Since its launch in 1988, the Global Polio Eradication Initiative has made substantial progress toward the eradication of wild poliovirus (WPV), including eradicating two of the three serotypes, and reducing the countries with ongoing endemic transmission of WPV type 1 (WPV1) to just Afghanistan and Pakistan. Both countries are considered a single epidemiologic block. Despite the occurrence of only a single confirmed WPV1 case during the first half of 2023, Pakistan experienced widespread circulation of WPV1 over the subsequent 12 months, specifically in the historical reservoirs of the cities of Karachi, Peshawar, and Quetta. As of June 30, 2024, eight WPV1 cases had been reported in Pakistan in 2024, compared with six reported during all of 2023. These cases, along with more than 300 WPV1-positive environmental surveillance (sewage) samples reported during 2023-2024, indicate that Pakistan is not on track to interrupt WPV1 transmission. The country's complex sociopolitical and security environment continues to pose formidable challenges to poliovirus elimination. To interrupt WPV1 transmission, sustained political commitment to polio eradication, including increased accountability at all levels, would be vital for the polio program. Efforts to systematically track and vaccinate children who are continually missed during polio vaccination activities should be enhanced by better addressing operational issues and the underlying reasons for community resistance to vaccination and vaccine hesitancy.

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.

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.

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.

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.

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.

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.

This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies.

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.

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.

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.

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.

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.

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.

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.

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 5x10(6) mouse intracerebral median lethal doses (MICLD50) of ERA-g333 by IM route, 10 received 5x10(6) 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 10(2.9) 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.

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 degrees C to 50 degrees 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 degrees C and 37 degrees C for 6 months, and at 50 degrees 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 degrees C to 37 degrees C and for up to 2 weeks at 50 degrees C.

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.

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.

The highest rate of human rabies deaths reported in the Americas is in Haiti, and most of these deaths result from rabies virus infections that occur after individuals are bitten by infected dogs and do not receive rabies post-exposure prophylaxis. One barrier to rabies prevention in Haiti is a lack of knowledge about this disease among healthcare professionals and community members. During the past 4 years, The US Centers for Disease Control and Prevention has collaborated with public health officials and partners to develop, test and refine educational materials aimed at filling this need for rabies education. This report summarizes the use of feedback from knowledge, attitudes and practises surveys; key informant interviews; and focus groups to develop culturally appropriate rabies prevention materials for community members, health officials, clinicians, laboratory professionals, veterinary professionals, government officials and national and local district leaders about ways to prevent rabies. These formative research methods were critically important in ensuring that the materials would be culturally appropriate and would stand the greatest likelihood of motivating Haitians to protect themselves from rabies. Centers for Disease Control and Prevention is using lessons learned in Haiti to develop and test materials in other countries with high rates of canine rabies.

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.

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody...test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42⁻100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19⁻95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally.

Haiti, a Caribbean country of 10.5 million people, is estimated to have the highest burden of canine-mediated human rabies deaths in the Western Hemisphere, and one of the highest rates of human rabies deaths in the world. Haiti is also the poorest country in the Western Hemisphere and has numerous economic and health priorities that compete for rabies-control resources. As a result, primary rabies-control actions, including canine vaccination programs, surveillance systems for human and animal rabies, and appropriate postbite treatment, have not been fully implemented at a national scale. After the 2010 earthquake that further hindered the development of public health program infrastructure and services, the U.S. Centers for Disease Control and Prevention worked with the Ministry of Public Health and Population and key health development partners (including the Pan-American Health Organization) to provide technical expertise and funding for general disease surveillance systems, laboratory capacity, and selected disease control programs; including rabies. In 2011, a cross-ministerial rabies consortium was convened with participation from multiple international rabies experts to develop a strategy for successful rabies control in Haiti. The consortium focused on seven pillars: 1) enhancement of laboratory diagnostic capacity, 2) development of comprehensive animal surveillance system, 3) development of comprehensive human rabies surveillance system, 4) educational outreach, 5) sustainable human rabies biologics supply, 6) achievement of sustained canine vaccination rates of ≥ 70%, and 7) finalization of a national rabies control strategy. From 2010 until 2015, Haiti has seen improvements in the program infrastructure for canine rabies control. The greatest improvements were seen in the area of animal rabies surveillance, in support of which an internationally recognized rabies laboratory was developed thereby leading to an 18-fold increase in the detection of rabid animals. Canine rabies vaccination practices also improved, from a 2010 level of approximately 12% to a 2015 dog population coverage level estimated to be 45%. Rabies vaccine coverage is still below the goal of 70%, however, the positive trend is encouraging. Gaps exist in the capacity to conduct national surveillance for human rabies cases and access to human rabies vaccine is lacking in many parts of the country. However, control has improved over the past 5 years as a result of the efforts of Haiti's health and agriculture sectors with assistance from multiple international organizations. Haiti is well situated to eliminate canine-mediated human rabies deaths in the near future and should serve as a great example to many developing countries struggling with similar barriers and limitations.

Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

Bartonellae are phylogenetically diverse, intracellular bacteria commonly found in mammals. Previous studies have demonstrated that bats have a high prevalence and diversity of Bartonella infections globally. Isolates (n = 42) were obtained from five bat species in four provinces of Thailand and analyzed using sequences of the citrate synthase gene (gltA). Sequences clustered into seven distinct genogroups; four of these genogroups displayed similarity with Bartonella spp. sequences from other bats in Southeast Asia, Africa, and Eastern Europe. Thirty of the isolates representing these seven genogroups were further characterized by sequencing four additional loci (ftsZ, nuoG, rpoB, and ITS) to clarify their evolutionary relationships with other Bartonella species and to assess patterns of diversity among strains. Among the seven genogroups, there were differences in the number of sequence variants, ranging from 1-5, and the amount of nucleotide divergence, ranging from 0.035-3.9%. Overall, these seven genogroups meet the criteria for distinction as novel Bartonella species, with sequence divergence among genogroups ranging from 6.4-15.8%. Evidence of intra- and intercontinental phylogenetic relationships and instances of homologous recombination among Bartonella genogroups in related bat species were found in Thai bats.

OBJECTIVE To assess the immunogenicity of thermostable live-attenuated rabies virus (RABV) preserved by vaporization (PBV) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. ANIMALS 8 gray foxes (Urocyon cinereoargenteus). PROCEDURES Endoscopy was used to place RABV PBV (n = 3 foxes), alginate-encapsulated RABV PBV (3 foxes), or nonpreserved RABV (2 foxes) vaccine into the duodenum of foxes. Blood samples were collected weekly to monitor the immune response. Saliva samples were collected weekly and tested for virus shedding by use of a conventional reverse-transcriptase PCR assay. Foxes were euthanized 28 days after vaccine administration, and relevant tissues were collected and tested for presence of RABV. RESULTS 2 of 3 foxes that received RABV PBV and 1 of 2 foxes that received nonpreserved RABV seroconverted by day 28. None of the 3 foxes receiving alginate-encapsulated RABV PBV seroconverted. No RABV RNA was detected in saliva at any of the time points, and RABV antigen or RNA was not detected in any of the tissues obtained on day 28. None of the foxes displayed any clinical signs of rabies. CONCLUSIONS AND CLINICAL RELEVANCE Results for this study indicated that a live-attenuated RABV vaccine delivered to the duodenal mucosa can induce an immune response in gray foxes. A safe, potent, thermostable RABV vaccine that could be delivered orally to wildlife or domestic animals would enhance current rabies control and prevention efforts.

BACKGROUND: Rabies imposes a substantial burden to about half of the world population. The World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. This could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. Here, we focused on the resources needed for the elimination of dog rabies virus by 2030. MATERIALS AND METHODS: Drawing from multiple datasets, including national dog vaccination campaigns, rabies literature, and expert opinion, we developed a model considering country-specific current dog vaccination capacity to estimate the years and resources required to achieve dog rabies elimination by 2030. Resources were determined based on four factors: (a) country development status, (b) dog vaccination costs, (c) dog rabies vaccine availability, and (d) existing animal health workers. Our calculations were based on the WHO's estimate that vaccinating 70% of the dog population for seven consecutive years would eliminate rabies. FINDINGS: If dog rabies vaccine production remains at 2015 levels, we estimate that there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination. We estimated a present cost of $6,300 million to eliminate dog rabies in all endemic countries, equivalent to a $3,900 million gap compared to current spending. To eliminate dog rabies, the vaccination workforce may suffice if all public health veterinarians in endemic countries were to dedicate 3 months each year to dog rabies vaccination. We discuss implications of potential technology improvements, including population management, vaccine price reduction, and increases in dog-vaccinating capacities. CONCLUSION: Our results highlight the resources needed to achieve elimination of dog-mediated human rabies deaths by 2030. As exemplified by multiple successful disease elimination efforts, one size does not fit all. We suggest pragmatic and feasible options toward global dog rabies elimination by 2030, while identifying several benefits and drawbacks of specific approaches. We hope that these results help stimulate and inform a necessary discussion on global and regional strategic planning, resource mobilization, and continuous execution of rabies virus elimination.

Earlier this year, Tony Fooks and colleagues described how, under a laboratory twinning project run by the World Organisation for Animal Health (OIE), the UK's OIE Reference Laboratory for rabies, based at the APHA in Weybridge, had been working with the Changchun Veterinary Research Institute in the People's Republic of China to help the institute develop into an OIE Reference Laboratory itself (VR, March 5, 2016, vol 178, pp 231-232). Now, the APHA is taking part in a further three-year project to build rabies diagnosis capability in Bangalore, India, as he and his colleagues explain below.

On September 18, 2014, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected rabies case in a Missouri resident. The patient, a man aged 52 years, lived in a rural, deeply wooded area, and bat sightings in and around his home were anecdotally reported. Exposure to bats poses a risk for rabies. After two emergency department visits for severe neck pain, paresthesia in the left arm, upper body tremors, and anxiety, he was hospitalized on September 13 for encephalitis of unknown etiology. On September 24, he received a diagnosis of rabies and on September 26, he died. Genetic sequencing tests confirmed infection with a rabies virus variant associated with tricolored bats. Health care providers need to maintain a high index of clinical suspicion for rabies in patients who have unexplained, rapidly progressive encephalitis, and adhere to recommended infection control practices when examining and treating patients with suspected infectious diseases.