A Decade of Vaccines

The untold story behind one of the most successful global health interventions of all time.

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Infectious disease is a war on many fronts. Sanitation removes germs from the environment, antibiotics fight active infections and vaccines provide immunity. Right now, the battle that’s dominating headlines is the coronavirus outbreak. While public health officials around the world scramble to prevent an epidemic (or worse, cover it up), scientists are racing to develop a vaccine. During the SARS outbreak in 2003, it took them 20 months to go from genetic sequence to clinical availability. This time around, they’re trying to do it in three. That sounds difficult, but achievable — after all, the science has come a long way in the last 17 years. Sequencing technologies have advanced exponentially, and we’ve learned many lessons in how to manufacture vaccines at scale. Consider how quickly the Ebola vaccine seemed to arrive. Surely we should be able to do the same for the coronavirus?

If you dig a little further though, you realise it’s not going to be that easy. The Ebola vaccine actually took decades to develop (the 2014 outbreak just added extra urgency). It involved a lot of patient, dedicated work by researchers toiling for years in obscurity, moments of real individual courage, plus a lot of good luck and fortunate timing. It’ll probably be made into a movie one day. You should read the whole story. On paper though, it should never have happened, and while that might be disheartening for those hoping for a quick coronavirus miracle it’s also a reminder that when it comes to understanding vaccines, it’s better to ignore the latest media frenzy and look at the bigger picture instead.

That picture, on the whole, is one of incredible success. In the last ten years, the vaccine for measles, a far more infectious and deadlier disease than the coronavirus, has saved 14 million lives alone. Every year, at least 116 million babies now receive three doses of the DPT vaccine for diphtheria, whooping cough and tetanus, about 5 million more than in 2010. The cost of fully immunising a child in low-income countries has fallen from $24.50 in 2013 to $18.00 today, and more new vaccines have been approved and deployed in the past decade than in any other in history: 116 low and middle income countries introduced at least one new vaccine, and there have been over 470 new introductions in total.

These vaccines now form the backbone of child and maternal health efforts around the world. The results speak for themselves. In 2010, seven million children died before reaching the age of five. Adjusting for population growth that figure today should be eight million — instead, it’s just over five million a year. While that’s still far too many, it also means there are quite literally, millions of children running around right now who would not have made it a decade ago. This is one of the greatest stories of all time, but it’s a tricky one to tell, because it’s buried in UN reports, and drowned out by dramatic news headlines and Facebook debates about whether it’s safe to vaccinate your child or not.

Which makes it of course, perfect fodder for this publication.

To tell this story we need to go back to a dark wintery night almost exactly ten years ago, to a small town in the Swiss Alps, when two of the world’s wealthiest people stood up in front of a sea of moisturised faces and expensive shoes, and made a $10 billion promise. “We must make this the decade of vaccines,” they said, “one in which the full benefits of immunisation are extended to every child on the planet.” It was the largest charitable pledge ever made to a single cause, and the announcement was celebrated by media outlets across the world. Vaccines are a miracle. He’s changing the world again through another cheap technology. A tremendous opportunity for transforming global health.

Image credit: World Economic Forum/Flickr

Today, the optimism of that moment seems to belong to a more innocent age, before the full fury of the backlash against the global elites had set in. It was a time before fake news, weaponised narratives, populist presidents and the entry of the word anti-vaxxer into our vocabulary. Back then, international gatherings of the world’s best and brightest still seemed to be able to get things done. Within two years of the announcement, a Global Vaccine Action Plan (GVAP) had been endorsed by 194 Ministers of Health at the World Health Assembly. It was one of the largest and most ambitious public health initiatives ever launched, the first ever global framework for delivering universal access to vaccines.

It piggybacked off the efforts of something called Gavi, the Vaccine Alliance, established at the turn of the century to make newer vaccines accessible to the poorest countries. Unlike Gavi, GVAP didn’t have any dedicated funding or political teeth, but what it lacked in resources, it made up for in vision, reinforcing immunisation as a global priority. The number of countries with technical vaccination advisory groups nearly tripled, from 41 in 2010 to 114 in 2018, and a raft of regional and national vaccine action plans were developed; all designed to align with the GVAP, opening avenues for funding bodies and building the political case for vaccination among national decision-makers.

It might seem strange that such a case needed to be built. After all, vaccines represent incredibly good value for governments. According to the World Health Organisation, every $1 spent on vaccines returns $16, and when considering broader economic and social benefits, the return on investment is 44. They’re highly effective, extremely safe, mostly affordable and not vulnerable to resistance, like antibiotics. Vaccines are so successful that it’s easy to take them for granted. They suffer from a similar curse to other public goods such as clean energy or education: while they’re a great investment, they require a lot of money upfront and strong regulatory support. If left up to market forces they would never reach the general public.

To move from clinical trials to large scale testing for example, you have to build special facilities and conduct trials on thousands of people in several countries. This can cost hundreds of millions of dollars. Only big pharma, large foundations or governments have the financial bandwidth to support that. Manufacturing is also a problem. There are only a few places in the world that can produce vaccines at scale, and they have serious backlogs. These activities can take a decade or more, and even when a new vaccine is ready for deployment, regulatory hurdles can add years. Distribution is difficult too: a ‘cold chain’ is required to keep vaccines at the right temperatures to be safe and effective. Some are sensitive to freezing, some to heat and others to light. This can be particularly tricky in rural areas or if there is not a constant electricity supply.

The world hasn’t stood still in the last decade either; accelerating urbanisation, migration and displacement, conflict and political instability have combined with vaccine unaffordability in middle income countries and the emergence of what public health officials now call vaccine hesitancy, and the rest of us call the anti-vaccination movement. The challenges, in other words, have been formidable. The result was that Gavi and GVAP didn’t meet their goals of extending the full benefits of immunisation to all children on the planet.

They gave it a pretty good crack though.

A young boy shows off his certificate of vaccination following the launch of an unprecedented vaccination campaign in 2015 by Médecins Sans Frontières, to immunise 220,000 children in Central Africa against nine different diseases. Image credit: MSF

Existing vaccines all received significant boosts. Many of them were for diseases most people don’t think about, or have never even heard of. The rotavirus vaccine for example, protects against the deadliest form of diarrhoea in young children, and is now available in 101 countries, and coverage increased from 9% to 35% between 2010 and 2018. Coverage of the vaccine for rubella, a viral disease that causes fetal death or defects in the brain, heart, eyes and ears, increased from 35% to 69% during the same time period, and the disease was eliminated in 81 countries. The proportion of children getting the vaccine for Hib, a bacterial infection that can cause deafness, brain damage and death increased from 40% to 72%, and it’s now available in 191 countries.

Ever heard of Japanese encephalitis? It affects people in Southeast Asia and the Western Pacific, causing inflammation of the brain. There’s no existing treatment, it kills 20–30% of the people who contract it and even if you do survive, there’s a 50/50 chance of permanent brain damage. The vaccine was added to Gavi’s funding list in the first half of the decade, and in 2015 Laos became the first country to add it to its immunisation schedule. Nepal, Myanmar, Cambodia, and Indonesia followed in quick succession, and by the end of 2018, over 18 million children had been immunised.

Or how about pneumococcal disease, the leading cause of pneumonia, killing more children than any other infection in the world. It also causes meningitis, which can leaves permanent disabilities, sepsis, which can lead to amputation or death, and ear infections, which can result in permanent deafness. In 2010, pneumonia killed 1.12 million children under the age of five in a single year, an almost unimaginable number. At the start of the decade a new vaccine, PCV13, was introduced, increasing the number of bacterium strains from seven to thirteen. By 2018, that vaccine reached 48% of children in the world, and the number of deaths that year decreased to half a million. Organisations like Medicines San Frontieres played a major role in this by persuading the big pharmaceutical manufacturers to drop the prices. Initially, it cost $100 for a single dose, but following a long campaign, Pfizer and GlaxoSmith Kline reduced the price to $3.30 in 2016, and then again to $2.90 in 2019.

Then there are the diseases you definitely have heard of. Between 2010 and 2018, coverage for the Hepatitis B vaccine increased from 73% to 84%. The vaccine for yellow fever, one of the many mosquito-borne diseases, was included in the immunisation programmes of 36 of the 40 countries at risk in Africa and the Americas, and coverage increased from 39% in 2010 to 49% in 2018. At the start of this decade, there were still 31 countries at risk from maternal and neonatal tetanus, which has a fatality rate of 70–100% among newborns. As of September 2019, that number had dropped to 12, and the number of children dying had halved.

It wasn’t just developing countries that benefited. The vaccine for human papillomavirus (HPV), a leading cause of cervical and other types of cancer, is now being delivered to adolescent girls in 90 countries. In England, the number of infections in sexually active 16 to 18 year old females has dropped to zero, compared to over 15% when the vaccination programme began in 2008. Scotland’s HPV vaccine program has seen a similarly positive trend, and Australia is on track to become the first country to eradicate cervical cancer with the next few decades.

Source: OurWorldinData (2020)

Are your eyes glazing over yet?

The problem with this blizzard of statistics is that while it proves we’ve saved millions of people and improved the quality of life for many more, it’s hard to connect with numbers on a page. That’s why it’s important to remind ourselves that there were real people behind these victories, a global community of tens of thousands of scientists, logistics suppliers, nurses, reporters, grey bureaucrats and colourfully dressed activists, people on bicycles and scooters and donkeys, funding agencies, advanced research hospitals and rural clinics. You don’t ever hear about these people in the news, but they’ve been out there for the past decade, working every day to save lives.

People like Madeleine, a nurse in the DRC, who delivers vaccines on foot across Kinshasa, using solar fridges to keep them cold during frequent power cuts, and Masculin, a town crier in Haiti, who walks around villages on Sundays announcing information about upcoming vaccination sessions. Volunteers like Jonathon, from Zambia, who realised help was needed after a cholera outbreak in 2018, and became heavily involved in administering oral cholera vaccines, and social workers like Feria, who fled violence in Syria to find shelter at an Iraqi refugee camp with her two young sons, and started volunteering as a polio vaccinator. “After what all these children have gone through they should not be sacrificed.”

It’s not just those on the frontlines. In the background are scientists like Dr Shrijana Shrestha, Dean of the Patan Academy of Health Sciences in Nepal, who is leading studies into the real life impact of the pneumococcal vaccine. Cold-chain specialists like Jahongir Mirzakarimov, from Uzbekistan, who’s been working as a vaccine warehouse manager for almost 40 years. “I think of vaccine safety 24 hours a day, 7 days a week. When I wake up and go to sleep, I always ask myself the same questions: whether the refrigerators are working, whether the electricity is on or if it has been cut off. It has never occurred to me to do any other work.”

Thanks to these and many others, it was a great decade for vaccine innovation. Improved vaccines were released for typhoid and HPV, and brand new ones for diseases that weren’t previously on the schedule. New delivery technologies, such as needle-free administration, blow-fill-seal primary containers and improved vaccine vial monitors were licensed and approved by the WHO. In 2012, a revolutionary vaccine for Meningitis A became the first to gain approval for use outside the cold chain — as long as four days without refrigeration and at temperatures of up to 40°C. By the end of 2018 it had reached more than 300 million people in 22 African countries in the meningitis belt. The impact was dramatic: the number of recorded epidemics dropped to their lowest-ever level.

Supply chain management changed too. In 2013, the WHO began stockpiling a new oral vaccine for cholera. At the time, Cholera epidemics were a common occurrence, yet the use of vaccines was low, meaning manufacturers had little incentive to increase supplies, keeping prices high. The massive orders for the stockpile though, dropped the prices, and meant the vaccines could arrive in countries within days. Over the next six years almost 60 million doses were shipped worldwide, and 104 cholera vaccination campaigns were run in 22 countries. By 2018, the global incidence of cholera cases had decreased by 60% and some of the world’s major cholera hotspots, including Haiti, Somalia and the DRC, had started making real progress in preventing and controlling a disease that at various time in human history has been called “The Great Death.”

Exciting progress was also made in vaccine development for other diseases. A malaria vaccine is currently undergoing pilot studies in three African countries, a tuberculosis vaccine has had success in clinical trials, efficacy trials are underway for two HIV vaccine candidates, and while progress towards a universal influenza vaccine has been slower, several candidates are in early clinical evaluation, and key priorities for future research have been identified. Typhoid and Ebola vaccines are beginning to be used in the field, and vaccines are in the pipeline for major killers such as respiratory syncytial virus, the most common cause of respiratory and breathing infections in children, causing an estimated 3 million hospitalisations and the deaths of 60,000 children under five every year.

Of course, it wasn’t all good news. There were setbacks too. In 2015, the world’s first dengue vaccine, Dengvaxia, was licensed and distributed in the Philippines. After more than 800,000 children had been vaccinated, the drug’s manufacturer announced that it might actually make dengue worse if given to those without prior exposure. Two children died, causing a major scandal. Outrage was amplified via Facebook, and stoked by politicians during election season. Public confidence in vaccine safety plummeted, the vaccination program was suspended, and within a year, dengue cases had shot up by 85%. The fall in trust also affected public willingness to accept the measles vaccine, prompting measles outbreaks, with 25,000 new cases and 355 deaths by March 2019.

Social media campaigns also disrupted MMR vaccination efforts in southern India, collapsed HPV vaccination efforts in Japan, provoked false scares of vaccine poisoning in Pakistan, and undermined vaccination programmes in Indonesia. Measles cases have rebounded in all six of the WHO regions. Global incidence doubled from 2017 to 2018; and then doubled again in 2019. In Europe, there’s been an 80-fold increase in reported cases in the last four years, and 37 deaths were recorded in the first six months of 2019. The Americas were certified as having eliminated measles in 2016, only to suffer outbreaks in multiple countries starting in 2017 and a loss of certification in 2018. Thousands of cases have been reported in Venezuela owing to the political and economic crisis, and have also appeared in Brazil, Colombia and Ecuador, and thanks to the tireless efforts of anti-vaccination groups, the United States is now at risk of losing its measles elimination status too.

Anti-vaccine protesters outside an event in Farmingdale, New York, in September 2019. Image credit: Steve Pfost/Newsday RM via Getty Images

The worst hit though, has been the Democratic Republic of Congo, where a current outbreak has killed 6,000 people, far more than have ever been killed there by Ebola. The virus has sliced through the country because so many of its people have not been protected. While average global coverage for measles is 86%, in the DRC it’s less than 50%. The epidemic has been aggravated by malnutrition, weak public health systems, suspicions borne of cultural beliefs and ongoing insecurity. Millions of people have been displaced by violence and are without any health care at all. Disease and bullets it turns out, are not separate problems but closely intertwined.

That said, the story of vaccines in this past decade is still an overwhelmingly positive one. The optimism of those early years wasn’t misplaced after all. Vaccines have been one of the biggest success stories of modern medicine — a complex, tangled mess of science, economics, politics, manufacturing, trade, and culture that somehow seems to work. The WHO estimates that vaccines prevented at least 20 million deaths in this decade, and many millions more were protected from suffering and disability. Successful immunisation programmes also enabled national priorities, like education and economic development, to take hold.

The goals that were set out back in 2010 are still within reach. In the decade ahead, immunisation could become not only one of the biggest success stories of modern medicine, but the greatest human success story ever. Technically, this is entirely feasible. In a world where vast social inequalities create unrest and disturbing instability, the game-changing power of universal coverage with safe, protective, and cost-effective vaccines deserves a much higher profile. And they should also give us hope as we move forward into the future, not just for public health, but for other problems that we face, like climate change, migration and inequality.

That’s something worth keeping in mind the next time you hear about a disease outbreak, or get into an argument on Facebook. Humans aren’t so bad, after all. You just need to know where to look sometimes.

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