STAT 6395

1
Spring , 2008

• STAT 6395
• Special Topic in Statistics
• Epidemiology

Filardo and Ng, 2008
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I. Epidemiology

• The study of the distribution and determinants of
  health-related states or events in specified
  populations and the translation of study results
  to control health problems

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Distribution

• Persons affected
• Place
• Time

Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Determinants

• All the physical, biological, social, cultural,
  and behavioral factors that influence health

Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Health-related states or events

• Diseases
• Mortality (death)
• Specific causes of death
• Injuries
• Disability
• Health-related behaviors
• Physiological measurements
• Results of preventive regimens
• Clinical outcomes
• Provision and use of health services

Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Specified populations

• Residents of a defined geographic area
• Students who attend a specified school
• Persons who belong to a specified organization
• Workers at a specified workplace

Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Translation

• Study Results

Scientific articles and presentations at meetings
Clinical guidelines
Prevention programs Quality of care improvement
programs Patient safety programs
Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Control

• Operations or programs aimed at reducing the
  adverse impact of the disease on the community
• Prevention
• Cure
• Management

Epidemiology The study of the distribution and
determinants of health-related states or events
in specified populations and the translation of
study results to control of health problems
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Primary prevention

• An action taken to prevent the development of a
  disease in a person who is well and does not have
  the disease in question

Operations or programs aimed at reducing the
adverse impact of the disease on the community
1) Prevention 2) Cure 3) Management
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Secondary prevention (Cure and management)

• The identification and treatment of people who
  have already developed a disease or precursors of
  the disease, through screening, at an early
  enough stage in the diseases natural history
  (early detection) such that intervention will be
  more effective than if the disease had been
  discovered later

Operations or programs aimed at reducing the
adverse impact of the disease on the community
1) Prevention 2) Cure 3) Management
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II. Objectives of Epidemiology

• To describe the extent of disease in the
  community
• To identify risk factors (factors that influence
  a persons risk of acquiring a disease) for
  disease and the etiology or cause of disease
• To study the natural history (course from onset
  to resolution) and prognosis of disease
• To evaluate both existing and new preventive and
  therapeutic measures (including health care
  delivery)
• To provide the foundation for developing public
  policy and regulatory decisions relating to
  environmental problems

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bottom line, Epidemiology research requires a
multidisciplinary effort and statisticians play a
key role in

• Hypothesis development
• Study execution

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Hypothesis development

• Epidemiologists study the specific distribution
  and determinants of specific diseases
• Development of hypotheses to test in an
  epidemiologic study requires in-depth knowledge
  of the disease and determinants under study
• Medical and biological sciences
• Social and behavioral sciences

Epidemiology Research ? hypothesis development
and study execution
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Study execution

• Statistics ------------gtBiostatistics
• Medical and biological sciences
• Social and behavioral sciences

Epidemiology Research ? hypothesis development
and study execution
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Biostatistics

• Separate chance observations from meaningful
  observations
• Sampling
• Sophisticated statistical analyses

Epidemiology Research ? Biostatistics, medical
and biological sciences, social and
behavioral sciences
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Medical and biological sciences

• Microbiology, e.g., to identify infectious
  agents
• Clinical medicine and pathology, (e.g., to
  identify cases of disease)
• Molecular biology, (e.g., to identify genotype of
  individuals)
• Biochemistry, (e.g., to measure serum hormone
  levels)

Epidemiology Research ? Biostatistics, medical
and biological sciences, social and
behavioral sciences
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Social and behavioral science

• Design questionnaires for obtaining valid
  information
• Design effective interventions for lifestyle
  changes

Epidemiology Research ? Biostatistics, medical
and biological sciences, social and
behavioral sciences
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Epidemiology Sub-disciplines

• Disease-specific subject matter
• Exposure-specific subject matter
• Health services research

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Disease-specific subject matter

• Infectious disease epidemiology
• HIV/AIDS epidemiology
• Malaria epidemiology
• Chronic disease epidemiology
• Cancer epidemiology
• Cardiovascular epidemiology
• Perinatal epidemiology
• Neuroepidemiology
• Psychiatric epidemiology

Epidemiology disciplines ? Disease-specific
subject matter, Exposure-specific subject
matter, Health services research
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Determinant (exposure)-specific subject matter

• Environmental epidemiology
• Occupational epidemiology
• Pyschosocial epidemiology
• Genetic epidemiology
• Nutritional epidemiology
• Pharmacoepidemiology

Epidemiology disciplines ? Disease-specific
subject matter, Exposure-specific subject
matter, Health services research
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Health services research

• Operations research the study of the placement
  of health services in the community and the
  optimum utilization of such services
• Program evaluation
• Clinical epidemiology or outcomes research the
  study of illness outcomes in persons seen by
  providers of health care evaluation of medical
  treatments

Epidemiology disciplines ? Disease-specific
subject matter, Exposure-specific subject
matter, Health services research
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Types of epidemiologic studies

• Experimental
• Observational (this course will focus on this
  second type of studies)

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Experimental Studies

• Studies in which conditions are under the control
  of the investigator(s).
• The investigators assigns subjects to different
  study groups. The effect of the treatment is
  determined by comparing the outcome of interest
  in these groups.

Type of studies ? Experimental, Observational
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Experimental studies (examples)

• Randomized clinical trial (unit of study is the
  individual)
• Community trial (unit of study is the community)

Type of studies ? Experimental, Observational
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Observational studies

• Studies in which the investigators does not
  control conditions, but rather observe nature
  taking its course by gathering information,
  recording, classifying, counting, and analyzing
  the collected data.
• Exposure and disease outcomes would have occurred
  whether or not the studies have been performed
  because there were no a priori intervention(s)
  on the part of the investigators.

Type of studies ? Experimental, Observational
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Observational studies (examples)

• Descriptive
• Analytic

Type of studies ? Experimental, Observational
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Descriptive studies

• Studies aimed at describing the distribution of
  disease or other health-related variables with
  respect to person (age, gender, race,
  socioeconomic status), place (census tract,
  county, state, country, urban/rural), and time
  (season, year)

Type of studies ? Experimental, Observational
(descriptive)
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Descriptive studies

• Often use routinely-collected data
• Can define high-risk groups
• Can be used for hypothesis generation, but
  generally not hypothesis testing

Type of studies ? Experimental, Observational
(descriptive)
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Analytic studies

• Test specific etiologic hypotheses
• To generate new etiologic hypotheses
• To suggest mechanisms of causation
• To generate preventive hypotheses
• To suggest or identify potential methods for
  disease prevention

In these studies, the epidemiologist observes the
relationship between an exposure and a disease or
other health outcome.
Type of studies ? Experimental, Observational
(analytic)
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Definition Exposure

• A potential causal agent or characteristic, such
  as infectious agent, behavior, dietary factor,
  medication, medical treatment, genetic makeup,
  environmental agent, or physiologic state (e.g.,
  serum level of a hormone or nutrient blood
  pressure).

An exposure may be harmful or beneficial
Type of studies ? Observational ? Analytic
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Types of analytic studies

• Cohort studies
• Case-control studies

Type of studies ? Observational
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Cohort studies

• A study in which a group of persons exposed to a
  factor of interest and a group of persons not
  exposed are followed

and compared with respect to the incidence rate
of the disease or other condition of interest

Time
Type of studies ? Observational ? Cohort studies
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Cohort studies (study schema)
Type of studies ? Observational ? Cohort studies
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Case-Control studies

• Studies in which a group of persons with a
  disease (cases) and a comparison group of persons
  without the disease (controls) are compared with
  respect to the history of past exposures to
  factors of interest

Present
Past
Type of studies ? Observational ? Case-Control
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Case-Control studies (study schema)

Type of studies ? Observational ? Case-Control
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Either descriptive or analytic studies

• Cross-sectional studies
• Ecologic studies

Type of studies ? Observational
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Cross-sectional studies

• Studies of the distribution of exposures and/or
  disease in a defined population at one given
  point in time

Type of studies ? Observational ? Cross-sectional
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Ecologic studies

• Studies of the association between exposures and
  disease in which the units of analysis are
  populations or groups of people, rather than
  individuals.
• This involves the assessment of the correlation
  of exposure rates and disease rates among
  different groups or populations.
• Causality, though???

Type of studies ? Observational ? Ecologic
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Types of Epidemiologic studies

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• Example involving several types of study designs

Ecologic study results
Case-Control study results
Cohort study results
Randomized controlled trial results
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Which type of study is the Gold Standard and/or
more common/feasible?

• Experimental
• Efficacy

Observational Effectiveness
controlled setting (difficult to reproduce in
real life)
real life setting
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Focus of this course is on observational
Epidemiologic research (research regarding the
direct study of disease in human populations)
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Some triumphs of observational Epidemiology

• Smoking causes lung cancer
• Identification of cardiovascular disease risk
  factors
• Characterization of how HIV spreads through a
  population
• Identification of occupational hazards (e.g.,
  asbestos)

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Three Eras of Epidemiology

• Sanitary (1800-1875)
• Infectious disease (1875-1950)
• Chronic disease (1950-present)

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Sanitary Era (1800-1875)

• Miasma theory of disease poisoning by foul
  emanations (miasma) from the soil, water, and
  air.
• Created national vital statistics systems much
  valuable descriptive epidemiology
• Demonstrated clustering of disease in slums and
  among the poor
• Solutions sewage systems, drainage, clean water
  supplies, garbage collection, decent housing
• Incorrect miasma theory, but solutions were a
  major contribution to public health

Lesson prevention doesnt necessarily require
understanding of cause
Sanitary, Infectious disease, Chronic disease
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Infectious disease Era (1875-1950)

• Germ theory single microscopic agents relate
  one-to-one to specific diseases
• Epidemiology took a back seat to laboratory
  science, although in the1920s-30s, the germ
  theory was broadened to accommodate the
  interactive roles of host (immune and nutritional
  status), environment, and agent in infectious
  disease
• Other epidemiologic contributions
• Occupational exposures as causes of cancer
• Specific vitamin deficiencies as causes of disease

Sanitary, Infectious disease, Chronic disease
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Chronic Disease (Modern) Era

• By end of World War II, infectious diseases were
  under control in the developed countries
  coronary heart disease and lung cancer were
  epidemic
• Multifactor causation of chronic disease
• Focus on identification and control of risk
  factors at the individual level
• Black box approach emphasis on risk factor
  identification with only a secondary concern
  about mechanism or pathogenesis

Most of the methodology we will cover in this
course was developed during this Modern Era.
Sanitary, Infectious disease, Chronic disease
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New Era(???)

• Emerging infectious diseases (e.g., HIV)
• Continued burden of infectious diseases in
  majority of world
• Traditional chronic disease epidemiology has hit
  a wall in its ability to discover important new
  risk factors
• Advances in molecular biology and genetics allow
  the study of pathogenesis and causality at the
  molecular and genetic levels using epidemiologic
  approaches
• The need to be concerned with causal pathways at
  multiple levels, including the societal level, as
  opposed to an exclusive focus on risk factors at
  the individual level, has become apparent to many

Sanitary, Infectious disease, Chronic disease, ???
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Levels of causality

• Societal or population
• Individual
• Biochemical
• Cellular
• Molecular

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What causes lung cancer?

• Individual/societal Cigarette smoking (nicotine
  addiction)
• Biochemical Specific chemicals in cigarette
  smoke that cause the mutations
• Cellular Specific phenotypic changes in the
  cells that result in loss of growth control
• Molecular Mutations in DNA

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What causes AIDS?

• Societal
• Poverty
• Prostitution
• Individual/societal a. Multiple sexual partners
  b. Intravenous drug use
• Biochemical
• Cellular Infection -the HIV viruses
  progressively destroy lymphocytes (a types of
  white blood cells)
• Molecular Mutations in DNA -the viral DNA is
  incorporated into the DNA of the infected
  lymphocyte

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On the mode of communication of cholera

• John Snow, M.D.
• London, 1855

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John Snow 1857
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Why study Snow?

• Appreciate those who came before us and paved the
  way
• Brilliant piece of work lucid and thorough
• Snows work on cholera illustrates a key
  epidemiologic principle

the most important information to have about any
communicable disease is its mode of communication
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John Snow (1813-1858)

• Physician
• Pioneer in both epidemiology and anesthesiology
• Experiments in administration of anesthesia
  himself may have contributed to his early death

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Snow administered chloroform to Queen Victoria
for the birth of Prince Leopold and Princess
Beatrice
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Cholera Acute Gastrointestinal Disease

• Incubation period 12-72 hours
• Sudden onset of severe vomiting
• Followed shortly by voluminous, watery,
  non-bloody diarrhea, described as rice water
  stool (white and opalescent)
• Abdominal cramps
• Severe cases severe dehydration, circulatory
  collapse, renal failure (death may occur within a
  few hours of first symptoms)
• Case fatality rate may range from 1-50,
  depending on strain of Vibrio cholerae and
  treatment

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In 1817, four years after John Snows birth,
cholera emerged from the Indian subcontinent,
where it had existed for centuries, to spread
across the world.
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Cholera Epidemics in Great Britain

• 1831-32
• 56,000 deaths
• 1848-49
• 125,000 deaths
• 1853-54
• Cholera returns to England

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Cholera Apparently contradictory facts in 1854

• Local spread with evidence of direct
  communication from person to person
• Failure to spread to many in close contact with
  the sick
• Cases occur without traceable relation to prior
  cases
• Highest rates in low-lying areas and in filthy
  environments - Exceptions too numerous to
  be disregarded
• Unpredictability of its spread around the world
  and its geographic distribution

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Cholera Miasma Theory

• Report of the London General Board of Health on
  cholera epidemic of 1848-49
• it appears as if some organic matter, which
  constitutes the essence of the epidemic, when
  brought in contact with other organic matter
  proceeding from living bodies, or from
  decomposition, has the power of so changing the
  condition of the latter as to impress it with
  poisonous qualities of a peculiar kind similar to
  its own.

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Cholera Elaborations of Miasma theory

• Localizing influences
• Predisposition
• Spontaneous generation of cholera poison
• Poison spread by diffusion through the
  atmosphere vs. poison attached itself to solid
  bodies
• Poison communicated by an effluvium (contagion)
  given off by the sick

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William Farr
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Farrs elaboration of Miasma theory

• Soil at low elevations, especially near the banks
  of the Thames River, contained much organic
  matter that produced deadly miasmata.
• Miasmata diffused through the atmosphere in a
  cloud or mist
• Concentration of miasmata would be greater at
  lower elevations than in higher elevations,
  accounting for the geographic distribution in the
  London epidemic of 1849.

Farrs theory did have some consistency with the
facts.
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John Snows Germ Theory

• Cholera caused by a germ cell, not yet identified
• 2 main modes of transmission of germ cell, which
  was found in the evacuations of cholera
  victims 1. Drinking water contaminated with
  sewage 2. Contaminated food, bedding, or clothing

Snow was firmly convinced of his theory by start
of 1853-54 epidemic.
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Snows ecologic observations prior to the 1853-54
epidemic
Cholera has never appeared except where there
has been ample opportunity for it to be conveyed
by human connections.

• Epidemics of cholera followed major routes of
  commerce and warfare.
• Cholera always appeared first at seaports, when
  extending to a new island or continent.

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Snows observations from case histories

• Cholera can be communicated from the sick to the
  healthy.
• Persons attending those with cholera do not
  necessarily become afflicted.
• Close contact with a cholera patient is not
  necessary to become afflicted.

Snows conclusion cholera is communicated
from person to person, but not through the air
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When cholera returned to London in August 1853,
Snow had a definite hypothesis
cholera was spread by contaminated water.
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Water supply of south districts of London
Lambeth Water Company

• Until 1852, drew water from the Thames River in
  London, contaminated with Londons sewage
• In 1852, moved intake 22 miles up river and far
  from the contaminated water

Southwark and Vauxhall Water Company

• Continued to draw water from the contaminated
  Thames

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Cholera Deaths in South Districts of London
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Cholera deaths (per 100,000) in south districts
of London

• District Water supply 1849
  1853
• Bermondsey SV 1610
  150
• St. Saviour SV, Lam 1530
  146
• St. George SV, Lam 1640
  143
• St. Olave SV 1810
  134
• Rotherhithe SV, Kent 2050
  112
• Newington SV, Lam 1440
  57
• Wandsworth SV, others 1000
  51
• Camberwell SV, Lam 970
  40
• Lambeth Lam, SV
  1200 34
• Notes 1. Lambeth was supplied mostly by
  Lambeth Water Co.
• 2. Rotherhithe supplied partly by Kent
  in 1853

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Cholera Deaths in south districts of London,
1853, sub-district analysis

• Water Cholera Deaths/
• Supply Population Deaths
  100,000
• SV 167,654 192
  116
• Lambeth 14,632 0
  0
• Both 301,149 182
  60

How many cholera deaths would we expect in
sub-districts supplied by Lambeth if they had the
same death rate as those supplied by SV?
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Cholera Deaths in south districts of London,
1853, sub-district analysis

• Water Cholera Deaths/
• Supply Population Deaths
  100,000
• SV 167,654 192
  116
• Lambeth 14,632 0
  0
• Both 301,149 182
  60

Expected deaths for Lambeth (116/100,000)14,632
16
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Additional Observations on Sub-districts

• Among the sub-districts supplied by both
  companies, those supplied mainly by Lambeth had a
  low death rate, while those supplied mainly by
  SV had a high death rate.
• Two sub-districts supplied only by SV also
  contained a number of pump-wells. These
  sub-districts had a low death rate.

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By the return of cholera in July 1854, Snow
recognized the full significance of the
intermixing of the water supplies of the 2
companies

• in the sub-districts supplied by both
  Companies, the mixing of the supply is of the
  most intimate kind A few houses are supplied by
  one Company and a few by the other, according to
  the decision of the owner or occupier at that
  time when the Water Companies were in active
  competition

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By the return of cholera in July 1854, Snow
recognized the full significance of the
intermixing of the water supplies of the 2
companies

• in many cases a single house has a supply
  different from that on either side. Each company
  supplies both rich and poor, both large houses
  and small there is no difference either in the
  condition or occupation of the persons receiving
  the water of the different Companies.

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An Experiment on the Grandest Scale

• no fewer than three hundred thousand people of
  both sexes, of every age and occupation, and of
  every rank and station, from gentlefolks down to
  the very poor, were divided into two groups
  without their choice

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An Experiment on the Grandest Scale

• one group being supplied with water containing
  the sewage of London,
• the other group having water quite free from
  such impurity

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What type of study John Snow conducted?

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What type of study John Snow conducted?

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Cohort Study

• A study in which a group of persons exposed to a
  factor of interest and a group of persons not
  exposed are followed and compared with respect to
  the incidence rate of the disease or other
  condition of interest.
• Exposed group persons using SV water supply
• Comparison group persons using Lambeth water
  supply

Compared cholera mortality rates in the two groups
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Calculation of mortality rates required
numerators and denominators

• Mortality rate in exposed group
• (Cholera deaths among persons supplied with SV
  water) / (Number of persons supplied with SV
  water)

Mortality rate in comparison group (Cholera
deaths among persons supplied with Lambeth water)
/ (Number of persons supplied with Lambeth water)
To determine numerators and denominators, Snow
needed a way to classify each death and every
person in the population by water supply
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The Numerators

• For each cholera death in the relevant districts,
  Snow obtained information on the water supply
• The inquiry was necessarily attended with a good
  deal of trouble.
• Chemical test problematic because SV water had
  40 times more NaCl than Lambeth

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The Denominators
a return had been made to Parliament of the
entire number of houses supplied with water by
each of the Water Companies, but ... the number
of houses which they supplied in particular
districts was not stated

• Therefore Snow had to include all the south
  districts of London in his study, not just the
  districts where the water supply was intermingled.

A daunting undertaking, so Snow obtained an
assistant (Mr. Whiting)
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Cholera deaths in south London districts during
first 4 weeks of 1854 Epidemic, by water supply

• 
  Deaths/
• Water Cholera
  10,000
• Supply Deaths Houses Houses
  
  
• SV 286 40,046
  71.4
• Lambeth 14 26,107
  5.4
• 
  Relative risk 71.4/5.4 13.2
• Thames 22
• Pump-wells 4
• Ditches 4
• Unknown 4
• London 277 287,345
  9.6
• (-SV)
• Note Houses, not persons, used in denominator

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More data
as the epidemic advanced, the disproportion
between the number of cases in houses supplied by
the Southwark and Vauxhall Company and those
supplied by the Lambeth Company, became not quite
so great, although it continued very striking

• Cholera likely was imported from Baltic Fleet to
  Thames River, which was initially the primary
  source of the epidemic
• Later, cholera was also spread by other means,
  diluting the water company effect

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Cholera deaths in south London districts during
first 7 weeks of 1854 Epidemic, by water supply

• 
  Deaths/
• Water Cholera
  10,000
• Supply Deaths Houses Houses
  
  
• SV 1263 40,046
  315
• Lambeth 98 26,107
  37
• 
  Relative risk 315/37 8.5
• London 1422 256,423
  59
• (-SV, Lambeth)

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Cholera deaths in south London districts during
last 7 weeks of 1854 Epidemic, by water supply

• 
  Deaths/
• Water Cholera
  10,000
• Supply Deaths Houses Houses
  
  
• SV 2353 40,046
  573
• Lambeth 302 26,107
  115
• Relative risk 573/115 5

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Cholera deaths in south London districts during
the 1854 epidemic, by water supply

• 
  
• Water Cholera Deaths/
• Supply Deaths Population 10,000
• SV 4,093 266,516
  153
• Lambeth 461 173,748
  26
• 
  Relative risk 153/26 5.9
• London 10,367 2,362,236
  43
• Note
• populations supplied by water companies estimated
  by Registrar General.

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Was the Use of Houses in the Denominators Valid?

• Water
  Persons/
• Supply Population Houses
  Household
• SV 266,516 40,046
  6.7
• Lambeth 173,748 26,107
  6.7
• London 2,362,236 322,576
  7.3

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Cholera Deaths in South Districts of London,
Sub-district Analysis, 1849 vs. 1854

• Water Cholera Deaths
• Supply 1849 1854
• SV 2261 2458
• Both 3905 2547
• Lambeth 1644 89
• Here we are back to ecologic analysis

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Cholera Outbreak in the Golden Square Area of
London, 8/31 - 9/9, 1854. Within 250 yards of the
intersection of Cambridge and Broad Streets,
there were more than 500 fatal cases
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Snow immediately suspected contamination of the
water of the much-used street pump on Broad
Street near Cambridge Street.
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Snow mapped the places of residence of cholera
decedents from August 31 - September 2 in the
broader neighborhoodand found that 73 of 83
deaths had taken place within a short distance of
the pump.
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Snow investigated the water source of the 73
decedents who lived near Broad Street pump

• 61 -- drank water from the pump
• 6 -- did not
• 6 -- could get no information

102
10 Deaths in houses located nearer to another
street pump

• 5 always used the Broad Street pump, as they
  preferred its water
• 3 (children) went to school near the Broad Street
  pump

103
Handle of the pump was removed on September 8

• Legend has it that the removal of the pump handle
  caused the end of the epidemic
• Snow himself wondered whether removing the pump
  handle had a beneficial effect
• Epidemic was already subsiding
• Much of the population in the neighborhood had
  fled

it is impossible to decide whether the water
from the pump still contained the cholera poison
in an active state.
104
Snows investigation of Golden Square Outbreak
workhouse near Broad St.

• Surrounded by houses in which deaths from cholera
  occurred
• Only 5 deaths among 535 inmates
• Workhouse had a pump-well on the premises
• Also received water from the Grand Junction Water
  Works
• Did not use Broad Street pump
• Would have expected more than 100 deaths based on
  mortality in surrounding streets

105
Snows investigation of Golden Square Outbreak
Brewery on Broad St.

• Located near the pump
• More than 70 workers
• None died of cholera
• Workers drank malt liquor, not water
• Deep well located in brewery
• Workers never obtained water from Broad Street
  Pump

106
Snows recommendations for prevention of cholera
during an epidemic

• Observe strictest cleanliness around the sick.
• Wash linens of patients as soon as they are
  removed.
• Boil water for drinking and preparing food
  (unless known to come from clean source).
• Wash or heat to 212F all food.
• Healthy should not live in same room as sick.
• Pit-men should work 4 hour shifts, and not eat in
  mines.
• Educate the people about communicability of
  cholera.

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Snows recommendations for long-term prevention
of cholera

• Effect good and perfect drainage.
• Provide water supply free from contamination with
  contents of sewers, cesspools, house-drains, and
  refuse of people who navigate the rivers.
• Provide model lodging-houses for the vagrant
  class and sufficient house room for the poor in
  general.
• Teach habits of personal and domestic cleanliness
  among the people.
• Screen persons arriving from infected places.

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Medical establishment slow to catch on

• 1855 report of Scientific Committee for
  Scientific Enquiries in Relation to the Cholera
  Epidemic of 1854 on the whole of evidence, it
  seems impossible to doubt that the influences,
  which determine in mass the geographical
  distribution of cholera in London, belong less to
  the water than to the air.
• 1856 Report on the last two cholera epidemics of
  London as affected by the consumption of impure
  water under the specific influence which
  determines an epidemic period, fecalized
  drinking-water and fecalized air equally may
  breed and convey the poison.

109
Sanitary movement eventually succeeded in spite
of its incorrect miasma theory

• Extensive improvements in several of Londons
  water supplies, including Southwark and Vauxhall,
  had already been ordered before the 1853-54
  epidemic.
• In next London epidemic (1866), William Farr
  himself used epidemiology to show that the source
  of the epidemic was impure water from the East
  London Water Company.

110
What We Know Now?

• Cholera caused by a bacterium (Vibrio cholerae
  discovered in 1883 by Robert Koch)
• Small intestine is primary site of infection
• Diarrhea caused by cholera toxin produced by
  Vibrio cholerae
• Treatment intravenous or oral fluid and
  electrolytes, depending on severity of illness
• Environmental reservoir for Vibrio cholerae in
  the sea, where it lives on zooplankton and
  shellfish

111
Vibrio Cholerae
112
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