Download Lecture 1: Infectious Diseases i th 21st C t in the 21st Century

Senior Freshman BY2209 Infection & Immunity
Lecture 1:
Infectious Diseases
i the
in
th 21st Century
C t
Prof Jay Hinton, Microbiology Department
Senior Freshman BY2209 Infection & Immunity
Course Overview
● Joint course, delivered by Microbiology,
Immunology & Genetic Departments
● An exciting multi-disciplinary course focusing
on:
 Key bacterial pathogens and how they cause
disease
 Strategies for controlling infections
 Vaccines
& Antibiotics
 How
H
h
humans cope with
ith iinfections...
f ti
 Immune responses
 Genetic susceptibility to infectious disease
Why is this one of the most
important courses you’ll do this
year at Trinity?
● Because Infectious Disease has had a huge
effect on shaping the world ...
A question...
● “Why has life expectancy doubled in the past
150 years?”
Average Age of Death, England
1837 1841
1837-1841
Manchester
(Manufacturing)
Liverpooll
(Commercial)
Wiltshire
(Agriculture)
“Persons” &
G t
Gentry
Tradesmen &
F
Farmers
Labourers &
S
Servants
t
38
20
17
35
22
15
50
48
33
● If this
thi was 1840...
1840
 Some of you would be dead
 Many of your parents would be dead
Aiello et al., (2008) Am. J. Infect. Control 36: S111-115
Average Age of Death, England
1837 1841
1837-1841
Manchester
(Manufacturing)
Liverpool
(Commercial)
Wilts
(A i lt
(Agriculture)
)
“Persons” &
Gentry
Tradesmen &
Farmers
Laborers &
Servants
38
20
17
35
22
15
50
48
33
Average life expectancy increased
between 19th & 20th Centuries
● From 40 (1848)
(
)
● ......to 69 (1970)
http://www.ohe.org/page/knowledge/schools/appendix/life_expectancy.cfm
Male Life expectancy, Ireland
1926 & 1999
80
70
60
57
50
40
2000
1975
Year
1950
1925
30
1900
Av
verage
e age at de
eath
77
Male Life expectancy U.S.A. 1900-99
WW II
70
HIV/ AIDS
60
Irish male life
expectancy
50
40
2000
1975
Year
1950
30
1925
“Spanish” Flu
pandemic (1918)
1900
Av
verage
e age at de
eath
80
Epidemics in New York City,
1804 -1918
1918
Aiello et al.,
al (2008) Am.
Am J.
J Infect.
Infect Control 36: S111
S111-115
115
Leading causes of death, USA
●
●
●
●
Diptheria
Diarrhoeal disease
TB
Pneumonia
1900
● Pneumonia
P
i
1998
Aiello et al., (2008) Am. J. Infect. Control 36: S128-151
Death from all infectious diseases
USA 1900 to 1996
USA,
1000
“Spanish” Flu
pandemic (1918)
800
Mortality
per
100,000
per
year
600
First use of
Penicillin
400
Polio vaccine
introduced
Chlorination of
water supplies
200
1900
1920
1940
1960
1980
Year
source: Centers for Disease Control
Infectious disease
● Infectious disease has had a huge effect on
the human race
● History has been shaped by a plethora of
epidemics and pandemics
●U
Until
til we started
t t d tto understand
d
t d the
th causes off
disease, we were unable to fight it...
What causes disease? (Pre-1850)
● Miasmatic theory
 Disease was transmitted by miasma
A p
poisonous vapour
p
or mist
● Cholera “miasma” transmitted in
the wind
Germ Theory (post 1850)
● Proposed that microorganisms are the cause
of many diseases
● Highly
g y controversial when first proposed
p p
● Cornerstone of modern medicine & clinical
microbiology
● Led to antibiotics and hygienic practices…
 Louis Pasteur
1822 – 1895
 Developed Pasteurisation in 1864
 Saved Millions of lives…
Robert Koch
1843-1910
● Founder of public health…
● Developed “Koch’s Postulates” (next lecture!)
In late 1800’s discovered causal agents of:
● Tuberculosis,
● Mycobacterium
y
tuberculosis
● Cholera
● Vibrio cholerae
● Anthrax.
 Bacillus anthracis
Vaccination
● Immunity to disease can be
generated by vaccination
● Important role in protecting
individuals against illness
● Vaccination works by safely
exposing individuals to a specific
pathogenic microbe
 Artificially increases immunity
Vaccination
Mortality due to Tuberculosis
1850 1970
1850-1970
Mycobacterium tuberculosis
Aiello et al., ((2008)) Am. J. Infect. Control
36: S116-127
Eradication of Diptheria in England
1860 - 1970
Corynebacterium diphtheriae
Aiello et al., (2008) Am. J. Infect. Control 36: S116-127
Worldwide eradication of Smallpox
by vacccination
● Began in 1950
Rahima Banu (aged 2)
Last human case (1975)
● Declared successful in 1980
Image: WHO
Eradication of Polio in USA by
vaccination 1950
vaccination,
1950-1990
1990
Aiello et al., ((2008)) Am. J. Infect. Control
36: S116-127
Vaccines
● Measles vaccine
introduced in 2000
 In 8 years, global
deaths reduced
by 78%
● 500,000 lives saved in
2008
● Estimate that 4.2 million p
people
p died
in 2005 due to vaccine-preventable diseases
30th January,
y, 2010
http://www.gatesfoundation.org/GlobalHealth/Pri_Diseases/Vaccines/Vaccine_Backgrounder.htm
Antibiotic treatment of pneumonia
saves lives in USA
USA, 1900 - 1970
Aiello et al., (2008) Am. J. Infect. Control 36: S116-127
How did we control
infectious disease?
● Vaccination
● Antibiotics
● Public health measures
 Public sanitation
 Chlorination of water supply
Aiello et al., (2008) Am. J. Infect. Control 36: S128-151
Incidence of typhoid,
typhoid USA
* Chlorination of water supply
How did we control
infectious disease?
● Vaccination
● Antibiotics
● Public health measures
 Public sanitation
 Chlorination of water supply
● Social measures
 Improving housing
 Reducing poverty & over
over-crowding
crowding
Personal Hygiene!
● Handwashing reduces
incidence of:
 Diarrhoeal disease
 Flu & Colds
Life expectancy increased...
● Everything looked very good in the 1960s!
1000
800
y
Mortality
per
100,000
per
p
year
600
First use of
P i illi
Penicillin
400
Polio vaccine
introduced
200
1900
1920
1940
Year
1960
1980
Prompting the US Surgeon General
to say to the US Congress - 1967…
1967
The war against
Infectious Disease
has been won...
Willi
William
H.
H Stewart
St
t
We should focus on
other areas of research
& public health...
● He was being overly
optimistic…
“It is time to close the book on infectious diseases and shift all
national attention and dollars to the ‘New
New Dimensions’
Dimensions of health:
chronic diseases”
Death from all infectious diseases
USA (after the Surgeon General in 1967...)
1967 )
1000
80
800
Mortality
per
100,000
per
year
60
40
600
20
400
1970
1980
1990
200
1900
1920
1940
1960
1980
Year
source: Centers for Disease Control
Causes of death due to bacterial
di
disease
worldwide
ld id (2002)
● Total = @ 8 million people per year
 500 people will die during my lecture...
“Other bacterial causes”
Diarrhoeal
22% is 1.8 million
deaths per year…
Two-thirds are children
22%
47%
20%
TB
Lower
Respiratory Tract
Diarrhoeal Disease
● Biggest cause of infant mortality worldwide
Why is infectious disease-related
mortality no longer decreasing?
● Increased antibiotic resistance
 Some treatments no longer work
● New disease
 “emerging infections”
Rise of antibiotic resistance in
bacteria...
bacteria
Multiple antibiotic resistance in S. Typhimurium
DT104 Humans,, England
g
and Wales
1981 – 2000
4500
4000
3500
sensitive
ACSSuT
ACSSuTTm
3000
2500
ACSSuTCp
SSu
others
2000
1500
1000
500
0
1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Why has antibiotic resistance
occurred?
● Pressure on doctors,
doctors by patients
patients, to prescribe
antibiotics even when they are not needed.
● Patients being prescribed antibiotics
without the doctor knowing the cause
of the infection.
infection
MRSA
● Use of antibiotics in animals for growth
promotion & prophylaxis
 Antibiotics enter the human food chain.
Human cases of S. Typhimurium DT104 Rtype ACSSuT, England 1999 & 2000
120
100
Outbreak
identified
1999
2000
80
60
40
20
0
1
3
5
7
9
11
13
15
17
19
21
23
25
27
29
31
Week of isolation
33
35
37
39
41
43
45
47
49
51
Multiple drug resistance, S. Typhimurium DT104.
H
Humans,
England
E l d and
dW
Wales
l
1990 – 2001
2500
2000
ACSSuT
ACSSuTTm
1500
ACSSuTCp
Licensing of
enrofloxacin for
veterinary use
1000
500
Quinolone-resistance
0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
Percent off isolate
es
Quinolone-resistant
Salmonella Typhimurium DT104 (UK)
18
16
14
12
10
8
6
4
2
0
Nov 93 – Enrofloxacin
licensed for animal
use
92
93
94
Chickens
Cattle
95
Pigs
96
Humans
97
The Need for New Antibiotics
● Infectious disease is the second major cause of death
in the US,
US and third worldwide
●
Infectious disease mortality


1900 - 1980: declined 20-fold
1980 - 1995: increased two-fold
●
Pathogen acquisition of multi-drug resistance is a
major contributor to death from
f
infectious
f
disease
●
A d then
And
th there
th
is
i the
th spectre
t off bio-terrorism……
bi t
i
Millennium Bugs-Emerging and Re-emerging
Infectious Diseases,, 1996-2006
Ebola and CCHF
Influenza H5N1
Hantavirus
Lassa fever
Monkeypox
Nipah Hendra
NV-CJD
Rift Valley Fever
SARS CoV
VEE
Yellow fever
West Nile
Plague
Brucellosis
E Coli O157
Multidrug resistant
Salmonella
Cryptosporidiosis
Leptospirosis
Lyme Borreliosis
Adapted from Dr. Roth WHO 2006
Emerging Infectious Diseases
(1940 – 2009)
● Viruses
 Ebola
 H5N1 flu
 H1N1 flu
 SARS virus
 West Nile Virus
● Bacteria
 Plague
 MDR Salmonella
 Clostridium difficile
 TB
● Bioterrorism
SARS
Impact of air travel
● No city on earth is more than 24 hours away
f
from
any other
th
● At any one moment @ half a million people are
flying in commercial aircraft worldwide
SARS: The first global epidemic
off the
th 21st
21 t century
t
(2003)
SARS outbreak: 8098 patients & 774 deaths. (The Independent 23.3.03)
Major factor behind Emerging
Infectious Diseases
Pathogens
g
Animals
Humans
2003
● Avian H5N1
● Outbreak began in 2003
y June 2009
● 261 deaths by
Public information in China -the do’s and dont’s for avian flu
Global Map of Emerging Infectious
Diseases (1940 – 2004)
Jones et al., (2008) Nature 451: 990-993
Influenza virus
(0.1 micrometre)
● 95% smaller than E.
E coli bacterium
N = Neuraminidase
H = Haemagglutinin
Influenza H1N1 Pandemic 2009
● Acute, highly contagious viral
infection
p
● Inhaled in droplets
 Grows in epithelial
p
y tract
in respiratory
● Rapidly mutations
 Constant changes in
genetic make up
Influenza H1N1 Pandemic 2009
● Started in Mexico in Feb 2009
 Outbreak Reported - 24th April 2009
 Pandemic declared - 29th April
p 2009
● Rapid spread worldwide
worldwide...
 Fortunately, not as dangerous as feared...
International spread of
Pandemic H1N1 (8th Nov)
● 8784 deaths in 207 countries (29
(29.11.09)
11 09)
Bioterrorism
● Anthrax
 Bacillus anthracis
● Need for antibiotics to
kill particular strains
Botulinum toxin
● Used in biological weapons..
● ...and as a temporary face-lift...
Botulinum toxin can be
ingested with food
● 30ng botulinum toxin can be lethal
● High fatality rate (~10% cases)
● Victims are paralysed for years...
 Need for long-term intensive care
The dangers of canning your own
vegetables!
USA, 1926
Take-Home...
● Bacteria, viruses & parasites cause serious
disease
 Decimated society prior to 20th Century
● We have had notable success against many
diseases
 Public health measures
 Vaccines
 Antibiotics
●E
Emerging
i pathogens
th
& antibiotic
tibi ti resistance
i t
remain serious threats for the 21st Century
We are relying on the next generation
of microbiologists...
microbiologists
● To meet the challenge
g of new pathogens
p
g
● To understand how new viruses & bacteria
cause disease
New Antibiotics
New Vaccines