# Presentation: 580855

## NVAC Meeting February 9-10 2005

***NVAC Meeting****** ******February 9-10 2005***

**Polio Eradication: ****Global Progress and ****Post-Eradication Strategies**

## Purpose

**For NVAC to: **
**Be informed and aware of key decisions and progress toward polio eradication. **
**Support US participation in the global stockpile and response  and access to mOPV**
**Support WHO's efforts to stop the proliferation of wild polioviruses for IPV production and program to assess safety and efficacy of Sabin-IPV **
**Endorse plans for a NAS meeting on ****antiviral agents **

## Overview

**Status of global polio eradication**
**Post-eradication era: ****policies, strategies, products**

## Progress by End 2004

- _1988_
- 350 000 cases
- 125 countries

**Progress by End 2004**

- _2004_
- 1227 cases (as of 02 Feb 05)
- 6 + 11 countries

**Notes:**
In 1988, the World Health Assembly passed a resolution to eradicate polio globally.
At the time, over 350,000 children were paralysed by polio in more than 125 countries.
Since then, the initiative has become the largest public health initiative in history, as 20 million volunteers have been involved in immunizing over 2 billion children across the world.
Six countries in the world remain polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan and Egypt.  However, 5 African countries re-established polio transmission due to an imported poliovirus.

## Reported Polio Cases'Comparison of 2002–2004*

**Reported Polio Cases**

***Data as of  01 Feb 2005**

**Notes:**
In the past year Asia and the Middle east nearly halved its numbers of polio cases from 330 in 2003 to 187 in 2004 (at 25 January 2005):
(132 cases in India, 50 in Pakistan and 4 in Afghanistan, 1 importation saudi arabia). 
Polio transmission in Asia is now limited to just six of 51 major geographic areas (i.e. state, province or region).
However, a large outbreak in Africa has created a major challenge

## Impact of 'Intensification', AsiaFocal Transmission in 2004

**Impact of 'Intensification', Asia****Focal Transmission in 2004**

**Pakistan/Afghan**

**India**

**Notes:**
Pakistan: 8 large-scale SIAs, including 7 NIDs reaching 33 million children each time and 1 SNID reaching 16 million children.
Afghanistan: 8 large-scale SIAs, including 4 NIDs reaching 7 million children each time, 2 SNIDs reaching 5 million children each time, and 2 mop-ups.
India: 8 large-scale Supplementary Immunization Activities (SIAs), including 5 National Immunization Days (NIDs) reaching 170 million children each time; 1 Subnational Immunization Day (SNID) reaching 130 million children; and 2 mop-up campaigns in the highest-risk areas reaching 84 million children each time. India in particular has made much progress toward polio eradication in 2004. fewest # of cases ever. 

In sum, Asia now has the best opportunity ever to interrupt transmission of wild poliovirus in 2005.  The fullest commitment of political and health leaders at all levels is needed to reach every child during upcoming polio campaigns 

## Challenge: tenacious viral transmission and ‘fatigue’ (public and staff)
Planned response: 
Use of type 1 monovalent OPV in  Egypt and parts of India by May 2005 
‘Underserved’ strategy
Integration with other interventions

**Planned response: **
- Use of type 1 monovalent OPV in  **Egypt** and parts of *India* by **May 2005 **
- ‘Underserved’ strategy
- Integration with other interventions

**Prospects – Asia & Egypt**

**Notes:**
Polio partners and vaccine manufacturers started development of a monovalent oral polio vaccine (type-1), to accelerate the interruption of wild poliovirus transmission in Egypt and parts of India. Seroconverson rates after 1 dose of mOPV are approximately double that of trivalent OPV. 

## Impact of OPV Suspension, NigeriaPoliovirus Spread, 2004

**Impact of OPV Suspension, Nigeria****Poliovirus Spread, 2004**

**Nigeria ****781 cases**
**Transmission re-established in 5 polio-free countries**

** ****Wild virus type 1**

** ****Wild virus type 3**

**Notes:**
In Africa, a polio epidemic spread from northern Nigeria to a total of 13 previously polio-free countries in 2003-2004.  In Burkina Faso, the Central African Republic, Chad, Côte d'Ivoire and the Sudan, poliovirus transmission was re-established (i.e. the imported poliovirus circulated for over six months following initial importations).
The epidemic was caused by the suspension of immunization activities in northern Nigeria and exacerbated by low population immunity levels in neighbouring countries.  Following the resumption of polio immunization activities on 31 July in Kano, Nigeria, large, synchronized campaigns were conducted across 23 countries in west and central Africa, reaching more than 80 million children each time.
The major country risks include Nigeria and Niger (where polio transmission has never been stopped), the Sudan (where the late 2004 outbreak threatens the polio-free status of Ethiopia and the Democratic Republic of the Congo) and Côte d'Ivoire (where immunization activities have not resumed following civil unrest in November 2004). 

## Summary

**	*****India & Egypt:***** **will intensify activities & add mOPV1 to stop polio during the 2005 low season.

**	*****Africa:***** **rapid progress possible, if
- NID quality improves & is sustained,
- large-scale, synchronized activities continue,
- surveillance gaps are addressed.

## Post-OPV Cessation Policies/Products

**February 2005**

## Priority of Post-OPV Cessation Planning

**".. to manage the risk of paralytic disease caused by any polioviruses among current and future generations of children."***** **
**                 ****[Elimination of risk not possible!]**
***WER 2004;39:349-355.**

**January 2005**

## Outbreaks of Circulating Vaccine-Derived Polioviruses (cVDPVs)

**Philippines **
**2001**
**3 cases**

**Hispaniola **
** ****2000**
**22 cases**

**Madagascar**
**2002**
**4 cases**

**China**
**2004**
**2 cases**

**January 2005**

## iVDPV & Long-Term Excretion: WHO Registry

**24 iVDPVs, including 22 long term excretors **
**2 currently known to excrete **
**7 type 1, 16 type 2, 1 type 3**
**cases have been from:**** Europe (9), USA (7), Japan (1), Argentina (1), Kuwait (1), Taiwan (1), Iran (1), Ireland/Zimbabwe (1), Thailand (1)**

**January 2005**

## Risks of Polio After 'Eradication'

**VAPP ****	****	****2-4/million birth****	****cohort ****	****250-500****	****stable**
**iVDPV****	****	****24 identified    ****	**** ****	****<1 ****	****	****decreases**
**	****	****	** (**since 1963)**
**cVDPV****	****	****1* per year****	****	**** 10****	****	****increases**

**IPV sites****	****1 accident (1990s)****	**** <1****	****	****decreases**
**Lab accident   ****	****1 investigation  ****	**** ****	****NK****	****	****decreases**
**Deliberate****	****0****	****	****	****NK****	****	****unknown**

- 			**Frequency****	****	****Annual****	****Evolution           **
**Risk****	****	****   to date****	****	****burden ****	****over time**

***based on current understanding**

**After interruption of wild poliovirus,**
**continued use of OPV will compromise**
**the goal of a polio-free world.**
**	****	****	****	****	****	**
**	****	****	****  ****Expert Consultation on Vaccine-derived**
**	****	****	****Polioviruses (VDPVs), Sept 2003, Geneva**** **

**January 2005**

## Policy Decision

**Cessation of OPV for routine immunization**
**Consensus of September 2003 ****(endorsed in September 2004) meeting **
**Risks > benefits in absence of wild poliovirus**
**Expectation of countries and stakeholders**
**High opportunity & financial costs of continued OPV.**

**Timing****: must occur while **_**population immunity**_** & **_**surveillance sensitivity**_** (for cVPDV emergence) are high.**

**January 2005**

## Prerequisites for OPV Cessation

**Appropriate containment of **_***all***_*** *****polioviruses.**
**Global surveillance & notification capacity.**
**mOPV stockpile & response mechanism.**
**Coordinated cessation of OPV.**
**'Post OPV' immunization policy in place.**

**January 2005**

## Routine Immunization Policy 

**Discontinue OPV (as recommended)**
_**Remaining options**_**:**
**Discontinue all polio vaccination **
**Replace OPV with IPV ****(country, region or globally)**
**Develop a new polio vaccine**** **

**January 2005**

## Polio Vaccine Use Worldwide, 2004

**Polio Vaccine Use ****Worldwide, 2004**

**IPV only**

**IPV/OPV **

**OPV only**

- The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
- Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
-  WHO 2005. All rights reserved

## Current WHO Statement on IPV

_**Most important considerations**_**:**
**Risk of importation / spread of wild PV**
**Vaccination coverage ****(IPV mostly direct effects)**

**January 2005**

## Products Pursued & Rationale I

**mOPV**
**Finish ****eradication in most difficult areas ****(anticipate licensure in Spring 2005 for mOPV1)**
**Serve as principle ****stockpile ****vaccine**
**Antivirals**
**Clear**** chronic excretion among long-term excretors**
**Available for ****post-exposure ****prophylaxis**
**Option for ****outbreak control**** (example:  pandemic flu)**

**January 2005**

## Sabin-IPV
Facilitate containment
Serve as "warm-base" for restart OPV production
Minimize the proliferation of new wild poliovirus amplification sites
Facilitate the replacement of all wild poliovirus in vaccine production (longterm objective)
“The AACPE (AdHoc Advisory Committee on Polio Eradication) is encouraged by the prospect of a potentially effective IPV using Sabin poliovirus strains, and urges acceleration of studies to demonstrate safety and protective efficacy....”  (WER 2004, 79,401-8)

**Facilitate ****containment**
**Serve as ****"warm-base"**** for restart OPV production**
**Minimize the proliferation of new ****wild poliovirus amplification sites**
**Facilitate the ****replacement**** ****of all wild poliovirus in vaccine production (longterm objective)**
**“*****The AACPE (AdHoc Advisory Committee on Polio Eradication) is encouraged by the prospect of a potentially effective IPV using Sabin poliovirus strains, and urges acceleration of studies to demonstrate safety and protective efficacy....”  ******(WER 2004, 79,401-8)***

- Products Pursued & Rationale II

**January 2005**

## Timelines depend primarily on interruption of wild poliovirus.
Policy directions will be reviewed as new data becomes available.

**Policy directions will be reviewed as new data becomes available.**

**OPV Cessation Strategy**

**January 2005**

## Schematic: Risks & Timelines

**Schematic: Risks & Timelines**

**Main Risk**
*   **Years after last wpv*
**Containment**
**Vaccines**
**Surveillance**

- 0

- 1

- 2

- 4

- 5

- 3

**	****	****	****Implement '*****BSL3*****	****	****	*****/ polio'***** for WPVs**

**    ****'Dangerous pathogen' lab & surveillance practices**

## Summary/Conclusions

**OPV cessation prerequisite for ****maintaining eradication, elements:**
**Poliovirus detection & notification**
**Stockpile & emergency response**
**Long-term containment**
**National immunization policy decisions**
**Key is to **_**manage**_** the risks ****(no ‘risk free’ option)**

**January 2005**

## Purpose

**For NVAC to: **
**Be informed and aware of key decisions ****and progress toward polio eradication. **
**Support US participation in the global stockpile ****& response and access to mOPV**
**Support WHO's efforts to stop the proliferation of wild polioviruses for IPV production and program to assess safety and efficacy of Sabin-IPV **
**Endorse plans for a NAS meeting on ****antiviral agents **

## THANK YOU!

## EXTRA Slides-Polio Eradication Status

## Selected Key Milestones

**Short-term (24 months):**
**License monovalent OPV & establish response mechanism.**
**Limit sites of wild poliovirus amplification (incl. IPV sites).**
**Consensus on long-term containment (*****GAP ed. III*****).**
**Introduce *****'National Guidelines for OPV Cessation'*****.**
**Medium term (24-60 months):**
**Align surveillance/diagnostics with that of ****dangerous pathogens.**
**Long-term:**
**Promote use of Sabin strains only for IPV manufacture.**

**October 2004**

**January 2005**

## Ongoing Work

**Risks measurement & management**
- iVDPVs: prevalence, re-introduction risk, clearance strategies (IgG, antivirals)
- cVDPV: define highest risk areas & potential strategies (e.g. limited pulses, IPV)
- IPV sites: define biosecurity 'gains' with Sabin; for new producers
- Lab stocks: verify survey/inventory process;
- Stockpiles: size of mOPV stockpiles; role of IPV; restart capacity (5 year period)
**IPV introduction**
- define country expectations re future polio immunization
- model impact (esp. in terms of cVDPV emergence)
- determine whether specific conditions warrant a WHO IPV recommendation
- protective efficacy of Sabin-IPV

**January 2005**

## Potential World Health Assembly Resolutions (May 2005)

**OPV Cessation:**** **consensus on globally coordinated OPV cessation as key goal of the eradication initiative.
**Containment (future handling of polioviruses):**** **consensus on need* *for safe storage at secure biosafety levels for Sabin, vaccine-derived & wild polioviruses *after* OPV cessation.
**Outbreak Response (reintroduction of polioviruses):** consensus on the need*** ***for vaccine stockpile and international controls, & mechanism for responding to polio outbreak should one occur.

## Framework for National Guidelines for OPV Cessation

**Rationale for OPV Cessation**
**Containment activities for OPV Cessation**
**Surveillance *****before, during & after *****OPV Cessation**
**Stopping routine use of OPV**
**Polio vaccine stockpiles & outbreak response**
**Implications of IPV introduction**

**January 2005**

## Summary/Conclusions II

**Prevention of wild poliovirus amplification sites of ****paramount ****importance**
**Development of mOPV, antiviral agents, and Sabin-IPV is ****integral part**** of post-OPV cessation planning**

**January 2005**

## Show me the money....for 2005-2008

**2005 **
**Financial Resource Requirements:****	****	****$ 615m **
**Contributions (Received/Projected): ****	****$ 515m**
**Funding Gap: ****	****	****	****	****	****$ 100m**
**2006-2008**
**Financial Resource Requirements:****	****	****$ 805m**
**Stockpile: ****	****	****	****	****	****$ 250m**

## Sudan as of 18 Jan 05

**Sudan had 112 cases.**
**Undetected circulation for several years.**
**Four rounds of NIDs planned for the first half of 2005. **
**Recently negotiated days of tranquility so that all children could be reached.**
**Concern about spread to Ethiopia, Eritrea, Uganda, Kenya and other countries.**

## Challenge:
largest outbreak in recent history.
Suspension of activities in Cote d’Ivoire
Low population immunity in affected areas
Possible spread to Ethiopia, DRC and other parts of E. Africa
Response: 
New WHO/UNICEF team in Nigeria
Improved NID quality
Improved AFP surveillance
Involvement of religious and local leaders 

- largest outbreak in recent history.
- Suspension of activities in Cote d’Ivoire
- Low population immunity in affected areas
- Possible spread to Ethiopia, DRC and other parts of E. Africa
**Response:**** **
- New WHO/UNICEF team in Nigeria
- Improved NID quality
- Improved AFP surveillance
- Involvement of religious and local leaders

**Prospects – Africa**

## Challenges

**Funding gap – G8 and new donors**
**Gaps in quality – both SIAs and surveillance  **
**Security/conflicts – polio ceasefires**
**Burnout – recognition, incentives, staff support**
**Political commitment, particularly in India, Pakistan and Egypt**

## Conclusions and Recommendations of the Ad Hoc Advisory Committee on Poliomyelitis Eradication, 21-22 Sept, 2004

**Interrupting WPV transmission**
**Global program priorities**
**Enhancing the impact of SIAs**
**Measures to limit the international spread of wild poliovirus**
**Plans for globally coordinated cessation of use of OPV**

## Overview

**Overriding priority**
**Risks of poliovirus infection **
**Policy decision**
**Prerequisites**
**Products pursued & rationale**
**Summary & conclusions**

**January 2005**