Progress Toward Poliomyelitis Eradication - Pakistan, January 2022-June 2023.

Since the establishment of the Global Polio Eradication Initiative in 1988, Pakistan remains one of only two countries (along with Afghanistan) with continued endemic transmission of wild poliovirus (WPV). This report describes Pakistan's progress toward polio eradication during January 2022-June 2023. During 2022, Pakistan reported 20 WPV type 1 (WPV1) cases, all of which occurred within a small geographic area encompassing three districts in south Khyber Pakhtunkhwa. As of June 23, only a single WPV1 case from Bannu district in Khyber Pakhtunkhwa province has been reported in 2023, compared with 13 cases during the same period in 2022. In addition, 11 WPV1 isolates have been reported from various environmental surveillance (ES) sewage sampling sites to date in 2023, including in Karachi, the capital of the southern province of Sindh. Substantial gaps remain in the quality of supplementary immunization activities (SIAs), especially in poliovirus reservoir areas. Despite the attenuation and apparently limited geographic scope of poliovirus circulation in Pakistan, the isolation of WPV1 from an ES site in Karachi is cause for concern about the actual geographic limits of transmission. Interrupting WPV1 transmission will require meticulous tracking and sustained innovative efforts to vaccinate children who are regularly missed during SIAs and rapidly responding to any new WPV1 isolations.

Assessing country compliance with circulating vaccine-derived poliovirus type 2 outbreak response standard operating procedures: April 2016 to December 2020.

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.

Historical reconstruction of inaccessibility status in Local Government Areas (LGAs) of Borno and Yobe States, Nigeria, 2010-2020.

Introduction: ultimately detected in 2016, wild poliovirus (WPV) transmission continued undetected after 2011 in Northeast Nigeria Borno and Yobe States in security-compromised areas, inaccessible due to armed insurgency. Varying inaccessibility prevented children aged <5 years in these areas from polio vaccination interventions and surveillance, while massive population displacements occurred. We examined progress in access over time to provide data supporting a very low probability of undetected WPV circulation within remaining trapped populations after 2016. Methods: to assess the extent of inaccessibility in security-compromised areas, we obtained empirical historical data in 2020 on a quarterly and annual basis from relevant polio eradication staff for the period 2010-2020. The extent of access to areas for immunization by recall was compared to geospatial data from vaccinator tracking. Population estimates over time in security-compromised areas were extracted from satellite imagery. We compared the historical access data from staff with tracking and population esimates. Results: access varied during 2010-2020, with inaccessibility peaking during 2014-2016. We observed concurrent patterns between historical recalled data on inaccessibility and contemporaneous satellite imagery on population displacements, which increased confidence in the quality of recalled data. Conclusion: staff-recalled access was consistent with vaccinator tracking and satellite imagery of population displacments. Despite variability in inaccessibility over time, innovative immunization initiatives were implemented as access allowed and surveillance initiatives were initiated to search for poliovirus transmission. Along with escape and liberation of residents by the military in some geographic areas, these initiatives resulted in a massive reduction in the size of the unvaccinated population remaining resident.

Seroprevalence of poliovirus antibodies in Nigeria: refining strategies to sustain the eradication effort.

Introduction: in 2016, a switch from trivalent oral poliovirus vaccine (OPV) (containing serotypes 1,2,3) to bivalent OPV (types 1,3) was implemented globally. We assessed the seroprevalence of poliovirus antibody levels in selected Nigerian states, before and after the switch, documented poliovirus type2 outbreak responses conducted and ascertained factors associated with immunity gaps based on seroprevalence rates. Methods: we conducted a secondary analysis of stored serum samples from the 2018 Nigeria National HIV/AIDS Indicator and Impact Survey. Serum from 1,185 children aged 0-119 months residing in one southern and four northern states were tested for serotype-specific PV neutralizing antibodies; seropositivity was a reciprocal titer ≥8. We conducted regression analysis to determine sociodemographic risk factors associated with low seroprevalence using SAS 9.4. Results: children aged 24-119 months (pre-switch cohort) had seroprevalence against PV1, PV2, and PV3, of 97.3% (95% CI:96.4-98.2), 93.8% (95% CI:92.2-95.5), and 91.3% (95% CI:89.2-93.4), while children aged <24 months (post-switch) had seroprevalence of 86.0% (95% CI:81.2-90.8), 55.6% (95% CI: 47.7-63.4), and 77.2% (95% CI:71.0-83.4) respectively. Regression analysis showed age <24 months was associated with lower seroprevalence against all PV serotypes, (p<0.0001); females had lower seroprevalence against PV1 (p=0.0184) and PV2 (p=0.0354); northern states lower seroprevalence against PV1 (p=0.0039), while well-water source lower seroprevalence against PV3 (p=0.0288). Conclusion: this study showed high seroprevalence rates against PV 1, 2, and 3 in pre-switch children (aged 24-119 months). However, post-switch children (<24 months) had low immunity against PV2 despite outbreak responses. Strategies to increase routine immunization coverage and high-quality polio campaigns can increase immunity against polio virus.

Lessons learned from early implementation of the Growing Expertise in E-health Knowledge and Skills (GEEKS) program in Nigeria, 2019 - 2021.

Introduction: the Growing Expertise in E-health Knowledge and Skills (GEEKS) program is an applied apprenticeship program that aims to improve informatics capacity at various levels of the national health system and create a sustainable informatics workforce. Nigeria adapted the GEEKS model in 2019 as a mechanism to strengthen data quality and use of routine immunization (RI) and vaccine-preventable disease (VPD) surveillance data among Expanded Programme on Immunization (EPI) staff. Since the start of the GEEKS-EPI program, there has not been a formal assessment conducted to measure the extent to which GEEKS-EPI has been able to build local informatics workforce capacity and strengthen RI and VPD surveillance (VPDS) data quality and use in Nigeria. Methods: we conducted a qualitative assessment to inform the extent to which GEEKS-EPI has been able to build informatics skillsets to enhance local workforce capacity, foster collaboration across government agencies, and create a sustainable informatics workforce in Nigeria. In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs) were held with GEEKS-EPI supervisors, mentors, and mentees from previous GEEKS-EPI cohorts. Results: while there were challenges reported during early implementation of the GEEKS-EPI program in Nigeria, particularly early on in the COVID-19 pandemic, participants and supervisors reported that the fellowship provided a framework for building a sustainable RI and VPDS informatics workforce through regular mentorship, peer-to-peer exchanges and Subject Matter Expert (SME)-led trainings. Conclusion: lessons learned from early implementation of GEEKS-EPI in Nigeria will help to inform its implementation in other countries, where strengthened national RI and VPDS informatics capacity is the primary objective.

Progress Toward Poliomyelitis Eradication - Pakistan, January 2021-July 2022.

After reporting a single wild poliovirus (WPV) type 1 (WPV1) case in 2021, Pakistan reported 14 cases during April 1-July 31, 2022. Pakistan and Afghanistan are the only countries where endemic WPV transmission has never been interrupted (1). In its current 5-year strategic plan, the Global Polio Eradication Initiative (GPEI) has set a goal of interrupting all WPV1 transmission by the end of 2023 (1-3). The reemergence of WPV cases in Pakistan after 14 months with no case detection has uncovered transmission in southern Khyber Pakhtunkhwa province, the most historically challenging area. This report describes Pakistan's progress toward polio eradication during January 2021-July 2022 and updates previous reports (4,5). As of August 20, 2022, all but one of the 14 WPV1 cases in Pakistan during 2022 have been reported from North Waziristan district in Khyber Pakhtunkhwa. In underimmunized populations, excretion of vaccine virus can, during a period of 12-18 months, lead to reversion to neurovirulence, resulting in circulating vaccine-derived polioviruses (cVDPVs), which can cause paralysis and outbreaks. An outbreak of cVDPV type 2 (cVDPV2), which began in Pakistan in 2019, has been successfully contained; the last case occurred in April 2021 (1,6). Despite program improvements, 400,000-500,000 children continue to be missed during nationwide polio supplementary immunization activities (SIAs),* and recent isolation of poliovirus from sewage samples collected in other provinces suggests wider WPV1 circulation during the ongoing high transmission season. Although vaccination efforts have been recently complicated by months of flooding during the summer of 2022, to successfully interrupt WPV1 transmission in the core reservoirs in southern Khyber Pakhtunkhwa and reach the GPEI goal, emphasis should be placed on further improving microplanning and supervision of SIAs and on systematic tracking and vaccination of persistently missed children in these reservoir areas of Pakistan.

Progress Toward Poliomyelitis Eradication - Pakistan, January 2020-July 2021.

When the Global Polio Eradication Initiative began in 1988, wild poliovirus (WPV) transmission was occurring in 125 countries; currently, only WPV type 1 (WPV1) transmission continues, and as of August 2021, WPV1 transmission persists in only two countries (1,2). This report describes Pakistan's progress toward polio eradication during January 2020-July 2021 and updates previous reports (3,4). In 2020, Pakistan reported 84 WPV1 cases, a 43% reduction from 2019; as of August 25, 2021, Pakistan has reported one WPV1 case in 2021. Circulating vaccine-derived poliovirus (cVDPV) emerges as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations and can lead to paralysis. In 2019, 22 cases of cVDPV type 2 (cVDPV2) were reported in Pakistan, 135 cases were reported in 2020, and eight cases have been reported as of August 25, 2021. Because of the COVID-19 pandemic, planned supplementary immunization activities (SIAs)* were suspended during mid-March-June 2020 (3,5). Seven SIAs were implemented during July 2020-July 2021 without substantial decreases in SIA quality. Improving the quality of polio SIAs, vaccinating immigrants from Afghanistan, and implementing changes to enhance program accountability and performance would help the Pakistan polio program achieve its goal of interrupting WPV1 transmission by the end of 2022.

A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis.

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

A rapid qualitative assessment of barriers associated with demand and uptake of health facility-based childhood immunizations and recommendations to improve immunization service delivery in Sokoto State, Northwest Nigeria, 2017.

Introduction: This rapid qualitative assessment aimed to understand factors associated with persistent low vaccination demand and uptake, and recommendations to improve health facility-based childhood immunization services in Sokoto State, Nigeria. Methods: In 2017, 20 focus group discussions and 16 in-depth interviews were conducted with administrative personnel, healthcare workers, caregivers, and community influencers across three local government areas in Sokoto state, Northwest Nigeria. Participants were purposefully selected to capture a range of perspectives regarding access to health services, campaign- and facility-based immunizations, confidence in immunizations, and recommendations to improve childhood immunization uptake. Results: One hundred and ninety-three individuals participated in the assessment. Commonly reported barriers to receiving childhood immunizations include: inadequacy of health services to meet community needs, preference for campaign vs. facility-based immunizations, the negative influence of rumors and misinformation, and opposition to vaccines among male heads of households. Recommendations to improve uptake of childhood immunizations include: improving immunization service delivery in health facilities, involving community leaders in building demand for immunization, and providing access to free health services and non-cash incentives. Conclusion: Rapid assessment results highlight community, facility, and administrative barriers associated with low demand for and uptake of health facility-based childhood immunizations and offer recommendations to improve immunization services in Sokoto state, Nigeria. Findings demonstrate the persistence of service and supply side barriers such as infrastructure and personnel issues, but also highlight the influence of behavioral factors such as low prioritization of receiving childhood immunizations, misinformation, and gender dynamics on whether communities accept or seek out immunization services.

Data management needs assessment for the scale-up of district health information system and introduction of routine (essential) immunization module in Bauchi State, Nigeria, 2015.

Introduction: the National Primary Health Care Development Agency, African Field Epidemiology Network, United States Centers for Disease Control and Prevention and the Bill and Melinda Gates Foundation are implementing a Routine Immunization (RI) Module as part of their Routine Health Data Management System based on the 2013 - 2015 Accountability Framework for RI in Nigeria. To inform planning and evidence-based decision making, a data management needs assessment was conducted in Bauchi state which was one of the states selected for the deployment of the DHIS2 RI module. Methods: desk reviews were conducted, and a semi-structured questionnaire was administered in four Local Government Areas (LGAs) in Bauchi state that were selected based on the initial evaluation of the performance of all 20 Bauchi LGAs. Ganjuwa and Shira were selected as high-performing LGAs and Alkaleri and Bogoro as low-performing LGAs. Four Health Facilities (HF) were selected in each LGA based on rural or urban classification, type of HFs (private or public), security and accessibility. Results: local Immunization Officers (LIOs) prepare monthly reports in high-performing LGAs, and Community Health Care workers are mostly (69%) responsible for report compilation at the HFs. Shira and Alkaleri met 77% and 44% of training indicator targets, respectively, in the previous 12 months. Data recording and reporting was the type of training received the most by health facility personnel. Functioning refrigerators were in all visited LGAs, working thermometer and updated temperature monitoring charts were available in all the cold chain stores. However, no health facility reported having available computers for data-related activities. Conclusion: this assessment provided an improved understanding of the Bauchi state Routine Health Data Management System and informed the content of the state-wide scale-up.

Strengthening facility-based immunization service delivery in local government areas at high risk for polio in Northern Nigeria, 2014-2015.

Introduction: The National Stop Transmission of Polio (NSTOP) program was created in 2012 to support the Polio Eradication Initiative (PEI) in Local Government Areas (LGAs) at high risk for polio in Northern Nigeria. We assessed immunization service delivery prior to the commencement of NSTOP support in 2014 and after one year of implementation in 2015 to measure changes in the implementation of key facility-based Routine Immunization (RI) components. Methods: The pre- and post-assessment was conducted in selected health facilities (HFs) in 61 LGAs supported by NSTOP in 5 states. A standardized questionnaire was administered to the LGA and HF immunization staff by trained interviewers on key RI service delivery components. Results: At the LGA level, an increase was observed in key components including availability of updated Reach Every Ward (REW) micro-plans with identification of hard to reach settlements (65.6% baseline, 96.8% follow-up, PR = 1.5 (95% CI 3.4 - 69.8), vaccine forecasting (77.1% baseline, 93.5% follow-up, PR =1.2 (95% CI 1.8 - 13.8), and timely delivery of monthly immunization reports (73.8% baseline, 90.2% follow-up; PR =1.2 (95% CI 1.2 - 9.0). At the HF level, there was an increase in percentage of HFs with written supervisory feedback (44.5% baseline, 82.5% follow-up, PR = 1.8 (95% CI 4.7 - 7.3), written stock records (66.5% baseline, 87.9% follow-up, PR = 1.3 (95% CI 2.9 - 4.7) and updated immunization monitoring charts (76.3% baseline, 95.6% follow-up, PR = 1.3 (95% CI 4.6 - 9.9). Conclusion: We observed an improvement in key RI service delivery components following implementation of NSTOP program activities in supported LGAs.

Enhancing acute flaccid paralysis surveillance system towards polio eradication: reverse cold chain monitoring in Nigeria, 2017 to 2019.

Introduction: Highly sensitive acute flaccid paralysis (AFP) surveillance is critical for detection of poliovirus circulation and documentation for polio-free certification. The reverse cold chain (RCC) is a system designed to maintain stool specimens in appropriate temperature for effective detection of poliovirus in the laboratory. We monitored the RCC of AFP surveillance in Nigeria to determine its effectiveness in maintaining viability of enterovirus. Methods: A descriptive cross-sectional study was conducted from November 2017 to December 2019. We included AFP cases from 151 Local Government Areas and monitored RCC of paired stool specimens from collection to arrival at laboratories. The national guideline recommends RCC temperature of +2 to +8°C and a non-polio enterovirus (NPENT) detection rate of ≥10%. We analyzed data with Epi Info 7, and presented results as frequencies and proportions, using Chi-square statistic to test for difference in enterovirus isolation. Results: Of the 1,042 tracked paired stool specimens, 1,038(99.6%) arrived at the laboratory within 72 hours of collection of second specimen, 824(79.1%) were maintained within recommended temperature range, and 271(26%) yielded enteroviruses: 200(73.8%) NPENT, 66(24.4%) Sabin, 3(1.1%) vaccine derived poliovirus type 2 and 2(0.7%) mixture of Sabin and NPENT. The NPENT and Sabin rates were 19.2% and 6.7% respectively. Twenty-five percent of 824 specimens maintained within recommended temperature range, compared with 29.8% of 218 specimens with temperature excursion yielded enteroviruses (P=0.175). Conclusion: the RCC of AFP surveillance system in the study area was optimal and effective in maintaining the viability of enteroviruses. It was unlikely that poliovirus transmission was missed during the intervention.

Modeling Poliovirus Transmission in Borno and Yobe, Northeast Nigeria.

Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.

Implementing the routine immunisation data module and dashboard of DHIS2 in Nigeria, 2014-2019.

In 2010, Nigeria adopted the use of web-based software District Health Information System, V.2 (DHIS2) as the platform for the National Health Management Information System. The platform supports real-time data reporting and promotes government ownership and accountability. To strengthen its routine immunisation (RI) component, the US Centers for Disease Control and Prevention (CDC) through its implementing partner, the African Field Epidemiology Network-National Stop Transmission of Polio, in collaboration with the Government of Nigeria, developed the RI module and dashboard and piloted it in Kano state in 2014. The module was scaled up nationally over the next 4 years with funding from the Bill & Melinda Gates Foundation and CDC. One implementation officer was deployed per state for 2 years to support operations. Over 60 000 RI healthcare workers were trained on data collection, entry and interpretation and each local immunisation officer in the 774 local government areas (LGAs) received a laptop and stock of RI paper data tools. Templates for national-level and state-level RI bulletins and LGA quarterly performance tools were developed to promote real-time data use for feedback and decision making, and enhance the performance of RI services. By December 2017, the DHIS2 RI module had been rolled out in all 36 states and the Federal Capital Territory, and all states now report their RI data through the RI Module. All states identified at least one government DHIS2 focal person for oversight of the system's reporting and management operations. Government officials routinely collect RI data and use them to improve RI vaccination coverage. This article describes the implementation process-including planning and implementation activities, achievements, lessons learnt, challenges and innovative solutions-and reports the achievements in improving timeliness and completeness rates.

SAFETY, IMMUNOGENICITY, AND EFFICACY OF INTRAMUSCULAR AND ORAL DELIVERY OF ERA-G333 RECOMBINANT RABIES VIRUS VACCINE TO BIG BROWN BATS (EPTESICUS FUSCUS).

Attenuated strains of rabies virus (RABV) have been used for oral vaccination of wild carnivores in Europe and North America. However, some RABV vaccines caused clinical rabies in target animals. To improve the safety of attenuated RABV as an oral vaccine for field use, strategies using selection of escape mutants under monoclonal antibody neutralization pressure and reverse genetics-defined mutations have been used. We tested the safety, immunogenicity, and efficacy of one RABV construct, ERA-g333, developed with reverse genetics by intramuscular (IM) or oral (PO) routes in big brown bats (Eptesicus fuscus). Twenty-five bats received 5×106 mouse intracerebral median lethal doses (MICLD50) of ERA-g333 by IM route, 10 received 5×106 MICLD50 of ERA-g333 by PO route, and 22 bats served as unvaccinated controls. Twenty-one days after vaccination, 44 bats were infected by IM route with 102.9 MICLD50 of E. fuscus RABV. We report both the immunogenicity and efficacy of ERA-g333 delivered by the IM route; no induction of humoral immunity was detected in bats vaccinated by the PO route. Two subsets of bats vaccinated IM (n=5) and PO (n=3) were not challenged, and none developed clinical rabies from ERA-g333. Scarce reports exist on the evaluation of oral rabies vaccines in insectivorous bats, although the strategy evaluated here may be feasible for future application to these important RABV reservoirs.

Inactivated Rabies Virus-Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge.

BACKGROUND: Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage. METHODS: We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV). RESULTS: Syrian hamsters immunized with FiloRab1 PBV-processed vaccines stored at temperatures of 4°C and 37°C for 6 months, and at 50°C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model. CONCLUSIONS: We successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4°C to 37°C and for up to 2 weeks at 50°C.

Progress Toward Poliomyelitis Eradication - Nigeria, January 2018-May 2019.

The number of wild poliovirus (WPV) cases in Nigeria decreased from 1,122 in 2006 to six WPV type 1 (WPV1) in 2014 (1). During August 2014-July 2016, no WPV cases were detected; during August-September 2016, four cases were reported in Borno State. An insurgency in northeastern Nigeria had resulted in 468,800 children aged <5 years deprived of health services in Borno by 2016. Military activities in mid-2016 freed isolated families to travel to camps, where the four WPV1 cases were detected. Oral poliovirus vaccine (OPV) campaigns were intensified during August 2016-December 2017; since October 2016, no WPV has been detected (2). Vaccination activities in insurgent-held areas are conducted by security forces; however, 60,000 unvaccinated children remain in unreached settlements. Since 2018, circulating vaccine-derived poliovirus type 2 (cVDPV2) has emerged and spread from Nigeria to Niger and Cameroon; outbreak responses to date have not interrupted transmission. This report describes progress in Nigeria polio eradication activities during January 2018-May 2019 and updates the previous report (2). Interruption of cVDPV2 transmission in Nigeria will need increased efforts to improve campaign quality and include insurgent-held areas. Progress in surveillance and immunization activities will continue to be reviewed, potentially allowing certification of interruption of WPV transmission in Africa in 2020.

Additional Progress in the Development and Application of a Direct, Rapid Immunohistochemical Test for Rabies Diagnosis.

Laboratory-based surveillance is fundamental to effective rabies prevention and control. The direct fluorescent antibody (AB) test (FAT) is the gold standard for rabies diagnosis. Recently, additional tests besides the FAT have been developed, such as the direct rapid immunohistochemical test (DRIT). In this study, our objective was to further refine technical aspects of the DRIT using a combination of two monoclonal ABs (MABs), 502 and 802, conduct additional testing among rabies reference laboratories using a diversity of animal species and rabies virus (RV) variants and compare the potential utility of the DRIT for end users via proficiency testing (PT) against the FAT. Considering the ideal molar ratios of biotin to AB in formulation of the DRIT conjugate, 3.9 was found to be superior to 7.4, for detection of RV antigens in the brain of a naturally infected raccoon. Optimization of the DRIT conjugate may also be dependent upon the apparent choice of specific viral antigens for testing, as a gray fox RV variant reacted less strongly than a raccoon RV variant in determining the working dilution of the MAB cocktail. Using the same MABs and protocol, the DRIT was compared to the FAT using more than 800 samples of mammalian brains, representative of more than 25 taxa, including in excess of 250 animal rabies cases from Europe and North America. Sensitivity was determined at 98% (96⁻100%, 95% CI) and specificity was calculated at 95% (92⁻96%, 95% CI). In a comparison among end users, PT of laboratory personnel resulted in values of 77⁻100% sensitivity and 86-100% specificity. Based upon these and previously reported results, the DRIT appears to be a suitable alternative to the FAT for use in lyssavirus diagnosis.

Progress Toward Poliomyelitis Eradication - Nigeria, January-December 2017.

Nearly three decades after the World Health Assembly launched the Global Polio Eradication Initiative in 1988, four of the six World Health Organization (WHO) regions have been certified polio-free (1). Nigeria is one of three countries, including Pakistan and Afghanistan, where wild poliovirus (WPV) transmission has never been interrupted. In September 2015, after >1 year without any reported WPV cases, Nigeria was removed from WHO's list of countries with endemic WPV transmission (2); however, during August and September 2016, four type 1 WPV (WPV1) cases were reported from Borno State, a state in northeastern Nigeria experiencing a violent insurgency (3). The Nigerian government, in collaboration with partners, launched a large-scale coordinated response to the outbreak (3). This report describes progress in polio eradication activities in Nigeria during January-December 2017 and updates previous reports (3-5). No WPV cases have been reported in Nigeria since September 2016; the latest case had onset of paralysis on August 21, 2016 (3). However, polio surveillance has not been feasible in insurgent-controlled areas of Borno State. Implementation of new strategies has helped mitigate the challenges of reaching and vaccinating children living in security-compromised areas, and other strategies are planned. Despite these initiatives, however, approximately 130,000-210,000 (28%-45%) of the estimated 469,000 eligible children living in inaccessible areas in 2016 have not been vaccinated. Sustained efforts to optimize surveillance and improve immunization coverage, especially among children in inaccessible areas, are needed.