The Coming Plague

N 1347, an epidemic of unimaginable ferocity getting worse. Pathogens began circulating struck Europe. People first experienced flu- regularly among humans only after we started Ilike symptoms, but within days painful farming and settled in towns. One reason was swellings developed, which turned black, that we caught infections from our livestock: split open and oozed pus and blood. The Great flu from ducks, tuberculosis from cows. Pestilence, later dubbed the Black Death, swept But crucially, there were enough of us in close across the continent within four years, killing proximity that a germ could always find a new up to half the population. The disease host and keep spreading, persisting among persisted in Europe until the 1700s, always people and adapting to us. circulating somewhere, killing people off. Now we are crowding into cities and We speak of it nowadays as history. In fact, it travelling more, especially within the tropics is more like natural history: infectious disease where pathogen diversity is highest. That plus is part of the ecology of our species. Until globalised trade, migration and climate 1900, and despite considerable competition change reshuffle wildlife, people and from violence and starvation, it was our pathogens. Farms and towns invade the biggest killer, causing half of all human habitats of animals with viruses that can jump deaths. Now, it accounts for fewer than a to us, or to our densely packed livestock, also quarter of all deaths worldwide, most of them booming as demand for animal protein soars. in poor, tropical regions. In rich countries it is Public health experts have been warning only a few per cent. And the toll is falling. for years of “emerging” diseases, which can But we shouldn’t be complacent: plagues go from unknown to epidemic if the pathogen will return. The 1960s notion that infectious mutates or the ecology of its hosts changes to disease was on the way out ended when HIV make its spread easier. And it is viruses that appeared in the 1980s. Since then, many epidemiologists are most worried about. infections like bird flu, SARS and Zika have Bacteria can be deadly, and antibiotic caused alarm. But it took a near-disaster – resistance could mean diseases from the worst ever outbreak of Ebola – to scare gonorrhoea to ordinary bladder infections the inertia out of governments. As a result, become incurable, but work has at least begun we are at last preparing for the inevitable. on new drugs. In contrast, viruses can evolve A clutch of programmes being launched this and spread faster, there are thousands we year will improve our grip on microbial killers. know nothing about, and we have few drugs And the world now has an emergency medical against them. The worst emerging infections response team – which, astonishingly, it never since 2000 have all been viruses. had before. But we aren’t there yet. If a novel None is more alarming than the 2014 virus struck now, we would still be in trouble. outbreak of Ebola in West Africa. The virus For all our high-tech modernity, and in infected 50 times more people than any many ways, because of it, the risk that new previous outbreak, and reached big cities

BRIAN LAROSSA BRIAN infectious diseases will evolve is actually for the first time. As a bat virus still >

The coming plague

A killer pandemic is now more likely than ever. Where will it come from and how can we beat it, asks Debora MacKenzie

25 February 2017 | NewScientist | 29 unaccustomed to humans, it spread fairly slowly, but an even slower international response allowed it to kill more than 11,000 people before old-fashioned methods, like isolating cases and quarantining their contacts, snuffed the outbreak out. There was no other option. We were unable to produce a vaccine in time even though we already had experimental Ebola drugs and vaccines, and their deployment was accelerated, with regulation and manufacture taking months instead of the usual years. Researchers have since discovered that as it spread the Ebola virus was adapting to people, and getting better at transmitting. It almost spiralled out of control in Nigeria. “The world was close to an abyss,” says Tom Frieden, outgoing head of the US Centers for Disease Control and Prevention. To combat the next plague, we will need vaccines, drugs and diagnostic tools – and just as importantly, some way to deploy them effectively. “We do not have that,” says Jeremy Farrar, head of UK medical research agency the Wellcome Trust. But we might if, in the wake of Ebola, we can build on momentum in three key areas: working out what the enemy is, arming ourselves against it and being ready to act forcefully and fast.

KNOW YOUR and his colleagues at the pathogens. They have found dengue and West Nile. Last University of Edinburgh, UK, 984 viruses, 815 of them new November, he reported that the ENEMY reviewed what we know about to science. In the process, they more species a flavivirus regularly First, what should we such viruses. They identified have mapped hotspots of viral infects, the more likely it is to prepare for? “Spotting 37 already able to spread from diversity and trained and infect humans as well. That makes the next HIV or SARS human to human, though equipped local labs to test for the riskiest flaviviruses a clutch of before it strikes is poorly, that could become more viruses and watch for disease. virtual unknowns: Usutu – a bird- virtually impossible,” contagious. These range from borne virus invading Europe – says Ab Osterhaus, head virtual unknowns like o’nyong- Ilheus, louping ill, Wesselsbron of the new Research nyong, an African virus that Predicting risk and Tyuleniy. Center for Emerging Infections causes debilitating joint pain, But which of these viruses should The Global Virome Project 1and Zoonoses in Hannover, to Rift Valley fever, a common we focus on? Some are obvious, wants to go further in learning Germany. “There are too many livestock illness. such as a Chinese virus closely about the enemy, genetically viruses in too many species, That’s just the viruses we know. related to SARS but different sequencing and mapping most of interacting with humans and A project called PREDICT, funded enough that prototype SARS the estimated half-million so-far evolving in unpredictable ways.” by the US Agency for International vaccines won’t work against it. undiscovered viruses in families To narrow the field, he says, we Development, is looking for Others might be identified using we know can infect humans. It need “a detailed understanding of others. In places, mostly tropical, a clue discovered by Kevin Olival reckons it will need $3.4 billion to when, where and how viruses are where humans and wild of the EcoHealth Alliance, who do that over the next decade, and moving from wildlife to people”. mammals interact, the project works with PREDICT. this year it will start canvassing Because, like the historical screens people, their food and He has statistically analysed all for funds. The hope is that plagues, the next big disease is their rodent, bat and primate the available data on the flavivirus knowing what viral diversity likely to be one that has made the neighbours, looking for genetic family, a troublesome lot carried exists and where could provide leap from other animals to us. sequences of viruses in families by mosquitoes and ticks that unexpected insights and spur In December, Mark Woolhouse known to spawn human includes yellow fever, Zika, investment in disease control.

30 | NewScientist | 25 February 2017 ARM YOURSELF THE NINE VIRUSES OF THE APOCALYPSE

Once we know what we are These are the diseases the World Crimean-Congo fighting, we have to arm Health Organization thinks we should haemorrhagic fever ourselves. Finding weapons find remedies for, fast. The first six Found across Africa, Asia and won’t be easy, though. The are its highest priority. south-east Europe, the virus is vaccines that defeated so many invading new territory as its tick infectious diseases in the 20th Lassa fever hosts capitalise on global warming. century were mostly made by This West African virus, It appeared in western Europe in government-owned firms that carried by the common 2010. Infected people generally have didn’t have to turn a profit and produced what Natal multimammate rat, a mild fever but some strains cause 2was needed as a “public good”. In the 1980s, infects 300,000 people severe haemorrhagic disease, with everything was privatised. That was good for a year. Most have no bleeding internally and from orifices, spurring profitable medicines for chronic symptoms, but it can cause from which 30 per cent of people die. conditions. But much medical innovation is diarrhoea and vomiting, then internal now done by small, start-up biotech firms, fluid accumulation, bleeding from Chikungunya which can’t afford to shepherd their products orifices, shock, seizure and coma. A virus spread by Aedes mosquitoes through the “valley of death” – the long, It kills some 5000 people annually. between monkeys and small expensive process of testing for safety and Initial symptoms resemble other local mammals in East Africa, Chikungunya efficacy, and establishing manufacturing diseases, making diagnosis tricky – started causing large epidemics processes and formulations for licensing. Only one reason West Africa was slow to around 2000 and exploded into Asia big pharma companies have the know-how spot Ebola. in 2005, after mutations made it and the $1 billion or so needed to bring a new better adapted to a new mosquito vaccine to market. But vaccines for common Nipah host. In 2014, it invaded the Americas diseases offer little profit; those against a virus This bat virus started and has occurred in Europe. It rarely that might or might not go epidemic are a killing people in 1999 in kills but causes debilitating joint commercial non-starter. Malaysia after pig farms pains, which can persist for months. There have been efforts to bring public good were built near fruit bats, back in. Since the 1990s, new treatments for which dropped half-eaten Zika diseases of poverty, like the meningococcal fruit into pigsties. People A monkey virus that has infected vaccine for Africa, were developed by public- get it from pigs and bats, but it can humans in Africa and Asia for decades, private partnerships between big pharma, also spread between humans. Nipah Zika suddenly entered the Americas in governments and large philanthropies like breaks out sporadically in and around 2013. In 2015, it was linked to a wave the Bill & Melinda Gates Foundation. “But densely populated Bangladesh, of severe birth defects including the momentum fell,” says Farrar. In 2013, causes inflammation of the brain microcephaly. Companies are already government and private research on and has a high fatality rate. working on vaccines but the WHO “neglected” emerging diseases amounted to wants extra research into the virus’s only 1.6 per cent of the $195 billion spent on Rift Valley fever effects on fetal brains. health R&D. Of that, only a fifth was private. Widespread across Africa, Now, because of Ebola, the momentum this virus invaded the Severe fever with may be back. Last May, the World Health Arabian Peninsula in 2000, thrombocytopenia syndrome Organization set out an “R&D blueprint for and could go further. It Flies under the radar – possibly action to prevent epidemics”, which aims to mainly infects cattle and because of its name. The virus, bring all parties together to develop responses is spread by mosquitoes; discovered in 2011, can cause fever before the next plague strikes. Committees are people can get it from mosquito bites and multi-organ failure, killing 12 per being set up to look for solutions to problems or by eating infected beef. Symptoms cent of people it infects. It has been that emerged during the Ebola outbreak, from are usually mild but it can cause found in east Asia, seems to be carried agreed protocols for quickly testing and haemorrhagic fever, which kills in by farm animals, and is spread by ticks. licensing experimental drugs and vaccines, half of cases. A nearly identical virus, called to liability insurance for using experimental heartland, has turned up in the US. products, to contracts ensuring information SARS, MERS and and biological samples are shared. emerging coronaviruses Novel agent But the most important goal is to accelerate These related bat viruses Given the rate at which previously R&D on nine priority pathogens (see “The nine infect a range of mammals unknown or obscure infections have viruses of the apocalypse”, right). Using an and have already emerged suddenly emerged in humans and approach pioneered for malaria vaccines, the in humans twice, resulting other animals, the WHO is leaving a WHO will find out what research is being done, in severe pneumonia: slot on its list for a germ we don’t yet get participants talking and push progress SARS in 2003 and MERS in 2014. know. Research here may include

RIGHT IMAGES ALL SPL towards vaccines, drugs and diagnostic > Both spread from human to human. looking for agents that might explode.

25 February 2017 | NewScientist | 31 tests. Any products must be affordable. That we need health workers close means their prices will be “delinked” from Be ready to the entire population, the cost of developing them, by making sure to act – everywhere, who know where companies are recompensed in other ways. fast to go if something funny is going So far no one knows how that will work, but it on – then labs to test samples, is already being discussed for new antibiotics. With potential and response teams,” says Seth The WHO is not alone in trying to encourage mass killers Berkley, head of GAVI, a global the forging of weapons. In January, the identified, and alliance that helps poor Coalition for Epidemic Preparedness drugs in hand, countries get routine vaccines. Innovations (CEPI) was launched at the World we will be on the Under a 2005 treaty called the Economic Forum in Davos, Switzerland, to right track. But we must also be International Health Regulations, help get experimental vaccines through the 3ready to act fast on a large scale. all 192 WHO member states must “valley of death”. CEPI, which is backed by Paradoxically, that means set up enough surveillance to tell Norway, India, the Gates Foundation and the getting more familiar with the WHO about any outbreak that Wellcome Trust, has commitments of $540 what is normal, so we can spot is serious, unusual or could million and, say organisers, is “on track” to ominous changes. trigger international travel or get $1 billion for the next five years. By then it One problem is that contagion trade restrictions. However, not hopes to have vaccines against Nipah, MERS is exponential: case numbers one world region, even Europe, and Lassa viruses tested for safety and rise very slowly at first, then sky- has done everything the treaty effectiveness in phase II trials. It even wants rocket. “First people complain requires. Africa, home of many to have small stockpiles of the promising that you are putting too much worrying viruses, has done least. vaccines for fast response to outbreaks. effort into a small problem. Later An international collaboration However, no one can afford phase III trials they say you were too slow,” says called the Global Health Security on larger numbers of people. And no one can Sylvie Briand, head of the Agenda is trying to help countries test whether a vaccine works until there is an pandemics department at the fill the gaps – and Ebola has scared outbreak. Those tests may have to be done in WHO. To better predict which many into listening. “There has a hurry once an epidemic starts. outbreaks might take off, the been a change of mindset,” says WHO now has teams looking Briand: watching existing health at the use of “big data”, such risks more closely will help MONEY as combining existing data sets countries spot new ones. MATTERS on climate, vaccination and As global economies become more interconnected, population immunity. It is also contagious diseases and their knock-on effects setting up networks of social Emergency responders spread more rapidly. “Nowadays the biggest risk scientists and anthropologists In addition, the WHO, which from epidemics is economic,” says Ramanan to explore ways to improve has always been a technical Laxminarayan of Princeton University. The 2003 communications among people agency, setting policies by slow SARS epidemic killed 800 people, for example, but swept up in plagues – a major consensus, has reinvented itself cost the world $54 billion in quarantine measures roadblock to rapid response to respond faster in an emergency. and lost trade and travel. The World Bank estimates during the Ebola outbreak. The Instead of independent offices that a flu pandemic as bad as the one in 1918 would first and fundamental problem in different countries spotting lop 5 per cent off world GDP and cause an $8 trillion there, however, was surveillance: emergencies – or not – according recession. The faster we respond to an epidemic, no one spotted the first few cases to their own criteria, the WHO the less expensive it will be. So we must be of Ebola before it spread widely. now has dedicated staff worldwide prepared – and that costs. Who will pay? “To get ready for the big one, who can do standardised One answer may be novel funding mechanisms. assessments of unusual events, Last May, the World Bank launched something new: deploy emergency teams within plague insurance. Rich countries are at risk from 72 hours and scale up quickly. epidemics that start in poor countries. So under the To aid coordination, they are Pandemic Emergency Financing Facility they can answerable to the head office buy insurance against severe flu, coronaviruses like in Geneva, a first for the WHO. s r e

SARS or MERS, filoviruses like Ebola, and diseases t The agency is also working that pass between animals and humans like Lassa. with the World Food Programme

Premiums are based on risk, calculated for the vski Reu/ to set up global supply chains for o fil bank by the epidemiological modelling company o equipment such as masks and Metabiota. If one of these diseases strikes a poor syringes. This year it will launch an

country, money to contain it can be released quickly Ognen Te online course to train emergency from the insurance pot. The bank also sells responders. And it is working “catastrophe” bonds to fund response to a wider Going global: international with the Inter-Agency Standing range of epidemics. flights spread pathogens Committee, a Geneva-based body

32 | NewScientist | 25 February 2017 Plagued by plagues Infectious disease used to account for half of all human deaths before the rise of modern medicine, now globalisation is renewing that threat

Athens Europe, Asia, Africa Europe Worldwide West Africa 430 BC 1347-1351 1665-1666 1918-1920 2013–2016 75,000–100,000 75-200 million 100,000 20-50 million 11,300+ Plague of Athens Black Death Great plague of London Spanish u Ebola Typhus/smallpox? Bubonic plague Bubonic plague Inuenza

1300 1400 1500 1600 1700 1800 1900 2000 Europe, Asia Mexico Asia, Europe Worldwide AD 541-542 1545 and 1576 1817-1824 1980s- 25-50 million 17 million 100,000+ 35 million Plague of Justinian Smallpox First cholera pandemic HIV pandemic Bubonic plague Cholera HIV that coordinates the world’s HOW YOU CAN REDUCE THE emergency responses to war and RISK OF A PANDEMIC natural disasters, which last year expanded its remit to epidemics. In our increasingly crowded, urban, globalised But, no matter how fast you world, a virus will eventually get out of control. detect outbreaks, or how many There are things we can all do to reduce the risks. drugs or vaccines you invent, Bear witness: Inform yourself and do what you you still face the problem of can to spread awareness of the risks, and of the producing and deploying enough responses being devised that desperately need of them to make a difference. support. Politicians control purses, so get tweeting. “You can’t build a vaccine factory Stand up to denialists: Some will say warnings and only switch it on in an about pandemics are a hoax, because SARS/bird emergency,” says Martin Friede flu/swine flu was supposed to kill us all and didn’t. at the WHO. Like standing armies, Here’s your riposte: a lot of people worked hard to production lines and staff need keep SARS contained; bird flu hasn’t gone rogue yet

honing and updating. CACCURI/CONTRASTO/EYEVINE ROBERTO but it’s a few mutations away; swine flu did kill and A possible solution for limited the next flu could kill far more. manufacturing capacity comes funding. “The really big problem Even supplying Prepare: You needn’t be a survivalist to from ongoing efforts to control is appreciating what is at stake,” equipment in a crisis prepare for the panic and disorder likely to attend flu – one pandemic we know for says Berkley. He says a pandemic will be a challenge a pandemic. Most countries have guidelines that sure will come. The flu vaccine is an “evolutionary certainty”. “If recommend stocking a few weeks’ worth of water, is made of a standard, benign flu people understood the risk, they food, medicines, flashlight batteries and such. virus with two new proteins from would want to be sure systems are Learn about the best ways to avoid people who whatever strain is circulating that in place to deal with it. The costs might be contagious. If you run a business, have year stuck onto it to induce of doing that are trivial compared a continuity plan. If you are a public official, check immunity to that strain. The to the cost of ignoring it.” whether your administration has a pandemic plan. vaccine changes every year, We have been jolted out of our If not, check out the WHO’s guidelines. If you speak but doesn’t need new plants complacency, but there’s still a for a health body or organisation, learn about or regulatory approval as the lot to be done. “With Ebola the communications in a pandemic because mistakes package is well tested. “We can world recognised that the largest can be deadly. Hint: trust people with the truth. produce safety-tested vectors at unmanaged risk to the global Keep watch: Countries don’t like to admit they scale, then drop in antigens of economy and security is have infectious diseases: it’s bad for business. interest if a new disease emerges,” infectious hazards,” says Bruce The ProMed global reporting site revealed SARS and says Berkley. “That way, you can Aylward, assistant director- MERS before the governments involved did. Now it build vaccine capacity for a general at the WHO. “Are we has helped launch Epicore. Medical and veterinary pathogen you don’t even know.” prepared for pandemics? workers sign up to it, then when ProMed gets wind That isn’t happening yet. Nor is Definitely not! Are we more of something it asks them what’s happening. it clear if the WHO will get enough prepared? Definitely.” n Replies appear on a web platform that can be set to funds to continue any of this partial or total confidentiality. Wherever you are, if work, especially with a new US Debora MacKenzie is a consultant you meet the criteria, sign up to Epicore. You could president who has opposed UN for New Scientist based in Brussels be the first to spot something amiss.

25 February 2017 | NewScientist | 33