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PATHOGENS AND PARASITES PLAGUES AND PANDEMICS

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LONDON (Reuters Life!) Jan 03 --Hundreds of thousands of Britons…struck down by a highly infectious stomach virus… swept the country during the holiday period, doctors said… "stay at home, take paracetamol and drink plenty of fluids."

Norovirus Sweeps Through Britain

Avian influenza – situation in Indonesia – 5 February 2008Indonesia… 2 new cases of human H5N1 avian influenza infection… a 29-year-old female from BantenProvince… developed symptoms on 22 January… hospitalized on 28 January… died on 2 February…

• 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 PARASITESPLAGUES PANDEMICS

"…and it was so typically brilliant of you to have invited an epidemiologist"

1. Pathogens and people

2

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"

HumansFunctional cells (other than blood, neurons ) 1012

Bacteria (Bacterioides, Clostridium, Escherichia…)On skin 1012

In mouth 1010

In gut 1014

>1kg >1000 species>1000 × 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 TB infection protects against atopic disorders?

(tuberculin positive Japanese children)

0.1

1

10

asthma eczema asthma eczema

Odd

s ra

tio (9

5%C

L)

occurrence

remission

source: Science 275, 77 (1977)

3

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 So

urce

: Tay

lor e

t al 2

001

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 m

illio

n po

pula

tion

Low-middle incomeHigh income

0

1

2

3

4

Low resp

iratory

HIV/AID

S

Diarrh

oea

Tuberculosis

Malaria

Measle

s

Pertuss

is

Tetanus

STDs exc

HIV

Meningitis

*

Tropica

l dise

ases

Hepati

tis B

Mill

ions

of d

eath

s in

200

2

Infectious causes of death in ICD-10

13/60m deaths in 2002 from infections 86% caused by top 5

2. How pathogens spread, and why they

stick around

"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

4060

80

0 15 30 45 6075 90

0.1

1.0

10.0

100.0

1000.0

D

4

World of WarcraftCorrupted Blood

an Epidemic Disease Model

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)

Prop

ortio

n m

onth

s w

ith n

o ca

ses

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 30Population 2000 (millions)

Ann

ual g

row

th ra

te (m

illio

ns)

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

Cas

es in

out

brea

k

0

20

40

60

80

100

Vacc

ine

upta

ke (%

)

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 bacilliSource: Gutierrez

PLoS Pathogens Sep 2005

TB: a human disease for 3 million years?

5

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

Dea

ths

(10,

000s

/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

6

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. Plagues – current and emerging

The growth of literature

on new threats from

infection

Situations vacant opportunities for new pathogens

Viruses pose the greatest risk

08

6

11

6

24

10

60

1872

0

10

20

30

40

50

anim

als

hum

ans

anim

als

hum

ans

anim

als

hum

ans

anim

als

hum

ans

anim

als

hum

ans

viruses bacteria fungi protozoa worms

% s

peci

es e

mer

ging number emerging

Sour

ce: T

aylo

r et a

l 200

1

Syphilis probably came from the Americas

"The French disease"Italians et al

"The Italian disease"French

"Christian disease"Arabs

Syphilis Yaws

7

0

20

40

60

80

100

0 2 4 6 8 10 12Weeks

Perc

ent s

urvi

ving

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)

Perc

ent s

trai

ns B

eijin

g

China

Viet Nam

3 Africancountries

Source: EID v12 p736 (2006)

MRSA: Methicillin resistant Staphylococus aureus

MRSA: coming out (of hospital)

In hospital 58%In community (after health care) 27%In community (not after health care) 14%

Of ≈ 100,000 invasive MRSA infectionsOf ≈ 20,000 deaths (1 in 5, > HIV/AIDS)Source: Klevens JAMA v298, p1763, 2007

USA 2005 Soon UK?

Chikungunya"No Longer a Third World Disease"

"explosive outbreak in a remote corner of France…"

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

8

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

ions

of f

lu d

eath

s 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 advanceStockpile Tamiflu or Relenza - and hopeGet pneumococcus vaccination Consider taking statinsBecome indispensable Stock up emergency suppliesMove to a rich country

During a pandemicWash your hands

oftenAvoid people Don't flee the cityGet infected early –

if you dare

Source: New Sci, 7 Jan 2006

9

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

Mill

ion

1980 1985 1990 1995 2000 2005

1 2 3 45 6

8

9

11

12

13

1415

16

7

10

1 Immune deficiency in gay men in USA2 Acquired Immune Deficiency

Syndrome (AIDS) is defined3 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 subsub--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 infection33 million people [30‒36 million] living with HIV, 2007

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)