Vaccine-derived Poliovirus Outbreaks Research Articles

Nutritional Status Link with Polioseronegativity Among Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Malnutrition is identified as a risk-factor for insufficient polioseroconversion in the context of a vaccine-derived polio virus (VDPV) outbreak prone region. To assess the prevalence of malnutrition and its link to poliovirus insufficient immunity, a cross-sectional household survey was conducted in the regions of Haut- Lomami and Tanganyika, DRC. In March 2018, we included 968 healthy children aged 6 to 59 months from eight out of 27 districts. Selection of study locations within these districts was done using a stratified random sampling method, where villages were chosen based on habitat characteristics identified from satellite images. Consent was obtained verbally in the preferred language of the participant (French or Swahili) by interviewers who received specific training for this task. Furthermore, participants contributed a dried blood spot sample, collected via finger prick. To assess malnutrition, we measured height and weight, applying WHO criteria to determine rates of underweight, wasting, and stunting. The assessment of immunity to poliovirus types 1, 2, and 3 through the detection of neutralizing antibodies was carried out at the CDC in Atlanta, USA. Of the study population, we found 24.7% underweight, 54.8% stunted, and 15.4% wasted. With IC95%, underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.96; [1.52-2.54]) were significantly associated with seronegativity to polioserotype 1. Underweight (OR=1.64; [1.20-2.24]) and the non-administration of vitamin A (OR=1.55; [1.20-2.01]) were significantly associated with seronegativity to polioserotype 2. Underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.80. [1.38-2.35]) were significantly associated with seronegativity to polioserotype 3. Underweight (OR=1.68; IC95% [1.10-2.57]) and the non-administration of vitamin A (OR=1.82; IC95% [1.30-2.55]) were significantly associated with seronegativity to all polioserotypes. This study reveals a significant association between underweight and polioseronegativity in children. In order to reduce vaccine failures in high-risk areas, an integrated approach by vaccination and nutrition programs should be adopted.

Poliovirus-Neutralizing Antibody Seroprevalence and Vaccine Habits in a Vaccine-Derived Poliovirus Outbreak Region in the Democratic Republic of Congo in 2018: The Impact on the Global Eradication Initiative.

Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6-47.0%), 41.1% (38.0-44.2%), and 38.0% (34.9-41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities-79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.

Poliovirus serological assay after the cVDPV1 outbreak in Papua New Guinea: a cross-sectional study from 2020 to 2021

In June 2018, a type 1 circulating vaccine-derived poliovirus (cVDPV1) outbreak was declared in Papua New Guinea (PNG), resulting in a total of 26 paralytic confirmed cases. Eight vaccination campaign rounds with bivalent oral poliovirus vaccine (bOPV) were carried out in response. Prevalence of neutralizing polio antibodies in children was assessed two years after the outbreak response was completed. We conducted a cross-sectional serological survey among children aged 6 months-10 years selected from six provinces in PNG to evaluate seroprevalence of neutralizing polio antibodies to the three poliovirus serotypes and analyse sociodemographic risk factors. We included 984 of 1006 enrolled children in the final analysis. The seroprevalence of neutralizing polio antibodies for serotype 1, 2 and 3 was 98.3% (95% CI: 97.4-98.9), 63.1% (95% CI: 60.1-66.1) and 95.0% (95% CI: 93.6-96.3), respectively. Children <1 year had significantly lower type 1 seroprevalence compared to older children (p<0.001); there were no significant differences in seroprevalence among provinces. PNG successfully interrupted transmission of cVDPV1 with several high coverage bOPV campaigns and seroprevalence remained high after two years. The emergence of cVDPV strains underscores the importance of maintaining high levels of routine immunization coverage and effective surveillance systems for early detection. World Health Organization through a Rotary International IPPC grant.

A circulating vaccine-derived poliovirus type 2 outbreak in a chronic conflict setting: a descriptive epidemiological study in South Sudan – 2020 to 2021

BackgroundIn this study, we describe the epidemiological profile of an outbreak of the circulating Vaccine Derived Polio Virus type 2 in South Sudan from 2020 to 2021.MethodWe conducted a retrospective descriptive epidemiological study using data from the national polio/AFP surveillance database, the outbreak investigation reports, and the vaccination coverage survey databases stored at the national level.ResultsBetween September 2020 and April 2021, 59 cases of the circulating virus were confirmed in the country, with 50 cases in 2020 and 9 cases in 2021. More cases were males (56%) under five (93%). The median age of the cases was 23.4 ± 11.9 months, ranging from 1 to 84 months. All states, with 28 out of the 80 counties, reported at least one case. Most of the cases (44, 75%) were reported from five states, namely Warrap (31%), Western Bahr el Ghazal (12%), Unity (12%), Central Equatoria (10%), and Jonglei (10%). Four counties accounted for 45.8% of the cases; these are Gogrial West with 12 (20%), Jur River with 5 (8.5%), Tonj North with 5 (8.5%), and Juba with 5 (8.5%) cases.The immunization history of the confirmed cases indicated that 14 (24%) of the affected children had never received any doses of oral polio or injectable vaccines either from routine or during supplemental immunization before the onset of paralysis, 17 (28.8%) had received 1 to 2 doses, while 28 (47.5%) had received 3 or more doses (Fig. 4). Two immunization campaigns and a mop-up were conducted with monovalent Oral Polio Vaccine type 2 in response to the outbreak, with administrative coverage of 91.1%, 99.1%, and 97% for the first, second, and mop-up rounds, respectively.ConclusionThe emergence of the circulating vaccine-derived poliovirus outbreak in South Sudan was due to low population immunity, highlighting the need to improve the country’s routine and polio immunization campaign coverage.

Strengthening immunization programs through innovative sub-national public-private partnerships in selected provinces in the Democratic Republic of the Congo

BackgroundLow immunization coverage rates in the Democratic Republic of Congo (DRC) have been reflective of challenges with vaccine access, support and delivery in the country. Motivated by measles and vaccine-derived polio virus (VDPV) outbreaks in 2016–17 and low vaccination rates, the provinces of Haut Lomami and Tanganyika were identified as pilot locations for an innovative approach focused on establishing a consortium of partners supporting local government. This approach was formalized through Memorandums of Understanding (MoUs) between the Bill and Melinda Gates Foundation and Provincial governments in 2018. A third province, Lualaba, established an MoU in 2021. MoU implementationThese MoUs were 5-year partnerships designed to aid provinces in meeting four key objectives: 80 % immunization coverage, management/elimination of polio/cVDPV outbreaks, improvement of vaccine accessibility, and transfer of immunization service management to provincial leadership. OutcomesDuring the MoU period, Haut-Lomami saw an increase in full immunization coverage, from 35.7 % (MICS 2018) to 88.9 % (VCS 2021–22), the highest in country. A sharp drop in percentage of zero-dose children was observed in the 3 provinces, confirming improved access to immunization services. Tanganyika saw initial improvement in full immunization coverage, followed by a drop in the VCS 2021–22 due to COVID-19 and healthcare worker strikes. Coverage improved in Tanganyika in the 2023 VCS. The 3 provinces increased their financial contributions to routine immunization and are now the top contributing provinces. While no cVDPV cases were recorded in 2020 and 2021, cVDPV1 and cVDPV2 outbreaks are afflicting the 3 provinces since 2022. ConclusionsUltimately, the provincial MoUs were successful in bolstering provincial autonomy and capacity building with the biggest success being a drop in zero-dose children. While not all objectives have been met, the MoU approach served as an innovative program for key aspects of strengthening routine immunization in the DRC.

Acute flaccid paralysis surveillance system data analysis, Pujehun, Sierra Leone, 2011-2020

The Acute Flaccid Paralysis (AFP) surveillance system was established to detect poliovirus and to measure progress toward Poliovirus eradication. Vaccine-derived poliovirus outbreaks have been reported worldwide in 2020, including in Sierra Leone. We analyzed AFP surveillance data to describe the distribution, epidemiological trend, and clinical characteristics of AFP cases. We analyzed secondary data of AFP cases in the Pujehun District for the period from 2011 to 2020. We collected data on key variables such as age, sex, clinical characteristics, outcome, non-AFP rate, stool adequacy, and non-Polio enteroviruses. We analyzed data using Microsoft Excel 2013 and Epi-Info 7 software. Results were reported in tables, graphs, and maps. A total of 60 AFP cases were reported with a median age of 3 years (range 0.7- 14), with no confirmed poliomyelitis. Under-five Children accounted for 46 (76.7%), with 27 females and 33 males. Of the sixty cases,17(28.3%) were hospitalized and 16(27%) were detected in the hospital. Ten (16.7%) cases were classified as non-Polio enteroviruses and 50 (83.3%) as negative. Sudden onset of paralysis was reported in 57 (96.6%) cases, paralysis progressed within 3 days in 44 (74.6%) cases, and 56 (94.6%) reported fever. Out of 33, the left legs 28 (84.9%) were the most affected sites. Majority of the cases, 35(58.1%) had received five and more doses of the Oral Polio vaccine. The stool adequacy was 54(90%) and the non-AFP rate was above 2.0 except in 2017 when it was 1.8. Of the 14 chiefdoms,12 (86%) met the minimum AFP reporting target (1/100,000 &lt; 15 years’ population). None of the AFP cases were confirmed as Poliovirus in Pujehun District. Case detection and reporting rate were high except for two chiefdoms. We recommended maintaining the AFP surveillance system in the district and replicate the strategies used to other districts.

Sensitive poliovirus detection using nested PCR and nanopore sequencing: a prospective validation study

Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct molecular detection and nanopore sequencing (DDNS) of poliovirus in stool samples is a promising fast method. Here we report prospective testing of stool samples from suspected polio cases, and their contacts, in the Democratic Republic of the Congo between 10 August 2021 and 4 February 2022. DDNS detected polioviruses in 62/2,339 (2.7%) of samples, while gold standard combination of cell culture, quantitative PCR and Sanger sequencing detected polioviruses in 51/2,339 (2.2%) of the same samples. DDNS provided case confirmation in 7 days (median) in routine surveillance conditions. DDNS enabled confirmation of three serotype 2 circulating vaccine-derived poliovirus outbreaks 23 days (mean) earlier (range 6–30 days) than the gold standard method. The mean sequence similarity between sequences obtained by the two methods was 99.98%. Our data confirm the feasibility of implementing DDNS in a national poliovirus laboratory.

Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3

Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence1–3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.

Surveillance To Track Progress Toward Poliomyelitis Eradication — Worldwide, 2021–2022

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of wild poliovirus (WPV) cases has declined by >99.9%, and WPV serotypes 2 and 3 have been declared eradicated (1). By the end of 2022, WPV type 1 (WPV1) transmission remained endemic only in Afghanistan and Pakistan (2,3). However, during 2021-2022, Malawi and Mozambique reported nine WPV1 cases that were genetically linked to Pakistan (4,5), and circulating vaccine-derived poliovirus (cVDPV) outbreaks were detected in 42 countries (6). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity allowing reversion to neurovirulence and can cause paralysis. Polioviruses are detected primarily through surveillance for acute flaccid paralysis (AFP), and poliovirus is confirmed through stool specimen testing. Environmental surveillance, the systematic sampling of sewage and testing for the presence of poliovirus, supplements AFP surveillance. Both surveillance systems were affected by the COVID-19 pandemic's effects on public health activities during 2020 (7,8) but improved in 2021 (9). This report updates previous reports (7,9) to describe surveillance performance during 2021-2022 in 34 priority countries.* In 2022, a total of 26 (76.5%) priority countries met the two key AFP surveillance performance indicator targets nationally compared with 24 (70.6%) countries in 2021; however, substantial gaps remain in subnational areas. Environmental surveillance expanded to 725 sites in priority countries, a 31.1% increase from the 553 sites reported in 2021. High-quality surveillance is critical to rapidly detect poliovirus transmission and enable prompt poliovirus outbreak response to stop circulation. Frequent monitoring of surveillance guides improvements to achieve progress toward polio eradication.

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2021-December 2022.

Circulating vaccine-derived poliovirus (cVDPV) outbreaks* can occur when oral poliovirus vaccine (OPV, containing one or more Sabin-strain serotypes 1, 2, and 3) strains undergo prolonged circulation in under-vaccinated populations, resulting in genetically reverted neurovirulent virus (1,2). Following declaration of the eradication of wild poliovirus type 2 in 2015 and the global synchronized switch from trivalent OPV (tOPV, containing Sabin-strain types 1, 2, and 3) to bivalent OPV (bOPV, containing types 1 and 3 only) for routine immunization activities† in April 2016 (3), cVDPV type 2 (cVDPV2) outbreaks have been reported worldwide (4). During 2016-2020, immunization responses to cVDPV2 outbreaks required use of Sabin-strain monovalent OPV2, but new VDPV2 emergences could occur if campaigns did not reach a sufficiently high proportion of children. Novel oral poliovirus vaccine type 2 (nOPV2), a more genetically stable vaccine than Sabin OPV2, was developed to address the risk for reversion to neurovirulence and became available in 2021. Because of the predominant use of nOPV2 during the reporting period, supply replenishment has frequently been insufficient for prompt response campaigns (5). This report describes global cVDPV outbreaks during January 2021-December 2022 (as of February 14, 2023) and updates previous reports (4). During 2021-2022, there were 88 active cVDPV outbreaks, including 76 (86%) caused by cVDPV2. cVDPV outbreaks affected 46 countries, 17 (37%) of which reported their first post-switch cVDPV2 outbreak. The total number of paralytic cVDPV cases during 2020-2022 decreased by 36%, from 1,117 to 715; however, the proportion of all cVDPV cases that were caused by cVDPV type 1 (cVDPV1) increased from 3% in 2020 to 18% in 2022, including the occurrence of cocirculating cVDPV1 and cVDPV2 outbreaks in two countries. The increased proportion of cVDPV1 cases follows a substantial decrease in global routine immunization coverage and suspension of preventive immunization campaigns during the COVID-19 pandemic (2020-2022) (6); outbreak responses in some countries were also suboptimal. Improving routine immunization coverage, strengthening poliovirus surveillance, and conducting timely and high-quality supplementary immunization activities (SIAs) in response to cVDPV outbreaks are needed to interrupt cVDPV transmission and reach the goal of no cVDPV isolations in 2024.

Epidemiology of type 2 vaccine-derived poliovirus outbreaks between 2016 and 2020.

The number and geographic breadth of circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks detected after the withdrawal of type 2 containing oral polio vaccine (April 2016) have exceeded forecasts.Using Acute Flaccid Paralysis (AFP) investigations and environmental surveillance (ES) data from the Global Polio Laboratory Network, we summarize the epidemiology of cVDPV2 outbreaks. Between 01 January 2016 to 31 December 2020, a total of 68 unique cVDPV2 genetic emergences were detected across 34 countries. The cVDPV2 outbreaks have been associated with 1596 acute flaccid paralysis cases across four World Health Organization regions: 962/1596 (60.3%) cases occurred in African Region; 619/1596 (38.8%) in the Eastern Mediterranean Region; 14/1596 (0.9%) in Western-Pacific Region; and 1/1596 (0.1%) in the European Region. As the majority of the cVDPV2 outbreaks have been seeded through monovalent type 2 oral poliovirus vaccine (mOPV2) use in outbreak responses, the introduction of the more stable novel oral poliovirus vaccine will be instrumental in stopping emergence of new cVDPV2 lineages.

Real-time prediction model of cVDPV2 outbreaks to aid outbreak response vaccination strategies.

Circulating vaccine-derived poliovirus outbreaks are spreading more widely than anticipated, which has generated a crisis for the global polio eradication initiative. Effectively responding with vaccination activities requires a rapid risk assessment. This assessment is made difficult by the low case-to-infection ratio of type 2 poliovirus, variable transmissibility, changing population immunity, surveillance delays, and limited vaccine supply from the global stockpile. The geographical extent of responses have been highly variable between countries. We develop a statistical spatio-temporal model of short-term, district-level poliovirus spread that incorporates known risk factors, including historical wild poliovirus transmission risk, routine immunization coverage, population immunity, and exposure to the outbreak virus. We find that proximity to recent cVDPV2 cases is the strongest risk factor for spread of an outbreak, and find significant associations between population immunity, historical risk, routine immunization, and environmental surveillance (p<0.05). We examine the fit of the model to type 2 vaccine derived poliovirus spread since 2016 and find that our model predicts the location of cVDPV2 cases well (AUC=0.96). We demonstrate use of the model to estimate appropriate scope of outbreak response activities to current outbreaks. As type 2 immunity continues to decline following the cessation of tOPV in 2016, outbreak responses to new cVDPV2 detections will need to be faster and larger in scope. We provide a framework that can be used to support decisions on the appropriate size of a vaccination response when new detections are identified. While the model does not account for all relevant local factors that must be considered in the overall vaccination response, it enables a quantitative basis for outbreak response size.

Emergence of vaccine-derived poliovirus type 2 after using monovalent type 2 oral poliovirus vaccine in an outbreak response, Philippines.

ObjectiveIn response to an outbreak of circulating vaccine-derived poliovirus (cVDPV) type 2 in the Philippines in 2019–2020, several rounds of supplementary immunization activities using the monovalent type 2 oral poliovirus vaccine (OPV) were conducted for the first time in the Western Pacific Region. After use of the monovalent vaccine, the emergence of vaccine-derived poliovirus unrelated to the outbreak virus was detected in healthy children and environmental samples. This report describes the detection of this poliovirus in the Philippines after use of the monovalent type 2 OPV for outbreak response.MethodsWe describe the emergence of vaccine-derived poliovirus unrelated to the outbreak detected after supplementary immunization activities using the monovalent type 2 OPV. This analysis included virus characterization, phylogenetic analyses and epidemiological investigations.ResultsThree environmental samples and samples from six healthy children tested positive for the emergent vaccine-derived poliovirus. All isolates differed from the Sabin type 2 reference strain by 6–13 nucleotide changes, and all were detected in the National Capital Region and Region 4, which had conducted supplementary immunization activities.DiscussionSince the 2016 removal of type 2 strains from the OPV, vaccine-derived poliovirus outbreaks have occurred in communities that are immunologically naive to poliovirus type 2 and in areas with recent use of monovalent OPV. To prevent the emergence and further spread of cVDPV type 2, several interventions could be implemented including optimizing outbreak responses by using the monovalent type 2 OPV, accelerating the availability of the novel type 2 OPV, strengthening routine immunization using inactivated polio vaccine and eventually replacing OPV with inactivated poliovirus vaccine for routine immunization.

Emerging challenges to realizing global polio eradication and their solutions

Background: The Global Polio Eradication Initiative (GPEI) promised to eradicate polio by 2000, yet the disease remains endemic in 2 countries. The current threat of resurgence in countries with low vaccine coverage and circulating vaccinederived poliovirus (cVDPV) outbreaks due to oral polio vaccine warrants a strategy review. Aims: To review the performance of the GPEI from a context based in Pakistan, identifying threats to success and suggesting strategy modifications to help achieve eradication. Methods: This was a desk review of the effectiveness of GPEI that was launched in 1988 to eradicate polio by 2000. Subsequent failure to eradicate led to multiple iterations in strategy and planning documents. These documents were reviewed alongside relevant literature to explore the reasons for failure and emergence of cVDPV. Results: GPEI has been effective in reducing the global polio disease burden by &gt; 99%, but it remains endemic in Pakistan and Afghanistan. cVDPV has caused multiple outbreaks since 2000, and caused 7 times more cases than wild poliovirus (WPV) globally in 2020. The Polio Eradication and Endgame Strategic Plan 2013–2018 aimed to eradicate WPV and cVDPV simultaneously. In 2019, Pakistan saw an upsurge in WPV amid an outbreak of cVDPV infection that continued throughout 2020. Wild polio eradication was not realized and the country was unable to transition to inactivated polio vaccine as predicted in the strategic plan. Conclusion: Over 20 countries now report cVDPV outbreaks and many others are at risk. A country-specific modified strategy is required to eradicate WPV and cVDPV simultaneously, more so in endemic countries.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2020-June 2021.

As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021)† (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).

Safety and Immunogenicity of Two Novel Type 2 Oral Poliovirus Vaccine Candidates Compared With Monovalent Type 2 Oral Poliovirus Vaccine in Children and Infants: Two Clinical Trials

There is an increasing incidence of paralytic poliomyelitis cases because of circulating vaccine-derived polioviruses over the past 3 years. The person-to-person transmission of circulating vaccine-derived polioviruses that are neurovirulent are primarily responsible for this emergence of these outbreaks; the World Health Organization has designated type 2 circulating vaccine-derived polioviruses as a Public Health Emergency of International Concern.Two novel oral poliovirus vaccines (OPVs), OPV2-c1 and OPV2-c2, were tested for safety and immunogenicity in infants and children. These 2 novel poliovirus vaccines had genetic modifications introduced to enhance the stability of the Sabin attenuations and reduce the risk of reversion to neurovirulence. A previous study in healthy adults was conducted.This study was a phase 2 study with low and high doses of 2 novel OPV2 candidates in Panama through a multicenter, partly masked randomized study. In the phase 2 study, children received 2 high doses of novel OPV2-c1 or novel OPV2-c2 28 days apart. Infants (at 18–22 weeks of age) received 1 low dose or high dose of novel OPV2-c1 or novel OPV2-c2; randomly selected subsets (n = 50) of each group received a second dose 28 days later. Parents monitored and reported adverse events postvaccination. Type 2 poliovirus neutralizing antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days postvaccination. The primary objective was the safety in all participants and noninferiority of the novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants.In the novel OPV2 study, 47 children received the OPV2-c1 vaccine, and 53 received the OPV2-c2 vaccine as their first dose. A total of 97 of 100 children received a second dose; 45 children obtained the OPV2-c1 vaccine, and 52 received the novel OPV2-c2 vaccine. A total of 574 infants received the first dose of the novel OPV2 vaccine. A total of 36% of children (17 of 47) after the OPV2-c1vaccine and 26% of children (14 of 53) after the OPV2-c2 vaccine reported adverse events, consisting of loss of appetite, crying, fever, and irritability. There were 9 serious adverse events after OPV2-c1 and 13 after OPV2-c2 noted postvaccination (mostly pneumonia or bronchiolitis; 1 death from severe pneumonia), but none were believed to be causally associated with the vaccine. Infants also experienced crying, irritability, fever, and vomiting. The authors reported no consistent pattern of laboratory abnormalities or changes in laboratory assessments in both infants and children. Evaluable seroconversion rates were 94% to 100% after 1 to 2 doses in the novel OPV2 groups. The low-dose and high dose OPV2-c1 and the high dose OPV2-c2 met noninferiority criterion. Almost all infants who received either high dose OPV2-c1 or OPV2-c2 had shedding of type 2 virus in stools at day 7.The novel OPV 2 candidates appeared to be safe and immunogenic in children and infants in Panama. These candidates may represent a mechanism to decrease transmission of circulating neurovirulent type 2 vaccine-derived polioviruses.In the study, the authors report both results with the novel OPV2 vaccine candidates and a baseline study with monovalent Sabin OPV2 before cessation of administration. Most doses were administered to infants who experienced mostly transient and mild adverse effects. Noninferiority criterion was met with the high dose and low-dose OPV2-c1 and high dose OPV2-c2 vaccines. These novel candidates potentially represent a mechanism for immunity against type 2 polioviruses and the OPV2-c1 vaccine was listed under the World Health Organization Emergency Use for use against type 2 circulating vaccine-derived poliovirus outbreaks. With further larger studies, researchers will shed further light on safety, tolerability, and immunogenicity.

Seroprevalence of hepatitis B virus infection markers among children in Ukraine, 2017

BackgroundBefore hepatitis B vaccine (HepB) introduction, level of endemicity of hepatitis B virus (HBV) in Ukraine was estimated as intermediate but the prevalence of HBV infection markers has not been measured in population-based serosurveys. Coverage with 3 doses of HepB, introduced in 2002, was 92%-98% during 2004–2007 but declined to 21%-48% during 2010–2016. To obtain data on HBV prevalence among children born after HepB introduction, we tested specimens from a serosurvey conducted in Ukraine in 2017, following circulating vaccine-derived poliovirus outbreak in 2015, among birth cohorts eligible for polio immunization response. MethodsThe serosurvey was conducted in Zakarpattya, Sumy, and Odessa provinces, and Kyiv City, targeting 2006–2015 birth cohorts. One-stage cluster sampling in the provinces and stratified simple random sampling in Kyiv were used for participant selection. All participants were tested for antibodies against HBV core antigen (anti-HBc). Anti-HBc-positive children were tested for HBV surface antigen (HBsAg). We also obtained information on HepB vaccination status for all children. ResultsOf 4,596 children tested, 81 (1.8%) were anti-HBc-positive and eight (0.2%) were HBsAg-positive. HBsAg prevalence was 0.7% (95% confidence interval, 0.3%-1.4%) in Zakarpattya, 0.1% (0.0%-0.4%) in Sumy, 0% (0.0%-03%) in Odessa, and 0.1% (0.0%-0.8%) in Kyiv. Across survey sites, the proportion of recipients of ≥ 3 HepB doses was 53%-80% in the 2006–2009 cohort and 28%-59% in the 2010–2015 cohort. ConclusionHBV prevalence among children in surveyed regions of Ukraine in 2017 was low, including in Zakarpattya—the only site above the 0.5% European Regional target for HBsAg seroprevalence. However, HepB vaccination was suboptimal, particularly among children born after 2009, resulting in large numbers of unvaccinated or incompletely vaccinated children at risk of future HBV infection. HepB coverage should be increased to further reduce HBV transmission among children in Ukraine and achieve regional and global hepatitis B control/elimination targets.

Real-time monitoring of a circulating vaccine-derived poliovirus outbreak immunization campaign using digital health technologies in South Sudan.

Introductionthe use of digital health technologies and geographical information systems (GIS) in the conduct of immunization campaigns had proven to be a success story, and is gaining acceptance towards improving supervision, accountability, and real-time access to quality information. The demand for real-time information by policymakers and stakeholders in the polio eradication programme is increasing towards ensuring a world free from all polioviruses. This study aims to develop a tool that monitor and evaluate the circulating vaccine-derived poliovirus (cVDPV) campaign processes in real-time using open data kits (ODK) to collect data, analyze and visualize using an interactive dashboard in Power BI, towards improving timeliness and completeness of data reporting and providing real-time quality information to stakeholders.Methodselectronic checklists were developed using open data kits (ODK) and uploaded onto android-based smartphones for data collection during a round of cVDPV outbreak response immunization. Supervisors were deployed to the field and the checklists were utilized at both stages of the campaign activities. A Power BI data visualization tool was used for reporting, analysis, and monitoring the activities of the campaign.Resultsan interactive dashboard was developed, providing real-time information that supports stakeholders during the campaign processes with improved timeliness and completeness of data reporting. The usage of the tool during the campaign enhanced close supervision, and increased transparency in data availability and accessibility by all partners.Conclusionthe study had shown that real-time information has significantly improved the smooth conduct of the immunization campaign processes through identifying gaps, and challenges in the field and can be utilized in similar resource settings including complex and humanitarian. It has demonstrated the capability of mobile phones using ODK for data collection and linked to a Power BI dashboard for enhanced supervision and transparency, and we encourage further studies to assess the effects of the tools on the campaign results.

Environmental Surveillance Complements Case-Based Surveillance of Acute Flaccid Paralysis in Polio Endgame Strategy 2019-2023.

The Polio Endgame Strategy 2019-2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of emergence for vaccine-derived poliovirus (VDPV) or wild poliovirus (WPV). We reviewed the impact of the case-based acute flaccid paralysis (AFP) surveillance (1991 to 2018) and environmental surveillance (2011 to 2018) in polio eradication in Shandong province of China. Clinical characteristics of AFP cases and enterovirus (EV) investigation of research samples were assessed. During the period, 10,224 AFP cases were investigated, and 352 sewage samples were collected. The nonpolio AFP rate sustained at over 2.0/100,000 since 1997. Of 10,224 cases, males and young children experienced a higher risk of severe diseases, and 68.5% suffered lower limb paralysis. We collected 1,707 EVs from AFP cases, including 763 polioviruses and 944 nonpolio enteroviruses (NPEVs). No WPV was isolated since 1992. The AFP surveillance showed high sensitivity in detecting 143 vaccine-associated paralytic poliomyelitis (VAPP) cases and 6 VDPVs. For environmental surveillance, 217 (61.6%) samples were positive for poliovirus, and altogether, 838 polioviruses and 2,988 NPEVs were isolated. No WPV was isolated in environmental surveillance, although one VDPV2 was identified. Phylogenetic analysis revealed environmental surveillance had the capacity to detect a large scope of NPEVs. The case-based AFP surveillance will be indispensable for detecting VAPP cases and VDPV circulation in countries using oral polio vaccine. Environmental surveillance is advantageous in identifying EV circulation and responding to ongoing circulating VDPV outbreaks and should be expanded to complement the AFP surveillance.IMPORTANCE Interrupting wild poliovirus transmission and stopping circulating vaccine-derived poliovirus (cVDPV) outbreaks have been proposed as two global goals by the World Health Organization in the Global Polio Eradication Initiative (GPEI). This analysis, based on the 28-year acute flaccid paralysis (AFP) surveillance and 8-year environmental surveillance, provides continued high-quality surveillance performance in achieving the GPEI and detecting the circulation of enterovirus. Given the ongoing cVDPV outbreaks in the world, we present the surveillance capacity of environmental surveillance in capturing enterovirus circulation. The final poliovirus (especially VDPV) elimination has become increasingly complex, and the case-based AFP surveillance alone will lead to difficulties in early detecting dynamics of poliovirus transmission and monitoring the extent of environmental circulation. This study goes beyond previous work to provide a detailed comprehensive evaluation of the enterovirus surveillance and can be used to formulate a set of implementation plan and performance indicators for environmental surveillance.