'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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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...
