November 2010 1

Eradication of Smallpox:

an unrepeatable success?

November 2010 2

Smallpox: Variola Major

50%

secondary

attack rate

20% - 40%

case fatality

100%

permanent

facial scarring

November 2010 3

Certification of smallpox eradication,

1980

November 2010 4

Dea

ths

(mill

ion

s)

< 5 years old > 5 years old

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

ARI AIDSDiarrhoea TB Malaria Measles

Sm

allp

ox

1967

Leading infectious causes of death in low-income countries

2008 (estimates), with deaths from smallpox, 1967

November 2010 5

Factors that uniquely favoured

smallpox eradication

Vaccine heat-stable, inexpensive to manufacture, easy to administer, effective when used within 4 days of exposure, protects with single inoculation, and safe from birth

Clinical diagnosis easy: every infection clinically expressed, characteristic rash distribution

Transmission: mainly face to face by droplet, not through environmental contamination

Immunity: permanent with no carrier state

No animal reservoir: human infection only

November 2010 6

Differential diagnosis of smallpox

SMALLPOX CHICKENPOX

At time of rash2–4 days before the rashFEVER

RASHPocks in several stagesPocks at same stageAppearance

RapidSlowDevelopment

More pocks on bodyMore pocks on arms & legsDistribution

Usually absentUsually presentOn palms & soles

Very uncommonMore than 10%DEATH

November 2010 7

Smallpox vaccine: an effective, yet

imperfect tool

1967 vaccination incidents in US alone:

• 9 deaths

• 4 permanent disabilities

November 2010 8

Smallpox, 1967:

endemic in 31 countries or territories

Endemic

Importation

Status of smallpox 1959

Probably endemic in 59 countries

or territories

November 2010 9

Smallpox eradication:

field strategies, 1967–1978

Search:

– house to house

– market

– public gatherings/festivals

Containment:

– isolate patient

– vaccinate household

members/contacts

– vaccinate 30 neighbouring

households

– + vaccinate rest of village/

neighbouring villages

November 2010 10

Intensified search:

smallpox eradication, 1967–1978

WHO Smallpox Recognition Card

November 2010 11

Simplified containment:

smallpox eradication, 1967–1978

Multipuncture vaccination

by bifurcated needle

November 2010 12

Contribution for Global Eradication

Programme, 1967–1979 (US$ 300 million)

Countries/territories that contributed in cash or in-kind

to the WHO Special Account for Smallpox Eradication

Additional bilateral support:

Council of Arab Ministers Fund,

OXFAM, Tata Iron & Steel,

UNDP, UNICEF … and others

November 2010 13

Ethiopia

Somalia

International partnership:

smallpox eradication, 1967–1978

November 2010 14

Smallpox, the last endemic infection,

Somalia, October 1978

November 2010 15

Smallpox eradication: a cost effective

decrease in human death and suffering

In 1967

– cost in lives over 1.5 million

– cost to the world US$ 1,400 million

– cost for vaccination in USA alone US$ 92.8 million• 9 deaths

• 4 permanent disabilities

1967–1979

– cost of eradication: US$ 300 million

USA saves equivalent of its investment in WHO smallpox eradication

campaign every 26 days

November 2010 16

Lessons learned: smallpox eradication

Disease eradication saves lives and decreases human suffering; is

costly, especially at the end stage when disease occurs among those

populations with least access to health care; is of necessity “vertical”;

and cannot be completed without strong international partnership

November 2010 17

The Birmingham outbreak of smallpox, 1978:

the last human cases

November 2010 18

Smallpox virus: officially remains

in 2 WHO Collaborating Centres

ATLANTA

KOLTSOVO

(SIBERIA)

November 2010 19

Lessons learned: smallpox eradication

Disease eradication saves lives and decreases human suffering; is costly,

especially at the end stage when disease occurs among those populations with

least access to health care; is of necessity “vertical”; and cannot be completed

without strong international partnership

As long as live virus exists there is a chance of smallpox transmission to

humans

November 2010 20

Human monkeypox 1970: identification of

a new infection in humans

November 2010 21

Human monkeypox, 1970–1995

Zoonosis (squirrels)

Sporadic West and Central Africa

72% of cases animal contact / 3% secondary

attack rate

3 generations maximum, occurred in 8%

secondary outbreaks

Case fatality: 10%

Rare in persons above 15 years of age

November 2010 22

1980: is human monkeypox a threat to

smallpox eradication?

Humans with smallpox vaccination appeared protected against human monkeypox infection

Smallpox vaccination discontinued with certification Reservoir of virus in nature: rodents/monkeys in tropical

rainforests West and Central Africa Sporadic breaches in species barrier between rodents

and humans Secondary/tertiary transmission usually among

unvaccinated contacts

November 2010 23

Epidemiological investigation of monkeypox in

unvaccinated cohort, West and Central Africa, 1981-

1982

Serosurveys and facial scar surveys in children with no vaccination scar

– Côte d'Ivoire, Sierra Leone, Congo and Democratic Republic of Congo

– children < 15 years of age, verified absence of vaccination scar

10, 653 children without vaccination scar examined, blood specimen obtained

– no serum antibody to orthopox virus detected– no facial scarring observed

Conclusion: replacement epidemiology not occurringSource: WHO

November 2010 24

0

10

20

30

40

50

60

70

80

Feb Apr Ju

nAug O

ctDec Feb A

pr Jun

Aug O

ct

Confirmed

Suspect

1996 1997

Human monkeypox outbreak, Democratic

Republic of Congo, 1996 – 1997 (N-511)

Source: WHO

November 2010 25

Human monkeypox, DRC 1970-2002:

possible increase post vaccine cessation

0

50

100

150

200

250

300

350

400

1970 1975 1980 1985 1990 1995 2000

Nu

mb

er

of

ca

se

s

November 2010 26

Is human monkeypox epidemiology changing as

smallpox herd immunity wanes?

Indice 1970 - 1995 1996 - 2008

% infections > 15

years

Rare 85%

Index case with

animal contact

72% 23%

Secondary attack

rate

3% 46%

Transmission

chains

(generations)

3 generations from

8% of index cases

9 generations from

16% of index cases

Case fatality rate 10% 10%

Conclusion: intensified surveillance

must continueSource: WHO

November 2010 27

Monkeypox Virus, animal and human

isolates, 1958 - 1996

79-je-cncr

79-je-cncw-n1

77-0666

74-0226

79-0005

70-congo-8

97-katako-kombe

96-katako-kombe

85-squirrel-bumba

70-0187-liberia

70-0266-sierra leone

58-copenhagen

79-je-cpcr

79-je-cpcw-n1

61-mcconnell, wash, dc

68-chimp, paris

58-pvm-copenhagen-orig

65-utrecht, netherlands

61-wmp-mcconnell

78-3945-benin

71-0082-nigeria

1870-vac-lister

1975-var-bangladesh

1937-cpx-br ighton

63

100

100

63

63

98

10

branch length

Source: CDC

November 2010 28

Smallpox eradication: the risk continues

Major increase in human monkeypox incidence 30 years after smallpox

vaccination campaigns cease in the Democratic Republic of Congo

Anne W. Rimoin,ab1 Prime M. Mulembakani,c Sara C. Johnston,d James O. Lloyd

Smith,be Neville K. Kisalu,f Timothee L. Kinkela,c Seth Blumberg,be Henri A.

Thomassen,g Brian L. Pike,h Joseph N. Fair,h Nathan D. Wolfe,h Robert L. Shongo,i

Barney S. Graham,j Pierre Formenty,k Emile Okitolonda,c Lisa E. Hensley,d Hermann

Meyer,l Linda L. Wright,m and Jean-Jacques Muyemben

Source: Proc Natl Acad Sci U S A. 2010 September 14; 107(37): 16262–16267.

Comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006–07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence.

Vaccinated persons had a 5.21-fold lower risk of monkeypox as compared with unvaccinated persons (0.78 vs. 4.05 per 10,000)

Improved surveillance and epidemiological analysis is needed to better assess the public health burden and develop strategies for reducing the risk of wider spread of infection .

November 2010 29

Human Immunodeficiency Virus (HIV), first

identified in 1981: 2008 estimates

32 million infections living with HIV

2 million deaths

1984: smallpox vaccine cannot safely

be used in HIV-infected persons

November 2010 30

Lessons learned: smallpox eradication

Disease eradication saves lives and decreases human suffering; is costly,

especially at the end stage when disease occurs among those populations with

least access to health care; is of necessity “vertical”; and cannot be completed

without strong international partnership

As long as live virus exists there is the chance of smallpox transmission

The interaction of previously unrecognized infectious diseases may close

the window of opportunity to eradicate and/or threaten eradication

November 2010 31

Reports of virus outside WHO repositories 2000:

real or perceived threat?

Updated WHO guidance

Industry scaled up smallpox vaccine production

Industrialized countries stockpiled smallpox vaccine/vaccinia immune globulin

Intensified research on new, safer vaccines, anti-virals and diagnostics in USA and Russia

November 2010 32

November 2010 33

WHO Fact Sheet on smallpox

WHO Smallpox Recognition Card

November 2010 34

Lessons learned: smallpox eradication

Disease eradication saves lives and decreases human suffering; is costly, especially at the end stage when disease occurs among those populations with least access to health care; is of necessity “vertical”; and cannot be completed without strong international partnership

As long as live virus exists there is the chance of smallpox transmission

The interaction of previously unrecognized infectious diseases may close the window of opportunity to eradicate and/or threaten eradication

Vaccine stockpiles must be maintained post-eradication: justifying eradication on cost savings from stopping vaccination no longer feasible

November 2010 35

Human Monkeypox, USA, 2003

November 2010 36

Human monkeypox by date of onset,

Illinois, Indiana, Kansas, Missouri, Ohio

and Wisconsin, 2003

November 2010 37

Lessons learned: smallpox eradication

Disease eradication saves lives and decreases human suffering; is costly, especially at the

end stage when disease occurs among those populations with least access to health care;

is of necessity “vertical”; and cannot be completed without strong international partnership

As long as live virus exists there is the chance of smallpox transmission

The interaction of previously unrecognized infectious diseases may close the window of

opportunity to eradicate and/or threaten eradication

Vaccine stockpiles must be maintained post-eradication: justifying eradication on cost

savings from stopping vaccination no longer feasible

Research and development of safer vaccines and anti-viral or bacterial drugs must be

continued post-eradication/countries must be prepared

A system must be in place for continued surveillance, investigation and

containment post-eradication

November 2010 38

Severe Acute Respiratory virus, 2003

Suspected animals in the chain

of transmission

The SARS Coronavirus

November 2010 39

Live animal markets, Guangdong Province,

2003

November 2010 40

SARS Epidemic curve, China,

2002 - 2003

Source: WHO

November 2010 41

Index case for international spread,

Hong Kong, 2003

Source: WHO

Global spread of SARS from Chinese medical doctotr,

Metropole Hotel, Hong Kong

November 2010 42

Probable SARS transmission, flight CA112,

March 2006

November 2010 43

SARS: cumulative number of probable cases

worldwide as of 25 June 2003

(N = 8 460 cases, 808 deaths)

China (5327)

Singapore (206)

Hong Kong (1755)

Viet Nam (63)

Europe:

9 countries (37)

Thailand (9)

Brazil (3)

Malaysia (5)

South Africa (1)

Canada (250)

USA (75)

Colombia (1)

Kuwait (1)

South Africa (1)

Korea Rep. (3)

Macao (1)

Philippines (14)

Indonesia (2)

Mongolia (9)

India (3)

Australia (5)

New Zealand (1)

Taiwan (686)

Mongolia (9)

Russian Fed. (1)

Japan (1)

November 2010 44

Strategies that contained SARS

outbreaks, 2003

Case identification (active surveillance)

Case isolation/hospital infection control

Contact tracing

Surveillance/quarantine of contacts

International travel recommendations based on epidemiological

evidence

Element of good fortune: did not spread to countries with weakest

health systems

November 2010 45

Probable cases of SARS by date of onset

worldwide, 1 March – 27 June 2003

November 2010 46

SARS, post-containment cases

2004

Singapore 1 laboratory accident recovered, no human to

2004 human transmission

Taiwan 1 laboratory accident recovered, no human to

2004 human transmission

China >4 laboratory accident (s) serious illness requiring

2004 respirator, human to

human transmission,

deaths

November 2010 47

Guinea worm, clinical manifestation and life

cycle

November 2010 48

Surveillance/mapping of Guinea worm and

water source

November 2010 49

Guinea worm eradication strategy

Filter drinking water Copepodocidal water treatment

November 2010 50

Reported Guinea worm, 1989 - 2009

eradication tools

November 2010 51

No reservoir in nature

Easy-to-administer

and effective vaccine

Feasibility of eradication

proven in industrialized countries

Up to 600 – 1000 asymptomatic infections

for each child with paralysis

Polio eradication:

scientific basis for eradication

November 2010 52

World Health Assembly Resolution:

polio eradication by year 2000

1. DECLARES the commitment of WHO to the global eradication of poliomyelitis by

the year 2000;

2. EMPHASIZES that eradication efforts should be pursued in ways which strengthen

the development of the Expanded Programme on Immunization as a whole, fostering

its contribution, in turn, to the development of the health infrastructure and of primary

health care;

FORTY-FIRST WORLD HEALTH ASSEMBLY GENEVA, 2-13 MAY

WHA41.28 Global eradication of poliomyelitis by the year 2000

November 2010 53

Specialised Reference Laboratory

Regional Reference Laboratory

National/ Sub-national Laboratory

Clinical/laboratory

surveillance of acute flaccid paralysis

November 2010 54

Virus linked to common ancestor, West and

Central Africa, 2004

November 2010 55

Routine childhood immunization

Routine childhood immunization in

national immunization programmes

High level advocacy and

political engagement

November 2010 56

Region DPT3estimate

Type 1(60%)

Type 3(90%)

Global 73% 44% 65%

AFR 49% 29% 44%

AMR 89% 54% 80%

EMR 70% 42% 63%

EUR 93% 57% 83%

SEAR 68% 41% 61%

WPR 88% 53% 79%

Weak national immunization programmes

Routine Polio

Coverage, by Region

November 2010 57

National immunization campaigns

2002: 100 countries

November 2010 58

2002: 100 countries2002: 100 countries

National and subnational camapaigns,

polio endemic countries, 2006 - 2009

National immunization campaigns

November 2010 59

District infected with wild polio virus type 1

District infected with wild polio virus type 3

District infected with more than one type of wild poliovirus

Wild Poliovirus infected districts,

10 May – 09 Nov 2010

November 2010 60

Circulating Vaccine-Derived Polio Virus,

2000-2010

- -

* circulating Vaccine -derived poliovirus ( cVDPV ) is associated with 2 or more cases of AFP.

Cases with less than 10 nt genetically related to these outbreaks and cases of ambiguous V accine -derived Poliovirus ( aVDPV ) are not reported here.

Figures exclude VDPV from non -AFP source. Figures may include different chains of transmission .

Data in WHO/HQ as of 14 Sep 2010

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Nigeria VDPV 2 1 21 68 63 153 11 2-Jul-05 26-Jul-10

Afghanistan VDPV 2 0 3 10-Jun-10 2-Jul-10

DR Congo VDPV 2 14 4 5 22-Mar-08 30-Jun-10

Ethiopia VDPV 3 0 1 5 27-Apr-09 17-May-10

India VDPV 2 0 15 1 14-Jun-09 18-Jan-10

Somalia VDPV 2 1 4 0 29-Jun-08 24-Dec-09

Guinea*** VDPV 2 0 1 0 6-May-09

Ethiopia VDPV 2 3 1 0 4-Oct-08 16-Feb-09

Myanmar VDPV 1 1 4 9-Apr-06 6-Dec-07

Niger*** VDPV 2 2 28-May-06 3-Oct-06

Cambodia VDPV 3 1 1 26-Nov-05 15-Jan-06

Indonesia VDPV 1 46 9-Jun-05 26-Oct-05

Madagascar** VDPV 2 1 4 3 13-Jul-05

China VDPV 1 2 13-Jun-04 11-Nov-04

Philippines VDPV 1 3 15-Mar-01 26-Jul-01

DOR/Haiti VDPV 1 12 9 12-Jul-00 12-Jul-01

** Madgascar: two different outbreaks (2001/02 and 2005)

*** Niger 2006 and Guinea 2009 cVDPVs are linked to the Nigeria outbreak

Last caseCountry Type

cVDPV

First case

November 2010 61

Laboratory specimens: risk of poliovirus

infection after eradication

Polio virus widespread in laboratories throughout the world:

– Known wild poliovirus

– Known Sabin poliovirus

– Potential infectious materials (wild and Sabin poliovirus)

– Wild and Sabin poliovirus used in production of inactivated polio vaccine (IPV)

November 2010 62

De novo synthesis of poliovirus:

a risk to eradication?

November 2010 63

Yellow fever (2.0%)

Poliomyelitis (0.0%)

Measles (44.0%)

Neonatal tetanus (11.0%)

Whooping cough (17.0%)

Diphtheria (0.2%)

Haemophilus influenza

type b (26%)

Source: WHO

Mortality from vaccine preventable diseases,

2000, children<15 years

November 2010 64

Measles elimination strategy, 2001

Strengthen routine immunisation system

to increase measles vaccination coverage

of children 9 months of age

Conduct measles vaccination

campaign before season of

transmission on annual or less

frequent basis

November 2010 65

Evolution of Measles Control Goals

Mortality

Reduction

Regional

Elimination

?

Global

Eradication

Immunization

coverage