Update on Wild Poliovirus Type 1 Outbreak - Southeastern Africa, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

Accelerated Immunodeficiency-associated Vaccine-derived Poliovirus Serotype 3 Sequence Evolution Rate in an 11-week-old Boy With X-linked Agammaglobulinemia and Perinatal Human Immunodeficiency Virus Exposure.

Primary B-cell immunodeficiencies are risk factors for the generation of vaccine-derived polioviruses. We report immunodeficiency-associated vaccine-derived poliovirus serotype 3 in an 11-week-old boy with X-linked agammaglobulinemia. Unique characteristics of this case include early age of presentation, high viral evolutionary rate, and the child's perinatal exposure to human immunodeficiency virus.

Update on Vaccine-Derived Poliovirus Outbreaks - Democratic Republic of the Congo and Horn of Africa, 2017-2018.

Widespread use of live attenuated (Sabin) oral poliovirus vaccine (OPV) has resulted in marked progress toward global poliomyelitis eradication (1). However, in underimmunized populations, extensive person-to-person transmission of Sabin poliovirus can result in genetic reversion to neurovirulence and paralytic vaccine-derived poliovirus (VDPV) disease (1). This report updates (as of February 26, 2019) previous reports on circulating VDPV type 2 (cVDPV2) outbreaks during 2017-2018 in the Democratic Republic of the Congo (DRC) and in Somalia, which experienced a concurrent cVDPV type 3 (cVDPV3) outbreak* (2,3). In DRC, 42 cases have been reported in four cVDPV2 outbreaks; paralysis onset in the most recent case was October 7, 2018 (2). Challenges to interrupting transmission have included delays in outbreak-response supplementary immunization activities (SIAs) and difficulty reaching children in all areas. In Somalia, cVDPV2 and cVDPV3 were detected in sewage before the detection of paralytic cases (3). Twelve type 2 and type 3 cVDPV cases have been confirmed; the most recent paralysis onset dates were September 2 (cVDPV2) and September 7, 2018 (cVDPV3). The primary challenge to interrupting transmission is the residence of >300,000 children in areas that are inaccessible for vaccination activities. For both countries, longer periods of surveillance are needed before interruption of cVDPV transmission can be inferred.

Diagnostic Assay Development for Poliovirus Eradication.

With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part in laboratory surveillance as the molecular detection method that can identify and distinguish wild and vaccine-like polioviruses isolated from acute flaccid paralysis cases or environmental sources. The need to detect new variants of WPV serotype 1 (WPV1) and the containment of all serotype 2 polioviruses (PV2) in 2015 required changes to the previous version of the method. The ITD version 5.0 is a set of six real-time reverse transcription-PCR (rRT-PCR) assays that serve as accurate diagnostic tools to easily detect and differentiate PV serotypes and genotypes. We describe the creation and properties of quantitation standards, including 16 control RNA transcripts and nine plaque-isolated viruses. All ITD rRT-PCR assays were validated using these standards, and the limits of detection were determined for each assay. We designed and pilot tested two new assays targeting recently circulating WPV1 genotypes and all PV2 viruses. The WPV1 assay had 99.1% specificity and 100% sensitivity, and the PV2 assay had 97.7% specificity and 92% sensitivity. Before proceeding to the next step in the global poliovirus eradication program, we needed to gain a better understanding of the performance of the ITD 5.0 suite of molecular assays and their limits of detection and specificities. The findings and conclusions in this evaluation serve as building blocks for future development work.

Stem Cell Transplant in Immune-deficiency-associated Vaccine-derived Poliovirus.

Patients with severe primary immunodeficiency are at risk for complications from live-attenuated vaccines. Here, we report a case of a vaccine-associated paralytic polio and Bacille Calmette-Guérin disease in a 6-month-old girl with severe combined immunodeficiency resulting from homozygous recombinant activating gene 1 deficiency. The patient was successfully treated with intravenous immunoglobulins and oral pocapavir for poliovirus, and antimycobacterial therapy for regional Bacille Calmette-Guérin disease, allowing stem cell transplant. Following transplantation, poliovirus type 3 with 13 mutations was detected from cerebrospinal fluid but not from stool, indicating ongoing viral evolution in the central nervous system despite pocapavir treatment. Clinical improvement and immune reconstitution allowed the patient to be successfully discharged with no further detection of poliovirus.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

Genetic and epidemiological description of an outbreak of circulating vaccine-derived polio-virus type 2 (cVDPV2) in Angola, 2019-2020.

After six years without any detection of poliomyelitis cases, Angola reported a case of circulating vaccine-derived poliovirus type 2 (cVDPV2) with paralysis onset date of 27 March 2019. Ultimately, 141 cVDPV2 polio cases were reported in all 18 provinces in 2019-2020, with particularly large hotspots in the south-central provinces of Luanda, Cuanza Sul, and Huambo. Most cases were reported from August to December 2019, with a peak of 15 cases in October 2019. These cases were classified into five distinct genetic emergences (emergence groups) and have ties with cases identified in 2017-2018 in the Democratic Republic of Congo. From June 2019 to July 2020, the Angola Ministry of Health and partners conducted 30 supplementary immunization activity (SIA) rounds as part of 10 campaign groups, using monovalent OPV type 2 (mOPV2). There were Sabin 2 vaccine strain detections in the environmental (sewage) samples taken after mOPV2 SIAs in each province. Following the initial response, additional cVDPV2 polio cases occurred in other provinces. However, the national surveillance system did not detect any new cVDPV2 polio cases after 9 February 2020. While reporting subpar indicator performance in epidemiological surveillance, the laboratory and environmental data as of May 2021 strongly suggest that Angola successfully interrupted transmission of cVDPV2 early in 2020. Additionally, the COVID-19 pandemic did not allow a formal Outbreak Response Assessment (OBRA). Improving the sensitivity of the surveillance system and the completeness of AFP case investigations will be vital to promptly detect and interrupt viral transmission if a new case or sewage isolate are identified in Angola or central Africa.

Sensitivity of the acute flaccid paralysis surveillance system for poliovirus in South Africa, 2016-2019.

Introduction. Global poliovirus eradication is a public health emergency of international concern. The acute flaccid paralysis (AFP) surveillance programme in South Africa has been instrumental in eliminating polioviruses and keeping the country poliovirus free.Gap statement. The sensitivity of surveillance for polioviruses by every African country is of global interest in the effort to ensure global health security from poliovirus re-emergence.Aim. To describe the epidemiology of polioviruses from AFP cases and environmental samples in South Africa and to report the performance of the AFP surveillance system for the years 2016-2019 against targets established by the World Health Organization (WHO).Methods. Stool specimens from AFP or suspected AFP cases were received and tested as per WHO guidelines. Environmental samples were gathered from sites across the Gauteng province using the grab collection method. Concentration was effected by the two-phase polyethylene glycol method approved by the WHO. Suspected polioviruses were isolated in RD and/or L20B cell cultures through identification of typical cytopathic effects. The presence of polioviruses was confirmed by intratypic differentiation PCR. All polioviruses were sequenced using the Sanger method, and their VP1 gene analysed for mutations.Results. Data from 4597 samples (2385 cases) were analysed from the years 2016-2019. Two cases of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) type 3 were detected in 2017 and 2018. A further 24 Sabin type 1 or type 3 polioviruses were detected for the 4 years. The national surveillance programme detected an average of 3.1 cases of AFP/100 000 individuals under 15 years old (2.8/100 000-3.5/100 000). The stool adequacy of the samples received was 53.0 % (47.0-55.0%), well below the WHO target of 80 % adequacy. More than 90 % of results were released from the laboratory within the turnaround time (96.6 %) and non-polio enteroviruses were detected in 11.6 % of all samples. Environmental surveillance detected non-polio enterovirus in 87.5 % of sewage samples and Sabin polioviruses in 12.5 % of samples.Conclusion. The AFP surveillance programme in South Africa is sensitive to detect polioviruses in South Africa and provided no evidence of wild poliovirus or VDPV circulation in the country.

Clearance of Immunodeficiency-associated Vaccine-derived Poliovirus Infection With Pocapavir.

Pocapavir exhibits antiviral activity against both polio and nonpolio enteroviruses. There is limited experience of the use of this investigational drug in young children with enteroviral infection. We describe the successful clearance of prolonged immunodeficiency-associated vaccine-derived type 3 poliovirus infection by pocapavir in an infant with underlying X-linked agammaglobulinemia.