First isolated in Malaysia in 1999, Nipah virus rapidly went from unknown to endemic in Bangladesh, which has seen an outbreak almost every year since 2001 (see Nikolay et al., pages 1804–1814) . Large gaps remain in our understanding, however, such as how the virus crossed India to spark an epidemic in Kerala on that country’s southwestern coast in 2018.

Several life-threatening viruses have been identified for the first time in the 21st century, including the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses. An association between Zika virus infection during pregnancy and microcephaly came to light only in 2015. Once seemingly confined by public health measures to sporadic episodes in rural areas, Ebola virus disease broke free in 2014, reaching urban centers and killing more than 11,000 people. Like all epidemics, it drew resources away from other critical health care needs and left a legacy of distrust and disconnection.

The World Health Organization (WHO), in conjunction with global experts, has drawn up a list of nine known infectious diseases and one unknown (Disease X) in a “Blueprint” for research and development (see box).1 These infections have the potential to cause public health emergencies, and we lack the tools to diagnose, treat, or prevent them. The world is therefore particularly vulnerable to these infections, and yet they’ve been neglected in research and development.

Blueprint Priority Diseases.* Given their potential to cause a public health emergency and the absence of efficacious drugs, vaccines, or both, there is an urgent need for accelerated research and development for the following diseases: • Crimean–Congo hemorrhagic fever (CCHF)

• Ebola virus disease and Marburg virus disease

• Lassa fever

• Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS) coronavirus

• Nipah and henipaviral diseases

• Rift Valley fever (RVF)

• Zika

• Disease X * From the World Health Organization.2 Known diseases are listed in alphabetical order.

The list is not exhaustive, and many infections pose a major threat. Yellow fever spread to Asia for the first time in 2016, and although it did not establish itself there, that continent could be at a very real risk: the vector is there in large, dense cities with nonimmune populations. The growing links between Africa and Asia increase the chances of future spread. It is sobering to imagine a yellow fever epidemic in a big Asian city. Though there is a highly effective yellow fever vaccine, the manufacturing capacity (and thus availability) is limited. Influenza, also not on the WHO list, remains a major seasonal problem every year and a perennial pandemic threat for which we still have limited countermeasures.

New patterns of viral emergence and spread are being driven by ecologic and sociologic changes, such as climate change, migration of vector species to new areas, changing interactions between people and animals, increasing connectivity between communities, more and faster travel, urbanization, and political instability and conflict. Our preparations for epidemics must keep pace with such changes.

The WHO remains the global resource for preparing for and responding to epidemics, and its Health Emergencies Program has made much progress since its launch in 2016. In addition, the Centers for Disease Control and Prevention, nongovernmental organizations such as Doctors Without Borders, and many other groups have long played invaluable global roles. What is lacking are clear definitions of the relationships among countries, the WHO, and organizations engaged in epidemic preparedness and response.

Declaring an emergency, the WHO’s responsibility, is a judgment call. Sometimes an outbreak turns out to have less impact than predicted. But instead of criticizing the WHO for being too quick to declare a pubic health emergency of international concern, as many people did at the time of the 2009 influenza pandemic, we should applaud quick and decisive public health action, which will often prevent a true crisis. Action comes with risk, but we should never underestimate the risk of inaction.

A consolidated approach to combating viruses requires sustained investment. It is right and necessary to use public money to secure global public health, and yet there remains a shortfall in funds even for the current Ebola outbreak in the Democratic Republic of Congo (DRC). We need more innovative approaches to funding this essential work — approaches that render investments by governments and businesses less risky. CEPI (the Coalition for Epidemic Preparedness and Innovation) and Gavi, the Vaccine Alliance, along with national funding agencies and philanthropic organizations, are leading the way by, for example, ensuring that critical research and development are undertaken and making commitments to purchase drugs and vaccines in advance of any epidemic in order to create incentives for pharmaceutical companies to target certain diseases.

A more productive, integrated approach to research would encompass disciplines such as context-specific social science, clinical and data sciences, and genomics and involve pursuit of innovative study designs and improved regulatory pathways. If trials of diagnostics, drugs, and vaccines became routine parts of responses to epidemics, with open multiyear and multicountry protocols prepared in advance, we could prevent potential lifesaving tools from being left to gather dust on shelves.

Effective prevention and response require strong public health systems that provide equitable, universal access to high-quality health care. Effective health care cannot be available if health care workers are not protected. In every outbreak, health care workers have died. Here, infection control and vaccines can make all the difference, allowing people to be treated without putting caregivers, nurses, doctors, and support staff at unacceptable risk.

Unfortunately, infection is not the only danger. In an increasingly fragmented and unstable world, armed conflicts occur frequently, and they significantly increase the risk of infectious disease outbreaks, which in turn exacerbate populations’ panic and fear. Conflicts fuel disease transmission as people try to move, often in secret, in order to escape — which can make providing care safely all but impossible.

Northeastern DRC has been tragically unstable for more than 20 years, and the devastating impact of that instability became evident when an Ebola outbreak began there in August 2018. Despite heroic efforts, it may be impossible to contain this outbreak as long as violence repeatedly cripples the public health response led by the DRC Ministry of Health, the WHO, and other partners. And every day the epidemic continues, the risk of a national and regional health disaster grows.

People face similar insecurity in many other places around the world: Yemen, Syria, and Venezuela come immediately to mind. A serious outbreak in any of these countries would be extremely challenging; more than one outbreak might prove too much for the world to handle. We therefore need a profoundly different approach when epidemics flare up in highly unstable regions.

The German government prioritized international epidemic preparedness throughout its presidencies of the Group of 7 (G7) and Group of 20 (G20) industrialized countries. As the host of the annual Munich Security Conference and a member of the United Nations Security Council, Germany is in a strong position to lead efforts to secure global health in insecure situations.2 Facing this challenge will require new approaches to resolving tensions within and between countries, local communities, armed factions, groups of health and humanitarian workers, and national and international security forces. Peace negotiators with experience in conflict resolution are needed in public health now. Without their skills, potential pandemics will fester unchecked in vulnerable regions of the world, leading, sooner or later, to catastrophe.

One further change can better prepare us for future epidemics: we have to expect them. The last entry in the WHO’s list of prioritized infections is “Disease X.” Nipah was Disease X until 20 years ago; SARS and MERS were also Disease X in their times. Twenty years before that, it was HIV/AIDS. It is the disease we don’t know yet, emerging somewhere in the world, barely noticed until it can no longer be ignored.

There is no justification for closing our eyes to such threats, hoping we’ll be safe, and then panicking when we realize we’re not. Nor can we treat each episode as a discrete one-off event. With the world more connected than ever, we all share the responsibility to be ready for inevitable disease outbreaks. People around the world should be able to have confidence that epidemics are being averted and that if they do face a public health emergency, their country and the global health community will be ready to stop it.