BACKGROUND: Trivalent oral poliovirus vaccine (tOPV) was globally replaced with bivalent oral poliovirus vaccine (bOPV) in April 2016 ("the switch"). Many outbreaks of paralytic poliomyelitis associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) have been reported since this time. The Global Polio Eradication Initiative (GPEI) developed standard operating procedures (SOPs) to guide countries experiencing cVDPV2 outbreaks to implement timely and effective outbreak response (OBR). To assess the possible role of compliance with SOPs in successfully stopping cVDPV2 outbreaks, we analyzed data on critical timelines in the OBR process. METHODS: Data were collected on all cVDPV2 outbreaks detected for the period April 1, 2016 and December 31, 2020 and all outbreak responses to those outbreaks between April 1, 2016 and December 31, 2021. We conducted secondary data analysis using the GPEI Polio Information System database, records from the Anonymized Institution Poliovirus Laboratory, and meeting minutes of the monovalent OPV2 (mOPV2) Advisory Group. Date of notification of circulating virus was defined as Day 0 for this analysis. Extracted process variables were compared with indicators in the GPEI SOP version 3.1. RESULTS: One hundred and eleven cVDPV2 outbreaks resulting from 67 distinct cVDPV2 emergences were reported during April 1, 2016-December 31, 2020, affecting 34 countries across four World Health Organization Regions. Out of 65 OBRs with the first large-scale campaign (R1) conducted after Day 0, only 12 (18.5%) R1s were conducted by the target of 28 days after Day 0. Of the 89 OBRs with the second large-scale campaign (R2) conducted after Day 0, 30 (33.7%) R2s were conducted by the target of 56 days after Day 0. Twenty-three (31.9%) of the 72 outbreaks with isolates dated after Day 0 were stopped within the 120-day target. CONCLUSION: Since "the switch", delays in OBR implementation were evident in many countries, which may be related to the persistence of cVDPV2 outbreaks >120 days. To achieve timely and effective response, countries should follow GPEI OBR guidelines.

Despite exhaustive and fully-financed plans to manage the risks of globally coordinated cessation of oral poliovirus vaccine (OPV) containing type 2 (OPV2) prior to 2016, as of 2022, extensive, continued transmission of circulating vaccine-derived polioviruses (cVDPVs) type 2 (cVDPV2) remains. Notably, cumulative cases caused by cVDPV2 since 2016 now exceed 2,500. Earlier analyses explored the implications of using different vaccine formulations to respond to cVDPV2 outbreaks and demonstrated how different properties of novel OPV2 (nOPV2) might affect its performance compared to Sabin monovalent OPV2 (mOPV2). These prior analyses used fixed assumptions for how outbreak response would occur, but outbreak response implementation can change. We update an existing global poliovirus transmission model to explore different options for responding with different vaccines and assumptions about scope, delays, immunization intensity, target age groups, and number of rounds. Our findings suggest that in order to successfully stop all cVDPV2 transmission globally, countries and the Global Polio Eradication Initiative need to address the deficiencies in emergency outbreak response policy and implementation. The polio program must urgently act to substantially reduce response time, target larger populations - particularly in high transmission areas - and achieve high coverage with improved access to under-vaccinated subpopulations. Given the limited supplies of nOPV2 at the present, using mOPV2 intensively immediately, followed by nOPV2 intensively if needed and when sufficient quantities become available, substantially increases the probability of ending cVDPV2 transmission globally.

In April 2016, a resolution by all members of the 68th World Health Assembly* in coordination with the Global Polio Eradication Initiative (GPEI) resulted in the removal of the Sabin-strain type 2 oral poliovirus vaccine (OPV) component from all immunization activities to avert outbreaks of type 2 circulating vaccine-derived poliovirus (cVDPV2). In the first quarter of 2016, house-to-house supplementary immunization activities (SIAs) with trivalent OPV (containing Sabin-strain types 1, 2 and 3) were conducted in 42 at-risk countries† in an effort to close type 2 immunity gaps in countries with chronically weak routine childhood immunization systems. However, the quality of SIAs in some countries was inadequate, and pockets of unimmunized and underimmunized children remained. Sabin-strain monovalent OPV type 2 (mOPV2) was then successfully used in response to many cVDPV2 outbreaks; however, some outbreaks in sub-Saharan Africa were not promptly controlled and spread to other countries. Where mOPV2 SIA quality was low, prolonged Sabin-strain type 2 circulation allowed new cVDPV2 outbreaks to emerge (1). In 2019, 358 cVDPV2 cases were reported, representing a fourfold increase over the 71 cases reported in 2018 and more than tripling the number of countries with outbreaks, from five (2) to 16. As of August 2, a total of 236 cVDPV2 cases in 17 countries have been reported in 2020. Among 33 cVDPV outbreaks reported during July 2018–February 2020, 31 (94%) were caused by cVDPV2 (1).

After the declaration of eradication of wild poliovirus type 2 in 2015, all countries using oral poliovirus vaccine (OPV) switched from using trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (containing types 1 and 3) in April 2016 (1). Vaccine-derived polioviruses (VDPVs), strains that have diverged from the live vaccine virus during prolonged circulation, can emerge rarely in areas with inadequate OPV coverage and can cause outbreaks of paralysis. Before the global switch from tOPV to bOPV, many circulating VDPV (cVDPV) outbreaks identified globally were caused by type 2 cVDPV (cVDPV2). After the switch, two large cVDPV2 outbreaks occurred in 2017 in the Democratic Republic of the Congo (continuing in 2018) and Syria (2,3).

Vaccination is an important and cost-effective disease prevention and control strategy. Despite progress in vaccine development and immunization delivery systems worldwide, populations in areas of conflict (hereafter, "conflict settings") often have limited or no access to lifesaving vaccines, leaving them at increased risk for morbidity and mortality related to vaccine-preventable disease. Without developing and refining approaches to reach and vaccinate children and other vulnerable populations in conflict settings, outbreaks of vaccine-preventable disease in these settings may persist and spread across subnational and international borders. Understanding and refining current approaches to vaccinating populations in conflict and humanitarian emergency settings may save lives. Despite major setbacks, the Global Polio Eradication Initiative has made substantial progress in vaccinating millions of children worldwide, including those living in communities affected by conflicts and other humanitarian emergencies. In this article, we examine key strategic and operational tactics that have led to increased polio vaccination coverage among populations living in diverse conflict settings, including Nigeria, Somalia, and Pakistan, and how these could be applied to reach and vaccinate populations in other settings across the world.

BACKGROUND: Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. METHODS: This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2.5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. FINDINGS: Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72.4-86.1) with mOPV1-1 week, 108/135 (80%, 73.2-86.8) with mOPV1-2 weeks, 129/148 (87%, 80.9-92.0) with mOPV1-4 weeks, and 107/136 (79%, 71.8-85.6) with bOPV-4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. INTERPRETATION: We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict-eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days. FUNDING: World Health Organization.

In 2012, the World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. Afghanistan and Pakistan are two of the three remaining countries (the other is Nigeria) where circulation of indigenous wild poliovirus (WPV) has never been interrupted. This report updates previous reports and describes polio eradication activities and progress in Afghanistan and Pakistan during January 2013-August 2014. In Afghanistan, 14 WPV cases were reported in 2013, compared with 37 cases in 2012; nine cases were reported during January-August 2014, compared with six cases during the same period in 2013. In Pakistan, 93 WPV cases were reported in 2013, compared with 58 cases in 2012; 170 cases were reported during January-August 2014, compared with 33 cases during the same period in 2013. All WPV cases reported during January 2013-August 2014 were WPV type 1 (WPV1). Vaccination campaigns have been banned since June 2012 in specific areas in Pakistan, where an estimated 300,000 children aged <5 years reside and where 69% of WPV cases have occurred in 2014. To accomplish the objectives of the Polio Eradication and Endgame Strategic Plan for 2013-2018 both countries should continue to negotiate access of vaccinators to insecure and temporarily inaccessible areas, improve immunization program performance to reach more children in accessible areas, and ensure that political and health leaders at all levels are fully committed to the program, including being committed to providing financial resources needed to fully implement all the recommendations of external technical advisory groups. Both countries should also continue to strengthen cross-border collaboration to improve surveillance and case detection, coordinate outbreak response, and maximize vaccination coverage of children moving between the two countries.

Pakistan is one of 3 countries where transmission of indigenous wild poliovirus (WPV) has never been interrupted. Numbers of confirmed polio cases have declined by >90% from preeradication levels, although outbreaks occurred during 2008-2013. During 2012 and 2013, 58 and 93 WPV cases, respectively, were reported, almost all of which were due to WPV type 1. Of the 151 WPV cases reported during 2012-2013, 123 (81%) occurred in the conflict-affected Federally Administered Tribal Areas (FATA) and in security-compromised Khyber Pakhtunkhwa province. WPV type 3 was isolated from only 3 persons with polio in a single district in 2012. During August 2012-December 2013, 62 circulating vaccine-derived poliovirus type 2 cases were detected, including 40 cases (65%) identified in the FATA during 2013. Approximately 350 000 children in certain districts of the FATA have not received polio vaccine during supplementary immunization activities (SIAs) conducted since mid-2012, because local authorities have banned polio vaccination. In other areas of Pakistan, SIAs have been compromised by attacks targeting polio workers, which started in mid-2012. Further efforts to reach children in conflict-affected and security-compromised areas will be necessary to prevent reintroduction of WPV into other areas of Pakistan and other parts of the world.

INTRODUCTION: Child Health Days (CHDs) are increasingly used by countries to periodically deliver multiple maternal and child health interventions as time-limited events, particularly to populations not reached by routine health services. In countries with a weak health infrastructure, this strategy could be used to reach many underserved populations with an integrated package of services. In this study, we estimate the incremental costs, impact, cost-effectiveness, and return on investment of 2 rounds of CHDs that were conducted in Somalia in 2009 and 2010. METHODS: We use program costs and population estimates reported by the World Health Organization and United Nations Children's Fund to estimate the average cost per beneficiary for each of 9 interventions delivered during 2 rounds of CHDs implemented during the periods of December 2008 to May 2009 and August 2009 to April 2010. Because unstable areas were unreachable, we calculated costs for targeted and accessible beneficiaries. We model the impact of the CHDs on child mortality using the Lives Saved Tool, convert these estimates of mortality reduction to life years saved, and derive the cost-effectiveness ratio and the return on investment. RESULTS: The estimated average incremental cost per intervention for each targeted beneficiary was $0.63, with the cost increasing to $0.77 per accessible beneficiary. The CHDs were estimated to save the lives of at least 10,000 or 500,000 life years for both rounds combined. The CHDs were cost-effective at $34.00/life year saved. For every $1 million invested in the strategy, an estimated 615 children's lives, or 29,500 life years, were saved. If the pentavalent vaccine had been delivered during the CHDs instead of diphtheria-pertussis-tetanus vaccine, an additional 5000 children's lives could have been saved. CONCLUSIONS: Despite high operational costs, CHDs are a very cost-effective service delivery strategy for addressing the leading causes of child mortality in a conflict setting like Somalia and compare favorably with other interventions rated as health sector "best buys" in sub-Saharan Africa.