing hospitalizations. COVID-19-related deaths are unfortunately still occurring, but the numbers remain far below what we saw in 2020 and 2021.
For most of the year, there have been fewer COVID deaths than in 2022, and deaths are well below 2020 and 2021 rates.
David Montgomery
The latest statewide wastewater data shows varying increases in COVID-19 levels throughout Minnesota. COVID-19 levels increased roughly 15 percent statewide when comparing the most recent week, Nov. 8, to one week earlier.
This statewide increase reflects increases in six of the seven regions in the University of Minnesotas Wastewater Surveillance Study, from an increase of roughly four percent in the Twin Cities Metro to 46 percent in the studys South Central region.
This weekly increase statewide corresponds to a monthly increase of 23 percent, as of Nov. 8.
The studys North West region was the only one to see a weekly decline.
Even with these recent increases in COVID wastewater levels, the levels remain below where they were last spring.
As a final reminder for those preparing for the upcoming holidays, in addition to taking advantage of flu and COVID-19 vaccines, as well as RSV vaccines for infants and those age 60 or older, both the state of Minnesota and the federal government are still offering free at home COVID-19 tests.
Researchers at the University of Wisconsin School of Medicine and Public Health are exploring the ideal vaccine booster strategy for immunosuppressed patients to protect those at higher risk of severe illness and complications from COVID-19 infection.
The goal of the clinical trial titled Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations, or ARMOR, is to determine whether a recombinant booster COVID-19 vaccine dose will improve sustained immunity against the virus that causes COVID-19 in people who live with inflammatory bowel disease, also called IBD, or solid organ transplant recipients and whose medical treatments involve staying on immunosuppressive drugs.
Jessie Geraci-Perez 608-220-1514 jgeraci-perez@uwhealth.org
Participants who enroll in this trial will receive the Novavax COVID-19 vaccine, which is a recombinant vaccine and differs from the Pfizer or Moderna drugs in that it directs the immune system to recognize specific pieces of the virus.
Solid organ transplant recipients take medications to suppress the immune system in order to prevent acute organ rejection. Similarly, patients with IBD are often prescribed immunosuppressant drugs to treat and manage their conditions.
Studies have shown that those who receive immunosuppressive medications, like corticosteroids, are at a higher risk for severe COVID-19 if they are infected, according to Freddy Caldera, DO, MS, associate professor of medicine at the UW School of Medicine and Public Health and gastroenterologist, UW Health.
The COVID-19 virus is here to stay, he said. As we learn more about COVID-19, our research must also evolve to protect patients who are more vulnerable to getting the disease and experiencing long-term complications.
A recent report from the Centers for Disease Control and Prevention indicates that one in five Americans infected with COVID-19 endure long-term complications including blood clots, neurological issues and kidney issues. The significant health risks faced by immunosuppressed patients demands further research to develop more effective vaccine strategies, according to Caldera.
There is a breadth of research on what happens immediately after infection however, we are still learning about the repercussions of getting COVID-19 and post-COVID complications, he said. As immunosuppressed populations return to more daily living, we must examine the best vaccine strategy to protect them from COVID-19, so they wont have to trade feeling well with protection from this virus.
The Novavax COVID-19 vaccine is one of the three that are recommended for the general population. This vaccine was updated in fall 2023 to include the spike protein from the Omicron variant lineage XBB. Researchers hypothesize that this type of vaccine, a recombinant vaccine, may prompt a more robust immune response than messenger RNA (mRNA) vaccines, like the Pfizer vaccine, according to Caldera.
With each new vaccine that is developed, we have the potential to deliver greater protection, he said. If we discover recombinant vaccines can induce a robust immune response protection for an entire respiratory virus season with a single dose, this would make them a better alternative to mRNA vaccines.
The trial takes place at University Hospital in Madison. Participants will receive the Novavax vaccine and have their blood drawn three times, once prior to vaccination, once 30 days after vaccination and once six months after vaccination. Researchers will assess immune system response after vaccination by evaluating levels of antibodies and T-cells. The cost of the vaccination is covered by the trial.
The study is run by the UW Clinical Trials Institute and funded by Novavax.
If you are interested in participating in the study and have IBD, email gihcro@medicine.wisc.edu or call (608) 262-5405. If you have had a solid organ transplant, please email yli2@clinicaltrials.wisc.edu or call (608) 263-3439.
This article has been reviewed according to ScienceX's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
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Small molecules called immunomodulators can help create more effective vaccines and stronger immunotherapies to treat cancer.
But finding the molecules that instigate the right immune response is difficult the number of drug-like small molecules has been estimated to be 1060, much higher than the number of stars in the visible universe.
In a potential first for the field of vaccine design, machine learning guided the discovery of new immune pathway-enhancing molecules and found one particular small molecule that could outperform the best immunomodulators on the market. The results are published in the journal Chemical Science.
"We used artificial intelligence methods to guide a search of a huge chemical space," said Prof. Aaron Esser-Kahn, co-author of the paper who led the experiments. "In doing so, we found molecules with record-level performance that no human would have suggested we try. We're excited to share the blueprint for this process."
"Machine learning is used heavily in drug design, but it doesn't appear to have been previously used in this manner for immunomodulator discovery," said Prof. Andrew Ferguson, who led the machine learning. "It's a nice example of transferring tools from one field to another."
Immunomodulators work by changing the signaling activity of innate immune pathways within the body. In particular, the NF-B pathway plays a role in inflammation and immune activation, while the IRF pathway is essential in antiviral response.
Earlier this year, the PME team conducted a high-throughput screen that looked at 40,000 combinations of molecules to see if any affected these pathways. They then tested the top candidates, finding that when those molecules were added to adjuvantsingredients that help boost the immune response in vaccinesthe molecules increased antibody response and reduced inflammation.
To find more candidates, the team used these results combined with a library of nearly 140,000 commercially available small molecules to guide an iterative computational and experimental process.
Graduate student Yifeng (Oliver) Tang used a machine learning technique called active learning, which blends both exploration and exploitation to efficiently navigate the experimental screening through molecular space. This approach learns from the data previously collected and finds potential high-performing molecules to be tested experimentally while also pointing out areas that have been under-explored and may contain some valuable candidates.
The process was iterative; the model pointed out potential good candidates or areas in which it needed more information, and the team conducted a high-throughput analysis of those molecules and then fed the data back into the active learning algorithm.
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After four cycles and ultimately sampling only about 2% of the librarythe team found high-performing small molecules that had never been found before. These top-performing candidates improved NF-B activity 110%, elevated IRF activity by 83%, and suppressed NF-B activity by 128%.
One molecule induced a three-fold enhancement of IFN- production when delivered with what's called a STING (stimulator of interferon genes) agonist. STING agonists promote stronger immune responses within tumors and are a promising treatment for cancer.
"The challenge with STING has been that you can't get enough immune activity in the tumor, or you have off-target activity," Esser-Kahn said. "The molecule we found outperformed the best published molecules by 20 percent."
They also found several "generalists"immunomodulators capable of modifying pathways when co-delivered with agonists, chemicals that activate cellular receptors to produce a biological response. These small molecules could ultimately be used in vaccines more broadly.
"These generalists could be good across all vaccines and therefore could be easier to bring to market," Ferguson said. "That's quite exciting, that one molecule could play a multifaceted role."
To better understand the molecules found by machine learning, the team also identified common chemical features of the molecules that promoted desirable behaviors. "That allows us to focus on molecules that have these characteristics, or rationally engineer new molecules with these chemical groups," Ferguson said.
The team expects to continue this process to search for more molecules and hope others in the field will share datasets to make the search even more fruitful. They hope to screen molecules for more specific immune activity, like activating certain T-cells, or find a combination of molecules that gives them better control of the immune response.
"Ultimately, we want to find molecules that can treat disease," Esser-Kahn said.
A team from the Pritzker School of Molecular Engineering (PME) at The University of Chicago tackled the problem by using machine learning to guide high-throughput experimental screening of this vast search space.
More information: Yifeng Tang et al, Data-driven discovery of innate immunomodulators via machine learning-guided high throughput screening, Chemical Science (2023). DOI: 10.1039/D3SC03613H
Journal information: Chemical Science
On November 14, the U.K. governmentannouncedthat theJoint Committee on Vaccination and Immunisation (JCVI) had recommended a vaccine against chickenpox (varicella) should be added to routine childhood immunisation programme. The vaccine is to be offered to all children in two doses, at 12 and 18 months of age. A final decision to introduce the vaccine has not been taken yet.
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JCVIs recommendation comes nearly three decades after theU.S. introduced it in 1996, and a body of evidence emphasising the benefits of varicella vaccination. Whilechickenpox in children is most often relatively mild, some can develop complications, including bacterial infections, and in rare cases can cause encephalitis, lung inflammation, and even stroke; it can also rarely cause deaths.
Even when thedisease clears, the virus stays dormant in the body and can get reactivated to cause herpes zoster (shingles), especially in adults.Exposure to the virus through children with chickenpox was expected to boost the immunity in adults and thus reduce the risk of shingles.It was theorised that vaccination of children will lead to loss of natural immunity boosting in adults, thus leading to significant increase in shingles cases. This was one of the reasons why routine administration of the vaccine in children did not begin in the U.K. earlier.
Unlike in children, chickenpox can be severe in adults. Thesecond reasonfor the U.K. not introducing varicella vaccination earlier was due to the worry that unvaccinated children will become more susceptible to getting chickenpox as adults, leading to severe infection or a secondary complication. Ironically, diseases like measles and rubella are more severe in adults than in children. Yet, children are routinely vaccinated leaving unvaccinated children at great risk of severe infection as adults.
Evidence did not support the assumption of increased shingles in adults in countries that have introduced chickenpox vaccination. While a2019 papershowed that varicella vaccination did not increase shingles incidence in adults, another studypublished in 2020found that 10-20 years after adults were exposed to infected children, the protective effect against shingles was just 27%. A2022 paperbased on 25 years of data (1995-2019) from the U.S. showed a sharp drop in the incidenceof chickenpox and shingles in children.In adults, shingles cases did not increase as feared. Rather, the rate of shingles in adults is expected to decline as vaccinated children become old, the study says. Unpublished results from a modelling study by the University of Cambridge found that the duration of protection from shingles was not 20 years as assumed but likely to be around three years, JCVIsaid on November 14.
Since its introduction in the U.S., the vaccinehas preventedover 91 million chickenpox cases, 2,38,000 hospitalisations, and almost 2,000 deaths. Thereturn on investmentwith net societal savings has been over $23 billion.
The evidence in favour of the chickenpox vaccine has been amply clear for a while. Once again, JCVI seems to have followed an ideology of infection being beneficial for children and at population level, Dr. Deepti Gurdasani, a clinical epidemiologist at the Queen Mary University of London toldThe Hinduby email. The thinking behind not recommending the vaccine prior to now was that this may lead to an increase in shingles incidence because of lack of boosting of the population by infected children. This has not come to pass. In fact, vaccination has been associated with a lower chance of reactivation and shingles compared to infection so far.
As per an unpublished study by the University of Bristol, complications from severe varicella were common, costly and placed a burden on health services. Uncomplicated varicella can also cause hospitalisation in very young children. The JCVI statement admits that thetrue extent of hospitalisation due to varicella was underestimated. The reason: hospitalisations were frequently due to secondary complicationsarising from infection and also childhood stroke, which were not always recorded.
There are several hundreds of thousands of cases of varicella each year in the U.K., most happening in under five-year-olds. While death is rare, hospitalisations do occur, with up to 4,000 admissions per year and 6.8 million in hospitalisation costs, and much greater costs associated with children being ill, Dr. Gurdasani says. On an economic level, chickenpox vaccination is a no-brainer. This has been clear for a really long time, as have the health benefits, which really begs the question why the JCVI has been so behind on this, and what the costs of these delays in introducing vaccination have been on both health and economy.It is unfortunate that decisions are often made on flawed thinking rather than evidence.
India is yet to include varicella vaccine in the universal immunisation programme. As per the NFHS-5 data for childhood vaccination, the coverage for severe diseases such as diphtheria and pertussis has only reached 76.6%. Expanding this program remains an immediate priority, says Dr. Rajeev Jayadevan, Member, Public Health Advisory Panel, Kerala State IMA. The actual disease burden of chickenpox and shingles, and hospitalisation costs in India are not known. As a result, the cost-benefit analysis of varicella vaccination has not been done. Published studies from Asia estimate 5 cases of shingles per 1,000 person-years, the risk increasing to 7.4-13.8 per 1,000 person-years in people over 50 years, Dr. Jayadevan says. Experts at the Indian Academy of Pediatrics believe the risk of shingles may be lower.
