PATHOGENS AND PARASITES PLAGUES AND PANDEMICS

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An

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: S

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Ch

ing

Fu

20

30

40

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1300 1400 1500 1600 1700 1800 1900 2000

Lif

e ex

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tan

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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

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Where 60 million people die double burden of disease in low-income countries

0

2

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Communicable,pregnancy,

nutrition

Non-communicable

Injuries

Dea

ths

per

mill

ion

po

pu

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Low-middle income

High income

0

1

2

3

4

Low resp

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HIV/A

IDS

Diarrh

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Tubercu

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Mal

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Mea

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STDs ex

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Men

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B

Mill

ion

s o

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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

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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

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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

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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

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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

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24

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an

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viruses bacteria fungi protozoa worms

% s

pe

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s e

me

rgin

g number emerging

So

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aylo

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2001

0

20

40

60

80

100

0 2 4 6 8 10 12

Weeks

Per

cen

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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)