If children in poor countries got the shots that rich countries take for granted, hundreds of thousands of young lives could be saved.
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Go see the child, Samir Saha said. Just sit with her. Probably the siblings will be there too, the brother and sister whose lives are also altered permanently.
‘This is why the vaccine is so important,’ Saha said.
‘We want to reduce this number to a minimum if not zero. So no other children will be like this.’
It was a little after dawn in Dhaka, the capital of Bangladesh, and Saha was in the back seat of his car, brooding. A uniformed driver threaded the Toyota through a cacophonous mess of jitneys, motorcycles, rickshaws, trucks, and battered buses with passengers hanging out the doors. “We could save the life, but we could not …” He left the sentence unfinished. “You’ll be seeing the scenario,” he said. “You’ll understand.”
Saha is a microbiologist, internationally renowned for his research on a bacterium called pneumococcus. The laboratory he founded is wedged into one corner of Dhaka Shishu, the biggest children’s hospital in Bangladesh. Just down the hall, rows of beds fill the open wards; during family hours, each bed seems to hold both a sick child and many attentive relatives. Inside the lab, white-jacketed men and women spend their days in intimate study of pneumococcal cells: hunting for them in vials of blood and other bodily fluids, smearing them into petri dishes, peering at them through microscopes.
Pneumococcal bacteria are ubiquitous in the modern world; easily spreadable through sneezing or casual contact, they can live without ill effect in the nasal passages of people with healthy immune systems. But when our defenses fail us, pneumococcus can migrate, multiply, and set off life-threatening infectious disease. Young children are especially vulnerable. Young children in places without ready access to antibiotics and good medical care are the most vulnerable of all. At the start of the 21st century, as the world’s first effective children’s vaccine became available in the United States and Canada, pneumococcal disease was killing more than 800,000 children worldwide every year—more than three-quarters of a million infants and kids under five, that is, dying not from some headline epidemic like Ebola or Zika but from a common organism that blew up into pneumonia (infected lungs) or meningitis (infected brain lining) or a mortal assault on the bloodstream. The vast majority of those deaths were occurring in impoverished countries such as Bangladesh.
In 2015 pneumococcal conjugate vaccine, as the children’s formulation is called, reached the Bangladeshis, and Saha’s research team is intently tracking its progress. If PCVs prove as effective around the world as vaccine experts hope, they promise both a greatly lowered mortality rate—that’s many thousands of small children staying alive instead of dying before they’re old enough to start school—and much less nonmortal sickness. Less of the rapid pneumonia breathing; less of the fever, the sucking chest, the rattling cough, the blue lips, the bedside watch by parents pulled away from the paid work that supports their other children. Less … suffering, I kept hearing Saha and his Bangladeshi colleagues say, as though sensing that an outsider might need help appreciating the stakes.
Because from the vantage of a country like the United States, it can be easy to imagine that the most pressing vaccine challenge of 2017 lies in convincing certain communities of skeptical parents that they really ought to inoculate their kids. Those efforts are important, to be sure. But even more urgent—more ambitious, more complex, involving many governments and billions of philanthropic dollars—is the international collaboration to get new vaccines to children in the developing world, where to this day the suffering caused by vaccine-preventable disease is as vivid and nontheoretical as the frantic families Saha sees every day in the halls of Dhaka Shishu.
This is why he was sending me to Sanjida Sahajahan, 11 years old, the middle child of a rickshaw repairman and his wife. Go now, Saha said, as we pulled up to the hospital’s main gate; when you come back, we shall discuss what you observed. Jamal and Tasmim will accompany you. That van in the parking lot is waiting.
The hospital van bumped through crowded Dhaka streets that kept narrowing until we were inching past market displays: piles of sweet potatoes and used clothes and car parts. The road ran out of vehicle room. We got out to walk. Jamal Uddin is a physician, Tasmim Sultana Lipi a community health worker, and the two of them knew the right muddy passageways to follow. Along metal-roofed buildings to either side, barred windows offered glimpses of family after family inhabiting separate single rooms.
Lipi nodded toward one of the doorways and ducked in. Observing neighborhood protocol, we all removed our shoes.
Sanjida, who had been carried into Dhaka Shishu at the age of three with what turned out to be pneumococcal meningitis, was propped up in a small plastic armchair beside the family bed. Meningitis is an inflammation, sometimes irreversibly destructive, of the membranes that surround the brain and spinal cord. Sanjida has no control over her head, her grimaces, or the sounds she makes—mewling cries, mostly, as she is unable to form words. Her mother, Nazma, had been outside with the baby when we arrived; in these rooms nine families share two toilets and a single tap, and now Nazma hurried in, holding the baby in one arm, wiping dry her face. She lowered herself onto a stool. She took Sanjida’s hand.
In Bangla, she told us the story: their bright, talkative three-year-old’s unexplained fever; the neighbors urging acetaminophen, for sale in a shop nearby; the fever receding after the pills; the fever rising again. A few days later came the first convulsion and the terrified journey to the hospital—by bus and motorcycle taxi, as a rickshaw repairman doesn’t have the means to summon an ambulance. By the time doctors saw Sanjida, she was losing consciousness. Her last understandable words, Nazma said, were “Hug me. I feel very bad.”
Sanjida’s father, Mohammad, stood quietly while Nazma spoke. Their 14-year-old son came in and picked up the baby and stood too; there was nowhere else to sit. A disassembled wheelchair had been shoved beneath the bed—a charity gift, Nazma said, very nice idea, but their living quarters were too small. A wall cabinet held toys and dishware, and now Mohammad pulled from a drawer a creased yellow card: Sanjida’s national health record. Here was her birth date, in September 2005.
And here, the first markings dated six weeks later, were the notations for Sanjida’s vaccinations. Like her older brother, Sanjida received every inoculation then in Bangladesh’s national immunization plan, on schedule and for free: whooping cough, measles, diphtheria, tuberculosis, tetanus, hepatitis B, polio. No smallpox; worldwide vaccination had already erased that disfiguring contagion from the planet by 1980, two centuries after the English physician Edward Jenner published his famous treatise on deliberately infecting children with cowpox, a mild virus that turned out to stimulate immunity against the far more serious smallpox.
An extraordinary global health history had been abbreviated, in a way, on Sanjida’s little yellow card. No one can tally accurately the total number of lives saved by widespread vaccination, but it remains one of the greatest achievements of modern medicine. Measles, for example, was killing more than two million children a year worldwide in the 1980s; by 2015, according to the World Health Organization, vaccination had dropped the death toll to 134,200. Mass vaccination has ended polio in all but three countries; Bangladesh and its giant neighbor India were pronounced polio free in March 2014. And when I asked Nazma how she first learned about vaccines—what gave her the idea that taking healthy babies for injections was a good idea?—she looked startled. Then she responded with a passionate outpouring that Uddin and Lipi distilled into English: But every Bangladeshi knows this.
On television—the Sahajahans’ is crammed in atop that wall cabinet—popular singers and athletes in public service ads praise the lifesaving gift of inoculation. Encouragements to vaccinate trumpet from thousands of minarets, like calls to prayer; Bangladesh is predominantly Muslim, and while pushing for polio inoculation in the late 1980s, health officials and Islamic leaders together came up with a plan for “mosque miking.” Once, in a village outside Dhaka, the local imam proudly pushed up a sleeve to show me the trace of his last tuberculosis vaccination. Protecting one’s health is part of a religiously observant life, he explained, and faithful parents are obliged to do the same for their children.
Delivering vaccines in Bangladesh isn’t easy. The terrain is crisscrossed by flooding rivers and barely passable roads, and the vaccines must be kept at just the right cold temperature to preserve their potency. Maintaining this “cold chain” is an urgent priority for immunization programs in all countries with hot climates and shaky power grids; a single faulty chiller or a rural power outage can wreck a whole batch of vaccine. But Bangladesh has worked hard to preserve the cold chain, equipping local health centers with solar panels, pressing bicycles and riverboats into service to ferry vaccines to the most remote clinics.
The Bangladeshi inoculation program is widely respected for its remarkable reach, in fact, and on the way back to Dhaka Shishu, the three of us silent and sad in the hospital van, I understood what Samir Saha most wanted me to see. By 2005, when the infant Sanjida got all her shots, the new vaccine against pneumococcal infection was routinely being injected into children all over the United States and was spreading fast across the developed world. The problem was in places like Bangladesh, which needed the vaccine far more desperately but couldn’t pay what the manufacturer had decided to charge.
Vaccines, with very few exceptions, are made by private companies, in business to return a profit. Until recently, their manufacture worldwide has been dominated by a few U.S. and European pharmaceutical giants. As officials of these companies point out when advocacy organizations like Doctors Without Borders press them to lower their prices (or else open their books to prove why they can’t), developing a new vaccine is especially expensive. After all, it typically involves injecting a disabled germ or fragment of a germ into healthy trial participants—followed by a drawn-out process of watching and waiting to make certain the vaccine isn’t harmful, that it stimulates an immune response against the infectious germ, and that the people who receive it contract the disease less often than those who don’t. All that takes years.
For a pneumococcal vaccine that worked right in children, it took decades. Good adult vaccines were on the market by the early 1980s, but they never set off the hoped-for immune response in small kids. It wasn’t until the late 1990s that researchers finally found a way to biologically amend, or “conjugate,” the contents of those adult vaccines so they would be recognized by immature immune systems.
Pneumococcus presents another vexing challenge: Saha and other scientists have identified nearly a hundred versions, or serotypes, of pneumococcal cells. Serotypes can be geographically distinct, and for reasons not yet fully understood, only a small number are dangerous. (Serotype 1, for example, causes comparatively little disease in the United States but is a prime source of pneumococcal illness and death in Africa and South Asia.) So a finished vaccine that works for children and targets exactly the right serotypes is really multiple vaccines, individually amended and tested and then mixed into one vial.
All these complications helped make the first children’s pneumococcal vaccine one of the most expensive in history. Called Prevnar, it was launched in early 2000 by the American pharmaceutical company Wyeth (which was later taken over by Pfizer). It was formulated to work against the seven serotypes responsible for most of the disease—in the United States, that is, which could absorb a children’s vaccine priced at $232 per four-dose course. Among the dangerous kinds of pneumococcus that vaccine was not formulated to fight off was serotype 1. Yet the poorest regions of Africa and South Asia are precisely where any pneumococcal infection is likeliest to kill a child or leave her crippled for life—not just because parents can’t reach a doctor in time but also because the bacteria do extra damage inside small bodies already weakened by malnutrition, other lingering diseases, and too much exposure to cook-fire smoke.
“When I started work on this, what kept me up at night was the inequity,” says Orin Levine, vaccine delivery director at the Bill and Melinda Gates Foundation. Years ago a colleague of his watched a woman in a Mali hospital lose a daughter to pneumococcal pneumonia; she’d lost another daughter the same way. Levine still remembers the mother’s name. His own daughters were about the same age.
“The chances of a kid dying of pneumococcal disease in the rich world were a hundredfold less,” he says. “Why was it that my kids could get the vaccine when Tiemany Diarra’s kids, Mali’s kids, needed it more and didn’t get it?”
He knew the answer, of course: The surest economic return to vaccine manufacturers doesn’t come from meeting the most critical need.
Imagine Levine's frustration echoed by a world of vaccine experts, and you understand the impetus behind the Global Alliance for Vaccines and Immunisation, or Gavi. This multibillion-dollar public-private collaboration got under way in 2000, just as PCVs reached the U.S. market. Kicked off in part by a $750 million pledge from the Gates Foundation, Gavi channels wealthy nations’ resources—private philanthropy plus government aid from such countries as the United States, the United Kingdom, and Norway—into vaccine support for poorer countries that apply for the aid. Gavi helps negotiate with vaccine companies to slash prices specifically for those large-volume sales; subsidies from the donor fund then reduce the cost to developing countries even further, so that they pay a small fraction of the usual market price.
“It’s been absolutely transformational—the financial muscle and the dedication that global actors and manufacturers and countries have agreed to,” says Katherine O’Brien, a pediatrician and pneumococcus expert who directs the International Vaccine Access Center at Johns Hopkins University. Gavi wasn’t assembled just to help with pneumococcal vaccine, O’Brien points out; the alliance concentrated at first on making established childhood inoculations like tetanus and hepatitis B more accessible.
PCVs joined the vaccine list only in 2010, after years of continued testing and negotiation. But the demand from developing countries was so high that soon Gavi was devoting a half billion donor dollars a year to PCV support—the alliance’s single biggest financial commitment. A special arrangement with Pfizer and GSK, the only companies currently making PCVs, is supposed to ensure there will be enough supply; both have promised to produce as much vaccine, at the Gavi-arranged discount, as each of the receiving countries agrees to buy.
With those deals in place, the manufacturers have also developed new formulations that extend the effectiveness of PCVs to include children a long way from the U.S. and Europe. In 2010 Pfizer released a new blend called Prevnar 13, designed to work against serotype 1 and five others not targeted in the original mix. The GSK product, introduced in 2009, also is configured to fight serotypes prevalent in Africa and Asia. And since March 2015, when Bangladeshi health officials received their inaugural delivery of Gavi-discounted PCV, vaccine shipments have arrived by air freight every three months from a GSK distribution center in Belgium.
“Small chiller boxes,” Saha told me. “Like when you are going camping. But these are a little more sophisticated, with monitoring systems for the temperature.”
The vaccines, health officials say, are reaching families all over the country. Bangladesh, at least so far, has experienced no surge of “vaccine hesitancy,” as global health experts prefer to call the problem of parents declining to vaccinate their children. Elsewhere in South Asia, suspicion and hostility have troubled recent inoculation campaigns; in Pakistan, for example, polio vaccinators a few years ago were turned away or attacked amid rumors both false and true. (False: that the vaccines were part of a Western plot against Islam. True: that the CIA used house-to-house vaccinators to hunt for Osama bin Laden.) And in parts of India, a measles-rubella vaccination campaign foundered earlier this year, after anonymous posts on social media claimed the vaccines were dangerous or even meant to sterilize the children of religious minorities.
Even in vaccine-receptive Bangladesh, Saha told me, he’s heard people wonder about the merits of adding PCVs to the already ambitious national inoculation effort. “I was on a talk show on the TV,” he said. “A banker’s wife, a powerful person, said, ‘Why are you talking about vaccines so much?’ ” Pneumonia and other pneumococcal infections are treatable with penicillin, the banker’s wife objected; Saha had just said so himself. “And my answer was: ‘Oh, madam. You want to wait until pneumonia develops, and then you should treat it?’ ”
Had she walked the Dhaka Shishu wards with Saha, this woman would have seen listless children lying under oxygen masks, the families gathered at their bedside or crowded somberly in the hallways, waiting for antibiotics to take hold. And those are the families who have made it to the hospital. “For the remotest places,” Saha said, “this”—the preemptive strike of a working vaccine—“is the only tool we have.” In the villages and poorest city slums, pneumococcus-sickened children still die by the thousands at home.
Sanjida Sahajahan made it to Dhaka Shishu, but doctors could do little for her. Saha carries special frustration about her case. His lab identified the pneumococcus that infected her brain: serotype 1, one of the varieties not targeted in the inaugural version of Prevnar. So even if Bangladesh had been able to afford the vaccine in 2005, it would not have protected Sanjida—because the manufacturer had launched a lifesaving product not meant for her part of the world.
“And it’s not only that child who is nonfunctional,” Saha said. “The mother is nonfunctional. She cannot go anywhere. Each and every member of that family is really half dead.”
He was quiet. “We gave them a wheelchair,” he said. “Was she using it?”
It was in pieces, I said, under the bed. Saha winced. But the two-month-old baby, Jannat—the parents showed us her health card too, I told him, and its new column with the check mark in place: pneumococcal conjugate vaccine. If the inoculation does its job, Jannat will be protected from the pathogen that devastated her sister, and when Saha thought about all this, the grief and hope all shoved together inside that very small home, he sighed. “We should still look at how many children we lost, and how many were disabled like this, in those 10 years while we were waiting for the vaccine,” he said. “But thank God we have got the vaccine now.”
The sprawling GSK campus in the Belgian city of Wavre is the biggest vaccine production facility in the world. The day I met Luc Debruyne, the company’s global vaccines president, I’d already been obliged twice to change clothes. Each vaccine’s biological and mixing work is hermetically contained inside its own separate building, and stepping into one of these dedicated structures requires a complete switch to clean-room suit, cleansed white shoes, and protective goggles and cap over eyeglasses and hair.
Those buildings, along with other parts of the company’s vaccine operation, represent an investment of more than five billion dollars over the past decade, Debruyne said. “It is a profitable business,” he added. “It needs to be profitable to be sustainable, to be able to offer massive volume and affordable pricing to the developing world.”
The children’s pneumococcal vaccine GSK delivers to Dhaka is a global production: Mixing starts at the company’s plant in Singapore, vaccine batches are sent to Belgium and then France for processing, and the vials are finally returned to Belgium for shipping. As I peered through those goggles at the great silvery machines and vats at Wavre, though, the product under preparation was another GSK offering—a vaccine against a pathogen called rotavirus, the leading cause of children’s diarrhea, which sickens millions every year. In the poorest countries of sub-Saharan Africa and South Asia, it kills by the hundreds of thousands. Many children in Dhaka Shishu are struggling to recover from it.
Bangladesh has Gavi approval to start receiving GSK’s rotavirus vaccine, probably sometime next year. After the negotiated discount and additional financial support, the government will pay about 50 cents for each two-dose course of a vaccine that currently costs an American physician $220. For an impoverished health system, that’s irresistible, but there’s a colossal catch. Gavi aid is supposed to be temporary—a means for poor countries to help more children grow up healthy, and in doing so help improve the countries’ own economies to the point where they can finance important vaccines on their own.
Once a recipient country rises above the world’s lowest per capita income levels, the Gavi subsidy is supposed to be phased out. “It’s called ‘transitioning,’ ” says Doctors Without Borders vaccine policy adviser Kate Elder. “But I’ve heard ministers of health call this being expelled.” Even though leaders of GSK and other major U.S. and European vaccine manufacturers have promised to maintain impoverished-country discounts, losing the subsidy still means a comparatively huge cost increase. In Bangladesh, for example, it could push the GSK pneumococcal vaccine cost from 60 cents to $9.15 per child.
That still looks like a bargain to an American doctor paying more than 50 times that much. But Doctors Without Borders and other critics argue that the prices big American and European drug companies charge for children’s vaccines are unacceptably high, even at a discount. A third of the world’s countries have not yet brought PCVs into their immunization programs; a key reason is long-term cost. From the drug companies, Elder says, “we get this a lot of the time: ‘Why aren’t you just celebrating the kids who do have access now?’ And we say, ‘Yes, but we want more.’ ”
One remedy may lie in emerging competition from outside the U.S. and Europe—from pharmaceutical companies in India, Brazil, Vietnam, Cuba, South Korea, and even Bangladesh, where a Dhaka enterprise now sells nearly a dozen kinds of vaccine, using ingredients shipped in from other countries. An enormous Indian manufacturer called the Serum Institute produces from scratch more than a billion doses a year of relatively inexpensive vaccines, shipping them throughout India as well as abroad. Disease experts at the Gates Foundation and PATH, a global health nonprofit also based in Seattle, are helping Serum develop its own children’s pneumococcal vaccine. Trials are underway in India and Africa, and that vaccine could be on the market by 2020.
Samir Saha is 62 now, with no imminent plans for retirement. It’s too soon to assess definitively the success of PCVs in Bangladesh, but the last time we walked through Dhaka Shishu together, he was upbeat. Only three pneumococcus patients were in the general ward that day, none appeared in grave danger, and one of Saha’s researchers was at a computer working on a bar graph that showed a tantalizing case drop for autumn 2016—one short bar, dwarfed by much taller ones from the six preceding autumns.
Saha pulled up a chair and looked closely at the graph. Let’s wait and see next year, he said. But he was smiling. “Good for the patients,” he said. “Less pneumonia in the hospital. Less death.” He waved his arm toward all the researchers bent over microscopes. “Jobless!” Saha joked, and his smile broadened. “All of them will be jobless!”
Originally published by National Geographic Magazine and natgeo.com in November 2017.
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July 19, 2022
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