Historical Review

Emerging infections: a perpetual challenge

David M Morens, Gregory K Folkers, Anthony S Fauci

Lancet Infect Dis 2008; Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific
8: 710–19
and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other
National Institute of Allergy emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants
and Infectious Diseases
(NIAID), National Institutes of
of disease emergence, including population growth, travel, and environmental disruption, have been increasingly
Health (NIH), Bethesda, MD, documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic
USA (D M Morens MD, determinants, transcending time, place, and human progress, govern disease generation? By examining a number of
G K Folkers MPH, A S Fauci MD)
historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of
Correspondence to: control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert,
Dr David M Morens, National
Institute of Allergy and
seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human
Infectious Diseases, National survival.
Institutes of Health, Building 31,
Room 7A10, 31 Center Drive, Introduction emergence—eg, microbial adaptation to new hosts (HIV
Bethesda, MD 20892, USA
[email protected] “Not a single year passes without [which]...we can tell the
infection, severe acute respiratory syndrome [SARS]),
world: here is a new disease!” population immunity pressures (influenza A), travel
(acute haemorrhagic conjunctivitis), animal migration
Rudolf Virchow, 18671
and movement (West Nile virus infection, H5N1 avian
Infectious diseases are responsible for 15 million (26%) influenza), microbial escape from antibiotic pressures
of 57 million annual deaths in a global population of (multidrug-resistant and extensively drug-resistant
6·2 billion,2 a proportion that could rise substantially as tuberculosis), mechanical dispersal (Legionnaires’
chronic diseases continue to be reclassified as disease), and others (panel, figure 1).3–7
infectious—eg, cervical cancer (human papillomavirus), Clearly, however, the terminology of emergence is not
Kaposi’s sarcoma (human herpesvirus 8), and Helicobacter entirely new.8,9 In the Old Testament, ancient China,
pylori ulcers, among others. classical Greece and Rome, and in subsequent centuries,
In recent years, the terms “emerging” (ie, newly new diseases have repeatedly been said to be “introduced”,
recognised) and “re-emerging” (previously recognised) or to “appear”, “approach”, “arise”, “breed”, “progress”,
infectious diseases have entered the vocabulary of “spread”, or “invade” etc.10–12 In this article we ask two
medical science.3–5 These infections also include basic questions. Are emerging infections a new
“deliberately emerging diseases”—eg, bioterrorism.5 phenomenon? And do fundamental determinants,
Concern about emerging infections has grown following transcending time, place, and human progress govern
the appearance of new diseases, such as HIV/AIDS, and their generation?
the re-emergence of others, such as dengue, and from Here we compare several historically notable emerging
appreciation of the complex determinants of their infections—selected non-systematically to include
examples deemed representative of a range and complexity
of circumstances, stretching over more than two
Panel: Factors involved in infectious disease emergence4–6 millennia—to modern emerging infectious diseases and
Often differing for newly emerging, re-emerging, and consider the circumstances of their emergence. Since
deliberately emerging diseases, these selected factors include these circumstances seem to have changed little over
genetic, biological, social, political, and economic centuries (see panel, table, and figure 2),13–27 it would
determinants suggest that fundamental determinants may underlie the
1 International trade and commerce seemingly arbitrary emergence of new infectious diseases.
2 Human demographics and behaviour
3 Human susceptibility to infection The Plague of Athens, 430–426 BC
4 Poverty and social inequality “The [pestilential disease] originated, so they say, in
5 War and famine Ethiopia in upper Egypt, and spread from there into
6 Breakdown of public-health measures Egypt itself and Libya and much of the territory of the
7 Technology and industry King of Persia. In the city of Athens it appeared
suddenly…As to the question of how it could first have
8 Changing ecosystems come about or what causes can be found…I must leave
9 Climate and weather that to be considered by other[s]…”
10 Intent to harm
Thucydides, on the Plague of Athens13
11 Lack of political will
12 Microbial adaptation and change
13 Economic development and land use The above passage is taken from one of the most famous
accounts of an emerging infection ever written:

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 Historical Review

A
Human African trypanosomiasis
Cholera
Marburg haemorrhagic fever
MDR/XDR tuberculosis
Plague
Human monkeypox
Chikungunya fever
Enterovirus 71
Hendra virus
Nipah virus
Vancomycin-resistant Staphylococcus aureus
H5N1 influenza
Escherichia coli O157:H7
SARS Anthrax bioterrorism†
Typhoid fever Hantavirus pulmonary syndrome
Rift Valley fever Dengue
Diphtheria Yellow fever
Drug-resistant malaria HIV
Ebola haemorrhagic fever Lassa fever
Cryptosporidiosis Lyme disease
West Nile virus Hepatitis C
Cyclosporiasis vCJD

B
The French pox (syphilis), 1494
The American plague (yellow fever), 1793
Hueyzahuatl (smallpox), 1520†
Anthrax, 1770†
Cholera, 1832
HIV/AIDS, circa 1930
Spanish influenza, 1918
Measles, 1875
The Black Death (plague), 1347–50
The Plague of Athens (unidentified disease), 430 BC

Newly emerging
Re-emerging
Deliberately emerging†

Figure 1: Newly emerging, re-emerging/resurging, and deliberately emerging diseases

(A) Selected emerging diseases of public-health importance in the past 30 years (1977–2007),2,5 with representative examples of where epidemics occurred. (B) Selected emerging diseases of public-
health importance in previous centuries (430 BC to 1981). MDR=multidrug-resistant. SARS=severe acute respiratory syndrome. vCJD=variant Creutzfeldt-Jakob disease. XDR=extensively
drug-resistant.

Thucydides’ chronicle of the Plague of Athens, which disease and the first unambiguous description of an
heralded the end of the Golden Age of Greece (figure 2).13,28 emerging infection. Noting universal susceptibility,
The aetiology of this fatal, complex, multisystemic multiple independent importations, and an association
disease has not been conclusively identified; hypotheses with war, crowding, and the breakdown of public-health
include anthrax, smallpox, typhus, and more than measures, Thucydides also distinguished between signs,
20 other infectious candidates.28 Thucydides’ vivid symptoms, complications, and variant clinical courses,
account nevertheless represents the first comprehensive and presented attack and case-fatality rates. His
clinical-epidemiological characterisation of an infectious compelling clinical, public-health, and societally

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 Historical Review

contextual description of an emerging disease was Multiple independent importations of the plague
studied by virtually all western and middle eastern prompted public-health action in Europe and
medical students for centuries, and profoundly neighbouring areas. Frightened citizens began isolating
influenced concepts of, approaches to, and even arriving ships for as long as 40 (quaranta) days, the origin
terminology of emerging infections well into the of quarantine.14 In a Europe emerging from feudalism,
19th century. government was now held accountable for public health.
“[E]veryone must reflect on and prevent the causes that
The Black Death, 1347–50 can produce a universal or local pestilence [an epidemic
“I think it may be said of the plague, as is said of the
or an outbreak]”, wrote Jacme d’Agramont in 1348. “And
wind, that it bloweth where it listeth, and wee heare the if perchance these can be removed they must be removed.
sound thereof, but know not where it cometh nor where And to this end an effort should be made by the Lords
it goeth...” [municipal officials] and their officers whose duty it is to
William Boghurst, circa 166529 look after the...well-being of the community”.33
The Black Death may also have been associated with
The Black Death of the 14th century (bubonic/pneumonic one of the earliest recorded examples of bioterrorism.24–26
plague, from the Latin plaga, a blow or stroke) killed In 1346 a Tartar army besieging the garrisoned Genovese
approximately 34 million Europeans and 16 million city of Caffa (now Feodosiya, Ukraine) was devastated by
Asians, placing it among the most fatal emerging plague. The Tartars reacted by catapulting “mountains”
infections in recorded history.30 The disease’s origin was (probably thousands) of plague corpses into the city,24,25
traced to China in the 1330s or even earlier, from where it allegedly transmitting it to the besieged Genovese.26
proceeded inexorably westward to Europe along caravan 600 years later, during World War II, Japanese troops
and shipping routes.14,30 The many inter-related were less successful in starting a plague epidemic by
determinants of, and risk factors for its emergence (table) dropping paper bags filled with infected fleas on Chinese
have been exhaustively documented and discussed (for cities.34,35
example, in reference 26).
Accounts of mass deaths, deserted towns, rotting When (Old and New) Worlds collide: the French
corpses, and free-roaming farm animals are documented pox, 1494
in countless texts, and survive today in many works of art “...nowadays we see maladies unknown to our forefathers
(figure 2). The plague is said to have spawned the springing up around us”.
Tanzwuth (dancing mania) epidemics of the next two
Ullrich von Hutten, 151936
centuries, in which bands of itinerant youths roamed the
countryside drinking, dancing frenetically, and tossing From the 15th through to the 19th century, a time when
each other into the air.31,32 previously isolated continents were discovering each other
and thereby exchanging microorganisms, re-emergence
Emerging disease Causal agent Estimated Disease factors (see of epidemic diseases associated with geographic spread of
number of panel) microbes became common. In December, 1494, a new
human deaths disease emerged in Italy;15,36,37 prostitutes from Naples soon
430–426 BCE Plague of Athens13 Unidentified 40 000 2, 5, 7, 9, 11 infected soldiers from an invading French army. By July
1340s Black Death14 Yersinia pestis ~50 million 2, 5, 6, 7, 8, 10, 11, 13 the disease was being diagnosed in mercenaries from
1494–99 French pox (syphilis)15 Treponema pallidum >50 000 1, 2, 5, 7, 11 Flanders, Gascony (southwest France), Switzerland, Italy,
1520–21 Hueyzahuatl (smallpox)16 Variola major 3·5 million 2, 7, 10, 11, 13 Spain, and elsewhere; they eventually returned home and
1700s European cattle Rinderpest virus, foot >15 000* 4, 5, 6, 7, 8, 9, 10, 11, spread it throughout Europe.
epizootics17 and mouth disease 13 The French pox (syphilis) shocked and terrified.36 “What
virus, Bacillus anthracis other contagion has ever spread so quickly to all the
1793–98 The American plague18 Yellow fever virus ~25 000 2, 3, 4, 5, 6, 7, 8, 9, 10, countries of Europe, Asia, and Africa?” asked Desiderius
12
Erasmus (“of Rotterdam”); “What other contagion takes
1832 Second cholera Vibrio cholerae 18 402 3, 5, 7, 8, 10
pandemic, Paris19
such a hold of the entire body...and tortures so cruelly...
1875 Fiji virgin soil epidemic20 Measles virus 40 000 2, 3, 5, 7, 9, 10, 11, 12
combin[ing] all that is dreadful in other contagions?”38
1918–19 Spanish influenza21 H1N1 influenza virus ≥50 million 1, 2, 5, 7, 11
Syphilis greatly influenced Fracastoro’s theory of
contagion,39,40 the cornerstone of contagionism for the
From 1981 AIDS pandemic22 HIV >25 million 1, 2, 4, 5, 7, 8, 9, 10, 12
next 300 years. The epidemic also prompted substantial
Mortality estimates are generally approximations based on speculative data. The numbers in the disease factors lay thought about disease emergence. Popular
column refer to factors associated with disease emergence, as listed in the panel, and apply only to the specific
explanations (God’s wrath, well poisoning, copulation
epidemics discussed here. *Human disease caused by rinderpest is not known, and by foot and mouth disease virus is
uncommon and rarely serious; human disease associated with anthrax was continually observed during the epizootics with monkeys) seemed inadequate for a disease that was
of the 18th century; one epidemic alone (in Saint-Domingue, Hispaniola) is said to have caused 15 000 deaths.23 obviously acquired by intimate human contact and
spread by human movement. In a nosological “epidemic”
Table: Examples of epidemic emerging infections of historical interest
pre-dating the “Spanish flu” by four centuries, Portuguese,

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Dutch, and north Africans called syphilis “the Castilian” A D

or “the Spanish” sickness. To Muscovites it became “the
Polish sickness”; to the Poles “the German sickness”; to
the Germans “the French sickness”; to the French “the
Neopolitan sickness”, and so on. Several years passed
before a connection was made between the appearance
of the French pox and the return of Christopher
Columbus from the New World (March 31, 1493), but
strong evidence for New World exportation was eventually
provided by testimony from Columbus’ men41 and by
physicians’ accounts that Hispaniola natives had been B C
affected by the disease since ancient times.42
Societal responses to syphilis in the 15th and
16th centuries were not unlike responses to AIDS
500 years later.43 Undeniable sexual transmission made
syphilis one of the few diseases of that era, including
leprosy, for which contact contagion was certain. Priests
denounced the wickedness and immorality of an age that
had provoked God’s anger in the form of a deadly
pandemic. Affected spouses, lovers, family, and friends Figure 2: Examples of modern and historically important emerging infectious diseases
were shunned and abandoned. The hospital bed linens of (A) Emerging epidemics caused by war and famine. Plague in an Ancient City, by Michael Sweerts, circa 1652,
represents the Plague of Athens.13 Oil on canvas, Los Angeles County Museum of Art, CA, USA. The infamous
Parisian patients were initially burned. Soon, victims
epidemic, the cause of which is still unidentified, occurred during the Peloponnesian wars between Athens and
were turned away entirely; then they were given 24 h to Sparta (430–426 BC). (B) Emerging epidemics associated with intent to harm. The Black Death (bubonic/
isolate themselves or leave the city on pain of death by pneumonic plague) of 14th century Europe was associated with a bioterrorist attack at Caffa.24–26 The untitled and
hanging. Charlatans with quack remedies, often painful anonymous painting has been referred to as Death Strangling a Victim of the Plague (circa 1376; Clementinum
Collection of Tracts by Thomas of Stitny, also known as Stitny Codex, University Library, Prague, Czech Republic).
and deadly, appeared everywhere to treat desperate and
Photo credit Werner Forman, Art Resource/NY. (C) Emerging epidemics due to travel and trade. Honoré Daumier’s
dying victims. Nothing worked. Syphilis and humanity depiction (hand-tinted woodcut) of the 1832 Paris choléra-morbus epidemic,27 which spread slowly from Asia to
therefore had to accommodate each other, and are still Europe along established travel routes.19 National Library of Medicine, History of Medicine Division. (D) Emerging
doing so 500 years later. epidemics associated with microbial adaptation and change. A Maori (New Zealand Polynesian) cenotaph
(monument honouring the dead) at a marae (meeting place), Te Koura, New Zealand, memorialises those who
died in the 1918–19 influenza pandemic. Photographed by Albert Percy Godber. Cenotaph designed and carved by
Microbial exchange and disease emergence in Tene Waiter. Alexander Turnbull Library, National Library of New Zealand, Wellington, New Zealand.
the age of discovery: Hueyzahuatl (smallpox),
1520 had died,49 presumably largely because of smallpox and
“After our fathers and grandfathers succumbed...dogs
additional imported diseases. Smallpox spread southward
and vultures devoured the bodies. So it was that we into South America, ultimately destroying two great
became orphans, oh, my sons! So we became when we civilizations, the Aztec and Inca empires, facilitating
were young. All of us were thus. We were born to die!” Spanish conquests that greatly altered history. Francisco
Cakchiquel Mayan on the hueyzahuatl epidemic of 1520–2144 Pizarro, who continued Spanish conquests of South
America in the 1530s, is alleged to have undertaken a
The 1493 European importation of syphilis from the New bioterrorist attack on native peoples using smallpox-
World did not imply unidirectionality of biological contaminated blankets.50 Mexico became a regional
conquests. Spanish adventurers under Hernando Cortés geographic reservoir for smallpox and was the source of
landed on the Yucatan Coast 25 years later and marched repeated exportations until the 1940s.
to the capital of Tenochtitlan (now Mexico City),
humiliating and imprisoning the Aztec ruler Moctezuma. Lessons from emerging epizootics, 1709–99
Before Cortés could defeat rival Spanish soldiers sailing “If there is, within medicine, any subject worthy of...
from Cuba to restore Moctezuma’s authority, the rival investigation...it is, without doubt, epidemic pestilential
soldiers landed a former slave infected with smallpox. diseases, obscure and hidden in their causes, rapid in
Over the next year the hueyzahautal (great eruption) their progression, frightening in their symptoms, and
raged over central America.44–47 deadly in their consequences.”
Although smallpox may have first emerged in central Félix Vicq-d’Azyr, 177651
Africa 5000 years previously—when an animal
orthopoxvirus jumped into human beings48—the disease The emergence of devastating cattle epizootics in 18th century
had probably not reached the New World. Historians Europe had a profound impact on concepts of, and
believe that about 3·5 million people in central Mexico responses to, human disease emergence.17 European
died in the first year of the hueyzahautal. By the end of epizootics of rinderpest,51 a highly contagious bovine
the century some 18·5 (74%) of the 25 million population paramyxovirus disease, appeared in 1709, to be followed

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 Historical Review

miles from the White House), to make anthrax and other

18
microbial weapons that were then used by paid agents to
Hinkler
16 infect US and Romanian cavalry horses.35 In World
War II, Japanese scientists undertook a human
14 bioterrorist campaign with anthrax and other agents.35 A
Sverdlovsk (Yekaterinburg, Russia) bioweapon facility
England to Australia (days)

12 Imperial HP 42/AW Atlanta/DH 96

accidentally released anthrax spores in 1979, killing more
10 than 60 people.57
Imperial Empire Boat
KLM/KNILM DC-3/L14
8
The American plague (yellow fever), 1793–98
6
BOAC Hythe “....much light might be thrown on the causes of violent
epidemics, by a series of careful observations, on their
4 NGAT DC-4 beginning and progress...about the time the yellow fever
Qantas L749
BOAC Britannia
made its appearance in this city...it was observed that
2 Qantas L1049G musquetoes invaded us in numberless swarms...”
BOAC 747 BA 747-400
BOAC Comet 4
0 Noah Webster, Dec 1 and 6, 179710
1925 1930 1940 1950 1960 1970 1980 1990 2000
Year 6 months after delivering his 1793 inaugural address, US
President George Washington was fleeing a deadly
Figure 3: Average travel time between England and Australia, 1925–2000
As travel times between distant places have decreased markedly in the past nine decades, the potential for human
emerging epidemic. The entire federal government, along
importation of diseases, especially those with long incubation periods—even if they are easily identifiable—is with physicians, merchants, and the middle and upper
greatly increased, thereby increasing the potential for re-emergence of epidemic diseases via spread into new classes, quickly followed. Philadelphia, then the nation’s
geographic areas. The serial generation time of measles is approximately 14 days. Adapted from Cliff et al, 2000,84 capital, became a ghost town with an empty harbour,
by permission of Oxford University Press.
deserted streets, shuttered shops, and rotting corpses.18
Within a few weeks yellow fever, or as Europeans called it
soon thereafter by epizootics of anthrax (1712) and foot “the American plague”, killed more than 5000 of about
and mouth disease (1755).17,52 Between 1709 and 1769, 50 000 Philadelphians.58 The disease then moved to the
more than 200 million western European cattle died of major US cities, including Baltimore, Boston, and New
rinderpest alone, equivalent to 20% of all dairy cows. York, and to many smaller towns.18,59 Recurrent yellow
Rinderpest elicited relatively sophisticated germ theories17 fever epidemics panicked the nation for six consecutive
such that immunisation against it was considered 8 years years, affecting nearly every American in some way.18,60,61
before the first western immunisation was introduced in Philadelphians who remained in the city formed
1720 (smallpox inoculation).52,53 Notably, rinderpest disease an emergency government, mobilising the most
was understood clinically and epidemiologically by about marginalised citizens—immigrants and African-
1770, more than a century before the causal agent was Americans—mistakenly believing the latter to be naturally
identified and characterised.17 resistant.18,62,63 Opposition by physicians to the use of
The epizootics of rinderpest, anthrax, and foot and quarantine measures put them in the middle of angry
mouth disease led to comparative animal study of disease political debates.18,58 National days of thanksgiving and
transmission, to the establishment of the world’s first prayer expressed the general belief that the epidemics were
veterinary schools, and to the first international human “a national judgment, and the[ir] removal...a national
disease surveillance/outbreak investigation system.17 blessing”.64
Directed by the prominent epizootic investigator In 1793, a young belle, Dolley Todd, watched both her
Félix Vicq-d’Azyr, surveillance for emerging diseases husband and infant son die in her arms of yellow fever,
relied upon field reports of diseases and their suspected then nearly died of it herself. 20 years later the remarried
risk factors.51,54 When outbreaks occurred, physicians or Dolley Madison nursed her second husband—President
veterinary students were dispatched to investigate and James Madison—when he nearly died in office of what
implement control measures.17,54 might have been yellow fever.60 Historians have claimed
Anthrax has long been associated with intent to harm. that deep social and political fault lines were opened up
More than two centuries before the 2001 anthrax attacks by the American plague of 1793–98, stamping the nation’s
in the USA,55 unscrupulous farmers in Saint-Domingue, character and “[shaking] the newly laid foundations of
Hispaniola, intentionally sent to market the meats of the Republic...[so that] the crises they aroused have never
infected livestock, producing in 1770 the deadliest anthrax been entirely put to rest”.58
epidemic on record. 15 000 people are said to have died of But the epidemics also led to important advances in
the disease, and another 15 000 from the slave revolt it public health, such as the establishment by Congress in
precipitated.23,56 During World War I, a German agent set 1798 of the Marine Hospital System,65 the forerunner of
up a laboratory in Chevy Chase, MD, USA (a mile from the US Public Health Service. In 1797, America’s first
the current National Institutes of Health, and several medical journal, The Medical Repository,66 was founded by

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three physicians who had survived the epidemic. By to be requisitioned to remove thousands of bodies,
emphasising emerging epidemics and in publishing bills citizens were horrified to see layers of corpses piled upon
of mortality and other epidemiological information, the them, claiming they heard cries and sobs coming from
new journal foreshadowed by two centuries the modern still-living victims. Rumours of mass poisoning of the
journal Emerging Infectious Diseases. In 1799, future water supply led vigilante mobs to roam the streets For Emerging Infectious Diseases
lexicographer Noah Webster expanded his yellow fever searching for suspected poisoners, attacking and journal see http://www.cdc.gov/
ncidod/EID/
research into a two-volume text on emerging pestilential sometimes killing innocent people.
diseases,10,67 which influenced epidemiological thought in Case lists published in the daily newspapers allowed
Europe and the USA for nearly a century.68 “armchair epidemiologists” to follow mortality and
morbidity trends. For the first time in history, a large-
“Modern” epidemiology joins emerging disease scale emerging epidemic was scientifically investigated
prevention: cholera, 1832 in “real time”, using census data in a prospective
“France and its capital have been visited by a fearful
population-based approach that featured analyses of
pestilence...It comes without any known cause; it morbidity and mortality stratified by age-group, sex,
disappears without any revealed reason. The bodies of occupation, socioeconomic status, and location, as well
its victims are in vain examined; death is interrogated: as calculation of case-fatality ratios, age-specific incidence
death betrays nothing.” rates, and attributable risks.19 “Modern” epidemiology
Louis-François Benoiston de Châteauneuf, 183469 was born during the 1832 epidemic, but was unable to
stop cholera emergence.
In 1830 cholera began to creep slowly from Asia towards
Europe along major waterways. It reached Archangel, The virgin soil epidemic (measles), Fiji, 1875
Russia, in May, 1831; St Petersburg in June; Constantinople “...The spirits flow away like running-water, au nanuma.
at the beginning of July; Pesth (Austro-Hungarian The sickness is terrible, au nanuma...We have fallen
Empire) in mid-July; and Vienna and Berlin at the upon a new age, io e. Infectious disease is spreading
beginning of August. among us, io e…“71
The French mounted an unprecedented response.19,70 A Fijian meke (dance/chant), circa 1792, describing the
On March 4, 1831, an interdisciplinary commission of the first Pacific-wide pandemic, lila balavu (an unidentified disease),
Académie royale de médecine was appointed; teams of probably imported by HMS Pandora while
scientists were sent to Russia and Poland to observe searching for mutineers of HMS Bounty
cholera first-hand. Coastal health agencies and new
quarantine stations were set up; 35 health inspection “Virgin soil epidemic” refers to an infectious disease
offices and commissions in the départements epidemic introduced into a completely susceptible
(administrative divisions) were established as well. population. The term seems to have taken hold following
Paris set up a 43-member central health commission an 1875 British parliamentary speech in which Colonial
on Aug 20, 1831, 12 subordinate commissions in the Secretary Lord Carnarvon described an epidemic that had
12 arrondissements (districts), and 48 commissions in the just killed a third of the population of Great Britain’s new
quartiers (quarters). The commissions were charged to (1) Crown Colony, Fiji.20,72
surveil, investigate, and report; (2) check private and The Fiji tragedy began innocently. On Jan 12, 1875,
public buildings for sewage connections, wells, cesspools, HMS Dido sailed into Fiji with its former king and queen,
latrines, and outhouses; (3) construct fountains, gutters, two of their sons, and a retinue of about 100 Fijians. As a
and public latrines; (4) educate the public; and (5) provide sign of good will, Queen Victoria had sent them all on a
charitable services for the poor. Teams of constable- post-cession sightseeing visit to Australia. 13 days into the
observers helped physicians undertake house to house 19-day return voyage, one of the sons developed fever and
“sanitary surveillance”. rash. The ship surgeon diagnosed measles, then prevalent
Despite all of these actions, on March 29, 1832, in Sydney, but as yet unknown in Fiji.
choléra-morbus exploded violently in Paris (figure 2).19,70 HMS Dido’s yellow quarantine flag was not flying when
Within a week, incident cases had reached 500 a day, and it sailed into the Fijian port. Arriving British dignitaries
over 1000 after 2 weeks, 85% of which were fatal. So compounded the mistake by focusing on a seemingly
many deaths were occurring that victims could neither more pressing problem: while in Sydney a just-married
be certified by physicians, nor transported, nor buried (now measles-infected) son of the king had acquired “a
fast enough. The government was forced to abandon drip” (gonorrhoea) that had to be kept from newspaper
prevention measures and shift into crisis management. reporters. During the ensuing discussions on board, no
Thousands of bodies were placed three layers deep in one seems to have considered the problem of 100 Fijians
mass graves, which sent a frightening stench over large potentially incubating measles. Nor did anyone notice
parts of the city. Corpse wagons were so hastily and that boats were bringing impatient passengers to shore,
shoddily built that they spilled corpses, viscera, and or that most of Fiji’s police force had sailed out to celebrate
putrid fluids into the streets.19 When furniture vans had on the ship.

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Worse yet, the mountain cannibal chiefs had been studied scientifically,80 a phenomenon important to
threatening to revolt against cession and, while the king understanding AIDS seven decades later.
was away, his brother, Ratu Savanaca Naulivou, had The pandemic’s unresolved mysteries have haunted
arranged a national meeting, unprecedented in size, at successive generations,78 providing a lesson about the
which the chiefs might be persuaded to join the unpredictability of emerging infections. More recently, it
government. On Jan 25, 13 days (about one measles has served as a benchmark for pandemic “worst-case
incubation period) after HMS Dido’s return, the meeting scenario” planning.81 While work on the potential for
was attended by 69 chiefs, 800 family and guests, and the emerging influenza pandemics continues, other
143-man police force, many already developing fevers worrisome diseases continue to emerge—eg, SARS,
and rashes.20 appearing in 2003 and caused by a virus genetically
The attendees returned to their homes throughout Fiji, unrelated to influenza that nonetheless mimics it in its
seeding a widespread and deadly measles epidemic that means of spread and its threat to public-health control.
killed a third of Fiji’s population, an estimated
40 000 people,20 and was exported to other Pacific islands Out of Africa: the HIV/AIDS pandemic, from
in a regional pandemic. To reduce fever, terrified Fijians 1981
lay down in the ocean and in streams and wrapped small “[The Spanish] influenza was the last of the classic
children in wet grass. Trying to stop epidemic spread, pestilences...AIDS...is the first of the postmodern
those who were unafflicted burned the villages of ill, with plagues.”
friends and family still trapped inside their dwellings.
Mirko D Grmek, 198982
Corpses lay everywhere in the open, scavenged by dogs
and wild pigs. The stench of destroyed villages was notable 27 years after its recognition, more than 25 million people
a mile away. Ratu Savanaca succumbed and his body was have died of AIDS; another 33 million remain infected
thrown into a communal pit. The mountain chiefs with HIV, most not yet receiving life-prolonging antiviral
revolted, killing and sometimes eating British subjects. therapy.22,82,83 To date, no one with HIV infection has been
They were defeated by British forces in The Little War, and cured. Within a few years the HIV/AIDS pandemic may
their leaders were hung. 20 years later, when Queen surpass the total lethality of the 1918 influenza pandemic
Victoria commissioned a study of Fiji’s population to achieve the dubious distinction of being the deadliest
decrease, the emerging measles epidemic was barely emerging disease in recorded history. Like the Black
mentioned;73 thus Fijian “racial degeneracy” remained the Death of the 14th century, AIDS has rapidly caused high
eugenics-inspired explanation for the decrease. The mortality and led to profound social and economic
cautionary tale of Fiji’s quintessential virgin soil epidemic disruption that creates conditions supporting further
remained in textbooks for another century, but the spread.82
determinants of its emergence were largely ignored. Since at least the time of Thucydides, one of the first
human responses to disease emergence has been to
Emerging pandemic mysteries: the Spanish question its origin. When identified in 1981, AIDS seemed
influenza, 1918–19 to be a completely new disease. Its early recognition in a
“It is quite probable that influenza will continue to be
peripatetic airline steward suggested (only partly correctly)
prevalent...all over the world for some years to come... that its emergence might have resulted from increased
May we hope that etiological and epidemiological work... human movement resulting from ever decreasing travel
will furnish us with more competent methods for times to multiple destinations.84 Moreover, rapid spread
prevention and delimation before the world is visited by via blood and body fluids within risk groups most capable
another pandemic.” of supporting such transmission (men who have sex with
Hans Zinsser, 192274 men, injection drug users, and transfusion recipients)
seemed to support recent emergence. Surprisingly,
The 1918 influenza pandemic, arguably the deadliest however, phylogenetic analyses of the virus suggest that
emerging pandemic to date, is believed to have killed HIV infection emerged as a human disease around 1900,85
50–100 million people within the first 2 years of its and by complex pathways. Multiple jumps, into
appearance (figure 2).75,76 The pandemic defied many of chimpanzees, of simian immunodeficiency virus (SIV)
the expectations surrounding influenza, appearing in strains restricted to different primate species,86 were
three waves within a 9–12-month period, providing apparently followed by SIV genetic recombinations that
conflicting evidence with regard to wave-to-wave produced new chimpanzee-adapted SIVs. It is likely that
protective immunity, and causing a higher than expected three of these recombinants then transferred
death rate across a wide age-range. The pandemic was independently into human beings, leading to parallel
also notable for a predominance of severe and fatal HIV emergences now represented by different HIV
disease in healthy young adults.77–79 The 1918 influenza clades.85
pandemic was one of the first infectious disease outbreaks About 1% of Europeans are resistant to HIV because of
in which microbial co-infections were appreciated and a homozygous 32 bp deletion in the gene encoding for

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 Historical Review

the major co-receptor for HIV, the human CCR5 cell- emergence than in the greater complexity of modern
surface molecule. This protective allele seems to have existence, which in turn leads to increased opportunities
appeared in the distant past and to have been positively for convergence of interactive risk determinants and
selected for over many centuries. Geneticists and greater speeds with which emergence can occur and
demographers generally agree that the driving force escape control measures. As long ago as 1918, in the era
behind this allele’s frequency was probably an infectious before commercial air travel, the second wave of the
disease, although historical, mathematical, and influenza pandemic appeared in different regions of the
archeological evidence is incomplete for the two chief world almost simultaneously. In 2008, air travel can bring
contenders, smallpox and plague.87 a new disease from any major city to any other in a day
(figure 3), while complex trade and distribution systems
Discussion can spread even a non-contagious infectious disease
Emerging infections have for millennia threatened the quickly beyond the reach of local public-health
survival of human societies who share ecosystems with containment, as exemplified by a US national ice cream-
rapidly evolving microbial organisms and their non- associated epidemic of salmonella in 199488 and a spinach-
human hosts, vectors, and reservoirs. Man’s struggle associated epidemic of Escherichia coli O157:H7 in 2006.89
against emerging infections has been a fundamental Moreover, recent recognition of the role of weather/
determinant of the existence and evolution of the human climate, climate cycles (eg, the El Niño southern
species. The possibility that individual and population oscillation), and global warming in the emergence of
resistance to emerging pandemic diseases results from diseases such as dengue and malaria suggests that risk
gene selection by previous emerging diseases underscores determinant complexities and interactions may increase.6
the complex nature of the human–microbial Although this article has emphasised emerging
interaction.87 pandemic diseases, emerging diseases with more limited
The ten historical emerging epidemics/epizootics (non-pandemic) spread, such as hantavirus pulmonary
examined here were selected non-systematically from syndrome and Lyme disease, have also presented
among many newly emerging and re-emerging diseases substantial public-health challenges. In other cases,
recorded over several millennia. We attempted to provide disease emergence may occur so insidiously that
examples that were not only well documented but also recognition is difficult (eg, tuberculosis during the
reflective of the range and complexity of individual and Renaissance [14–17th centuries]). In recent times we have
interacting risk determinants. Although these examples seen an extraordinary growth in re-emergence of
cannot be considered representative of all of the many infectious diseases, a phenomenon that apparently began
hundreds of historically documented emerging diseases, in the Age of Discovery (15–18th centuries), when
inclusion of those widely considered among the most microbes came into contact with new human populations,
important, such as the Black Death, Spanish influenza, and which is still accelerating as population growth and
and AIDS, serves to highlight determinants relevant at travel provide better avenues of escape for microbes
least to emerging diseases with pronounced impact on entrenched in complex localised ecosystems (eg,
human beings. geographic extension of arboviral diseases such as
Comparison of historical determinants of emergence dengue, Japanese encephalitis, West Nile virus, and
and those associated with modern emerging diseases chikungunya infections).
suggests that they are largely the same.5 Prominent
among these are determinants reflecting human mobility Conclusion
such as demographics/behaviour and trade/commerce, Well-understood determinants of modern disease
host susceptibility factors, and poverty/social inequality emergence, typically acting in concert, have been
(panel and table).5 For example, although separated by associated throughout recorded history with the
millennia, the spread along trade routes of newly emergence of major diseases. These determinants have
emerging diseases in ancient Greece (the Plague of been similar in their explosiveness, impact, and elicitation
Athens), in medieval Europe (the Black Death), and of public-health control responses. Whether the nature
across the African continent (AIDS), are similar in their and pattern of these determinants are changing or will
dependence on human modes and patterns of movement. change in the future remains speculative. That most of
Other less universal determinants of historical emergence the historical emerging diseases we examined were
have nonetheless appeared repeatedly in association associated with unique patterns of common determinants
with varying other cofactors—eg, the role of technology suggests to us that an increasingly complex modern
and industry in the re-emergence of diseases such as world will probably provide increasing opportunities for
dengue and chikungunya, spread by the Aedes aegypti disease emergence. For centuries a fundamental
mosquito, which oviposits preferentially in modern challenge to the existence and well-being of societies—as
products such as discarded tyres and tin cans. reflected by scientific attention, as well as in art, religion,
If there is anything new in disease emergence today, it and culture—emerging infections remain among the
seems to be less in the nature of specific determinants of principal challenges to human survival.

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 Historical Review

Conflicts of interest 25 Wheelis M. Biological warfare at the 1346 siege of Caffa.

We declare that we have no conflicts of interest. Emerg Infect Dis 2002; 8: 971–75.
26 Benedictow OJ. The territorial origin of plague and of the Black
Acknowledgments Death. In: Benedictow OJ. The Black Death, 1346–1353. The
We thank Jeffery K Taubenberger and the staff of the History of Complete History. Chapter 5. Woodbridge, Suffolk: Boydell Press,
Medicine Division and the Public Services Division, National Library of 2004: 35–54.
Medicine, National Institutes of Health, for assistance with the 27 Daumier H. Quatrième satire. Souvenirs du choléra-morbus; Notes.
manuscript and for obtaining some of the cited references. In: Fabre A-H. Némésis médicale illustré. Recueil de satires...
References Contenant trente vignettes dessinées par M. Daumier, et gravées
1 Virchow R. Ueber die neueren Fortschritte in der Pathologie, mit par la meilleurs artistes, avec un grand nombre de culs-de-lampe,
besonderer Beziehung auf öffentliche Gesundsheitspflege und etc. Tome premier. Paris: Bureau de la Némésis Médicale,
Aetiologie. (Rede, gehalten in der zweiten allgemeinen Sitzung der 1841: 63–89, 91–94.
Deutsches Naturforscher-Versammlung zu Frankfurt a M am 28 Morens DM, Littman RJ. Epidemiology of the “Plague of Athens”,
20 September 1867). In: Virchow R. Gesammelte Abhandlungen aus 430–426 BC. Trans Am Philol Assoc 1992; 122: 271–304.
dem Gebiete der öffentlichen Medicin und der Seuchen-lehre. Erster 29 Boghurst W. Loimographia: an account of the Great Plague of
Band. XI. Berlin: August Hirschwald, 1879: 96–107. London in the year 1665. London: Shaw & Sons, 1979.
2 WHO. The world health report 2007—a safer future: global public 30 Kohn GC. The Wordsworth encyclopedia of plague and pestilence.
health in the 21st Century. Geneva: World Health Organization, New York: Facts on File, 1995.
2007. http://www.who.int/whr/2007/en/index.html (accessed 31 Hecker JF. Die Tanzwuth, eine Volkskrankheit im Mittelalter.
Sept 15, 2008). Nach den Quellen für Aerzte und gebildete Nichtärzte.
3 Lederberg J, Shope RE, Oaks SC, eds. Emerging infections: microbial Berlin: Enslin, 1832.
threats to health in the United States. Washington, DC: Institute of 32 Morens DM. Mass fainting at medieval rock concerts. N Engl J Med
Medicine, National Academy Press, 1992. 1995; 333: 1361.
4 Stephens DS, Moxon ER, Adams J, et al. Emerging and reemerging 33 Jacme J. Regiment de preservació a epidemia o pestilència e
infectious diseases: a multidisciplinary perspective. Am J Med Sci mortaldats. Lerida: Council of Lerida, 1348.
1998; 315: 64–75. 34 Christopher GW, Cieslak TJ, Pavlin JA, Eitzen EM. Biological
5 Morens DM, Folkers GK, Fauci AS. The challenge of emerging and warfare. A historical perspective. JAMA 1997; 278: 412–17.
re-emerging infectious diseases. Nature 2004; 430: 242–49. 35 Koenig RL. The fourth horseman. New York: Public Affairs, 2006.
6 Smolinski MS, Hamburg MA, Lederberg J, eds. Microbial threats to 36 von Hutten U. De guaiaci medicina et morbo gallico liber unis.
health: emergence, detection, and response. Washington, Mogu[n]tiae (Mainz): Joannis Scheffer, 1519.
DC: National Academies Press, 2003.
37 de Vigo G. Practica in arte chirurgica copiosa... continens novem
7 Parrish CR, Holmes EC, Morens DM, et al. Cross-species virus libros... Rome: Stephanum Guillireti & Herculem Bononiensem
transmission and the emergence of new epidemic diseases. socium, 1514.
Microbiol Mol Biol Rev 2008; 72: 457–70.
38 Erasmus D. Lingua sive, de linguae usu, atque abusu, Liber unus.
8 Ampel NM. Plagues—what’s past is present: thoughts on the origin 1520.
and history of new infectious diseases. Rev Infect Dis 1991; 13: 658–65.
39 Fracastoro G. Syphilis, sive morbus gallicus. Veronæ, 1530.
9 Krause RM. The origin of plagues: old and new. Science 1992;
40 Fracastoro G. De sympathia et antipathia rerum liber unus. De
257: 1073–78.
contagione et contagiosis morbis et curatione libri iii.
10 Webster N. Letters on yellow fever addressed to Dr William Currie. Venetiis: heredes Lucaeantonii Iuntae Florentini, 1546.
Supplement to The Bulletin of the History of Medicine. No 9.
41 de Oviedo y Valdés GF. La historia general de las Indias. Con
Baltimore: Johns Hopkins University Press, 1947.
privilegio imperial... Fin de la primera parte dela general y naturel
11 Haeser H. Historische-pathologische Untersuchungen. Als Beiträge hystoria delas indias yslas y tierra firme del mar oceano.
zur Geschichte der Volkskrankheiten. Dresden: Gerhard Fleischer, Sevilla: Iuam Cromberger, 1535.
1839–41.
42 Díaz de Isla R. Tractado c[on]tra el mal serpentino: que vulgarmente
12 Cheng KF, Leung PC. What happened in China during the 1918 en España es llamado bubas q fue ordenado en el Ospital de Todos
influenza pandemic? Int J Infect Dis 2007; 11: 360–64. Los Santos de Lisbona. Sevilla: D de Robertis, 1539.
13 Thucydides. The hystory, writtone by Thucidides the Athenyan, of 43 Sontag S. AIDS and its metaphors. New York: Farrar, Straus &
the warre: whiche was betwene the Peloponesians and the Giroux, 1989.
Athenyans. London: William Tylle, 1550.
44 Hernández Arana F, Díaz F. [Translated by Brinton DC]. The annals
14 Hecker JF. Der schwarze Tod im vierzehnten Jahrhundert. of the Cakchiquels. Philadelphia: University of Pennsylvania, 1885.
Berlin: Friedrich August Herbig, 1832.
45 de Sahagún B. Historia general de las cosas de Nueva España.
15 Quétel C. Le mal de Naples: histoire de la syphilis. Paris: Éditions [“Florentine Codex”]. Mexico City: Alejandro Valdes, 1829.
Seghers, 1986.
46 Cook SF, Borah W. The Indian population of central Mexico,
16 Crosby AW. The Columbian exchange: biological and cultural 1531–1610. Berkeley: University of California Press, 1960.
consequences of 1492. Westport, Connecticut: Greenwood Press, 1972.
47 Borah W, Cook SF. Additional remarks. In: Cook SF, Borah W. The
17 Morens DM. Characterizing a “new” disease: epizootic and Aboriginal population of central Mexico on the eve of the Spanish
epidemic anthrax, 1769–1780. Am J Public Health 2003; 93: 886–93. conquest. VII. Berkeley: University of California Press, 1963: 89–92.
18 Powell JH. Bring out your dead; the great plague of yellow fever in 48 Fenner F. Smallpox: emergence, global spread, eradication.
Philadelphia in 1793. New York: Arno Press, 1970. Hist Philos Life Sci 1993; 15: 397–420.
19 Benoiston de Châteauneuf L-F, Chevallier J-B, Devaux L, et al. 49 Cartwright FF, Biddiss MD. The impact of infectious diseases.
Rapport sur la marche et les effets du choléra-morbus dans Paris et In: Cartwright FF, Biddiss MD. Disease and history. Chapter 5.
les communes rurales du département de la Seine. Paris: Imprimerie London: Rupert Hart-Davies, 1972: 113–36.
Royale, 1834.
50 Riedel S. Biological warfare and bioterrorism: a historical review.
20 Morens DM. Measles in Fiji, 1875. Thoughts on the history of Proc (Bayl Univ Med Cent) 2004; 17: 400–06.
emerging infectious diseases. Pac Health Dialog 1998; 5: 119–28.
51 Vicq-d’Azyr F. Contenant les moyens curatifs. In: Vicq-d’Azyr F.
21 Jordan EO. Epidemic influenza: a survey. Chicago: American Exposé des moyens curatifs & préservatifs qui peuvent être
Medical Association, 1927. employés contre les maladies pestilentielles des bêtes à cornes.
22 Fauci AS. HIV and AIDS: 20 years of science. Nat Med 2003; Première partie. Paris: Mérigot l’aîné, 1776.
9: 839–43. 52 Ramazzini B. De contagiosa epidemia, quæ in Patavino Agro,
23 Morens DM. Epidemic anthrax in the eighteenth century, the & tota ferè Veneta. Ditione in Boves irrepsit. Dissertatio habita in
Americas. Emerg Infect Dis 2002; 8: 1160–62. Pavatino Lyceo A’ Bernardino Ramazzini, Practicæ Medicinæ
24 de’Mussis G. Manuscript R 262; fos 74r. Library of the University of Professore Primario. Die IX. Novembris MDCCXI. Patavii: Jo[annis]
Wroclaw, Poland, c 1348. Baptistæ Conzatti, 1712.

718 www.thelancet.com/infection Vol 8 November 2008

 Historical Review

53 Boylston Z. An historical acount of the small-pox inoculated in new 71 Motonicocoka I [translator]. The story of the lila balavu (wasting
England, upon all sorts of persons, whites, blacks, and of all ages sickness) and of the cocadra (dysentery); and the meke relating to
and constitutions. London: S Chandler, 1726. these events. In: Corney BG, Stewart J, Thomson BH. Report of the
54 Desaive J-P, Goubert J-P, Le Roy Ladurie E, Meyer J, Muller O, commission appointed to inquire into the decrease of the native
Peter J-P. Médecins, climat et épidémies à la fin du XVIIIe siècle. population, with appendices. Appendix I. Suva,
Paris: Mouton, 1972. Fiji: John Edward March, 1896.
55 Jernigan DB, Raghunathan PL, Bell BP, et al. Investigation of 72 Molyneux H. 50 000 natives die at Fiji. In: The Times (London),
bioterrorism-related anthrax, United States, 2001: epidemiologic June 9, 1875: 7.
findings. Emerg Infect Dis 2002; 8: 1019–28. 73 Corney BG, Stewart J, Thomson BH. Report of the commission
56 Justin M-P. Livre troisième. In: Justin M-P. Histoire politique et appointed to inquire into the decrease of the native population, with
statistique de l’ Île d’Hayti, Saint-Domingue, écrite sur les appendices. Suva, Fiji: John Edward March, 1896.
documents officiels et des notes communiquées par 74 Zinsser H. The etiology and epidemiology of influenza. Medicine
Sir James Barskett. Paris: Brière, 1826: 109–25. 1922; 1: 213–309.
57 Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk 75 Johnson NP, Mueller J. Updating the accounts: global mortality of
anthrax outbreak of 1979. Science 1994; 266: 1202–08. the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 2002;
58 Krieg JP. The American plague. In: Krieg JP. Epidemics in the 76: 105–15.
modern world. Chapter 3. New York: Twayne Publishers, 76 Murray CJ, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of
1992: 41–67. potential global pandemic influenza mortality on the basis of vital
59 Spalding L. A dissertation on the bilious malignant fever which registry data from the 1918–20 pandemic: a quantitative analysis.
prevailed in the country adjacent to Dartmouth College, in the Lancet 2006; 368: 2211–18.
summer of 1798. The Medical Repository 1805; 3: 5–13. 77 French H. The clinical features of the influenza epidemic of
60 Ketcham R. Wartime president. In: Ketcham R. James 1918–19. In: Great Britain. Ministry of Health. Reports on public
Madison: a biography. Chapter 20. Charlottesville: University of health and medical subjects. No 4. Report on the pandemic of
Virginia Press, 1990: 534–72. influenza, 1918–19. Chapter III. London: His Majesty’s Stationery
61 Murphy J. Confusion, distress, and utter desolation. In: Murphy JP. Office, 1920: 66–109.
An American plague. Chapter 4. New York: Clarion Books, 78 Morens DM, Fauci AS. The 1918 influenza pandemic: insights for
2003: 35–45. the 21st century. J Infect Dis 2007; 195: 1018–28.
62 Jones A, Allen R, Clarkson M, Woodward WW. A narrative of the 79 Taubenberger JK, Hultin JV, Morens DM. Discovery and
proceedings of the black people, during the late awful calamity in characterization of the 1918 pandemic influenza virus in historical
Philadelphia, in the year 1793: and a refutation of some censures, context. Antivir Ther 2007; 12: 581–91.
thrown upon them in some late publications. Philadelphia: 80 Morens DM, Taubenberger JK, Fauci AS. Predominant role of
William W Woodward, 1794. bacterial pneumonia as a cause of death in pandemic
63 Allen R. The life, experience, and gospel labours of the Rt Rev influenza: implications for pandemic influenza preparedness.
Richard Allen to which is annexed the rise and progress of the J Infect Dis 2008; 198: 962–70.
African methodist episcopal church in the United States of 81 United States Department of Health and Human Services. HHS
America. Containing a narrative of the yellow fever in the year of pandemic influenza plan. Washington, DC: US Government
Our Lord 1793: with an address to the people of colour in the United Printing Office, 2005.
States. Philadelphia: Martin & Boden, 1833. 82 Grmek MD. Histoire du sida: début et origine d’une pandémie
64 Linn W. A discourse delivered on the 26th day of November, 1795; actuelle. Paris: Éditions Payot, 1989.
Being the day recommended by the Governor of the state of 83 UNAIDS. AIDS epidemic update: December 2006.
New-York to be observed as a day of thanksgiving and prayer, on Geneva: UNAIDS, 2006. http://www.unaids.org/en/
account of the removal of an epidemic fever, and for other national KnowledgeCentre/HIVData/EpiUpdate/EpiUpdArchive/2006/
bessings. New York: T and J Swords, 1795. Default.asp (accessed Sept 15, 2008).
65 Furman B. John Adams—federal health insurance for seamen 84 Cliff AD, Haggett P, Smallman-Raynor M. The changing
exposed to epidemics 1790–1800. In: Furman B. A profile of the accessibility of islands. In: Cliff AD, Haggett P,
United States Public Health Service, 1798–1948. Chapter 1. Smallman-Raynor M. Island epidemics. Oxford: Oxford University
Washington, DC: US Government Printing Office, 1973: 1–21. Press, 2000: 165–236.
66 Kahn RJ, Kahn PG. The Medical Repository—the first US medical 85 Worobey M, Gemmel M, Teuwen DE, et al. Direct evidence of
journal (1797–1824). N Engl J Med 1997; 337: 1926–30. extensive diversity of HIV-1 in Kinshasa by 1960. Nature 2008;
67 Webster N. A brief history of epidemic and pestilential diseases 445: 661–64.
with the principal phenomena of the physical world, which precede 86 Bailes E, Gao F, Bibollet-Ruche F, et al. Hybrid origin of SIV in
and accompany them, and observations deduced from the facts chimpanzees. Science 2003; 300: 1713.
stated. Hartford, Connecticut: Hudson & Goodwin, 1799. 87 Novembre J, Galvani AP, Slatkin M. The geographic spread of the
68 Hirsch A. Handbuch der historisch-geographischen Pathologie. ΔCCR5 32 HIV-resistance allele. PLoS Biol 2005; 3: 1954–62.
Stuttgart: Ferdinand Enke, 1881–86. 88 Hennessy TW, Hedberg CW, Slutsker L, et al. A national outbreak
69 Benoiston de Châteauneuf L-F. Précautions prises par of Salmonella enteritidis infections from ice cream. N Engl J Med
l’administration avant l’invasion du choléra. In: Benoiston de 1996; 334: 1281–86.
Châteauneuf L-F, Chevallier J-B, Devaux L, et al. Rapport sur la 89 Cooley M, Carychao D, Crawford-Miksza L, et al. Incidence and
marche et les effets du choléra-morbus dans Paris et les communes tracking of Eschericia coli O157:H7 in a major produce production
rurales du département de la Seine. Chapitre premier. region of California. PLoS One 2007; 11: 1–16.
Paris: Imprimerie royale, 1834: 11–19.
70 Morens DM. “Epidemiology is born”: cholera in Paris, 1832.
In: Bernier RH, St Pierre JL, eds. Epidemiology wit & wisdom.
Roswell, Georgia: The Epidemiology Monitor Press, 2000: 98–101.

www.thelancet.com/infection Vol 8 November 2008 719