Poliovirus

Emergence of vaccine-derived poliovirus in high-income settings in the absence of oral polio vaccine use

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On June 22, 2022, the UK Health Security Agency announced that vaccine-derived poliovirus type 2 (VDPV2) had been repeatedly detected in sewage in London, UK.

 Several weeks later, the New York State Department of Health reported a case of acute flaccid paralysis caused by VDPV2 in an unvaccinated individual; the first case of poliomyelitis in almost a decade in the USA.

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 A similar virus has also been detected in sewage from Jerusalem, Israel.

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These events herald an unexpected and concerning development in the fight against polio; they demonstrate that vaccine-derived polioviruses (VDPVs) can emerge in high-income settings with good sanitation where the live oral polio vaccine (OPV) is not in use. Moreover, these incidents indicate that VDPV2 transmission might be more widespread than is currently understood, risking further cases of paralytic disease among undervaccinated individuals. There is limited precedent for responding to VDPV2 transmission in these settings, and thus the impact of all interventions made by the UK and USA must be closely evaluated.

VDPVs are not a new phenomenon. It is well recognised that the live, highly attenuated poliovirus strains (Sabin 1, 2, and 3), which constitute the trivalent OPV can, on occasion, mutate sufficiently to regain virulence and cause outbreaks of poliomyelitis.

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 Although genetic reversion to generate circulating VDPVs (cVDPVs) is infrequent, it occurs more readily in settings of persistently low immunisation coverage, where extensive viral replication and person-to-person transmission are possible.

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 In recent years, there has been a marked increase in cVDPV outbreaks and resultant cases of paralytic poliomyelitis in susceptible individuals. In 2020, there were 1113 cases of poliomyelitis caused by cVDPVs across 27 countries, compared with 140 wild poliovirus type 1 cases limited to Afghanistan and Pakistan; this represented the highest total number of poliomyelitis cases in over a decade.

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 The majority of cVDPV strains have evolved from the Sabin 2 virus, and thus are designated as cVDPV2.

The rise in the number and scale of cVDPV2 outbreaks over the past 4 years is multifactorial. In 2016, there was a synchronised global withdrawal of Sabin 2-containing trivalent OPV, and a switch to bivalent OPV (Sabin 1 and 3) in countries using the OPV, designed to limit the emergence of further VDPV2 strains and eliminate the risk of vaccine-associated paralytic poliomyelitis caused by Sabin 2.

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 Although most countries eliminated Sabin-like poliovirus type 2 (SL2) transmission following the switch, some cVDPV2 transmission continued, leading to sporadic cVDPV2 outbreaks as poliovirus type 2 mucosal immunity declined.

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 Sabin monovalent OPV type 2 (mOPV2) was used to address these outbreaks, but many such campaigns were delayed and provided insufficient coverage, leading to further emergence and transmission of cVDPV2.

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 The COVID-19 pandemic compounded the issue; routine polio vaccination, surveillance, and cVDPV2 outbreak response activities were suspended for 4 months in 2020 to protect communities and health workers, enabling further spread of cVDPV2.

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 Furthermore, many of the large cVDPV2 outbreaks have emerged in countries such as Afghanistan, which are beset by conflict, with highly mobile populations and inadequate health infrastructures.

The discovery of VDPV2 in London and New York (NY, USA) should come as a wake-up call. As the full extent of VDPV2 transmission in these cities is evaluated, the factors underlying such transmission in settings with exclusive inactivated polio vaccine (IPV) use, high national vaccine coverage, and good sanitation must also be fully assessed.

A possible explanation would be that VDPV2 has emerged following shedding and subsequent circulation of SL2 by individuals who were vaccinated overseas with Sabin mOPV2, and ongoing VDPV2 transmission is occurring in undervaccinated communities. Rockland (NY, USA), the county where a case of poliovirus has been identified, has routine childhood immunisation coverage of 42%, the lowest in New York,

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 and inactivated polio vaccine vaccination coverage in London has fallen in recent years, with coverage as low as 73·6% in some boroughs.

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 However, the finding of virus in sewage over several months from a large population and with high genetic diversity of the isolated viruses implies that transmission could be widespread.

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The USA and the UK have exclusively used IPV since 2000 and 2004, respectively.

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 Although two or more doses of IPV provide excellent humoral immunity, protecting fully-vaccinated individuals from developing poliomyelitis caused by all strains of poliovirus, including VDPV2, IPV is less effective than OPV at inducing intestinal mucosal immunity, meaning IPV-vaccinated individuals might theoretically be able to shed polioviruses in their stool, facilitating transmission.

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 However, there are currently few real-world data to evidence this, and the previous success of the IPV in eliminating polio in the Netherlands and Scandinavian countries suggests that a more complex picture of poliovirus immunity and VDPV2 transmission in London and New York might emerge.

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There is evolving evidence of genetic linkages between the polioviruses detected in London and New York, and also with SL2 viruses identified in sewage from Jerusalem in June, 2022.

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 Israel boasts high vaccination coverage with both the IPV and bivalent OPV (97·6% and 88·3% for the IPV and bivalent OPV, respectively), but despite this, has also recently identified circulating vaccine-derived poliovirus type 3, with one case of poliomyelitis occurring on March 7, 2022.

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The rise in VDPV2 transmission presents a conundrum for global polio eradication. Eradication of both wild polioviruses and VDPVs is dependent on complete interruption of transmission; this is assumed to be conditional on induction of robust mucosal immunity through use of the OPV. However, VDPV interruption cannot be completed until OPV use is ceased. A potential solution to this dilemma is the development of more genetically stable oral poliovirus vaccine strains, which are less likely to evolve into VDPVs. Indeed, in 2020, a novel OPV-2 (nOPV2) vaccine was granted Emergency Use Listing status by WHO and has since been used extensively in cVDPV2 outbreak settings, with surveillance data indicating a high likelihood of success without the same risk of emergence of cVDPV2 as with standard OPV.

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Both London and New York represent very different settings to those where nOPV2 is currently being deployed, with regard to both coverage and type of polio immunity, sanitation standards, and surveillance systems. It is, therefore, conceivable that alternative strategies could be sufficient to interrupt VDPV2 transmission and prevent cases of poliomyelitis in these settings. Intensified surveillance, catch-up IPV immunisation programmes with prioritisation of unvaccinated individuals, and IPV booster programmes might all have a part to play. However, there is limited precedent for the management of VDPV2 transmission in IPV-only vaccinated populations, and although there is promise with options such as nOPV2, the dynamics of response strategies in these settings remain to be fully evaluated.

Ultimately, the isolation of VDPV2 in both the UK and USA in recent weeks mandates three urgent interventions. First, poliovirus surveillance is needed in affected countries and more broadly in countries without any surveillance to understand the extent of VDPV2 transmission worldwide and to mount timely and appropriate responses. Second, an urgent emphasis must be placed on improving vaccination coverage; while polioviruses remain in circulation, all unvaccinated and undervaccinated individuals remain at risk of this paralysing disease, and inadequately immunised populations could be contributing to ongoing transmission in communities. Third, evaluation of interventions is needed to assess the extent to which improving coverage of the unvaccinated, using catch-up doses for the undervaccinated, giving extra booster doses in wider populations, or aligning regulatory and operational preparedness for use of live oral vaccines (such as the nOPV2) are needed to control these new and unexpected outbreaks. Building momentum to adequately fund the implementation of the Polio Eradication 2022–26 strategy will be key to permanently stopping polio transmission and the risk of paralysis everywhere.

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 Failure to get this right threatens the global progress towards polio eradication.

Source: The Lancet

A Never-Before-Seen Virus Was Just Found in the Sea, and It Kills Bacteria

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When you think of a virus, you likely think of the microscopic agents that make life on land feel like a snot-infused hell. There are 219 virus species known to infect humans — rhinovirus, the poliovirus, influenza strains, and the like, which invade living cells, rapidly multiply, and make you sick.

In the ocean, there are approximately 10 million viruses in every milliliter of water. On Wednesday, scientists announced they discovered a new, never-before-seen family of viruses to add to the mix: abundant, bacteria-killing non-tailed viruses possibly related to bacterial viruses that invade the human gut. This discovery was published in Nature and made by scientists from MIT and the Albert Einstein College of Medicine.

This group of viruses — named Autolykiviridae after Autolycus, a particularly elusive character from Greek mythology — was never analyzed before because previous tests haven’t been able to detect them. While most viruses on land andin the ocean are double-stranded DNA viruses equipped with a “tail” that infects bacteria, this new group belongs to the non-tailed family, which have been historically much harder to analyze.

The Autolykivirdae are thought to play an important ecological role in the ocean as major bacteria-killers. In the study, the researchers collected samples of water off the coast of Massachusetts, and the viruses found in the samples were then incubated alongside a family of marine bacteria called Vibrionaceae. The researchers then analyzed the genomes of the viruses that successfully infected the bacteria. Of the 200 viruses collected, 18 were previously unrecognized and were non-tailed — the Autolykivirdae.

bacteria samples
Co-author Kathryn Kauffman processes seawater samples.

They then turned the new group of viruses loose on 300 strains of marine bacteria and compared how much damage the new group inflicted in contrast to tailed viruses. While the new group made up just 10 percent of the viruses observed, they did 40 percent of bacterial killing. Since these microscopic, oceanic predators were able to infect marine bacteria taken from outside of Massachusetts waters, the researchers were led to believe this group could potentially thrive throughout the ocean.

“When we found that, we were surprised,” co-author Martin Polz, Ph.D., announced in a statement released Wednesday.

Polz and his team also suspect that this new group of viruses are not ocean-specific and could be common within the human biome as well. The viruses, related to an ancient lineage that has been found previously in animals and eukaryotic organisms like algae, could have an effect on the human gut microbiome, say the researchers.

While we don’t typically think of viruses as good, some viruses can protecthumans against bacteria, instigating events like the creation of mucus, which can drive out germs. We don’t have a great sense of what exactly they do, but the gastrointestinal tracts of mammals are full of viruses — suggesting they likely play an important job in maintaining our health.

If you want to learn more about this new group of viruses, check out this explainer from study co-author Libusha Kelly, Ph.D., an assistant professor at the Albert Einstein College of Medicine.

Polio Virus in Syria and Israel May Endanger Europe.

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Two infectious disease experts warn that a new polio outbreak in Syria caused by wild-type polio virus 1 (WPV1) and asymptomatic cases in Israel might endanger Europe and other neighboring regions, according to correspondence published online November 8 in the Lancet.

“[The World Health Organization] has confirmed an outbreak of at least ten cases of polio in Syria, where vaccination coverage has dramatically decreased during the civil war,” write Professor Martin Eichner, from the Institute of Clinical Epidemiology and Applied Biometry, University of Tübingen, and Stefan Brockmann, from the Department for Infection Control, Reutlingen Regional Public Health Office, Germany. “Furthermore, [WPV1] has been isolated from sewage and faeces from asymptomatic carriers in Israel since February, 2013.

“Moreover, hundreds of thousands of people are fleeing Syria and seek refuge in neighbouring countries and Europe,” they continue. During the Hajj in Saudi Arabia last month, visitors from countries with known polio transmission were vaccinated, but Syria was not included with those countries.

“The potential risk of transmission to [the European Union (EU)] and elsewhere documents the need for strong ongoing global efforts to eradicate this disease,” CDC Director Tom Frieden, MD, MPH, told Medscape Medical News. “Polio anywhere is a threat of polio everywhere.”

The situation in the Middle East, combined with the vaccination approach used in Europe, is concerning, according to the authors. Most EU countries currently use inactivated polio vaccine (IPV) rather than oral polio vaccination (OPV). Similar to many other regions, most EU states discontinued use of OPV because of rare reports that it caused acute flaccid paralysis (AFP), even though OPV offers high protection against acquiring and transmitting the infection. Only some EU member states still permit OPV use, and none has a stockpile of it.

In contrast, the more widely used IPV is highly effective in preventing AFP and active polio disease, but is only partially effective in preventing infection with polio virus. For decades, Europe has been free of circulating polio viruses and, therefore, IPV has been sufficient.

However, IPV will only continue to be effective in preventing transmission if vaccination coverage continues to be very high, if hygienic standards are good throughout the population, and if there is low crowding. These conditions could easily be disrupted by the present situation of large numbers of refugees fleeing from Syria to Europe and other neighboring countries.

If the polio virus is reintroduced into the community, herd immunity may be insufficient to prevent sustained transmission in European regions where vaccination coverage is low, such as Bosnia and Herzegovina (87%), Ukraine (74%), and Austria (IPV coverage rate 83%).

For every 200 WPV1 infections, only 1 results in symptomatic polio. Therefore, hundreds of individuals could be infected and the virus could circulate for nearly a year before an outbreak could be identified from a single case of AFP.

“Vaccinating only Syrian refugees — as has been recommended by the European Centre for Disease Prevention and Control — must be judged as insufficient; more comprehensive measures should be taken into consideration;” the authors conclude. “Routine screening of sewage for poliovirus has not been done in most European countries, but this intensified surveillance measure should be considered for settlements with large numbers of Syrian refugees.”

Implications for the United States

In the United States, routine vaccination against polio currently uses IPV, which may create concerns similar to those now affecting Europe.

“The IPV vaccine is effective at preventing disease, but [OPV] is more effective at preventing even asymptomatic infection,” Jennifer L. Lyons, MD, from the Division of Neurological Infections, Department of Neurology, Brigham and Women’s Hospital in Boston, Massachusetts, told Medscape Medical News. “However, the OPV has been associated with a low but known risk of vaccine-related infection and, as such, is no longer routinely used.”

“It is difficult to project the effect that this scenario will have on the US, but vigilance is always good practice,” Dr. Lyons said. “Adherence to vaccination guidelines and maintenance of proper hygiene are likely the best preventive measures to take.”

Dr. Frieden told Medscape Medical News that IPV is used in Israel, as well as in the EU and the United States. “There have been no cases of indigenous polio in these regions, an especially significant fact considering that poliovirus has been found in environmental sewage samples in Israel,” Dr. Frieden said. “IPV is effective in protecting individuals against polio. The US has been free of indigenous polio since 1979.”

He also noted that the risk of importations of any infectious disease, including polio, into the United States is always a concern and highlights the importance of being vaccinated and of working to control infectious diseases wherever they are spreading.

“CDC works to minimize the risk for polio in the US through its traveler’s health and global migration program and global health program,” Dr. Frieden concluded. “We collaborate closely with international organizations and other countries to implement international and US guidance on vaccination for immigrants. In response to the polio cases in the Middle East and Horn of Africa, CDC has issued new recommendations for polio vaccine use among high-risk refugee populations and is working with international partners to implement them. Through the Global Polio Eradication Initiative, CDC works intensively with international health partners and Rotary International to eradicate polio at its source.”

Polio Injection Shrinks Woman’s Brain Tumor.

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Stephanie Lipscomb, 22, used to have a cancerous tumor the size of a lime in her brain. Monday, she learned that it’s the size of a pea, and it’s still shrinking even though she hasn’t had any chemotherapy or radiation in more than a year.

Doctors at Duke University Medical Center attribute the shrinkage to the modified polio virus they injected into her tumor in May 2012, causing it to shrink without damaging surrounding healthy brain cells.

“Throughout this whole process, I never thought I was going to die,” she said, adding that she’s a religious person. “This is just another part of my story.”

Lipscomb was finishing up her freshman year at the University of South Carolina Upstate in 2010 when headaches began to plague her as she juggled nursing classes and waitressing. At first, doctors told her she had chronic migraines and gave her caffeine pills. Later, they said she had a sinus infection and gave her antibiotics.

Nothing worked.

“I was pitiful,” she said. “By that point, my migraines were so bad, I couldn’t eat anything without throwing it back up. I couldn’t bathe myself. I couldn’t dress myself.”

So she called her grandparents, who were nearby. They took her to the emergency room, fearing meningitis.

When Lipscomb’s CT brain scans came back, they found a tumor the size of a tennis ball behind her right eye. It was a glioblastoma – the most aggressive kind of brain cancer. She was only 20 years old and told she would live five more years at best.

Read about the former Phillies catcher with brain cancer.

The typical glioblastoma patient has between 14 and 18 months to live from the time he or she is diagnosed, said Dr. Annick Desjardins, Lipscomb’s neuro-oncologist at the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center. Even after surgery, these types of tumors usually return, signaling that the patient will die in three to eight months.

So when Lipscomb’s tumor returned two years after her initial surgery to remove it, Desjardins gave her the option of enrolling in a clinical trial that would use the polio virus’s scariest feature: it’s ability to unlock a cell, enter it and kill it.

Not all brain cancer patients were eligible, Desjardins said. Lipscomb’s tumor was in the right frontal lobe, the area of the brain the controls planning and social skills. Had it been in the area that controls motor skills, vision or language, doctors wouldn’t have offered the treatment because it would have been too dangerous to tamper with those areas of the brain.

Lipscomb’s mom was on the fence about using the virus.

“She was like, ‘What? They’re gonna put polio in my daughter? What the heck are they thinking?'” Lipscomb said. “I had to break it down a little more for my mom since I’m a nursing major.”

Using polio to treat cancer has been Duke neurosurgeon Dr. Mattias Gromeier’s goal for two decades, during which he created and studied a modified version of the virus under a microscope and in monkeys.

Lipscomb became Gromeier’s first human patient, and so far, she has survived longer than she would have with standard treatment, Desjardins said.

“It has been most gratifying,” Gromeier said.

The standard polio virus uses a receptor molecule present on brain cells to “unlock” them. The virus then enters the cell and replicates until the cell dies. Gromeier’s modified version of polio is spliced with a rhinovirus, which causes the common cold. This allows it to enter healthy brain cells using the same receptor molecule – which is also found in most cancers – but the virus is unable to replicate, so it can’t hurt the cells.

However, because cancer cells have a different biochemical makeup than regular brain cells, the modified virus is able to enter them, replicate and kill them much like normal polio does. As such, the virus leaves healthy brain tissue unharmed, but it targets and destroys cancer.

Once Lipscomb and her mom were on board, doctors used a catheter to enter Lipscomb’s brain and slowly inject the virus over six and a half hours.

It took several months for the virus to start killing Lipscomb’s cancer cells, but on Monday, she learned that the tumor was only the size of a pea. Desjardins told her it could come back, but the tumor was still shrinking.

“It was probably one of the most exciting scans I have ever seen of my brain,” Lipscomb said. “I don’t think it’s going to come back.”

Of the eight patients treated with the modified polio virus, two have not responded well. Three patients have been improving over the last few months and it is too soon to tell how well three other patients will respond, Gromeier said. He does not know why the tumors didn’t shrink in two of the patients.

Another clinical trial is in the works so Gromeier can continue his research.

Since even non-glioblastoma cancer cells have the receptor polio needs to unlock it, Gromeier has been able to shrink melanoma, prostate, colorectal and pancreas cancers in a lab. Still, he has yet to do trials on animals or humans.

Source: http://abcnews.go.com