Update on Vaccine-Derived Polioviruses — Worldwide, January 2017–June 2018

Since the Global Polio Eradication Initiative was launched in 1988 (1), the number of polio cases worldwide has declined by >99.99%. Among the three wild poliovirus (WPV) serotypes, only type 1 (WPV1) has been detected since 2012. This decline is attributable primarily to use of the live, attenuated oral poliovirus vaccine (OPV) in national routine immunization schedules and mass vaccination campaigns. The success and safety record of OPV use is offset by the rare emergence of genetically divergent vaccine-derived polioviruses (VDPVs), whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (2). Circulating VDPVs (cVDPVs) can emerge in areas with low immunization coverage and can cause outbreaks of paralytic polio. In addition, immunodeficiency-associated VDPVs (iVDPVs) can emerge in persons with primary immunodeficiencies and can replicate and be excreted for years. This report presents data on VDPVs detected during January 2017-June 2018 and updates previous VDPV summaries (3). During this reporting period, new cVDPV outbreaks were detected in five countries. Fourteen newly identified persons in nine countries were found to excrete iVDPVs. Ambiguous VDPVs (aVDPVs), isolates that cannot be classified definitively, were found among immunocompetent persons and environmental samples in seven countries.

Since the Global Polio Eradication Initiative was launched in 1988 (1), the number of polio cases worldwide has declined by >99.99%. Among the three wild poliovirus (WPV) serotypes, only type 1 (WPV1) has been detected since 2012. This decline is attributable primarily to use of the live, attenuated oral poliovirus vaccine (OPV) in national routine immunization schedules and mass vaccination campaigns. The success and safety record of OPV use is offset by the rare emergence of genetically divergent vaccine-derived polioviruses (VDPVs), whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (2). Circulating VDPVs (cVDPVs) can emerge in areas with low immunization coverage and can cause outbreaks of paralytic polio. In addition, immunodeficiency-associated VDPVs (iVDPVs) can emerge in persons with primary immunodeficiencies and can replicate and be excreted for years. This report presents data on VDPVs detected during January 2017-June 2018 and updates previous VDPV summaries (3). During this reporting period, new cVDPV outbreaks were detected in five countries. Fourteen newly identified persons in nine countries were found to excrete iVDPVs. Ambiguous VDPVs (aVDPVs), isolates that cannot be classified definitively, were found among immunocompetent persons and environmental samples in seven countries.
Global eradication of type 2 WPV (WPV2) was declared in 2015; type 3 WPV (WPV3) was last detected in 2012. The number of detected WPV1 cases has reached a historic low (22 cases in 2017 and 18 as of September 2018) in two of the three countries with endemic WPV1 transmission (Afghanistan and Pakistan); in Nigeria, WPV1 was last detected in September 2016. After the emergence of multiple cVDPV2 outbreaks during the preceding 15 years, in April 2016, all OPV-using countries switched from using trivalent OPV (tOPV; Sabin types 1, 2, and 3) to bivalent OPV (bOPV; Sabin types 1 and 3). To control and prevent cVDPV2 outbreaks, approximately 100 million doses of monovalent type 2 OPV (mOPV2) have been distributed in 11 countries (4). To maintain protection from poliovirus type 2 paralysis, 176 OPVusing countries have introduced at least 1 dose of injectable inactivated polio vaccine beginning in 2015.

Properties and Virologic Characterization of VDPVs
Poliovirus isolates are characterized by laboratories of the Global Polio Laboratory Network. VDPV screening is conducted using real-time reverse transcription-polymerase chain reaction nucleic acid amplification, followed by sequencing of the VP1 region. VDPVs are isolates that are >1% divergent (for PV1 and PV3) or >0.6% divergent (for PV2) in VP1 nucleotide sequences from the corresponding OPV strain (3). Starting August 1, 2016, use of the VDPV2 screening assay was discontinued, and all PV2 isolates have been sequenced. VDPVs are further classified as 1) cVDPVs, when evidence of person-to-person transmission in the community exists; 2) iVDPVs, when they are isolated from persons with primary immunodeficiencies; and 3) aVDPVs, when they are clinical isolates from persons with no known immunodeficiency and no evidence of transmission, or they are sewage isolates that are unrelated to other known VDPVs and whose source is unknown (2).

Detection of cVDPVs
During January 2017-June 2018, cVDPV circulation was detected in six countries, an increase of one since the previous reporting period (3) ( Figure 1); five countries reported cVDPV2 circulation (Democratic Republic of the Congo [DRC], Kenya, Nigeria, Somalia, and Syria); cVDPV1 was reported in Papua New Guinea (Table). Cases of cVDPV (in patients with acute flaccid paralysis [AFP]) continued to be identified from the previously reported (3) cVDPV2 outbreaks in Syria and DRC (5,6). No additional cases were reported from the cVDPV2 outbreaks first reported in Nigeria and Pakistan in 2016. New outbreaks were reported in DRC (three cVDPV2 emergences); Somalia (one cVDPV2 emergence and one cVDPV3 emergence) with linked cVPDV2 isolation in sewage in Kenya (7); Nigeria (two cVDPV2 emergences); and Papua New Guinea (one cVDPV1 emergence) (Table). During the reporting period, 113 cVDPV2 cases were detected (Table), including 74 in Syria, 33 in DRC, four in Nigeria, and two in Somalia. The large cVDPV2 outbreak in Syria (3) was apparently interrupted in 2017; the last reported cases had paralysis onset in September 2017. Three cVDPV1 cases were detected in Papua New Guinea, and three cVDPV3 cases were detected in Somalia (Table). Sixty-two cVDPVs were isolated from sewage sampling in environmental surveillance sites in Kenya, Nigeria, and Somalia. After June 2018, newly identified VDPVs linked to emergences during the reporting period were detected in all outbreak countries except Syria. During January 2017-June 2018, among 119 cVDPV cases, 113 (95%) were cVDPV2, which represented a serotype profile similar to that of the previous 12 years ( Figure 2).  Papua New Guinea. During April-June 2018, circulating VDPV1s were isolated from three patients with AFP and two contacts in the provinces of Easter Highlands and Morobe. Reported routine vaccine coverage at the subnational level has been low (50%) for years; bOPV outbreak response campaigns are ongoing.

Detection of aVDPVs
During January 2017-June 2018, the number of countries with detected aVDPVs decreased to seven from 11 described in the previous report (3) (Table). Among 28 detected aVDPVs, 23 were type 2 (aVDPV2) (predominantly after mOPV2 responses to cVDPV outbreaks), four were type 3 (aVDPV3), and one was type 1 (aVDPV1); 23 (82%) aVDPVs were isolated from environmental samples. Detection of aVDPVs in settings with <60% polio vaccination coverage might indicate a risk for cVDPV emergence and further spread. A highly divergent aVDPV2 (8.4% VP1 divergence) was isolated from an environmental sample collected in metropolitan Melbourne, Australia on November 21, 2017. This environmental isolate had genomic sequence characteristics compatible with iVDPVs.  WHO-United Nations Children's Fund coverage estimates, http://www.who.int/gho/immunization/poliomyelitis/en/. National data might not reflect weaknesses at subnational levels. § § Duration of cVDPV circulation was estimated from extent of VP1 nucleotide divergence from the corresponding Sabin OPV strain; duration of iVDPV replication was estimated from clinical record by assuming that exposure was from initial receipt of OPV; duration of aVDPV replication was estimated from sequence data. ¶ ¶ Not cumulative data.

Discussion
During January 2017-June 2018, the number of reported cVDPV outbreaks and the total number of reported cVDPV cases in these outbreaks increased from the January 2016-June 2017 reporting period (3); new cVDPVs were detected in DRC, Kenya, Nigeria, Papua New Guinea, and Somalia during the January 2017-June 2018 reporting period. Cases have continued to be identified in 2018 after this reporting period in DRC, Nigeria, Papua New Guinea, and Somalia.
The continued expansion of sewage sampling (244 sites in 41 countries) (8) has increased the frequency of detection of WPV, VDPV, and residual PV2 excretion after mOPV2 vaccination during outbreak responses. As of April 2018, the number of environmental sites in countries with recent active WPV transmission (Afghanistan, Nigeria, and Pakistan) increased from 21 at the end of 2011 to 153. Partially as a result of supplemental surveillance measures for VDPVs among patients with primary immunodeficiencies (9), the number of known iVDPV excretors has increased; the antiviral pocapavir has recently been used to treat iVDPV excretors under compassionate use protocols in three countries (Task Force for Global Health, personal communication, October 2018).
Gaps in immunity to poliovirus type 2 remain in highrisk areas and continue to increase with time after the 2016 tOPV-to-bOPV switch. Continued detection of VDPV2s in 2017 and into 2018 underscores the existence of substantial populations of children who missed PV2 immunization before the switch. Some cVDPV2 detections occurred in or US Department of Health and Human Services/Centers for Disease Control and Prevention near security-compromised areas (DRC, Somalia, and Syria), where surveillance quality is uncertain. Likewise, new type 1 and type 3 cVDPV outbreaks highlight the importance of maintaining high levels of poliovirus immunity against these serotypes, as well as sensitive AFP surveillance. During the reporting period, VDPV cases outnumbered WPV cases; however, documentation of eradication of WPV is required before global OPV use can cease. Cessation of all OPV use after certification of polio eradication will eliminate the risk for VDPV emergence.