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GLOBAL POLIOMYELITIS ERADICATION
John F. Modlin, M.D.
Deputy Director, Polio Research
Professor of Pediatrics and Medicine
Geisel School of Medicine at Dartmouth
© 2014 Bill & Melinda Gates Foundation
September 24, 2016
Magnetic Resonance Images of the Spinal Cord.
DeVries AS et al. N Engl J Med 2011;364:2316-2323
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Po
lio
myeli
tis C
ases
IPV
licensed Reported Paralytic Poliomyelitis United States
1920 - 1960
In 1988, the World Health Assembly,
the governing body of the World Health
Organization (WHO) resolved to eradicate
poliomyelitis by the year 2000.
The Polio Partnership
10 million
volunteers
Private Sector
UNF, Gates Foundation
Aventis, De Beers
OPV Producers
Donor Governments
Australia, Austria, Belgium, Canada,
Denmark, Finland, France, Germany,
Ireland, Italy, Japan, Luxemburg, Malaysia,
Monaco, Netherlands, New Zealand, Norway,
Portugal, Spain, Sweden,
Russian Federation,
UK, USA
World Bank
European Union
UN Agencies
e.g. Office of the
Secretary General
Specialized Labs
CDC, ERC, NIV, RIVM
NIID, NIBSC, KTL, ISS
Instituts Pasteurs
NGOs
e.g. IFRC, ICRC, MSF
CPHA, CARE
WHO, Rotary
CDC, UNICEF
Health Ministries
& ICCs
Live Attenuated Oral Poliovirus Vaccine (OPV,
Sabin)
• attenuated by multiple passage in
primates and cell culture
• immune response depends on viral
replication
• transmitted to contacts
• efficacy
– high in developed countries
– lower in underdeveloped countries
• oral administration
• low cost
• rare cause of vaccine associated paralytic
poliomyelitis (VAPP)
The Polio Eradication Program
1. Routine Immunization 2.
Surveillance/LabNet
3. Polio Immunization
Campaigns (NIDs) 4. Mop-ups
© Bill & Melinda Gates Foundation | 19
© 2012 Bill & Melinda Gates Foundation | Pic courtesy : RTL-East , NPSP-WHO
22
GEOGRAPHIC COVERAGE IMPROVEMENT WAS SIMILAR REGARDLESS OF WHEN TRACKING BEGAN
Polio Programmatic – Presentation
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2015
2016
Po
lio c
ases
(th
ou
san
ds)
125 Polio Endemic
countries
Wild Poliovirus Eradication 1988-2016
1988 2014
Last type 2 polio
in the world
Last Polio Case in
India
Last Polio Case
in Africa
2016
3 Polio Endemic
countries
2 Polio Endemic
countries
Index WPV1 NIE-BOS-GZA-16-007 Onset: 13-Jul-2016
Contact WPV1 NIE-BOS-JRE-16-044
Onset: 6-Jul-2016
Borno WPV1 outbreak: location of 3 reported WPV1 cases
New WPV1 case NIE-BOS-MNG-16-010
Onset: 6 Aug 2016
THE LAST 1% IS THE HARDEST
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2009 2010 2011 2012 2013 2014 2015
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359
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Last Reservoirs in Unstable, Challenging Locations
• inaccessible due to insecurity, attacks from Islamist extremists
• religious and cultural opposition
Scientific Challenges
• Low trivalent OPV efficacy in many resource poor regions
• Emergence of vaccine derived polioviruses (VDPV)
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Per dose protective efficacy of tOPV
against type 1 poliovirus, India 1997-
2005
Location Vaccine efficacy (%)
(95% CI)
Rest of India 21 (15 - 27)
Bihar 18 (9 - 26)
Uttar
Pradesh
9 (6 - 13)*
Grassley N, et al. Science 2006.
* significantly different than rest of India, p < 0.01
India, 2008-2009
SEROCONVERSION AFTER 2 OPV DOSES
Sutter RW, et al. Lancet 2010 376.210.
cVDPV
• Sustained viral
replication via person-
to-person transmission
in a setting of
– low OPV coverage
– declining natural
immunity
iVDPV
• Sustained viral
replication in a person
with a primary B cell
immunodeficiency
syndrome
– rare event
Polio Eradication
VDPV “paradigms”
Risk associated with OPV: cVDPV outbreaks,
2000-2013
Type 2 (478 cases)
Type 1 (79 cases)
Type 3 (9 cases) 12 countries have had a
type 2 cVDPV persistent cVDPV outbreaks
Global Wild Poliovirus & cVDPV Cases1, Previous 12 Months2
1Excludes viruses detected from environmental surveillance. 2Onset of paralysis 14 Sep 2015 – 13 Sep 2016
Endemic country
Wild poliovirus type 1 cVDPV type 1
cVDPV type 2
Nigeria 06-Aug-16 3 NA 0
Guinea NA 0 14-Dec-15 5
AFR 06-Aug-16 3 14-Dec-15 5
Pakistan 27-Jul-16 33 NA 0
Afghanistan 11-Aug-16 16 NA 0
EMR 11-Aug-16 49 0
Lao People's
Democratic RepublicNA 0 11-Jan-16 10
WPR 0 11-Jan-16 10
Myanmar NA 0 05-Oct-15 1
SEAR 0 05-Oct-15 1
Global 11-Aug-16 52 11-Jan-16 16
NA: most recent case had onset of paralysis prior to rolling 12 months.
Country
Wild poliovirus cVDPV
Onset of most
recent case
Total
WPV1
Onset of most
recent case
Total
cVDPV
Data in WHO HQ as of 13 September 2016
Index WPV1 NIE-BOS-GZA-16-007 Onset: 13-Jul-2016
Contact WPV1 NIE-BOS-JRE-16-044
Onset: 6-Jul-2016 cVDPV2
23 March 2016
Borno WPV1 outbreak: location of 3 reported WPV1 cases
Accessibility status end-
August 2016
New WPV1 case NIE-BOS-MNG-16-010
Onset: 6 Aug 2016
- 24 mo old male / IDP family in Monguno, originally from Marte (adjacent district)
- onset of paralysis 6 August
- fever at onset, rapid progression of paralysis both arms
- Zero OPV dose
- WPV1 from both specimens
- closely related to Jere case (5 nt difference)
Monguno Ward
About 2 million population displaced with establishment of 34 Camps
New formal and Informal camps and IDPs settlements established. IDPs also settled in host communities
Huge influx of internally displaced population mostly in Maiduguri and adjacent areas
HALF OF BORNO HAS MISSED >50% OF ALL PLANNED POLIO CAMPAIGNS SINCE 2014
REGIONAL OUTBREAK RESPONSE • Five countries response: Nigeria, Chad,
Cameroon, Niger and CAR
• Epi, surveillance and immunity gaps, historical
export of virus from Nigeria and population
movement all factored into scope of response
• Coordination being managed by newly formed
Lake Chad Task Team in Ndjamena – multi-
agency, multi-country
• Shortfall of 140 million doses of bOPV; cuts to
planned SIA calendar and supplies from India
under negotiation; also potential to rescope
size of response after third round
• Outbreak cost = $104M (minus $22M in
planned SIAs for the region in Q3-4/16 and
$17M in budget space from reduced SIA
calendar)
Zone 1
10.8 million
children
August
Zone 2
41.5 million
children
Sept-Oct-Nov
Polio Virus Transmission Pakistan and Afghanistan
One Epidemiological Block- Last 6 months
45 Data as of 17 Aug 2016
Corridors of active transmission link
reservoirs on both sides of the border: • Nangarhar/Kunar - Khyber/Peshawar/Bannu
• Kandahar - Helmand/Balochistan (Quetta
block)
Most recent case onset:
AFG: 29 May ‘16
PAK: 18 June ‘16
© Bill & Melinda Gates Foundation | 47
PAKISTAN
255,983
609,316
16,576
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600000
700000
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Mar
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Jan
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Sep
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Jan
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Sep
2013 2014 2015
Ina
cc
es
sib
le c
hil
dre
n
Khyber-Peshawar-Nangarhar corridor
Quetta block – Greater Kandahar
Karachi
Virus geographically isolated Almost all children are accessible….
…. And fewer children are being missed
Quality of activities is improving
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0 20 40 60 80 100
KPK
FATA
Balochistan
Sindh
Punjab
% passed lots (Sept) % passed lots (Oct)
% passed lots (Nov) % passed lots (Dec)
% passed lots (Jan)
UC LQAS % Passed lots (0-3/60 missed children)
4-5 June 2015
Female Community Volunteers in high threat areas of Pakistan
4-5 June 2015
IMPROVING IMMUNITY STATUS OPV STATUS AMONG AFP CASES 6-59 MONTHS, BY TIER, 2010-2016
PO
LIO
CA
SE
S
NP
-AF
P
Tier 1 (Core) Tier 2 (High risk) Others
AFGHANISTAN – IMMUNITY UP AND IMPORTATIONS DOWN
Current Type 1 immunity (6-59 months)
11 11
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2013 2014 2015 2016
Importations from Pakistan by year
Based on modeled NP-AFP dose history
• Immunity gaps remain, particularly in South
• However, % of NPAFP cases in South <3 doses has
reduced from 10% in 2014 to less than 4% in 2016
Denotes areas with chronic inaccessibility for polio campaigns
DETERIORATING SECURITY
SOURCE: Protected Internet Exchange (PiX) Afghanistan SOURCE: Institute for the Study of War
Some reports indicate up to 50% of the country is controlled by insurgent groups
20
VDPV2 ACTIVE OUTBREAKS & EVENTS IN 2016
Myanmar – 5 tOPV SIAs* Last Case (15NT) = 10/5/15
Nigeria – 1 mOPV2 SIA* ES Positive Sample (20NT) = 3/23/16
Guinea – 3 tOPV SIAs* Last Case (23NT) = 12/14/15
Kenya – 1 tOPV SIA* ES Positive Sample (7NT) = 4/29/16
*since positive sample identified
DRC – 3 tOPV SIAs* ES Positive Sample (16NT) = 3/4/16
aVDPV case (6 NT) = 3/15/16
Syria – 0 tOPV SIA* Single Case (6NT) = 5/15/16
Senegal – 1 tOPV SIA* ES Positive Sample = 4/4/16
Egypt – 1 tOPV SIA* ES Positive Sample (7NT)= 4/26/16
Nigeria - cVDPV2 outbreak
• cVDPV type 2 found in the Environment
– Sampling site: Maiduguri, Borno state, Nigeria (in security level 5)
– Sequencing: 32nt diff from Sabin 2
• 20nt different from closest matching sequence (2013 Borno virus)
– Part of the ‘Chad emergence group cVDPV-A’ that circulated in Lake Chad area 2012-2014
– Most recent related viruses reported from Nigeria: November 2014, in Yobe and Kano (AFP cases)
– Duration of undetected circulation: Nov 2014 – March 2016
• Swift response conducted
– Release of mOPV2 authorized by WHO DG for three rounds
Environment surveillance March 2016
Most recent cVDPV2:
Maiduguri, Borno, collection date 23 Mar 16
59
Rukshar Khatoon West Bengal, India
January 2011
62
With continued use of tOPV, the number of cases related to vaccine-derived polioviruses will exceed those related to wild poliovirus.
Patel, et al. Expert Rev. Vaccines 2015 .1.online
GPEI STRATEGY FOR POLIO ERADICATION AND MAINTENANCE
2014 2017 2018 2020 2019 2016 2015
tOPV-bOPV
Switch
Use of IPV, bOPV & tOPV
Last use
of bOPV Global
Certification
bOPV + 1 dose IPV in routine
immunization
≥ 1 IPV doses
64
RISK OF cVDPV EMERGENCE POST-CESSATION
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Risk* of cVDPV2 Emergence in Countries: Tier 1 Countries or Risk Moderate to High
*The probability of any cVPDV2 emergences post-switch based on modeling cVDPV2 emergences as a function of type 2 immunity and population size and assuming declining risk over time (IDM modelling work).
Moderate Risk High Risk
10/5/2016 IPV introduction 66
Role of OPV post-eradication
Maintaining a stockpile of
monovalent OPVs (mOPV1,
mOPV2, mOPV3)
Using mOPVs to control outbreaks
of cVDPVs or re-introduction from a
manufacturing site, research facility,
or diagnostic laboratory
Stockpile of mOPVs would allow a
type-specific response for rapid
interruption of outbreak
POLIO
OUTBREAK post-
eradication
mOPV1
mOPV2
mOPV3
IPV DEMAND AND SUPPLY
M
50M
100M
150M
200M
250M
300M
350M
400M
450M
2016 2017 2018 2019 2020 2021 2022 2023 2024
Low Probability
Medium Probability
High Probability
Non-PQ China Supply
Current PQ Supply
Two Dose Demand
One Dose Demand
Note: Demand for all 124 introducing countries including China and India; includes RI only. Supply as of March 2016.
Source: GAVI SDF v.12, GPEI IPV supply update, 2016, BMGF analysis, February 2016.
From 2020, there should be adequate supply to meet even 2-dose IPV demand. While the probability of technical and
regulatory success (PTRS) varies across pipeline candidates, the future market is likely to be very competitive.
Global Certification
Doses/y
ear
67
A SAGE 2-dose
recommendation would require
an additional ~40-60M IPV
doses (beyond Sanofi’s and
SII’s current supply projections)
to meet demand from 2019 or
2020
Most likely new products to
come to market in this
timeframe and address this
potential shortage include a
new Sabin IPV manufacturer
and additional capacity from
existing manufacturers
The 2020+ IPV market is
forecast to turn more
competitive as new potential
suppliers enter, including
Intravacc tech transfer
recipients
© 2015 Bill & Melinda Gates Foundation |
CONFIDENTIAL
Microneedle patch application
requires minimal training
Vaccinator applies patch to patient
10 patches in a blister tray Vaccinator peels a patch from the tray
Patient wears patch for 10 min and discards
Dissolving Patch
• Dissolving polymer microneedles (~100 needles)
• No applicator needed
P1 P3 AAA
C G
A
U
G
G A A C G C G
C A A U G
C U
A G G C
A G C C U
A
C G C C
U G
C G
A C
G A
A C
C C A
G U U C C
A A
A
U G G C
A A U
C G C U
A U A
A
A
500
490
510
520
480
530 470
S15 dom V
P2
X
NOPV-2 CANDIDATES: MODIFIED IN SABIN 2 GENOMES
Codon Replacement Region:
40% Saturation of CpG Dinucleotides within
Synonymous Codons
cre
+ or 3Dpol
hifi & rec
mutations
S2/cre5/S15domV
“CpG40”
NIBSC, CDC, UCSF
5’ UTR
cre
The work we do is
complicated.
Why we do it is not.
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