PATHOGENS AND PARASITES PLAGUES AND PANDEMICS
CH
RIS
TO
PH
ER
DY
E
An
imat
ion
: S
hih
Ch
ing
Fu
20
30
40
50
60
70
80
1300 1400 1500 1600 1700 1800 1900 2000
Lif
e ex
pec
tan
cy a
t b
irth
(ye
ars) Wrigley & Schofield
Human Mortality Database
Clark
The Great Escape Life expectancy in England 1300-2000
• 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"?
PATHOGENS PARASITES PLAGUES PANDEMICS
1. Parasites and diseases
Life's three domainsArchaea 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 pathogensViruses 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 bacteriaHumans + 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
… to the perils of parasitism
From the power of partnership…
← Ganges Delta: Vibrio (cholera) mixing pool
Vibrio fischeri: drives light organs of squids →
← Vibrio cholerae: potentially lethal human diarrhoea
Vibrios: mutualists and pathogens
1415 organisms pathogenic to humans (exc. arthropods)
• Viruses & prions 217• Bacteria & rickettsia 538• Fungi 307• Protozoa 66• Helminths (worms) 287
• Zoonotic (from animals) 868• "Emerging" 175 S
ou
rce:
Tay
lor
et a
l 20
01
Where 60 million people die double burden of disease in low-income countries
0
2
4
6
8
Communicable,pregnancy,
nutrition
Non-communicable
Injuries
Dea
ths
per
mill
ion
po
pu
lati
on
Low-middle income
High income
0
1
2
3
4
Low resp
irato
ry
HIV/A
IDS
Diarrh
oea
Tubercu
losi
s
Mal
aria
Mea
sles
Pertu
ssis
Tetan
us
STDs ex
c HIV
Men
ingiti
s*
Tropic
al d
isea
ses
Hepat
itis
B
Mill
ion
s o
f d
eath
s in
200
2Infectious causes of death in ICD-10
13/60m deaths in 2002 from infections 86% caused by top 5
2. Parasite spread and persistence in
populations
"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
Concepts and models020
40
60
80
015
3045
6075
90
0.1
1.0
10.0
100.0
1000.0
D
Reproduction and persistence: the key to epidemiology and evolution
Basic case reproduction number: R0 = 15/9 = 1.8 (>1)Epidemic wanes as pathogen runs out of hosts (death, immunity)
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12Generations of cases
No
. cas
es p
er g
ener
atio
n
Cook Is.Greenland
Faroe Is.
Bermuda
Gilbert Is.
New Hebrides
Tonga
Guam
New Caledonia
Fr. Polynesia
Solomon Is.
Samoa
Iceland Fiji
Hawaii
0
0.2
0.4
0.6
0.8
1
0.1 1 10
Population size (millions)
Pro
po
rtio
n m
on
ths
wit
h n
o c
ases
Measles can't survive on small islands
Cities with most measles have:
High birth and immigration rates (>200,000 per yr)
Poor vaccination coverageSource: Strebel 2001
Measles: penalty for living in cities
Tokyo
Jakarta
KarachiMumbai
DhakaLagos
Mexico City
New York
Sao PaoloLos Angeles
Buenos Aires
Rio de J
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
5 10 15 20 25 30
Population 2000 (millions)
An
nu
al g
row
th r
ate
(mill
ion
s)
Moderate-highincidenceLow incidence
Jansen: Science 301, 804 (2003)
0.8
0.80.70.9
0.30.40.6
0
10
20
30
40
50
60
70
1995 1996 1997 1998 1999 2000 2001 2002 2003
Ca
se
s in
ou
tbre
ak
0
20
40
60
80
100
Va
cc
ine
up
tak
e (
%)
reproduction numbers
Measles in the UKlower vaccine uptake leads to larger outbreaks
time present: M tuberculosis complex
bottleneck 35 000 yrs BP
3 million yrs BP: ancestral smooth tubercle bacilli
Source: Gutierrez PLoS Pathogens Sep 2005
TB: a human disease for 3 million years?
Signs of silent TB infection
Tuberculin or Mantoux
test
Plague – Yersinia pestisrats – fleas – people
0
1
2
3
4
1590 1597 1604 1611 1618 1625 1632 1639 1646
De
ath
s (
10
,00
0s
/yr)
>120,000 London plague deaths, 1590-1650from Graunt's Bills of Mortality
Rats as plague reservoirs
human infections
plague cases in rats
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 NursingWhat 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 Germsby David S. Barnes, 2006
Clearing the air: Dr. André-Justin Martin led the municipal disinfection service in 1890s Paris
Lambeth
4 deaths/1000
Southwark & Vauxhall
32 deaths/1000
Morbid matters: cholera
London July-Aug 1854 Both companies
3. Future plagues
The growth of literature
on new threats from
infection
SARS Bird flu
Beijing TB
AIDS
malariaDrug
resistance
Situations vacant opportunities for new pathogens
Viruses pose the greatest risk
08
6
11
6
24
10
60
18
72
0
10
20
30
40
50
an
ima
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hu
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an
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hu
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an
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an
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an
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viruses bacteria fungi protozoa worms
% s
pe
cie
s e
me
rgin
g number emerging
So
urc
e: T
aylo
r et
al
2001
0
20
40
60
80
100
0 2 4 6 8 10 12
Weeks
Per
cen
t su
rviv
ing
Beijing TB strains kill mice quickly
Control strain H37Rv
Beijing strains
Cin Exp Imm v133 p30 (2003)
Beijing/W TB strains tend to be in younger people in Viet Nam and Africa
0
20
40
60
80
<30 30-49 50+
Age group (yr)
Per
cen
t st
rain
s B
eijin
g
China
Viet Nam
3 Africancountries
Source: EID v12 p736 (2006)
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)
• 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
Evolution as seen in the ERMethicillin-resistant Staphylococcus aureus
(MRSA)
Brucellosis
E Coli O157
Multidrug resistant Salmonella
Plague
Ebola and CCHF
Influenza H5N1
Hantavirus
Lassa fever
Monkeypox
Nipah Hendra
NV-CJD
Rift Valley Fever
SARS CoV
VEE
Yellow fever
West Nile
Emerging and re-emerging zoonoses, 1996–2004
Cryptospporidiosis
Leptospirossis
Lyme Borreliosis
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
Model spread from Hong Kong
SARSSevere acute respiratory syndrome
Origin bats in China
Transmission among humans
Case fatality 4% – up to 1000 deaths
Confirmed Human and Animal H5N1 Infections since 2003 and Poultry Distribution
How many people will die in the next flu pandemic?
0
10
20
30
40
50
1918-20 1957-58 1968-70
Mill
ion
s o
f fl
u d
ea
ths Re-running the 3
pandemics of the 20th century
Spanish Flu H1N1 Asian Flu
H2N2
Hong Kong Flu
H3N2
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 AIDS25 years of AIDS
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
40
30
20
10
0
50
35
25
15
5
45
Mil
lio
n
1980 1985 1990 1995 2000 2005
1 2 3 45 6
8
9
11
12
13
14
1516
7
10
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
People People living living with with HIVHIV
Children Children orphaned orphaned by AIDS in by AIDS in sub-sub-Saharan Saharan AfricaAfrica
1.1
HIV infected in 2005: 40 million
Died in 2005: 3 million
Total deaths: 25 million
A global view of HIV infection38.6 million people [33.4‒46.0 million] living with HIV, 2005
15%+
5%+
1%+
0.5%+
0.1%+<0.1%+
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)