The Threat of Infectious Disease and the Evolution of the Threat

Infectious disease has been a formidable force in shaping human history. In the times past, most people died from two causes: violence and infectious disease, with deaths from infectious disease being many times more common. Bubonic plague killed between a third and a half of the population of Europe in the Middle Ages, thus changing the course of Europe and the world forever. Smallpox killed half a billion people in the 20th century alone before being finally eradicated in 1982.

Oftentimes more people die from infectious disease than from combat even in times of war. Napoleon started the war with over half a million soldiers and only a few thousand staggered back. Most died from trench fever, typhoid and other infections, with immune systems of soldiers weakened by malnutrition, cold and other stressors during movement of the Napoleonic troops through Russia. More recently, more people died due to the Spanish flu pandemic of 1918 than died in combat in World War I.

In the mid to late 20th century, with the advent of antibiotics and dramatic advances in the biological sciences, it seemed that we have conquered infectious disease–and, at least in the western world, we largely have for some period of time. We can now treat, have eradicated or decreased the incidence of infectious diseases. We can now effectively treat plague, cholera and numerous other infectious. We have eradicated smallpox, are close to eradicating polio, and have dramatically decreased the occurrence of other historical killers such as diphtheria, whooping cough, measles, and others through vaccination campaigns. Despite the many remaining challenges including antibiotic resistance and global access to curative drugs, we have developed drugs to treat many infectious diseases.

But now it is time to rethink the notion that we have conquered infectious disease. Due to human activity, the threat of infectious disease is making a come-back. Unfortunately, at this point we are ill equipped to deal with a number of scenarios, particularly those involving large-scale infectious disease outbreaks–pandemics. Pandemics pose some of the biggest threats to humanity, both as far as infectious disease risks as well as overall existential threats more broadly. In terms of impact on human population, this threat is as high as nuclear annihilation, climate change, and global instability for a variety of reasons. Pandemic risk is closely tied to climate change, technological disruption, as well as other factors relating to human activity.

Pandemics challenge our society’s ability to withstand them. Severe pandemics can lead to mass panic and disruption of society and governments. In September 2014, the United Nations Security Council declared the Ebola virus outbreak in the West Africa a “threat to international peace and security”. The resolution was the first in the history of the Security Council to deal with a public health crisis. In response, the United States sent in troops to assist in disaster response. The prowess of U.S. military in logistics and operations proved critical in helping to stabilize the region during this societal disruption.

Different Patterns of Spread of Infectious Diseases

The risk of pandemics has been increasing and accelerating significantly over the last several decades. Since the 1980s, we have seen a three-fold increase in the number of global epidemics. Climate change has been driving increased risk as mosquitos and other vectors spreading diseases such as dengue, chikungunya, zika moved up north. Also, different ways of using land, increased contact between humans and wild animal populations, urbanization and global travel have all contributed. As a result, we have seen a change in the pattern of spread of infectious organisms: some organisms which historically spread only locally have spread in ways we have never seen before, with dire consequences.

One example of this is the Ebola outbreak of 2014-2015. Historically, Ebola outbreaks involved tens to a few hundred people, and have been limited to one or a few remote villages in Africa. For the first time in history, we have seen this disease affect a continent, claiming tens of thousands of lives and wrecking fear and havoc on the entire world. Notably, this Ebola outbreak was caused by the same Ebola virus as the previous 20 outbreaks of Ebola occurring in Africa between 1976- 2014. Why was this outbreak different? The difference in 2014 and 2016 outbreak is attributed to the fact that people are no longer isolated in remote villages–they travel. And when they do, they travel to cities, which, with the rise of urbanization, are now more heavily populated, but still lack the needed health infrastructure. Furthermore, people travel by planes at higher rates. All of this contributed to the number of people infected. It is also an example of a trend which is bound to continue. Although Ebola outbreak was the most recent dramatic example, the same dynamics also apply to the spread of flu and other infectious organisms.

With humans encroaching on traditionally animal habitats, there has also been an increase in the emergence of new infectious diseases affecting humans. This is significant since most pandemics stem from infectious organisms typically infecting animals becoming capable of infecting and spreading between humans.

The Challenges of Preparedness and Response

Medical Countermeasures

Pandemics pose a number of unique challenges to our society’s ability to withstand them. One of the challenges is our ability to develop medical countermeasures. Since we know how to develop vaccines and drugs, why can’t we just develop drugs and vaccines to control pandemics? To examine this question, let’s start with the most common pandemic which predictably happens every year–seasonal flu. In 2018 seasonal flu claimed about 80,000 lives in the United States alone. It would seem that for a pandemic which happens yearly, claims thousands of lives yearly, and results in billions of economic costs predictably every year, we would by now have great medical countermeasures. However, despite the fact that much effort is expended every year in designing and making a flu vaccine, the effectiveness of this vaccine varies significantly year to year.

There are a number of factors which can make creation of good flu vaccine challenging.

Influenza virus is remarkable for its high rate of mutation, compromising the ability of the immune system to protect against new variants. As a consequence, new vaccines are produced each year to match circulating viruses. Currently, vaccine production takes, on average, six months from the selection of seed strains to the final vaccine product. The decision of which influenza antigens to include in the vaccines is made in advance of the influenza season and is based upon global surveillance of influenza viruses circulating at the end of the prior influenza season. In some years certain influenza viruses may not appear and spread until later in the influenza season, making it difficult to prepare a candidate vaccine virus in time for vaccine production. This can make vaccine virus selection very challenging. As a result, sometimes there are mismatches between the vaccine strain and the circulating strain that result in reduced efficacy of the vaccine. Can we come up with a vaccine which would be effective against all flu viruses? Ongoing research is focused on developing a universal vaccine that would elicit protective antibodies directed against conserved viral proteins.

What is the effectiveness of the flu vaccine? It depends on the type of the vaccine and it also varies every year and depends on how good a match is between the viral strains used to make the vaccine and the viral strains actually circulating in the population. During the 2004 to 2005 influenza season, the antigenic match was only 5 percent compared with 91 percent during the 2006 to 2007 season, which resulted in vaccine effectiveness of 10 versus 52 percent, respectively.1 During the 2014 to 2015 influenza season in the United States, influenza A H3N2 viruses predominated and more than half of these viruses contained H3N2 antigen that was antigenically different (drifted) from that included in that season’s influenza vaccines. The adjusted overall vaccine effectiveness for the 2014 to 2015 influenza season was 19 percent; for H3N2-associated illness, the vaccine effectiveness was only 6 percent.2

Despite the fact that flu vaccine has varying effectiveness, vaccination does reduce mortality from influenza significantly, and yet only 40% of the population gets the vaccine. The resistance to vaccinations is not unique to influenza. With the rise in anti-vaccination movement, we have recently seen outbreaks of measles and pertussis, both of which are prevented by vaccines with long standing record of safety and efficacy. Given this, what vaccination rates can we expect for newer, less tested vaccines? What percentage of the population would be comfortable getting vaccinated with a vaccine which was developed quickly in response to a novel viral pandemic? What if this vaccine was approved by the FDA under Emergency Use Authorization, which is a legal means for the FDA to approve new therapeutic and diagnostic tools during a declared emergency with more limited testing than it would normally require? How many people would feel comfortable getting immunized with a vaccine with an incompletely understood safety profile? This is one of the many challenges unique to pandemic preparedness and response.

And what about drugs? For immunocompetent population, antivirals like Tamiflu only shorten flu symptoms by a day and offer no mortality benefit. Despite the public panic of trying to get Tamiflu during some of the more severe influenza seasons and the pharmacies running out of Tamiflu, the benefit of Tamiflu and other influenza antivirals is marginal in immunocompetent populations. It does offer more potential benefit to people whose immune systems may be compromised.

How about medical counter-measures such as drugs and vaccines for other viruses and what would it take for us to be prepared for a pandemic due to an emerging infection? Most pandemics caused by emerging infectious diseases are due to organisms which have recently appeared within a population or whose incidence or geographic range is rapidly increasing or threatens to increase in the near future. Most of these arise from human interaction with animals. There are over 200 species of viruses and 500 species of bacteria capable of infecting humans. Focusing on viral infections which are far more likely to cause a pandemic than bacterial infections, there are numerous strains of viruses within each of the specie. This leaves us with thousands of various strains of viruses capable of causing a pandemic. Also, viruses mutate, some very frequently, which increases this number significantly. Additionally, with advances in synthetic biology, it is possible to manipulate viruses to make them more lethal and infectious–those can be released accidentally or nefariously. Although numerous measures have focused on prevention of this occurrence including attempt to regulate biology more tightly and secure it through the NSABB (National Science Advisory Board for Biosecurity) and other governing or advising organizations, ultimately perfect control is not possible. Unless specified beforehand in a grant application or another form of disclosure, it is exceedingly difficult to monitor what kinds of biological experiments one is setting up in their lab or garage, or what kinds of samples one may store in their lab freezer.

This leaves us with a virtually infinite number of viruses to which our population is vulnerable. It costs hundreds of millions of dollars to develop a vaccine or a drug. It would therefore take infinite amount of resources in an attempt to have a vaccine or a drug for every possible pathogen. While it is sensible to have drugs or vaccines to some more commonly occurring organisms, this quick calculation makes it apparent that this strategy will leave large gaps in our preparedness.

How about developing a drug or a vaccine at the very start of an epidemic in order to quickly control it? This reactive approach is politically tempting, and one frequently tried in the past, but which generally fails. The reason is simply the timeframe. It takes years to develop, test, and produce vaccines or drugs. While in an emergency this time may be shortened, it will still likely take a few years to develop and produce a new drug or a vaccine, by which time the epidemic would have already ran out and claimed the lives it was going to claim. It is hard to speed up drug or vaccine development by spending large amounts of money in response to an outbreak. In the past when U.S. Government has reacted to outbreaks by spending large amounts of money, as happened during the Ebola outbreak of 2014-2016, it has not made significant difference. We are still limited by what is possible as far as the speed of development, clinical testing, and production. We still don’t have an FDA approved Ebola vaccine, although numerous ones have been developed and some are used, apparently with success, in Africa. Despite significant advances in the biological sciences over the past century, ironically, in the scenarios involving pandemics due to emerging infectious diseases, we are not in a dramatically different place as far as availability of specific countermeasures compared to where we were a century ago.

Surge Capacity

Thanks to the advancement in the medical sciences, even without having specific drugs or vaccines to treat infections, patients today are far more likely to survive thanks to the availability of supportive medical treatments such as fluid resuscitation, ability to help patients breath with the help of respirators, and other medical measures designed to support vital functions while the body’s immune system mounts a response to an infectious organism. This is why Influenza or Ebola patients, for example, are far more likely to survive with supportive medical treatment than without it.

In a pandemic scenario, however, the availability of supportive medical treatment is not a given. This has to do with limited ability of hospitals or the medical system more broadly to handle a sudden influx of patients, which is known as surge capacity. In an event of a significant pandemic, our surge capacity will likely be outstripped given limited amount of hospital beds and medical personnel to staff the beds, as well as limited equipment, medications and other supplies needed to care for additional patients. Managing an infectious disease outbreak can also be more complicated since it may require additional kinds of resources such as negative pressure rooms and quarantine facilities.

We have experienced limited surge capacity at Stanford first hand. A number of times over the past several years, for weeks to months at a time, we had to open “The Tent”. The Tent is a portable medical tent without running water which Stanford purchased in order to accommodate the influx of patients in disaster situations. We would open the Tent right outside the Emergency Department on the lawn by the parking lot at Stanford hospital in order to accommodate the increase in the number of patients during the flu season. Thus, Emergency Department created extra capacity with 8 additional patient chairs, and an additional physician as well as nurses and techs to take care of patients. We have the luxury of the benign weather in California to be able to operate part of an Emergency Room in a tent during the winter. Given that Stanford hospital has been operating close to capacity, as many hospitals throughout the country do in order to optimize operations and be fiscally responsible, during those times we had insufficient amount of space in the Emergency Department to accommodate the yearly influx of patients. Part of the reason for this is that we had numerous admitted patients being boarded in the Emergency Department due to a lack of availability of inpatient beds. If we have to set up our disaster Tent during the predictable yearly flu season, one can imagine that an influx of patients which is significantly beyond those experienced during the yearly flu season will be challenging and potentially impossible to accommodate as far as medical surge capacity.

We have plans to operate in disaster situations and flex our surge capacity, but the capacity to flex is limited. Our flexing involves putting admitted patients in the hallways, in addition to placing them in rooms, and discharging borderline patients who might be able to be reasonably discharged under these circumstances. Treating patients in the hallways and discharging patients who might be better served in the hospital under normal circumstances puts a stress on the system as well as on the patients. These disaster plans are generally supposed to last for hours to days following disaster, not months, as would be required in a case of a significant pandemic. This does not only apply to Stanford hospital, but is a typical situation in many if not most hospitals throughout the nation.

Another example of the limited medical surge capacity specifically around high consequence infectious disease became apparent during the Ebola outbreak of 2014-2015. During the outbreak, hospitals throughout the country including Stanford were rapidly preparing to receive and treat Ebola patients. Per CDC guidelines, the treatment area for such patients, in addition to the patient rooms, needed a “warm zone” as well as the “cold zone”. The “warm zone” is an area right outside the patient room where providers would take off personal protective equipment (PPE) and which may be contaminated with infectious organisms. The “cold zone” is a zone right outside the “warm zone” where providers would put PPE on, where clean supplies would be contained and where medical charting and other duties not directly involving direct patient contact can take place. The patient rooms themselves would need to have the capacity to suck the potentially infected air out of the rooms and release it into the atmosphere–these are called negative pressure rooms. There are only two such places at Stanford hospital: two rooms in the Emergency Department which are part of the Pediatric area, and the Stanford’s Critical Care Unit for cardiac patients.

If Stanford was to receive one or two suspected Ebola cases, those patients would be placed in the pediatric zone rooms, and if three or more patients would need to be cared for, Cardiac Intensive care unit would be converted into an Ebola care ward. To the chagrin of the cardiologists at Stanford, this would necessitate cancelling all cardiac catheterizations and heart surgeries. Thus, merely three suspected Ebola cases would significantly disrupt Stanford’s normal hospital operations and ability to provide medical care. The Cardiac Intensive care unit could accommodate additional 8 patients. Thus, Stanford as a whole was prepared to accommodate 10 suspected Ebola patients. One can imagine that in an outbreak of highly pathogenic flu or another emerging infection, the number of patients seeking medical care would be hundreds or thousands of times higher, thus overwhelming the system.

Many are under a hopeful impression that in a disaster situation involving pandemic with high consequence infectious organisms Federal Government through agencies like FEMA would step in and provide the medical surge capacity required. While indeed FEMA and other governmental and non-governmental organizations have been instrumental in responding to various disasters in the past such as earthquakes and floods, pandemics are not localized events. We would expect that most if not all areas of the country would be affected, far outstripping the federal and state resources required to provide additional medical capacity. Most of disaster response takes place on a local level, using local resources.

If Not Drugs, Vaccines, or Increased Surge Capacity, Then What?

If we are unlikely to have drugs or vaccines to counter infectious organisms during a pandemic, and if our medical surge capacity may be outstripped, what are we left with? We are left with an approach we have used for centuries to counter infectious disease, namely public health measures such as isolation, quarantine and other forms of infection control. This will be our strongest leverage point and our biggest opportunity. This strategy has a track record of success in a variety infectious disease outbreaks in the past. Despite the fact that it is a centuries-old approach, it makes sound sense to put resources behind it and innovate around it using modern tools.

Rapid Diagnostics and Surveillance: Lessons from Ebola

Rapid diagnostics and surveillance have been challenging for most outbreaks in the past for a variety of reasons, but this is one of our biggest points of leverage in controlling infectious disease outbreaks, and also most realistically doable given the state of technology and the cost/benefit equation. Although this was not available at Stanford hospital during 2014–2015 Ebola outbreak, a time is close when rapid and accurate point of care diagnostic testing for emerging infections will be widely clinically available. This will be very helpful in optimizing utilization of the scarce medical resources and patient outcomes, since a determination could be made quickly whether a patient is infected and therefore whether or not they need to be isolated.

During the 2014–2015 Ebola outbreak, the plan at Stanford was to send samples from suspected Ebola patients to the Center for Disease Control (CDC) lab for confirmation. If the patient was confirmed positive for Ebola, the plan was to transfer the patient to an Ebola-designated treatment hospital—at that time it was UCSF. And, if the patient could be medically managed at home, to discharge them. The turnaround time given specimen travel and analysis time by the CDC lab was expected to take several days to a week. That would mean that a patient with suspected Ebola would have to be quarantined and treated in the Emergency Room for up to a week, taking up valuable medical resources. Due to high containment, Ebola patient would take up several times more resources than a regularly admitted patient, potentially disrupting provision of intensive cardiac care since the Cardiac Care Unit would be converted to an Ebola ward. All of this could be avoided by having a rapid and accurate point of care diagnostic test. For other kinds of lab testing for clinical purposes, a policy was made by Stanford hospital to only use point-of-care bedside testing for suspected Ebola patients. A rapid point of care diagnostic test which could be used at the bedside would optimize resource allocation.

During the Ebola epidemic in Africa, suspected patients were often quarantined together. Given limited resources, separate rooms were generally not available. Patient with malaria and other viral or bacterial diseases and patients with Ebola were often in the same living quarters: in the beginning of the illness, these diseases can be indistinguishable from each other clinically. This unfortunately made possible transmission of Ebola to patients with non-Ebola infections. A rapid and accurate test which could be used in the field would have precluded this from happening.

This is applicable not only to Ebola outbreaks but to most scenarios involving pandemics. In pandemic scenarios, it is likely that large numbers of patients will present to Emergency Departments and clinics. It would be very helpful to be able to rapidly distinguish between those who are sick due to a dangerous pathogen from those who are not and make treatment and quarantine decisions rapidly and accurately. This is key to getting an outbreak under control.

Quarantine, Isolation, and Other Infection Control Measures

Quarantine has been used extensively in the past during epidemics. The word quarantine comes from an Italian term “quaranta giorni”, meaning forty days, the period that all ships were required to be isolated before passengers and crew could go ashore during the Black Death plague epidemic. A quarantine is used to separate and restrict movement of people who may have possibly been exposed to an illness or to restrict transport of possibly contaminated goods; quarantine is designed to prevent the spread of communicable diseases. Quarantine is different from medical isolation, which is to separate ill persons who have communicable disease from those who are healthy.

Outbreaks have been avoided in the past using the above measures alone. One example of this involved SARS. On March 7, 2003, two patients with SARS arrived in Canada and both promptly presented to the local hospitals—one in Vancouver and the other one in Toronto. No outbreak resulted in Vancouver. Toronto had a SARS outbreak with 247 probable cases and 44 deaths. Half of these were in healthcare workers. Vancouver is a useful point of reference for Toronto’s response to SARS. Main difference? Immediate medical isolation upon presentation to the hospital in Vancouver, which included respiratory isolation and the use of N95 respiratory masks.

This decision was not only a result of a good call by an ER doctor in Vancouver—this was a team effort and no accident. This decision stemmed from months of monitoring, careful planning, and excellent communication by the local public health department, which was on a lookout for a highly pathogenic form of bird flu coming out of Asia and communicated these alerts to the local medical providers. As a result, although SARS and bird flu are caused by different viruses, a sick patient with flu-like symptoms with recent travel to Asia immediately got isolated with respiratory precautions. In Toronto, medical isolation with respiratory precautions was delayed and numerous medical and non-medical staff were exposed, got infected, and died due to a resulting SARS outbreak.3

Another example involved using infection control measures in non-medical settings, which were instrumental in mitigating infection rates during the Spanish flu pandemic of 1917–1918. This entailed the loss of civil liberties, especially in U.S. cities. As demonstrated by the research through the National Institute of Health (NIH) and the Centers for Disease Control (CDC), cities using aggressive measures had significantly lower infection and mortality rates.4,5,6 As documented by numerous historians, the first line of defense was educational campaigns regarding hygiene, such as spitting and coughing into handkerchiefs, and banning common cups and utensils.7

The use of more aggressive interventions required the closing of schools, the restriction of large gatherings, and isolations and quarantines.7,8 While some have argued that cities with rigorous closings and illegal gatherings fared no better than other cities, the examples of positive effects resulting from aggressive interventions are compelling.7 Cities that implemented social measures within a few days of the first few cases of flu did better than cities that waited a few weeks to respond; the peak weekly death rates of the former were halved compared to the latter.7,9 St. Louis had implemented measures within 2 days of their first reported cases, which resulted in a death rate l/8 the number of fatalities in Philadelphia, the worst hit city. The City of Brotherly Love failed at keeping people apart by allowing a city-wide parade to be thrown. The results show a necessity for isolation measures. Other examples of these interventions include Kansas City banning weddings and funerals with greater than twenty persons, New York City staggering factory shifts to reduce the waves of commuter traffic, and Seattle ordering its constituents to wear face masks in all public places. A clear negative correlation between the time of implemented measures and mortality can be observed, along with another negative correlation between the number of measures and mortality. The statistics are publicly available and can be found on the CDC’s website.

Even with initial control measures, the second and third waves of Spanish flu caught cities that ended their nonpharmaceutical interventions off guard, demonstrating the importance of not lifting nonpharmaceutical interventions prematurely. For example, San Francisco reduced their mortality rate by 25%, but 90% of their deaths occurring between September 1918 to May 1919 could have been avoided if they had kept their initial controls in place.4,9 They had previously closed schools and theaters and boasted their law mandating the use of masks in all public places. Catchy sayings, such as “protect your jaws from septic paws,” were promoted by the Board of Health, the Red Cross, and the mayor himself; violators of public mandates faced jail time. After signs of the flu waned, sirens wailed on November 21st, 1919; masks came off, schools resumed session, and theaters reopened their doors. This also highlights the need for situational awareness and surveillance–the earlier we are aware of a potentially dangerous outbreak, the earlier we can institute infection control measures including isolation and quarantine, thus giving us a chance to prevent or curtail an outbreak. The premature celebrations left members of the public volatile and the next two cycles of flu once again ravaged the city.

While in retrospect it may seem obvious that rapid implementation of these sweeping measures saved lives, they were met with considerable opposition. Significantly, this resistance did not come from specific ethnic or racial groups being made scapegoats for the outbreak, as had happened in previous epidemics. The Spanish influenza moved so quickly and so indiscriminately among the population that it could not easily be blamed on immigrants or the poor.10 Instead, the lines of resistance reflected divisions between the public health departments and the communities they served.

Implementing social-distancing measures in these big cities presented a massive public health challenge.11 They had complex economies dependent on both industry and commerce that could easily be damaged by quarantines and closures. As had happened in earlier epidemics, businessmen resisted the idea of mass closures of transportation and businesses that would cause economic distress both to owners and workers. Some employees filed lawsuits to recover lost wages due to such a closure. Big cities also had large public-school systems, flourishing commercial entertainment districts, and extensive systems of mass transit, all of which formed fertile ground for the spread of influenza. School closures left parents with children to provide for during the day. Shutting down saloons and theaters meant not only lost revenue for owners but also lost pleasures for their customers. To inflict such economic damage on a city’s economy required a public health emergency without precedent.

Hence, a number of cities including New York felt that the most practical strategy was to move quickly to isolate the acutely ill in hospital wards or at home and to direct an intensive public education effort about personal hygiene to everyone else.

Public-gathering bans also exposed tensions about what constituted essential vs. unessential activities. Those forced to close their facilities complained about those allowed to stay open. For example, in New Orleans, municipal public health authorities closed churches but not stores, prompting a protest from one of the city’s Roman Catholic priests. Theater owners often voiced the “why us and not them” argument. In many cities they were the first, and sometimes the only, businesses to be shut down. In response, some of them asked that the closing order be extended to department stores and public transport.11

Perhaps the most important “lesson” taught by the Spanish flu pandemic was the realization that those measures that worked the best to control a highly infectious disease—bans on public gatherings, school closures, and strict quarantine and isolation—were precisely the ones most difficult to implement. In the modern times, the amount of resistance to these measures will likely be no different. Also, in an event of a serious pandemic, some measures such as those involving closure of county or state borders in a quarantine may be impractical since they will not be able to be enforced. The manpower required to do so will outstrip the need. Even more so due to the fact that a significant proportion of law enforcement personnel may themselves fall ill or be taking care of their own ill family members or providing for the safety of their families in an event of societal disruption secondary to a massive pandemic. The mandatory quarantines will also likely fuel public distrust in the government and may even fuel public unrest and societal disruption, as we have seen happen in the most recent Ebola outbreak in Africa.

In light of all this, a combination of select public health control measures with empowering individuals and organizations to self-quarantine or use other measures to decrease or stop the transmission of infectious organisms may be the most practical and effective approach.

Other Infection Control Measures and Opportunities for Innovation

As discussed above, due to the fact that we are unlikely to have drugs or vaccines available in time to counter an emerging infection in a pandemic, we will instead need to rely on infection control measures to get ahead of it. This does not mean we cannot utilize modern technology, however—quite the opposite. This is an area which is currently underinvested but which holds much promise and opportunity if we innovate around it. What might this look like? If we are able to keep everybody home for a month or two, we would stop the cycle of transmission and illness and be done containing a pandemic.

How do we enable that? Perhaps people can work or study remotely from home while they get automated delivery of food, water, and basic supplies via driverless cars or drones. Keeping everybody home for a month at this point in time may be an unrealistic goal given the current state of technology, but it may be more achievable as technology advances. Even if part of the population can be isolated in this way for a period of time, this may help us get ahead of an outbreak. Also, perhaps people would prefer to self-quarantine if they face a possibility of catching an infection with high mortality rates if they leave their homes. They would just need to be enabled to self-quarantine, either with the use of technology or simple personal disaster preparedness. If we are prepared in this way, we are also likely to decrease the chances of public chaos and breakdown of society in an event of a deadly pandemic and will significantly decrease the burden on hospitals and medical infrastructure as a side-effect.

How about creative use of UV lights, which we know effectively kill germs? Those could be used in public transport, offices, and schools. Or the use of germicidal ozone? Air filters? Wider use of negative pressure rooms, to remove air with germs and replace it with the one without? Or altering humidity and temperature in hospitals and buildings, since both have been shown to affect the spread of some infectious organisms including influenza?12 Or creating better personal protective equipment that everybody, not only medical personnel, can safely and easily use? The opportunities to innovate are numerous. The attractiveness of these approaches is that they can be used for every bug or at least a large group of bugs, unlike the traditional pharmacologic countermeasures, which generally use a one bug per drug approach.

Are We Prepared for Pandemics, and What Should Be the Next Steps?

Are we prepared to withstand pandemics due to organisms with high mortality rates? According to the Blue Ribbon Study Panel on Biodefense (BRSPB) in 2015, we are not.13 The Blue Ribbon Study Panel on Biodefense is a privately funded entity established in 2014 to provide a comprehensive assessment of the state of U.S. biodefense efforts, and to issue recommendations that will foster change. It is the only body of bipartisan high-level policymakers to do so.

The study covered human-generated (terrorist and accidental) and naturally occurring biological threats. The study culminated in a report to the public that Congress released on October 28, 2015. BRSPB’s final report had 33 recommendations and over 80 specific items associated with those recommendations. The study assessed biological threat awareness, prevention and protection, surveillance and detection, and response and recovery. Current and former members of Congress, former administration officials, state and local representatives, thought leaders, and other experts provided their perspectives on current biodefense efforts, including strengths, weaknesses, and opportunities. While much good work has been achieved toward biodefense, these meetings have revealed systemic challenges in the enterprise designed to protect Americans from a biological event.

Some of the challenges highlighted include lack of senior national leadership to centralize efforts of the various governmental agencies working on issues related to biosecurity. The Panel proposed empowering the vice president with jurisdiction and authority over biodefense responsibilities. Other recommendations included measures to enhance national biosurveillance capability, improving public health emergency capabilities and hospital preparedness, incentivizing innovation in countermeasure development and deployment, and rapid point-of-care diagnostics, leading the way toward establishing an agile global public health response apparatus. In 2018, the Blue Ribbon Study Panel also issued their budget recommendations to increase return on investment in biodefense.14 Much is left for us to do to enhance our ability to withstand serious pandemics. Concerted effort with an innovative and collaborative mindset will save lives and enhance our nation’s safety, security, and resilience to pandemic threats.

Dr. Milana Boukhman Trounce is a clinical professor at the Stanford University School of Medicine and an emergency medicine physician.



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