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2 Pandemics, Epidemics, and Outbreaksfree

  • Peter C. Doherty
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What is the exact definition of pandemic?

p. 42A novel infection—new and previously unconfronted—that spreads globally and results in a high incidence of morbidity (sickness) and mortality (death) has, for the past 300 years or more, been described as a “pandemic.” The word derives from pan—“across”—and demos, meaning “people” or “population.” A pandemic spreads across all people. The 1918–1919 flu virus disseminated worldwide, without regard to race, location, cultural belief system, or social status.

There is, though, some disagreement about how and when the term should be used. Until very recently, evidence of contagion monitored by the rapid spread of unfamiliar and generally distressing symptoms was still the main measure of a new, readily transmitted disease. Before the germ theory of infection became established in the mid- to late nineteenth century and for many years thereafter, the prevalence and severity of clinical impairment was all that we had to go on. As summarized in the previous chapter, that situation has now vastly changed, with the 150-year—and continuing—progression in the unraveling of infectious diseases and the incredible advances in both understanding and diagnostic technology that advanced gradually p. 43until the 1980s or so, to gather ever increasing momentum with the molecular biology revolution of the past 30 years. Now, modern science provides us with tests that enable the identification of any causative organism both quickly and definitively.

This capacity for rapid diagnosis means that we no longer rely solely, if at all, on seeing severe symptoms. A readily detectable infectious agent that, like the 2009 SW flu virus, tends to cause relatively mild disease in most people but spreads rapidly around the planet will, according to currently used criteria, legitimately be described as causing a pandemic. That’s where confusion can arise: the general sense is that “pandemic” is synonymous with catastrophe. With both the media and the broader population ultimately perceiving that the 2009 SW flu pandemic was no more dangerous than the familiar, recurring, “seasonal” influenza epidemics, many had the sense that the regulatory and public health authorities had vastly overstated the level of risk.

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Who declares a pandemic?

Pandemic infections are, by definition, global problems that cannot be dealt with exclusively by individual nation-states. Epidemiologists, statisticians, and other professionals working at the World Health Organization (WHO) based in Geneva, Switzerland, have the responsibility for declaring whether or not a pandemic is occurring. Charged with monitoring and protecting human health everywhere on the planet, the WHO is one of the better functioning agencies of the United Nations. Unlike some UN operations, it rarely attracts the ire of political extremists and xenophobes. Even so, the June 11, 2009, WHO decision to raise the level of influenza pandemic alert from Phase 5 to Phase 6 ultimately stimulated a great deal of negative media commentary. This first flu pandemic of the twenty-first century just wasn’t up to expectations! p. 44Nonetheless, working with various national bodies, the WHO generally does a good job, and the 2009 influenza experience illustrates the various stages that culminate in the declaration of a pandemic.

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Was the H1N1 “swine flu” really so mild?

It gets a mixed review. Part of the perception that the 2009 H1N1 SW flu was not so bad reflects that those in the 65+ age groups, who are usually the most vulnerable in a typical influenza epidemic, were relatively unaffected due to protective immunity acquired by exposure to a cross-reactive virus that had since disappeared from human populations. As we discussed in the previous chapter, immune memory can last for 50, even for 70 or more years. On the other side of good/bad equation for the 2009 virus was the evidence of more severe disease and a greater incidence of hospitalization in indigenous communities than is usually seen with influenza. This could be a reflection of poor background health due to diabetes, malnutrition, alcoholism, and so forth, but there are also some indications of a genetic susceptibility component.

In addition, when compared with the normal “seasonal” flu strains, the admission of pregnant women in the third trimester to critical care beds was very high, and it seemed to affect a disproportionate number of fit, young adults. Some were saved by being hooked up to an ECMO (extra corporeal membrane oxygenation) machine that effectively rested their lungs during the process of natural repair. While 50% of those who would likely have died without ECMO made a full recovery, this is a scarce, expensive technology, and along with the available critical care beds, that emergency resource was quickly overwhelmed. The normal load of, for example, pediatric cardiac repair operations had to be cancelled until the emergency was over.

In reality, the WHO was not doing so badly when it called the 2009 influenza a pandemic. Though the WHO (like any p. 45global operation, public or private) has its limitations, only an international organization can (with the help of national agencies) take the ultimate responsibility for declaring that humanity is facing a pandemic. That has to be done with care and must follow established guidelines. The rules have to be clearly thought through and stated, as the ensuing response will require the deployment of substantial administrative and physical resources. Sounding the pandemic alarm can’t simply be left to the ad hoc judgment of a select few key individuals, no matter how wise and well-informed they may be. The turnover rate for WHO officials can be high and even mandatory, given strict rules governing the duration of contracts, retirement at age 60, and so forth. Being part of a global agency, WHO officers may also come from very different cultural and economic backgrounds. What ranks as common sense for one particular group may seem less clear for others.

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How does the WHO operate?

While the central office is in Geneva, the planet is divided for administrative purposes into 6 regions: Africa, Europe, the Eastern Mediterranean, Southeast Asia, the Western Pacific, and the Americas. Each has a WHO office that serves between 11 and 53 different countries and, as can be seen in Figure 2.1, the division is not strictly geographic. The Regional Office for the Western Pacific, which includes nations as diverse in geography, size, and location as Australia, China, and Tuvalu, is located in Manila, while that for Southeast Asia is in New Delhi. Some Indonesian territories located, for example, to the west of China on a standard global map come under the South-east Asia office.

With influenza, the WHO defines six grades of Pandemic Alert Phase, based on the incidence of the disease and the extent of spread within and between the various regions. The criteria are published and available on the Web for all to see. A Phase 2 Alert, for example, merely informs public health officials, the p. 46 p. 47media, and anyone who cares to look that a new influenza virus has emerged from some animal reservoir (such as pigs, in the case of the 2009 pandemic) and is causing infection in people. Phase 4 means that human-to-human transmission is at a level where there is a continuing, sustainable outbreak within a community. Phase 5 means that the outbreak has now spread to at least two countries in a particular WHO region. The final Phase 6 Alert is issued when human-to-human spread progresses from one WHO region to a second and significant numbers of people are infected.

Figure 2.1. This figure illustrates the extent of the different WHO regions, which relate to the location of the WHO regional offices, rather than to any strict geographic division of the planet. The fact that a Phase 6 Pandemic Alert is issued when a novel, rapidly spreading influenza A virus is found to cause disease in more than one region illustrates how, if that criterion is used, a pandemic could be legitimately declared for, say, a mosquito-borne pathogen (like the Chikungunya alphavirus) that is expanding its territorial impact while still operating within the confines of one continental land mass. Chikungunya, which comes out of Africa, has in fact already extended beyond that range by moving around the Indian Ocean rim, down into Indonesia and Irian Jaya, and up into Italy.

Reproduced with permission from the World Health Organization.

This classification system, which depends on the distribution and prevalence of the infection, means that the declaration of a Phase 6 influenza pandemic alert does not basically depend on the virulence, or pathogenicity, of the particular influenza A virus. But, given that the terms “pandemic” and “catastrophe” are synonymous to most people, why not change the definition? The problem is that doing so means coupling two different criteria and deciding ahead of time on outcomes that may not ultimately prove to be valid. For example, an influenza infection that seems to be not too bad when it occurs among those who are adequately housed and fed in a wealthy country may prove to be a true catastrophe for the less fortunate. Differences between rich and poor nations involve more than food and shelter, and include a multitude of factors like the availability of medical oxygen support and rapid access to the appropriate antibiotics for treating secondary bacterial infections that can deliver the coup de grace in a viral pneumonia.

Then, apart from any social disadvantage, there is the genetic variation that can distinguish ethnic groups and the threat, particularly with influenza, that the virus may mutate to a more virulent form. “Pandemic” applies to all populations equally, even when they are not in fact equal. Once a novel pathogen starts to spread rapidly and widely, a pandemic must be declared.

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Should the pandemic classification system be refined?

p. 48There are many who think so. One possibility would be to have it reflect two numbers: the first denoting how bad a disease is clinically, and the second the extent of transmission. Thus, we might describe a generally mild but highly transmissible disease as a Level 2/6 pandemic—low clinical profile but high potential of transmission. That would pretty much characterize what happened in 2009 with the H1N1 SW flu, while the 1918–1919 influenza might have been a 5/6. Why 5/6 and not 6/6? Well, it doesn’t look to have been as severe overall as the greater than 50% mortality associated with the relatively small number (less than 600 so far) of cases caused by the H5N1 “bird flu” virus. There is, though, some discussion that, because these H5N1 viruses (and the vaccines made from them) tend to stimulate suboptimal antibody responses in humans, the background infection rates may have been greatly underestimated, at least in those Asian communities where there is the possibility of widespread contact with infected domestic ducks, quail, and chickens.

The only time we might have seen anything like a “6/6” severity in humans during recorded history was the successive outbreaks of plague in medieval Europe. The worst possible “fast” 6/6 scenario is the hypothetical disease portrayed in the movie Contagion, where just about everyone who is infected seems to die horribly and the virus transmits with extraordinary ease. The fact that in the absence of drug treatment HIV/AIDS eventually kills almost everyone it infects would make it a “slow” 6/1 if we just rely on numbers and count all members of the community, rather than limiting our survey to those who are sexually active, are injecting drug users, or happen to be born to an untreated HIV carrier. On the other hand, if we accept the influenza criteria for extension to different regions, HIV could also be described as a “slow” 6/6 pandemic. With regard to AIDS, the WHO did not make a big deal about declaring a pandemic alert. That would have been pointless, p. 49as the disease had been so widely publicized over the 6 years from the time the first cases were diagnosed in New York and California until the 1987 launch of the Global Program on AIDS. The AIDS pandemic is now in its third or, perhaps, its fourth decade, but who would quibble about the difference?

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How does a pandemic differ from an epidemic or an outbreak?

These different categorizations are somewhat arbitrary, as they depend both on the novelty of a particular infection and the extent of global spread. As discussed in more detail in the later chapter on influenza, an “immune-escape” variant of an influenza A virus strain that has been circulating for years in human populations and spreads worldwide is said to be causing a “seasonal epidemic,” while a new virus that has emerged from some animal reservoir (pigs in 2009) is described as a pandemic pathogen. In subsequent chapters, some of the infections we will consider have to date caused little more than very limited, geographically constrained outbreaks. Even so, chance often plays a considerable part in determining the spectrum of what actually happens, so telling the stories of these “experiments of nature” provides insights into potential, future pandemics.

Every pandemic begins as a perhaps unrecognized outbreak that in turn leads to an epidemic. Again, it’s a matter of novelty and transmission. A prominent example of a disease that emerged suddenly from a wildlife reservoir is the 2002 severe acute respiratory syndrome (SARS). It began as an outbreak, became an epidemic, and at least as far as the U.S. Centers for Disease Control and Prevention (CDC) were concerned, was the first pandemic of the twenty-first century. It certainly fulfilled the WHO’s Phase 5 Influenza Alert criterion by spreading between humans in more than two countries in a WHO region (Western Pacific: China, Singapore, Vietnam) and then crossed the final Phase 6 Alert bridge by transmitting to, and causing further cases in, a second region: Toronto in the Americas. But, while SARS was also carried to other nations (including p. 50Australia and the United States) by infected travelers, there was no additional (or secondary) spread to colleagues, family members, or medical personnel. In the following chapter, we discuss what did happen with SARS in more detail, and you will realize that this was purely a matter of chance. The difference between SARS and the 2009 influenza pandemic was that, though both were caused by novel viruses, the number of SARS cases remained relatively small throughout. That’s where SARS may fail the WHO’s pandemic test.

There’s no doubt that SARS would, however, satisfy the criteria for traditional and sometimes historic terms like “plagues” and “pestilences” that have much the same connotation as “epidemic” or “pandemic.” The term “plague” is used both in a generic sense, to characterize any widespread infection, and to describe the plague, the terrible systemic disease caused by the bacterium Yersinia pestis that is normally maintained in a rodent (rat, mouse, squirrel)–flea (Xenopsylla cheopsis) transmission cycle. In the absence of any understanding of the cause, Y. pestis caused recurrent outbreaks and epidemics that killed millions of people in fourteenth to eighteenth-century Europe. A classical zoonosis, the severe respiratory form (pneumonic plague) can sometimes be associated with human-to-human spread. Such outbreaks occur occasionally in India, and Y. pestis was used as a biological warfare agent in World War II. Now, if caught early, it can be readily treated with standard antibiotics like streptomycin and tetracycline.

“Pestilence” has tended to fall out of modern usage, and it is most often encountered within a medieval or religious context (and perhaps the occasional heavy metal band). In Albrecht Durer’s Four Horsemen of the Apocalypse, the fourth, or pale, horseman is variously described either as “death” or “pestilence.”

Like many of the terms in this book, “plague” has a figurative dimension and is often used as a verb, for example, “Drug crime plagues the city.” And we speak about mouse or rat plagues—think of the Pied Piper of Hamelin—and p. 51grasshopper plagues (though some prefer “grasshopper epidemics”), such as the locusts described in the Bible in the book of Exodus. The pied piper story concerns the death of just about all Hamelin’s children. One speculation is that they were lured away to the disastrous (and perhaps equally mythical) Children’s Crusade of 1212, while another idea is that their disappearance is a metaphor for what happened during a plague outbreak.

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Do all pandemics involve infection?

One difficulty in all this is what we mean by “infection.” The WHO definition strictly links pandemics to diseases caused by viruses, bacteria, and the like but, of late, this term is also being used to describe global trends for the increased incidence of chronic human conditions. Hence there is the Alzheimer’s disease pandemic, the diabetes pandemic, the chronic obstructive pulmonary disease (COPD) pandemic, the cardiovascular disease pandemic, the obesity pandemic, and so on. There is plenty of medical evidence that viral and bacterial infections can play a part in the development of COPD, and may also be responsible for the early tissue damage that ultimately leads to some forms of diabetes and heart disease. However, it has not been possible to establish the sort of firm links that make a case for preventing diabetes or heart problems by, say, developing a vaccine against a particular pathogen.

Also, when we discuss obesity, cardiovascular disease, and diabetes, for example, what immediately comes to the fore is the cultural, profit-driven “pandemic” of “fast foods,” carbonated drinks with high sugar content, and so forth that seems to be ever expanding in geographical reach. Morgan Spurlock’s 2004 documentary Supersize Me tells how, if this type of diet doesn’t kill you in the short term, it can definitely decrease your life expectancy. The U.S. government, for example, still spends billions of dollars in agricultural subsidies that both block export opportunities for poorer countries and support p. 52the production of extraordinarily damaging products like high fructose corn syrup. Europe is no better.

Then, there is the rapidly expanding cultural context that thrives on the contagion of random thoughts, attitudes, and information spread globally with incredible speed via web-based mechanisms like blogs, Twitter, Facebook, and YouTube. In the world of the Internet, “going viral” means that some story or idea has spread with incredible speed. Especially among the young, this more “democratic” web-based opinion is serving to dilute and even neutralize the misinformation and focus on the trivial that is the stock in trade of regressive newspaper editors, professional gossip columnists, radio “shock jocks,” and so forth. At times, the Internet serves up examples of “good pandemics.”

Describing the rapid dissemination of ideas and physiological conditions like obesity as a “pandemic” is undoubtedly legitimate by the criterion that many are affected and that the problem extends to more than two of the WHO regions. However, I will stick to the more traditional meaning: that of diseases caused by infectious microorganisms, particularly viruses. As discussed earlier, the viruses we’re talking about here aren’t patterns in cyberspace or code invented by some Internet saboteur but are physical entities that have some form of outer coat (protein, carbohydrate, and lipid), transmit their information via a nucleic acid (RNA or DNA) core, infect human beings (and other vertebrates), and primarily cause physiological problems.

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What does the term “zoonosis” mean?

A zoonosis is simply an infection that transmits from animals to people. Though, as discussed in detail throughout this book, occasional zoonotic spread is the ultimate cause of many human disease outbreaks and ultimately pandemics, medical practitioners watch for a whole spectrum of familiar zoonotic infections that never evolve to spread horizontally between p. 53people. A classical example is the chronic, febrile debilitating disease toxoplasmosis, an infection caused by the protozoan Toxoplasma gondii that we typically contract from domestic cats. Pregnant women need to be particularly careful and practice scrupulous hand and other hygiene when around cats, as T.gondii can transmit vertically across the placenta and is a possible cause of miscarriage. Then there’s hydatid disease, in which we contract the larval form of the sheep tapeworm (Echinococcus granulosis) by inadvertently ingesting food (or soil for a small child) that has been contaminated with dog feces. Big, fluid-filled hydatid cysts can then form in sensitive organs subsequent to the larvae invading across the gut wall and disseminating throughout the body. Prior to the introduction of effective public health measures that prevent dogs from consuming sheep offal, the removal of these space-occupying hydatid cysts was a major reason for neurosurgery in, for example, northern Greece.

On the other hand, while viruses like the 1968 Hong Kong flu that likely came into the human population from pigs and ducks (see Figure I.1) make the transition from being zoonotic to pandemic infections, the idea that a patient has contracted the flu from a source other than an infected human will be the last thing in the mind of your local doctor. The exception would be if someone presents with a very severe respiratory infection in a Southeast Asian country where the H5N1 bird flu is still active in domestic chicken populations.

In the strict etymological sense, an “epizootic” or “panzootic” is the animal equivalent of a human pandemic or epidemic. Tellingly, the terms “panzootic” and “epizootic” are now more commonly used by medical public health professionals than by those concerned with veterinary problems. During the course of a recent visit to Rome as part of the celebration and formal recognition of the global eradication of the cattle disease rinderpest, I realized that those associated with the UN Food and Agriculture Organization and the OIE (Organization Internationale des Epizootiques) prefer to use p. 54the terms “pandemic” and “epidemic” when describing the distribution profiles for veterinary infectious diseases. My personal view is that the terms “panzootic” and “epizootic” are redundant and, following current English usage, we might well consign them to the deep history of the language. “Pandemic” and “epidemic” should be sufficient for our purpose.

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What is an endemic infection, and how does it differ from an epidemic infection?

Again, word usage is not all that precise. An endemic infection is one that has been well established over time in a particular institution, place, or demographic, whether local or worldwide. Diseases like HIV/AIDS and hepatitis C are endemic infections, though many would also think of them as the cause of continuing epidemics and pandemics. The dengue viruses, for example, which cause infections of limited duration, are maintained in a human/mosquito transmission cycle that is endemic to tropical regions such as Southeast Asia and the Caribbean. Such viruses spread north and south from their normal host range only when warm conditions are accompanied by heavy rainfall. Organisms like the typhoid- and cholera-causing bacteria are endemic to regions and populations in which there is no steady supply of clean water.

The term “endemic” can also be used in regard to potential pathogens that are ubiquitous in the environment but only become prominent when, for example, there is the possibility of widespread physical trauma as a consequence of violent conflict. Triggered by consistent dampness and unsanitary conditions, the fungal infection that caused trench foot was endemic to the northern European battlefields of World War 1. Further exposure of the damaged tissue to the ubiquitous soil bacterium Clostridium perfringens commonly led to gas gangrene, leaving surgeons with no alternative but to amputate. Regular changes of socks, together with rubbing whale fat into the feet, greatly reduced the incidence of this infectious p. 55disease. Gas gangrene, in which the anerobic (does not require oxygen) C. perfringens makes gas-producing toxins deep in muscle tissues subsequent to soil contamination of a gunshot, or other penetrating injury, continues to be a major problem where wounded combatants cannot get rapid access to medical or surgical intervention.

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Are plants also included in the world of pandemics?

Following the epizootic/panzootic line for animals, the correct word for widely disseminated novel plant infections would probably be “epiphytic/panphytic,” following the Greek phytos for plants. But an epiphytic (Greek epi for “upon” or “on”) plant is one that parasitizes the surface of another, not something that spreads wildly across the environment. In fact, we talk about the pandemic of Dutch Elm disease caused by the fungus Opheostoma ulmi. It makes sense to set aside the fine points of philology and describe a widespread infection in any species as epidemic or pandemic.

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In Summary

As is commonly the case, while terms like “pandemic,” “epidemic,” “outbreak,” and “endemic” can be assigned precise meanings, as in the WHO pandemic influenza alert phases, they are also used in much less precise and overlapping ways. When you encounter evocative terms like “pandemic” and “epidemic” in dramatized personal accounts and, more generally, in the visual and print media, it’s worth having a level of understanding that allows some critical assessment of how dangerous a developing situation may actually be.