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Cholera is making a comeback — and the world doesn’t have enough vaccines

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Thursday, May 2, 2024

A nurse administers a dosage of the cholera vaccine during the launch of the campaign to immunize people in affected areas, at the Kuwadzana Polyclinic in Harare on January 29, 2024. | Jekesai Njikizana/AFP via Getty Images “A billion people at risk”: How worldwide cholera outbreaks are threatening lives. Amid a global resurgence of cholera, the world is fighting with one hand tied behind its back. The global stockpile of the oral cholera vaccine — a supply whose needs are difficult to predict and fill anyway — has dwindled to nearly nothing after the Indian drug manufacturer that produced about 15 percent of the world’s supply stopped making the vaccine last year. While other companies are setting up new production capacity, the stockpile is now effectively nonexistent. Demand is so great that as soon as doses are produced, they must immediately ship to one of the world’s current cholera hot spots. This crisis is symptomatic of a larger problem: the persistent lack of political will and financial investment to dramatically reduce cholera deaths. Cholera flourishes in areas where there is contaminated water, poor sanitation, and people living in crowded conditions — like the city of Rafah, currently home to more than 1 million Palestinians displaced by Israel’s war in Gaza. Cholera has not yet been detected there, since no one from outside Gaza can bring it in, but an outbreak would be catastrophic given the decimation of Gaza’s health care system and the lack of access to humanitarian goods like clean water and medication. The disease is typically spread when an infected person or people contaminate a water source by defecating in or near it. People get sick after drinking the contaminated water, suffering from acute diarrhea and vomiting — which can, without treatment, kill an infected person within a day. It’s a disease that rich countries with clean water and good sanitation infrastructure do not have to worry about anymore. But cholera cases are rising worldwide now after a period of decline from 2017 through 2021, according to the World Health Organization’s cholera team leader Philippe Barboza. There are currently active cholera outbreaks in Zambia, Mozambique, Sudan, the Democratic Republic of the Congo, Syria, Ethiopia, Somalia, Zimbabwe, and Haiti. “Once it is there in these situations, because of the very poor water and sanitation and hygiene situation, it can spread like wildfire,” Paul Spiegel, director of the Johns Hopkins Center for Humanitarian Health, told Vox. As many as 143,000 people die from this preventable disease each year — which could even be an underestimate, since some countries do not have the capacity to detect or compile data on cholera cases. According to some metrics, it is becoming more fatal because many infected people do not have adequate access to health care. Concurrent outbreaks throughout the world are straining the global health sector’s resources to respond. “It’s a really horrible way to die,” Mohammad Fadlalla, an Ohio-based physician who volunteers with Medecins Sans Frontieres and has responded to multiple cholera outbreaks, told Vox. With the increase in outbreaks and limited countermeasures, particularly vaccines, “We are talking about a billion people at risk” in the immediate term, Barboza said. “And this is an underestimate. This is a very conservative estimate.” Why aren’t there enough cholera vaccine doses? There are a few intersecting crises that have led to cholera’s comeback and the world’s limited capacity to combat it. One pivotal moment came in 2020, when Shantha (now Sanofi India), a fully owned subsidiary of French pharmaceutical company Sanofi based in India, announced that it would stop manufacturing its oral cholera vaccine at the end of 2022. “We took this decision in a context where we were already producing very small volumes versus the total demand for cholera vaccines and in the knowledge that other cholera vaccine manufacturers (current and new entrants) had already announced an increased supply capacity in the years to come,” Sanofi told the Guardian in 2022. The company said at the time that it had shared information about how its vaccine was manufactured with public health partners like the International Vaccine Institute (IVI), which has transferred the vaccine technology to new manufacturers. But those contingencies weren’t enough to offset a total shutdown by the company that was manufacturing about 15 percent of the global vaccine supply depending on the year, as Jerome Kim, director general of the IVI, told Vox. That left just one other manufacturer, South Korea’s EuBiologics, in the market as global cholera cases surged. “WHO has contacted [Sanofi] several times to ask first to increase [vaccine production], second to maintain, and third, to postpone their decision,” Barboza said. “So we have tried all the possible things and the rationale of [Sanofi is], ‘Oh, no, there will be other manufacturers that are coming.’” In an email to Vox, Sanofi said that the decision to exit the cholera vaccine market was not about profitability, but rather based on an understanding that EuBiologics would increase its output and other manufacturers would enter the market. EuBiologics will produce as many as 50 million doses of an oral cholera vaccine this year. The WHO announced in April that it approved a simplified, but still effective, version of the present formula for use, which will help mitigate the vaccine shortage. The world has already been forced to start rationing vaccine doses. In 2022, the WHO recommended halving the vaccine dose from two to one, which downgrades the vaccine’s efficacy but does offer protection for a year or more, and obviously increases the number of people who can receive some protection with limited supplies. Last year, all of the 36 million regimens were distributed to 72 million people to take one dose each. Today, with only EuBiologics now producing a cholera vaccine, doses are allocated as soon as they are made to one of the areas with an active outbreak, said Derrick Sim, managing director of vaccine markets and health security at Gavi, the international vaccine alliance. Because of the global shortfall, there are no vaccine doses available for preventive campaigns that would keep cholera out of communities in the first place. And absent an international commitment to improve the water supply and sanitation in poor countries at risk for cholera outbreaks — an approximately $114 billion yearly commitment — vaccination would be a powerful tool for preventing sickness and death from cholera in areas where outbreaks could occur. There are some important developments in vaccine technology in the pipeline, such as a temperature-stable pill form that would be much easier to transport and administer than the current liquid form, which must be kept between 2 and 8 degrees Celsius. At least three companies are currently working to develop new cholera vaccines, but they won’t be on the market until at least the end of 2025, and potentially years later. Gavi, which supports vaccine programs in developing countries and has contributed to the vaccination of nearly 1 billion children since its founding in 2000, is also working with smaller manufacturers in developing countries in Africa to bolster the global supply and produce the vaccine closer to where it will ultimately be used, Sim said. But developing cholera vaccines — from research to improve them to transferring the vaccine technology to new manufacturers, from clinical trials to purchasing and distributing them — also requires money. The WHO budgeted about $12 million for its cholera vaccination efforts last year, but that number will need to increase as cases do. That could potentially help address some of these supply issues — but it also highlights why they exist in the first place. “The big manufacturers are not interested in investing in a vaccine that only the poor countr[ies] can buy,” Barboza said, “and that will cost only $1.50 or $1 per dose.” Why are cholera cases rising in the first place, in the 21st century no less? At the time Sanofi decided to exit the cholera vaccine market in 2020, cholera was trending downward after a 20-year high in 2017. The Global Task Force for Cholera Control — a collaboration between the WHO, GAVI, and other stakeholders — had released a road map to reducing cholera deaths by 90 percent by 2030, and poor and developing countries where cholera is endemic or an active concern were implementing national cholera vaccination plans. In retrospect, experts believe the world missed an opportunity to work aggressively toward prevention, an effort that would have been aided by Sanofi’s continued production of its cholera vaccines. But Covid-19, which diverted resources and attention away from most other global diseases including cholera; an increase in displacement due to violence and conflict; and extreme weather events caused by climate change that both displace people and make environments more conducive to cholera have combined to allow the disease to spread more rapidly. Four of the five worst years for cholera in recent history have come since 2017. This is all the more concerning because cholera is fairly simple to prevent, with the supplies to provide clean drinking water and sanitation. It’s easy to treat, too: All it takes to cure cholera in most cases is clean water and oral rehydration salts, antibiotics in the worst-case scenarios. With proper medical intervention, no one should die from it. In situations of extreme instability like in Sudan, or where the medical sector has been decimated as in Gaza, those interventions become more challenging. And while some countries have long had routine cholera outbreaks, it’s not always easy to predict when or where they’ll hit, or how big they will grow, because contaminated water sources and infected people can cross borders, as likely occurred in Lebanon in 2022. Cholera is common in neighboring Syria, where the Assad regime has decimated local infrastructure and displaced hundreds of thousands of people. Though Lebanon had not experienced an outbreak since 1993, conditions were ripe for it. Years of government corruption and incompetence have led to a breakdown in public infrastructure including health care and sanitation — all of which helped trigger the outbreak in 2022. That outbreak saw at least 6,000 confirmed and suspectd cases. In August 2023, Fadlalla was responding to an outbreak in Al Qadarif, Sudan, which has been in a devastating civil conflict for a year now. “A lot of the governmental institutions were [at the time] eight months without their people getting paid their salaries, and the bureaucracy was not really functioning or operating,” he said. “And this is including the Ministries of Health. The whole medical sector was not getting paid, supplies were not getting restocked.” Climate change and the conflict and displacement related to it also significantly contribute to the uptick in cholera outbreaks, according to experts Vox spoke with. Higher temperatures and changing weather patterns make the environmental conditions ripe for outbreaks in new places unused to the disease. But climate change is not going to be reversed any time soon, nor is the global community going to commit to improving sanitation in developing countries or mitigating displacement. So in the meantime, vaccines remain one of the most important ways to prevent cholera deaths. “It’s not that nothing is happening,” Barboza said. “There are a lot of things that are happening, but are they acting fast enough, with enough money?”

A patient tips their head back and opens their mouth while a nurse drops liquid onto their tongue.
A nurse administers a dosage of the cholera vaccine during the launch of the campaign to immunize people in affected areas, at the Kuwadzana Polyclinic in Harare on January 29, 2024. | Jekesai Njikizana/AFP via Getty Images

“A billion people at risk”: How worldwide cholera outbreaks are threatening lives.

Amid a global resurgence of cholera, the world is fighting with one hand tied behind its back.

The global stockpile of the oral cholera vaccine — a supply whose needs are difficult to predict and fill anyway — has dwindled to nearly nothing after the Indian drug manufacturer that produced about 15 percent of the world’s supply stopped making the vaccine last year. While other companies are setting up new production capacity, the stockpile is now effectively nonexistent. Demand is so great that as soon as doses are produced, they must immediately ship to one of the world’s current cholera hot spots.

This crisis is symptomatic of a larger problem: the persistent lack of political will and financial investment to dramatically reduce cholera deaths.

Cholera flourishes in areas where there is contaminated water, poor sanitation, and people living in crowded conditions — like the city of Rafah, currently home to more than 1 million Palestinians displaced by Israel’s war in Gaza. Cholera has not yet been detected there, since no one from outside Gaza can bring it in, but an outbreak would be catastrophic given the decimation of Gaza’s health care system and the lack of access to humanitarian goods like clean water and medication.

The disease is typically spread when an infected person or people contaminate a water source by defecating in or near it. People get sick after drinking the contaminated water, suffering from acute diarrhea and vomiting — which can, without treatment, kill an infected person within a day.

It’s a disease that rich countries with clean water and good sanitation infrastructure do not have to worry about anymore. But cholera cases are rising worldwide now after a period of decline from 2017 through 2021, according to the World Health Organization’s cholera team leader Philippe Barboza. There are currently active cholera outbreaks in Zambia, Mozambique, Sudan, the Democratic Republic of the Congo, Syria, Ethiopia, Somalia, Zimbabwe, and Haiti.

“Once it is there in these situations, because of the very poor water and sanitation and hygiene situation, it can spread like wildfire,” Paul Spiegel, director of the Johns Hopkins Center for Humanitarian Health, told Vox.

As many as 143,000 people die from this preventable disease each year — which could even be an underestimate, since some countries do not have the capacity to detect or compile data on cholera cases. According to some metrics, it is becoming more fatal because many infected people do not have adequate access to health care. Concurrent outbreaks throughout the world are straining the global health sector’s resources to respond.

“It’s a really horrible way to die,” Mohammad Fadlalla, an Ohio-based physician who volunteers with Medecins Sans Frontieres and has responded to multiple cholera outbreaks, told Vox.

With the increase in outbreaks and limited countermeasures, particularly vaccines, “We are talking about a billion people at risk” in the immediate term, Barboza said. “And this is an underestimate. This is a very conservative estimate.”

Why aren’t there enough cholera vaccine doses?

There are a few intersecting crises that have led to cholera’s comeback and the world’s limited capacity to combat it. One pivotal moment came in 2020, when Shantha (now Sanofi India), a fully owned subsidiary of French pharmaceutical company Sanofi based in India, announced that it would stop manufacturing its oral cholera vaccine at the end of 2022.

“We took this decision in a context where we were already producing very small volumes versus the total demand for cholera vaccines and in the knowledge that other cholera vaccine manufacturers (current and new entrants) had already announced an increased supply capacity in the years to come,” Sanofi told the Guardian in 2022.

The company said at the time that it had shared information about how its vaccine was manufactured with public health partners like the International Vaccine Institute (IVI), which has transferred the vaccine technology to new manufacturers.

But those contingencies weren’t enough to offset a total shutdown by the company that was manufacturing about 15 percent of the global vaccine supply depending on the year, as Jerome Kim, director general of the IVI, told Vox. That left just one other manufacturer, South Korea’s EuBiologics, in the market as global cholera cases surged.

“WHO has contacted [Sanofi] several times to ask first to increase [vaccine production], second to maintain, and third, to postpone their decision,” Barboza said. “So we have tried all the possible things and the rationale of [Sanofi is], ‘Oh, no, there will be other manufacturers that are coming.’”

In an email to Vox, Sanofi said that the decision to exit the cholera vaccine market was not about profitability, but rather based on an understanding that EuBiologics would increase its output and other manufacturers would enter the market.

EuBiologics will produce as many as 50 million doses of an oral cholera vaccine this year. The WHO announced in April that it approved a simplified, but still effective, version of the present formula for use, which will help mitigate the vaccine shortage.

The world has already been forced to start rationing vaccine doses. In 2022, the WHO recommended halving the vaccine dose from two to one, which downgrades the vaccine’s efficacy but does offer protection for a year or more, and obviously increases the number of people who can receive some protection with limited supplies. Last year, all of the 36 million regimens were distributed to 72 million people to take one dose each. Today, with only EuBiologics now producing a cholera vaccine, doses are allocated as soon as they are made to one of the areas with an active outbreak, said Derrick Sim, managing director of vaccine markets and health security at Gavi, the international vaccine alliance.

Because of the global shortfall, there are no vaccine doses available for preventive campaigns that would keep cholera out of communities in the first place. And absent an international commitment to improve the water supply and sanitation in poor countries at risk for cholera outbreaks — an approximately $114 billion yearly commitment — vaccination would be a powerful tool for preventing sickness and death from cholera in areas where outbreaks could occur.

There are some important developments in vaccine technology in the pipeline, such as a temperature-stable pill form that would be much easier to transport and administer than the current liquid form, which must be kept between 2 and 8 degrees Celsius. At least three companies are currently working to develop new cholera vaccines, but they won’t be on the market until at least the end of 2025, and potentially years later. Gavi, which supports vaccine programs in developing countries and has contributed to the vaccination of nearly 1 billion children since its founding in 2000, is also working with smaller manufacturers in developing countries in Africa to bolster the global supply and produce the vaccine closer to where it will ultimately be used, Sim said.

But developing cholera vaccines — from research to improve them to transferring the vaccine technology to new manufacturers, from clinical trials to purchasing and distributing them — also requires money. The WHO budgeted about $12 million for its cholera vaccination efforts last year, but that number will need to increase as cases do.

That could potentially help address some of these supply issues — but it also highlights why they exist in the first place.

“The big manufacturers are not interested in investing in a vaccine that only the poor countr[ies] can buy,” Barboza said, “and that will cost only $1.50 or $1 per dose.”

Why are cholera cases rising in the first place, in the 21st century no less?

At the time Sanofi decided to exit the cholera vaccine market in 2020, cholera was trending downward after a 20-year high in 2017. The Global Task Force for Cholera Control — a collaboration between the WHO, GAVI, and other stakeholders — had released a road map to reducing cholera deaths by 90 percent by 2030, and poor and developing countries where cholera is endemic or an active concern were implementing national cholera vaccination plans.

In retrospect, experts believe the world missed an opportunity to work aggressively toward prevention, an effort that would have been aided by Sanofi’s continued production of its cholera vaccines.

But Covid-19, which diverted resources and attention away from most other global diseases including cholera; an increase in displacement due to violence and conflict; and extreme weather events caused by climate change that both displace people and make environments more conducive to cholera have combined to allow the disease to spread more rapidly.

Four of the five worst years for cholera in recent history have come since 2017.

This is all the more concerning because cholera is fairly simple to prevent, with the supplies to provide clean drinking water and sanitation. It’s easy to treat, too: All it takes to cure cholera in most cases is clean water and oral rehydration salts, antibiotics in the worst-case scenarios. With proper medical intervention, no one should die from it.

In situations of extreme instability like in Sudan, or where the medical sector has been decimated as in Gaza, those interventions become more challenging.

And while some countries have long had routine cholera outbreaks, it’s not always easy to predict when or where they’ll hit, or how big they will grow, because contaminated water sources and infected people can cross borders, as likely occurred in Lebanon in 2022. Cholera is common in neighboring Syria, where the Assad regime has decimated local infrastructure and displaced hundreds of thousands of people. Though Lebanon had not experienced an outbreak since 1993, conditions were ripe for it. Years of government corruption and incompetence have led to a breakdown in public infrastructure including health care and sanitation — all of which helped trigger the outbreak in 2022. That outbreak saw at least 6,000 confirmed and suspectd cases.

In August 2023, Fadlalla was responding to an outbreak in Al Qadarif, Sudan, which has been in a devastating civil conflict for a year now.

“A lot of the governmental institutions were [at the time] eight months without their people getting paid their salaries, and the bureaucracy was not really functioning or operating,” he said. “And this is including the Ministries of Health. The whole medical sector was not getting paid, supplies were not getting restocked.”

Climate change and the conflict and displacement related to it also significantly contribute to the uptick in cholera outbreaks, according to experts Vox spoke with. Higher temperatures and changing weather patterns make the environmental conditions ripe for outbreaks in new places unused to the disease.

But climate change is not going to be reversed any time soon, nor is the global community going to commit to improving sanitation in developing countries or mitigating displacement. So in the meantime, vaccines remain one of the most important ways to prevent cholera deaths.

“It’s not that nothing is happening,” Barboza said. “There are a lot of things that are happening, but are they acting fast enough, with enough money?”

Read the full story here.
Photos courtesy of

Egypt’s Famed Pyramids Overlooked a Long-Lost Branch of the Nile

A former stretch of the Nile River, now buried beneath the Sahara Desert, may help scientists understand how Egyptians built the pyramids and adapted to a drying landscape

Lost Branch of the Nile May Solve Long-Standing Mystery of Egypt’s Famed PyramidsA former stretch of the Nile River, now buried beneath the Sahara Desert, may help scientists understand how Egyptians built the pyramids and adapted to a drying landscapeBy Riis WilliamsThe Step Pyramid of Djoser, constructed during the third dynasty of Egypt. Atop a rocky, arid plateau in the Sahara’s Western Desert in Egypt stands the last of the Seven Wonders of the Ancient World: the Great Pyramid of Giza. The 455-foot-tall stone structure and several smaller pyramids in the area have long provided research material for scientists working to decipher ancient Egyptians’ inscriptions to figure out how they constructed such massive monuments—and to understand why they built them so far from the Nile River, the lifeblood of their great civilization.Geomorphologist Eman Ghoneim says she has pondered that last mystery for years. “I was born and lived most of my life in Egypt,” she says, “and one question that I remember asking myself since I was very young is: ‘Why did our ancestors build pyramids in this specific, odd place—and why so far from the water?’ I had this feeling like there was something more there.”The Bent Pyramid at the necropolis of Dahshur. The pyramid was constructed during Egypt’s fourth dynasty.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.Ghoneim, a professor at the University of North Carolina Wilmington, recently showed that at the time they were built, the pyramids were in fact much closer to water. (They stand more than five miles from the Nile’s closest bank today.) By analyzing batches of satellite images and sediment samples collected from deep beneath the desert’s surface, she and her research team located a long-lost ancient branch of the Nile that once ran through the foothills just beside the Giza pyramid field. It’s likely that this channel, which the study team named the Ahramat (“pyramid” in Arabic), is how builders transported materials to the pyramid construction grounds, Ghoneim says. Knowing its course can help archeologists search for potential sites of ancient human settlements that may be buried beneath vast, dusty plain. The researchers detailed their discovery in a study published on Thursday in Communications Earth & Environment. Scientists have long suspected that the Nile—which runs northward for roughly 4,100 miles from Lake Victoria in Tanzania, Kenya and Uganda to the Mediterranean Sea—once had several offshoots. Past research indicates that during the middle of the Holocene epoch, about 10,000 to 6,000 years ago, the Nile floodplain was a lush, marshy habitat that narrowed and became largely barren after a long period of scant rainfall and increased aridity in the Late Holocene.Eman Ghoneim’s research team organizes collected soil samples.Today’s scorched, unforgiving Sahara is a tricky place to conduct the kind of fieldwork involved in searching for former river channels. Before braving the environment for a dig, the research team used radar satellites to peer beneath the top layer of earth and produce images of the subsurface. These revealed subtle patterns and textures in the ground’s layers near the pyramids—features that differed from other areas of the desert and hinted at the long-ago presence of running water. “We were looking at these meandering natural features closer to the [pyramid] field, like long depressions and troughs, now covered up entirely by farmlands and sand,” Ghoneim says. “It can be very hard to see if you don’t know what to look for.”Ghoneim and her colleagues then traveled to Egypt, where they used large drills to excavate two “cores,” or cylinders of earth, extending dozens of miles below the surface. When the drill pulled up sand from deep below, Ghoneim knew the team had found remnants of a lost river. “There is, of course, sand on the surface,” she says. “But the presence of sand and other coarse sediments underneath the surface—instead of clay or silt—indicates that there was once running water in the area.”The water course of the ancient Ahramat Branch borders a large number of pyramids dating from Egypt’s Old Kingdom to its Second Intermediate Period and spanning between its third and 13th dynasties.The researchers tracked the Ahramat’s former course for nearly 40 miles. Ghoneim says it may have run even longer, and more research could determine the channel’s general depth and width. It’s unclear why the waterway ran dry, but the team speculates that a combination of tectonic plate movements, windblown sand and the severe drought in the Late Holocene spelled its demise.Dev Niyogi, a geology professor at the University of Texas at Austin, who was not involved in the new study, says understanding how ancient societies were shaped by their ever changing landscapes and waterways can help guide modern efforts to develop infrastructure wisely in an era of climate change. The ancient Nile branch also serves as a reminder that “resilient human societies are never rigid,” says Adam Rabinowitz, an archeologist and classics professor also at U.T. Austin, who is currently working on a project designed to ready Texans for dramatic, climate-driven changes to the state’s water availability over the next 25 years. “We have to explore how past societies responded to similar climate-related challenges ... so that we can better understand the human experience of living through and adapting to a major environmental change.”Ghoneim says she hopes to continue piecing together a map of the Nile’s former life by further studying the Ahramat and other river channels that may be lost beneath the desert. “For most cities, we’re not talking about how water helped the building of pyramids but rather how human civilizations otherwise depended on it and adapted to its changes,” she says. “And when we learn from the past, we can prepare for the future.”

Hochul Meets the Pope, and Reflects on Her Father and Irish Catholicism

At a climate change summit at the Vatican, Gov. Kathy Hochul positioned New York State as a leader in pursuing environmental goals, but also recalled her late father.

As Gov. Kathy Hochul of New York waited for Pope Francis in Clementine Hall, an ornate room with marble walls and frescoed ceilings in the Vatican’s papal apartments, her thoughts drifted to her father.Ms. Hochul was last in Rome seven years ago with her father, who was celebrating his 80th birthday. He passed away suddenly in October, while the governor was on another diplomatic trip abroad, visiting Israel. And now, as she sat in the Vatican, she recalled her upbringing as a “social justice Catholic,” and how it shaped her political journey.“It was a profound experience for me, sitting there reflecting on my family’s teachings,” Ms. Hochul said on Thursday. “I was thinking in that room that this is really a culmination of a lifetime dedicated to service.”The governor was in Italy for just over 24 hours to attend a summit on climate change hosted by the pope at the Vatican. It was the second such trip taken by a New York leader in a week: Mayor Eric Adams of New York City met with the pope on Saturday.Ms. Hochul arrived in Rome on Wednesday for a series of private meetings and a reception with Gov. Maura Healey of Massachusetts and Gov. Gavin Newsom of California. On Thursday morning, the entire conference, which consisted of mayors, governors, climate activists and academics, gathered in the papal apartments for a private audience with Pope Francis. Some attendees wore suits, while others wore tribal attire, including feather headdresses, or more casual tourist clothes. Many brought gifts for the pope: bottles of wine, statues, flags.Subscribe to The Times to read as many articles as you like.

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