Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomised, controlled trial.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was developed by modifying the Sabin strain to increase genetic stability and reduce risk of seeding new circulating vaccine-derived poliovirus type 2 outbreaks. Bivalent oral poliovirus vaccine (bOPV; containing Sabin types 1 and 3) is the vaccine of choice for type 1 and type 3 outbreak responses. We aimed to assess immunological interference between nOPV2 and bOPV when administered concomitantly. METHODS: We conducted an open-label, non-inferiority, randomised, controlled trial at two clinical trial sites in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomly assigned (1:1:1) using block randomisation, stratified by site, to receive nOPV2 only, nOPV2 plus bOPV, or bOPV only, at the ages of 6 weeks, 10 weeks, and 14 weeks. Eligibility criteria included singleton and full term (≥37 weeks' gestation) birth and parents intending to remain in the study area for the duration of study follow-up activities. Poliovirus neutralising antibody titres were measured at the ages of 6 weeks, 10 weeks, 14 weeks, and 18 weeks. The primary outcome was cumulative immune response for all three poliovirus types at the age of 14 weeks (after two doses) and was assessed in the modified intention-to-treat population, which was restricted to participants with adequate blood specimens from all study visits. Safety was assessed in all participants who received at least one dose of study product. A non-inferiority margin of 10% was used to compare single and concomitant administration. This trial is registered with ClinicalTrials.gov, NCT04579510. FINDINGS: Between Feb 8 and Sept 26, 2021, 736 participants (244 in the nOPV2 only group, 246 in the nOPV2 plus bOPV group, and 246 in the bOPV only group) were enrolled and included in the modified intention-to-treat analysis. After two doses, 209 (86%; 95% CI 81-90) participants in the nOPV2 only group and 159 (65%; 58-70) participants in the nOPV2 plus bOPV group had a type 2 poliovirus immune response; 227 (92%; 88-95) participants in the nOPV2 plus bOPV group and 229 (93%; 89-96) participants in the bOPV only group had a type 1 response; and 216 (88%; 83-91) participants in the nOPV2 plus bOPV group and 212 (86%; 81-90) participants in the bOPV only group had a type 3 response. Co-administration was non-inferior to single administration for types 1 and 3, but not for type 2. There were 15 serious adverse events (including three deaths, one in each group, all attributable to sudden infant death syndrome); none were attributed to vaccination. INTERPRETATION: Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2, but not for types 1 and 3. The blunted nOPV2 immunogenicity we observed would be a major drawback of using co-administration as a vaccination strategy. FUNDING: The US Centers for Disease Control and Prevention.

Progress Toward Polio Eradication - Worldwide, January 2020-April 2022.

In 1988, the World Health Assembly established the Global Polio Eradication Initiative (GPEI). Since then, wild poliovirus (WPV) cases have decreased approximately 99.99%, and WPV types 2 and 3 have been declared eradicated. Only Afghanistan and Pakistan have never interrupted WPV type 1 (WPV1) transmission. This report describes global progress toward polio eradication during January 1, 2020-April 30, 2022, and updates previous reports (1,2). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* Five WPV1 cases were reported from Afghanistan and Pakistan in 2021, compared with 140 in 2020. In 2022 (as of May 5), three WPV1 cases had been reported: one from Afghanistan and two from Pakistan. WPV1 genetically linked to virus circulating in Pakistan was identified in Malawi in a child with paralysis onset in November 2021. Circulating vaccine-derived polioviruses (cVDPVs), with neurovirulence and transmissibility similar to that of WPV, emerge in populations with low immunity following prolonged circulation of Sabin strain oral poliovirus vaccine (OPV) (3). During January 2020-April 30, 2022, a total of 1,856 paralytic cVDPV cases were reported globally: 1,113 in 2020 and 688 in 2021, including cases in Afghanistan and Pakistan. In 2022 (as of May 5), 55 cVDPV cases had been reported. Intensified programmatic actions leading to more effective outbreak responses are needed to stop cVDPV transmission. The 2022-2026 GPEI Strategic Plan objective of ending WPV1 transmission by the end of 2023 is attainable (4). However, the risk for children being paralyzed by polio remains until all polioviruses, including WPV and cVDPV, are eradicated.

Progress Toward Polio Eradication - Worldwide, January 2019-June 2021.

In 1988, when the Global Polio Eradication Initiative (GPEI) began, polio paralyzed >350,000 children across 125 countries. Today, only one of three wild poliovirus serotypes, type 1 (WPV1), remains in circulation in only two countries, Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2019-June 30, 2021 and updates previous reports (1,2). In 2020, 140 cases of WPV1 were reported, including 56 in Afghanistan (a 93% increase from 29 cases in 2019) and 84 in Pakistan (a 43% decrease from 147 cases in 2019). As GPEI focuses on the last endemic WPV reservoirs, poliomyelitis outbreaks caused by circulating vaccine-derived poliovirus (cVDPV) have emerged as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations (3). In 2020, 32 countries reported cVDPV outbreaks (four type 1 [cVDPV1], 26 type 2 [cVDPV2] and two with outbreaks of both); 13 of these countries reported new outbreaks. The updated GPEI Polio Eradication Strategy 2022-2026 (4) includes expanded use of the type 2 novel oral poliovirus vaccine (nOPV2) to avoid new emergences of cVDPV2 during outbreak responses (3). The new strategy deploys other tactics, such as increased national accountability, and focused investments for overcoming the remaining barriers to eradication, including program disruptions and setbacks caused by the COVID-19 pandemic.

Progress Toward Polio Eradication - Worldwide, January 2018-March 2020.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2018-June 2019.

Certification of global eradication of indigenous wild poliovirus type 2 occurred in 2015 and of type 3 in 2019. Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988 and broad use of live, attenuated oral poliovirus vaccine (OPV), the number of wild poliovirus cases has declined >99.99% (1). Genetically divergent vaccine-derived poliovirus* (VDPV) strains can emerge during vaccine use and spread in underimmunized populations, becoming circulating VDPV (cVDPV) strains, and resulting in outbreaks of paralytic poliomyelitis.† In April 2016, all oral polio vaccination switched from trivalent OPV (tOPV; containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV; containing types 1 and 3) (2). Monovalent type 2 OPV (mOPV2) is used in response campaigns to control type 2 cVDPV (cVDPV2) outbreaks. This report presents data on cVDPV outbreaks detected during January 2018-June 2019 (as of September 30, 2019). Compared with January 2017-June 2018 (3), the number of reported cVDPV outbreaks more than tripled, from nine to 29; 25 (86%) of the outbreaks were caused by cVDPV2. The increase in the number of outbreaks in 2019 resulted from VDPV2 both inside and outside of mOPV2 response areas. GPEI is planning future use of a novel type 2 OPV, stabilized to decrease the likelihood of reversion to neurovirulence. However, all countries must maintain high population immunity to decrease the risk for cVDPV emergence. Cessation of all OPV use after certification of polio eradication will eliminate the risk for VDPV emergence.

Progress Toward Polio Eradication - Worldwide, January 2017-March 2019.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, transmission of wild poliovirus (WPV) has been interrupted in all countries except Afghanistan, Nigeria, and Pakistan. WPV type 2 (WPV2) was declared eradicated in 2015; WPV type 3 has not been detected since 2012 (1). After the certification of the eradication of WPV2, a global switch from trivalent oral poliovirus vaccine (tOPV, containing vaccine virus types 1, 2, and 3) to bivalent oral poliovirus vaccine (bOPV, containing types 1 and 3) was completed in April 2016. Nigeria last reported WPV type 1 (WPV1) cases in 2016. This report describes global progress toward poliomyelitis eradication during January 1, 2017-March 31, 2019, and updates previous reports (1,2). Afghanistan and Pakistan reported their lowest annual number of WPV cases (22) in 2017; however, 33 WPV1 cases were reported in 2018. During January-March 2019 (as of May 3), 12 WPV1 cases had been reported worldwide, four more than the eight reported during the corresponding period in 2018. The occurrence of polio cases caused by circulating vaccine-derived poliovirus (cVDPV) is rare and occurs where oral poliovirus vaccine (OPV) coverage has been low and vaccine virus reverts to neurovirulence (3). Eight countries (Democratic Republic of the Congo [DRC], Indonesia, Mozambique, Niger, Nigeria, Papua New Guinea, Somalia, and Syria) reported 210 cVDPV cases during 2017-2019 (as of May 3). Reaching children during supplemental immunization activities (SIAs), accessing mobile populations at high risk, and variations in surveillance performance represent ongoing challenges. Innovative efforts to vaccinate every child and strengthen coordination efforts between Afghanistan and Pakistan will help achieve eradication. For cVDPV outbreak responses to promptly stop transmission, intensified programmatic improvements are needed to make the responses more effective and limit the risk for generating future outbreaks.

Progress Toward Polio Eradication - Worldwide, January 2016-March 2018.

In 1988, when an estimated 350,000 cases of poliomyelitis occurred in 125 countries, the World Health Assembly resolved to eradicate polio globally. Transmission of wild poliovirus (WPV) continues uninterrupted in only three countries (Afghanistan, Nigeria, and Pakistan) (1), and among the three serotypes, WPV type 1 (WPV1) remains the only confirmed circulating type. This report describes global progress toward polio eradication during January 2016-March 2018, and updates previous reports (2). In 2017, 22 WPV1 cases were reported, a 41% decrease from the 37 WPV1 cases reported in 2016. As of April 24, 2018, eight WPV1 cases have been reported (seven in Afghanistan and one in Pakistan), compared with five cases during the same period in 2017. In Pakistan, continuing WPV1 transmission has been confirmed in multiple areas in 2018 by isolation from wastewater samples. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016 (3); although WPV was not detected in 2017 or in 2018 to date, limitations in access for vaccination and surveillance in insurgent-held areas in northeastern Nigeria might permit continued undetected poliovirus transmission. Substantial progress toward polio eradication has continued in recent years; however, interruption of WPV transmission will require overcoming remaining challenges to reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015.

BACKGROUND: Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. METHODS: Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. RESULTS: Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). CONCLUSIONS: Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.

Progress Toward Poliomyelitis Eradication--Nigeria, January 2014-July 2015.

Since the 1988 launch of global poliomyelitis eradication efforts, four of the six World Health Organization (WHO) regions have been certified polio-free. Nigeria is one of only three countries, along with Afghanistan and Pakistan, where transmission of wild poliovirus (WPV) has never been interrupted. During 2003-2013, northern Nigeria served as a reservoir for WPV reintroduction into 26 previously polio-free countries. In 2012, the Nigerian government launched a national polio eradication emergency plan to intensify efforts to interrupt WPV transmission. This report describes polio eradication activities and progress in Nigeria during January 2014-July 2015 and updates previous reports. No WPV cases have been reported to date in 2015, compared with a total of six cases reported during 2014. Onset of paralysis in the latest reported WPV type 1 (WPV1) case was July 24, 2014. Only one case of circulating vaccine-derived poliovirus type 2 (cVDPV2) has been reported to date in 2015, compared with 20 cVDPV2 cases during the same period in 2014. Pending final laboratory testing of 218 remaining specimens of 16,617 specimens collected since January 2015, Nigeria could be removed from the WHO list of polio-endemic countries in September 2015. Major remaining challenges to the national polio eradication program include sustaining political support and program funding in the absence of active WPV transmission, maintaining high levels of population immunity in hard-to-reach areas, and accessing children in security-compromised areas of the northeastern states.

Use of group quarantine in Ebola control - Nigeria, 2014.

On July 20, 2014, the first known case of Ebola virus disease (Ebola) in Nigeria, in a traveler from Liberia, led to an outbreak that was successfully curtailed with infection control, contact tracing, isolation, and quarantine measures coordinated through an incident management system. During this outbreak, most contacts underwent home monitoring, which included instructions to stay home or to avoid crowded areas if staying home was not possible. However, for five contacts with high-risk exposures, group quarantine in an observation unit was preferred because the five had crowded home environments or occupations that could have resulted in a large number of community exposures if they developed Ebola.

Progress toward poliomyelitis eradication--Nigeria, January 2013-September 2014.

In 1988, the World Health Assembly resolved to interrupt wild poliovirus (WPV) transmission worldwide. By 2013, only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. Since 2003, northern Nigeria has been a reservoir for WPV reintroduction into 26 previously polio-free countries. In May 2014, the World Health Organization declared the international spread of polio a Public Health Emergency of International Concern. Nigeria's main strategic goal is to interrupt WPV type 1 (WPV1) transmission by the end of 2014, which is also a main objective of the Global Polio Eradication Initiative's Polio Eradication and Endgame Strategic Plan for 2013-2018. This report updates previous reports (4-6) and describes polio eradication activities and progress in Nigeria during January 2013-September 30, 2014. Only six WPV cases had been reported in 2014 through September 30 compared with 49 reported cases during the same period in 2013. The quality of supplemental immunization activities (SIAs) improved during this period; the proportion of local government areas (LGAs) within 11 high-risk states with estimated oral poliovirus vaccine (OPV) campaign coverage at or above the 90% threshold increased from 36% to 67%. However, the number of reported circulating vaccine-derived poliovirus type 2 (cVDPV2) cases increased from four in 2013 to 21 to date in 2014, and surveillance gaps are suggested by genomic sequence analysis and continued detection of WPV1 by environmental surveillance. Interrupting all poliovirus circulation in Nigeria is achievable with continued attention to stopping cVDPV2 transmission, improving the quality of acute flaccid paralysis (AFP) surveillance, increasing vaccination coverage by strengthened routine immunization services, continuing support from all levels of government, and undertaking special initiatives to provide vaccination to children in conflict-affected areas in northeastern Nigeria.

Ebola virus disease outbreak - Nigeria, July-September 2014.

On July 20, 2014, an acutely ill traveler from Liberia arrived at the international airport in Lagos, Nigeria, and was confirmed to have Ebola virus disease (Ebola) after being admitted to a private hospital. This index patient potentially exposed 72 persons at the airport and the hospital. The Federal Ministry of Health, with guidance from the Nigeria Centre for Disease Control (NCDC), declared an Ebola emergency. Lagos, (pop. 21 million) is a regional hub for economic, industrial, and travel activities and a setting where communicable diseases can be easily spread and transmission sustained. Therefore, implementing a rapid response using all available public health assets was the highest priority. On July 23, the Federal Ministry of Health, with the Lagos State government and international partners, activated an Ebola Incident Management Center as a precursor to the current Emergency Operations Center (EOC) to rapidly respond to this outbreak. The index patient died on July 25; as of September 24, there were 19 laboratory-confirmed Ebola cases and one probable case in two states, with 894 contacts identified and followed during the response. Eleven patients with laboratory-confirmed Ebola had been discharged, an additional patient was diagnosed at convalescent stage, and eight patients had died (seven with confirmed Ebola; one probable). The isolation wards were empty, and 891 (all but three) contacts had exited follow-up, with the remainder due to exit on October 2. No new cases had occurred since August 31, suggesting that the Ebola outbreak in Nigeria might be contained. The EOC, established quickly and using an Incident Management System (IMS) to coordinate the response and consolidate decision making, is largely credited with helping contain the Nigeria outbreak early. National public health emergency preparedness agencies in the region, including those involved in Ebola responses, should consider including the development of an EOC to improve the ability to rapidly respond to urgent public health threats.

Measles and rubella vaccination coverage in Haiti, 2012: progress towards verifying and challenges to maintaining measles and rubella elimination.

OBJECTIVES: We conducted a nationwide survey to assess measles containing vaccine (MCV) coverage among children aged 1-9 years in Haiti and identify factors associated with vaccination before and during the 2012 nationwide supplementary immunisation activities (SIA). METHODS: Haiti was stratified into five geographic regions (Metropolitan Port-au-Prince, North, Centre, South and West), 40 clusters were randomly selected in each region, and 35 households were selected per cluster. RESULTS: Among the 7000 visited households, 75.8% had at least one child aged 1-9 years; of these, 5279 (99.5%) households consented to participate in the survey. Of 9883 children enrolled, 91% received MCV before and/or during the SIA; 31% received MR for the first time during the SIA, and 50.7% received two doses of MCV (one before and one during the 2012 SIA). Among the 1685 unvaccinated children during the SIA, the primary reason of non-vaccination was caregivers not being aware of the SIA (31.0%). Children aged 1-4 years had significantly lower MR SIA coverage than those aged 5-9 years (79.5% vs. 84.8%) (P < 0.0001). A higher proportion of children living in the West (12.3%) and Centre (11.2%) regions had never been vaccinated than in other regions (4.8-9.1%). Awareness, educational level of the mother and region were significantly associated with MR vaccination during and before the SIA (P < 0.001). CONCLUSIONS: The 2012 SIA successfully increased MR coverage; however, to maintain measles and rubella elimination, coverage needs to be further increased among children aged 1-4 years and in regions with lower coverage.

Seroprevalence of measles and rubella antibodies in pregnant women Haiti, 2012.

BACKGROUND: Haiti had set a national goal to eliminate measles and rubella, as well as congenital rubella syndrome (CRS) by 2010. A 2007-2008 nationwide measles and rubella vaccination campaign targeting 1-19 years, however, reached only 79% of the target population. To assess whether population immunity was adequate to support elimination, we conducted a national serosurvey. METHODS: We systematically selected 740 serum specimens collected from pregnant women in a 2012 national antenatal HIV sentinel serosurvey across four age strata: 15-19, 20-24, 25-29 and 30-39 years. Sera were tested for measles and rubella specific immunoglobulin G antibodies (IgG) using commercial immunoassays. We classified sera as seropositive, seronegative or indeterminate per manufacturer's instructions, and analyzed seroprevalence according to age strata, and rural or urban residence. We assessed immunity by estimating antibody concentrations in international units per milliliter (IU/mL) for seropositive and indeterminate sera. Measles IgG concentrations >0.12 IU/mL and rubella IgG concentrations >10 IU/mL were considered clinically protective. RESULTS: Of 740 sera, 696 (94.1%) were seropositive and 20 (2.7%) were indeterminate for measles IgG; overall 716 (96.8%) sera had IgG concentrations >0.12 IU/mL. For rubella IgG, 691 (93.4%) sera were seropositive and 1 (0.1%) was indeterminate; a total of 687 (92.8%) had IgG concentrations >10 IU/mL. Measles seropositivity varied across age strata (p=0.003); seropositivity increased from 88.6% among 15-19 year olds to 98.4% among 30-39 year olds (Cochran-Armitage trend tes t ≤ 0.0001). Rubella seropositivity did not differ across age strata. There were no statistically significant differences in measles or rubella seropositivity by urban versus rural residence. CONCLUSION: Despite previous low vaccination coverage for measles, results from this serosurvey indicate high levels of measles and rubella seropositivity in pregnant women, and contribute to the evidence for measles, rubella and CRS elimination from Haiti by the target date.

Cholera surveillance during the Haiti epidemic--the first 2 years.

BACKGROUND: In October 2010, nearly 10 months after a devastating earthquake, Haiti was stricken by epidemic cholera. Within days after detection, the Ministry of Public Health and Population established a National Cholera Surveillance System (NCSS). METHODS: The NCSS used a modified World Health Organization case definition for cholera that included acute watery diarrhea, with or without vomiting, in persons of all ages residing in an area in which at least one case of Vibrio cholerae O1 infection had been confirmed by culture. RESULTS: Within 29 days after the first report, cases of V. cholerae O1 (serotype Ogawa, biotype El Tor) were confirmed in all 10 administrative departments (similar to states or provinces) in Haiti. Through October 20, 2012, the public health ministry reported 604,634 cases of infection, 329,697 hospitalizations, and 7436 deaths from cholera and isolated V. cholerae O1 from 1675 of 2703 stool specimens tested (62.0%). The cumulative attack rate was 5.1% at the end of the first year and 6.1% at the end of the second year. The cumulative case fatality rate consistently trended downward, reaching 1.2% at the close of year 2, with departmental cumulative rates ranging from 0.6% to 4.6% (median, 1.4%). Within 3 months after the start of the epidemic, the rolling 14-day case fatality rate was 1.0% and remained at or below this level with few, brief exceptions. Overall, the cholera epidemic in Haiti accounted for 57% of all cholera cases and 53% of all cholera deaths reported to the World Health Organization in 2010 and 58% of all cholera cases and 37% of all cholera deaths in 2011. CONCLUSIONS: A review of NCSS data shows that during the first 2 years of the cholera epidemic in Haiti, the cumulative attack rate was 6.1%, with cases reported in all 10 departments. Within 3 months after the first case was reported, there was a downward trend in mortality, with a 14-day case fatality rate of 1.0% or less in most areas.