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- Herausgeber: Icon Books
- Kategorie: Wissenschaft und neue Technologien
- Serie: Hot Science
- Sprache: Englisch
'A book that couldn't be more timely, providing an accessible introduction to epidemiology.' Kirkus A compelling and disquieting journey through the history and science of epidemics. For centuries mankind has waged war against the infections that, left untreated, would have the power to wipe out communities, or even entire populations. Yet for all our advanced scientific knowledge, only one human disease - smallpox - has ever been eradicated globally. In recent years, outbreaks of Ebola and Zika have provided vivid examples of how difficult it is to contain an infection once it strikes, and the panic that a rapidly spreading epidemic can ignite. But while we chase the diseases we are already aware of, new ones are constantly emerging, like the coronavirus that spread across the world in 2020. At the same time, antimicrobial resistance is harnessing infections that we once knew how to control, enabling them to thrive once more. Meera Senthilingam presents a timely look at humanity's ongoing battle against infection, examining the successes and failures of the past, along with how we are confronting the challenges of today, and our chances of eradicating disease in the future.
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Veröffentlichungsjahr: 2020
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viiFor my parents Amirtha and Sivam, husband Ian, and son Reuban
ABOUT THE AUTHOR
Meera Senthilingam is a journalist, editor and public health researcher specializing in global health and infectious disease. She has worked with multiple media outlets including CNN and the BBC, and research institutions including the London School of Hygiene and Tropical Medicine and the Wellcome Trust.
CONTENTS
INTRODUCTION: ROOM 911
Every outbreak has its source, its origin, and its index case. It has a place and person where it all began and where history was made. In 2003, the outbreak was Severe Acute Respiratory Syndrome, SARS, which went on to become a global pandemic, a public health emergency of international concern – and it began with a doctor and a popular tourist hotel.
On 21 February, Dr Liu Jianlun checked in to room 911 of the Metropole hotel in the urban area of Kowloon in Hong Kong. Liu was in town for a family gathering, but was tired after an exhausting few months at the hospital where he worked in Guangzhou, China. A sudden outbreak of a pneumonia-like infection had struck the port city of Guangzhou, with the wider province of Guangdong seeing more than 1,500 cases since November the previous year. Liu himself hadn’t been feeling well on his departure, but had persevered with his journey. Once in town, he chose to explore, as the city had changed since his last visit. But by the next day, 22 February, he was too ill to continue, xiiexperiencing a fever, shortness of breath and low oxygen levels. He admitted himself to the nearest hospital, Kwong Wah Hospital in Kowloon, where he would die nine days later.
For the virus that killed him, Liu had been the vessel as it embarked upon a global journey. In Hong Kong alone, 1,755 people were infected with the same virus and by July 2003, less than five months later, more than 8,000 people were infected across 32 countries and administrative regions worldwide, of whom more than 810 died.
Called to the scene in Kowloon to check on the ‘very unusual patient’ was Professor Yuen Kwok-yung, Chair of Infectious Diseases at Hong Kong University and a physician at Queen Mary’s hospital on the Hong Kong Island side of the city. ‘The patient was very sick and they were already putting up all the infection control measures,’ said Yuen. Liu’s brother-in-law, a Hong Kong resident, was soon admitted to the same hospital with similar symptoms, having come in contact with Liu (now known by all involved as the ‘index case’, the case that brought the infection to the attention of health authorities). Both patients were originally diagnosed with mild flu of unknown origin and given medication accordingly, but to no effect. This opened up a mystery for Yuen’s team to solve.
In the hospital Liu had been working at in Guangzhou, more than 100 medical staff had become infected while treating patients, which Yuen describes as very surprising. ‘Usually influenza is easily controllable, with masks for example,’ said Yuen. ‘But this was not.’ A lung biopsy from Liu soon revealed something else was at play, a previously unseen disease. It would become known as Severe Acute Respiratory Syndrome (SARS), part of a family of viruses xiiiknown as coronaviruses, which include the common cold. SARS had originated from an unknown animal, though bats are suspected to have transmitted the virus to the civet cat, which then spread it to humans. The challenge to control the virus began instantly, as Liu’s night at the hotel had made this a global race. The virus was already in bodies and on planes headed to countries as far apart as Singapore and Canada, which would each see over 200 cases.
There was no vaccine or treatment for the disease. Instead, extensive global surveillance and coordination to quarantine cases and trace their contacts enabled the outbreak, now considered a pandemic, to end five months later.
But the memory of SARS was overshadowed at the end of 2019 by a viral relative that would wreak greater havoc across the planet. A new coronavirus emerged at a seafood market in the city of Wuhan, China, again from an unknown animal source, infecting over 9,800 people and killing over 210 in less than one month. The disease, named COVID-19, caused fever, tiredness and a dry cough and caused some people to have difficulty breathing, or worse, with the elderly being the most severely affected; it reached nineteen countries during that first month. The majority of cases, though – more than 9,700 – were in China, which experienced rapid spread and saw cases reported in every province within weeks, though one province, Hubei, remained the epicentre.
The city of Wuhan was put on lockdown, major airline operators cancelled flights into China, tourists in the country at the time were repatriated by their respective governments, borders were closed to Chinese nationals and airport checks were put in place across the world. Mobility was put on pause and the WHO warned of stigma emerging against the Chinese population.
xivBut China and the world had learned from SARS: health systems had strengthened significantly and the Chinese government was ready to do whatever it took to stop another contagion, including building additional hospitals in a matter of days as the country’s own health system became overwhelmed. By March, case numbers topped 100,000 (more than 80,000 of which were in China), with over 4,000 deaths, but this period was also a turning point in the outbreak, both within and outside of China. China saw the number of new cases reported each day beginning to decline, though controversy surrounded the transparency of officials and the changing definition of what constituted a case.
As China experienced a decline in new cases, however, new focal points emerged in other parts of the world, most notably in South Korea, Italy and Iran, which each saw several thousand cases by early March. Seventy-two countries were now reporting cases and a cruise ship named the Diamond Princess was forced to dock off the coast of Japan to quarantine its passengers, among whom 706 cases were reported, forcing countries to send repatriation flights to collect their citizens. The WHO instructed all countries to ensure adequate preparedness plans were in place, ensuring they were ready to manage imported and locally transmitted cases, with laboratories capable of confirming probable cases and hospitals prepared to isolate and treat patients accordingly.
More flights were cancelled and quarantine zones put in place; some borders were closed; health systems were restructured. Meanwhile, multiple research efforts were underway to develop a vaccine and therapeutics. Experts believed the decline in China should become possible elsewhere once a peak was reached and the virus could be contained. xvEventually. Meanwhile, the world awaited the arrival – and spread – of the virus in their region.
But one thing is certain: these coronavirus cousins have held the world to account. SARS set a global health precedent, teaching us that when it came to infections, there were no longer any borders or limits and the world needed to work together to fight, or ideally prevent, a worldwide pandemic. Almost twenty years later, COVID-19 showed we still weren’t ready to do this as efficiently as we might, enabling a local outbreak to spiral into one significantly affecting the world at large.
1
TWENTY-FIRST-CENTURY INFECTIONS
Novel virus infects thousands in one day.
Measles causes national emergency.
More Ebola cases reported in the Democratic Republic of Congo.
Seasonal ’flu predicted to cause thousands of deaths this winter.
In this day and age, outbreaks are daily news across most regions, available to read about soon after they occur, reaching the mainstream when the cases, disease, or location are big enough. Today we face a plethora of potential infectious adversaries: new and ancient, unknown and reborn. But regularity and familiarity make an infection no less feared when it arrives on one’s doorstep. Outbreaks continue to elicit panic in the majority. Viruses, bacteria, fungi, parasites, and other microorganisms harbour the ability to penetrate human barriers with ease and break through defences with the sole purpose of attack, even when they are being watched closely.
2For centuries, humanity has fought contagion, working hard to catch, treat or prevent disease, but success has been limited, short-term, and any progress met with an onslaught of new arrivals – or the same enemy in new armour. The war continues today, as only one battle has truly been won to date, against smallpox, an ancient virus once feared throughout the world and thought to date back at least 3,000 years to the Egyptian era. The virus killed 300 million people in the twentieth century alone and its end is considered to be the biggest achievement in international public health. But most experts know another victory of this sort will be challenging, most likely impossible, as smallpox was a comparatively straightforward target. Multiple efforts beforehand had failed: first against hookworm, then yaws, then malaria, and current efforts to end two other diseases – polio and Guinea worm – are lagging decades behind.
The success of smallpox, however, set the world on a new trajectory where a disease could be destroyed, in this case using immunization as a valuable and strategic weapon. It’s unlikely we will rid the world of all infections, but after the success of smallpox, there is at least motivation to try.
The beginning of the end
When one imagines an outbreak, one thinks of a disease surging through a population, knocking down everyone in its path with extreme, debilitating and often fatal symptoms. This was the reality of smallpox, known to some as ‘the scourge of mankind’, making it a priority to protect the world against it.
The virus behind the disease, variola, invaded almost anyone it came into contact with, causing a fever followed 3by a distinctive rash. Fluid-filled spots containing the virus would take over the body, bringing death to many and leaving survivors scarred. The disease killed approximately three out of every ten infected. The world was officially rid of smallpox in 1980 after an eradication effort that had begun thirteen years prior. But it could be said that the path towards ending the disease began almost 200 years earlier, on the arm of an eight-year-old boy named James Phipps.
Phipps was the son of a gardener who just happened to work for Edward Jenner, an English physician and scientist who would come to be known as the father of immunology. For years, Jenner had heard rumours that milkmaids exposed to cowpox become naturally protected against smallpox. The cowpox virus closely resembles variola and word had spread that humans who came into contact with cowpox developed a milder disease they soon recovered from, which left them immune to its more fatal relative.
With experimentation being more rogue and unrestricted at the time, Jenner decided to test the theory that cowpox could be given deliberately to humans as a means of protection – and Phipps would be his proof. In May 1796, Jenner found milkmaid Sarah Nelmes, a recent cowpox patient. Nelmes apparently caught the virus from a cow called Blossom (whose horn is now on display in Jenner’s house in Berkeley, Gloucestershire; her hide is kept in the St George’s Medical School library in Tooting, south London). Jenner sampled the virus lurking in Nelmes’s lesions and used it to inoculate young Phipps. The eight-year-old went on to develop a mild fever and loss of appetite but recovered after ten days. Two months later, in July, Jenner exposed Phipps to smallpox and no symptoms or lesions developed. He appeared to be protected. Jenner went on to successfully repeat this on more 4people over the following two years, again poor labourers, their children or inmates of workhouses. In the coming years, however, people across all classes were inoculated and vaccination (after the Latin for ‘cow’) soon became widely accepted.
The idea that our bodies could be protected against infection, using an infection, was born and smallpox would eventually become the target of a global defence, creating a biological shield that would one day span across the planet. But the road to get there would be far from straightforward.
Ending smallpox
An intensified programme to eradicate smallpox began in 1967, when there were still more than 10 million cases occurring across 43 countries. By this point, the disease had already been eliminated – meaning it had stopped spreading in a particular geographical region – in North America and Europe, following an initial effort to end the disease, launched by the World Health Organization (WHO), in 1959. The programme had focused on vaccinating the masses and the target had been to get at least 80 per cent vaccine coverage in every country in order to reach the herd immunity threshold, a level of coverage where the chances of unvaccinated people getting the disease is extremely low. (The threshold varies from one disease to another, based on how easily the infection transmits between people.) But South America, Asia and Africa continued to see millions of cases, while Europe and North America were still seeing imported cases, particularly as air travel rose in popularity. Governments across all regions were therefore motivated to end the disease, which would require a change in strategy.
5‘Little attention was paid to the reporting and control of cases and outbreaks, which we felt were the most important things,’ the late Dr Donald A. Henderson told the WHO in a 2008 interview. Henderson, who died in 2016 at the age of 87, had led the international effort to end smallpox despite criticism that it was an impossible task. He had emphasized that simply vaccinating everyone against smallpox, or any disease, was not always feasible and therefore should not be the sole strategy. Public health teams needed to understand the severity of the situation – how many were affected and where – to better target their resources as well as to contain those infected to stop them spreading the disease further. ‘We made a very strong point about the need for surveillance of cases and their containment,’ he said.
Epidemiologist Dr William Foege soon implemented a surveillance and containment strategy under Henderson’s leadership and significant reductions were quickly accomplished. For example, Foege’s team used limited resources to focus solely on outbreak-affected areas when working in eastern Nigeria in 1967, identifying cases and vaccinating everyone within a defined radius of an outbreak, known as ring vaccination. This curtailed the outbreak within five months, despite just 750,000 people of the 12 million people living in the region receiving the vaccine.
The method was proven to work again and again and was simply much more efficient than trying to reach everyone, says Dr Donald Hopkins, who led the effort to control smallpox in Sierra Leone in 1967. The disease typically affected 5 per cent of a population at most at any one time, Hopkins explains, so the aim was to identify that 5 per cent and focus efforts there. Using this approach, Hopkins’ team saw results within months in Sierra Leone, and within a few years in the 6West African region as a whole, despite the region having the worst infrastructure of any they were working in globally.
The situation was much more difficult in populous India, Hopkins notes, as four years after success in West Africa, teams were still failing see an impact there. Government teams set out to visit every household in the country in the space of ten days in 1973 to identify the true extent of cases and stop the disease spreading more quickly. Some states were found to have twenty times more cases than previously reported. Once this was known, resources were deployed with greater accuracy and India reported its last case of smallpox about one year later. This surveillance-based approach has since become the backbone of outbreak control.
‘The concept was that if we could discover the cases more quickly than before, the containment teams could interrupt the chains of transmission,’ Henderson told the WHO, explaining teams could then break those chains by vaccinating possible contacts in areas where there were cases. Additional factors further aided the success of the global eradication campaign: for example, community teams ventured out to people rather than waiting for them to come to health facilities, meaning they reached everyone, including the most remote. A further development was the introduction of a bifurcated needle in 1968, a thin metal rod with two prongs that would hold a dose of the vaccine for more efficient injection into the skin. The beauty of this ingenious tool was its simplicity when compared to the jet injectors previously used; it enabled 100 doses to be delivered from a single vial.
But despite these factors coming together to bring immediate progress in reducing cases, the road to eradication took twelve years, with societal and political elements coming into play, such as civil wars, extreme weather, poor 7infrastructure and, importantly, convincing people the vaccine was safe. As these hurdles were overcome and cases of smallpox decreased, the need for resources in order to find the remaining cases increased. The cost per case rose significantly as teams travelled farther and wider to find the final few. But they did find them.
On 26 October 1977, experts found and isolated the last case of naturally occurring smallpox in 23-year-old hospital cook Ali Maow Maalin. Maalin, from Merca, Somalia, had worked as a vaccinator in the smallpox programme, yet had avoided the vaccine himself due to a fear of needles. The virus caught up with him as he helped direct a driver taking two children to a nearby smallpox isolation camp. Nine days later Maalin developed symptoms. He was told to stay home while special teams were sent to vaccinate the households around his location, successfully reaching more than 54,000 people in two weeks. Maalin recovered and smallpox was over. Almost.
Janet Parker, a medical photographer, and her mother were the last official cases of smallpox, in August 1978. Parker is presumed to have contracted the virus at Birmingham University medical school, where research on the virus was taking place. She became ill on 11 August and developed the signature rash on the 15th, but was not diagnosed with smallpox until nine days later. She died on 11 September. Her mother, who had been caring for her, also contracted the disease, but survived. Parker had access to the laboratory where a smallpox specimen was contained, but it is unclear if she was infected by entering that laboratory or by the ventilation system taking the virus from the laboratory to her office in the same block, explains David Heymann, Professor of Infectious Disease Epidemiology at the London 8School of Hygiene and Tropical Medicine, who worked with the eradication programme for two years.
This event instigated a programme of consolidation or destruction of remaining specimens of the virus, explains Heymann. This took place during the Cold War, and countries were offered the choice of giving their smallpox stocks to the United States, to the USSR, or destroying their stocks under a set protocol. Both the US and Russia continue to hold on to the stocks given to them, monitored and handled by the World Health Organization under a WHO agreement set in 1979. The US stock is held at the Centers for Disease Control and Prevention (CDC) in Atlanta and the Russian stock at a research laboratory in Siberia. The two facilities are inspected by the WHO every two years.
Debates on whether these last remaining stocks of smallpox should be destroyed have been ongoing for decades. Research on the virus continues today, following anthrax attacks in the United States in 2001, during which anthrax spores were found lacing mail sent to news agencies and congressional offices. This led to the development of bioterrorism preparedness programmes, which include research on smallpox, looking for better diagnostic tests, antiviral medications and safer vaccines. But gene technology has enabled the smallpox virus to be fully sequenced, meaning that the virus can be reconstructed for research purposes if needed, which some experts, including Heymann, believe removes the need for live virus stocks to be stored. The World Health Assembly, the decision-making body of the WHO, has requested the review of research using the live smallpox virus on multiple occasions, with the 69th assembly calling upon an Advisory Committee to review this in May 2016. At the 72nd assembly in 2019, the committee 9stated that research using the virus was still needed to continue the development of antiviral medicines for smallpox preparedness, so the stocks remain.
Officially, though, smallpox has been eradicated, with Ali Maow Maalin being the last face of the smallpox pandemic that plagued the world for millennia. The eradication laid the groundwork for the routine vaccination programmes now implemented globally, in the WHO’s Expanded Programme on Immunization, protecting children from multiple childhood diseases including measles, polio and tetanus. Could these too be eradicated? Most experts say no, but polio efforts are underway. ‘Even towards the end of smallpox eradication, the senior staff never talked about potential eradication of any other disease,’ Henderson told the WHO.
Smallpox had many factors on its side: the vaccine was heat stable and did not require refrigeration for storage, an invaluable property in the remote, tropical settings in which the vaccine was used; immunization required just a single vaccine dose; and everyone who had the disease could be identified by its distinctive rash and therefore easily isolated and their contacts vaccinated. Other diseases do not have this combination of winning elements; some have just a few, and most only one or two. But as pandemics and global health emergencies increase in frequency, how can teams not hope to at least try to rid the world of some of them for good?
When to reach for zero
Eradicating a disease means permanently removing all traces of its pathogen, be it a virus, bacteria, parasite or any other infectious microorganism. It involves bringing the number 10of pathogens found anywhere on the planet down to zero, then keeping them at bay, forever. As desirable as it may be to achieve this for every disease, the reality is that precise scientific and political criteria are required to even attempt it and very few infections fit the bill. At the moment, the International Task Force for Disease Eradication has identified eight possibilities: Guinea worm, also known as dracunculiasis, poliomyelitis (polio), mumps, rubella, lymphatic filariasis, cysticercosis, measles, and yaws.
The scientific criteria include a disease being epidemiologically vulnerable to attack, such as it not spreading easily, being easily diagnosed, or an infection leading to lifelong immunity in those who survive. An effective intervention must also be available, such as a vaccine or a cure to halt the disease in its tracks. Some evidence must also be available of the disease having been eliminated already in a particular region, demonstrating the possibility of its removal on a wider scale. With the exception of not spreading easily, all of these points applied to smallpox.
Politically speaking, governments worldwide need to care about the disease, its impact, and possible harm; eradication efforts need to be affordable and cost-effective; and complete removal of the disease needs to have a significant benefit over simply controlling the disease long term. ‘The motivations of countries play into it,’ explains Hopkins. In an ideal scenario, eradication efforts would also fit into other health programmes, or vice versa, to provide maximum healthcare benefits to people when they are reached. With all that in mind, experts within the task force identified the above eight diseases that show promise for eradication, but today just two have official programmes in place: Guinea worm and polio, since 1980 and 1988, respectively.
11Yaws, a chronic, debilitating, bacterial infection that affects the skin, bone and cartilage, was among the first diseases targeted for eradication, in the 1950s, as it can be cured with inexpensive antibiotics. But success was limited. ‘That programme really never finished,’ says David Heymann of the London School of Hygiene and Tropical Medicine. ‘I think it just stopped because of lack of engagement of the global community in eradicating it,’ he adds, highlighting that cases were dotted around the globe and typically infected neglected populations, such as the Pygmies of Central Africa. Efforts to eradicate the disease were renewed by the WHO in 2012, but yaws is still prevalent, with more than 80,000 suspected cases in 2018, though just 888 were confirmed using laboratory tests. Fifteen countries remain endemic for the disease, meaning they experience continuous transmission.
Guinea worm is possibly one of the most gruesome diseases you could imagine, where drinking contaminated water leads to the development of a metre-long worm, or many worms, inside the body, which then burst out of the skin one year after infection. More on this disease in chapter 3, but its easy diagnosis, possibilities for prevention through simple interventions to stop people drinking contaminated water, and the economic benefits to be gained from its demise made it a top candidate for eradication soon after the victory over smallpox. The recent discovery of the parasite also infecting dogs, however, has recently brought the idea of eradication into question.
Polio then showed promise as it had an effective vaccine, immunity against the disease was lifelong, and the disease only affects humans, meaning there were no animals to deal with that could act as reservoirs or spread the disease, as is 12the case with malaria, for example. Elimination of polio had also been achieved in the Americas, showing it was possible to stop transmission of the disease. But complete eradication of polio would be far from easy, as the vaccine is not heat stable and requires multiple doses. (More on the successes and struggles to date in chapter 3.)
While these two programmes continue, the World Health Organization also has a number of others underway working to eliminate, not eradicate, diseases such as rabies, leprosy (yes, it still exists), and the blinding eye infection trachoma. ‘In general, elimination doesn’t mean getting to zero, so it’s by definition a much easier target than zero,’ says Hopkins. But it depends on how you define elimination, he points out, be it stopping a disease in an area or reducing levels of the disease to a manageable level. Hopkins believes the important thing is to reduce the greatest amount of suffering. In some instances, this only requires control of a disease, in others its elimination and in a few instances its eradication, which will be difficult and expensive. Each disease is unique and for humankind it’s about knowing your enemy, picking your battles and knowing when to sign a treaty, fight regionally or declare a world war.
This is an emergency
A century ago, from 1918 to 1920, the world grappled with the most severe and deadly pandemic in recent history. An H1N1 influenza virus, thought to have originated from birds, swept across the planet infecting 500 million people – one third of the world’s population at the time – and killing 50 million people, according to the US Centers for Disease 13Control and Prevention. This was the Spanish flu pandemic, in which infections were powerful enough to kill young, healthy adults, not just the elderly and infirm as per regular, seasonal influenza. Striking at a time when vaccines and treatments were not available and a world war was underway, the virus unsurprisingly had devastating consequences as the only weapons to hand were isolation and quarantine along with attempts to promote good hygiene. H1N1 would leave its mark as something to be feared throughout history, ending in 1920 with no clear understanding about how it was stopped.
In 1957, another influenza strain emerged in East Asia, H2N2, triggering a pandemic known as the Asian flu, first reported in Singapore and spreading as far as the United States, killing an estimated 1.1 million people worldwide. Yet another strain, H3N2, began spreading in the United States in 1968, killing a further 1 million people worldwide. These latter two pandemics are lesser known, but their damage was extensive and reminded populations at the time of the damage a new infection, particularly influenza, can do.
In 2003 we saw SARS, a previously unknown virus, surge across an unprotected population to infect thousands across Asia and reach all corners of the globe. Six years later, in 2009, we were reminded of the power of influenza as a new form of H1N1 emerged in Mexico, soon reaching the United States, Canada and promptly the rest of the world. The severity of the pandemic was lower than predicted, but 214 countries globally reported cases and at least 18,500 people died, though some studies show this to be a vast underestimate, with one study by the CDC suggesting fifteen times more people died, an estimated 14284,000. This time the world had antiviral treatments and vaccine technologies as well as international agreements to help countries work together to curtail the spread, but there was a new societal norm to contend with: population mobility. People harbouring the virus were on planes and trains travelling to new destinations before they even knew they were sick, helping H1N1 reach six continents within just nine weeks of it first being reported. (More on this pandemic in chapter 7.)
Most recently, as 2019 gave way to 2020, a novel coronavirus emerged in the populous city of Wuhan, China, infecting more than 100,000 people and killing over 3,500 by early March. Though initially the majority of cases occurred within the country, with transmission aided by its timing during the lunar new year, international spread of the virus promptly became a concern as over 20,000 cases were reported outside of China: across more than 100 countries by this point. Advances in technology meant the virus was identified within weeks and multiple efforts to produce a vaccine, using the DNA of the virus, were soon underway. However, China had to battle its worst outbreak ever and soon after so did many other countries, notably Italy, South Korea and Iran. As a result, air travel was restricted and people the world over were advised not to travel to these countries, while those already there were told by their respective governments and health authorities to leave and self-isolate. Cases from China created hotbeds in other countries, from which people soon travelled to tens of other countries worldwide.
According to the Swedish flight information service Flightradar24, more than 200,000 flights take place globally every day, and the World Tourism Organization recorded over 1.3 million international tourists arriving at borders in 2017.
