Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa

Abstract

Background: Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation.

Methods: We used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels.

Findings: Type 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81-93) in January-June, 2016 to 14% (9-37) in January-June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (<1-6%) in January-June, 2016 to 35% (24-47) in January-June, 2020. The probability of cVDPV2 poliomyelitis among children under 5 years was negatively correlated with OPV-induced and IPV-induced immunity and mOPV2 campaigns (adjusted odds ratio: OPV 0·68 [95% CrI 0·60-0·76], IPV 0·82 [0·68-0·99] per 10% absolute increase in estimated population immunity, mOPV2 0·30 [0·20-0·44] per campaign). Vaccination campaigns in response to cVDPV2 outbreaks have been smaller and slower than our model shows would be necessary to reduce risk to low levels, covering only 11% of children under 5 years who are predicted to be at risk within 6 months and only 56% within 12 months.

Interpretation: Our findings suggest that as mucosal immunity declines, larger or faster responses with vaccination campaigns using type 2-containing OPV will be required to stop cVDPV2 transmission. IPV-induced immunity also has an important role in reducing the burden of cVDPV2 poliomyelitis in Africa.

Funding: Bill & Melinda Gates Foundation, Medical Research Council Centre for Global Infectious Disease Analysis, and WHO.

Translation: For the French translation of the abstract see Supplementary Materials section.

Figure 1

Population immunity induced by oral and inactivated poliovirus vaccine among children under 5 years and the incidence of poliomyelitis caused by cVDPV2 in Africa (A) Weighted median population immunity against type 2 poliovirus induced by OPV2 in provinces with and without mOPV2 use and IPV and annual cVDPV2 cases (grey bars) at 6-month intervals between January, 2015, and June, 2020. Shaded ribbons indicate population-weighted IQR. (B) Provinces (first-level administrative divisions) conducting mOPV2 campaigns between April 2016, and June 2020, with shading corresponding to the date of implementation of the first campaign. cVDPV2=circulating type 2 vaccine-derived poliovirus. IPV=inactivated poliovirus vaccine. mOPV2=monovalent type 2 oral poliovirus vaccine. OPV=oral poliovirus vaccine.

Figure 2

Estimated population immunity against type 2 poliomyelitis in children under 5 years induced by OPV (A–B) or IPV (C–D) Nigeria inset enlarged to show detail. cVDPV2=circulating type 2 vaccine-derived poliovirus. IPV=inactivated poliovirus vaccine. OPV=oral poliovirus vaccine.

Figure 3

cVDPV2 risk (A) and number of mOPV2 SIAs required to reduce risk to low levels (B–D) in 2020 (A) Predicted risk of detecting a cVDPV2 case between July 1 and Dec 31, 2020. Risks were categorised as follows: very low, 97·5th percentile of risk less than threshold (probability 0·07); low, 50th percentile of risk less than threshold; medium, 50th percentile of risk greater than threshold; and high, 2·5th percentile of risk greater than threshold. (B) Number of mOPV2 SIAs (proportion of all children under 5 years targeted) delivered between Jan 1 and June 30, 2020. (C) Number of mOPV2 SIAs (single campaign covering all children under 5 years) required between Jan 1 and June 30, 2020, to reduce predicted risk in all locations to low or very low levels. (D) mOPV2 SIAs (proportion of all children under 5 years targeted) completed or planned between July 1 and Dec 31, 2020. Cases of circulating vaccine-derived type 2 poliomyelitis between July 1 and Dec 31, 2020 are shown as black crosses. Nigeria inset enlarged to show detail. cVDPV2=circulating type 2 vaccine-derived poliovirus. mOPV2=monovalent type 2 oral poliovirus vaccine. SIAs=supplementary immunisation activities.

Figure 4

Comparison of mOPV2 SIAs and predicted circulating vaccine-derived type 2 risk in children under 5 years, 2017–2020 cVDPV2=circulating type 2 vaccine-derived poliovirus. mOPV2=monovalent type 2 oral poliovirus vaccine. SIAs=supplementary immunisation activities. Low risk=low or very low risk. High risk=high or medium risk.