Epidemiology counts.

Simon Wessely, Director, Kings Centre for

Military Health Research, Kings College
London

Before we can count we have to

know what we are counting..

Case definitions.

CDC 1988
Australian
Oxford 1991
CDC 1994
London
Canadian

Ref

Year

Total Citations

Citations per
year

Citations 2007

Holmes et al

1988

1016

48

14

Lloyd et al
Australian

1990

198

10

Sharpe et al
1991 Oxford

1991

402

22

18

Fukuda et al
1994 CDC

1994

1256

84

90

Carruthers et al
Canadian

2003

? 25

How common is it?

Wessely et al, Am J Public Health, 1997

Population based study: Chicago

Point prevalence 0.4% (0.3- 0.6%)
Female excess
Commoner in ethnic minorities

Jason et al, Arch Int Med 2003

Population based interview study:

Georgia
2.5% (1.8 to 5.9)
Female excess
No link to ethnicity

Reeves et al, BMC Population Metics, 2007

Epidemiology counts.
0.6-2.6% fulfil criteria for CFS in primary care
depending on criteria
Excluding co morbid psych conditions
prevalence falls to 0.1-0.6%
Most people dont use a label like ME or CFS
to describe their condition
The public health impact of CFS in primary care
is considerable. Many are severely disabled and
up to 75% are depressed or anxious

A word of caution All of these definitions are arbitrary

We are dealing with a dimensional, not

categorical, variable

Pawlikowska et al, BMJ 1994

CDC defined symptoms of CFS

1988

1994

Fever/Chills
Fever/Chills
Sore
Sore throat
throat
Sore
Sore glands
glands
Muscle
Muscle Problems
Problems
Myalgia
Myalgia
Post
Post exertional
exertional fatigue
fatigue
Headaches
Headaches
Joint
Joint disturbance
disturbance
Neuropsycological
Neuropsycological
Sleep
Sleep problems
problems

Sore throat
tender glands
Muscle pain
Post exertional malaise
new headaches
Multi joint pain
Subjective memory impairment
unrefreshing sleep

Association between fatigue and psychological distress

in a population based sample

Pawlikowska et al, 1994

WARNING
The more symptoms included in the case
definition, the greater the association with
psychological morbidity
The more disability included in the case
definition, the greater the association with
psychological morbidity

What can epidemiology tell us

about risk factors/aetiology?

Some proposed risk factors for

CFS

Activity avoidance / physical de-conditioning

Atopy
Genetics
Neuro endocrine
Over activity
Post-viral / Immune dysfunction
Psychiatric disorders
Response to toxic hazards
Sleep disturbance

 the problems of bias,confounding, reverse

causality and chance that spoilsport
epidemiologists use to judge each others
associations

Selection bias.

CFS and social class

COMMONER IN LOW SES

NO ASSOCIATION WITH SES

UK Primary care

Georgia

Chicago
French primary care
Australian community study
San Francisco community
study

Confounding.

HAVE THE SAMARITANS REDUCED THE SUICIDE RATE?

Confounders are alternative

explanations for observed
differences

24 hour Urinary free cortisol (UFC): CFS

v Controls (Demitrack et al, 1991)

24 h Urinary Free Cortisol

Output
100

nmol/h/24h

80
60
UFC

40
20
0
'Pure' CFS n=89 CFS + Psych
n=32

Controls n=64

Cleare et al, Am J Psych 2001

Cleare et al, Am J Psych, 2001

Bias and how to avoid it.

The further away you are from the community,
the greater the risk of bias
Trust studies in which exposures or risk factors
are measured before outcomes (ie CFS)

Insert picture of Jeremy Paxman

What can prospective studies tell us

about the risk factors for CFS?

CFS and Psychiatric Disorder

Definite association between CFS and
psychiatric disorders
Depression
Anxiety
Personality factors
Casecontrol or cross sectional studies
Direction of causation unknown

Consequence, risk factor, or

confounder?

Psychiatric
Disorder

CFS

Psychiatric
Disorder

CFS
Psychiatric
Disorder

Other
CFS

Current psychiatric disorder in CFS compared

with medical controls
Control
Control group
group

Psych
Psych
disorder
disorder in
in
CFS
CFS

Psych
Psych disorder
disorder
in
in controls
controls

Relative
Relative
risk
risk

Neuromuscular
Neuromuscular

72%
72%

36%
36%

2.0
2.0

Rheumatoid
Rheumatoid

45%
45%

6%
6%

7.5
7.5

Myopathy
Myopathy

41%
41%

12.5%
12.5%

3.3
3.3

Multiple
Multiple sclerosis
sclerosis 23%
23%

8%
8%

2.9
2.9

ENT/
ENT/ dermatology
dermatology 77%
77%

50%
50%

3.4
3.4

Multiple
Multiple sclerosis
sclerosis 45%
45%

16%
16%

2.8
2.8

Risk factor or confounder?

Psychiatric
Disorder

CFS
Psychiatric
Disorder

Other
CFS

1946 National Birth Cohort

MRC survey of Health and Development

Random social class stratified sample of 5362
participants from all single legitimate births in
one week of March 1946
Prospectively followed for 53 years
Over 20 separate data collections
Representative of the national population
(Wadsworth
(Wadsworth et
et al.
al. 2006)
2006)

Prior Psychiatric Disorder

Combining measures of individual psychiatric
disorder up to the age of 36 years (any prior
psych illness):

OR (adjusted for sex) - 2.65

(1.26 5.57, p=0.01)

CFS and exercise

Many patients report previous over activity
Chronic illness/bed rest can cause physical deconditioning
Graded exercise therapy
Lower levels of activity in childhood assoc with
subsequent CFS (Viner
(Viner and
and Hotopf,
Hotopf, 2004)
2004)

Percentage
Percentage

Percentage of participants engaging in more than weekly

exercise at different ages

Fatigue
Fatigue

60
60
50
50
40
40
30
30
20
20
10
10
0
0
31
31

36
36

43
43

53
53

Age
Age (years)
(years)
Those
Those with
with CFS
CFS at
at age
age 53
53 years
years

Those
Those with
with no
no CFS
CFS at
at age
age 53
53 years
years

Pattern of persistent exercise

56% of the individuals who reported weekly
exercise at age 31 were still engaging in weekly
sports at age 43 yrs
These persistently active individuals had an
adjusted OR for CFS/ME at age 53 yrs of 10.8 (2.7
43.8, p=0.001)
Harvey, Wadsworth, Wessely. Hotopf. Psychological
Medicine 2008; Psychosomatic Medicine, 2008

Post infectious fatigue syndromes

1892
1892
1892
1892
1911
1911
1922
1922
1922
1922
1931
1931
1939
1939
1946
1946
1946
1946
1970
1970
1982
1982
1984
1984
1985
1985
1988
1988
1989
1989
1990
1990
1991
1991
1992
1992
1993
1993
1996
1996
2001
2001

Influenza
Influenza
Typhoid
Typhoid
Alimentary
Alimentary bacteria
bacteria
Streptococcus
Streptococcus
all
all vaccinations
vaccinations
Encephalitis
Encephalitis lethargica
lethargica
Brucellosis
Brucellosis
Yellow
Yellow fever
fever vaccination
vaccination
Schistosomiasis
Schistosomiasis
St
St Louis
Louis encephalitis
encephalitis
Epstein
Epstein Barr
Barr virus
virus
Varicella
Varicella
Coxsackie
Coxsackie
HHV-6
HHV-6
Tetanus
Tetanus
Lyme
Lyme
HTLV-2
HTLV-2
Spumavirus
Spumavirus
Parvovirus
Parvovirus
Mycoplasma
Mycoplasma
Ross
Ross River
River virus
virus

Glandular fever and CFS

Relative risk of CFS following glandular fever vs
URTI:
CFS (Oxford) 3.9 (1.2-12.4)
CFS (CDC)
5.1 (0.7-39)

Over 3000 new cases of CFS in England and

Wales each year due to glandular fever
White et al, Lancet 1998

Chronic Fatigue and CFS after acute viral

infection in primary care
Criteria
Criteria

Viral
Viral (N=1010)
(N=1010)
354
354 (35.0%)
(35.0%)

Non-viral
Non-viral
(N=975)
(N=975)
344
344 (35.2%)
(35.2%)

All
All fatigue
fatigue cases
cases

OR(95%
OR(95% CI)
CI)
1.0
1.0 (0.8-1.2)
(0.8-1.2)

Chronic
Chronic fatigue
fatigue

100
100 (9.9%)
(9.9%)

114
114 (11.7%)
(11.7%)

0.8
0.8 (0.6-1.1)
(0.6-1.1)

Oxford
Oxford CFS
CFS

14
14 (1.3%)
(1.3%)

19
19 (1.9%)
(1.9%)

0.7
0.7 (0.4-1.6)
(0.4-1.6)

CFS
CFS CDC
CDC 1994
1994

55 (0.5%)
(0.5%)

11
11 (1.1%)
(1.1%)

0.4
0.4 (0.15-1.3)
(0.15-1.3)

Wessely et al, Lancet, 1995

CFS and previous psychiatric disorder:

Odds ratios for Developing CFS at Stage 3
Criteria

GHQ stage one

Oxford CFS

6.2

Previous psychiatric
diagnosis
3.9

CFS CDC 1994

5.2

2.8

CFS CDC 1988

6.4

9.3

Wessely et al, Lancet, 1995

Risk factors for developing CFS

Gender
Lower socio economic class
Childhood illness
Musculo skeletal pain
No sport in spare time
History of allergies
Recent ingestion of raw milk
Family member with CFS
Hempel et al, 2008

Risk factors for developing CFS

infectious/quasi infection

EBV
Viral meningitis
Q fever
Ross River Virus
Sick certification after viral infection
Days spent in bed at start of infection

Psychiatric risk factors for

developing CFS

Previous mood disorder

Previous anxiety disorder
emotional instability
Poor self rated health
Childhood trauma
Hempel et al, 2008

Any proposed model for CFS must

therefore explain
Genetics
Gender
Links with prior psych/personality variables
Why do some but not other infective agents trigger CFS?
Complex links with activity

Kings
Centre for
Military
Health
Research

www.kcl.ac.
uk/kcmhr