Impact of Infectious Diseases on
Development of Human Societies
Antiquity to Middle Ages
Emigration from rain forests
humans, Homo sapiens, evolved in Africa 200,000
to 400,000 years ago
something made them leave this seemingly hospitable
environment ... perhaps they were trying to "escape"
infectious diseases, such as malaria?
diseases such as sleeping sickness may have limited
their spread out of the forests into the grasslands in
Africa
Elimination of prey and "weeds"
intensive cultivation of agricultural crops became
necessary as human populations increased and large-bodied prey
were essentially eliminated
they learned to control "weeds" by "slash and burn"
in forests, by flooding, and by plowing (developed in the
Mediterranean region about 3000 BC)
along with this cultivation of plants for food, humans
domesticated a number of animals ... and got diseases from
them as the animal's microbes evolved to infect humans
Development of endemic levels of infectious diseases
major civilizations probably developed their own "mixes"
of communicable diseases 10,000 to 2500 years ago ... when
cities large enough to support endemic diseases arose
large-scale ritual gatherings probably also contributed
to the spread of infectious diseases among settlements
due to urban crowding and farming practices in nearby
agricultural regions, infections transmitted by water
ingestion, skin contact and insect bites probably flourished
during these times
as these populations adapted to infectious agents (and
the infectious agents to them) over thousands of years,
certain diseases became endemic in the cities
once these diseases stabilized, these populations
became biological threats to their more distant neighbors
because they carried diseases to which they were resistant but
to which their neighbors were susceptible
this may have simplified territorial expansion, due to
inntroduction of new diseases with expansion into new
territories
however, when these civilizations tried to expand into
certain regions which had their own reservoirs of infectious
diseases, they would have encountered new diseases that
limited their expansion
perhaps people have never inhabited some regions (i.e.,
African Savannas) to any significant degree because the
other animals that live there carry infectious agents (such
as trypanosomes) that humans have been unable to "adjust"
to
early thoughts about cause and transmission of
infectious diseases
ancient Egyptians and Indians thought pestilences were
punishments inflicted on humans by supernatural beings as
retribution for "wicked" behavior
the Hippocratic school (400 BC to 500 AD) believed that
diseases resulted from imbalance of the four humors: blood
(sanguine), yellow bile (choleric), black bile (melancholic)
and mucous (phlegmatic)
Impact of selected diseases
Impact of selected diseases
Malaria is transmitted by mosquitoes not by bad ("mal")
air
Alexander the Great's armies may have spread malaria
as they moved about on their campaigns (Alexander died of it
in 323 BC)
malaria and plague (plus lead poisoning and social
factors) contributed to the decline and fall of Rome,
because more than 60% of Romans were chronically infected during
Julius Caesar's reign in the first century BC
"Roman airs" affected Rome for 500 years, with periodic
epidemics, incapacitating most of the farmers , increasing
infant mortality and greatly decreasing adult life expectancy
to avoid malaria's effects, they began conscripting the
Roman army from conquered Germanic lands (cold) during the
fourth century AD
African sleeping sickness is transmitted from wildebeasts
to people by tsetse fly bites, and was most likely a major limiting
factor in the spread of humans onto the African Savannas (the herbivore
herds that live there act as reservoirs)
Schistosomiasis is transmitted by a fluke (flatworm) that
lives (for part of its life cycle) in red snails that live in shallow
water (rice paddies, etc.) and has clearly been present in Egypt
since ancient times
Tuberculosis is older than Homo sapiens - it affects
many animal species, and we may have transmitted it to cattle after
we domesticated them
signs of tubercular bone damage are apparent in Stone
Age and Egyptian skeletons, and the first known human victim was
a young male buried near Heidelberg about 5000 BC
tuberculosis was in the Americas in pre-Columbian times,
as documented by skeletal remains and depiction of hunchbacks on
Peruvian pottery and in Mexican art
concern about tuberculosis appears to have fostered prejudice
in India (laws to prevent transmission in 1000 BC may have
led to strictures against intermarriage of castes) as well as in Greece
and Rome ... in both cases, it was thought that TB susceptibility
was inherited and that susceptibles could be detected by physiotype (tall,
slender frame, light skin, fair hair)
Smallpox was prevalent in Africa, India and the Mediterranean
area by 1100 BC
we know that Pharaoh Ramses V died of smallpox, and it appears
that smallpox led to the fall of Athens to Sparta about 400
BC)
smallpox also played a role in the downfall of Rome
Cholera is ubiquitous because its etiologic agent
normally lives in water attached to the outer surfaces of crustaceans
cholera has caused much trouble, especially in India,
where religious rituals involving bathing in the Ganges River
(heavily contaminated with human fecal matter containing Vibrio
cholerae) are a problem
Plague has caused periodic epidemics for thousands of years
a 50-year plague epidemic began in Egypt in 540 AD,
then spread rapidly to Alexandria and Palestine via the fleas
of rats traveling with traders
it encompassed Europe and Asia, but is referred to as
the Justinian plague because it occurred during the reign
of this Byzantine emperor
with a death toll of 100 million people, this epidemicstopped not
because the bacterium vanished, but because it killed
so many that the critical mass of susceptibles needed
to sustain it was lost
Plague in the Ancient World
this plague was probably the deciding factor in ushering
in theDark Ages which began with the fall of the
Roman Empire
besides playing a major role in the decline and fall of the
Roman Empire, this epidemic delayed development of medicine
and the germ theory of disease because the Christian church
became de facto doctor to both the soul and the body,
replacing the progressive Greek and Roman doctors' idea that
disease is caused by pathogenic agents with the idea that disease
results from vice and sin
Leprosy has been with us for thousands of years, as
indicated by ancient bans on lepers in both Jewish and Old Testament
Christian writings
in Europe special houses (called lazars ...
after St. Lazarus, the patron saint of lepers) were set
aside for lepers as early as 4th century AD, as the Roman
government became Christian and adopted biblical injunctions
about treatment of persons with disfiguring skin diseases
- this is probably where our concept of quarantine came
from
leprosy became well established in Europe (France
and Britain) and the Mediterraneancoastlands (Egypt)
during the 6th century AD, then prevalence of this
disease declined greatly during the 14th century perhaps
because plague and tuberculosis were on the upswing
and they may have simply out-competed it because they
are "quicker"
pathogens
Middle Ages to Dawn of Microbiology as a
Science
Exploration, mass migration and war
Exploration, migration and warfare
were quite common during this time period
these factors often promoted the spread of previously
localized infectious diseases to new populations in
different parts of the world
some cases, disease assisted
"invaders" in their conquests; in others, it opposed them
Impact of selected diseases
Plague
- two epidemics of this disease occurred during this period
one epidemic, called black
death, black plague, or bubonic
plague, began late
in 1346 in Crimea,
reached England by summer, then spread
throughout Europe, including
Scandinavia and Russia, lasted 15 years (1346-1361)
and killed ~27 million
people
the pneumonic form (transmitted
person-to-person) was common, especially during the
winter; it killed so quickly (~95% mortality) that
healthy people abandoned coughing relatives, including
their children, and buried their dead in mass graves, if
at all
How
to avoid the plague (historical account) ... medical "garb"
in 1348, Pope Clement VI encouraged a pilgrimage
to Rome for mass prayers to end the plague (90% of
the pilgrims died of plague)
out of frustration, a scapegoat was found;
even though they were dying at the same rate as others,
Jews were
accused of poisoning wells; when they
"confessed" during torture, they were killed (despite
Pope Clement VI's two papal bulls declaring the Jews
innocent)
after about 300 years, plague
returned in 1665-1666; it focused on London,
killing 2000 people each week during the summer of 1665
Malaria
continued to be prevalent in Africa and other
indigenous areas
was also prevalent in the US from colonial times
through the 19th century, affecting Virginia marshes, New
England and even the midwest, including Ohio and Indiana
(50-90% prevalence)
Smallpox was prevalent in Africa, India and the
Mediterranean area by 1100 BC
we know that Pharaoh Ramses V died of smallpox,
and it appears that smallpox led to the fall of Athens to
Sparta about 400 BC)
it was greatly feared, as indicated by the fact
that Asians, Africans and Latin Americans developed the idea
of gods of smallpox and European Catholics adopted a
patron saint of smallpox victims (St. Nicaise of
Rheims)
the crusaders were afflicted with smallpox and
brought it to Europe from the Mediterranean region (1096 -
1291 AD)
smallpox (together with measles and gonorrhea) was a
major deciding factor in the conquest of the Aztecs and
Incas by the Spaniards
smallpox succeeded plague, leprosy and syphilis as
Europe's foremost pestilence during the latter half of
the 16th century
continuing frequent smallpox epidemics throughout
the 17th and 18th centuries killed about 400,000 people
each year and substantially altered the balance of power
as they killed five reigning European monarchs
this led to adoption of variolation ... which had
long been practiced in China and the Mediterranean region
and was introduced to England from Constantinople by Lady
Mary Wortley Montagu
frequent large-scale epidemics also occurred in the
US
half the residents of Boston were afflicted in 1721
(15% died)
Cotton Mather (who learned of variolation from
one of his African slaves) began actively promoting
variolation
unfortunately, the early US settlers used smallpox as
a weapon against the Native Americans ... they gave them
blankets that were known (to the settlers, but not to the
unsuspecting indians) to have been used by smallpox
victims, which caused widespread smallpox among the
Native Americans
between 1786 and 1796, Edward Jenner (inspired by
information about cowpox from a milkmaid) modified
variolation into vaccination
despite the Royal Society's refusal to publish his
work and the abuse he received from the popular press,
Jenner persevered; his efforts came to fruition after the
efficacy of vaccination was realized and promoted by
Lister and Cline
after worldwide acceptance of vaccination, incidence
of smallpox declined steadily ... there has not been a case
of "natural" smallpox anywhere in the world since
1977
nevertheless, some medical historians believe that
smallpox has killed more people than all other infectious
diseases combined
Impact of European diseases on the New World
European explorers brought waves of pestilence
(gonorrhea, measles, mumps, scarlet fever, smallpox, typhus)
and death to the Americas
as they spread throughout Central and South America,
these diseases killed 50 to 90% of the highly
susceptible natives in a few years
Spaniards (and slave ships from Africa)
spread smallpox to the West Indies and Central
America
they brought it to Hispanola in 1507 and Cuba in
1519
then, in 1520, Narvaez' conquistadors brought
smallpox from Cuba to Tenochtitlan (Mexico), where it
killed 3.5-15 million Aztecs in 2 years
reduced numbers of natives helped make conquering and
settlement much easier for Europeans, but more
importantly, the natives' belief in their gods, their
leaders and their way of life was undermined by disease
Impact of New World diseases on Europe -
Syphilis???
there is an ongoing controversy about the origin of
syphilis
some scholars think that Columbus' men brought
syphilis back from the West Indies in 1493, then were
influential in its spread throughout Europe from
Spain
others think that syphilis
was already present in Europe before 1493, but
was not noticed due to low incidence before then
Charles VIII of France (who died of syphilis in
1498) went to war against Naples in 1494-1495 with
soldiers from all over Europe; since some of them had
syphilis, they spread it to other soldiers during the
war and then throughout Europe as they went home
the ensuing 16th century pandemic influenced sexual
mores because its transmission allowed clergy to explain
syphilis as a punishment for "sins of the flesh" (even
lepers refused to accept syphilitics into their
colonies)
condoms (then called "overcoats" and made of
waxed linen, with ribbons for drawstrings) were
invented as a mode of "safe sex"
because physicians were powerless to cure
syphilis, and often refused to try, barbers and bath
attendants devised the "quicksilver cure" in which
the patient was repeatedly immersed in a barrel of hot
mercuric sulfide ... this eventually led to the idea that
chemicals could be used to treat diseases
Tuberculosis is
older than Homo sapiens - it
affects many animal species, and we may have transmitted it to
cattle after we domesticated them
signs of tubercular bone damage are apparent in
Stone Age and Egyptian skeletons, and the first
known human victim was a young male buried near
Heidelberg about 5000 BC
tuberculosis was in the Americas in pre-Columbian
times, as documented by skeletal remains and depiction
of hunchbacks on Peruvian pottery and in Mexican art
concern about tuberculosis appears to have
fostered prejudice in India (laws to prevent
transmission in 1000 BC may have led to strictures against
intermarriage of castes) as well as in Greece and
Rome ... in both cases, it was thought that TB
susceptibility was inherited and that susceptibles could
be detected by physiotype (tall, slender frame, light
skin, fair hair)
Cholera is ubiquitous because its etiologic
agent normally lives in water attached to the outer surfaces of
crustaceans
cholera has caused much trouble, especially in
India, where religious rituals involving bathing in
the Ganges River (heavily contaminated with human fecal
matter containing Vibrio cholerae) are a problem
John Snow
linked the Broad Street pump to London the cholera
epidemic of1848, then showed that sewage-contaminated
drinking water also caused the 1854 epidemic
this led to his proposal that cholera is caused by
some active agent in the water
his lasting proposal that the concept of
commonality is of fundamental importance in
determining the cause of epidemics, led to his now being
known as the "father of epidemiology"
Development of medical concepts
Syphilis was important in establishing European
moral attitudes about sex, as well as leading to the
development of preventive measures (condoms) and
suggesting the idea that chemicals could be used to treat
diseases
Smallpox stimulated the development of
vaccination from the ancient practice of variolation
Cholera played an important role in development
of epidemiology, especially establishment of the concept of
commonality
Era of Public Health to Discovery of
Antibiotics
Advances in microbiology that fostered development of
public health
Development
of the germ theory of disease
Greek and Roman physicians thought tiny animals caused diseases, but lost influence
when they couldn't eliminate plagues in 50 to 640 CE (common era)
Frascatoro proposed
the idea in 1546 that invisible
living (animate) particles cause disease, but his idea wasn't taken seriously because
he had no evidence to back his hypothesis except the contagious nature of some diseases
Bassi published
the first evidence for disease of microbial etiology when he described how silkworms
get il
segno by infection with a fungus (Botrytis bassiana) and proposed a "parasite
theory of disease" in 1835
Semmelweis explained
how physicians transmitted puerperal fever to women they assisted in childbirth in a lecture
in 1850 and was promptly denounced, then fired
Pasteur "rediscovered" Bassi's
conclusions about il segno in 1865-1871
Lister, in the 1860s, used phenol (antimicrobial) sprays to develop the concept
of antiseptic surgery
Koch showed
that anthrax is caused by a bacterium in 1876, described how to isolate and grow bacteria,
then published Koch's postulates (first described in 1840 by Henle) concerning etiology
of tuberculosis in 1884
Lister promoted
sterile surgery and began using carbolic acid as a disinfectant during surgery
Water
purification, sewage collection and treatment
Romans developed sophisticated drinking water
and sewer systems (even indoor plumbing), but these
ideas were lost during the Dark Ages
most villages, towns, and cities had problems
with certain diseases due to fecal contamination of their
drinking water because they lacked sewer systems
development of good public sanitation facilities
during the 18th and 19th centuries in what are now
"developed" countries, drastically decreasing their
incidence of epidemics of cholera, typhoid and
dysenter
Development and applications of immunology concepts
Jenner developed
smallpox vaccine, and by doing so helped us (eventually) understand the concept of attenuation as
well as paving the way for eradication of the naturally-occuring form of disease in the world
today
Pasteur developed
fowl cholera, anthrax, rabies vaccines (1881-1885)
Mechnikov proposed
the phagocytic theory of
immunity in 1884
von
BehringandKitasato discovered
in 1890 that immunity against diphtheria and tetanus is due
to toxin-neutralizing antibodies, leading to the humoral
theory of immunity and
development of vaccines against diphtheria, tetanus, pertussis, yellow
fever, plague, etc.
Discovery and development of early antimicrobial agents
Ehrlich's student
Hata synthesized arsphenamine
(salvarsan) which is effective
against syphilis in 1908 and it was first marketed in 1910
Flemming discovered
a mold that makes
penicillin in 1928
Domagk synthesized prontosil,
the first
sulfanilamide, in 1932
Chain and Florey purified penicillin,
demonstrated its effectiveness in 1941 ... Flemming,
Chain and Florey received the Nobel Prize for this in 1945
Impact of selected diseases
Typhoid and Dysentery
these are spread by poor sanitation; in the
Battle of Crecy in 1346, the French waited to shoot the
British until they were squatting, defenseless
because Prince Edward died of dysentery during
the Hundred Years War, Britain had to deal with bubonic
plague under the leadership of ten year-old Richard II (who
abdicated and starved himself to death in prison)
during the US Civil War (1861-1865) 81,360
soldiers died of typhoid or dysentery (and many more died of
other infectious diseases), whereas only 93,443 died as a
direct result of wounds
with introduction of sanitation engineering in
late 19th century, deaths due to these diseases plummeted
(WWII was the first war in which the death toll due to
wounds was greater than that due to infectious disease)
"Typhoid" Mary
Mallon (1870-1938) was a cook who,
starting in 1900, caused more than a dozen typhoid outbreaks
because she was a carrier of Salmonella typhi; when
epidemiologist George Soper, knowing she was the common
element in many epidemics, tracked her down (a second time)
in 1915, she was arrested and held in quarantine the rest of
her life
Tuberculosis
despite knowing what caused it, there was no cure for
tuberculosis (also known as consumption or white death) and
by the 19th century, as many as one-fourth of the graves
in Europe held its victims
in the Eastern US, tuberculosis accounted for
only 0.5% of deaths in the 19th century, but became a
leading cause of death by 1900, as cities continued to
grow (more than 200,000 TB deaths in the US in 1924)
Influenza
spread by military personnel during
WWI
1918-1919
pandemic spread around the world from
a military camp in the US within three months
prevalence up to 90% (Samoa) and death rates (most
victims actually died of pneumonia, a secondary infection)
up to 60% (Alaskan Eskimos)
25-37 million people died in
18 months
although this
strain of influenza virus disappeared in 1919, other
strains of this highly mutable virus continue to cause
pandemics
Diphtheria
First described by Hippocrates
Named diphtheria in 1855… Greek for "pair of leather scrolls”
Frequently called "strangling angel of children"
Many diphtheria epidemics struck Europe over the years
US affected in 1700s
Elisha Otis, inventor of the first safe elevator, died of diphtheria in 1861
100,000-200,000 cases and 13-15,000 deaths/year in 1920s
Vaccine developed in the 1920s… diphtheria incidence declined thereafter
Iditarod Trail Sled Dog Race commemorates delivery of diphtheria antitoxin to Nome, Alaska, during a blizzard
Last 50 Years
Many new antimicrobial agents were discovered in the last
50 years
Current public health methods include:
Water purification, sewage collection and treatment
Water
purification is now accomplished by a combination of
filtration or sedimentation, coagulation, carbon treatment,
and chlorination
Drinking water is derived from rain, stored as surface or ground water
Sewage
is collected via sewer systems, where bacterial by-products
kill most pathogens before they reach wastewater treatment plants where treatment
consists of:
tertiary
- chemical removal of eutrophic agents, heavy
metals and hard-to-digest organic compounds; frequently
employs chlorination
as the last step before discharging the purified water
from the treatment plant
Vaccination
DTP - diphtheria, pertussis, tetanus vaccine is
used routinely now
Polio vaccines introduced in 1955 (Salk; killed
virus) and in 1961 (Sabin; modified live virus) have largely
eliminated this disease in the US
MMR - measles, mumps, rubella (modified live
viruses) vaccine developed in the 1960s has markedly reduced
incidence of these diseases in the US
Influenza vaccines developed yearly are
frequently effective
Smallpox vaccine was used to eradicate smallpox
worldwide in 1977
Hib - Haemophilus influenzae b vaccine
developed in the 1980s protects infants from some forms of
otitis media, pneumonia and meningitis
Hepatitis A vaccine has now been approved in the
US
Hepatitis B vaccine is a recombinant vaccine
developed in the 1990s
Chickenpox vaccine developed in Japan in the
1990s is effective and has now been approved in the US
Decline of public health infrastructure
our water purification systems, sewers and sewage
treatment plants are decaying, over-worked, outmoded and in
drastic need of modernization
many vaccines are available, but others need to be
generated, and policies to promote their use, especially among
the disadvantaged, are sorely needed
Impact of selected diseases
Lyme
Disease
since it was first
recognized in Lyme and East Haddam, Connecticut in
1975, Lyme disease has increased from 59 to more than 11,000
cases per year and is now the most frequently diagnosed
tick-borne disease in the US
there is a newly-developed vaccine, and
antibiotic treatment is effective in stopping the infection
and its late-occurring damage (arthritis, etc.)
Legionnaire's Disease
First recognized in Philadelphia at American Legion convention in 1976
Linked to inhalation of water droplets from water-cooled air conditioners
Ebola
Most prevalent in Africa, where it was first identified in 1976
Since then there have been ~1100 cases, of which ~800 have died
Ebola periodically causes a few hundred cases with each short-lived outbreak
AIDS
HIV (human immunodeficiency virus may have originated in Africa, then spread globally via
promiscuous sexual behavior and IV drug abuse
31-36 million people were living HIV-infected worldwide in 2008
2.4–3.0 million people became infected with HIV in 2008
1.7–2.4 million people died of HIV related causes in 2008
MRSA
Emerging disease has intensified during the last 40 years
Evolved from controllable nuisance into serious public health concern
Originally this was predominantly a hospital-acquired disease
Community acquired strains of MRSA that infect otherwise healthy people are now becoming more prevalent