Virus World

Despite its elimination in the US in 2000, measles cases are being reported across the country. As of February 22, 35 cases have been reported this year in Arizona, California, Florida, Georgia, Indiana, Louisiana, Maryland, Minnesota, Missouri, New Jersey, New York City, Ohio, Pennsylvania, Virginia, and Washington, according to the US Centers for Disease Control and Prevention (CDC). The CDC cautioned in a January alert that between December 1, 2023, and January 23, 2024, the agency was informed of 23 confirmed cases, most among children and adolescents who were eligible for vaccination but had not received the vaccine. Seven of those cases were imported by international travelers—travel-related cases present a danger to people who are unvaccinated and undervaccinated.

Tina Tan, MD, president-elect of the Infectious Diseases Society of America, said it’s important to understand how quickly measles can spread. “We live in a very mobile world where I don’t think people realize that an infectious disease can travel from one side of the world to the other in less than 24 hours,” she said in an interview with JAMA. According to the CDC, clinicians should especially watch for measles symptoms among patients who traveled abroad to countries with ongoing outbreaks. As of early February, Yemen, Azerbaijan, Kazakhstan, India, Ethiopia, and Russia had the world’s highest case numbers.

Measles Virus “Cooperates” With Itself To Cause Fatal Encephalitis Scientists discover a new mechanism for how the measles virus can cause a rare but fatal neurological disorder, subacute sclerosing panencephalitis. Researchers in Japan have uncovered the mechanism for how the measles virus can cause subacute sclerosing panencephalitis, or SSPE, a rare but fatal neurological disorder that can occur several years after a measles infection. Although the normal form of the measles virus cannot infect the nervous system, the team found that viruses that persist in the body can develop mutations in a key protein that controls how they infect cells. The mutated proteins can interact with its normal form, making it capable of infecting the brain. Their findings will be reported today (January 27) in the journal Science Advances. If you are of a certain age, you may have had measles as a child. Many born after the 1970s have never gotten it thanks to vaccines. The condition is caused by the virus of the same name, which is one of the most contagious pathogens to this day. The World Health Organization estimates that nearly nine million people worldwide were infected with measles in 2021, with the number of deaths reaching 128,000....

Research cited published in  Science Advances (Jan. 27, 2023):

https://www.science.org/doi/10.1126/sciadv.adf3731

For the past couple of years, COVID has affected the way we live, shop, and work. It spreads easily, so we have had to take measures to stop it in its tracks. Have you ever wondered about other fast spreading viruses humanity has had to deal with in the past? This This infographic from NYRequirements takes a look:

Adenovirus vectors deliver the genetic instructions for SARS-CoV-2 antigens directly into patients' cells, provoking a robust immune response. But will pre-existing immunity from common colds take them down?  Six vaccine candidates in clinical trials for COVID-19 employ viruses to deliver genetic cargo that, once inside our cells, instructs them to make SARS-CoV-2 protein. This stimulates an immune response that ideally would protect recipients from future encounters with the actual virus. Three candidates rely on weakened human adenoviruses to deliver the recipe for the spike protein of the pandemic coronavirus, while two use primate adenoviruses and one uses measles virus. Most viral vaccines are based on attenuated or inactivated viruses. An upside of using vectored vaccines is that they are easy and relatively cheap to make. The adenovirus vector, for example, can be grown up in cells and used for various vaccines. Once you make a viral vector, it is the same for all vaccines, says Florian Krammer, a vaccinologist at the Icahn School of Medicine at Mount Sinai. “It is just the genetic information in it that is different,” he explains. Once inside a cell, viral vectors hack into the same molecular system as SARS-CoV-2 and faithfully produce the spike protein in its three dimensions. This resembles a natural infection, which provokes a robust innate immune response, triggering inflammation and mustering B and T cells. But the major downside to the human adenoviruses is that they circulate widely, causing the common cold, and some people harbor antibodies that will target the vaccine, making it ineffective.

CanSino reported on its Phase II trial this summer of its COVID-19 vaccine that uses adenovirus serotype 5 (Ad5). The company noted that 266 of the 508 participants given the shot had high pre-existing immunity to the Ad5 vector, and that older participants had a significantly lower immune response to the vaccine, suggesting that the vaccine will not work so well in them. “The problem with adenovirus vectors is that different populations will have different levels of immunity, and different age groups will have different levels of immunity,” says Nikolai Petrovsky, a vaccine researcher at Flinders University in Australia. Also, with age, a person accumulates immunity to more serotypes. “Being older is associated with more chance to acquire Ad5 immunity, so those vaccines will be an issue [with elderly people],” Krammer explains. Moreover, immunity against adenoviruses lasts for many years. “A lot of people have immunity to Ad5 and that impacts on how well the vaccine works,” says Krammer. In the US, around 40 percent of people have neutralizing antibodies to Ad5. As part of her work on an HIV vaccine, Hildegund Ertl of the Wistar Institute in Philadelphia previously collected serum in Africa to gauge resistance levels to this and other serotypes. She found a high prevalence of Ad5 antibodies in sub-Saharan Africa and some West African countries—80 to 90 percent. A different group in 2012 reported that for children in northeast China, around one-quarter had moderate levels and 9 percent had high levels of Ad5 antibodies.  “I don’t think anyone has done an extensive enough study to do a world map [of seroprevalence],” notes Ertl. 

J&J’s Janssen is using a rarer adenovirus subtype, Ad26, in its COVID-19 vaccine, reporting in July that it protects macaques against SARS-CoV-2 and in September that it protects against severe clinical disease in hamsters. Ad26 neutralizing antibodies are uncommon in Europe and the US, with perhaps 10–20 percent of people harboring antibodies. They are more common elsewhere. “In sub-Saharan Africa, the rates are ranging from eighty to ninety percent,” says Ertl. Also critical is the level of antibodies in individuals, notes Dan Barouch, a vaccinologist at Beth Israel Deaconess Medical Center and Harvard Medical School. For instance, there was no neutralizing of Ad26-based HIV and Ebola vaccines in more than 80,000 people in sub-Saharan Africa, he says. “Ad26 vaccine responses do not appear to be suppressed by the baseline Ad26 antibodies found in these populations,” because the titres are low, Barouch writes in an email to The Scientist. Barouch has long experience with Ad26-based vaccines and collaborates with J&J on their COVID-19 vaccine. The Russian Sputnik V vaccine, approved despite no published data or Phase 3 trial results, starts with a shot of Ad26 vector followed by a booster with Ad5, both of which carry the gene for the spike protein of SARS-CoV-2. This circumvents a downside of viral vector vaccines, specifically, once you give the first shot, subsequent injections will be less efficacious because of antibodies against the vector. Ertl says she has no idea of the proportion of the Russian population with Ad26 or Ad5 antibodies, and there seems to be little or no published data from countries that have expressed interested in this virus, such as Venezuela and the Philippines...

Prophylactic vaccination is the most effective intervention to protect against infectious diseases. The commonly accepted paradigm is that immunization with both attenuated virus (live but with substantially reduced virulence) and inactivated (killed virus particles) vaccines induces adaptive and generally long-term and specific immunity in the form of neutralizing antibodies and/or activating pathogen-specific cellular immune responses. However, an increasing body of evidence suggests that live attenuated vaccines can also induce broader protection against unrelated pathogens likely by inducing interferon and other innate immunity mechanisms that are yet to be identified. The stimulation of innate immunity by live attenuated vaccines in general, and oral poliovirus vaccine (OPV) in particular, could provide temporary protection against coronavirus disease 2019 (COVID-19).

OPV was developed by Albert Sabin in the 1950s and consists of live attenuated polioviruses of the three serotypes. Early clinical studies showed that besides protecting against poliomyelitis, OPV reduced the number of other viruses that could be isolated from immunized children, compared with placebo recipients. Additional evidence of nonspecific effects of OPV came from the 1959 poliomyelitis outbreak in Singapore caused by type 1 poliovirus that was successfully stopped by the use of monovalent OPV that contained only type 2 poliovirus (1). Monovalent OPVs do not induce cross-neutralizing antibodies that target other virus serotypes, so the most plausible explanation was viral interference, which presumably is mediated by innate immunity.

Large-scale clinical studies of OPV for nonspecific prevention of diseases were carried out in the 1960s and 1970s. These involved more than 60,000 individuals and showed that OPV was effective against influenza virus infection, reducing morbidity 3.8-fold on average (2, 3). OPV vaccination also had a therapeutic effect on genital herpes simplex virus infections, accelerating healing. OPV not only demonstrated positive effects against viral infections but also had oncolytic properties, both by directly destroying tumor cells and by activating cellular immunity toward tumors (2). These observations were among the first examples of viral oncotherapy, which is being actively pursued.

Published in Science (June 12, 2020):

https://doi.org.10.1126/science.abc4262

New research shows the virus can have devastating effects on the immune system that persist much longer than the illness itself. Measles is far more dangerous than most people realize, new research shows. The disease itself can cause a severe and sometimes deadly illness, but two new studies published on Thursday found that even when patients recover, the virus can inflict lasting harm on their immune systems. The weakened immunity leaves a child vulnerable for several years to other dangerous infections like flu and pneumonia. The damage occurs because the virus kills cells that make antibodies, which are crucial to fighting off infections.

Scientists call the effect “immune amnesia.” During childhood, as colds, flu, stomach bugs and other illnesses come and go, the immune system forms something akin to a memory that it uses to attack those germs if they try to invade again. The measles virus erases that memory, leaving the patient prone to catching the diseases all over again. The findings make the need for measles vaccination even more urgent, because it protects children against much more than measles, the researchers said.

“When parents say no to getting a measles vaccine, you’re not just taking a risk of your kid getting measles, you’re causing them to lose this amazing resource of defenses they’ve built up over the years before measles, and that puts them at risk of catching other infections,” said Dr. Michael J. Mina of the Harvard Medical School and Brigham and Women’s Hospital, the lead author of one of the new studies, published in the journal Science. “You’ve got to watch your kid’s back for a few more years.” In fact if a person who has received vaccinations for other diseases contracts measles, it may wipe out the protection those vaccines had provided. Revaccination could help restore the child’s immunity, the researchers said.

The second study, by a different team, was published in Science Immunology. “This is wonderful science,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University, who was not involved in the research. “These are two wonderfully complementary studies that have provided a basic immunologic understanding of a phenomenon that has been recognized for a long time, mainly that measles infection causes immune suppression.” The studies arrive at a time of heightened concern about measles, as outbreaks flare up in the United States and other developed countries where vaccines had largely eradicated the disease, but where a growing number of parents have begun to refuse vaccination. Some claim religious reasons, and some mistakenly fear a link to autism, based on research that has been discredited as fraudulent.

Globally, the measles vaccine is estimated to have saved 21 million lives between 2000 and 2017. But there are still more than 7 million cases and 100,000 deaths a year, many in developing countries where people lack access to the vaccine. Most who die are children younger than five years. Vaccination involves two injections, usually given when children are one year old and then four years old. The same shots (commonly referred to as MMR) include vaccines against mumps and rubella, and a newer version also protects against chickenpox.

Findings reported in two studies published on November 1, 2019:

https://doi.org/10.1126/science.aay6485

https://doi.org/10.1126/science.aay6125

Urgent measures are needed now to stop further spread, the World Health Organization says. Health chiefs are warning that cases are still rising and "urgent measures" are needed to prevent further spread. Some 42,200 people were infected in 2023, compared to 941 during the whole of 2022. The WHO believes this is a result of fewer children being vaccinated against the disease during the Covid pandemic. In the UK, health officials said last week that an outbreak of highly contagious measles in the West Midlands could spread rapidly to other towns and cities with low vaccination rates. More than 3.4 million children under the age of 16 are unprotected and at risk of becoming ill from the disease, according to NHS England. Millions of parents and carers are being contacted and urged to make an appointment to ensure their children are fully vaccinated against measles. The measles, mumps and rubella (MMR) vaccine is given in two doses - the first around the age of one and the second when a child is about three years and four months old. The vaccine is very effective at protecting against measles, but only 85% of children starting primary school in the UK have had both jabs.

Speaking about the situation in Europe, Dr Hans Kluge, regional director at the WHO, said: "We have seen, in the region, not only a 30-fold increase in measles cases, but also nearly 21,000 hospitalisations and five measles-related deaths. This is concerning. "Vaccination is the only way to protect children from this potentially dangerous disease." Measles can be a serious illness at any age. It often starts with a high fever and a rash, which normally clears up within 10 days - but complications can include pneumonia, meningitis, blindness and seizures. Babies who are too young to have been given their first dose of vaccine, pregnant women and those who have weakened immune systems are most at risk. During pregnancy, measles can lead to stillbirth, miscarriage and a baby being born with a low birth weight. All countries in the European region are being asked to detect and respond to measles outbreaks quickly, alongside giving vaccines to more people. The WHO said measles had affected all age groups last year - young and old alike. Overall, two in five cases were in children aged 1-4, and one in five cases were in adults aged 20 and above. Between January and October 2023, 20,918 people across Europe were admitted to hospital with measles. In two countries, five measles-related deaths were also reported.

Pandemic effect

Vaccination rates for the first dose of the MMR vaccine, which protects against measles, slipped from 96% in 2019 to 93% in 2022 across Europe. Uptake of the second dose fell from 92% to 91% over the same period. That seemingly small drop in vaccination take-up means more than 1.8 million children in Europe missed a measles vaccination during those two years. "The Covid-19 pandemic significantly impacted immunisation system performance in this period, resulting in an accumulation of un-[vaccinated] and under-vaccinated children," the WHO reported. With international travel booming once again, and social-distancing measures removed, the risk of measles spreading across borders and within communities is much greater - especially within under-vaccinated populations, it said. Even countries that have achieved measles elimination status are at risk of large outbreaks, the WHO warned. It says that 95% of children need to be vaccinated with two doses against measles in all communities to prevent the spread of the highly-contagious disease.

The flare-up of one of the world’s most infectious diseases has taken hold among church congregations that have rejected vaccinations.  A measles outbreak in Zimbabwe has now killed nearly 700 children, in a rapidly accelerating and “deeply concerning” flare-up of the highly contagious disease.  Health officials told the Telegraph they were alarmed by both the speed of the spread and the high fatality rate of the outbreak, which has seen the recent death toll jump by dozens each day. The flare-up of one of the world’s most infectious diseases has taken hold among church congregations that have rejected vaccinations for religious reasons. Deaths had reached 698 by September 4, according to the nation’s health ministry, up from less than a quarter of that a fortnight earlier. Officials reported that 37 children died on September 1 alone.  The outbreak is thought to be the worst for some time in the southern African nation of 15 million. The last outbreak 11 years ago was far less severe, health sources told the Telegraph. Unicef said that in the worst affected eastern province of Manicaland, nearly one-in-10 of those getting the disease were dying. That rate is higher than in other recent African outbreaks. The UN body said it was “deeply concerned with the numbers of cases and deaths among children due to a measles outbreak in Zimbabwe”. Cases first emerged in April and the virus has since spread quickly among congregations of Zimbabwe’s Apostolic churches, who have long rejected vaccinations and modern medicine.

Faith healers and anti-vaxxers

Dr Johannes Marisa, the president of the Medical and Dental Private Practitioners of Zimbabwe Association, told The Associated Press that the government may need to force children to be vaccinated. He said: “Because of the resistance, education may not be enough so the government should also consider using coercive measures to ensure that no one is allowed to refuse vaccination for their children.” He urged the government to “consider enacting legislation that makes vaccination against killer diseases such as measles mandatory”.  Zimbabwe’s Cabinet has already invoked a law used to respond to disasters to deal with the outbreak and has launched a mass vaccination campaign, which will target two million children under five years. Nationwide, the vaccination rate was around 85 per cent in 2020, having fallen back on previous years when it at times touched 95 per cent.  The country’s Apostolic churches or sects are thought to be followed by around one-in-five of the population. Their teachings regularly include a potent mix of opposition towards Western medicine and belief in faith healing and prayer, meaning the congregations have become a stronghold of anti-vaccination sentiment.  As the outbreak has worsened and pressure has mounted, some church leaders have in recent weeks appeared to change their stance and called on followers to get their children vaccinated. The virus causes fever, coughing and a tell-tale rash, but in some cases it causes complications that can be fatal. Complications include blindness, brain swelling, severe diarrhoea and dehydration, ear infections, or severe respiratory infections such as pneumonia. It is one of the world’s most contagious diseases, with a reproduction rate as high as 18 – compared to an R rate of between 2 and 3 for the original strain of Covid.  Before mass vaccinations began in the 1960s, the disease flared up in occasional epidemics, killing an estimated 2.6m children each year. More than 140,000 people died from measles in 2018 – mostly children under the age of five years, despite the availability of a safe and effective vaccine, according to the World Health Organization. The virus is so contagious that more than 90 per cent of the population needs to be immunised to prevent outbreaks.

Scientists find relatives of rubella in bats, wild mice, and zoo animals. The virus that causes rubella, or German measles, finally has company. Scientists had never identified close relatives of the virus, leaving it as the only member of its genus, Rubivirus. But with a report in this week’s issue of Nature, rubella has gained a family. One of its two newfound relatives infects bats in Uganda; the other killed animals from three different species in a German zoo and was found in wild mice living nearby as well.  The findings strongly suggest that at some point in the past, a similar virus jumped from animals to humans, giving rise to today’s rubella virus, the researchers say. Although neither of the new viruses is known to infect humans, the fact that a related virus jumped species raises concerns that the two viruses or other, as-yet-unknown relatives could cause human outbreaks. “We would be remiss not to be concerned, given what’s going on in the world today,” says epidemiologist Tony Goldberg of the University of Wisconsin, Madison, a senior author of the study. Highly infectious, the rubella virus usually causes rashes and fever, but in pregnant women it can lead to miscarriages, stillbirth, and babies born with congenital rubella syndrome, which includes deafness and eye, heart, and brain problems. An estimated 100,000 newborns are affected by the syndrome annually, mostly in Africa, the western Pacific, and the eastern Mediterranean; in many other countries the measles, mumps, and rubella (MMR) vaccine has made it a rarity.

Many mass immunization efforts worldwide were halted this spring to prevent spread of the virus at crowded inoculation sites. The consequences have been alarming. As poor countries around the world struggle to beat back the coronavirus, they are unintentionally contributing to fresh explosions of illness and death from other diseases — ones that are readily prevented by vaccines. This spring, after the World Health Organization and UNICEF warned that the pandemic could spread swiftly when children gathered for shots, many countries suspended their inoculation programs. Even in countries that tried to keep them going, cargo flights with vaccine supplies were halted by the pandemic and health workers diverted to fight it.

“A devil’s choice.” That’s how Seth Berkley, head of GAVI, the Vaccine Alliance, describes the dilemma facing global health organizations in the past few weeks. They could either continue to support mass vaccination campaigns in poor countries and risk inadvertently helping to spread COVID-19—or recommend their suspension, inevitably triggering an upsurge of many other infectious diseases.

In the end, they chose the latter. As Science reported last week, the Global Polio Eradication Initiative on 24 March recommended suspending polio vaccination campaigns until the second half of the year. Two days later, the World Health Organization’s (WHO’s) Strategic Advisory Group of Experts on Immunization (SAGE) issued a broader call, recommending that all preventive mass vaccination campaigns for other diseases be postponed. “Any mass campaigns would go against the idea of social distancing,” says Alejandro Cravioto of the National Autonomous University of Mexico’s faculty of medicine, who chairs SAGE.

But experts say the fallout from the wrenching decision will be huge and may last long after the pandemic subsides. It comes on top of the damage COVID-19 will do to the fragile health systems in many countries. Mass vaccination campaigns against a host of diseases are already grinding to a halt in many countries. For many children, these campaigns are the only chance to get vaccines. Some 13.5 million have already missed out on vaccinations for polio, measles, human papillomavirus, yellow fever, cholera, and meningitis since the suspensions began, Berkley says. “I tell you those numbers will be much larger than what we see today.”...