315

HISTORY OF MEDICINE

What caused the Black Death?

C J Duncan, S Scott
...............................................................................................................................

Postgrad Med J 2005;81:315–320. doi: 10.1136/pgmj.2004.024075

For the whole of the 20th century it was believed that the But this unknown disease had not disappeared
completely and there were epidemics scattered
Black Death and all the plagues of Europe (1347–1670) through Europe during the 1350s.5 Thereafter,
were epidemics of bubonic plague. This review presents the plague was permanently established in
evidence that this view is incorrect and that the disease was France with epidemics every year that cycled
round the main trading routes. From there,
a viral haemorrhagic fever, characterised by a long infected travellers carried the disease by road
incubation period of 32 days, which allowed it to be and river across the continental landmass and by
spread widely even with the limited transport of the Middle sea to Britain and Ireland. But all these
peripheral epidemics died out completely and
Ages. It is suggested that haemorrhagic plague emerged were restarted by fresh infectives coming from
from its animal host in Ethiopia and struck repeatedly at the focus in France.4
European/Asian civilisations, before appearing as the The epidemics progressively increased in
spread, frequency, and ferocity (fig 1) with a
Black Death. The CCR5-D32 mutation confers protection pronounced rise after 1550 because transport
against HIV-1 in an average of 10% of the people of improved and the population of the towns
European origin today. It is suggested that all the Dccr5 steadily grew (that is, there was a greater
number of susceptibles). Contemporary
alleles originated from a single mutation event that accounts, pattern of spread, and mortality all
occurred before 1000 BC and the subsequent epidemics of confirm that the same pathogen was responsible
haemorrhagic plague gently forced up its frequency to for all the plagues, including the first strike of
the Black Death.
561025 at the time of the Black Death. Epidemics of
haemorrhagic plague over the next three centuries then PUBLIC HEALTH MEASURES
steadily raised the frequency in Europe (but not elsewhere) Even in the 14th century the health authorities
to present day values. in northern Italy had established the importance
of a 40 day quarantine period, which became the
...........................................................................
gold standard for continental Europe for the next
300 years. The 40 day quarantine was not

I
mmediately on its arrival in 1347 in the port of adopted in England until the 16th century and
Messina in Sicily the Great Pestilence (or Black even then it was changed to 30 days only to find
Death as it was named in 1823 because of the that this was completely ineffective, whereupon
black blotches caused by subcutaneous haemor- this regulation was speedily rescinded.
rhages that appeared on the skin of victims) was The complete success of the quarantine period
recognised as a directly infectious disease. Michael confirms that the plague was a directly infectious
of Piazza, a Franciscan friar who wrote 10 years disease and it also shows that it had a long
after the Black Death had arrived, said ‘‘The incubation period. Towns in France gradually
infection spread to everyone who had any inter- realised that the danger lay in the arrival of an
course with the disease’’.1 Indeed, they believed infected traveller who may well have come from
(incorrectly) that priests who heard the confes- a considerable distance. Entry was denied if they
sions of the dying ‘‘were immediately overcome by had come from a town that had suffered an
death, so that some even remained in the rooms of epidemic. Later, in addition to inspecting travel-
the dying.’’1 Case mortality was 100%. They lers on arrival, the authorities also required proof
realised that safety lay in fleeing but this, very that all the towns through which they had
effectively, served only to spread the infection. journeyed were completely free of plague.
The Black Death moved as a wave northwards Once an epidemic had erupted, those displaying
See end of article for through Europe at an average speed of about symptoms were removed to emergency primitive
authors’ affiliations 4 km per day and reached the Arctic Circle by isolation hospitals called pest (an abbreviation of
.......................
1350, remarkable progress in the days of very pestilence) houses, which were hurriedly erected
Correspondence to: limited means of transport.2–4 Even more outside the town. Once a plague case had been
Professor C J Duncan, impressively: it had earlier appeared in Asia identified, the family was locked up in the house,
School of Biological
Sciences, University of
Minor and the Crimea and moved south through the well known cross was daubed on the door, and
Liverpool, Life Sciences Antioch; it was present in the Levant and spread a watchman was appointed to stand guard. These
Building, Liverpool L69 along the north African coastlands and to Mecca measures were less successful in containing an
7ZB, UK; sscott@liverpool. in Saudi Arabia, covering, in all, some seven epidemic because, as shown below, victims were
ac.uk million square km. When it had burnt itself out, more infectious before the appearance of the
Submitted 13 May 2004 40% of the population of Europe had been killed. symptoms.
Accepted 30 July 2004 This outbreak was a pandemic on a scale never Despite only sketchy medical knowledge at the
....................... before experienced (or since). time, the epidemiology of the plague was fully

www.postgradmedj.com
316 Duncan, Scott

diseases objectively and for the whole of the 20th century

this view, based solely on the appearance of one symptom,
was universally accepted without question.
60

THE BIOLOGY OF BUBONIC PLAGUE

To be able to refute unequivocally the belief that Yersinia pestis
Number of epidemics

was the pathogen of the Black Death it is necessary to

40
understand fully the complicated biology of bubonic plague.
The key lies in the difference between susceptible and
resistant rodent species. Susceptible species, like rats, die
from the infection and an outbreak of human bubonic plague
was often presaged by the appearance of hundreds of dead
20 rats. Obviously, no outbreak can be maintained for any
length of time and bubonic plague cannot become endemic
where all the local species are susceptible. In central Colorado
an isolated colony of prairie dogs (Cynomys gunnisoni) was
wiped out when Yersinia pestis was introduced.10
0 In Siberia and Mongolia, for example, susliks and
1400 1500 1600 tarabagans are susceptible and subject to recurrent, short
Years term outbreaks that might eventually eliminate the plague
focus through lack of hosts; but the local gerbils and voles are
Figure 1 Number of places in Europe reporting a plague epidemic, more resistant to Y pestis and so they can serve to maintain
1350–1670. Note the increased frequency after 1550. Data from the endemic state in the area because they do not die from an
Biraben.5
infection.10
In warm climates, rodents breed throughout the year and
understood at least by the middle of the 17th century. Daniel may produce up to nine litters. In this way, the density of a
Defoe6 had perspicaciously noted that, in the Great Plague of population of rodents living under favourable conditions
London in 1665, ‘‘because of its infectious nature, the disease increases rapidly and outbreaks of bubonic plague can occur
may be spread by apparently healthy people who harbour the at any time of year. The turnover of a rodent population in a
disease but have not yet exhibited the symptoms. Such a subtropical area can be very high: as fast as they breed,
person was in fact a poisoner, a walking destroyer perhaps for infections (including Yersinia) and predators act to reduce
a week or a fortnight before his death, who might have their numbers. This process generates regular cycles in the
ruined those that he would have hazarded his life to save… population of rodents and prevents the establishment of a
breathing death upon them, even perhaps his tender kissing stable, plague resistant population. Therefore, any focus of
and embracings of his own children.’’ bubonic plague in rodents in subtropical climates is in a
Clearly, they recognised that victims were infectious before continual state of population flux.
the symptoms appeared, the lengthy duration of the The spread of bubonic plague through a rodent population
incubation period, the necessity of a 40 day quarantine, and is critically dependent on active fleas. At least 30 species of
the dangers of droplet infection. But there were many flea have been proved to be vectors and, as more than 200
features of the epidemics that were mystifying and they also species of rodent can carry plague, the host-vector permuta-
clung to their beliefs in divine intervention, transmission via tions in the Asian subcontinent are formidable and the
contaminated clothing and bedding, movements of the population dynamics complex.3 10
planets, and poisonous miasmas. Flea reproduction is strongly dependent on environmental
and other factors: temperature and humidity greatly affect
YERSINIA PESTIS AND BUBONIC PLAGUE both egg laying and the development of the larvae.
Even before 1347, bubonic plague had been grumbling along Temperatures between 18˚C and 27˚C and a relative humidity
for centuries in Asia with occasional severe epidemics. But of 70% are ideal, whereas temperatures below 7˚C are
from the mid-19th century the disease gathered momentum deleterious to all developmental stages except the adult.
and erupted in Canton and Hong Kong in 1894, Calcutta in The fleas, the rats, the resistant rodents, and the susceptible
1895, and Bombay in 1896 and the pandemic of the 20th rodents each need specific conditions for the successful
century had begun. Steamships carried infected rats and fleas completion of their life cycle and the overall maintenance of
from the infested warehouses of the Chinese ports to many of their populations. All are potentially capable of prodigious
the warmer parts of the world, wherever suitable rodent reproduction. These life cycles and the environmental
hosts could be found. But endemic bubonic plague never requirements for reproduction have to intermesh successfully
became established in Europe, despite numerous introduc- if an infection of Yersinia pestis is to be established in rodents.
tions in the 20th century. The dynamics of bubonic plague are complicated but rodents
The complex aetiology and biology of bubonic plague was usually keep within their home range and the disease spreads
elucidated by Yersin7 and the Plague Commission of India8: it only slowly through the countryside.3 10
is a disease of wild rodents in which the bacterial pathogen,
Yersinia pestis, is spread by infected fleas. Occasionally today it SPREAD OF BUBONIC PLAGUE TO HUMANS
is transmitted to humans from peridomestic rats and there If an infected wild rodent strays near human habitations and
are some 1600 cases a year.9 The characteristic (but not then shares its fleas with rats living around the settlement,
specific) symptom of bubonic plague in humans is the Yersinia can spread from rodent to rat, and from rat to man.
appearance of the bubo. The rat is just an intermediary and is not a reservoir of
However, once Yersin had announced his seminal results, bubonic plague: its role is to die and then pass on the
it was realised that victims of haemorrhagic plague also infection. A number of dead rats will usually be found during
sometimes presented with swollen lymph glands. It was, an outbreak of bubonic plague in humans: in a small village
apparently, immediately assumed that the Black Death was perhaps just a few; in a large South African township perhaps
caused by bubonic plague. Nobody compared the two many barrow loads.

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What caused the Black Death? 317

There are several other ways in which Yersinia pestis can back, and thighs were the most common site. Necropsies
spread from a focus among local rodents to humans: when showed general necrosis of the internal organs.
humans go out and invade an area where the rodents are
infected—for example when hunting or picnicking—they WHY YERSINIA PESTIS WAS NOT RESPONSIBLE FOR
may catch bubonic plague directly from the fleas living on the THE PLAGUES OF EUROPE
wild rodents.10 The following is a brief summary of the evidence:

(1) There were two authentic plague epidemics in Iceland

MANIFESTATIONS OF BUBONIC PLAGUE IN
in the 15th century that persisted through the freezing
HUMANS conditions of winter.12 No rats were present on the
Patients with bubonic plague, who have been bitten by an island and the conditions were inimical for flea activity.3
infected flea, are not normally infectious to other people and
can be nursed in open wards. Notably, the incubation period (2) The brown rat (Rattus norwegicus) did not arrive in
Europe until 60 years after the plagues had disap-
is typically two to six days after exposure and the
peared.3 The black rat (Rattus rattus) was absent in rural
characteristic symptom is the bubo. Typically the onset is
England13; no rat species were available to spread the
sudden with chills and rigors and a rise of temperature to
disease throughout the country.
38.8˚C–39.4˚C. The patient has a severe, splitting headache
and often pains in the limbs, the back, and abdomen. They (3) There are no resistant rodents present in Europe (and
become confused, restless, irritable or apathetic, their speech never were), which are essential for the establishment
slurred, and they may vomit. Within a day or two the person of focus of bubonic plague.3 10
is prostrate with all the symptoms of shock. Most patients die (4) The plagues were confined to Europe where the CCR5-
between the third and sixth day: if they are alive on the D32 mutation is now found, whereas bubonic plague,
seventh day they may struggle through to recovery.10 which was not a serious disease until the late 19th
However, in about 5% of the cases of bubonic plague the century, was confined to Asia where CCR5-D32 is
Yersinia reaches the lungs and the patient coughs out the absent4 14 (see below).
bacteria in the sputum, which may be inhaled by anyone in (5) The case mortality in haemorrhagic plague was 100%
close contact who then gets pneumonic plague. The victim and the total mortality recorded in an epidemic was
dies between the third and sixth day and, without medical very much greater (usually at least 10-fold) than that in
treatment, pneumonic plague is invariably fatal.10 an outbreak of bubonic plague: humans can be infected
Pneumonic plague cannot occur in the absence of the with Yersinia pestis without suffering from the disease
bubonic form, not can it persist independently. While and there are clinical forms (pestis minor) where there
pneumonic plague increased the mortality locally in an is no danger of dying. In victims who present with fever
epidemic focus, it was rarely responsible for spreading and the bubo, between 30% and 50% die if not treated.10
Yersinia pestis over any distance—mortally sick people were This level of mortality is insufficient to force up the
unable to move very far in the few days before death. CCR5-D32 mutation to present day levels.15
Furthermore, transmissibility of pneumonic plague is low: (6) Flea reproduction was impossible in the climatic
the average number of secondary cases per primary case (Ro) conditions of northern Europe.3
based on past outbreaks was only 1.3.11 (7) The Black Death spread remarkably rapidly—from Sicily
to the Arctic Circle in less than three years and covered
MANIFESTATIONS OF HAEMORRHAGIC PLAGUE vast areas of Europe. Many of the subsequent epidemics
We believe that the Black Death was caused by a disease that jumped over 300 km. This is in complete contrast with
was completely different from bubonic plague and, to avoid an epidemic of bubonic plague that moves very
confusion, have named it haemorrhagic plague. Case slowly4 14; the black rat has a home range of 100 metres
mortality was 100% and the disease was directly infectious. and rarely strays outside it.16
In the Plague of Athens, victims were stricken suddenly with (8) The bacterium Yersinia does not use the CCR5 receptor.17
severe headaches, inflamed eyes, and bleeding in their (9) The 40 day quarantine for the plague was rigorously
mouths and throats. The next symptoms were coughing, established and completely successful for 300 years. It
sneezing, and chest pains followed by stomach cramps, corresponds with the long incubation period that has
intensive vomiting and diarrhoea, and unquenchable thirst. been established for the plagues of Europe.4 Quarantine
The skin was flushed, livid, and broken with small blisters measures are not applicable to bubonic plague.4 14
and open sores. The patients burned with fever so extreme (10) The plagues were recognised as a directly infectious
that they could not tolerate being covered, choosing rather to disease and it was established that it was not safe to
go naked. Their desire was to cast themselves into cold water, come within four metres of an infected person.4
and many of those who were unsupervised did throw
(11) Both normal and CCR5 deficient mice have been
themselves into public cisterns, consumed as they were by infected with Yersinia pestis but there were no differences
unceasing thirst. Many became delirious.3 In the Black Death, between the two groups in either bacterial growth or
prolonged bleeding from the nose and vomiting blood was survival time.17
regarded as a fatal prognostic.1 Some of the earliest signs
were blisters (the ‘‘blains’’) or carbuncles on the skin and (12) The report that DNA specific for Y pestis was amplified
from 16th and 18th century human teeth believed to be
these were followed by the buboes. Gui de Chauliac,
from French plague victims18 and 14th century French
physician to the Papal Court at Avignon during the Black
Black Death victims19 has not been confirmed and the
Death, saw clearly that the buboes were by no means an
results have been ascribed to contamination.20
invariable symptom and that the mortality was of two types.
One died from the first in three days. The second presented
with apostumes and carbuncles on the external parts, PROFILE OF AN EPIDEMIC OF HAEMORRHAGIC
principally on the armpits and groin and, from this, the PLAGUE
victim died in five days.2 But the most feared signs were the A full scale plague epidemic developed only in a town above a
haemorrhagic spots (God’s tokens), which varied in size and certain minimum size. Mortality was low in villages. Figure 2
colour and could occur anywhere, although the neck, breast, illustrates the profile of a typical epidemic that began in the

www.postgradmedj.com
318 Duncan, Scott

spring. It follows the pattern of a person to person infection, person avoiding contact with any of the cases will be q and,
but is characterised by its slow generation and its long with all the Ct cases, will be
duration of eight or nine months. The epidemic falls into
three stages:

(1) Rising. Mortality rises exponentially, dependent on the

transmission rate. Once the epidemic has killed a And the probability of any given person having at least one
proportion of the population, the transmission rate starts adequate contact with any of the cases will be
to fall and, concomitantly, the mortality rate decreases
because there are fewer susceptibles around to infect.
(2) Plateau. When the transmission rate = 1, the mortality
rate remains static. In the next time period (t+1), the number of contacts
(3) Decaying. Once the pool of remaining susceptibles is between cases and susceptibles is given by
depleted below a critical level, the transmission rate falls
to ,1 and, inevitably, the epidemic fizzles out.

REED AND FROST MODELLING Computer modelling of Reed and Frost dynamics shows
The unpublished mathematical model of the epidemics of that the duration of an epidemic is strongly dependent on the
directly infectious diseases developed by Reed and Frost21 serial generation time of the disease.4 The epidemic at
may be summarised as follows. In a closed population of size Newcastle (fig 2) suggests a long serial generation time of
N within which people intermingle fairly uniformly, it is 22 days and a low Ro of 3.
assumed that, in a certain period of time t, every person will These conclusions are illustrated in figure 3, which shows
have about the same number of contacts with other the results of modelling epidemics of influenza (incubation
individuals, K. If t is made equal to the serial generation period = 2–3 days) and a hypothetical plague (incubation
time, the individuals infected during one period will then be period = 32 days), with Ro standardised at 3. N = 1200.
infectious during the next.
The probability of an adequate contact between any two
given individuals during time t will be DETERMINATION OF THE CHARACTERISTICS OF THE
DISEASE
From the Elizabethan period vicars and parish clerks were
required to mark the registers of plague burials with a ‘‘P’’ or
‘‘Pest’’. Detailed analysis of some 100 plague epidemics
recorded in parish registers, coupled with family reconstitu-
and tion enabled the tracing of the lines of infection both within
and between households and the determination of the vital
characteristics of the pathogen4:

(1) An epidemic was often specifically recorded as being

will be the probability of any given person avoiding adequate
started by a visiting stranger or by a resident returning
contact with any other given person during time t.
from a visit to a place where the plague was raging.
Thus, the population is at any time, t, composed of cases,
Ct, and susceptibles, St, and the probability of any given (2) There was a considerable delay, often more than 15 days,
between the death of the primary case and the first
secondary case.
(3) Transmission was much easier within, rather than
Plateau between, households.

400
Fizzling out
800
320 (A)
Rising
Influenza
Weekly plague deaths

600
240
Number of cases

Plateau
400
160
Rising Fizzling
out
(B)
200
Plague
80

0
0 0 40 80 120 160 200 240
0 5 10 15 20 25 30 35 Days after primary infection
Weeks after start of epidemic
Figure 3 Computer modelling of epidemics of influenza (incubation
Figure 2 Weekly plague burials at Newcastle upon Tyne after the start period = 2–3 days) and a plague (incubation period = 32 days) in the
of the epidemic on 14 May 1636. same community, with Ro standardised at 3. N = 1200.

www.postgradmedj.com
What caused the Black Death? 319

(4) Transmission was much more difficult in the colder

months and probably impossible out of doors in the Box 1 Epidemics of haemorrhagic plague in
depth of winter. history
(5) Four metres was established as a safe distance of
separation out of doors. (1) Haemorrhagic fevers in the Nile valley in Pharaonic
(6) From April to October, Ro = 3 to 4, but with a range of 1 Egypt, 1500–1350 BC.
to more than 20, depending on circumstances. (2) Viral haemorrhagic fevers were reported in ancient
(7) The characteristic symptom was the appearance of Mesopotamia ‘‘If … his epigastrium [has] a piercing
haemorrhagic spots. pain, blood flows incessantly [from his mouth], his arms
are continually weak, depression continually falls upon
By the following of the lines of infection, particularly in the him [and] his eyes are suffused with blood [it is] ‘Hand
early and late stages of an epidemic, it is possible to of Marduk’; he will be worried and die.’
determine the following: (Mesopotamian diagnostic handbook circa 721–453
BC).
36

N Latent period = 12 days (occasionally 10 days) (3) Plague of Athens 430–427 BC. Originated in Ethiopia.
N Infectious period before symptoms = 20–22 days The description of the symptoms given by Thucydides
correspond closely with those of haemorrhagic pla-
N Incubation period = 32 days
gue.37 38
N Period of symptoms = 5 to 6 days (range = 2–15 days).
Victim probably less infectious during this time. (4) Plague of Justinian AD541–2; continued sporadically
until AD700. Originated in Ethiopia. The description of
N Total infectious period = 25–27 days the symptoms given by Procopius correspond closely
N Total time from point of infection to death = 37–38 days,
in agreement with the 40 day quarantine instituted in the
with those of haemorrhagic plague.39
(5) Plagues of Islam AD627 to 744.33
14th century.
(6) Haemorrhagic plague in Asia minor and the Levant (the
It was the very long incubation period that, even in the plague focus), 1345–48.2 40
days of very limited transport, allowed travellers and traders (7) Haemorrhagic plagues of Europe, 1347–1670.
to spread the plague widely throughout Europe and across (8) Epidemics of haemorrhagic plague in Denmark and
the sea to England, Ireland, and Iceland. Sweden, 1710–11.41
(9) Sporadic epidemics in Poland through the 18th
RESISTANCE century.41
During the Black Death in 1348 there was evidence of a few
people who were resistant to the disease. For example, a
monk who was the sole survivor in a monastic community, NATURE OF THE PATHOGEN
having nursed and buried his fellow inmates. By the 17th There is no known disease today that presents with the
century, inspection of the burials registers of London suggests symptoms of haemorrhagic plague. The studies with the CCR-
that the percentage of the resident population showing 5 receptor suggest that the pathogen was viral and the
resistance had risen considerably, with the greatest mortality symptoms and necropsy reports of haemorrhagic plague are
among naive immigrant apprentices and maidservants from closest to those of Ebola and Marburg, particularly the
the provinces.4 necrosis of the internal organs and the haemorrhagic
Current studies in molecular biology throw light on this manifestations,32 suggesting that the pathogen may have
phenomenon. The transmembrane CCR5 chemokine receptor is been a filovirus. ‘‘Filoviruses are the prototypical emerging
used by HIV strains to enter cells of the immune system.22–24 The pathogens: they cause a haemorrhagic disease of high case-
CCR5-D32 deletion prevents the expression of the receptor and fatality associated with explosive outbreaks due to person-to-
provides almost complete resistance to HIV-1 infection in person transmission, have no known treatment, occur
homozygous people and partial resistance in the heterozygous
state.25–29 The average frequency of the CCR5-D32 deletion allele
is estimated at 10% in European populations, but is virtually Key references
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