Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine

Figures & data

Table 1. Categories of serotype 2 vaccine-derived poliovirus (VDPV2) events detected since the tOPV-bOPV switch and as of April, 2018, based on our subjective interpretation from limited information [48,49,54,55].

Category	Most likely source	Number of events detected in			Countries that detected the virus (number of independent events in country if not 1)	Number of AFP cases^b
		2016^a	2017	2018^b
cVDPV2	Pre-switch tOPV use	3^c	3	0	Nigeria (2), Pakistan, Democratic Republic of the Congo (DRC), Syria, Somalia, Kenya (0)^d	99
	Unauthorized post-switch tOPV use	0	1	0	DRC	2
	Post-switch authorized mOPV2 use	0	0	1	Nigeria	0
iVDPV2	Pre-switch tOPV use	6	3	0	Nigeria, Argentina, Egypt (3), West Bank and Gaza, Pakistan, Iran, Israel	5
aVDPV2, tail of ‘normal’ excretion distribution from OPV recipients and close contacts^e	Pre-switch tOPV use	8	0	0	India (2), Yemen, Pakistan (3), Afghanistan, Somalia	3
	Post-switch authorized mOPV2 use	0	13	0	Nigeria (9), Pakistan (4)	0
aVDPV2, unusually long transmission chain^e	Pre-switch tOPV use	2	1	0	Mozambique, Pakistan, India	1
	Post-switch authorized mOPV2 use	0	0	1^f	Nigeria	0
aVDPV2 in environment, likely from immunodeficient excretor	Pre-switch tOPV use	0	1	0	Australia	0
Other aVDPV2^g	Pre-switch tOPV use	1	0	0	Russia	0

Abbreviations: AFP, acute flaccid paralysis, aVDPV2, serotype 2 ambiguous vaccine-derived poliovirus; cVDPV2, serotype 2 circulating vaccine-derived poliovirus; DRC, Democratic Republic of the Congo; iVDPV2, serotype 2 immunodeficiency-associated vaccine-derived poliovirus; mOPV2, serotype 2 monovalent OPV; OPV, oral poliovirus vaccine, tOPV, trivalent OPV

^a Post-switch only (i.e. April or May 2016, depending on country)

^b Through April, 2018 (note that Somalia,, Nigeria, and DRC reported cVDPV2 cases during mid-2018)

^c Includes one event representing a renewed detection (environmental sample collected in March, 2016, but cVDPV2 notified days after the switch) of a persistent transmission of a cVDPV2 last detected in 2014 [49]

^d Kenya detected the cVDPV2 from Somalia in an environmental sample collected in March, 2018 [54]

^e Unusually long chain for transmission differentiated from ‘normal’ excretion distribution using a cut-off of six months since last known homotypic OPV use

^f Unauthorized post-switch mOPV2 or tOPV use also possible based on circumstantial information

^g Insufficient information available to establish nature of this event

Figure 1. Risks overtime, by serotype and source and defined as the probability of a detected outbreak that triggers an outbreak response (i.e. oSIAs) and based on runs that assumed OPV13 cessation in 2019 [38,40]. (a) All serotypes, triggering events only (including cVDPVs in the event of insufficient OPV intensification). (b) Serotype 1, triggering events and associated outbreaks. (c) Serotype 2, triggering events and associated outbreaks. (d) Serotype 3, triggering events and associated outbreaks.

Figure 2. Distribution of the number of polio cases after homotypic OPV cessation in the global model base case and analysis of stock-outs (to determine whether a stock-out would occur for a given iteration, we assumed an initial and desired filled stockpile level of 100 million doses with 400 million bulk doses and a one-year filling time.). (a) Serotype 1. (b) Serotype 2. (c) Serotype 3.

Figure 3. Conditional probability of uncontrolled outbreaks (i.e. more than 50,000 polio cases, which triggers an OPV restart in the global model [38]) as a function of the number of polio cases, based on the results from Figure 2.

Figure 4. Kinetics of 57 global model iterations that resulted in an OPV restart for different categories of times between homotypic OPV cessation and the initiating event that eventually triggers the OPV restart. (a) Global model base case, with IPV replacing mOPV for oSIAs from 5 years after homotypic OPV cessation (but no other changes in outbreak response strategy). (b) No oSIAs from 5 years after homotypic OPV cessation.

Table 2. Recommended strategies to minimize the risk of an OPV restart and qualitative impacts and resource needs.

Risk management strategy	Impacts	Level of internal (national) resources required	Level of external (GPEI or post-GPE international donors) resources required
Maintain high OPV coverage prior to OPV cessation	++++ serotype-specific population immunity to transmission prior to OPV cessation significantly impacts cVDPV risks and probability of OPV restart	+ for countries that currently conduct OPV SIAs	++ for countries that currently conduct OPV SIAs with external support
Coordinate OPV cessation globally	+++ critical to minimize post-OPV cessation cVDPV risks	+ for countries that currently use OPV	+ for coordination and monitoring
Perform aggressive outbreak response using mOPV in near-term after OPV cessation	+++ essential to stop transmission of live polioviruses post-OPV cessation to prevent OPV restart	++ for countries with post-OPV cessation outbreaks	+ for countries that currently conduct OPV SIAs with external support
Perform aggressive outbreak response using available resources in long-term after OPV cessation	+++ essential to stop transmission of live polioviruses post-OPV cessation to prevent OPV restart	++ for countries with post-OPV cessation outbreaks	+ for countries that currently conduct OPV SIAs with external support
Outbreak response poliovirus vaccine global stockpiles	+++ essential to support outbreak response activities		+ for OPV +++ for IPV long-term
Continue AFP surveillance	+++ essential through OPV-cessation	+ for countries that use AFP	++ for supporting the Global Polio Laboratory Network
Continue or add environmental surveillance (ES)	+ may help with confidence about no live poliovirus transmission, impact depends on design of the system	++ for countries that choose to include ES	++ for coordination and support of countries that require external resources
IPV use after cessation of last OPV serotype	+++ essential in countries that continue to produce poliovirus vaccines, store live polioviruses, and/or sustain potential iVDPVs + provides limited insurance that protects vaccinated individuals	++++ for 2-dose schedule	++++ for countries that require external support
Ensure containment	+++ essential to prevent the reintroduction of live polioviruses after OPV-cessation	+ for most countries +++ for countries that choose to maintain stocks of live polioviruses	++ for global coordination
Development of polio antiviral drugs	? depends on characteristics of products actually developed (e.g. efficacy, cost, ease of delivery, etc.)		++ to finish development
Prevention of iVDPV outbreaks by screening for PIDs	? depends on ability to detect iVDPVs and efficacy of polio antiviral drugs	++ for countries with potential iVDPV excretors	++ for countries that require external support
Develop new OPV and or IPV seed strains	? depends on characteristics of products actually developed		+++ for development

Jorba J, Diop OM, Iber J, et al. Update on vaccine-derived polioviruses - worldwide, January 2016-June 2017. MMWR Morb Mortal Wkly Rep. 2017;66(43):1185–1191.

 PubMed Web of Science ®Google Scholar

Etsano A, Damisa E, Shuaib F, et al. Environmental isolation of circulating vaccine-derived poliovirus after interruption of wild poliovirus transmission - Nigeria, 2016. Morbidity Mortality Weekly Report. 2016;65(30):770–773.

 PubMed Web of Science ®Google Scholar

World Health Organization. Polio this week as of 17 April 2018. 2018. Available from: http://polioeradication.org/polio-today/polio-now/this-week/

 Google Scholar

World Health Organization. Circulating vaccine-derived poliovirus. 2018. Available from: http://polioeradication.org/polio-today/polio-now/this-week/circulating-vaccine-derived-poliovirus/

 Google Scholar

Duintjer Tebbens RJ, Thompson KM. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential OPV cessation risk management strategy. Epidemiol Infect. 2017;145(2):217–226.

 PubMed Web of Science ®Google Scholar

Duintjer Tebbens RJ, Pallansch MA, Cochi SL, et al. An economic analysis of poliovirus risk management policy options for 2013-2052. BMC Infect Dis. 2015;15:389.

 PubMed Web of Science ®Google Scholar