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BACKGROUND Outbreaks of circulating vaccine-derived polioviruses (cVDPVs) pose a threat to the eventual eradication of all polioviruses. In 2017, an outbreak of cVDPV type 2 (cVDPV2) occurred in the midst of a war in Syria. We describe vaccination-based risk factors for and the successful response to the outbreak. METHODS We performed a descriptive analysis of cVDPV2 cases and key indicators of poliovirus surveillance and vaccination activities during 2016-2018. In the absence of reliable subnational coverage data, we used the caregiver-reported vaccination status of children with non-polio acute flaccid paralysis (AFP) as a proxy for vaccination coverage. We then estimated the relative odds of being unvaccinated against polio, comparing children in areas affected by the outbreak to children in other parts of Syria in order to establish the presence of poliovirus immunity gaps in outbreak affected areas. FINDINGS A total of 74 cVDPV2 cases were reported, with paralysis onset ranging from 3 March to 21 September 2017. All but three cases were reported from Deir-ez-Zor governorate and 84% had received

Among the three wild poliovirus (WPV) serotypes, only WPV type 1 (WPV1) has been reported in polio cases or detected from environmental surveillance globally since 2012. Pakistan remains one of only three countries worldwide (the others are Afghanistan and Nigeria) that has never had interrupted WPV1 transmission. This report documents Pakistan's activities and progress toward polio eradication during January 2017-September 2018 and updates previous reports (1,2). In 2017, Pakistan reported eight WPV1 cases, a 60% decrease from 20 cases in 2016. As of September 18, 2018, four cases had been reported, compared with five cases at that time in 2017. Nonetheless, in 2018, WPV1 continues to be isolated regularly from environmental surveillance sites, primarily in the core reservoir areas of Karachi, Quetta, and Peshawar, signifying persistent transmission. Strategies to increase childhood immunity have included an intense schedule of supplemental immunization activities (SIAs), expanding and refining deployment of community-based vaccination implemented by community health workers recruited from the local community in reservoir areas, and strategic placement of permanent transit points where vaccination is provided to mobile populations. Interruption of WPV1 transmission will require further programmatic improvements throughout the country with a focus on specific underperforming subdistricts in reservoir areas.

Since the 1988 inception of the Global Polio Eradication Initiative (GPEI), progress toward interruption of wild poliovirus (WPV) transmission has occurred mostly through extensive use of oral poliovirus vaccine (OPV) in mass vaccination campaigns and through routine immunization services (1,2). However, because OPV contains live, attenuated virus, it carries the rare risk for reversion to neurovirulence. In areas with very low OPV coverage, prolonged transmission of vaccine-associated viruses can lead to the emergence of vaccine-derived polioviruses (VDPVs), which can cause outbreaks of paralytic poliomyelitis. Although WPV type 2 has not been detected since 1999, and was declared eradicated in 2015,* most VDPV outbreaks have been attributable to VDPV serotype 2 (VDPV2) (3,4). After the synchronized global switch from trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (types 1 and 3) in April 2016 (5), GPEI regards any VDPV2 emergence as a public health emergency (6,7). During May-June 2017, VDPV2 was isolated from stool specimens from two children with acute flaccid paralysis (AFP) in Deir-ez-Zor governorate, Syria. The first isolate differed from Sabin vaccine virus by 22 nucleotides in the VP1 coding region (903 nucleotides). Genetic sequence analysis linked the two cases, confirming an outbreak of circulating VDPV2 (cVDPV2). Poliovirus surveillance activities were intensified, and three rounds of vaccination campaigns, aimed at children aged

Since October 2016, Afghanistan and Pakistan have been the only countries with reported cases of wild poliovirus type 1 (WPV1) (1). In Afghanistan, although the number of cases had declined during 2013-2016, the polio eradication program experienced challenges during 2017-2019. This report describes polio eradication activities and progress in Afghanistan during January 2018-May 2019 and updates previous reports (2,3). During May-December 2018, insurgent groups (antigovernment elements) banned house-to-house vaccination in most southern and southeastern provinces, leaving approximately 1 million children inaccessible to oral poliovirus vaccine (OPV) administration. During January-April 2019, vaccination targeting children at designated community sites (site-to-site vaccination) was permitted; however, at the end of April 2019, vaccination campaigns were banned nationally. During 2018, a total of 21 WPV1 cases were reported in Afghanistan, compared with 14 during 2017. During January-May 2019, 10 WPV1 cases were reported (as of May 31), compared with eight during January-May 2018. Sewage sample-testing takes place at 20 sites in the highest-risk areas for poliovirus circulation; 17 have detected WPV1 since January 2017, primarily in the southern and eastern provinces. Continued discussion with antigovernment elements to resume house-to-house campaigns is important to achieving polio eradication in Afghanistan. To increase community support for vaccination, collaboration among humanitarian service agencies to address other urgent health and basic needs is critical.

Despite recent progress toward global polio eradication, endemic transmission of wild poliovirus (WPV) continues to be reported in Afghanistan and Pakistan. The Afghanistan program must overcome many challenges to remain on track toward achieving the objectives set in the 2013–2018 strategic plan of the Global Polio Eradication Initiative (GPEI). Cross-border transmission of WPV type 1 (WPV1) continues to occur among children traveling to and from Pakistan. The country's routine immunization system remains weak and unable to reach recommended benchmarks in most regions; hence, the national Polio Eradication Initiative (PEI) relies mainly on providing children aged

To cause meningitis the extracellular pathogen Neisseria meningitidis has to traverse the blood-cerebrospinal fluid (B-CSF) barrier. Postulating a transcellular passage, meningococci (MC) have been shown to adhere to and enter B-CSF barrier forming human brain microvascular endothelial cells (HBMEC). Furthermore, electron microscopy studies demonstrated that intracellular MC reside within membrane-bound compartments, both solitary and in groups. To investigate the ability of MC to survive and replicate intracellularly, prolonged gentamicin protection assays were performed. Encapsulated bacteria were found to survive and, after an initial delay, to replicate within HBMEC, whereas the number of intracellular capsule-deficient mutants decreased continuously. This strongly suggests that the capsule plays a pivotal role in the intracellular survival of MC. Further investigations were initiated to characterise the membrane-bound compartment, the Neisseria-containing vacuole (NCV). Immunfluorescence microscopy studies showed that NCVs interact with the endocytic pathway acquiring the early endosomal marker protein, transferrin receptor (TfR), and the late endosomal/lysosomal marker protein Lamp-1.