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Shot To Protect Against Polio And Five Other Diseases Is Approved By Gavi

Why It Matters: Combining vaccines could offer longevity.

Oral polio vaccines, administered in droplet form, have driven down polio cases by more than 99 percent in recent decades. But because the drops contain live viruses — detectable in the excrement of children who get the vaccine — the virus can spread and cause new infections in countries with poor sanitation. The new vaccine won't have this problem.

"More children today, in 2023, are paralyzed from circulating vaccine-derived polio than wild polio," said Dr. James Campbell, a pediatric infectious disease expert at the University of Maryland School of Medicine who studies vaccine development.

He called the Gavi approval an "important step" in quelling the virus globally because it will give children in low- and middle-income countries access to a product that pediatricians in the United States and Europe have long offered.

The shot is also expected to help prevent infections because of its logistical ease. Since the polio vaccine will be wrapped into a combination product that is already being distributed to children, scientists say countries who use it will be less likely to see a resurgence of polio once the oral vaccines are scaled back.

Background: Polio has remaining strongholds in Afghanistan and Pakistan.

Polio, officially known as poliomyelitis, is a highly infectious viral disease transmitted mainly through feces in places with poor sanitation. The virus multiplies in the intestine and invades the nervous system, causing paralysis. Even a single existing case is problematic, experts say, because it could lead to a global resurgence.

The United States has long used an inactivated polio vaccine, or IPV, instead of the oral drops, and Gavi has been helping lower income countries buy it for the past 10 years. But the new six-in-one vaccine, called a hexavalent, will also protect children against hepatitis B, Haemophilus influenzae, tetanus, diphtheria and pertussis.

Adding polio protection to the existing five-component vaccine will raise its cost, but public health officials say the move is still economically advantageous. Fewer vaccine doses overall will help to decrease small expenses that add up, including syringes, serum refrigerators and appointments with health workers.

What's Next: A global rollout is on the horizon.

Countries that Gavi serves will now be able to apply for funding for the vaccine, which could become available as soon as 2024. It is administered in three doses within the first months of life — plus a subsequent booster shot before age 2 — and UNICEF has estimated that the global market for the new vaccine could reach 100 million annual doses by 2030.


What To Know About Polio Vaccines And Symptoms

New York health officials are warning about the likely spread of polio after the virus was detected in wastewater in New York City, Rockland County and Orange County. Rockland County health officials identified a case of paralytic polio in an unvaccinated adult last month.

Both are signs of undetected transmission, officials said.

Permanent paralysis from polio is rare, representing around 1 in 200 infections according to the World Health Organization, so detecting a single case suggests the presence of many more.

"Based on earlier polio outbreaks, New Yorkers should know that for every one case of paralytic polio observed, there may be hundreds of other people infected," New York State Health Commissioner Dr. Mary Bassett said last week.

"Coupled with the latest wastewater findings, the Department is treating the single case of polio as just the tip of the iceberg of much greater potential spread," she added.

The health department recommends that any New Yorkers who haven't received polio vaccines get them right away.

Here's how polio spreads and how well vaccines protect against the disease.

What is polio?

Polio is a highly infectious disease caused by the poliovirus. The disease was eradicated in the U.S. In 1979, and the country hasn't seen a case of domestically acquired wild polio since. The recent New York patient was infected with vaccine-derived polio, a strain linked to weakened, live virus from an oral polio vaccine that's no longer administered in the U.S. It marks the first U.S. Of vaccine-derived polio since 2013.

Vaccine-derived polio can arise after people take the oral polio vaccine then briefly shed the virus in a community with a low vaccination rate. The virus can then spread among unvaccinated people, and if it circulates widely enough, it can mutate to be more virulent.

"[For] public health people everywhere, like myself, this just makes us want to cry," said Lynelle Phillips, an assistant teaching professor at the University of Missouri School of Health Professions and board president of the Missouri Immunization Coalition.

"Hopefully this is just an aberrant situation and we can get it under control," she said. "But my heart breaks for that person that has flaccid paralysis from a totally preventable disease."

Around 72% of people infected with polio have no visible symptoms, according to the Centers for Disease Control and Prevention. Another 25% may develop flulike symptoms such as sore throat, fatigue, fever, nausea, headache or stomach pain, which tend to resolve after a few days.

In rare cases, the virus can invade the nervous system and cause meningitis (swelling of the brain and spinal cord membranes), paresthesia (the feeling of pins and needles in the legs), or irreversible paralysis, usually on one side of the body.

"It's a double-humped disease. It starts off with a minor illness, with coldlike symptoms, sore throat, things like that. Then the patient usually gets better for a day or so and the paralysis sets in," said Walter Orenstein, associate director of the Emory Vaccine Center.

People with paralysis often lose the ability to move an arm or leg. Between 2% and 10% of cases of paralytic polio are fatal, since the virus can destroy the nerves that control breathing.

How does polio spread?

Polio spreads primarily through contact with the feces of an infected person, though in rarer cases people can pass the virus through droplets from coughs or sneezes.

"In general, people don't have good hand hygiene and that's how it spreads from person to person," said Vincent Racaniello, a microbiology and immunology professor at Columbia University.

People with asymptomatic or mild cases are the primary drivers of transmission, he said, since they're most likely to engage in social interactions and their cases are more common overall. But anyone with polio can shed the virus and potentially be contagious.

People are more likely to be exposed at home or in high-risk congregational settings like prisons or nursing homes, Phillips said.

Racaniello said it's likely that the poliovirus has been circulating in U.S. Wastewater for some time, even if no cases have been detected.

"I think this virus has been in our sewers for many, many years," he said.

How well do polio vaccines work?

The U.S. Offers a four-dose series of an inactivated poliovirus vaccine. The CDC recommends that people receive their first dose at 2 months old, followed by single doses at 4 months and between 6 and 18 months, plus a booster dose between ages 4 and 6.

All 50 states and the District of Columbia require the vaccine for students entering kindergarten.

If you're not sure whether you received your polio shots, your state's immunization registry may have a copy of your records. The CDC also advises contacting doctors you saw during childhood or schools you attended or to find out. If no records are available, talk to your doctor about getting vaccinated or antibody tested.

The CDC recommends that people above age 4 who haven't gotten vaccinated should receive three doses instead of four. Those who are partially vaccinated should finish their vaccination course, no matter how much time has elapsed since their initial shots.

As of 2019, nearly 93% of U.S. Children had received three doses of the polio vaccine by age 2, according to the CDC. But vaccination rates in Rockland and Orange Counties are far lower: around 60%.

"We rarely see a problem except in communities that are undervaccinated," Racaniello said. "For the general population, if you're vaccinated, I don't think it's as a concern for you."

According to the CDC, 99% of children who get the recommended polio doses are protected against disease, but protection takes weeks to build up. Racaniello estimated that people have 50% to 60% protection two weeks after receiving the first dose. The second dose should increase that protection to 90%, followed by 99% after three doses, experts said.

Racaniello said the vaccine is meant to keep people from getting sick rather than prevent the virus from entering our cells. But Orenstein said vaccines may stave off some infections and help lower transmission.

Vaccinated people should be protected for life, though the New York State Health Department said Thursday that vaccinated adults who are at increased risk of exposure to polio can receive a booster dose.

"The prevailing idea has always been that vaccine immunity is lifetime," Racaniello said. "I got my polio vaccine in the 60s and I think I'm still protected."

However, Phillips said it's hard to know how strong vaccine protection remains over time.

"We couldn't really test whether it's lifelong immunity because we didn't have any polio around," she said. "Unfortunately, we have the opportunity to test that now."

Aria Bendix

The Case For India Switching From The Oral To The Inactivated Polio Vaccine

This article is a response to 'The case for the oral polio vaccine in the world's quest for eradication', July 21, 2023, by Vipin M. Vashishtha and Puneet Kumar.

In 2022, after more than a decade of remaining polio-free, the U.S., the U.K, Israel and Canada reported type 2 vaccine-derived poliovirus in environmental samples. The U.S. (Rockland County in New York) also reported one case of polio in a young adult caused by type 2 vaccine-derived poliovirus (VDPV) in July 2022.

What caused the type 2 VDPV case to emerge in the U.S.?

Vaccine coverage

Vaccine coverage with three routine doses of inactivated polio vaccine (IPV) in the U.S. Was 92% in 2021. However, vaccine coverage in Rockland County in New York, where the young adult was infected by poliovirus and developed flaccid lower limb weakness, was very low —  60.3% in August 2022, and the zip code-specific coverage was as low as 37.3% — according to an August 2022 report in the Morbidity and Mortality Weekly Report (MMWR). Most importantly, the young adult who got polio was unvaccinated.

In March 2022, a three-year-old child in Jerusalem city, Israel developed polio due to type 3 VDPV. Like the young adult in New York, the child in Jerusalem city was not vaccinated. The type 3 VDPV virus was detected in six more children who were asymptomatic. "Of these seven children, one had incomplete polio immunisation while the other six were unvaccinated," says a WHO report.

No matter the polio status of a country and which vaccine is being used, as long as wild poliovirus is present and any country continues to use the oral polio vaccine (OPV), the risk of polio emergence, including in polio-free countries, is real in a globalised village especially when vaccine coverage is low. While increasing vaccination coverage nationally and at a community level will help prevent children from getting polio disease, complete eradication from the world will become possible only when wild polioviruses are wiped out and the use of OPV is stopped.

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Type 2 poliovirus has been responsible for over 95% of VDPV cases, and since 1999, when wild poliovirus type 2 was eradicated, all polio cases caused by type 2 virus have been either due to VDPV or vaccine-associated paralytic poliomyelitis (VAPP). Since the global switch from trivalent (containing types 1, 2, and 3) to bivalent (containing types 1 and 3) OPV in 2016, no child in India has been vaccine-protected with OPV against type 2 virus. All the protection has come only from IPV, which contains types 1, 2 and 3. Yet not a single type 2 VDPV case in India has been reported since 2016. This further demonstrates why India can safely switch to exclusive-IPV immunisation at the earliest.

Since wild and VDPV cases are still reported in Pakistan and Afghanistan, the compulsion to maintain a very high polio vaccine coverage in India cannot be overemphasised. Also, India has remained polio-free since January 2011 even as wild poliovirus and VDPV cases have been reported in Pakistan and Afghanistan, thanks to high polio vaccine coverage here. Any individual travelling to India from a polio-endemic country is required to get immunised with a dose of OPV prior to travel, to reduce the risk of spreading the virus here.

The need to maintain high polio vaccine coverage in India arises even without considering the risk of imported cases, as continued use of bivalent OPV in India carries the risk of type 1 and type 3 VDPV and VAPP cases emerging. VDPV cases can emerge only when enough people are not vaccinated against polio.

Decreasing VAPP incidence

Despite wild type 2 poliovirus being non-existent and not used in oral vaccines, type 2 VDPV has caused many cases each year even after the global switch to bivalent OPV in 2016. Nearly 40% of vaccine-associated paralytic poliomyelitis (VAPP) are caused by type 2 oral polio vaccine. Almost all VDPV and VAPP cases have been reported in the last two decades are from countries that continue using oral polio vaccine. In contrast, countries that switched to inactivated polio vaccine have remained polio-free (both VDPV and VAPP), except in 2022.

Many developed countries discontinued OPV use and switched over to IPV a few decades ago. The U.S., for example, moved to IPV in a sequential manner in 1997 where both IPV and OPV vaccines were used. The rationale: "This strategy was intended to decrease the incidence of VAPP while maintaining high levels of population immunity to polioviruses to prevent poliomyelitis outbreaks should wild poliovirus be reintroduced to the U.S.," as per a January 1997 MMWR report. The risk associated with VAPP if OPV was used was estimated to be 30-40 cases during 1997-2000 (an average of 8-10 VAPP cases per year) in the U.S., while the sequential vaccination schedule was expected to reduce VAPP cases by at least half.

In addition to the risk of causing VDPV and VAPP, the OPV in India, contrary to popular notion, was found to have low seroconversion rates for types 1 and 3 — about 65% — and 96% for type 2. Low vaccine efficacy resulted in "increasing numbers of vaccine-failure polio as trivalent OPV coverage increased in India".

Seroconversion after each additional dose was at the same frequency as after the first dose, notes a 2016 paper published in Indian Pediatrics. Children in India, even after receiving half-a-dozen doses, were still at risk of getting infected by poliovirus. As many as 10 doses of OPV vaccine were required to attain a three-dose vaccine efficacy seen in other countries. Wild poliovirus transmission was interrupted in most parts of India only when an average of eight-nine OPV doses were given to a child.

Seroconversion

Compared with poliovirus-naïve children, those infected with wild poliovirus shed the least amount of virus and for a shorter duration when challenged with OPV. Children vaccinated with OPV and then challenged with OPV shed a lesser amount of virus and for a shorter duration than those given IPV and challenged with OPV.

According to virologist Dr. Jacob John, virus shedding goes on beyond 24 hours and continues for a few weeks even in children initially given OPV and then challenged. "This clearly demonstrates that mucosal immunity is not absolute in the case of OPV," he says. "Virus shedding in the stools does not automatically translate into transmission."

The ease of administering OPV is often cited as a reason for continuing the use of OPV. But due to shortage of IPV, countries were encouraged to opt for a fractional dose of IPV vaccine administered intradermally prior to the global switch. India has been using a fractional dose (0.1 ml) of IPV vaccine administered intradermally at 6 and 14 weeks since 2016. Administering an intradermal vaccine is more challenging than an intramuscular dose. Yet India has been successfully immunising millions of children each year with fractional IPV doses. Since January 2023, a third fractional dose of IPV at 9-12 months has been included in the national immunisation programme.

A trial conducted in India found that two fractional doses of IPV administered intradermally at six and 14 weeks followed by bivalent OPV at birth, and age six, 10, and 14 weeks is effective and provides over 95% seroconversion against poliovirus types 1 and 3 and over 85% seroconversion against type 2 poliovirus.

Manufacturing OPV is indeed easy and such vaccines are also cheap. Traditionally, IPV was manufactured using wild polioviruses. But IPV can be manufactured using the attenuated viruses (Sabin IPV). Bharat Biotech, which has a BSL-3 manufacturing facility, was at an early stage of manufacturing Sabin IPV vaccines in 2020 when the pandemic struck and the manufacturing facility was instead used to produce Covaxin. When Bharat Biotech is licensed to manufacture Sabin IPV, India will no longer need to rely on other countries for vaccine supply.

Ground to switch

The addition of a third fractional dose of IPV at 9-12 months in the national immunisation programme will further boost the protection against all three types of polioviruses, both wild and VDPV. Considering that India has not reported any case of wild poliovirus or VDPV since it was certified polio-free and even when other countries reported VDPV cases during the pandemic, India can plan to make a switch from OPV to IPV once the vaccine coverage reaches over 85% across the country with the revised immunisation schedule of IPV at nine months.

In an April 2020 report, WHO's Strategic Advisory Group of Experts on Immunization (SAGE) wanted countries planning to move from bivalent OPV to IPV-only immunisation schedule to exercise caution and recommended that these countries should instead take a "gradual approach, first introducing a second dose of IPV into routine immunisation". Seroconversion after two fractional doses of IPV given at six and 14 weeks in Indian children was already 95% against poliovirus type 1 and type 3 and over 85% against type 2 poliovirus. The additional fractional dose of IPV given intradermally at 9-12 months is expected to boost the seroconversion, particularly for type 2, which is currently only over 85%.

Like the U.S. In 1997, India has made ground to switch over to exclusive IPV in a sequential manner since 2016 with the introduction of two fractional doses of IPV. The addition of a third fractional dose at 9-12 months is in line with this sequential switch and the recommendation by SAGE. The move to exclusive use of IPV for polio immunisation in India can begin once we have the evidence for very high seroconversion for all three types of polioviruses.

All countries that have made a switch from OPV to IPV have only considered the last instance of wild poliovirus and VDPV cases within their borders. India too should adopt such an approach and after evidence of very high seroconversion after three fractional doses of IPV and once high vaccine coverage has been achieved using three fractional IPV doses.






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