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Background: Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010-11 led the Executive Board of WHO in January, 2012, to declare polio eradication a "programmatic emergency for global public health". We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines.Methods: We did a matched case-control analysis based on a database of 46,977 children aged 0-14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0-2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan.Findings: Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6-18·8) compared with 34·5% (16·1-48·9) for monovalent OPV (p=0·007) and 23·4% (10·4-34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006-11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced population immunity to poliovirus serotype 1 in FATA and Balochistan and associated increases in the incidence of poliomyelitis.Interpretation: The effectiveness of bivalent OPV is comparable with monovalent OPV and can therefore be used in eradicating serotype 1 poliomyelitis whilst minimising the risks of serotype 3 outbreaks. However, decreases in vaccination coverage in parts of Pakistan and southern Afghanistan have severely limited the effect of this vaccine.Funding: Poliovirus Research subcommittee of WHO, Royal Society, and Medical Research Council. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

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 U.S. Centers for Disease Control and Prevention Polio 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Competing Interests: No conflicts of interest were reported.

Background: To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation., Methods: Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community., Results: The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8-35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4-63.0), with significant variation in site-specific estimates (median varied from 33.3-79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2-98.7), assuming four samples per month for each site., Conclusions: ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance.

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., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

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.

An outbreak of invasive aspergillosis occurred in a community hospital in temporal association with construction activity. Epidemiological investigation showed that patients who are at highest risk comprise a small group and are readily identifiable. Clinicians should strive to protect these patients, following guidelines published by the Centers for Disease Control and Prevention.