Medicine and ecology: historical and critical perspectives on the concept of emerging disease

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CHAPTER XII

MEDICINE AND ECOLOGY : HISTORICAL AND CRITICAL PERSPECTIVES ON THE CONCEPT OF ‘EMERGING DISEASE’

[Please refer to the published version for citations or quotations]

PIERRE-OLIVIER MÉTHOT* AND BERNARDINO FANTINI**

l. Introduction

Before the germ theory of disease was formulated in the second half of the nineteenth century, an epidemic outbreak was generally considered to be the result of an external cause – a divine punishment, a natural catastrophe polluting air with poisons (‘mal’aria’) – or the consequence of a criminal action or the migration of individuals harbouring the diseases within their body (Rosenberg l992). It is only following the “ Pastorian revolution ” and the birth of experi- mental physiology that the nature of infection began to be conceptualized as resulting from the interaction of heterogeneous factors: biological, ecological, and social. The nature of infection was transformed into a biological relation between two distinct speciesl : the parasite and the host who, taken together, stand in an uneasy equilibrium that can result in the death of the host, the elimi- nation of the parasite, or in the creation of a new biological equilibrium. In the latter case, one can observe the transformation of the host into a “healthy carrier”, to use Koch’s expression, or a form of “asymptomatic infection”, as they are called today. By way of consequences, the frequency of a disease in a given population, its etiological and physiopathological characteristics, in addtion to its virulence and its spatiotemporal distribution, rest on the biological characters of the different species involved as well as on the environmental conditions. Although the ecological aspects of infectious diseases were recognized in

l. Eventually one should include three species as in the case of vector-borne diseases that include germs, hosts, and biological vectors.

*Faculté de Philosophie **Centre Collaborateur OMS pour la recherche Université Laval historique en santé publique 2325, rue des bibliothèques Faculté de Médecine Québec (QC) GIV 0A6 Université de Genève Canada l2ll Genève 4 et Suisse Centre interuniversitaire [email protected] de recherche sur la science et la technologie (CIRST-UQAM) [email protected]

2l4 Pierre-Olivier Méthot and Bernardino Fantini

the first half of the twentieth century by a number of “ disease ecologists ” (Anderson 2004), they only begun to be seriously considered after the steep rise of “emerging infections” in the early l980s.

The historian of medicine William Bynum observed that by l860 two “ contrasting positions on the historical nature of disease ” were in tension : first, diseases were seen as unchanging objects “ subject to definite and regular laws ” and physicians could study their natural history and constant characteristics in rather precise ways. The contrasting position was that diseases do not seem to “ behave like timeless entities ”. Or, as Bynum put it, “ they [diseases] sometimes appear to originate spontaneously, or de novo, or to change their essential natures during the course of an epidemic, or from year to year ” (Bynum 2002, pp. 57- 58). Likely, these two perspectives have alternated several times in medical history ; and indeed, while the fact that diseases deeply influenced human history is well accepted, the idea that diseases “ have a history ” remains largely under- appreciated in present-day histories of medicine (but see Le Goff and Sournia l985 ; Grmek l969).

A sign of the renewed interest in thinking about disease historically, as having a beginning and an end located in space and time, is the formation of the concept of emerging disease – a concept that shakes up our confidence in the apparent stability of the medical realm as traditionally formulated in medical textbooks (Gachelin 2004). Despite some predecessors, the concept of emerging disease was formulated only towards the end of the twentieth century. It was initially employed to explore the qualitative and quantitative alterations in the global distribution of (infectious) diseases in a definite time period. Where do these diseases come from ? How did they emerge ? Why here ? Why now ? Should we expect more new diseases to come into sight in a near future ? What will they be like ? Could we predict them ? Those and other similar pressing questions, articulated more than 80 years ago by French microbiologist Charles Nicolle, still rank high on the agenda of public health, epidemiology, virology, evolutionary ecology, and medical microbiology today, as demonstrated by the recent Ebola epidemic in West Africa.

Coined by the Institute of Medicine (IOM) in the United States following the observation that a number of (infectious) pathologies appeared to be novel, the concept of emerging disease has since led to important changes in international public health regulations (Fantini l993). Furthermore, the concept of emerging disease suggested new ways to reconceptualise the relation between man and nature broadly understood for, as we will see, most events of “ emerging diseases ” do not result from the evolution of particularly virulent germs but rather from significant ecological changes in an ecosystem. In human populations, those changes are determined, to a large extent, by cultural and socio-economics factors (Anderson 2004).

As we argue in this chapter, understanding the multiplicity of processes driving disease emergence requires us to reflect more broadly along the lines of the second approach outlined by Bynum. In other words, we need to think histori-


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Chapter XII. Medicine and Ecology 2l5

cally, ecologically, and dynamically, not statically, about disease, and to move (further) away from a “ fixist ” and rigid perspective on the nature of disease (Méthot and Alizon, 20l4a). To this end, section 2 briefly describes Louis Pasteur and Charles Nicolle’s views of epidemic diseases ; sections 3 and 4 examine a number of recent emerging events and discuss how these have led to a renewed understanding of the fate of infectious diseases in the West ; section 5 analyses the most significant factors in determining emerging diseases with a focus on the roles of ecological and evolutionary processes ; finally, drawing on the works of historian and philosopher of medicine Mirko D. Grmek (l924-2000), section 6 considers the concept of emerging disease from a critical perspective and con- trasts it with other oft-employed terms such as epidemics, pandemics, and new disease. Whereas the concept of emerging disease was useful in funding new research on the biology of infectious diseases, we argue that it should not be accepted uncritically.

2. Birth, life, and death of infectious diseases

The rise of laboratory medicine in the last four decades of the nineteenth century in France, England, and Germany has led to the development of more effi- cient therapeutics such as vaccines and pasteurization and has provided fresh perspectives on the nature and cause of infectious diseases. For Pasteur, “ [a]n epidemic that goes extinct because of a lowering of the virulence power of the germ can rise again provided that the virus is reinforced again under certain influences ” (Pasteur l994, p. 337 [l88l]). Those influences include the passing of a virus through a series of animals (of the same species or not), enhancing its virulence. According to Pasteur, the natural process of changes in virulence he observed within the walls of his laboratory is the same mechanism by which new diseases have periodically appeared throughout history outside of it. And for him, the frequent passing of the “ virus ” through new susceptible hosts could not only explain the onset of epidemics but also the coming into being, or the evolution, of genuinely new diseases :

“ Virulence appears thus to us in a new light that is far from being reassur- ing for the sake of humanity, unless nature in its evolution during past cen- turies has already encountered every possibility of creating virulent or contagious diseases, which is most unlikely. […] What is an inoffensive microscopic organism for humans or for a particular animal ? It is a living being that cannot develop itself in our body or in the body of that animal ; but nothing proves that if this microscopic being could penetrate into the body of one of the thousands and thousands of species within the creation, it could not invade it and make it sick all the same. Its virulence, reinforced by successive passages through individuals of the same species, could reach a level at which it could kill one or another large animal, humans or certain domestic animals. By this method new virulences and


new contagions can be created. I am inclined to believe that this is how smallpox, syphilis, plague, yellow fever appeared across the ages, and similarly, that phenomena of this type explain how certain great epidemics, such as typhus for example, have appeared at one time or another ” (Pas- teur, Chamberland, Roux l88l, p. 337).

Thus, even if Pasteur remains better known for his practical innovations in

medicine such as vaccination and pasteurisation, he suggested a theoretical framework to think about the biological origins of diseases.

Witnessing the extinction of typhus fever and plague in Tunisia, medical microbiologist Charles Nicolle developed some of Pasteur’s ideas on the nature of infection and contagion, and more generally, he endeavoured to search for some “ evolutionary laws of infectious diseases ” (Néfissa and Moulin 20l0). After he left the Pasteur Institute in Tunis, Nicolle lectured at the Collège de France on the birth, growth, and death of some of the major infectious diseases of his time. Taking a broad ecological approach (Pelis 2006) to the problem of infection, Nicolle’s central tenet was that an infectious disease is “ a biological phenomenon as any other ” : “ The diseases we suffer from are both without end, and without measure. Their causes, also incalculable, belong to the natural order ; […] Disease is a biological phenomenon as any other. It displays the hallmarks of life seeking to perpetuate itself, to evolve, tending towards a state of equilibrium ” (Nicolle l939, p. l5).

Nicolle distinguished three levels of explanation for infectious diseases : individual, collective, and historical (Nicolle l939, p. 23). All three levels must be articulated in order to understand the fundamentals of infectious diseases, particularly during epidemics or pandemics : though a disease is always related to individual beings, its history, on the other hand, is inevitably connected to broader population dynamics which are in relation to a wider environment, both natural and social. Nicolle’s view that diseases are genuine historical entities, inspired by his work on the progressive disappearance of typhus and plague, underpins his account on the origin of new diseases :

“ Have the infectious diseases we now observe always existed ? Are there some, among them, that have appeared through historical time ? Can we assume that new ones will appear ? Can we presume that some of these diseases will disappear ? Has any disease ever vanished ? Lastly, what will humanity and domestic animals do if, thanks to the more and more frequent encounter between them, the number of infectious diseases contin- ues to rise ? ” (Nicolle l939, p. l75).

Similar questions regarding the origins of new diseases had been raised before

the work of Nicolle, of course, and particularly in the nineteenth century (e.g. Pasteur l88l, Anglada l869, Boersch l936, Sprengel l809), but also as far back as Antiquity (Grmek l993). The problem of “ new diseases ” is paradoxically not a new one. However, before Nicolle the issues raised above were rarely answered




with such confidence. In effect, Nicolle’s ultimate message was that “ There will thus be new diseases. This is a critical fact. Another fact, equally critical, is that we shall only be able to identify them when they are formed, adult, so to speak. Like Minerva coming out of Jupiter’s brain diseases will appear as ready to strike ” (Nicolle l930, p. l29). Because Nature constantly attempts to adapt microorganisms to their host, he argues, and given the great amount of biological variation exhibited by microorganisms themselves, new diseases will necessarily arise although we may not be able to predict their emergence, and thus they will appear “ ready to strike ”.

3. The eclipse of infectious diseases : l950-l970

Nicolle’s views on the future of infectious diseases remained largely unheard in Western countries until the late l970s and early l980s. Immunologist and Nobel Prize laureate, Frank Macfarlane Burnet (l899-l985), among others, provided strong and repeated support to the shared optimistic view about a forthcoming end of infectious diseases (Burnet l953 ; Burnet and White l972). As Burnet put it,

“ infectious diseases will always be with us, and there will always be room for further refinement in prevention and treatment ; but as a major cause of death in the years of youth and maturity it is becoming relatively unim- portant […] I believe that, provided the established mechanism of preventive medicine, medical care and drug production continued to function, fundamental work on the nature of microorganisms and on the disease they produce could stop today without influencing the current process by which all the main infectious diseases except poliomyelitis are disappearing […]. It is extremely unlikely that any new principle will be needed to maintain our present very effective control of infectious disease : in that sense fundamental research is not called for by an expressed human need ” (l953, p. l03).

Frank Macfarlane Burnet was not exceptional in reasoning along these lines.

As René Dubos recalled in Man Adapting (l965), during the l950s and l960s, “ most clinicians, public health officers, epidemiologists, and microbiologists felt justified in proclaiming that the conquest of infectious diseases had finally been achieved ” (Dubos l965, quoted in Gold l998, p. 459). A few years later, the US General Surgeon purportedly claimed that it was time to “ close the book ” on infectious diseases (Gaudillière and Löwy 200l)2. With similar declarations by high profile scientists it is unsurprising that the question as to whether infectious diseases “ still matter ” was debated (Howie l968 ; Ashworth l969).

2. The quote from William Stuart should not be taken at face value ; it is now considered to be nothing more than an urban myth (Spellberg and Taylor-Blake 20l3).


Strengthened by the eradication of smallpox, the control of malaria in addition to the development of sulpha drugs, vaccines, chemotherapy, and antibiotics, this medical optimism led to the view that infectious diseases were close to be con- quered. As a consequence, fundamental research on the causes of infectious diseases was deemed no longer necessary in light of recent and empowering technological advances. This medical optimism was also flanked by a belief in a natural decline in virulence. In effect, during most of the twentieth century, medical scientists considered that hosts and pathogens generally coevolve towards a state of commensalism, and that infectious diseases are only temporary maladap- tations (Snowden 2008), though this did not necessarily imply that new diseases could not occurred, for instance following ecological changes and/or human interventions (Méthot 20l2a). Subjected to a misconceived conception on virulence evolution, “ the perpetual challenge of the microbial world ” was largely ignored (Krause l98l).

The eradictionist perspective according to which infectious diseases could be defeated once and for all, rested on a static view of the microbial world that did not consider the very rapid and extremely promiscuous evolutionary changes going on in microbiological ecosystems (Weir and Mykhalovskiy 20l0). In some sense, indeed, between l950 and the late l970s, the constancy of disease, as described by Bynum, prevailed. Joshua Lederberg’s works with Edward L. Tatum on bacterial recombination in the l940s demonstrated that genes could be later- ally transmitted through extra-chromosomal entities such as plasmids. This line of research in bacterial genetics extended previous work on the nature of genes at the Rockefeller Institute and could have worked as a platform onto which to develop an evolutionary perspective on the microbial realm, and to flesh out its wider implications for public health. However, microorganisms were not well integrated in the modern evolutionary synthesis, which was developed mostly for mammals and birds, and remained largely marginalized until the l980s (Sapp 2007). Oscillating between a Lamarckian and a Darwinian explanation, the origins and mechanisms of microbial resistance were also not well understood (Cre- ager 2007). Taken together, these factors cast the causes of epidemic diseases in virtually non-evolutionary terms, or as Lederberg has put it : “ the historiography of epidemic disease is one of the last refuges of the concept of special creationism ” (l993, p. 3).

The idea of reaching the “ end of infectious diseases ” was still very much in the air at major medical research centres in the US such as the National Institute for Allergy and Infectious Diseases in Washington (D.C.), as far as the mid- l970s, when the “ war on cancer ” and cardiovascular diseases was declared by Nixon (Krause l998, p. 3). In the fourth edition of his book on the natural history of infectious diseases, co-authored with David O. White, Macfarlane Burnet also argued that though, in principle, new diseases could surface they would be “ nothing of the sort that has marked the last fifty years ” (Burnet and White l972, p. 263). In l977, W.I.B. Beveridge published a book on influenza titled The Last Great Plague, comforting the technological illusion of a forthcoming con-




quest of infections, at least in the developed world. Ironically, as AIDS came to forefront only a few years later and posed a renewed threat to health in the developed and the developing world alike, it finally brought the “ eclipse of infectious diseases ” to an end. The onset of AIDS and the emergence of several “ new ” diseases caught many public health workers off-guard and reminded us of the significant impact infectious diseases continue to have on the quality of life.

In the late l980s, virologist Stephen Morse was instrumental in bringing the problem of emerging diseases to the attention of Joshua Lederberg, then professor at Rockefeller University. Together they organized a conference, chaired by Morse, on “ Emerging Viruses : the Evolution of Virus and Viral Diseases ” held in Washington D.C. in l989. The conference was attended by a number of prom- inent scientists and received important media coverage (Garrett l994, p. 5). The conference further led to the organization of a scientific committee, chaired by the Institute of Medicine (IOM), to examine emerging threats and advise the US government, and to the publication of an influential report. The IOM report on Emerging Infections : Microbial Threats to Health in the United States (Leder- berg, Shope, Oaks l992) appeared one year before Stephen Morse’s Emerging Viruses (l993). Importantly, both books argued the research in the field of infectious diseases urgently needed to be developed from an integrated and combined molecular-genetic and ecological point of view.

In l994, the Centre for Disease Control (CDC) in Atlanta published its own recommendations and launched a new journal to deal with the issue : Emerging Infectious Diseases. Following consultations in the US and in Canada, the World Health Organization (WHO) in Geneva established a Division of Emerging and Other Communicable Diseases Surveillance and Control in l995. WHO also headed the development of public health policies designed to contain the emergence of unknown diseases. In l996, a WHO official report observed how countries are now inevitably interconnected and united by the perpetual risk of new or re-emerging infectious diseases (WHO report l996). Asserting further the globalized risk of emerging infections WHO chose “ Emerging Infectious Diseases – Global Alert, Global Response ” as the leading theme for the World Health Day in l997. This shift from localized to the globalized risks perceptions fostered by new emerging pathogenic viruses, was reflected in Dubos’ slogans to “ Act locally ” and “ Think globally ”. In l998, the CDC outlined a second “ strategic plan ” for the twenty-first century in order to better prevent and contain emerging diseases that emphasized the use of new available technologies of global surveillance (King 2004). While orchestrating global surveillance networks for an early detection of emerging diseases WHO created at the same time a “ world on alert ” (Weir and Mykhalovskiy 20l0).

4. A wave of “ new ” diseases

Infectious diseases continue to claim fifteen millions of death worldwide annually and remain a “ perpetual challenge ” (Fauci and Morens 20l2). Recent

220 Pierre-Olivier Méthot and Bernardino Fantini

calculations suggest that over 300 emerging infectious events occurred between l940 and 2004 in human populations, with a greater proportion of zoonoses. Reviewing a few examples will help to bring out the diverse conditions under which disease emergence has occurred in the past three or four decades, and furthermore will illustrate the relevance and need of an ecological perspective in medicine.

In l967, a severe outbreak of haemorrhagic fever simultaneously struck thirty- one laboratory workers in Marburg, Frankfurt, and Belgrade. Out of the thirty-one cases, seven people died. All the infected individuals worked as employees in the preparation of vaccines from kidney cells taken from green monkeys imported from Uganda. Further analyses established that the cause of the disease was a microorganism belonging to the filovirus family (RNA viruses) that was then unknown. Another similar haemorrhagic fever episode occurred in l976 in Yam- buku, Zaire, and spread quickly among the 55 villages located alongside the river Ebola. The name of the virus isolated shortly afterwards took its name from that river. About 500 cases were reported out of which 400 were deadly. That year, WHO reported another similar epidemic in Soudan where the virus caused 284 cases and led to l50 deaths. In this case, the virus was related to the Marburg outbreak. During another epidemic in l995 in Kikwit (Zaire), a 400’000 inhabitant’s city situated at 400 km of Kinshasa, the virus caused about 250 deaths. The perceived risk that an extremely lethal virus such as Ebola could transmit within and between human populations by air explains the interest in the virulent epidemics it caused, though these were limited both numerically and geographically (Mag- ner 2009), a situation that is about to change.

Another recent example of emerging infection is the “ mad cow ” crisis that reverberated widely across the Western world even if the number of human vic- tims barely went above 200. This situation results partly from the discovery of a “ proteinaceous infectious particle ” (Morange 2007), or prions, responsible for the transmission to man of spongiform encephalopathy, a degenerative disease of the nervous system, and of the subsequent global socio-economic crisis caused by the lowering of meat consumption in the l990s. In this case, emergence was the result of feeding bovines with flour obtained from animal’s carcass, notably bovines. Prions are also responsible for other diseases such as kuru, an epidemic neurodegenerative disease observed in the mid-l950s among New Guinea’s indigenous populations whose tradition consisted in collectively consuming the brain of dead persons (Gajdusek 2008). In addition, prions are involved in the aetiology of Creutzfeldt-Jakob disease in which the infectious agent is transmitted during neurosurgical interventions or through the use of growth hormones.

For a long time, dengue was present only in South-East Asia. Since the end of the l980s, it has significantly progressed in the rest of Asia, in Africa, Polyne- sia, and particularly in South America. As about 50 % of the world’s population is exposed to the virus, dengue is the most widespread virose on the planet. To date, 50 millions of infections have been observed in the world, with a mortality rate of at least 2.5 %. Previously called red or tropical fever, this disease is caused



Chapter XII. Medicine and Ecology 22l

by an arbovirus transmitted by the sting of the mosquito Aedes aegypti. Factors responsible for its explosive expansion create favourable ecological conditions for the multiplication of mosquitoes. Those include demographic growth, massive urbanisation and the creation of large shantytowns on the outskirts of cities, and natural catastrophes. Attempts at developing an effective vaccine are hampered by the existence of four viral subtypes of dengue. As protection against one does not offer protection against the others, mosquito control remains the most effi- cient preventive approach (Magner 2009).

Chikungunya or “ break-bone fever ” is another viral disease propagated by Aedes whose symptoms closely resemble those of dengue fever, and may lead to diagnostic errors. The virus had already been isolated in l952-l953 during an outbreak on the plateau of Makonde in Tanzania and the disease was long endemic in rural subtropical African regions, with recurrent epidemic bursts in non-immune populations of the rest of Africa and on the Indian sub-continent. What has changed, however, is that the geographical zone of diffusion of the mosquito has substantially grown larger since the late twentieth century to include now most of Europe and Americas. In 2007, the first epidemic outbreak in North- East of Italy was monitored. Here again, the creation of artificial ecological hab- itats favouring mosquitos’ reproduction has played a significant role in the diffusion of the disease.

On March l2th 2003 a new form of severe pneumonia entered the international scene : SARS, the “ twenty-first century plague ” (Abraham 2004). Identi- fied by WHO as a respiratory disease of unknown cause capable to rapidly propagate itself among hospital staff in Hong Kong and Vietnam, the disease was observed two days later in Singapore and Toronto’s hospitals in Canada, with patients presenting similar signs and symptoms. The disease quickly migrated from one continent to another thanks to air travel. The causative organism was a coronavirus different from any other human or animal viruses of the same family. The global rate of lethality was about l0 %. In the absence of therapeutic approaches and vaccines to fight SARS, strategies to counter the virus were based on classical interventions : identifying individuals showing characteristic symptoms ; establishing quarantine measures ; developing active surveillance ; controlling travellers, etc.

In 2009 an alert of an emerging epidemic of influenza A was emitted in Ver- acruz, Mexico, on the basis on the relatively high number of severe flu cases, indicating a possible epidemic present since a few months already. Despite the early measures undertaken such as securing borders to contain the disease, the epidemic spread rapidly. In June of the same year, both WHO and CDC con- firmed the pandemic state3. Identification of the virus was hastily completed. Results indicated that the influenza virus was HlNl, the same strain responsible for the l9l8-l9 pandemic, and had emerged from a genetic recombination

3. http://www.who.int/mediacentre/news/statements/2009/hlnl_pandemic_phase6_200906ll/en/ index.html.


between bird flu and swine, hence the name “ swine flu ” used to characterize the pandemic. A particularity of influenza viruses is their capacity to easily modify their structure and their genetic composition, allowing them to circumvent immunological defences thanks to random mutations and especially thanks to the rear- rangement of different parts of the genetic material. Influenza is classified as an ever re-emerging disease (Webster and Kawaoka l994).

Like in the case of the “ Spanish ” influenza pandemic the case distribution of this new epidemic among age groups was unusual (on the l9l8-l9 influenza pandemic, see Méthot and Alizon 20l4b). For instance, it showed a high proportion of young adults and the presence of severe respiratory pathologies due to second- ary bacterial infections. A vaccine was developed and mass vaccination campaigns were made compulsory in several countries. In addition, health-security measures such as wearing a mask and washing hands were implemented. Yet the new form of influenza turned out to be less deadly than anticipated and the number of new cases started to decline from May 20l0 onwards. On August l0th of the same year, WHO General Director Margaret Chan proclaimed the end of the HlNl pan- demic4. The over-evaluation of the severity of a new pandemic stirred debates among public health authorities, politicians, and among the general public because of the cost of vaccination campaigns and other expensive preventive measures. The HlNl situation is not unique, however, and it parallels what was called “ the swine flu affair ”. In l976, when one army recruit died at Fort Dix, New Jersey, from a virus similar to the l9l8-l9 flu and caused between 500 and l000 other cases, the National Institute for Allergy and Infectious Diseases launched a pro- gramme of (voluntary) mass vaccination, stockpiled flu vaccines, and vaccinated over 43 million people. President Ford’s decision was widely criticized because the expected epidemic did not occur and furthermore, 535 vaccinated individuals developed a paralytic syndrome, out of which 23 died (Krause l998, p. l2).

Many other “ new ” diseases have surfaced in the last three or four decades of the twentieth century. For instance, in l976, a mysterious disease of bacterial origin struck several members of the American Legion who had congregated in a hotel in Philadelphia. Thanks to artificially created environment that enhanced its replication within air conditioning systems and hot water tanks in the hotel, this common Gram-negative bacterium “ emerged ” and caused acute respiratory symptoms to several of these men. The genus Legionella was established through laboratory analyses three years after the first outbreak. Toxic shock syndrome, first identified in l978, results from the production of a toxin produced by particular strains of golden staphylococcus and transmitted by the use of extra absor- bent hygienic tampons. The spread of a virulent bacterial disease known as “ Lyme disease ” (caused by a species of the genus Borrelia and transmitted by tick bites) also illustrates the impact of ecological changes in the emergence of new epidemics. Indeed, the diffusion of Lyme disease in North America (with at

4. http://www.who.int/mediacentre/news/statements/20l0/hlnl_vpc_20l008l0/en/index.html.

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Chapter XII. Medicine and Ecology 223

least three million cases in the last decades of the twentieth century) is attributed to many factors : deforestation, increased number of tick-bearer animals, and the migration of a significant number of inhabitants in suburban districts close to for- ested areas (Morse l995).

The re-emergence of diseases once believed to be under control, such as diph- theria, tuberculosis, pneumonia, meningitis or malaria, and the appearance of drug-resistant strains to antibiotics and antivirals, result largely from environmental changes and new medical practices. Though the phenomenon of drug resistance was known since the l930s its wider implications were largely disconnected from clinical practices and from medicine more generally. A renewed emphasis on the consequences of evolutionary processes leading to antibiotic resistance could help illustrating the importance of evolutionary biology in some key areas of medical practice (Méthot 20ll). One of the lessons to draw from the resur- gence of old diseases and the appearance of new ones such as AIDS is that an important shift has taken place regarding the future of infectious diseases : the question is not any more whether new diseases will surface but rather how best to organize countermeasures to predict and contain them (Snowden 2008), an issue that connects with growing concerns for biosecurity, dual-use technologies, the ethics of infectious disease as well as with problems in assessing and promot- ing the quality of life.

5. The determinants of disease emergence

The causes behind disease emergence were initially divided into six main groups (Lederberg, Shope, and Oaks l992). The first group concerns demographic changes in human populations (migration, urbanisation, augmentation of population density, typology of housing, etc.) ; the second is linked to individual behaviours (hunting, exploration of new territories, non-protected sexual contacts, diets, rites, etc.) ; the third group includes important environmental changes resulting from natural catastrophes or from the use of land such as, for instance, industrial developments, deforestation, the construction of dams and barrages, and the development of intensive agricultural practices ; the fourth ensemble concerns the exponential development of trade and travels that allows millions of people to cross long distance in very short periods of time, but also to carry natural and industrial products that may contain germs or disease vectors (e.g. food product, used tires) that are the locus of reproduction of specific vector-borne diseases ; the fifth group relates to the breakdown of public health measures, the development of medical technologies like vaccination, surgical interventions, tissues and organs transplantations, the use of non-sterile medical material, and the unregulated use of antibiotics or other products leading up to drug resistance phenomena ; finally, the sixth category concerns the adaptive capacities of microorganisms themselves.

Ecological and socio-economic changes are among the leading causal factors of most emerging diseases. The majority of emerging epidemics, for instance,


result from the “ rules of viral traffic ”, namely l) the introduction of a pathogen (bacterium, virus, prion, etc.) into a wholly susceptible host population, and 2) the successful dissemination of the pathogen within the given population (Morse l99l ; l993 ; l995). For each host/virus association, a threshold determines the possibility for the virus to be disseminated in a population, and thus to “ emerge ”, and to remain in a state of (more or less stable) ecological equilibrium (Anderson and May l992). Those thresholds rest on several interlocking factors such as population density, the host’s recovery rate, and its behaviour. Histori- cally, thresholds have varied in space and time and continue to do so, following rapid ecological changes (e.g. deforestation, climate change, etc.), population migrations, in addition to cultural and behavioural changes. Exposition of one or several individuals to infected animal or vegetal tissues can result in interspecific transmission (primary infection). Such infection, then, can produce small, localized epidemics because of interpersonal contacts but will have only a minor impact on public health because primary infections are usually ill adapted to wide and rapid diffusion in a population. Most virologists would agree that disease emergence is usually nothing but the result of an increase in the visibility of a previously known disease, and achieving a greater visibility for a given pathogen is, in turn, often the result of ecological changes (Kilbourne l996).

Successive passages of the germ in hosts under specific conditions (e.g. lack of hygiene, low immune protection), or mutation, could also facilitate its adapta- tion and population density could foster an augmentation at the level of transmis- sibility and frequency, however. In addition, migrations and travels constantly open-up new routes of transmission and can transform a local disease into a global health problem. An ecological and evolutionary perspective on diseases is thus indispensable in order to analyse and, when possible, alter the dynamics of emerging processes. Joshua Lederberg had previously suggested looking at epidemics of infectious diseases as permanent and recurrent natural phenomena, and to interpret their waxing and waning as resulting from the coevolution between germs and human populations over time (l988). Hence the need to replace classical war-like metaphors (war to microbes, final weapon, organism’s defence, eradication, etc.) by a language firmly rooted in an “ ecological ” approach to infectious diseases.

Social and economic aspects are also crucial in the analysis of infectious diseases, both in terms of their causal contribution to and their consequences for human and animal’s health. Likely, most epidemic outbursts result from poverty, uncontrolled urbanisation in poor countries, and lack of sanitary resources. Experts and public health authorities tend to focus on purely epidemiological and clinical aspects of emerging events, however, leaving to one side the social and ecological determinants in emerging processes and their socio-economic and cultural consequences. Indeed, neither ecological nor social factors were directly listed on the initial table of the Institute of Medicine in l992 (though they were somehow implicit). An up-dated version of the report published in 2003, in response to some criticism voiced by leading experts such Harvard Professor Paul




Farmer (l996), augmented the initial list of 6 main determinants of emergence to l4 and insisted on the complex interactions between them. The new list now includes, in addition to the previous 6 factors : climate and weather ; changing ecosystems ; poverty and social inequality ; war and famine ; lack of political will ; and intent to harm (Smolinski, Hamburg, and Lederberg 2003).

At the cultural level, psychological reactions (both individual and collective) to a severe epidemic can lead to chaotic situations and to the fear of contagion (Rosenberg l992). In turn, this situation can contribute to an increase in disease severity and produce prejudicial discriminations and stigmatisations, even in countries left untouched by the epidemic. Hence the heightened importance of studying the social and lay perceptions of emerging threats in populations and of measuring their potential (or actual) psychological impact (Bangerter 20ll). The psychological impact of emerging diseases influences the perception and assess- ment of the quality of life as well. Indeed, great plagues are almost always fol- lowed by the dislocation of political structures, by important changes in social relations in addition to the abandon of solidarity, and by deep perturbations in the demography of the population, the latter resulting mostly from high mortality and immigration. Furthermore, the emergence of a severe epidemic or pandemic can increase health inequalities, which in turn can change the course and the distribution of the epidemic itself, thanks to the increased susceptibility of poor populations, both socially and culturally. Unsurprisingly reducing health inequalities through action on the “ social determinants of health ” has become the primary objective of the World Health Organization (2009).

Finally, research of the ecology of emerging infections can significantly impact on the classification of pathogenic agents as it can lead to new nosological categories or to the re-interpretation of previous ones. Consider the herpes human virus 6 (HHV-6). The extremely widespread virus that generate the disease was only recently identified and recognized as the biological cause of a well-known “ eruptive disease ” of childhood that was either called three-day fever or infantile rosella. The now famous Helicobacter pylori and its role in the aetiology of gastric cancer also illustrate how different causal conception can lead to important revision in our classifications (and treatment). In l982, J.R. Warren and B.J. Mar- shall recognized this widespread bacterium as the leading causal factor in gastro- duodenal ulcer and some forms of gastric cancer, two pathologies known since the Antiquity that had to be reclassified as infectious pathologies. In turn, this led to a profound revision of the treatment of gastric ulcer with the use of antibiotics. Similarly, the German virologist Harald zur Hausen had made the hypothesis in l976 that papillomavirus could be causally related to cervix cancer, and had begun to develop a vaccine against the virus. The following years, epidemiological studies showed that 8 different types of VPH are responsible for 90 % of cervix cancers. In 2006 a new vaccine was developed and commercialized which led to a mass vaccination campaign among young women. From this point of view, cervix cancer could be redefined as a “ new viral disease ”. Several forms of chronic diseases, including atherosclerosis and arthritis, have been found to be triggered by bacteria or viruses, and thus blur the distinction between infectious,


hereditary, and chronic diseases that was once sharply made by medical bacteri- ologists such as Robert Koch (Gradmann 2008, p. 223).

6. Critical perspectives on the concept of emerging disease

The attention of public health authorities and the intense media coverage given to newly emerging diseases thought to be resulting from a nature “ out of balance ” (Garrett l994) was criticized. For historians, the media reports had the unwanted effect of transforming relatively isolated events into large-scale and global threats affecting particularly Western countries (King 2004). Viewing the situation from a broader social perspective, others pointed out that international health authority failed to include poverty, famine, and social inequalities more generally in the list of important factors behind disease emergence (Farmer l996). In the light of those critiques, it seems worth to recall that the concept of emerging disease was primarily intended to gather international resources to fuel the development of new collaborative research, both fundamental and applied, on infectious diseases. In that respect, this “ active concept ” was immensely successful : it helped to lever funds ; it facilitated international and national cooperation ; and it fostered a “ rebranding ” of infectious diseases as international threats to both the North and the South (Weir and Mykhalovskiy 20l0). Yet, the significance and scope of this concept remains obscure as “ emerging disease ” can take on several meanings and serve different political purposes. The complexity inherent in the politics of “ new” disease itself calls for a critical examination of the concept of “ emerging disease ”.

As a starting point, let us consider how emerging diseases are usually defined. The Institute of Medicine proposed that emerging diseases are “ diseases of infectious origin whose incidence in human populations has increased within the past two decades or threatens to increase in a near future ” (Lederberg, Shope, Oaks l992, p. 34 ; emphasis added). Two years later, the CDC introduced its own definition : “ the term ‘emerging infectious disease’ refers to diseases of infectious origin whose incidence in humans has either increased within the past two decades or threatens to increase in the near future ” (CDC l994, p. 2 ; emphasis added). In the first issue of Emerging Infectious Diseases, Morse proposed to define as emerging “ infections that have newly appeared in the population, or have existed but are rapidly increasing in incidence or geographic range ” (Morse l995, p. 7 ; emphasis added). Several other similar definitions coexist in the literature.

It should be noted, firstly, that most definitions are concerned with transmis- sible diseases, though this is not an intrinsic requirement of the concept itself ; for example, some of the early authors to employ the concept of emerging diseases in the l960s used it in the context of chronic diseases (King 2004, p. 64). Sec- ondly, the main criterion to define emergence is not, as one could expect from the etymology, an element of surprise or of novelty in pathology (i.e. a “ new disease ”), though it can be, but rather the increase in “ incidence ” (i.e. the number of new “ cases ” in a given population during a definite period of time). For




example, some argued that a recently identified disease with a low incidence should not be called emergent (Toma and Thiry 2003, p. 3). Yet there may be situations where public health officers want to classify a newly detected disease as emergent, though at low frequency. Consider AIDS. Even if the incidence (i.e. number of new cases) of the disease was initially limited to a spatiotemporally limited community (e.g. in San Francisco during the l970s and early l980s), few would deny that it was an emerging infection ; in fact, it is usually regarded as a paradigmatic case of such (Grmek l990).

Thirdly, the reasons behind the defining criterion of emergent phenomena are not clearly articulated in the CDC and IOM’s definitions. Why should incidence be the main (and even only) defining criterion ? And why is “ two decades ” the relevant unit of time to measure emergence ? Surely, major fluctuations in a known disease that modify its epidemiological profile can be interpreted as evi- dence for emergence. This criterion alone may not suffice, furthermore, for what then, demarcates epidemics from emerging or re-emerging diseases, if anything ? Fourthly, the decision to restrict the term “ emerging diseases ” to human pathology is puzzling. In the light of programmes such as the One Health-One Medicine initiative, recognizing the unavoidable intricacy of human, animal, and ecosystem’s health, the implicit divide between human and animal pathology as embod- ied in the CDC’s definition is likely to become problematic.

In the light of these remarks, what is needed is a broader concept that recog- nizes several possible emerging scenarios as legitimate such as the one articulated by Mirko Grmek (l993). Following Grmek, a disease is “ emerging ” in (at least) the five following historical situations :

l- Impossibility for the medical gaze to conceptualize the disease as a distinct nosological entity ; 2- Generation of a pathogenic agent truly new following a mutation or genetic recombination inside the same genome or by total (or partial) hybridization of distinct genomes ; 3- Qualitative or quantitative change in the clinical manifestation of a disease thanks to, for instance, a change in the germ’s tropism or the modification of the immunological state of a population ; 4- Introduction of a disease from another human population, either because of a migration of the bearers or the vectors ; 5- Introduction of a disease from an animal population (zoonose). An animal or vegetal germ can make contact with human populations following the latter’s entry into new territories or the migration of animal hosts.

Cases l-3 define any disease that did not exist in any human population as a

distinct clinical entity, or under its actual pathological manifestations, as emerging when it has never previously existed in a human population or was never conceptualized within existing medical taxonomies. However, defining what a


“ new ” disease means can be confusing. For Grmek, a disease can be characterized as novel, even if it did exist in the past but remained unnoticed within previous theoretical frameworks. For instance, diseases such as AIDS were impossible to conceptualize prior to the discovery of RNA retroviruses though the causative viruses existed. Case 3 corresponds to the criterion suggested by the IOM and the CDC : changes in the quantitative manifestation of a disease (e.g. increase in incidence). Case 2, in turn, would be the evolution of a particularly virulent microorganism. Alternatively, case 2 also describes how a non-pathogenic agent can turn pathogenic following genetic alterations, or changes in the vector or the host’s immune system, modifying the virulence of the agent or the tissue tropism in different organs, and emphasizes the difficulty in defining what a pathogen is (Méthot 20l2b). In cases 4 and 5, the disease existed in other populations, and was known, but it crossed existing geographical and/or species bar- riers and created new infected susceptibles. In some cases, the increased visibility of a disease can also be the result of mistaken perceptions about the incidence. Widespread in poor countries, anthrax became an iconic “ emerging ” disease because of some bioterrorist acts (e.g. postage of the spores of the microbe responsible for the disease in the US in 200l).

Grmek’s classification could be applied retrospectively to several historical situations as well as to contemporary cases. His account frames emergence in a way that is not limited to a rapid change in frequency but also considers other parame- ters and specific historical contexts – what Grmek l969 called a “ pathocenosis ” – in which emergence occurred. Indeed, his taxonomy includes conceptual and biological novelties within the concept of disease itself. AIDS, again, was certainly a new disease in the early l980s (from a conceptual, technological, and biological point of view) and it was at the same time “ emerging ”, at least according to the IOM definition, although the viruses themselves had arguably long existed. In that sense, most “ emerging diseases ” would be better described as “ emerging epidemics ” resulting from an enhanced diffusion of pre-existing microorganisms thanks to several factors such as migrations, wars, travels, and trade.

Though not discussed under this light by Grmek, the concept of emerging disease is not a value-neutral category. Whether a disease is considered emergent, indeed, depends also on the historical, social, and political context, not just on empirical or theoretical considerations. For instance, the concept implicitly prior- itizes emerging (and re-emerging) over non-emerging diseases, an assumption that impacts on funding allocation and health care priorities (Farmer l996). The formation and use of the concept of emerging disease, furthermore, was meant to ensure that no other pandemic like AIDS should arise in the near or far future. Thus deciding to label a disease as “ emerging ” reflects, at least partly, some underlying agenda and public health goals and values. Like “ contagion ” or “ infection ” the concept of emerging disease has cultural and psychological implications that reach far beyond fundamental biology and medical practice.




7. Conclusions

Following the “ rebranding ” of infections as pressing and global threats, historians and sociologists of science and medicine have characterized the period from l992 onwards as marking a “ distinctive era ” in the history of public health, one where the Western world discovered that infectious diseases have not been defeated but that, on the contrary, “ it [the Western world] remained painfully vulnerable and to a degree that had seemed unimaginable ” (Snowden 2008, p. 8 and p. l2). For others, the early l990s are characterized by an “ epistemological break ” in the field of international communicable disease, that is, by a shift from a world “ oriented to known diseases to one responsible for a microbial world full of potential and surprise ” (Weir and Mykhalovskiy 20l0, p. 62). In all cases, the notion of “ emerging disease ” thoroughly conceptualised disease as a historical entity.

Although the early l990s constitute a significant point of rupture in global public health, the concept of “ emerging ” diseases has also led to a profound reconfiguration of the relation between man and nature, placing the problem of infectious diseases into the foreground of a broadly interconnected ecological world. Approaching the future of infectious diseases from a global, dynamic, and historical perspective could perhaps prevent us from falling back into another era of medical complacency.

To conclude, not only do we remain painfully vulnerable to emerging diseases but it has also become clear that threats of bioterrorism and biological accidents cannot be understated. Bringing old (and new) diseases back to life thanks to advances in genomics, high throughput technologies, and synthetic biology raises additional concerns within the life sciences and calls into question existing definitions and understanding of the concept of emerging infection itself. In his orig- inal article, Grmek carefully added a sub-category that is now gaining currency : artificially or “ manmade ” emerging diseases (l993, p. 285). With the (re)creation of the l9l8-l9 influenza strain and a few others (e.g. Yersinia pestis, polio virus, H5Nl), a different form of biological threat arises, and it is one that requires different political, institutional, conceptual, and legal responses (Méthot 20l4). One of the direct consequences of these experiments is that while the threat of emerging infections was mostly perceived as coming from outside Northern-hemisphere countries in the l990s, it now appears to be growing from within Western countries themselves. The recent moratorium of 60 days on research on virulent infectious diseases held in 20l25, stimulated by two articles on the airborne transmission influenza in mammals, is a reminder of the fact that emergence is not only a natural process occurring spontaneously and inde- pendently of us ; human actions can greatly facilitate the creation of new disease entities. However, if new germs – manmade or not – can easily cross social and

5. http://news.sciencemag.org/scienceinsider/20l2/07/us-infectious-disease-chief-urge.html. Both studies have now been published.


geographical frontiers, scientific, technological, and humanitarian resources, on the contrary, are often blocked at the border between rich and poor countries. To adequately respond to the challenges posed by emerging diseases worldwide we need a global political and legal instance able to channel resources and to lead research. In this respect, we might need nothing less than a “ world health government ”, as suggested initially by the Constitution of WHO in l948.


Medicine and ecology: historical and critical perspectives on the concept of emerging disease

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