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Introduction to epidemiology

PhD course Winter 2014

University of Copenhagen

Anders Koch, senior researcher, Ph.D. MPH

Statens Serum Institut

&

Registrar, infectious Diseases

Rigshospitalet University Hospital

Objectives of epidemiology course

Learn why epidemiology is so basic and important for medicine and public health

Realise why epidemiological methods are important to YOUR research

Become acquainted with epidemiological principles and terminology

Become acquainted with common study types

Promote

• Understanding & interpretation of epidemiologic data

• Good epidemiologic research

• Understanding of decisions made on epidemiologic data

The first and today’s lecture

• Background, definition and change over time

• Descriptive studies

• Frequency measures

• Time and population at risk

• Analytical studies (a little)

Cholera epidemics England 1831-1854

Lancet, "History of...the...cholera in England and Scotland". 1831-32

King Cholera dispenses contagion: The London cholera epidemic of 1854

The medical profession…

"Long life to our Central Board . . . May we preserve our health by bleeding the country . . .”

George Cruikshank (1792-1878): The Central Board of Health: Cholera Consultation (London: S. Knight, 1832)

The father of epidemiology:

John Snow 1813 - 1858

• Obstetrician in Frith Street, London

• Administered chloroform to Queen Victoria during childbirth

• Considered cholera to be caused by polluted water

• Prevailing theory breathing in of vapour or contagious substance in the athmosphere (miasma)

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Water supply in London 1854

Southwark & Vauxhall (green)

Lambeth (red)

Cholera morbidity 1854

• Evidence leading to general recordings of source of water supply

No. of houses

Deaths from cholera

Deaths/10,000 houses

Southwark and Vauxhall Company

40,046 1,263 315

Lambeth Company 26,107 98 37

Rest of London 256,423 1,422 59

Broad Street, Soho 1854 The pump in Broad Street

• Cholera outbreak 19. aug. – 30. sept. 1854

• 616 dead

• Sick persons short distance to particular pump

• Most sick persons direct access to pump

• Snows microscopy: White, fluffy particles in water

• Widow in Hampstead who had died from cholera had daily her waiter get water from Soho pump

Intervention

• Anecdote: Snow sneaked out at night and removed pump handle making the epidemic stop

• Reality: Handle removed by public health authorities on Snows Snows suggestion September 8th; the removal had no effect on epidemic

Snows epidemiology

• ’… it is obvious that no experiment could have been devised which would more thoroughly test the effect of water supply on the progress of cholera than this…. To turn this experiment to account, all that was required was to learn the supply of water to each individual house where a fatal attack of cholera might occur.’

• Theory about spread of infectious diseases in general and specifically about the spread of cholera before knowledge of the cause of cholera

• Concepts

– Randomisation (rich/poor, males/females, children/elderly)

– Mortality rates

– Intervention

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Snow’s tracks in history

Society for Epidemiological Research,

slogan competition 1981:

Epidemiologists Love Snow Jobs

Netdoktor, februar 2001

Definition

• Epi (on) demos (people, population) logos (knowledge of) =

The knowledge of what happens to people

• ’The study of the distribution and determinants of health

related states or events in specified populations, and the

application of this study to control of health problems’ (Last

1988)

• ’The study of the distribution and determinants

of disease frequency’

Purposes of epidemiology

1. Identification of cause and determinants of disease

2. Determination of burden of disease in a community

3. Study natural history and prognosis of disease

4. Evaluate preventive and therapeutic measures

5. Provide foundation for developing public health policy

PREVENTION!

Epidemiology: Definition & objectives

”The outbreak in epidemic form of a disease of

pseudo-scientific meticulosis. The symptoms of

the condition are characterised by:

a) evidence of a certain degree of cerebral exaltation; b) an inherent contempt for those who cannot understand logarithms, and c) the replacement of humanistic and clinical values by mathematical formulae.

The systemic effects of this disease are apparent; patients are degraded from human being to pricks in a column, dots in a field, or tadpoles in a pool; with the eventual elimination of the responsibility of the doctor to get the individual back to health.”

Epidemiology is (also)…

Logic and common sense!

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On epidemiologic studies

It is more important to increase the quality of data

in the collection phase than to apply sophisticated

statistics

A. Bradford Hill

Garbage in, garbage out!

Causes of death US

Evolvement of epidemiology

• In the 1950’erne shift from infectious diseases to chronic diseases (coronary disease, cancer, etc.) – advent of antibiotics

• Diseases with different natural histories– From diseases with short latency periods (weeks to years)

– To diseases with long latency periods (years to decades)

• Changing effects of determinants– From large to moderate effects

• Framingham study 1949- (coronary diseases)

• Denmark in the lead (Cancer Registry, CPR)

US Surgeon General William

Stewart

Talk to the Congress 1969:

The war against pestilence is over and now it is time to close the book on infectious disease

Result:

Low priority to infectious disease and microbiological research in Western Europe and the USA

1982

Lancet. 1982 May 15;1(8281):1083-7. Related Articles,Links

Risk factors for Kaposi's sarcoma in homosexual men.

Marmor M, Friedman-Kien AE, Laubenstein L, Byrum RD, William DC, D'onofrio S, Dubin N.

An investigation of 20 homosexual men with histologically confirmed Kaposi's sarcoma and 40 controls revealed significant associations between Kaposi's sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposi's sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).

2009

Swine flu symptom checker:

If you wake up looking like this, don’t go to work

Miranda Carnewro, 18, and Jorge Juarez, 18, wears a masks as they wait to clear U.S. Customs crossing from Ciudad Juarez, Mexico, into El Paso, Texas, Monday, April 27, 2009. (AP Photo/LM Otero)

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Epidemiological way of thought

(Infectious diseases)

• Is there a problem ?

• What characterises the problem?

– When does it occur?

– Where does it occur?

– Who’s problem is it?

• Hypothesis (what is the cause of the problem)

• Is the hypothesis correct?

• Devise public health measures

}}

Descriptive epidemiology

Analytic epidemiology

Basic epidemiological assumption

Exposure Outcome

(more about this later in the course)

Diseases can be characterised

• How many?• Absolute/relative

• Where?• When?• Who?

• Gender, age, race, etc..

• Descriptive epidemiology

Disease patterns can be analysed

Frequency & distribution

Determinants

Application

Characteristic A

Characteristic B

Descriptive & analytic epidemiology

Randomised intervention

Epidemiologic focus

Case control study

Cohort study

Case report/series Ecological study(correlational study)

Cross sectional study

generating testing

Hypothesis-

Incidence report

Excess leukemia cases in soldiers 2001?

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Descriptive and analytic study types

Descriptive studies Analytic studies

Case reports/series Case-control studies

Correlational studies Cohort studies

Cross sectional surveys Randomised/Intervention trials

Promed Mail

February 10, 2003

WHO issues a global alert about cases of atypical pneumonia

“The signs and symptoms of the disease….include initial flu-like illness (rapid onset of high fever followed by muscle aches, headache and sore throat)…..most common symptoms. Early laboratory findings may include thrombocytopenia (low platelet count) and leucopenia (low white blood cell count)…some, but not all……followed by bilateral pneumonia, in some cases progressing to acute respiratory distress requiring assisted breathing on a respirator. Some patients are recovering but some patients remain critically ill.”

http://www.who.int/csr/sars/archive/2003_03_12/en/

Case-reports and -series

"These types of studies in which typically an astute clinician identifies an unusual feature of a disease or a patient's history, may lead to the formulation of a new hypothesis."

"This design has historical importance in epidemiology, as it was often used as an early means to identify the beginning or presence of an epidemic…….. Investigation of the activities of the affected individuals in the case series can then lead to formulation of a hypothesis."

"While case reports and case series are very useful for hypothesis formulation, they cannot be used to test for the presence of a valid statistical association."

H&B 106-7

When is too much too much?

• Endemy– The habitual presence of a disease within a

given geographic area

• Epidemic– Occurrence of a disease of in a community

or region of a group of illnesses of similar

nature, clearly in excess of normal

expectancy and derived from a common or

a propagated source

• Pandemy– An epidemic spanning more continents

What is this pattern?

URILRI

Inci

denc

e

Aug. Dec. Apr. Aug. Dec. Apr. Aug.

1996 1997 1998

Respiratory tract infection in children in Greenland

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When does the observed number

exceed the expected?

• 500 cases of pneumonia in Zealand in toddlers January 2001,

but 50 cases in June. Epidemic?

– Every winter 500 cases - RS-virus

• 2 cases of malignant Kaposis sarcoma in young males in San

Fransisco. Epidemic?

• 2 cases of anthrax in Copenhagen. Epidemic?

• 2 cases of anthrax in Van, Eastern Turkey. Epidemic?

Measures of frequency

• Prevalence (prevalence rate)

Number of sick persons at given time

Number of persons in the population

– Point prevalence – prevalence at given time (Christmas eve)– Periodic prevalence – prevalence in a period (Christmas holiday)

Number of new cases of disease in a specific period

Sum of time at risk for the population

• Incidence (incidence rate)

The concept of time at risk

Time not at risk

Real time

� Time at risk

”Start” ”End”

Why different measures ?

• Prevalence measures the presence of disease at a

specific time in a population

• Measure of burden of disease

• Incidence measures the frequency of disease per

unit of time

• Measure of risk

Factors affecting prevalence

Beaglehole et al., Basic Epidemiology, WHO 1993.

• Longer duration of disease

• Prolongation of life without cure

• Increase in new cases

• In-migration of cases

• Out-migration of healthy

• In-migration of susceptibles

• Improved diagnostic facilities

• Shorter duration of disease

• Higher case-fatality rate from disease

• Decrease in new cases

• In-migration of healthy

• Out-migration of cases

• Improved cure rate

Prevalence = Incidence * duration of disease

What measure to use?

The measure depends on the question!

Relevance of HIV prevalence DK 2009

(5,300 persons, 0.2%)?

Relevance of HIV incidence DK 2009

(236 new cases)?

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Other important rates

• Attack rate

• Case-fatality rate

• Mortality

• CF rate may be high, but mortality low, if disease

is rare!

Sick

Exposed

Dead

Sick

Dead per disease/year

Total population

Khanty-Mansiyskiy autonomus okrug - UGRA

Age-sex structure of patients with new cases of tuberculosis (KMAO 2011)

Age

Num

ber

of c

ases

Population at risk

• Crucial to the calculation of frequency and rates that the population at risk is defined! Who is at risk?

• Influenza

– All who have not been infected with the (this year) prevailling serotypes or are unvaccinated

• Cervical cancer

– Women aged 25-69 years

• Breast cancer

– All

• Salmonella outbreak in restaurant

– All who have tasted the food

• Hospital infections

– Salmonella in the central kitchen

– Defect bedpan disinfector in ward

Background population

• England 1983: ’Windscale – the Nuclear Factory’ (Sellafield)

• Statistically significant excess number of cases of childhood

leukemia in the village Seascale

• Should the plant be shut down?

The Texas sharpshooter

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Descriptive and analytic study types

Descriptive studies Analytic studies

Case reports/series Case-control studies

Correlational studies Cohort studies

Cross sectional surveys Randomised/Intervention trials

Correlational/ecological studies

In correlational studies, measures that represent characteristics of entire populations are used to describe disease in relation to some factors of interest such as age, calendar time, utilization of health services or consumption of a food, medication or other product. (H&B p 102)

Correlation (0 < r < 1)

Correlation (-1 < r < 0)

Occurrence

”Exposure”

No correlation (r = 0)

Correlational/ecological studies

Dietary fat and breast cancer by country

City bikes ensures HIV treatment

January 9, 2014

Correlational studies

• Correlation does not necessarily imply a valid statistical association

• Lack of correlation does not necessarily imply absence of a valid statistical association

Descriptive and analytic study types

Descriptive studies Analytic studies

Case reports/series Case-control studies

Correlational studies Cohort studies

Cross sectional surveys Randomised/Intervention trials

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Cross sectional surveys

• Studies, in which exposure and outcome are determined

simultaneously

• It cannot always be determined which came first, the exposure or

the outcome

• Data on risk factor associations may therefore represent both

survival and etiology

• It cannot be ruled out that the exposure under observation has

changed after and maybe because of the outcome

Risk of Trichinella infection in

Greenlanders

OR (95% CI)

Occupation as hunter or fisherman

No 1

Yes 8.68 (1.74-43.31)

Intake of Polar bear meat

No 1

Yes 1.26 (1.01-1.57)

The Lancet 1999Causal association between MMR and

neuropsychiatric disorders?

Subsequent actions

10 of 11 original authors, 2004:

• We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient. However, the possibility of such a link was raised and consequent events have had major implications for public health. In view of this, we consider now is the appropriate time that we should together formally retract the interpretation placed upon these findings in the paper, according to precedent.4 We were unable to contact John Linnell.

BMJ, 2010:

• In a statement published online (www.thelancet.com) the editors of the Lancet said: "Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al are incorrect, contrary to the findings of an earlier investigation.

• "In particular, the claims in the original paper that children were ‘consecutively referred’ and that investigations were ‘approved’ by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record."

• Cohort studies

– Information on exposure and outcome in the whole study population

– Frequent outcomes

• Case-control studies

– Only information about sample from the population

– More rare disease

• Randomised controlled studies

Analytic study types

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Descriptive epidemiology

Advantages

• Cheap & quick

• May provide important overview

Disadvantages

• No information on the individual

• No control for confounding

• May involve bias

• Results may be ambiguous

• Can not test (causal) hypotheses

Descriptive vs. analytic epidemiology

Analytic epidemiology

Disadvantages

• Expensive

• Laboreous

• May involve bias

Advantages

• Information on the individual

• Control for confounding

• Results less ambiguous

• Can test (causal) hypotheses

U-land undersøger…..

Når intervieweren mærker at personen i den anden ende af røret er ved at miste interessen, må man sikre sig, at røret ikke bliver smækket på:

"Så ved man at det måske regner eller sner, hvor kunden bor, og så snakker man lidt om det, mens man skynder sig selv at udfylde hvad man regner med kunden ville have svaret."

Skulle folk alligevel smække røret på, fortsætter de mest rutinerede interviewere alligevel:

"Man lader som om kunden stadig er i røret - man taler videre, så de andre ved siden af ikke opdager det, og udfylder hvad man regner med kunden ville have sagt."

http://www.econ.ku.dk/milhoj/stik/uland%20unders%C3%B8ger.htm

Summary 1/2

• Epidemiology the study of the distribution and determinants of

disease frequency

• Change from infectious diseases to chronic diseases in 20th

century (but infectious diseases are not outdated)

• Epidemiological way of thought identification of problem,

description in time, place and person, setting up hypothesis

and subsequent testing

• Diseases can occur endemic, in epidemics and in pandemics

Summary 2/2

• Frequency measures include prevalence and incidence

• Descriptive studies include case reports/series, correlation and cross-sectional studies

• Descriptive studies may yield ideas, but cannot test hypotheses

• Analytic study types include cohort studies, case-control studies and randomised controlled trials

• Analytic studies can test hypotheses

And the next times…

Analytic studies (cohort studies, case control studies) and much, much more…