MERS as (another) messenger of prevention

It's hard for me to know how to interpret the MERS situation in South Korea. At a high level, a recently recognized viral respiratory pathogen has traveled halfway around the world and is causing morbidity and mortality in a small section of an immunologically naive population. It appears to be associated with hospitals. What do we take away from this? Lessons will be learned when the event subsides and people study what happened, but to me, MERS reminds us that outbreaks of pathogens for which there are no vaccines or drug therapies underscore the importance of prevention.

When possible, preventing pathogens from physically reaching or entering a host by respiratory, percutaneous, alimentary, blood et al pathways is preferable to relying on pharmaceutics. Drugs tend to be complex and costly to develop, can take a long time to enter the marketplace, and -- especially in the case of antibiotics and antivirals -- they can become obsolete over time. Moreover, drugs are often toxic to the patient. Prevention is applicable in situations when appropriate drugs don't exist (e.g., for newly emerged pathogens), when it isn't possible to administer drugs in a timely manner, or when patients cannot tolerate them. 

Consider two anecdotes related to the spread of MERS virus in South Korean hospitals. As described by Choe Sang-Hun, it appears that the index patient in the South Korean event had "coughed and wheezed his way through four hospitals before officials figured out, nine days later, that he had something far more serious and contagious." Furthermore, ED wait times in Korea can be extraordinarily long by US standards. Another patient, who waited two-and-a-half days in the emergency department before a hospital bed became available, infected 55 additional individuals during their wait. Apparently, 2.5 days isn't an unusually long waiting time in some Seoul hospitals. 

Applying effective prevention measures to patients suspected of infection is the only way of stopping the chain of transmission in such environments. Unfortunately, it is unclear how to achieve good infection control for MERS and a range of other pathogens. Eli Perencevich described the issue clearly, as usual, in the Controversies in Hospital Infection Prevention blog recently: 

. . . we don't actually know how to achieve good infection control for MERS and the other diseases he [Tom Frieden] mentioned [measles, DR-TB, SARS, Ebola]. If only we invested in studies to understand how to best implement PPE in these [hospital] settings. One could imagine improved PPE technology, refined PPE donning and doffing algorithms and enhanced environmental cleaning as potential targets for future studies examining optimal protection from MERS. Not coincidentally, many of these are the same targets that Mike, Dan and I mentioned in our Ebola+PPE editorial several months ago. If we invest in infection prevention technology and implementation research, our health care system will be safer regardless of the pathogen du jour.

And that's the point that MERS makes me think about. Yes we need antimicrobials and vaccines that work against specific pathogens, of course we do, but developing such drugs is a major effort. Biochemical pathways must be understood, pathogen life histories and survival strategies must be elucidated, and the host response must be characterized among many, many other things. Doesn't it make sense that research on pathogen-agnostic approaches to prevention, which don't require such specific and complex information, might be simpler and broadly applicable? 

Investing in research on infection prevention approaches, and how to implement them sustainably in realistic clinical environments, would pay benefits far beyond helping to thwart the spread of exotic and newly emerged pathogens. We may learn how to better control and prevent the usual suspects of hospital associated infection, which, afterall, are responsible for a tremendous burden of disease day in and day out.

(image source: Wikipedia)

When it comes to measles, it is a small world after all

Dan Diamond wrote an essay recently in Forbes in which he notes the asymmetry of public reaction to Ebola versus measles. He describes how on the one hand, even though Ebola was unlikely to cause an epidemic in the US the public went nuts with Fearbola, while on the other hand measles represents a much more realistic threat of spread but people are somewhat apathetic about it. It seems a valid observation.

It may be difficult to understand public perception of threat when it comes to infectious disease, but, epidemiologically speaking, there are some important differences between the two, as partially summarized in the table below.

	Measles	Ebola
R0	~7-18	~2
Serial interval	8-12 days	5-15 days
Incubation period	10-12 days	2-12 days
CFR	3%	25-90%
Infectious period	~ 4 days before rash to several days after onset of rash	At onset of symptoms
Vaccine preventable	Yes	No

Importantly, persons infected with measles virus are infectious before they begin to feel ill, so they are able to spread the virus in the course of their normal activities. Fearbola -- the epidemic of hyped and often unfounded messages surrounding the threat of Ebola to the US -- struck in part because of the high case fatality rate (CFR) and the lack of a vaccine conveying immunity to the Ebola virus. That contrasts strongly with measles. Even though the measles outbreak that started at Disneyland Resort Theme Parks in California is expanding, I doubt there will be a Fearmeasles epidemic, even though measles can be fatal and cause long term sequelae.

That said, this is a fascinating event due partially to people's attitudes regarding vaccines. Recently, the ramifications of such attitudes, in terms of implications for public health agencies, has been expressed very clearly by Lisa Aliferis (writing for NPR):

Local health officers in counties [in California] affected are busy tracing those who infected patients have been in contact with. Dr. Erica Pan, deputy health officer of Alameda County, says the county has shifted resources from Ebola preparedness to contact tracing for measles. Last year there were four cases of measles in Alameda County, she said, "but we had 400 contacts to investigate."

This is remarkable. On 23 January, the California Department of Health reported that in LA and Orange counties alone there were 31 confirmed cases. A simple back-of-the-envelope calculation suggests that if 4 cases required 400 contacts to be investigated (100 contacts per case on average), then 31 cases could require 3100 contacts to be investigated. No wonder health departments are refocusing resources away from Ebola and onto measles.

People who do not vaccinate their children, or catch up on missed vaccines as adults, do not only place themselves in danger of infection, they place the community in danger. Moreover, they cause scarce public health resources to be spent on controlling a vaccine preventable disease. It's ironic that the lyrics to It's a small world -- the theme song of a ride at Disneyland of the same name -- read

It's a world of laughter, a world of tears.
It's a world of hopes and a world of fears.
There's so much that we share,
That it's time we're aware
It's a small world after all. 

Indeed.

(image source: Wikipedia)

Follow up: An IGY for medicine

Happy New Year to all!

A quick follow up to the recent IGY for medicine post. A colleague in Sierra Leone commented about the post that

The pipe dream is actually happening: it's the Ebola response. In many ways, what you suggest for an International Biomedical Year is exactly what's happening now in West Africa. It's an amazing international effort. The sentiment and organizations are definitely present there, though perhaps the coordination could be improved. That said, if the world NGOs and governmental organizations collaborated like they are for Ebola on other efforts, though more focused as you suggest on research and treatment, a ton could be accomplished.

There's a very positive thought to begin 2015.

The epidemiology of Fearbola

In the mid-19th Century, a newspaper could reach several thousand people daily or weekly. By the mid-20th Century, TV and radio reached 10s to 100s of millions of people instantaneously and possessed a multinational reach. Today, with the Internet, and satellite TV and radio, it is possible to reach 100s of millions of people or more across the globe within minutes. This vast and practically instantaneous reach of technology feeds a seemingly insatiable, 24/7 appetite for news and information. What are the implications of this for fighting epidemics? 

We've seen some of the consequences in the Ebola outbreak this year. On the one hand, the ability of aid groups to spread information broadly has been helpful for raising awareness and bringing additional resources to bear on the epidemic. On the other hand, news headlines resulted in near-hysteria and much counterproductive behavior in the US and other developed nations. Examples were highlighted in a previous post, and many, many others have offered similar observations and commentary.

Perhaps the reactions observed in the US have been understandable, as many ingredients were present for an epidemic of sensationalism and fear: An active public imagination rooted in previous popular books and movies, a government that addressed the issue late and with almost Pollyannaish credibility at first, and a wealth of news outlets offering non-expert commentary while playing to the continuous news cycle.

The resulting epidemic of "Fearbola" should thus not be surprising. It is sobering, however, for it provides a warning for domestic public health agencies: Understand how to administer effective public health messages that are relevant and appealing to the constant clamor of CNN, Fox, and the like, or else risk being drowned out by noise and hype. What if this epidemic had been of a pathogen possessing a short serial interval and high virulence, transmissibility, and R₀? The medical system may or may not be prepared, but it seems clear that our risk communication strategies are not. Would the news coverage we saw during the Ebola hysteria in recent months have served the public well if this had been a bona fide threat to US public health?

It's important to understand how the epidemic of fear and hype came into being and propagated so well. I tend to think of messages as themselves being infectious. From that perspective, the ideas that resulted in the hysteria surely had R₀ > 1. For ideas related to "dread threats", such as virulent infections with no known cure, is this unavoidable given the high contact rate (e.g., frequency of checking for news and rumors combined with near-constant coverage), short serial internal (e.g., rush to post on social media), broad coverage, and rapid dissemination of modern communications?

If so, we must learn how to craft public health messaging strategies so that authoritative messages will out-compete hype and fear in our hyper-connected world. If we don't learn how to do so, we run the risk that important messages will be drowned out by high-incidence, fearful messages in future outbreaks of international public health importance.

(image source: David Hartley)

Ebola: Encouraging news but far from victory

Recent statistics from West Africa suggest that the epidemic of Ebola virus disease is declining in some areas. While this is welcomed and good news, it's important to remind ourselves that the public health emergency is not over and that significant uncertainties remain. Dr. Joanne Liu, the current president of MSF, described the reasons in an interview with Julia Belluz:

Strictly speaking, when we look at our figures, there is deceleration in the number of cases in a few spots in Liberia and Guinea, but they are still on the rise in Sierra Leone.

There are a few things we need to be conscious about: we have had those decelerations in the past. Basically, it happened while it was spreading in other communities and after that, there was another surge in other hot spots. So we need to make sure it’s an opportunity to consolidate our Ebola isolation centers and case management, strengthen the community information and education. That is key. We need to use this time for that. But the main thing is to not let down our guard.

There’s no room for complacency, no room for mistakes. Every time you go down that path, you pay: you get infected, more people are infected. Ebola does not allow you to make mistakes.

This is certainly true. I think it's also a critical time in another way: With the medical aid in the region and the momentum it is gaining, it would be a shame not to begin asking what will happen when the epidemic is finally conquered. Will the international community simply pull out, leaving a vacuum made more acute by the scores of local healthcare workers lost to Ebola itself? Or, is there a way that the current activity could bolster and influence medicine and public health there for years to come? Some ideas may be creeping into the conversation: US and Liberian officials have decided to reduce the number of Ebola treatment units planned and are discussing spending the money saved on programs aimed at combating future epidemics.

For now, however, we must avoid complacency and remain committed to providing the resources needed to fight the ongoing epidemic. I don't think it's too early to begin conceiving a foundation for improving regional medical and public health capabilities more broadly, however. Perhaps some of the capabilities on site in the affected areas now can be transitioned into a sustainable, effective medical and public health presence at the appropriate time. Not doing so would be a missed opportunity.

(image source: USAID/ Carol Han)

Planning for the unplannable: What about next time?

A recent article in Forbes, written by Scott Gottlieb, began by observing that

The response by public health officials and local providers to the first case of Ebola diagnosed on U.S. soil has been marked by some tragic missteps. Mistakes have resulted in the avoidable secondary spread of the infection to healthcare workers. This is an appalling outcome to a crisis . . . But, sadly, it should neither be surprising, nor foretell a future marked by continued blunders.

As he suggests, I'd really like to think that the response to the events in Dallas will result in better ED and hospital care. It's important to learn from errors, and this seems to be happening: There's been a dramatic increase in infection control awareness since late September.

That seems like a good thing, but there's more to the picture. Alison Bruzek wrote an interesting piece for NPR last week on how, for hospitals, doing more on Ebola can mean less elsewhere. A passage from the article illustrates the point:

For infection preventionists, a normal routine includes "Looking at the lab results[.] [W]e're looking at what new patients maybe came onto a unit, we're taking calls from the unit, [and answering questions like] 'What do you think I should do about this particular thing?'" says Linda Greene, an infection prevention manager and member of APIC's regulatory review panel. But now, Green says, if the infection preventionist is working on training with personal protective equipment for Ebola, their other tasks aren't getting done as promptly or efficiently as they could be. As a result, Greene [says] the fear is that they'll "miss red flags" for patients with the flu or antibiotic-resistant bacteria.

How can this be avoided? It's difficult for many reasons, including that hospitals, financially speaking, are zero sum propositions: Annual budgets govern allowances for departments. A previous blog discussed the trade off between different infection prevention activities given a constant budget through a fictional story. Bruzek's article highlights how focus here might lead to shortcomings there, all things being equal (i.e., budgets and resources being constant), in a real situation.

One might think that hospitals should simply do a better job of planning for contingencies like the Ebola preparations in which they are now engaged. Perhaps they could, but it's not necessarily simple; budgetary contingencies are usually for things that are random but can be conceived and planned for. Nobody forecast this Ebola event or the implications for US healthcare, and no hospital could rightly be expected to have included Ebola preparations in their fiscal year planning.

Moreover, this situation may have been unplannable. While analyses of public health threats, including bioterrorism, have considered a broad range of issues, I don't have the sense that anyone truly anticipated the extent of the hospital, media, or political issues encountered in the US recently. Nonetheless, the need to prepare for complex unexpected events cannot be denied.

So how do we plan for the unplannable? To address the issues mentioned in Bruzek's article would require specialized human resources and the funds to engage them on a surge basis, in addition to money for PPE. Planning for the availability of such human, material, and financial resources is not easy when they are required randomly, rarely, and -- as in this case -- widely. It's important for public health researchers, professional organizations, and trade groups to study and address such issues, because if there's one thing nature has taught us, it is that there will be a next time.

Fearbola

Some people in the US have absolutely panicked over the threat of Ebola at home. To cite but a few examples:

• A Portland, Oregon, high school canceled a visit by African students, citing concerns about Ebola. The 18 visiting students came from Republic of Congo, Niger and Ivory Coast, none of which currently have reported cases of Ebola, according to the WHO.
• Two children who recently moved to the US from Rwanda are being kept home from school after parents at an elementary school in New Jersey voiced concerns. Rwanda is in East Africa, over 2,500 miles from the West African areas where Ebola virus is currently circulating.
• An assistant principal at a North Carolina middle school has to spend 21 days working from home when she returns from a mission trip to South Africa, by order of the school board. The chairperson of the school board explained why: "It’s not that we think that she poses any type of risk, but it's public perception here that we're concerned about.

More examples are described in a recent CNN article, which also notes that:

This is getting ridiculous. While the threat of Ebola is very real in Africa, the paranoia it's generated in the United States is unreal.

Many baseless actions are being taken out of "an abundance of caution", and it's not only in the US: A recent article by Andrew Higgins describes similar behavior in Europe.

While listening to the radio while working today, it struck me how someone having a case of air sickness on a commercial jetliner now makes the national news. Perception of risk is a notoriously sticky subject, but perhaps it's a good time to begin a conversation on how to educate people better on the topic. Could some basic elements of risk assessment be taught, for example, in high school?

(image source: Wikipedia)

Ebola versus influenza and some thoughts on screening

My colleague Eli Perencevich wrote an interesting blog this week in which he discusses airport screening. He points out that some of the discussion surrounding travel restrictions and Ebola are related to ideas from (and models of) epidemics of respiratory viruses, including the 2009 H1N1 pandemic. In the post he highlights some of the important differences between Ebola and influenza:

. . . Ebola is slower moving, has a much longer incubation period (especially compared to the duration of a transcontinental flight), and is not contagious before symptoms develop. What does this mean? It means that if Ebola was as infectious as influenza, millions would have already died - apocalypse. It also means that since Ebola is not transmissible during its long incubation period, it may be possible to quickly isolate patients when symptoms develop. Thus, airport screening on exit or entry could limit transmission and perhaps through early diagnosis allow Ebola infected patients to receive life saving treatment more quickly. 

Later in the post he highlights the need for mathematical model-based analysis of the impact of specific Ebola screening programs. I recommend reading the blog.

As I mentioned in a comment to the piece, in addition to incubation period, it's useful to consider the serial interval (the period between infection and transmission; sometimes also referred to as the generation interval or generation time) and basic reproduction ratio (R₀). As discussed before, estimates for R₀ for Ebola in this event are similar to estimates of R₀ for pandemic influenza events. White and Pagano estimate the serial interval for a 1995 outbreak of Ebola in Congo to be 5.4-7.6 days and the WHO Ebola Response Team estimates the serial interval for the current epidemic to be near 15 days. By comparison, estimates of the serial interval for the 2009 pandemic of influenza fall in the range of 2.5-3.0 days. Ebola has much longer serial intervals than does influenza.

What do we take away from this? One thing is that the serial interval is important for understanding the speed of spread. Perencevich observes that

. . . the first case of Ebola is thought to have occurred 307 days ago on December 6th in a two-year old boy. Since that time there have been an estimated 8,032 cases (granted these could be underestimates). If you compare a similar 307-day period for 2009 H1N1, April 12, 2009 to February 12, 2010 CDC estimated that between 42 million and 86 million cases occurred in the US with a mid-level estimate of 59 million people infected. Think about that -- 7,300 times more cases of H1N1 using the mid-level estimate during the same 307 days.

It's clear, then, that equating influenza and Ebola on the basis of R₀ alone is misleading. Thinking of R₀ as a reproductive factor for each generation of infection (at the beginning of an epidemic in a susceptible population) and the serial interval as how rapidly generations of infection occur, however, it becomes clearer that the much shorter serial interval of influenza is related the explosive emergence of influenza cases in 2009-10 relative to Ebola in 2013-14, despite the similar R₀ values. It's more complex than this in reality; Wallinga and Lipsitch present a detailed mathematical treatment of how generation intervals shape the relationship between epidemic growth rates and reproductive numbers, and Lipsitch et al illustrate, within the context of SARS, how incubation period, serial interval, and epidemic growth rate combine to produce estimates of R₀.

Another thing to ponder is that longer serial intervals can, depending on the length of the incubation period, give more time to institute control measures. On the one hand, the long serial interval relative to incubation period in the case of Ebola may suggest a higher likelihood of detecting an infectious traveler in an airport than there is for influenza. On the other hand, the extremely low incidence of Ebola in passengers must also be considered; it may not be an efficient activity to devote resources to.

I agree with Eli that mathematical models can help shed light on such questions. Perhaps such models have been published, I admit to falling behind on the mathematical epidemiology of Ebola results in the last two weeks. 

(image source: David Hartley)

Ebola, EHRs, and the difficulty of communication

A quick update to a point discussed in the last post. On Thursday night, the Dallas hospital treating the patient suffering from Ebola virus disease explained the mix-up over his travel history. A news release on the hospital's website reads:

10/02/2014
 . . . Protocols were followed by both the physician and the nurses. However, we have identified a flaw in the way the physician and nursing portions of our electronic health records (EHR) interacted in this specific case. In our electronic health records, there are separate physician and nursing workflows.

The release then explained that the flaw had been remedied, by relocating the "travel history documentation to a portion of the EHR that is part of both workflows" and to "specifically reference Ebola-endemic regions in Africa".

The promptness of the communication was reassuring and helpful, and suggested that an analysis of the situation had been undertaken promptly, a cause of the error identified, and action taken to fix it. But 24 hours after the news release, a perplexing clarification was posted:

10/03/2014
We would like to clarify a point made in the statement released earlier in the week. As a standard part of the nursing process, the patient's travel history was documented and available to the full care team in the electronic health record (EHR), including within the physician’s workflow.

There was no flaw in the EHR in the way the physician and nursing portions interacted related to this event.

It's difficult to interpret the dissonance of these two releases, and I think they highlight a hugely important in hospital care: the challenges of effective communication between all members of the healthcare team.

Joyce Frieden wrote a very nice essay on the Dallas episode (published before the hospital's "clarification"), which I recommend reading. One passage describes some of the challenges to effective communication in the clinic:

Although the EHR could have been configured to import the nursing notes -- or at least their key items -- into doctor's notes automatically, "I'm sure some doctors would say it would be a bad idea because it would fill their notes with stuff they're not interested in," he [Dr Dean Sittig] continued. "So that's the culture of the two professions not respecting what each profession does. Whereas before docs had to flip through the nurse's notes to get to where they wanted, now they're on a separate tab. The flaw was that they weren't pushed into the doctor's face."

The importance of effective communication, from the perspective of the Magnet® process, has been discussed by Swanson and Tidwell, who note that 

One characteristic of exemplary professional practice is meticulous attention to communication processes. . . . This use of SBAR has created a standardized approach to information sharing. It has created a shared mental model for effective information transfer by providing a standardized structure for concise, factual communication among clinicians, whether it is nurse-to-nurse, doctor-to–doctor, or nurse-to-doctor communication. It is now used to ensure that patient information is consistently and accurately communicated, especially during critical events, shift handoffs, and patient transfers between levels of care. [Emphasis added.]

Apparently this critical nurse-doctor communication and information transfer didn't occur during the patient's hospital visit on September 26th.

Effective communication is a human process. Software should be used to improve that process, not replace it.

(image source: David Hartley)

Ebola and the cult of vitamin R

This week saw the appearance of Ebola virus disease in a Liberian visitor to the United States. Active transmission here is not expected and public health authorities have done extensive contract tracing. Fifty individuals who were potentially exposed to the virus are being monitored and a small number are in isolation. 

First, a brief description of the episode. A man who had direct contact on September 15th with a woman suffering from advanced Ebola virus disease in Monrovia, Liberia, traveled to Dallas, Texas, to visit relatives. He flew from Monrovia to Brussels on the 19th of September and took a connecting flight to Washington DC before catching a final flight to Dallas, arriving on the 20th. He was screened for fever and exposure at the airport before departing Liberia; apparently, his answers to a screening questionnaire were inaccurate. After arriving in Dallas he remained asymptomatic for several days and began suffering symptoms on the 24th. On the 26th he presented to the hospital. (Note: some news accounts report the date as the 25th.) At this first visit he was evaluated, prescribed antibiotics, and sent home to the relatives with whom he was staying in Dallas. He subsequently deteriorated and was transported to the ED by ambulance on the 28th. The positive test for Ebola virus was received on the 30th.

Many details about this event are unsettling. To me, especially disappointing is that the man's travel history was not a factor in the clinical diagnosis on the 26th, although a nurse was informed that he was visiting from Liberia. The nurse entered the information into the electronic health record (EHR), following protocol, but that didn't trigger suspicion. The hospital has since clarified why: There are separate physician and nursing workflows, and patient travel history did not automatically appear in the physician's standard workflow. The doctor never saw the information.

I think it's also interesting that the man was prescribed antibiotics for what turned out to be a viral illness. In a sense, this is a familiar story: change the name of the virus and it's a scene that occurs daily in many clinics and office visits. It seems ironic that, a week after the White House released its National Strategy for Combating Antibiotic-resistant Bacteria, this physician-patient encounter resulted in the apparent inappropriate prescription of antibiotics. As the National Strategy tells us, 

. . . a growing body of evidence demonstrates that programs dedicated to improving antibiotic use, known as "antibiotic stewardship" programs, can help slow the emergence of resistance while optimizing treatment and minimizing costs. These programs help providers prescribe the right antibiotic for the right amount of time and prevent prescription of antibiotics for non-bacterial infections. It is imperative that such programs become a routine and robust component of healthcare delivery in the United States. (emphasis added)

To be fair, the man may have had a bacterial infection at the first hospital visit, in addition to the unsuspected Ebola virus infection. We don't know; it's a matter of his private health record. However, I am reminded of how a physician colleague once described the pervasive inappropriate, and often rushed, use of antibiotics,

It's a common problem. Patients present with vague complaints that are plausibly due to bacterial infection and there is a very low threshold for prescribing antibiotics. The patients often request or insist on it, and it often seems harmless to acquiesce. In fact, many doctors view prescribing them as a protection mechanism in case there is an infection or one develops. It's so common that in many clinics and EDs ceftriaxone is referred to as "vitamin R".

Perhaps the antibiotic prescription dimension of the encounter on the 26th is all too understandable.

One can hope that a thorough, transparent investigation and analysis of this entire episode can produce helpful knowledge on how to harden healthcare systems for routine healthcare as well as extraordinary events like this one. In the meantime, the CDC has produced clear guidance for evaluating patients with a history of traveling to epidemic regions.

Acknowledgement: The title is inspired from a Medscape Connect item entitled "The cult of Vitamin R", which no longer appears to be available online.

(image source: Wikipedia)

Epidemiology and behavior in the time of Ebola

This week the WHO Ebola Response Team published a paper raising the notion that Ebola could become endemic in the human population of West Africa. The idea hadn't occurred to me previously, and it struck me as very unlikely. After all, this is a directly transmissible disease that, as many have told us, we know how to control.

After reflecting on the possibility, however, I don't think it can be discounted out of hand. On the one hand, breaking the chain of transmission can be achieved theoretically with careful attention to infection control and prevention practice, which is well defined in the healthcare environment. On the other hand, this isn't a nosocomial outbreak. Community transmission is the major driver of incident cases, so changing human behavior in the community must occur if this epidemic is to be stopped. In general behavior is hard to affect, and in this case it may be even harder, given recent descriptions of distrust between healthcare providers and the community.

As I've mentioned before, one of the uses of mathematical modeling is to support clear and careful thinking. In this case, epidemiologists have applied models to estimate the basic reproduction ratio, R₀, and have found it to be greater than 1, consistent with estimates from past outbreaks. Such an R₀ suggests that the virus has the potential to circulate permanently in the human population at some non-zero endemic prevalence. Endemic prevalence levels could be, relatively speaking, high or low (or intermediate). If low enough, the disease could fade out stochastically on its own, but at higher prevalences the continual danger of sporadic cases could persist indefinitely. Models can help us gain a sense of the relative likelihood of such outcomes.

The risk factors for acquiring Ebola virus infection are well known. If effective interventions reducing risky behavior are instituted widely and adhered to, they may reduce the effective reproduction ratio, R_eff, to less than 1, thereby breaking the chain of transmission. Achieving that must entail not only nosocomial infection control but also infection prevention through behavioral change in the community.

Changing behavior surely involves building and rebuilding trust between healthcare providers and local people. I suspect and hope that the recent massive pledges of, and plans for, assistance will help build the necessary rapport and trust. Maybe the construction of clinic facilities that better support effective care will help advance such endeavors. One thing is certain, however: the longer those pledges take to become reality, the more likely the worst scenarios for the course of this epidemic become.

(image source: Wikipedia)

Ebola: Mutation, selection, and all that

The New York Times recently published an op-ed on the Ebola situation in western Africa. One of the things discussed by Michael Osterholmn in that essay is the possibility that "an Ebola virus could mutate to become transmissible through the air." I think this is an interesting idea; if the currently circulating virus were to become dramatically more transmissible, it would make an already desperate situation dire.

The issue of mutation and selection is complex, as described in an excellent post by Jamie Jones. What selective pressures are acting upon Ebola viruses circulating in western Africa currently, and how those might alter the clinical epidemiology of the disease, are interesting and relevant questions.

Many have reacted to the question of how real the risk described by Osterholm is. I think positing such possibilities, and the ensuing discussion, is helpful. Even if the possibility is a false alarm, having people think through the issue, likelihood, and potential impact has value. It should not, however, distract us from important and desperately needed public health operations on the ground, or advocacy efforts to increase the resources for those operations.

(image source: Wikipedia)

On truthiness, celebrities, and math

Katy Waldman recently published an article discussing how people's minds tend to grasp at the "low-hanging cognitive fruit" in daily life. She describes how sometimes we accept ideas as facts according their "truthiness" (a term coined by Steven Colbert in 2005). It's an interesting article and I recommend reading it. It makes me wonder about the role of truthiness in health-related behavior.

Colbert has described the notion of truthiness:

It used to be, everyone was entitled to their own opinion, but not their own facts. But that's not the case anymore. Facts matter not at all. Perception is everything. It's certainty. . . . Truthiness is "What I say is right, and [nothing] anyone else says could possibly be true." It's not only that I feel it to be true, but that I feel it to be true. There's not only an emotional quality, but there's a selfish quality.

Waldman surveys some of the evidence for truthiness: how people, instead of analyzing data critically to draw conclusions, sometimes accept ideas based on seemingly unrelated criteria, like the aesthetic presentation of a written message or the familiarity of a message bearer's name.

Within the realm of health behavior, truthiness can be devastating. In epidemiology, for example, it is often said that people who suffer from a condition tend to look for and find a cause, whether one exists or not. Truthiness reminds me of Jenny McCarthy's views on vaccination and autism, which she described during an interview on The Oprah Winfrey Show:

Winfrey: So what do you think triggered the autism [in your son]? I know you have a theory.
McCarthy: I do have a theory.
Winfrey: Mom instinct.
McCarthy: Mommy instinct. You know, everyone knows the stats, which being one in one hundred and fifty children have autism.
Winfrey: It used to be one in ten thousand.
McCarthy: And, you know, what I have to say is this: What number does it have to be? What number will it take for people just to start listening to what the mothers of children who have autism have been saying for years? Which is that we vaccinated our baby and something happened. . . .
McCarthy: Right before his MMR shot, I said to the doctor, I have a very bad feeling about this shot. This is the autism shot, isn’t it? And he said, “No, that is ridiculous. It is a mother’s desperate attempt to blame something on autism.” And he swore at me. . . . And not soon thereafter, I noticed that change in the pictures: Boom! Soul, gone from his eyes.

The post hoc, ergo propter hoc fallacy of the passage has a high truthiness to many, even though scientific bodies have debunked the notion that vaccination causes autism.

How do "truthy" fringe ideas persist and grow in the general population? Deffuant and coworkers in 2002 published a study applying agent-based modeling to analyze the propagation of extremist views. Nigel Gilbert's book describes the study succinctly:

In Duffuant et al's model, agents [individuals] have an opinion . . . and a degree of doubt about their opinion, called uncertainty . . . An agent's opinion segment is defined as the band centered on the agent's opinion, spreading to the right and left by the agent's value for uncertainty. Agents interact randomly. When they meet, one agent may influence the other if their opinion segments overlap. If the opinion segments do not overlap, the agents are assumed to be so different in the opinions that they have no chance of influencing each other. If an agent does influence another, the opinion of one agent (j) is affected by the opinion of another agent (i) by an amount proportional to the difference between their opinions, multiplied by the amount of overlap divided by agent i's uncertainty minus one. The effect of this formula is that very uncertain agents influence other agents less than those that are certain.

 . . . The model shows that a few extremists with opinions that are not open to influence from other agents can have a dramatic effect on the opinions of the majority . . .

In the case of vaccination and autism, the high truthiness (to some) of the idea that MMR vaccine causes autism produces a group of people very certain in their beliefs. Duffuant et al, working within the context of political ideas, show that such a group can impact the opinions of others, thereby propagating their ideas.

Perhaps similar dynamics apply to the case of vaccination, and potentially other health-related memes such as the raw milk movement. I also wonder about the truthiness of the local myths surrounding Ebola and how those might spread more widely, potentially affecting public health in outbreak areas adversely.

(image source: Wikipedia)

Why model infectious disease: Ebola

Several weeks ago I wrote a blog on why modeling infectious disease is useful. Now seems like a good time to highlight a few issues regarding "why model?" within the context of the current Ebola event. Science Insider recently published a very nice piece on Ebola modeling and some initial results from different groups working the issue. Discussing the article with a few colleagues who are not modelers, however, I sensed some skepticism regarding the past track record of models and why it's useful to model this outbreak.

As described by many authors previously (see the links in the previous blog), a major use of modeling is to help researchers think carefully about a problem. That's especially true in the current situation, where models can help analyze complex issues. A few examples include:

• What can be derived from data in hand, or data that can be collected, to improve our ability to clarify the situation? 
• Can we infer how quickly the virus is being transmitted and whether it is decreasing, increasing, or staying the same (questions regarding the basic reproduction ratio, R₀, and the effective reproduction ratio, R_eff)?  
• If vaccines become available, what coverage and efficacy might be necessary to control the outbreak (i.e., reduce R_eff below 1)? What vaccination strategies are likely to make optimal use of resources?
• Are there combination interventions that might prove effective at reducing the incidence of infection? 
• What is the likelihood of Ebola cases arriving in distant nations via air travel? 

In short, there are plenty of questions that modeling can help elucidate.

One should be skeptical about any epidemiologic method, including mathematical and computer modeling, when the stakes for public health are so high. Ultimately, however, policymakers need timely and defensible analytic guidance to support allocation of scarce resources. Modeling is one component of such guidance.

(image source: David Hartley)

Nowhere is it written that dangerous pathogens must have high basic reproduction ratios

As discussed previously, there are lessons aplenty to learn from the ongoing Ebola outbreak in West Africa. One simple lesson is this: Even with a low basic reproduction ratio (symbolized mathematically as R₀), a pathogen can still spread widely under the right conditions.

Current estimates of the basic reproduction number for this Ebola outbreak are roughly in the range of 1.3-2.5. That's pretty modest when compared with other notorious agents. Estimates of R₀ for smallpox outbreaks, for example, were typically 4-10 and those for cholera epidemics can be in the range of 3-12. Measles outbreaks can have R₀ values of up to 18.

R₀ itself is sometimes thought of as a surrogate for "epidemic potential". Certainly, and by definition, pathogens with high R₀ spread quickly, whereas pathogens with lower R₀ don't. Does this mean that pathogens possessing relatively low values of R₀ have lower potential to harm public health?

Certainly not. In fact, pandemic influenza viruses, for example, often fall in the range 1.5-2.0. Pathogens associated with lower values of R₀ can spread widely if control efforts are not effective. In the case of pandemic influenza, control measures include vaccination and handwashing. In the current Ebola situation, due to a range of social, economic, and political factors, it has been difficult to implement widespread, effective control measures. The infection has thus spread and will likely continue do so in the region.

Does this have implications for other infections? It absolutely does. One could imagine some theoretical pathogen, for example, that is spread predominantly by hands (call it "pathogen X") and that is not killed by alcohol based hand rub (ABHR). Then, in circumstances where ABHRs are used in place of handwashing, one might imagine that pathogen X could, over time, become widely prevalent, even if it does not possess a high R₀. Pathogen X might be similar to Clostridium difficile; one estimate of R₀ for C. difficile is in the range 0.5-1.5.

For this reason, we should not think only in terms of R₀ for classifying pathogens as dangerous or not. While high R₀ pathogens spread quickly, leaving little time to react and take action, Ebola in West Africa this year demonstrates that a pathogen possessing a more modest R₀ can result in a dangerous public health situation. 

There's a story, which is possibly apocryphal, that Enrico Fermi once remarked that nowhere is it written that the laws of physics must be linear. I think there's an analogue that should be kept in mind in infectious disease epidemiology: Nowhere is it written that dangerous pathogens must have high R₀.

(image source: ECDC) 

Outbreaks and do-overs

The current Ebola outbreak in Western Africa has been remarkable in terms of the number of cases and deaths; length and geographic extent of the outbreak; and its designation as a public health emergency of international concern. What could have been done differently to change the course of events? Thorough analyses of the outbreak and response will be done, and that will take time, but I think there are several things to consider.

More international assistance early in the outbreak. Early intervention is a mantra of modern medicine and public health, and indeed organizations like MSF and others brought impressive resources to bear early in the outbreak. Yet, transmission wasn't controlled and the epidemic grew. More resources are needed urgently. In hindsight, greater multilateral international aid earlier in the outbreak was needed, but how can nations know when NGO efforts need supplemental resources? Perhaps studying the early phases of this outbreak can suggest a way.

Better communication. The social disruption evident in this event is painfully clear and may have been intensified by the difficulty of communicating important public health messages. Anecdotes of healthcare workers being attacked and of disbelief that Ebola virus even exists are but two examples.

Balanced communications in the United States was mixed. On the one hand, many valid messages were circulated, including that Ebola poses little risk to the US general population. On the other hand, one expert told Congress that

We know how to stop Ebola with strict infection control practices, which are already in widespread use in American hospitals, and by stopping it at the source in Africa.

The second part of the statement is true enough: stopping an outbreak before it spreads is canonical in public health. However, the first part of the statement implies that strict infection control practice can prevent infection of healthcare workers and others in a hospital. That's a little problematic. If that were so, there wouldn't be problems with hospital-associated infection in the US.

By that calculus, for example, the 2011 outbreak of KPC-producing Klebsiella pneumoniae at the NIH shouldn't have occurred -- and yet the infection control practice in that event was meticulous from the initial presentation of the patient at the facility. What if an Ebola patient isn't recognized immediately when presenting at a US emergency department? And if a case is recognized, is infection control as it is actually carried out in practice likely to be effective? Such questions apply to any nosocomial pathogen, and I think it's important to ask: Given that KPC escaped a patient's room even with full precautions, why not Ebola?

Drug therapy. There are no approved treatments for, or vaccines against, Ebola virus infection. The development of new drugs is a scientifically, economically, and politically complex activity. The urgent need for new antibiotics, for example, has been discussed in connection with a large and growing need. The CDC recently reported that

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections. Many more people die from other conditions that were complicated by an antibiotic-resistant infection. 

That's a massive burden of disease compared to the Ebola outbreak at present. Every case of any infection deserves effective management, but where is the incentive for drug development for Ebola and other exotic, low incidence infections? It is literally taking on act of Congress to help spur new antibiotic drug development in the US. Clearly drug therapies for Ebola would have been beneficial in this outbreak, and how to incentivize development seems an important question. In the absence of effective therapies and drug regimens, misinformation about bogus cures inevitably spreads and requires time and resources to counter.

Certainly these and related issues will be discussed and studied in depth in the coming months and years. Answers to the question of what could we do better next time must be found, because there will be future outbreaks of virulent emerging infections. How will we react?

(image source: CDC) 

Public health events and open source software

As a quick follow up to the last post on Ebola and the one before that on open source software and computing, a great example of the intersection of public health, computing, and free analytic software has recently been published. In his Ecologically Oriented blog, Jim Bouldin has written about some of the statistics of the West African Ebola outbreak from its inception. In the piece he posts R code for scraping and analyzing up-to-date WHO data on cases and deaths in Africa. The post illustrates how data can be acquired and analyzed using robust open source software and how results -- including the code used to generate them -- can be promulgated rapidly. Bravo!

Ebola: Thoughts on a public health disaster

The current outbreak of Ebola hemorrhagic fever in western Africa has been ongoing for months. It is a remarkable and tragic event. Sadly, there is no known cure, the case fatality proportion is high (historically 50-90%), and prevention is difficult in the areas where the virus is currently spreading.

Nations outside Africa are now recognizing the possibility of Ebola-infected travelers returning home. Importation of disease is a public health issue for other infections, such as measles, outbreaks of which are commonly sparked by visitors returning from areas where cases are prevalent. In the case of Ebola, one traveler died on the last leg of a West African trip, before returning home to Minnesota, so there's good reason to believe that importation could occur. It's probably unlikely, however, given the current level of awareness. Some African airlines, for example, have curtailed air service in affected areas and are screening passengers for signs of illness. International guidance on passenger screening is being evaluated as well. Moreover, CDC has issued interim guidance regarding Ebola for airline flight crews, cleaning personnel, and cargo personnel.

If an infected or infectious traveler does return, is it unlikely to result in the dramatic transmission currently observed in Africa. The current heightened awareness makes it very likely that travelers returning from affected areas would be evaluated for possible Ebola infection should they develop illness and present to a healthcare provider. The CDC has issued guidance advising healthcare workers to

be alert for signs and symptoms of EVD [Ebola virus disease] in patients with compatible illness who have a recent (within 21 days) travel history to countries where the outbreak is occurring, and should consider isolation of those patients meeting these criteria, pending diagnostic testing. 

Infection control procedures are standard and the necessary supplies are plentiful in Western hospitals, making it unlikely that an Ebola patient would cause secondary infections in healthcare settings.

Moreover, Ebola virus is much less transmissible than many other viruses. Measles virus, for example, has basic reproduction ratios in the range of 11-18, whereas those for Ebola have been estimated to be between 1-2. For comparison, the basic reproductive ratio for influenza is estimated to be 3-4, for rubella 6-7, and for chickenpox 10-12. The ratio for pertussis is similar to that of measles. One wonders what the basic reproduction ratio is for the current outbreak in Africa is (and if analytic approaches using social media might be helpful for estimating it).

Given that the current outbreak is so large compared to past outbreaks of Ebola, we might learn some lessons about this exotic disease. For example, are there transmission pathways that we don't know of at present? Aerosol transmission is thought to play only a minor role if any in transmission of human strains of Ebola virus, but perhaps new information will emerge from future epidemiological studies of the current outbreak.

What is for sure is that the events in Africa are a tremendous human tragedy. I hope that the desperate measures of closing schools and nonessential government services will help to control the spread of the virus. It isn't clear that it will.

(image source: Wikipedia)