This chapter is about pandemics, a somewhat ambiguous term, defined in the Oxford English Dictionary as ‘a disease prevalent throughout a country, a continent, or the world’. In present modern usage the term takes greater cognizance of its original Greek derivation and is largely restricted to global prevalence (pan demos) – all people. The same source tells us that plague has a broader meaning, implying a sudden unexpected event that is not necessarily a disease, but introducing the concept of acute, lethal, and sudden danger-characteristics that are connoted but not specifically denoted by the term ‘pandemic’.
It will become apparent that glimpses of the future must consider the emergence of new pathogens, the re-emergence of old ones, the anthropogenic fabrication of novel agents, and changes in the environment and in human behaviour. In other words ‘the problem’ in addressing infectious disease threats is not one but many separable problems, each of which must be isolated in traditional scientific fashion and separately evaluated as components of what I like to call ‘holistic epidemiology’. This emerging discipline comprises microbial and human genetics, human behaviour, global ecology, toxicology, and environmental change.
As we leave our mothers’ wombs and enter this vale of tears (and sometimes before) we are invaded by microbes that may become our lifelong companions, profiting from this intimate relationship by the food and shelter that our bodies offer. They, in turn, often provide us with nutrients or vitamins derived from their own metabolic processes and may even immunize us against future assaults by related but less kindly microbes. In other words, we and they (usually) coexist in a state of armed neutrality and equilibrium.
But humans bear a chronic burden of infectious diseases. Included in this burden are some diseases that have demonstrated a capacity to break out in pandemic form, depending on the circumstances that are defined later. The less overt contributors to human misery will be briefly reviewed before discussing the nature of the acute aberrations that comprise the more dramatic pandemics and plagues that suddenly burst forth in a catastrophic manner.
Beginning at the end of the nineteenth century and culminating in the middle of the twentieth, the battle with infections seemed allied with the recognition of their microbial cause and the consequent development of vaccines, environmental sanitation, and later, antimicrobial drugs. In high income regions the accustomed childhood infections became a rarity with the development of vaccines for diphtheria, pertussis, measles, rubella, varicella, mumps, and poliomyelitis. It is paradoxical that poliomyelitis, or ‘infantile paralysis’, emerged as a consequence of the improved sanitation of food and water that postponed infection of infants and young children to later life when susceptibility to paralysis increases (Horstmann, 1955).
Important recent studies in which population census and income level of different regions have been determined have documented the expected, that is, that the price of poverty is an increased burden of infection – particularly of the intestinal tract – and that even diseases such as tuberculosis and measles for which there are drugs and vaccines continue to burden a large part of the world. The childhood mortality from measles in Africa is expected to reach half a million in 2006 and accounts for 4% of the total deaths of children each year, and yet the disease is a current and logical target for eradication because, as was the case with smallpox, the virus has no venue other than humans, and the present vaccine is highly effective.
Tuberculosis, an ancient disease never adequately suppressed by vaccine or antibiotics, is now resurgent, aided by the new, cryptic, and terrible challenge: HIV/AIDS. In regions of poor environmental sanitation, which include much of sub-Saharan Africa, diarrhoeal diseases persist, killing millions each year, mostly children.
We are not writing here about abstruse, unsolved scientific and medical problems but obvious economic ones. This is nowhere better documented than in the rates of perinatal mortality in low and high income groups; a disparity of more than 12-fold (according to WHO statistics for 2001). The unglamorous but nonetheless deadly infantile diarrhoeas and ‘lower respiratory infections’ are among the commonplace diseases that encumber humankind in poverty-stricken areas of the globe. The leading infectious causes of death in 2002 (comprising almost 20% of all causes) are shown in Table 14.1. About 75% of all deaths from infectious diseases are geographically localized to Southeast Asia and sub-Saharan Africa.
Table 14.1 Leading Global Causes of Deaths Due to Infectious Diseases1
Although the proximate causes of pandemics are microbial or viral, there are ancillary causes of almost equal importance. These include human behaviour, season of the year and other environmental conditions, and the state of induced or innate immunity. These will be discussed in the context of specific disease paradigms.
In the short list of causes of past plagues identified in Table 14.2 are the viruses of smallpox, influenza and yellow fever, the bacterial causes of plague, cholera and syphilis, and the protozoan cause of malaria.
Adhering to this ‘short list’ pro temps, the sources of these pathogens in nature are illustrative of the variety of mechanisms by which they survive, and often flourish. Only one, the cholera Vibrio, is capable of independently living freely in the environment. The plague bacillus (Yersinia pestis) has its primary home in rodents, in which its spread is facilitated through the bites of rat fleas, which may seek food and shelter in humans when the infection has killed their rodent hosts. The Plasmodia of malaria have a complicated life cycle in which their multiplication in both vertebrates (including humans) and mosquitoes is required. The arbovirus cause of yellow fever is transmitted from one to another (in the case of urban yellow fever in humans) by mosquitoes that act essentially as flying hypodermic needles, or, in the case of jungle yellow fever, from animals (principally monkeys) via mosquitoes.
Table 14.2 Some Examples of Historically Significant Pandemics and Epidemics
Microbes (bacteria and protozoa) and viruses can enter the human body by every conceivable route: through gastrointestinal, genitourinary, and respiratory tract orifices, and through either intact or injured skin. In what is known as vertical transmission the unborn infant can be infected by the mother through the placenta.
Table 14.3 A Comparison of Prototype Pandemic Agents
Of these routes, dispersal from the respiratory tract has the greatest potential for rapid and effective transmission of the infecting agent. Small droplet nuclei nebulized in the tubular bronchioles of the lung can remain suspended in the air for hours before their inhalation and are not easily blocked by conventional gauze masks. Also, the interior of the lung presents an enormous number of receptors as targets for the entering virus. For these reasons, influenza virus currently heads the list of pandemic threats (Table 14.3).
If a disease is literally pandemic it is implicit that it is attended by high morbidity, that is, many people become infected, and of these most become ill – usually within a short period of time. Even if symptoms are not severe, the sheer load of many people ill at the same time can become incapacitating for the function of a community and taxing for its resources. If a newly induced infection has a very high mortality rate, as often occurs with infections with alien agents from wild animal sources, it literally reaches a ‘dead end’: the death of the human victim.
Smallpox virus, as an obligate parasite of humans, when it moved into susceptible populations, was attended by both a high morbidity and a high mortality rate, but it was sufficiently stable in the environment to be transmitted by inanimate objects (fomites) such as blankets. (Schulman and Kilbourne, 1963).
Influenza, in the terrible pandemic of 1918, killed more than 20 million people but the overall mortality rate rarely exceeded 23% of those who were sick.
Even before the birth of microbiology the adverse effects of filthy surroundings on health, as in ‘The Great Stink of Paris’ and of ‘miasms’, were assumed. But even late in the nineteenth century the general public did not fully appreciate the connection between ‘germs and filth’ (CDC, 2005). The nature of the environment has potential and separable effects on host, parasite, vector (if any), and their interactions. The environment includes season, the components of weather (temperature and humidity), and population density. Many instances of such effects could be cited but recently published examples dealing with malaria and plague are relevant. A resurgence of malaria in the East African highlands has been shown to be related to progressive increases in environmental temperature, which in turn have increased the mosquito population (Oldstone, 1998; Saha et al., 2006). In central Asia plague dynamics are driven by variations in climate as rising temperature affects the prevalence of Yersinia pestis in the great gerbil, the local rodent carrier. It is interesting that ‘climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague (epidemic) arose in the same region (Ashburn, 1947).
Differences in relative humidity can affect the survival of airborne pathogens, with high relative humidity reducing survival of influenza virus and low relative humidity (indoor conditions in winter) favouring its survival in aerosols (Simpson, 1954). But this effect is virus dependent. The reverse effect is demonstrable with the increased stability of picornaviruses in the high humidity of summer.
One has no choice in the inadvertent, unwitting contraction of most infections, but this is usually not true of sexually transmitted diseases (STD). Of course one never chooses to contract a venereal infection, but the strongest of human drives that ensures the propagation of the species leads to the deliberate taking of risks – often at considerable cost, as biographer Boswell could ruefully testify. Ignorant behaviour, too, can endanger the lives of innocent people, for example when parents eschew vaccination in misguided attempts to spare their children harm. On the other hand, the deliberate exposure of young girls to rubella (German measles) before they reached the child-bearing age was in retrospect a prudent public health move to prevent congenital anomalies in the days before a specific vaccine was available.
Sudden epidemics of infection may follow in the wake of non-infectious catastrophes such as earthquakes and floods. They are reminders of the dormant and often unapparent infectious agents that lurk in the environment and are temporarily suppressed by the continual maintenance of environmental sanitation or medical care in civilized communities. But developing nations carry an awesome and chronic load of infections that are now uncommonly seen in developed parts of the world and are often thought of as diseases of the past. These diseases are hardly exotic but include malaria and a number of other parasitic diseases, as well as tuberculosis, diphtheria, and pneumococcal infections, and their daily effects, particularly on the young, are a continuing challenge to public health workers.
The toll of epidemics vastly exceeds that of other more acute and sudden catastrophic events. To the extent that earthquakes, tsunamis, hurricanes, and floods breach the integrity of modern sanitation and water supply systems, they open the door to water-borne infections such as cholera and typhoid fever. Sometimes these illnesses can be more deadly than the original disaster. However, recent tsunamis and hurricanes have not been followed by expected major outbreaks of infectious disease, perhaps because most of such outbreaks in the past occurred after the concentration of refugees in crowded and unsanitary refugee camps. Hurricane Katrina, which flooded New Orleans in 2005, left the unusual sequelae of non-cholerogenic Vibrio infections, often with skin involvement as many victims were partially immersed in contaminated water (McNeill, 1976). When true cholera infections do occur, mortality can be sharply reduced if provisions are made for the rapid treatment of victims with fluid and electrolyte replacement. Azithromycin, a new antibiotic, is also highly effective (Crosby, 1976a).
The course of history itself has often been shaped by plagues or pandemics.1 Smallpox aided the greatly outnumbered forces of Cortez in the conquest of the Aztecs (Burnet, 1946; Crosby, 1976b; Gage, 1998; Kilbourne, 1981; Wikipedia), and the Black Death (bubonic plague) lingered in Europe for three centuries (Harley et al., 1999), with a lasting impact on the development of the economy and cultural evolution. Yellow fever slowed the construction of the Panama Canal (Benenson, 1982). Although smallpox and its virus have been eradicated, the plague bacillus continues to cause sporadic deaths in rodents, in the American southwest, Africa, Asia, and South America (Esposito et al., 2006). Yellow fever is still a threat but currently is partially suppressed by mosquito control and vaccine, and cholera is always in the wings, waiting – sometimes literally – for a turn in the tide. Malaria has waxed and waned as a threat, but with the development of insecticide resistance to its mosquito carriers and increasing resistance of the parasite to chemoprophylaxis and therapy, the threat remains very much with us (Table 14.1).
On the other hand, smallpox virus (Variola) is an obligate human parasite that depends in nature on a chain of direct human-to-human infection for its survival. In this respect it is similar to the viral causes of poliomyelitis and measles. Such viruses, which have no other substrates in which to multiply, are prime candidates for eradication. When the number of human susceptibles has been exhausted through vaccination or by natural immunization through infection, these viruses have no other place to go.
Influenza virus is different from Variola on several counts: as an RNA virus it is more mutable by three orders of magnitude; it evolves more rapidly under the selective pressure of increasing human immunity; and, most important, it can effect rapid changes by genetic re-assortment with animal influenza viruses to recruit new surface antigens not previously encountered by humans to aid its survival in human populations (Kilbourne, 1981). Strangely, the most notorious pandemic of the twentieth century was for a time almost forgotten because of its concomitance with World War I (Jones).
The word ‘plague’ has both specific and general meanings. In its specific denotation plague is an acute infection caused by the bacterium Yersinia pestis, which in humans induces the formation of characteristic lymph node swellings called ‘buboes’ -hence ‘bubonic plague’. Accounts suggestive of plague go back millennia, but by historical consensus, pandemics of plague were first clearly described with the Plague of Justinian in AD 541 in the city of Constantinople. Probably imported with rats and their s in ships bearing grain from either Ethiopia or Egypt, the disease killed an estimated 40% of the city’s population and spread through the eastern Mediterranean with almost equal effect. Later (AD 588) the disease reached Europe, where its virulence was still manifest and its death toll equally high. The Black Death is estimated to have killed between a third and two-thirds of Europe’s population. The total number of deaths worldwide due to the pandemic is estimated at 75 million people, where of an estimated 20 million deaths occurred in Europe. Centuries later, a third pandemic began in China in 1855 and spread to all continents in a true pandemic manner. The disease persists in principally enzootic form in wild rodents and is responsible for occasional human cases in North and South America, Africa, and Asia. The WHO reports a total of 1000–3000 cases a year.
Cholera, the most lethal of past pandemics, kills its victims rapidly and in great numbers, but is the most easily prevented and cured – given the availability of appropriate resources and treatment. As is the case with smallpox, poliomyelitis, and measles, it is restricted to human hosts and infects no other species. Man is the sole victim of Vibrio cholerae. But unlike the viral causes of smallpox and measles, Vibrio can survive for long periods in the free-living state before its ingestion in water or contaminated food.
Cholera is probably the first of the pandemics, originating in the Ganges Delta from multitudes of pilgrims bathing in the Ganges river. It spread thereafter throughout the globe in a series of seven pandemics covering four centuries, with the last beginning in 1961 and terminating with the first known introduction of the disease into Africa. Africa is now a principal site of endemic cholera.
The pathogenesis of this deadly illness is remarkably simple: it kills through acute dehydration by damaging cells of the small and large intestine and impairing the reabsorption of water and vital minerals. Prompt replacement of fluid and electrolytes orally or by intravenous infusion is all that is required for rapid cure of almost all patients. A single dose of a new antibiotic, azithro mycin, can further mitigate symptoms.
It has been stated that ‘no other single infectious disease has had the impact on humans … [that] malaria has had’ (Harley et al., 1999). The validity of this statement may be arguable, but it seems certain that malaria is a truly ancient disease, perhaps 4000–5000 years old, attended by significant mortality, especially in children less than five years of age.
The disease developed with the beginnings of agriculture (Benenson, 1982), as humans became less dependent on hunting and gathering and lived together in closer association and near swamps and standing water – the breeding sites of mosquitoes. Caused by any of four Plasmodia species of protozoa, the disease in humans is transmitted by the Anopheles mosquito in which part of the parasite’s replicative cycle occurs.
Thus, with its pervasive and enduring effects, malaria did not carry the threatening stigma of an acute cause of pandemics but was an old, unwelcome acquaintance that was part of life in ancient times. The recent change in this picture will be described in a section that follows.
There is no ambiguity about the diagnosis of smallpox. There are few, if any, asymptomatic cases of smallpox (Benenson, 1982) with its pustular skin lesions and subsequent scarring that are unmistakable, even to the layman. There is also no ambiguity about its lethal effects. For these reasons, of all the old pandemics, smallpox can be most surely identified in retrospect. Perhaps most dramatic was the decimation of Native Americans that followed the first colonization attempts in the New World. A number of historians have noted the devastating effects of the disease following the arrival of Cortez and his tiny army of 500 and have surmised that the civilized, organized Aztecs were defeated not by muskets and cross bows but by viruses, most notably smallpox, carried by the Spanish. Subsequent European incursions in North America were followed by similar massive mortality in the immunologically naïve and vulnerable Native Americans. Yet a more complete historical record presents a more complex picture. High mortality rates were also seen in some groups of colonizing Europeans (Gage, 1998). It was also observed, even that long ago, that smallpox virus probably comprised both virulent and relatively avirulent strains, which also might account for differences in mortality among epidemics. Modern molecular biology has identified three ‘clades’ or families of virus with genomic differences among the few viral genomes still available for study (Esposito et al., 2006). Other confounding and contradictory factors in evaluating the ‘Amerindian’ epidemics was the increasing use of vaccination in those populations (Ashburn, 1947), and such debilitating factors as poverty and stress (Jones).
That traditional repository of medical palaeo-archeology, ‘an Egyptian mummy’, in this case dated at 2400 BC, showed characteristic signs of tuberculosis of the spine (Musser, 1994). More recently, the DNA of Mycobacterium tuberculosis was recovered from a 1000-year-old Peruvian mummy (Musser, 1994).
The more devastating a disease the more it seems to inspire the poetic. In seventeenth century England, John Bunyan referred to ‘consumption’ (tuberculosis in its terminal wasting stages) as ‘the captain of all these men of death’ (Comstock, 1982). Observers in the past had no way of knowing that consumption (wasting) was a stealthy plague, in which the majority of those infected when in good health neverbecame ill. Hippocrates’ mistaken conclusion that tuberculosis killed nearly everyone it infected was based on observation of far advanced clinically apparent cases.
The ‘White Plague’ of past centuries is still very much with us. It is one of the leading causes of death due to an infectious agent worldwide (Musser, 1994). Transmitted as a respiratory tract pathogen through coughs and aerosol spread and with a long incubation period, tuberculosis is indeed a pernicious and stealthy plague.
If tuberculosis is stealthy at its inception, there is no subtlety to the initial acquisition of Treponema pallidum and the resultant genital ulcerative lesions (chancres) that follow sexual intercourse with the infected, or the florid skin rash that may follow. But the subsequent clinical course of untreated syphilis is stealthy indeed, lurking in the brain and spinal cord and in the aorta as a potential cause of aneurysm. Accurate figures on morbidity and mortality rates are hard to come by, despite two notorious studies in which any treatment available at the time was withheld after diagnosis of the initial acute stages (Gjestland, 1955; Kampmeir, 1974). The tertiary manifestations of the disease, general paresis tabes dorsalis, cardiovascular and other organ involvement by ‘the great imitator’, occurred in some 30% of those infected decades after initial infection.
Before the development of precise diagnostic technology, syphilis was often confused with other venereal diseases and leprosy so that its impact as a past cause of illness and mortality is difficult to ascertain.
It is commonly believed that just as other acute infections were brought into the New World by the Europeans, so was syphilis by Columbus’s crew to the Old World. However, there are strong advocates of the theory that the disease was exported from Europe rather than imported from America. Both propositions are thoroughly reviewed by Ashburn (1947).
Influenza is an acute, temporarily incapacitating, febrile illness characterized by generalized aching (arthralgia and myalgia) and a short course of three to seven days in more than 90% of cases. This serious disease, which kills hundreds of thousands every year and infects millions, has always been regarded lightly until its emergence in pandemic form, which happened only thrice in the twentieth century, including the notorious pandemic of 19181919 that killed 20–50 million people (Kilbourne, 2006a). It is a disease that spreads rapidly and widely among all human populations. In its milder, regional, yearly manifestations it is often confused with other more trivial infections of the respiratory tract, including the common cold. In the words of the late comedian Rodney Dangerfield, ‘it gets no respect’. But the damage its virus inflicts on the respiratory tract can pave the way for secondary bacterial infection, often leading to pneumonia. Although vaccines have been available for more than 50 years (Kilbourne, 1996), the capacity of the virus for continual mutation warrants annual or biannual reformulation of the vaccines.
Towards the end of the twentieth century a novel and truly dreadful plague was recognized when acquired immunodeficiency disease syndrome (AIDS) was first described and its cause established as the human immunodeficiency virus (HIV). This retrovirus (later definitively subcategorized as a Lenti [slow] virus) initially seemed to be restricted to a limited number of homosexual men, but its pervasive and worldwide effects on both sexes and young and old alike are all too evident in the present century.
Initial recognition of HIV/AIDS in 1981 began with reports of an unusual pneumonia in homosexual men caused by Pneumocystis carinii and previously seen almost exclusively in immunocompromised subjects. In an editorial in Science (Fauci, 2006), Anthony Fauci writes, ‘Twenty five years later, the human immunodeficiency virus (HIV) … has reached virtually every corner of the globe, infecting more than 65 million people. Of these, 25 million have died’. Much has been learned in the past 25 years. The origin of the virus is most probably chimpanzees (Heeney et al., 2006), who carry asymptomatically a closely related virus, SIV (S for simian). The disease is no longer restricted to homosexuals and intravenous drug users but indeed, particularly in poor countries, is a growing hazard of heterosexual intercourse. In this rapidly increasing, true pandemic, perinatal infection can occur, and the effective battery of antiretroviral drugs that have been developed for mitigation of the disease are available to few in impoverished areas of the world. It is a tragedy that AIDS is easily prevented by the use of condoms or by circumcision, means that in many places are either not available or not condoned by social mores or cultural habits. The roles of sexual practices and of the social dominance of men over women emphasize the importance of human behaviour and economics in the perpetuation of disease.
Other viruses have left jungle hosts to infect humans (e.g., Marburg virus) (Bausch et al., 2006) but in so doing have not modified their high mortality rate in a new species in order to survive and be effectively transmitted among members of the new host species. But, early on, most of those who died with AIDS did not die of AIDS. They died from the definitive effects of a diabolically structured virus that attacked cells of the immune system, striking down defences and leaving its victims as vulnerable to bacterial invaders as are the pitiable, genetically immunocompromised children in hospital isolation tents.
Influenza continues to threaten future pandemics as human-virulent mutant avian influenza viruses, such as the currently epizootic H5N1 virus, or by recombination of present ‘human’ viruses with those of avian species. At the time of writing (June 2007) the H5N1 virus remains almost exclusively epizootic in domestic fowl, and in humans, the customary yearly regional epidemics of H3N2 and H 1 N1 ‘human’ subtypes continue their prevalence. Meanwhile, vaccines utilizing reverse genetics technology and capable of growing in cell culture are undergoing improvements that still have to be demonstrated in the field. Similarly, antiviral agents are in continued development but are as yet unproven in mass prophylaxis.
The ancient plague of tuberculosis has never really left us, even with the advent of multiple drug therapy. The principal effect of antimicrobial drugs has been seen in the richer nations, but to a much lesser extent in the economically deprived, in which the drugs are less available and medical care and facilities are scanty. However, in the United States, a progressive decline in cases was reversed in the 1980s (after the first appearance of AIDS) when tuberculosis cases increased by 20%. Of the excess, at least 30% were attributed to AIDS-related cases. Worldwide, tuberculosis is the most common opportunistic infection in HIV-infected persons and the most common cause of death in patients with AIDS.
The two infections may have reciprocal enhancing effects. The risk of rapid progression of pre-existing tuberculosis infection is much greater among those with HIV infection and the pathogenesis of the infection is altered, with an increase in non-pulmonary manifestation of tuberculosis. At the same time, the immune activation induced by response to tuberculosis may paradoxically be associated with an increase in the viral load and accelerated progression of HIV infection. The mechanism is not understood.
Certain microbial species produce toxins that can severely damage or kill the host. The bacterial endotoxins, as the name implies, are an integral part of the microbial cell and assist in the process of infection. Others, the exotoxins (of anthrax, botulism), are elaborated and can produce their harmful effects, as do other prefabricated, non-microbial chemical poisons. These microbial poisons by themselves seem unlikely candidates as pandemic agents. Anthrax spores through the mail caused 17 illnesses and 5 deaths in the United States in 2001 (Elias, 2006). Accordingly, a one billion dollar contract was awarded by the U.S. Department of Health and Human Services for an improved vaccine. Development was beset with problems, and delivery is not expected until 2008 (Elias, 2006). In any case, as non-propagating agents, microbial toxins do not seem to offer a significant pandemic threat.
Iatrogenic diseases are those unintentionally induced by physicians and the altruism of the dead – or, ‘The way to [health] is paved with good intentions’. An unfortunate result of medical progress can be the unwitting induction of disease and disability as new treatments are tried for the first time. Therefore, it will not be surprising if the accelerated and imaginative devising of new technologies in the future proves threatening at times. Transplantation of whole intact vital organs, including heart, kidney, and even liver, has seen a dramatic advance, although as an alien tissue, rejection by the immune system of the patient has been a continuing problem.
Reliance on xenotransplantation of non-human organs and tissues such as porcine heart valves does not seem to have much future because they may carry dangerous retroviruses. In this connection, Robin Weiss proposes that ‘we need a Hippocratic oath for public health that would minimize harm to the community resulting from the treatment of Individuals’ (Weiss, 2004).
All these procedures have introduced discussion of quality of life (and death) values, which will and should continue in the future. Based on present evidence, I do not see these procedures as instigators of pandemics unless potentially pandemic agents are amplified or mutated to virulence in the immunosuppressed recipients of this bodily largesse.
How complicated can things get? A totally unforeseen complication of the successful restoration of immunologic function by the treatment of AIDS with antiviral drugs has been the activation of dormant leprosy as a consequence (McNeil, 2006; Visco-Comandini et al., 2004).
There is evidence from studies of isolated populations that such populations, because of their smaller gene pool, are less well equipped to deal with initial exposure to unaccustomed infectious agents introduced by genetically and racially different humans. This is suggested by modern experience with measles that demonstrated ‘intensified reactions to [live] measles vaccine in [previously unexposed] populations of American Indians’ (Black et al., 1971). This work and studies of genetic antigen markers in the blood have led Francis Black to propose, ‘[P]eople of the New World are unusually susceptible to the diseases of the Old not just because they lack any [specific] resistance but primarily because, as populations, they lack genetic heterogeneity (Black, 1992, 1994). They are susceptible because agents of disease can adapt to each population as a whole and cause unusual damage’ (Black, 1992, 1994). If I may extrapolate from Black’s conclusions, a population with greater genetic heterogeneity would fare better with an ‘alien’ microbial or viral invasion.
Although present-day conflicts, warlike, political, and otherwise, seem to fly in the face of attaining genetic or cultural uniformity and the ‘one world’ ideal, in fact, increasing genetic and cultural homogeneity is a fact of life in many parts of the world. Furthermore, barriers to communication are breached by the World Wide Web, the universal e-mail post office, by rapid and frequent travel, and the ascendancy of the English language as an international tongue that is linking continents and ideas as never before.
We have already seen the rapid emergence of the respiratory virus, SARS, in humans and its transport from China to Canada. We also have learned that, unlike influenza, close and sustained contact with patients was required for the further perpetuation of the epidemic (Kilbourne, 2006b). This experience serves to emphasize that viruses can differ in their epidemic pattern of infection even if their target and site of infection are the same.
With this caveat, let us recall the rapid and effective transmission of influenza viruses by aerosols but the highly variable experience of isolated population groups in the pandemic of 1918. Groups sequestered from the outside world (and in close contact in small groups) prior to that epidemic suffered higher morbidity and mortality, suggesting that prior more frequent experience with non-pandemic influenza A viruses had at least partially protected those in more open societies. The more important point is that such ‘hot houses’ could favour the emergence of even more transmissible strains of virus than those initially introduced. Such hot houses or hotbeds in sequestered societies would be lacking in our homogenized world of the future.
To consider briefly the more prosaic, but no less important aspects of our increasingly homogeneous society, the mass production of food and behavioural fads concerning their consumption has led to the ‘one rotten apple’ syndrome. If one contaminated item, apple, egg, or most recently spinach leaf, carries a billion bacteria – not an unreasonable estimate – and it enters a pool of cake mix constituents, and is then packaged and sent to millions of customers nationwide, a bewildering epidemic may ensue.
Although the production and dangers of factitious infectious agents are considered elsewhere in this book (see Chapter 20), the present chapter would be incomplete without some brief consideration of such potential sources of plagues and pandemics of the future.
No one has yet mixed up a cocktail of off-the-shelf nucleotides to truly ‘make’ a new virus. The genome of the extinct influenza virus of 1918 has been painstakingly resurrected piece by piece from preserved human lung tissue (Taubenberger et al., 2000). This remarkable accomplishment augurs well for the palaeo-archeology of other extinct viral ‘dodos’, but whether new or old, viruses cannot truly exist without host cellular substrates on which to replicate, as does the resurrected 1918 virus, which can multiply, and indeed, kill animals. The implications are chilling indeed. Even confined to the laboratory, these or truly novel agents will become part of a global gene pool that will lie dormant as a potential threat to the future.
Predictive principles for the epidemiology of such human (or non-human) creations can perhaps be derived from the epidemiology of presently familiar agents, for example, pathogenesis (Kilbourne, 1985).
If sins of omission have been committed here, it is with the recognition that Pandora’s Box was full indeed and there is space in these pages to discuss only those infectious agents that have demonstrated a past or present capacity for creating plagues or pandemics, or which now appear to be emerging as serious threats in the future. I now quote from an earlier work.
In anticipating the future, we must appreciate the complexity of microbial strategies for survival. The emergence of drug-resistant mutants is easily understood as a consequence of Darwinian selection. Less well appreciated is the fact that genes for drug resistance are themselves transmissible to still other bacteria or viruses. In other instances, new infectious agents may arise through the genetic recombination of bacteria or of viruses which individually may not be pathogenic. By alteration of their environment, we have abetted the creation of such new pathogens by the promiscuous overuse or misuse of antimicrobial drugs. The traditional epidemiology of individual infectious agents has been superseded by a molecular epidemiology of their genes. (Kilbourne, 2000, p. 91)
Many of my colleagues like to make predictions. ‘An influenza pandemic is inevitable’, ‘The mortality rate will be 50%’, etc. This makes good press copy, attracts TV cameras, and raises grant funding. Are influenza pandemics likely? Possibly, except for the preposterous mortality rate that has been proposed. Inevitable? No, not with global warming and increasing humidity, improved animal husbandry, better epizootic control, and improving vaccines. This does not have the inevitability of shifting tectonic plates or volcanic eruptions.
Pandemics, if they occur, will be primarily from respiratory tract pathogens capable of airborne spread. They can be quickly blunted by vaccines, if administrative problems associated with their production, distribution, and administration are promptly addressed and adequately funded. (A lot of ‘ifs’ but maybe we can start learning from experience!)
Barring extreme mutations of the infective agent or changed methods of spread, all of them can be controlled (and some eradicated) with presently known methods. The problem, of course, is an economic one, but such organizations as the Global Health Foundation and the Bill and Melinda Gates Foundation offer hope for the future by their organized and carefully considered programs, which have identified and targeted specific diseases in specific developing regions of the world.
In dealing with the novel and the unforeseen – the unconventional prions of Bovine Spongio form Encephalitis that threatened British beef (WHO, 2002) and the exotic imports such as the lethal Marburg virus that did not come from Marburg (Bausch et al., 2006) – we must be guided by the lessons of the past, so it is essential that we reach a consensus on what these lessons are. Of these, prompt and continued epidemiological surveillance for the odd and unexpected and use of the techniques of molecular biology are of paramount importance (admirably reviewed by King et al. [2006]). For those diseases not amenable to environmental control, vaccines, the ultimate personal suits of armour that will protect the wearer in all climes and places, must be provided.
Should we fear the future? If we promptly address and properly respond to the problems of the present (most of which bear the seeds of the future), we should not fear the future. In the meantime we should not cry ‘Wolf!’, or even ‘Fowl!’, but maintain vigilance.
All suggestions are accessible to the general intelligent reader except for the Burnet book, which is ‘intermediate’ in difficulty level.
Burnet, F.M. (1946). Virus as Organism: Evolutionary and Ecological Aspects of Some Human Virus Diseases (Cambridge, MA: Harvard University Press). A fascinating glimpse into a highly original mind grappling with the burgeoning but incomplete knowledge of virus diseases shortly before mid-twentieth century, and striving for a synthesis of general principles in a series of lectures given at Harvard University; all the more remarkable because Burnet won a shared Nobel Prize later for fundamental work on immunology.
Crosby, A.W. (1976). Epidemic and Peace, 1918 (Westport, CT: Greenwood). This pioneering book on the re-exploration of the notorious 1918 influenza pandemic had been surprisingly neglected by earlier historians and the general public.
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