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Animation: Shih Ching Fu
CHRISTOPHER DYE
PATHOGENS AND PARASITES
PLAGUES AND PANDEMICS
Life expectancy at birth (years)
The Great Escape
80
Life expectancy in England 1300-2000
Wrigley & Schofield
70
Human Mortality Database
Clark
60
50
40
30
20
1300
1400
1500
1600
1700
1800
1900
2000
PATHOGENS PARASITES
PLAGUES
PANDEMICS
• How many kinds of pathogens are there,
and what kinds of diseases do they
cause? What are we and why do we
suffer?
• How do pathogens spread and persist?
How does epidemiology explain parasite
lifestyles?
• What epidemics will we face in future?
What are "the coming plagues"?
1. Parasites and diseases
Life's three domains
Archaea Bacteria Eukaryotes
Archaea -- one cell -- few parasites?
(Extreme bacteria)
Bacteria -- one cell -- parasites,
commensals, mutualists…
Eukaryotes – one or many cells -protozoa (malaria), fungi
(ringworm), worms (hookworm),
insects, arachnids (ticks)
Non-living pathogens
Viruses
Prions Parasitic DNA
Viruses -- genes in a protective protein shell -Ebola, measles, polio, cancers
Prions -- infectious protein particles -transmissible spongiform encephalopathies
(TSEs) -- Creutzfeld-Jakob disease (kuru,
vCJD), bovine spongiform encephalopathy
(BSE or mad cow disease)
Parasitic DNA -- transposons -- mobile genetic
elements -- heritable disorders -- hemophilia,
severe combined immunodeficiency,
porphyria, cancer
People are mostly bacteria
Humans + bacteria = "super-organisms"
Humans
Functional cells (other than blood, neurons ) 1012
Bacteria (Bacterioides, Clostridium, Escherichia…)
On skin
1012
In mouth
1010
In gut
1014
>1kg
>1000 species
>100 × as many genes
From the power of partnership…
… to the perils of parasitism
Vibrios: mutualists and pathogens
← Ganges Delta: Vibrio (cholera)
mixing pool
Vibrio fischeri: drives light organs of
squids →
← Vibrio cholerae: potentially lethal
human diarrhoea
•
•
•
•
•
Viruses & prions
Bacteria & rickettsia
Fungi
Protozoa
Helminths (worms)
• Zoonotic (from animals)
• "Emerging"
217
538
307
66
287
868
175
Source: Taylor et al 2001
1415 organisms pathogenic
to humans (exc. arthropods)
Deaths per million population
Where 60 million people die
double burden of disease in low-income countries
8
6
Low-middle income
High income
4
2
0
Communicable,
pregnancy,
nutrition
Noncommunicable
Injuries
Infectious causes of death in ICD-10
Millions of deaths in 2002
4
3
2
1
0
13/60m deaths in
2002 from infections
86% caused by top 5
2. Parasite spread
and persistence in
populations
D
1000.0
100.0
10.0
1.0
0
20
40
0.1
0
15
30
Concepts and models
60
45
60
80
75
90
"All that is simple is false and all that is
complex is useless" P Valéry
"Everything should be made as simple
as possible, but not simpler" A Einstein
Why replace a world you don't
understand with a model of the world
you don't understand? P Richardson &
R Boyd
Reproduction and persistence:
the key to epidemiology and evolution
No. cases per generation
12
10
8
6
4
2
0
1 2 3 4 5 6 7 8 9 10 11 12
Generations of cases
Basic case reproduction number: R0 = 15/9 = 1.8 (>1)
Epidemic wanes as pathogen runs out of hosts (death, immunity)
Proportion months with no cases
Measles can't survive on small islands
1
0.8
Tonga
Gilbert Is.
Fr. Polynesia
Cook Is.
Greenland
Samoa
New Hebrides
Faroe Is.
Solomon Is.
New
Caledonia
0.6
Iceland
Bermuda
0.4
Fiji
Guam
0.2
Hawaii
0
0.1
1
Population size (millions)
10
Measles: penalty for living in cities
0.7
Annual growth rate (millions)
Dhaka
0.6
Karachi
0.5
Cities with most
measles have:
Moderate-high
incidence
Low incidence
Lagos
Mumbai
High birth and
immigration
rates (>200,000
per yr)
Jakarta
0.4
0.3
0.2
Rio de J
0.1
Buenos
Aires
Los
Angeles
Sao Paolo
New York
Mexico
City
Poor vaccination
coverage
Tokyo
0
5
10
15
20
25
Population 2000 (millions)
30
Source: Strebel 2001
Measles in the UK
lower vaccine uptake leads to larger outbreaks
70
Jansen: 0.4
Science 301, 804 (2003)
0.6
0.3
80
50
reproduction
numbers
0.9
0.7
0.8
60
40
0.8
30
40
20
20
10
0
0
1995 1996 1997 1998 1999 2000 2001 2002 2003
Vaccine uptake (%)
Cases in outbreak
60
100
TB: a human disease for 3 million years?
time present: M tuberculosis complex
bottleneck 35 000 yrs BP
Source: Gutierrez
PLoS Pathogens Sep 2005
3 million yrs BP: ancestral
smooth tubercle bacilli
Signs of silent TB infection
Tuberculin
or Mantoux
test
Plague – Yersinia pestis
rats – fleas – people
>120,000 London plague deaths, 1590-1650
from Graunt's Bills of Mortality
Deaths (10,000s/yr)
4
3
2
1
0
1590 1597 1604 1611 1618 1625 1632 1639 1646
Rats as plague reservoirs
plague cases in rats
human infections
London, Thames, summer 1858
"The Great Stench"
"The sewage of three millions of
people has been brought… to
seethe and ferment… in one vast
open cloaca… Parliamentary
committee rooms rendered barely
tolerable…"
Winslow 1943
Notes on Nursing
What It Is, and What It Is Not
by F Nightingale, 1860
"of the fatal effects of the effluvia
from excreta it would seem
unnecessary to speak were they
not so constantly neglected"
F Nightingale
The Great Stink of Paris and the
Nineteenth-Century Struggle Against
Filth and Germs
by David S. Barnes, 2006
Clearing the air:
Dr. André-Justin
Martin led the
municipal
disinfection service
in 1890s Paris
Morbid matters: cholera
London July-Aug 1854
Both
companies
Southwark &
Vauxhall
32 deaths/1000
Lambeth
4 deaths/1000
3. Future plagues
The growth
of literature
on new
threats from
infection
malaria
Drug
resistance
Beijing
TB
AIDS
SARS
Bird flu
Situations vacant
opportunities for new pathogens
Viruses pose the greatest risk
number emerging
72
18
6
11
30
60
20
24
10
10
8
6
0
viruses
bacteria
fungi
protozoa
humans
animals
humans
animals
humans
animals
humans
animals
humans
0
worms
Source: Taylor et al 2001
40
animals
% species emerging
50
Beijing TB strains kill mice quickly
Percent surviving
100
80
Control strain H37Rv
60
40
20
Beijing
strains
0
0
2
4
Cin Exp Imm v133 p30 (2003)
6
Weeks
8
10
12
Percent strains Beijing
Beijing/W TB strains tend to be in
younger people in Viet Nam and Africa
Source: EID v12 p736 (2006)
80
China
60
Viet Nam
40
3 African
countries
20
0
<30
30-49
Age group (yr)
50+
The (re)growing problem of
hospital infection
Directly Rostov entered the [hospital] he was
enveloped by a smell of putrefaction…
"What do you want, sir?" said the doctor.
The bullets having spared you, do you
want to try typhus? This is a pesthouse,
sir."
"How so?" asked Rostov.
"Typhus, sir. It's death to go in.
Tolstoy, War and Peace (Ch XVII)
Evolution as seen in the ER
Methicillin-resistant Staphylococcus aureus
(MRSA)
• Commonest cause of skin and soft tissue infections in
USA -- now in the "community"
• Also resistant to oxacillin, penicillin and amoxicillin
• USA 2004: 320 of 422 adults had "staph" -- 78% of these
had MRSA
Source: NEJM v355 p666 2006
Emerging and re-emerging
zoonoses, 1996–2004
Ebola and
CCHF
Influenza H5N1
Hantavirus
Lassa fever
Monkeypox
Nipah Hendra
NV-CJD
Rift Valley
Fever
Brucellosis
SARS CoV
Cryptospporidiosis
E Coli O157
VEE
Leptospirossis
Multidrug resistant
Salmonella
Yellow fever
Lyme Borreliosis
Plague
West Nile
Apocalypse
soon?
•
•
•
•
Unavoidable transmission route
Highly infectious
High proportion of people exposed
Transmission rapid compared with
response time (everyone gets infected
before knowing)
• Fatal
INFECTION TRANSMITTED VIA THE GLOBAL AVIATION NETWORK?
Real spread from China & Hong Kong
SARS
Severe acute respiratory
syndrome
Origin bats in China
Transmission among
humans
Case fatality 4% – up to
1000 deaths
Model spread from Hong Kong
Confirmed Human and Animal H5N1 Infections since 2003
and Poultry Distribution
How many people will die in
the next flu pandemic?
Millions of flu deaths
50
Re-running the 3
pandemics of the
20th century
40
30
20
10
Spanish Flu
H1N1
Asian Flu
H2N2
Hong
Kong Flu
H3N2
1957-58
1968-70
0
1918-20
How to survive a flu pandemic?
In advance
 Stockpile Tamiflu or
Relenza - and hope
 Get pneumococcus
vaccination
 Consider taking
statins
 Become
indispensable
 Stock up emergency
supplies
 Move to a rich
country
During a pandemic
 Wash your hands
often
 Avoid people
 Don't flee the city
 Get infected early –
if you dare
Source: New Sci, 7 Jan 2006
25 years of AIDS
People
living
with
HIV
Million
50
45
40
35
30
25
20
15
1 Immune deficiency in gay men in USA
2 Acquired Immune Deficiency
Syndrome (AIDS) is defined
3 The Human Immune Deficiency
Virus (HIV) is identified as the cause
of AIDS
4 In Africa, a heterosexual AIDS
epidemic is revealed
8 The first therapy for AIDS –
zidovudine, or AZT -- is
approved for use in the USA
10
5
1
2
3 4
5
6
9
15
16
14
9 In 1991-1993, HIV
prevalence in young
pregnant women in Uganda
and in young men in
Thailand begins to
decrease
10 Highly Active Antiretroviral
Treatment launched
13
11
10
12
7 8
Children
orphaned
by AIDS in
subSaharan
Africa
1985
Died in 2005:
3 million
Total deaths:
25 million
0
1980
HIV infected in
2005: 40 million
1990
1995
2000
2005
1.1
A global view of HIV infection
38.6 million people [33.4‒46.0 million] living with HIV, 2005
0.1%+
<0.1%+
1%+
0.5%+
5%+
15%+
HIV infection in adults
From natural history to public health
• Parasitism adopted as a "lifestyle" by many
kinds of living and non-living agents
what is self and non-self?
• Despite huge parasite diversity, very few
cause most human deaths
most are preventable or curable
• Pandemics most likely to be a lethal virus
with transmission rapid compared with
reaction time
influenza (weeks), HIV/AIDS (years)