Presentation from the European Scientific Conference on Applied Infectious Disease Epidemiology (ESCAIDE), published by the European Centre for Disease Prevention and Control (ECDC)

1. November 20101
Eradication of Smallpox: an unrepeatable success?

2. November 20102Smallpox: Variola Major
50% secondary attack rate20% -40% case fatality100% permanent facial scarring

3. November 20103
Certification of smallpox eradication, 1980

4. November 20104
Deaths (millions)
< 5 years old> 5 years old
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
ARI
AIDS
Diarrhoea
TB
Malaria
Measles
Smallpox 1967
Leading infectious causes of death in low-income countries2008 (estimates), with deaths from smallpox, 1967

5. November 20105
Factors that uniquely favoured smallpox eradication
Vaccineheat-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

6. November 20106
Differential diagnosis of smallpox
SMALLPOX
CHICKENPOX
At time of rash
2–4 days before the rash
FEVER
RASH
Pocks in several stages
Pocks at same stage
Appearance
Rapid
Slow
Development
More pocks on body
More pocks on arms & legs
Distribution
Usually absent
Usually present
On palms & soles
Very uncommon
More than 10%
DEATH

7. November 20107
Smallpox vaccine: an effective, yet imperfect tool1967 vaccination incidents in US alone:
•9 deaths
•4 permanent disabilities

8. November 20108
Smallpox, 1967: endemic in 31 countries or territoriesEndemic
Importation
Status of smallpox 1959
Probably endemic in 59 countries or territories

9. November 20109
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

10. November 201010
Intensified search: smallpox eradication, 1967–1978
WHO Smallpox Recognition Card

11. November 201011
Simplified containment: smallpox eradication, 1967–1978
Multipuncture vaccination by bifurcated needle

12. November 201012
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

13. November 201013Ethiopia
Somalia
International partnership: smallpox eradication, 1967–1978

14. November 201014
Smallpox, the last endemic infection, Somalia, October 1978

15. November 201015Smallpox eradication:a cost effective decrease in human death and suffering
In 1967
–cost in livesover 1.5 million
–cost to the worldUS$ 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

16. November 201016
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

17. November 201017
The Birmingham outbreak of smallpox, 1978: the last human cases

18. November 201018Smallpox virus: officially remains in 2 WHO Collaborating Centres
ATLANTA
KOLTSOVO
(SIBERIA)

19. November 201019
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

20. November 201020Human monkeypox 1970: identification of a new infection in humans

21. November 201021Human 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

22. November 201022
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

23. November 201023
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 occurring
Source: WHO

24. November 2010 24
0
10
20
30
40
50
60
70
80
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Confirmed
Suspect
1996 1997
Human monkeypox outbreak, Democratic
Republic of Congo, 1996 – 1997 (N-511)
Source: WHO

25. November 201025Human monkeypox, DRC 1970-2002: possible increase post vaccine cessation
0
50
100
150
200
250
300
350
4001970
1975
1980
1985
1990
1995
2000
Number of cases

26. November 201026
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 continue
Source: WHO

27. 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

28. November 201028
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 riskof monkeypox as compared with unvaccinated persons (0.78 vs. 4.05 per 10,000)
Improved surveillance and epidemiological analysis is neededto better assess the public health burden and develop strategies for reducing the risk of wider spread of infection .

29. November 201029
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

30. November 201030
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

31. November 201031
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

32. November 201032

33. November 201033WHO Fact Sheet on smallpox
WHO Smallpox Recognition Card

34. November 201034
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

35. November 201035
Human Monkeypox, USA, 2003

36. November 201036
Human monkeypox by date of onset,
Illinois, Indiana, Kansas, Missouri, Ohio
and Wisconsin, 2003

37. November 201037Lessons 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

38. November 201038
Severe Acute Respiratory virus, 2003
Suspected animals in the chain
of transmission
The SARS Coronavirus

39. November 201039
Live animal markets, Guangdong Province, 2003

40. November 201040
SARS Epidemic curve, China, 2002 -2003
Source: WHO

41. November 201041Index case for international spread, Hong Kong, 2003
Source: WHO
Global spread of SARS from Chinese medical doctotr,
Metropole Hotel, Hong Kong

42. November 201042Probable SARS transmission, flight CA112, March 2006

43. November 201043
SARS: cumulative number of probable cases worldwideas 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)
Korea Rep. (3)
Macao (1)
Philippines (14)
Indonesia (2)
Mongolia (9)
India (3)
Australia (5)
New Zealand (1)
Taiwan (686)
Russian Fed. (1)
Japan (1)

44. November 201044Strategies 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

45. November 201045
Probable cases of SARS by date of onset worldwide, 1 March –27 June 2003

46. November 201046
SARS, post-containment cases 2004
Singapore 1laboratory accidentrecovered, no human to 2004human transmission
Taiwan1laboratory accidentrecovered, no human to 2004human transmission
China >4laboratory accident(s) serious illness requiring 2004respirator, human to human transmission, deaths

47. November 201047Guinea worm, clinical manifestation and life cycle

48. November 201048
Surveillance/mapping of Guinea worm and water source

49. November 201049
Guinea worm eradication strategy
Filter drinking water
Copepodocidal water treatment

50. November 201050Reported Guinea worm, 1989 -2009 eradication tools

51. November 201051
No reservoir in nature
Easy-to-administerand 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

52. November 201052
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 Immunizationas 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 MAYWHA41.28 Global eradication of poliomyelitis by the year 2000

53. November 201053Specialised Reference Laboratory
Regional Reference Laboratory
National/ Sub-national LaboratoryClinical/laboratorysurveillance of acute flaccid paralysis

54. November 201054
Virus linked to common ancestor, West and Central Africa, 2004

55. November 201055Routine childhood immunization
Routine childhood immunization in national immunization programmes
High level advocacy and political engagement

56. November 2010 56
Region DPT3
estimate
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

57. November 201057
National immunization campaigns
2002: 100 countries

58. November 201058
2002: 100 countries
2002: 100 countriesNational and subnational camapaigns, polio endemic countries, 2006 -2009
National immunization campaigns

59. November 201059
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 poliovirusWild Poliovirus infected districts, 10 May –09 Nov 2010

60. November 201060
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 case
Country
Type
cVDPV
First case

61. November 201061
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)

62. November 201062
De novo synthesis of poliovirus: a risk to eradication?

63. November 201063
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

64. November 201064
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

65. November 201065
Evolution of Measles Control Goals
Mortality
Reduction
Regional
Elimination
?
Global
Eradication
Immunization
coverage