World Polio Day 2023: Global eradication of poliovirus is in reach

Pakistan: Nationwide Polio Campaign Targets Over 40 Million Children

Islamabad — 

Pakistan launched a week-long nationwide polio vaccination campaign Monday, as the country remains one of only two around the world where the paralyzing virus still exists.

This year, so far, Pakistan has reported five cases of the highly infectious disease. The latest polio eradication campaign will target more than 44 million children across much of the country, as well as in Pakistani-administered Kashmir.

The South Asian nation came close to eradicating polio in 2021 when it reported only one case of paralysis from the virus. However, last year the country saw a spike with 20 cases on the record. The virus generally spreads through the fecal matter of a carrier that has contaminated the water supply.

Two of this year's five cases were detected in the country's most populous city Karachi in the southern province of Sindh. This came after the city recorded zero cases in the last two years.

A spokesperson of the provincial Emergency Operation Center, Syed Nofil Naqvi, told VOA both cases are children from Afghan families settled in Pakistan for years.

Naqvi blamed cross-border movement between Pakistan and Afghanistan for the disease. Afghanistan, the only other country fighting to eliminate the virus has reported six cases so far in 2023.

"The environmental samples found across Pakistan are genetically linked to Afghanistan," Naqvi said.

To counter the spread of the virus through travelers, Naqvi said, polio teams vaccinate children at bus stops and other transit points.

All of Pakistan's remaining polio cases this year came from Bannu, a town in the northern province of Khyber Pakhtunkhwa. Muhammad Zeeshan Khan, deputy coordinator for the provincial Emergency Operation Center, told VOA all three families had refused to vaccinate their children.

"We tried a lot to convince them. One child's family agreed to giving polio drops but the child had not received an [initial] injection [to build immunity]. This [refusal] is the reason that all three children succumbed to paralysis." Khan said the families worried the vaccine might harm their children.

Parents' refusal to give the oral polio vaccine to their children is one of the primary reasons polio virus still exists in Pakistan.

Polio workers and the security personnel protecting them frequently come under lethal attacks from parents and militants who see the vaccination drive as part of a foreign conspiracy to render Pakistani children impotent or to give them ingredients not permissible for Muslims to consume.

A health worker administers a polio vaccine to a child in a neighborhood of Lahore, Pakistan, Nov. 27, 2023.

Provincial officials in Khyber Pakhtunkhwa recorded more than 16,000 refusals in October. According to Khan, Peshawar, the provincial capital, recorded nearly 8000 refusals followed by Bannu, and North Waziristan where most of Pakistan's polio cases were recorded last year.

Khyber Pakhtunkhwa recorded 14 incidents of violence against polio teams this year.

To counter such misconceptions, authorities have been engaging local clerics and influencers, and running expensive TV and radio campaigns to convince parents to vaccinate their children.

Still, other parents refuse and bargain for unmet civic needs. The National Emergency Operation Center's plans for the latest campaign show several communities in Khyber Pakhtunkhwa have refused to vaccinate their children until gas, roads or teachers are provided.

"For us, the biggest concern is the child whose family has refused [to vaccinate]," said Khan.

In any campaign cycle thousands of children are also "missed" because they are not home, or the family is unwilling to allow the vaccination team inside if a male member of the household is not present.

Data shows over 13 percent of children in Quetta, Baluchistan's provincial capital, missed getting the vaccine last time. In Khyber Pakhtunkhwa, nearly 1.2 percent of children or more than 90,000 were missed as well.

However, Khan said many of the missed children get vaccinated as guests in whichever community they are temporarily present.

In Quetta too, nearly half the children who were missed at one point were eventually covered, according to data.

Still, in parts of Khyber Pakhtunkhwa and Balochistan that border Afghanistan the vaccination campaign will either be conducted later or postponed indefinitely, primarily due to security reasons.

As hundreds of thousands of polio workers and security personnel go door to door this week in areas facing a high risk of polio, Naqvi is hopeful Pakistan will get closer to eliminating the crippling disease.

"We are using a positive way of giving the message," Naqvi said. From posting signs that said "Caution! Your area has polio," he said, we now say, "we can eliminate polio."

A previous version of this story included an incorrect figure for the number of children being targeted by the campaign. Pakistan is hoping to vaccinate more than 40 million children.

Polio Could Be Eradicated Within 3 Years — What Happens Then?

Benjamin Thompson

Welcome back to the Nature Podcast, this week: what happens after polio is eradicated...

Shamini Bundell

...And the space explosion that's baffling scientists. I'm Shamini Bundell...

Benjamin Thompson

...And I'm Benjamin Thompson.

<Music>

Benjamin Thompson

Since 1988, cases of polio have fallen by more than 99%. In the late 1980s, between 3-400,000 people were being paralysed by wild polio every year — so far this year only 10 cases have been recorded, in Afghanistan and Pakistan, the only countries which still see transmission of wild polio. This is leading many observers to predict that polio could be eradicated within the next three years. And yet, the picture is more complex than the basic numbers suggest. There are two core types of vaccine which form the basis of the eradication campaign. The first — based on an inactivated version of the virus — prevents disease, but not infection or spread and is administered through a needle. This is used to great effect in places where polio is not spreading, to protect people from disease. The second, based on an attenuated or weakened version of the virus, can prevent transmission and is given orally. This vaccine, which is cheap, easy to administer, and slows the spread, has helped reduce case numbers dramatically in countries which did see active spread. However, it also presents a risk — in a very small number of cases, the weakened polio virus in the oral vaccine can mutate, regaining some ability to infect others. This has led to outbreaks of what is known as vaccine-derived polio and there were about 800 cases reported last year according to CDC data. Nonetheless, public health efforts to curb both wild and vaccine-derived polio press on — and hopes are high for eradication. But that would still not be the end of the story. This week in Nature reporter Aisling Irwin has been investigating what needs to happen after polio is eradicated and reporter Noah Baker called up Aisling to find out more.

Noah Baker

So Aisling, it does appear that the end of polio might be around the corner. Now I think the whole time I've been at Nature I've been saying that, but many people are predicting an eradication of polio within the next couple of years. But that isn't the end of the story, right? And a lot of researchers are thinking very seriously about what would need to happen next to make sure that even if polio is eradicated, that it stays eradicated.

Aisling Irwin

Yes, that's right. And you've touched on something really important, though, which is that one could argue that we should just focus everything on eradication. But if we don't have the world set up to usher in that new world where polio is eradicated, we do have the problem that it could, could come back. We're still going to need to keep the virus in a number of labs and places like that, because we still need to manufacture vaccine and that needs the virus, which means that we really have to get our containment act together. Another one, which was totally unknown when the campaign started is that there are people who are born with an incomplete immune system.And a small number of those people, the small number of types of these immunodeficiencies,if these people are given the oral vaccine, they can't throw it off, and it stays in them and it can stay in them for decades, although it's often less than that. And while it's sitting there, it's not doing nothing. It's accumulating mutations and can revert to polio. So, it is something that's a bit of a headache.

Noah Baker

It's interesting to me, people may think, hey, if it's eradicated, why do we need a vaccine? But that's precisely the reason is that there are many places in which another outbreak could happen. And I noticed that in your Feature that you've written, there is a lede at the beginning of your feature you open with a kind of a hypothetical situation in 2040, where polio has been eradicated for a decade, but there's an outbreak. Can you tell me why you open with that? Because I think that really gets to the nub of why we do need to continue studying and keeping samples of polio in labs.

Aisling Irwin

Yes, I mean, the key to this is that eradication is not extinction. And I wanted to start the feature with a scenario that would demonstrate to people that this is not just a theoretical risk, this is something that will only be averted if all the many people in the various WHO committees and the people responsible for polio in all their nations keep working on it and keep the barriers up.

Noah Baker

Yeah, there is a story here. It's a short, but very powerful one. Can you tell us that story?

Aisling Irwin

Yeah, so we have a lab somewhere in Europe, where a technician has opened a vial that had been mislabelled. And this has happened, and it had polio in it. And quite soon after becoming infected, she travels to the other side of the world to visit her family who are in a war-torn country where a lot of the health system has broken down. And so she inadvertently passes it on to family members. And because there's low immunity-levels to polio, because there's little vaccination in that country, it spreads.

Noah Baker

And the world needs to react.

Aisling Irwin

That's right. Now, this requires a number of adverse events. So hopefully, it won't happen. But it is not pulled out of the sky, I've spoken to modelers that it could happen.

Noah Baker

And I think surely people broadly listening to this as well as public health experts will still have the coronavirus pandemic very much in their minds and be aware of how quickly a public health crisis can get out of hand if it is not tackled quickly. And I can imagine a world in which there is a complacency that builds around polio because of this sense of eradication. And it is very much a message I'm getting from your Feature that we must not become complacent about something like polio.

Aisling Irwin

That's right. I mean, in a funny way, one thing the pandemic has done that's positive is that it has put surveillance right up high on the political agendas of many leaders. That's what one of my interviews was telling me. And so money has gone into new techniques that can detect polio and other vaccine-preventable diseases much more quickly. And the world is working very hard at the moment to make surveillance really good everywhere, wastewater surveillance, looking for signs of the virus. Um, so that we will be in a – we hopefully will be in a position to sound the alarm early on.

Noah Baker

So, surveillance is one thing we can do or that policymakers can do to try to prevent something like a resurgence after this hypothetical eradication. I'm aware there's quite a few hypotheticals in this conversation, but that's what we need to do, we need to think in hypotheticals — that's very much part of the point. And then we've also discussed, you know, we need to maintain vaccine production capacity, or at leastresearch to make sure that those samples are there. Is there anything else that needs to be done that your sources are telling you are the next steps that need to be done?

Aisling Irwin

In terms of vaccination, we need to find ways of making vaccines without using live virus, because then vaccine manufacturing facilities won't even need to have the virus, so we won't have that containment problem. And there is some really exciting work going on with virus-like particles and mRNA vaccines, which could be used in the future to make the injectable vaccine. You really do need live virus if you're going to make oral vaccine, but hopefully, we won't be needing that for more than another few years.

Noah Baker

So, there's a lot to think about but overall, is it fair for a listener to take away a sense of hope? Are you hopeful about the eradication of polio?

Aisling Irwin

Well, there's much bigger brains than me who say that they're hopeful, so I'll go with them. But I was quite taken with Aidan O'Leary's comment – he directs the polio eradication campaign – because he's pointed out that the polio campaign has created a huge network of assets, whether it be vehicles, networks that can penetrate almost everywhere in the world, and these are being transferred to countries and hopefully integrated into their immunisation campaigns and their basic health systems. So, the best-case scenario is that as polio is eradicated, the world becomes stronger and strengthened by what its left behind. I think we just all have to make sure that that's the way it goes.

Benjamin Thompson

That was Aisling Irwin talking to Noah Baker. For more on this, you can read Aisling's feature all about the polio endgame — we'll put a link in the show notes.

Shamini Bundell

Later in the show, unusually bright explosions in space that scientists can't explain. Right now though, it's time for the Research Highlights, with Dan Fox.

<Music>

Dan Fox

Botulinum toxin, the bacterial protein sold to smooth wrinkles under the brand names like Botox, has been found to also reduce uncontrolled shaking of the head, known as head tremor. Head tremor affects around 4 to 5% of people over 65 years old and can lead to social isolation and depression. Previous studies have suggested that it could be relieved by injections of botulinum toxin, which paralyses muscles by blocking nerve cells release of a chemical messenger. But most of these studies were either small or failed to account for the placebo effect. Now though, a group of researchers have conducted a more thorough assessment. 117 people with an average age of 65 were randomly assigned botulinum toxin or placebo, receiving two injections 12 weeks apart. 6 weeks after the second injection, nearly a third of people who had received botulinum had much less severe tremors compared with just 9% of participants in the placebo group. But 47% of participants who were treated with botulinum toxin experienced side effects such as head and neck pain, difficulty swallowing and neck stiffness. Read that research in full in the New England Journal of Medicine.

<Music>

Dan Fox

Conservation of seabirds that congregate on islands to breed may seem straightforward: protect the island colony, job done. But seabirds spend most of their lives at sea, where safeguarding them is much more challenging. Illustrating this, researchers tracked 348 seabirds of nine species that were nesting across the tropical western Indian Ocean. They recorded the birds' movements between 2008 and 2015 during the part of the year when the birds were not breeding. The team hoped that the data would reveal biodiversity hotspots, such as seasonal feeding grounds. Instead, the research showed that the birds wandered over huge areas and no obvious bird-diversity hotspots emerged. In fact, to draw a line around an area of ocean containing two-thirds of the tracked species requires encircling more than 16 million square kilometers. The authors suggest that conservation of these birds will require an ocean wide perspective. You don't have to scour the seas to find that research, it's in Current Biology.

Benjamin Thompson

Finally on the show, it's time for the Briefing Chat, where we discuss a couple of articles that have been featured in the Nature Briefing. Shamini why don't you go first this week?

Shamini Bundell

Yeah, so I have been reading a News Explainer article in Nature. And it's about problems with getting monkeys for research and this is apparently becoming an increasing issue. In particular, the problem of basically, monkey smuggling or monkey laundering, as some people are calling it.

Benjamin Thompson

Right, well, this doesn't sound too clever at all, what's the top line here?

Shamini Bundell

So, long-tailed macaques are the species that they're mainly focusing on here. And they are used for a lot of infectious-disease research and vaccine development, just sort of due to the similarities with humans, there are a good model for that. And the idea is that researchers would use captive-bred monkeys that have been bred in sterile conditions to be free from diseases and things like that. And a lot of these animals used to come from China, but in 2020 — at the start of the pandemic — China basically halted wildlife export to reduce the potential spread of disease. And since then, the availability of these monkeys for research hasn't recovered.

Benjamin Thompson

And from what it sounds like you're saying then, to fill that gap, there are people who are potentially trying to circumvent those official routes. Is that the case?

Shamini Bundell

Yeah basically, wild-captured monkeys are now being caught and sent off and potentially labelled as captive-bred, and provided for research. Potentially also, monkeys bred in conditions that don't meet the standard. So, one example given in the article is that since China's now exporting fewer monkeys, Cambodia is filling a lot of that gap. But if you look at, for example, there was a report that looked at like the jump in macaque exports from Cambodia over a few years, and they're exporting so many more monkeys now that it is not possible for those all to be coming from the credited registered breeding farms ‑ like the numbers just don't add up. And then there's other evidence in November last year, some people were arrested, including wildlife officials from Cambodia, charged with smuggling wild long-tailed macaques from Cambodia to the US for research. And again, allegedly, they were labelled as captive-bred.

Benjamin Thompson

So, potentially then, researchers are unknowingly using monkeys that aren't from a source they were expecting and this, I suppose, could have an effect on their science.

Shamini Bundell

Yeah, quite a lot of potential effects. The obvious one is that these animals aren't necessarily disease-free. And when you're studying infectious diseases and vaccines and the immune response, the starting baseline is actually really important. There was an example of a particular immunologist who got this shipment of 20 animals and was doing some preliminary chest X-rays, found one of them had latent tuberculosis, which means they couldn't use any of those animals. And if they hadn't spotted it, then you've got potentially – you've got symptoms that you might think or maybe that's a result of the drug, but it's actually not because you don't know their medical history, as it were. So yeah, a big problem. And also just the fact that there's the welfare angle in that wild monkeys are gonna be a lot more stressed and unhappy in a captive situation. But actually, that also too could change your results if you've got extremely stressed animals that might change their immune responses. And a researcher is quoted in this piece as saying, "we know through doing experiments that healthy, happy animals result in the most consistent data."

Benjamin Thompson

Are monkeys, as you say, are still required in medical research. What's being done to alleviate situations like this?

Shamini Bundell

It's going to be a difficult one to sort of crack down on, there's a lot of macaques being legally traded for research. So, to try and find the illegal ones could be tricky. There are a few sort of suggestions given here, including the research institutions should themselves be inspecting the facilities to make sure that wherever these monkeys are being bred are in line with regulations. Another idea would be genotyping research monkeys, and actually, that way, you would be able to keep track of where actually the different animals have come from. So yeah, sort of interesting issue there that I suspect not many people will be aware of. So, Ben, what have you got for us this week?

Benjamin Thompson

I've got a story that I read about in Nature, and it's based on a Nature paper, and I know that you love a mystery –

Shamini Bundell

– ohh a murder mystery in an ancient manor house... It was the butler –

Benjamin Thompson

– I mean, no, it's nothing to do with manor houses or anything like that- this is a space mystery–

Shamini Bundell

– oh, okay yeah –

Benjamin Thompson

– in fact, it's kind of a double mystery, to be honest with you. And it's about these kind of weird explosions that researchers can't quite explain.

Shamini Bundell

Weird explosions, I mean, I know there are a lot of weird signals and blips that come from space, we talk about fast radio bursts all the time, and people working out where these different signals that we see here from Earth have come from. So what kind of explosions are these? I presume this is something new?

Benjamin Thompson

Well, it's quite new actually. So the story revolves around an explosion that happens around a billion light years away from Earth. But wait, after this explosion several months after, in fact –

Shamini Bundell

– yeah –

Benjamin Thompson

– it seems to, like, flash at the same brightness more than a dozen times like as bright –

Shamini Bundell

– oh –

Benjamin Thompson

– and as powerful as the original explosion. And researchers hope that this can help explain the first one, which is something that's called luminous fast blue optical transient. Now, these are things that defy explanation. There's only about half a dozen or so that have been seen since they were first identified in 2018. And they all have kind of science names, but they have these amazing nicknames: the Cow, the Koala, the Camel, the Finch — and as I say, they are weird. The Cow was 100 times brighter than a supernova but then it dimmed really quickly, in less than a few days, which would normally take like a regular sort of star exploding supernova several weeks to occur. So, there's a lot going on here. So we've got mysterious space explosion, and the most recent one, which has been called the Tasmanian devil that's got subsequent mysterious flashes or flares that happened months after the fact.

Shamini Bundell

That's definitely adding to the mystery. I mean, first off, I love that they've named weird explosions after various animals. That's great —good work astronomers there. And so, when they saw the Tasmanian devil explosion, I guess they thought like, 'ah, yes, another one of the mystery explosions'. And then these extra flashes happened, which were just even more befuddling. I mean, I have no theories, do they have theories?

Benjamin Thompson

There are theories. And you're right, befuddling is the right word. Nobody's ever seen I don't think anything quite like this —

Shamini Bundell

— it's weird yeah —

Benjamin Thompson

— and so it's these flares then, these sort of flashes that might explain what causes these luminous fast blue optical transients. And there are several ideas that have been floating about. One is that a failed supernova, so a star collapsing into a black hole or a neutron star before it can kind of explode for real, an intermediate-mass black hole consuming a star and then finally something hitting a type of hot star called a Wolf-Rayet star. But in this case, the researchers behind this work reckon that the later flashes could support the failed supernova idea —

Shamini Bundell

— ah –

Benjamin Thompson

— and this is what they think might be happening, right? So, perhaps a star maybe 20 times the mass of the Sun was running out of fuel, and it collapsed, leaving a dense neutron star or a black hole inside the remnants of the star. And whatever's at the centre is potentially spinning around and firing out jets of energy, kind of like a lighthouse —

Shamini Bundell

— oh —

Benjamin Thompson

— so that's what we're seeing here on Earth, after the fact.

Shamini Bundell

Because I suppose they would have had a bunch of theories so far to explain what they'd seen and then these sort of periodic flashes suddenly meant they had to come up with a whole new explanation or potentially throw out some of the old ones.

Benjamin Thompson

I mean, this is obviously kind of speculation currently. But what needs to happen now is more research. But particularly, apparently, determining the mass of the object that made the flashes would help pin down what was going on. Right, so, if it was a huge mass then probably it was this intermediate black hole that was causing it. If was a bit smaller than potentially it was the failed supernova. But I think what this does show is that there are explosions very different to sort of the classic supernova that are occurring in space right now.

Shamini Bundell

But wait a sec, if they're getting these sort of mysterious signals, and they don't really know the mechanism, how can they work back to figure out the mass?

Benjamin Thompson

So in the article, they say that when you're measuring a fast varying signal, you can use how quickly that signal is varying to estimate the size of the object that's emitting it. Okay, so high speed will indicate that the object is rapidly rotating, suggesting that it is a lower mass thing. So potentially a failed supernova, for example.

Shamini Bundell

Oh I see, I suppose to the intermediate black hole. And I guess they're working on this as we speak.

Benjamin Thompson

Yeah, so researchers expect to find a lot more of these. And the Vera C. Rubin Observatory is currently under construction in Chile and will be hopefully running next year, and expects to find absolutely loads of these. And of course, this is a mystery, right? Or it remains a mystery. But potentially, it might tell us a little bit more about what happens when stars die, if that's what it is, right, because we always think of supernovas as these kind of giant explosions. But perhaps it could be that there's a lot more going on that we don't really have a full idea of just yet.

Shamini Bundell

Just like a classic murder mystery, maybe it'll be who killed the giant star slash intermediate black hole? Well, I'm sure we'll be at some point in the future reporting on the solution to this mystery once the clever space detectives have solved it. So, thank you Ben. And listeners, for more on these stories and then also where you can sign up to the Nature Briefing which is an email newsletter, which will send you more stories like these, you can check out the show notes for some links.

Benjamin Thompson

And that's all we've got time for this week. As always, you can keep in touch with us on X we're @NaturePodcast, or you could send an email to podcast@nature.Com. I'm Benjamin Thompson...

Shamini Bundell

...And I'm Shamini Bundell. See you next time.

Final Round Of Polio Vaccination Starts This Weekend

The final round of mass polio vaccinations will start today and go on until next week on Wednesday.

The exercise is in response to the outbreak of vaccine-derived polio, which has a total of 16 cases reported.

Eight of the cases have already been confirmed while the other eight suspected cases are being processes at the Kenya Medical Research Institute.

This is the worst outbreak of the vaccine-derived polio in the country.

"Polio vaccination campaign will take place in seven high-risk counties namely, Kiambu, Kajiado, Machakos, Kitui, Lamu, Tana River, Nairobi, Garissa, Mandera and Wajir," Public Health PS Mary Muthoni said.

According to the ministry, the wild polio, the virus which circulates naturally in the environment, was eliminated in Kenya in 1984.

The current outbreak is linked to vaccine-derived strains of the virus. 

On extremely rare occasions, the weakened virus in the oral vaccine, when shed through stool, can infect an unvaccinated person and regain strength, becoming just as dangerous as the original virus.

"All cases have been reported in Garissa county in Hagadera and Daadab Refugee camps,"  Dr Emmanuel Okunga, head of the division of disease surveillance and response, told the media last month.

The cases sequenced so far have been traced to Somalia, where the infected refugee children came from.

The first cases were reported in May, rising to six in July.

In response, the Ministry vaccinated 1.9 million children in Kiambu, Kajiado, Garissa and Nairobi counties between August 24  and 28.

The second round took place in October in 10 high-risk counties namely, Mandera, Wajir, Tana River, Lamu, Kitui, Machakos, Kiambu, Kajiado, Nairobi and Garissa, targeting 3,119,158 children.

Muthoni said all children under 15 years in all refugee camps in Garissa as well Fafi and Daadab Subcounties were vaccinated.

"For a long time, it has been assumed that polio largely affects children under five years of age. However, the confirmation of the virus in a seven-year-old child re-affirms that polio is a threat to all persons irrespective of age in areas where population immunity is compromised," she said.

Polio has no treatment and the disease can only be prevented through vaccination.

"Every member of the public should report suspected polio cases among children under 15 years who develop sudden onset of weakness (paralysis) of the hands or legs or both without a history of injury to the nearest health facility or chief including nyumba kumi," Muthoni said.

Last year, globally, there were nearly 800 cases of vaccine-derived polio, according to the Global Polio Eradication Initiative.

Of the 15 polio cases reported in the first quarter of 2023, 14 are from strains of the virus that mutated from the oral polio vaccine used in lower-income nations such as Kenya.

This vaccine is made with a living, weakened virus.

It is preferred because it is cheap and easy to administer. Two doses confer lifetime immunity.

WHO says the vaccine itself does not cause the disease so there is completely no risk when one is immunised with it.

However, children immunised with it can shed the live virus in their stool, which can then spread through sewage in places with poor sanitation.

If the virus stays weak, it can expose an unvaccinated person to polio and give them immunity. But if it mutates and regains virulence, someone who is not vaccinated can become sick with vaccine-derived polio after contact with the contaminated wastewater.

Initial symptoms are fever, fatigue, headache, vomiting, stiffness of the neck and pain in the limbs.

"One in 200 infections leads to irreversible paralysis (usually in the legs). Among those paralysed, five–10 per cent die when their breathing muscles become immobilised," WHO says.

Experts have also developed a safer, novel oral polio vaccine, which contains a virus that has been weakened so much that it may not even resuscitate under most circumstances.

There is also the inactivated poliovirus (injectable) vaccine used in developed countries which is extremely effective. It requires four injections. But is expensive and requires trained medical staff to carry out such campaigns.

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