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Problem Urbanization, large dog populations and failed control efforts have contributed to continuing endemicity of dog-mediated rabies in KwaZulu-Natal province, South Africa. Approach From 2007 to 2014 we used a OneHealth approach to rabies prevention, involving both the human and animal health sectors. We implemented mass vaccination campaigns for dogs to control canine rabies, and strategies to improve rabies awareness and access to postexposure prophylaxis for people exposed to rabies. Local setting A rabies-endemic region, KwaZulu-Natal is one of the smallest and most populous South African provinces (estimated population 10 900 000). Canine rabies has persisted since its introduction in 1976, causing an average of 9.2 human rabies cases per annum in KwaZulu-Natal from 1976 to 2007, when the project started. Relevant changes Between 2007 and 2014, the numbers of dog vaccinations rose from 358 611 to 395 000 and human vaccines purchased increased form 100 046 to 156 996. Strategic dog vaccination successfully reduced rabies transmission within dog populations, reducing canine rabies cases from 473 in 2007 to 37 in 2014. Actions taken to reduce the incidence of canine rabies, increase public awareness of rabies and improve delivery of postexposure prophylaxis contributed to reaching zero human rabies cases in KwaZulu- Natal in 2014. Lessons learnt Starting small and scaling up enabled us to build strategies that fitted various local settings and to successfully apply a OneHealth approach. Important to the success of the project were employing competent, motivated staff, and providing resources, training and support for field workers. Probleme L'urbanisation, les importantes populations canines et les mesures de lutte inefncaces ont contribue a l'endemlcite persistante de la rage transmise par les chlens dans la province du KwaZulu-Natal, en Afrique du Sud. Approche De 2007 a 2014, nous avons applique l'approche <> pour la prevention de la rage, et mobilise les secteurs de la sante humalne et de la sante animale. Nous avons mene des campagnes de vaccination massive des chiens en vue de lutter contre la rage canine, et deploye des strategies pour mleux sensibiliser la population a la rage et ameliorer l'acces des personnes exposees a la rage a la prophylaxle post-exposition. Environnement local Le KwaZulu-Natal, ou la rage est endemique, est l'une des provinces d'Afrique du Sud les plus petites et les plus peuplees (population estimee a 10 900 000 habitants). La rage canine persiste depuis son apparition en 1976, ayant provoque en moyenne 9,2 cas de rage humaine par an au KwaZulu-Natal entre 1976 et 2007, annee qui a marque le lancement du projet. Changements significatifs Entre 2007 et 2014, le nombre de vaccinations pratiquees sur des chiens est passe de 358 611 a 395 000, tandis que le nombre de vaccins humains achetes est passe de 100 046 a 156 996. La vaccination strategique des chiens a permis de faire reculer la transmission de la rage au sein des populations canines, le nombre de cas de rage animale passant de 473 en 2007 a 37 en 2014. Les actions prises pour reduire l'incidence de la rage canine, sensibillser la population a la rage et ameliorer l'acces a la prophylaxle post-exposition ont permis qu'aucun cas de rage humaine ne soit declare au KwaZulu-Natal en 2014. Lecons tirees En demarrant nope projet sur une petite echelle, puis en lui donnant une ampleur accrue, nous avons pu elaborer des strategles adaptees aux differents contextes locaux et appllquer avec succes l'approche <>. Le succes du projet a repose en grande partie sur le recrutement de professionnels competents et motives, et la mise a disposition de ressources, de formations et d'un soutien pour les agents locaux. Problema La urbanizacion, las grandes poblaciones de perros y los esfuerzos fallidos de control han contribuido a la continuacion de la transmision de la rabia por perros en la provincia de KwaZulu-Natal, Sudafrica. Enfoque De 2007 a 2014, se utilizo un enfoque <> para la prevencion de la rabia, que involucraba a los sectores de salud humana y animal. Se implementaron campanas de-vacunacion masiva para perros para controlar la rabia canina, asi como estrategias para mejorar la concienciacion sobre la rabia y el acceso a la profilaxis posterior a la exposicion para las personas expuestas a la rabia. Marco regional Una region endemica de la rabia, KwaZulu-Natal es una de las provincias sudafricanas mas pequenasy pobladas (poblacion estimada en 10 900 000). La rabia canina ha persistido desde su aparicion en 1976, causando una media de 9,2 casos de rabia en humanos al ano en KwaZulu-Natal entre 1976 y 2007, cuando comenzo el proyecto. Cambios importantes Entre 2007 y 2014, el numero de vacunas administradas a perros aumento de 358 611 a 395 000, mientras que las vacunas humanas adquiridas aumentaron de 100 046 a 156 996. La vacunacion estrategica en los perros redujo con exito la transmision de la rabia en las poblaciones caninas, lo que redujo los casos de rabia animal de 473 en 2007 a 37 en 2014. Las medidas adoptadas para reducir la Incidencia de la rabia canina, aumentar la concienciacion publica sobre la rabia y mejorar el suministro de profilaxis posterior a la exposicion contribuyeron a que en KwaZulu-Natal no se dieran casos de rabia humana en 2014. Lecciones aprendidas Empezar a pequena escala y despues incrementar los esfuerzos permitio crear estrategias que se ajustasen a los diversos marcos regionales e implementar con exito un enfoque <>. Para que el proyecto tuviera exito, fue importante contar con personal competente y motivado, asi como ofrecer recursos, formacion y apoyo a los trabajadores de campo. [phrase omitted], Introduction Rabies is a fatal zoonotic disease, causing tens of thousands of human deaths each year. (1) Most human rabies cases worldwide are caused by dog bites (2) and are [...]

Melinda Hergert,1 Kevin le Roux,2 Louis H Nel3,4 1Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, 2KwaZulu-Natal Department of Environment, Agriculture and Rural Development, Government Veterinary Services, Pietermaritzburg, 3Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa; 4Global Alliance for Rabies Control, Manhattan, KS, USA Abstract: Canine rabies has been enzootic in the dog population of the KwaZulu-Natal ­province of South Africa since the mid-1970s and has been associated with high rates of human exposures and frequent transmissions to other domestic animal species. Several decades of control efforts, consisting primarily of mass vaccination programs, failed to sufficiently curb rabies in this province. For meaningful progression toward better control and elimination, the factors contributing to the persistence of this disease need to be elucidated and addressed. This paper reports evaluated observations from survey records captured through a cross-sectional observational study regarding owned canine populations in this South African province. We used logistic regression modeling to predict variables associated with risk of nonvaccination of rabies in owned dogs. The study indicated that husbandry practices, rabies knowledge, geographical area/location, and the ages of dogs were important factors associated with the risk of nonvaccination. High population turnover, together with large free roaming dog populations, compromised the levels of vaccination achieved and contributed to the persistence of dog rabies in the province. Dog owners in this study also reported that they were more likely to present their dogs for vaccination when the vaccines were free of charge (52%) and less than a kilometer from their homes (91%). It has been suggested that effective dog rabies control requires 70% or more of the dog population to be vaccinated. Our data showed that this figure was not reached in the surveyed dog population. Keywords: dog population, canine rabies, rabies vaccination, vaccination campaigns, ­KwaZulu-Natal, South Africa, dog owners

Louise H Taylor,1 Louis H Nel1,21Global Alliance for Rabies Control, Manhattan, KS, USA; 2Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa Abstract: The rabies virus, a public health scourge from ancient times, is currently responsible for an estimated 59,000 human deaths a year, almost all transmitted via dog bites. It causes considerable economic impacts on developing countries, primarily in Africa and Asia, which can least afford these losses. However, despite its almost 100% case fatality rate, canine rabies is a completely preventable disease, and historic examples of canine rabies elimination in the developed world attest to this. Over the last decade, programs based on eliminating the source of the disease from dogs have shown success in reducing the public health burden of canine rabies in developing countries, notably across Latin America, and this has contributed to the growing evidence base necessary to change attitudes toward the feasibility of global canine rabies elimination. More recently, assessments of the current economic burden of canine rabies and the potential cost savings achievable through mass dog vaccinations have been added to this evidence base. Tools and support are available from the international community to help countries move progressively toward canine rabies elimination, and there is optimism that global freedom from canine rabies can be achieved within the next few decades. Keywords: canine rabies, epidemiology, elimination, zoonosis, rabies virus

The KwaZulu Natal and Eastern Cape provinces of South Africa have experienced a serious dog rabies epidemic over the past three decades. Towards a better understanding of this epidemic, we have previously analysed nucleotide sequences of 142 rabies virus specimens that were obtained from these regions during 2003-2004 and provided a molecular description of the geographical distribution of rabies viral variants in the affected provinces. Here, as an extension, we studied five human cases that occurred during 2002-2003 and demonstrated the use of the sequence database in tracking unknown human rabies case histories. We were able to identify the geographical origin of viruses responsible for each human infection and in one case obtained evidence that suggested a non-bite transmission of rabies virus from an infected dog to a child. We argue for the value of this information in surveillance and epidemiological study and in the follow-up and management of potential exposures. [ABSTRACT FROM AUTHOR]

We determined complete genome sequences of lineage 2 West Nile virus (WNV) strains isolated from patients in South Africa who had mild or severe WNV infections. These strains had previously been shown to produce either highly or less neuroinvasive infection and induced genes similar to corresponding highly or less neuroinvasive lineage 1 strains in mice. Phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially the nonstructural protein 5 gene, were most variable. All South African lineage 2 strains possessed the envelope-protein glycosylation site previously postulated to be associated with virulence. Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study. [ABSTRACT FROM AUTHOR]

With the global impetus for the elimination of canine-mediated human rabies, the need for robust rabies surveillance systems has become ever more important. Many countries are working to improve their rabies surveillance programs and, as a result, the reported use of lateral flow devices (LFDs) is increasing. Despite their known diagnostic limitations, previous studies have hypothesised that the benefits associated with LFDs could make them potentially quite useful towards improving the overall robustness of surveillance programs. To test this, a best practice standard operating procedure was developed which was used to guide the implementation of the ADTEC LFD as a diagnostic screening tool in Zanzibar. Over the course of the first 22 months of this investigation, 83 samples were subjected to in-field diagnostic screening, coupled with subsequent laboratory confirmation, and only one false-negative result was detected. Furthermore, the findings of our investigation indicated that the routine use of LFDs as a diagnostic screening tool resulted in a four-fold increase in the number of samples subjected to rabies diagnosis per month and a three-fold increase in the number of wards where samples were collected per year. Our findings suggest that LFDs could play a noteworthy role in improving the robustness of surveillance systems by increasing the number of samples tested and promoting diagnostic screening in areas distant from laboratories. Their implementation would, however, need to be carefully controlled through standardised protocols that align with the international best practices to ensure their judicious use., Competing Interests: The authors declare no conflicts of interest.

Despite the implementation of various control strategies aimed at eliminating canine-mediated rabies, the disease is still endemic in up to 150 countries across the world. Rabies remains endemic to South Africa, with various reservoir species (both wildlife species and domestic dogs) capable of maintaining rabies infection, and the epidemiology of the disease is yet to be adequately defined. As such, this study used surveillance data collected between 1998 and 2019 from the two diagnostic laboratories in the country for a statistical space-time analysis to determine regions where significant disease clusters could occur. In addition, the robustness of surveillance activities across the country was evaluated through the mathematical evaluation and visualization of testing rates based on the average number of samples tested per species group. In our study, various significant disease clusters were detected for domestic animals, wildlife and livestock. The significant disease clusters for domestic animals and livestock were primarily restricted to eastern South Africa, while the significant disease clusters in wildlife species were detected across northern and western South Africa. Furthermore, the testing rates identified districts from various provinces where surveillance activities could be considered inadequate, consequently influencing the geographical range of the observed clusters. These results could be used to direct intervention campaigns towards high-risk areas, while also allocating the required resources to improve surveillance in the surrounding areas where surveillance was deemed inadequate.

Tools and resources that could increase dog vaccination coverage have become increasingly critical towards progressing the goal to eliminate dog-mediated human rabies by 2030. In this regard, dog collars that are fitted during vaccination campaigns could potentially enhance owner participation. The use of dog collars will, however, increase the cost per dog vaccinated and the impact and benefit of this practice should be elucidated. This study evaluated the impact of dog collars by testing the perception and related behavioural influences in communities in Zanzibar. In this cross-sectional investigation-conducted approximately two months after the implementation of a mass dog vaccination (MDV) where dog collars were provided to vaccinated dogs-data were collected from 600 respondents in 56 municipal wards in Zanzibar. Descriptive analyses and logistic regressions were undertaken to determine the impact the collars had on respondents with regards to (i) engaging with the community dogs, (ii) health seeking behaviour after exposure, and (iii) overall participation during dog vaccination campaigns. From the data, it was evident that the collars had a positive impact on the community's perception of dogs, with 57% of the respondents feeling safer around a dog with a collar, while 66% of the respondents felt less safe around a dog without a collar. Furthermore, the collars had a positive impact on participation during dog vaccination campaigns. Of the 142 respondents who owned dogs, 64% reported that the collars made them more likely to take their dogs for vaccination, and 95% felt that the collar was an important sign of the dog's vaccination status. This study demonstrated that dog collars could not only improve participation during dog vaccination campaigns, but that they could also play a significant role in the community's perception of rabies vaccination campaigns and vaccinated dogs in general.

There has been a renewed focus on threats to the human-animal-environment interface as a result of the COVID-19 pandemic, and investments in One Health collaborations are expected to increase. Efforts to monitor the development of One Health Networks (OHNs) are essential to avoid duplication or misalignment of investments. This Series paper shows the global distribution of existing OHNs and assesses their collective characteristics to identify potential deficits in the ways OHNs have formed and to help increase the effectiveness of investments. We searched PubMed, Google, Google Scholar, and relevant conference websites for potential OHNs and identified 184 worldwide for further analysis. We developed four case studies to show important findings from our research and exemplify best practices in One Health operationalisation. Our findings show that, although more OHNs were formed in the past 10 years than in the preceding decade, investment in OHNs has not been equitably distributed; more OHNs are formed and headquartered in Europe than in any other region, and emerging infections and novel pathogens were the priority focus area for most OHNs, with fewer OHNs focusing on other important hazards and pressing threats to health security. We found substantial deficits in the OHNs collaboration model regarding the diversity of stakeholder and sector representation, which we argue impedes effective and equitable OHN formation and contributes to other imbalances in OHN distribution and priorities. These findings are supported by previous evidence that shows the skewed investment in One Health thus far. The increased attention to One Health after the COVID-19 pandemic is an opportunity to focus efforts and resources to areas that need them most. Analyses, such as this Series paper, should be used to establish databases and repositories of OHNs worldwide. Increased attention should then be given to understanding existing resource allocation and distribution patterns, establish more egalitarian networks that encompass the breadth of One Health issues, and serve communities most affected by emerging, re-emerging, or endemic threats at the human-animal-environment interface., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rabies is a viral zoonosis that causes an estimated 59,000 preventable human fatalities every year. While more than 120 countries remain endemic for dog-mediated rabies, the burden is the highest in Africa and Asia where 99% of human rabies cases are caused by domestic dogs. One such rabies-endemic country is South Africa where an estimated 42 preventable human deaths occur every year. Although canine rabies had been well described for most of the provinces in South Africa, the epidemiology of rabies within the North West Province had not been well defined prior to this investigation. As such, the aim of this study was to use nucleotide sequence analyses to characterise the extant molecular epidemiology of rabies in the North West Province of South Africa-with specific focus on the interface between dogs and sylvatic species. To this end, Rabies lyssavirus isolates originating from the North West Province were subjected to molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology on two distinct gene regions, viz. the G-L intergenic region and partial nucleoprotein gene. Our results provided strong evidence in support of an endemic cycle of canine rabies in the East of the province, and three independent endemic cycles of sylvatic rabies spread throughout the province. Furthermore, evidence of specific events of virus spill-over between co-habiting sylvatic species and domestic dogs was found. These results suggest that the elimination of canine-mediated rabies from the province will rely not only on eliminating the disease from the dog populations, but also from the co-habiting sylvatic populations using oral rabies vaccination campaigns.

Introduction: Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys., Methods: Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs., Results: Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies., Conclusion: There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies., Competing Interests: The authors have declared that no competing interests exist.

Rabies has been listed as a priority zoonotic disease in many African countries and the countdown to reach the goal of eliminating dog-mediated human rabies deaths by 2030 means that disease control measures need to be applied fast. In this context, an essential pillar of any national plan to control rabies is the implementation of reliable diagnostic techniques to ensure the success of field surveillance systems. Although many African countries have received international support for the control of rabies-some countries, like Benin, have not received a similar level of support. Indeed, until 2018, Benin was not able to diagnose rabies and rabies diagnosis in animals as well as humans relied solely on observed clinical symptoms. Although the Central Veterinary Laboratory (CVL) of Parakou had the equipment to implement two recommended tests, the lack of specific reagents and skills prevented the implementation of a rabies diagnostic service. Here we present the joint efforts of the national authorities in Benin, intergovernmental agencies, and non-governmental organizations to assess the strengths and weaknesses of the government's rabies control efforts. We have applied the Stepwise Approach toward Rabies Elimination (SARE) analysis, implemented rabies diagnostic capacities at the CVL of Parakou, characterized strains of rabies virus circulating in Benin, and finally integrated an inter-laboratory comparison program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Djegui, Gourlaouen, Coetzer, Adjin, Tohozin, Leopardi, Mauti, Akpo, Gnanvi, Nel and De Benedictis.)

Lyssaviruses cause the disease rabies, which is a fatal encephalitic disease resulting in approximately 59,000 human deaths annually. The prototype species, rabies lyssavirus, is the most prevalent of all lyssaviruses and poses the greatest public health threat. In Africa, six confirmed and one putative species of lyssavirus have been identified. Rabies lyssavirus remains endemic throughout mainland Africa, where the domestic dog is the primary reservoir - resulting in the highest per capita death rate from rabies globally. Rabies is typically transmitted through the injection of virus-laden saliva through a bite or scratch from an infected animal. Due to the inhibition of specific immune responses by multifunctional viral proteins, the virus usually replicates at low levels in the muscle tissue and subsequently enters the peripheral nervous system at the neuromuscular junction. Pathogenic rabies lyssavirus strains inhibit innate immune signaling and induce cellular apoptosis as the virus progresses to the central nervous system and brain using viral protein facilitated retrograde axonal transport. Rabies manifests in two different forms - the encephalitic and the paralytic form - with differing clinical manifestations and survival times. Disease symptoms are thought to be due mitochondrial dysfunction, rather than neuronal apoptosis. While much is known about rabies, there remain many gaps in knowledge about the neuropathology of the disease. It should be emphasized however, that rabies is vaccine preventable and dog-mediated human rabies has been eliminated in various countries. The global elimination of dog-mediated human rabies in the foreseeable future is therefore an entirely feasible goal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scott and Nel.)

Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers-using a novel selection method-were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.

Despite being vaccine preventable, the global burden of dog rabies remains significant, and historically it is the rural and marginalized communities in developing countries of Africa and Asia that are most threatened by the disease. In recent years, the developing world has been experiencing unprecedented increases in urbanization, with a correspondingly massive increase in municipal solid waste generation, among other things. Inefficient and inadequate waste collection and management, due to lack of resources and planning, led to significant increases in the volumes of waste on the streets and in open dumps, where it serves as food sources for free-roaming dogs. In this commentary, we discuss examples of poor waste management and the likely impact on rabies control efforts through the sustenance of free-roaming dogs in some dog rabies-endemic countries. We aim to stress the importance of implementing strategies that effectively address this particular issue as an important component of humane dog population management, as it relates to aspirations for the control and elimination of dog rabies per se.

Background: Rabies remains endemic to the Harare Metropolitan Province of Zimbabwe, with a lack of public participations potentially contributing to the limited success in eliminating the disease. We hypothesized that rabies intervention campaigns were less successful than they could be as a result of poor understanding of the disease at the community level, and thus aimed to identify the knowledge, attitudes, and practices towards rabies in the province., Methods: A cross-sectional survey, using a semi-structured questionnaire, was implemented between January 2017 and June 2018 across the province and data were collected from 798 respondents. Frequency distributions and logistic regressions were undertaken to determine the factors associated with the adequacy of the prevailing rabies knowledge, pet ownership characteristics and the existing preventative practices., Results: The results of our study suggested that the majority of the respondents (92%) had heard of rabies. However, the level of rabies knowledge could be classified as "adequate" in only 36% of respondents. The multivariate logistic regression analysis indicated that pet ownership and type of occupation were statistically associated with a better understanding and knowledge of the disease. Off all the respondents, 49% owned at least one dog or cat and suburb density and occupation were statistically associated with owning a pet. Amongst the pet owners, 57% consulted an animal health practitioner at least once a year and 75% were aware of a rabies vaccine for their pets. The multivariate logistic regression analysis indicated that age, education and gender were statistically associated with pet owners taking their pet(s) to an animal clinic., Conclusion: This study showed that the majority of the respondents lacked comprehensive knowledge about rabies, with the knowledge pertaining to health seeking behaviour and the importance of rabies vaccination being the most lacking. Additional public education relying on key messages, aimed at the different target audiences, is required in the province., Competing Interests: The authors have declared that no competing interests exist.

Domestic dogs are responsible for 99% of all cases of human rabies and thus, mass dog vaccination has been demonstrated to be the most effective approach towards the elimination of dog-mediated human rabies. Namibia demonstrated the feasibility of this approach by applying government-led strategic rabies vaccination campaigns to reduce both human and dog rabies incidences in the Northern Communal Areas of Namibia since 2016. The lessons learnt using paper-based form for data capturing and management of mass dog vaccination campaign during the pilot and roll out phase of the project (2016-2018) led to the implementation of a simple and accurate data collection tool in the second phase (2019-2022) of the rabies elimination program. In this paper, we describe the implementation of such custom-developed vaccination tracking device, i.e. the Global Alliance for Rabies Control (GARC) Data Logger (GDL), and the integration of the collected data into a website-based rabies surveillance system (Rabies Epidemiological Bulletin-REB) during 2019 and 2020 campaigns. A total of 10,037 dogs and 520 cats were vaccinated during the 2019 campaign and 13,219 dogs and 1,044 cats during the 2020 campaign. The vaccination data were recorded with the GDL and visualized via REB. Subsequent GIS-analysis using gridded population data revealed a suboptimal vaccination coverage in the great majority of grid cells (82%) with a vaccination coverage below 50%. Spatial regression analysis identified the number of schools, estimated human density, and adult dog population were associated with the vaccination performance. However, there was an inverse correlation to human densities. Nonetheless, the use of the GDL improved data capturing and monitoring capacity of the campaign, enabling the Namibian government to improve strategies for the vaccination of at-risk areas towards achieving adequate vaccination coverage which would effectively break the transmission of rabies., Competing Interests: The authors have declared that no competing interests exist.

Background: Rabies lyssavirus (RABV) is the aetiologic agent of rabies, a disease that is severely underreported in Nigeria as well as elsewhere in Africa and Asia. Despite the role that rabies diagnosis plays towards elucidating the true burden of the disease, Nigeria-a country of 180 million inhabitants-has a limited number of diagnostic facilities. In this study, we sought to investigate two of the World Organization for Animal Health (OIE)-recommended diagnostic assays for rabies-viz; the direct fluorescent antibody test (DFA) and the direct rapid immunohistochemical test (dRIT) in terms of their relative suitability in resource-limited settings. Our primary considerations were (1) the financial feasibility for implementation and (2) the diagnostic efficacy. As a case study, we used suspect rabies samples from dog meat markets in Nigeria., Methods/principal Findings: By developing a simple simulation framework, we suggested that the assay with the lowest cost to implement and routinely use was the dRIT assay. The costs associated with the dRIT were lower in all simulated scenarios, irrespective of the number of samples tested per year. In addition to the cost analysis, the diagnostic efficacies of the two assays were evaluated. To do this, a cohort of DFA-positive and -negative samples collected from dog meat markets in Nigeria were initially diagnosed using the DFA in Nigeria and subsequently sent to South Africa for diagnostic confirmation. In South Africa, all the specimens were re-tested with the DFA, the dRIT and a quantitative real-time polymerase chain reaction (qRT-PCR). In our investigation, discrepancies were observed between the three diagnostic assays; with the incongruent results being resolved by means of confirmatory testing using the heminested reverse transcription polymerase reaction and sequencing to confirm that they were not contamination., Conclusions/significance: The data obtained from this study suggested that the dRIT was not only an effective diagnostic assay that could be used to routinely diagnose rabies, but that the assay was also the most cost-effective option among all of the OIE recommended methods. In addition, the results of our investigation confirmed that some of the dogs slaughtered in dog markets were rabies-positive and that the markets posed a potential public health threat. Lastly, our data showed that the DFA, although regarded as the gold standard test for rabies, has some limitations-particularly at low antigen levels. Based on the results reported here and the current challenges faced in Nigeria, we believe that the dRIT assay would be the most suitable laboratory test for decentralized or confirmatory rabies diagnosis in Nigeria, given its relative speed, accuracy, cost and ease of use., Competing Interests: The authors have declared that no competing interest exist

The elimination of canine rabies through the implementation of high coverage mass dog vaccination campaigns is a complex task, particularly in the resource-limited countries of the rabies endemic world. Here we demonstrated the feasibility of applying targeted rabies vaccination campaigns to deliver more impactful intervention campaigns in resource-limited settings using evidence and lessons learnt from other diseases. With the use of strategic rabies intervention programs, we demonstrate the noteworthy reduction of rabies cases in two very different African settings. The strategic intervention was most significantly aided by the use of a custom-developed vaccination tracking device (the Global Alliance for Rabies Control (GARC) Data Logger) and an integrated rabies surveillance system (the Rabies Epidemiological Bulletin). Our first case study, an island-wide strategic dog vaccination on Tanzania's Unguja island, reduced the incidence of rabies by 71% in the first 16 months of implementation. In the second case study, a similar approach was applied in the metropolitan capital city of Zimbabwe and the incidence of rabies declined by 13% during the first 13 months of implementation. The methodologies and results presented here suggest that, in resource-limited settings, an optimal approach towards the elimination of dog rabies would revolve around strategic interventions, subject to the use of appropriate planning, surveillance, and vaccination tools.

Rabies is a neglected disease mostly affecting the developing world. Accurate and reliable diagnostic and surveillance data forms the foundation for the formulation and monitoring of control strategies. Although various sensitive and specific tests are available for detection of rabies virus, implementation of these tests in low-resource settings are challenging and remains limited. In this study, we describe the developed of a reverse transcription recombinase polymerase amplification assay for the detection of rabies virus. The analytical sensitivity of this assay was determined to be 562 RNA copies and was performed in 20 minutes. The diagnostic sensitivity of the RT-RPA was 100% for detection of rabies virus in field samples. In conclusion, the RT-RPA assay allowed for very quick and sensitive detection of rabies virus and could be adapted for use in low-source settings., Competing Interests: The authors have declared that no competing interests exist.

We present a new modeling tool that can be used to maximize the impact of canine rabies management resources that are available at the local level. The model is accessible through a web-based interface that allows for flexibility in the management strategies that can be investigated. Rabies vaccination, sterilization, chemo-contraception, and euthanasia can be specified and limited to specific demographic groups. Additionally, we allowed for considerable complexity in the specification of management costs. In many areas, the costs of contacting additional dogs increases as management effort increases, and this can have important strategic implications. We illustrated the application of the model by examining several alternative management strategies in an area of Mpumalanga Province, South Africa. Our results based on this dog population suggested that puppies should be vaccinated and sterilization would not be optimal if the spatial extent of management is not large (and perhaps not even then). Furthermore, given a sufficient budget, it was evident that vaccination campaigns should be repeated annually., Competing Interests: The authors have declared that no competing interests exist.

Background: Canine rabies has been enzootic in the dog population of the KwaZulu-Natal province of South Africa since the mid-1970s and has been associated with high rates of human exposures and frequent transmissions to other domestic animal species. Several decades of control efforts, consisting primarily of mass vaccination programs, have previously failed to sufficiently curb rabies in the province. Despite this history of canine rabies, the target canine population has never been extensively studied or quantified. For efficient and effective vaccination campaign planning, the target population must be evaluated and understood. This study reports evaluated observations from survey records captured through a cross sectional observational study regarding canine populations and dog owners in rabies enzootic KwaZulu-Natal province, South Africa. The objective of this study was to aid government veterinary services in their current and ongoing efforts to eliminate canine rabies in the province by gaining information about the size and distribution of the owned dog population., Results: Thirty-eight percent of the households owned one or more dogs, with rural areas surveyed containing a significantly higher number of owned dogs than urban areas. The mean dog/person ratio for this study was 1:7.7 (range 1:5.4-1:31). The provincial sex ratio was 1.5:1 male to female, with the percentages for male dogs across the communities ranging from 53 to 61.5%. The age structure of this dog population indicates a high turnover rate. Dogs were kept mostly for guarding homes or livestock. Eighty-four percent of dogs had received a rabies vaccine at some point in their lifetime, almost all during a rabies campaign., Conclusions: The study indicates the majority of owned dogs can be handled by at least one member of the household, thus can be made readily accessible for rabies vaccination during a campaign. Characteristics of owned dogs in the province were similar to those studied in other African countries; however, there were remarkable differences in age, sex and husbandry practices compared to dogs in eastern or northern Africa. These geographical differences lend credence to the theory that canine populations are heterogeneous; therefore, target populations should be evaluated prior to intervention planning.

The drive towards the worldwide elimination of dog-mediated human rabies by 2030 is the first step towards the ultimate goal of dog rabies elimination - as dogs account for more than 99% of human rabies cases globally - and has gained considerable momentum since this resolution was taken at a global meeting in Geneva in December 2015. For dog rabies-endemic countries and regions, dedicated regional networks may offer unique opportunities to take advantage of this global momentum. Towards this goal, the Pan-African Rabies Control Network (PARACON) was created in 2015, and the past year has seen the formation of the Asian Rabies Control Network (ARACON). ARACON provides opportunities for member countries to share lessons learnt and challenges faced, while also introducing them to programmatic support tools such as the Stepwise Approach towards Rabies Elimination (SARE) assessment and the Rabies Epidemiological Bulletin (REB). During the inaugural ARACON meeting, member countries evaluated their progress and developed country-specific Practical Workplans based on their SARE outcomes. The results from the national-level SARE assessments were considered at the regional level and, after discussion among countries, consensual agreement was reached that the target date of regional freedom from dog-mediated human rabies by 2020 was not feasible, and a new regional target of 2030 was set. With this new regional target, ongoing support will continue to be provided to countries through regional structures such as ARACON. However, the responsibility remains with the countries to use the available tools and resources to progress towards the new regional goal of dog-mediated human rabies elimination by 2030., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rabies control worldwide has been inadequate and neglected for many decades, and the disease continues to predominantly affect poor communities in Africa and Asia. As a zoonosis for which the main reservoir and vector, the domestic dog (Canis familiaris), is an economically non-viable species, the absence of cross-sectoral cooperation has been a major factor in the lack of effective control efforts. A shift in global focus is required to concentrate on the fact that rabies has the highest case fatality ratio of all infectious human diseases and that it still affects human health more significantly than many other infectious diseases that are perceived to pose more significant risks. Equally necessary is an acknowledgement that rabies control is complex and that the task of creating and executing a strategic plan for the disease can be overwhelming for those governments in the developing world where dog rabies is most problematic. Nonprofit organisations operate independently of governments and intergovernmental organisations and can play a dynamic role in inter-sectoral collaboration and the creation of approaches and strategies for the control of complex diseases such as rabies. In 2008, the Global Alliance for Rabies Control (GARC) established Partners for Rabies Prevention (PRP), a widely representative group of rabies stakeholders and experts, which endeavours to support public-private rabies control activities throughout the world. After a landscape analysis, the PRP proceeded to develop and launch the Blueprint for Rabies Prevention and Control (comprising the Blueprint for Canine Rabies Prevention and Control; the Blueprint for Fox Rabies Prevention and Control and the Rabies Surveillance Blueprint). Subsequently, the Stepwise Approach towards Rabies Elimination (SARE) was embedded into the Canine Rabies Blueprint. The SARE is a planning and self-assessment tool that countries can use to develop activities and monitor progress towards a national programme and strategy for sustainable rabies control and elimination. Each of the elements needed to execute the SARE-derived strategy is cross-linked to the Canine Rabies Blueprint, which provides the specific methods and tools required, supported by references and examples. Together, the Canine Rabies Blueprint and the SARE should be regarded as a novel and dynamic operational toolkit, and a resource that provides comprehensive information for the development and implementation of rabies control strategies, built entirely on the principles of 'One Health'.

Background: The Philippines has built an extensive decentralised network of Animal Bite Treatment Centers (ABTCs) to help bite victims receive timely rabies post-exposure prophylaxis (PEP) at little cost. This study surveyed patients in the community and at ABTCs of three provinces to assess animal bite/scratch incidence, health-seeking behaviour and PEP-related out-of pocket expenses (OOPE)., Methodology and Principal Findings: During community surveys in 90 barangays (neighbourhoods), 53% of households reported at least one animal bite /scratch injury over the past 3 years, similar across urban and rural barangays. Overall bite/scratch incidences in 2016-17 were 67.3, 41.9 and 48.8 per 1,000 population per year for Nueva Vizcaya, Palawan and Tarlac respectively. Incidences were around 50% higher amongst those under 15 years of age, compared to -those older than 15. Household awareness of the nearest ABTCs was generally over 80%, but only 44.9% sought proper medical treatment and traditional remedies were still frequently used. The proportion of patients seeking PEP was not related to the distance or travel time to the nearest ABTC. For those that did not seek medical treatment, most cited a lack of awareness or insufficient funds and almost a third visited a traditional healer. No deaths from bite/scratch injuries were reported. A cohort of 1,105 patients were interviewed at six ABTCs in early 2017. OOPE varied across the ABTCs, from 5.53 USD to 37.83 USD per patient, primarily dependent on the need to pay for immunization if government supplies had run out. Overall, 78% of patients completed the recommended course, and the main reason for non-completion was a lack of time, followed by insufficient funds. Dog observation data revealed that 85% of patients were not truly exposed to rabies, and education in bite prevention might reduce provoked bites and demand for PEP. An accompanying paper details the ABTC network from the health provider's perspective., Competing Interests: Funding for this investigator-sponsored study was provided by GlaxoSmithKline Biologicals SA. ACBA, SIJ, MLLM, MPZDC, DAL, MCR, MCLQ, and LHT were funded proportionate to their time spent on the study. GlaxoSmithKline Biologicals SA reviewed and approved the protocol, but did not influence the project implementation, data collection, analysis or interpretation. They were also provided with an opportunity to review a preliminary version of this report for factual accuracy but the authors are solely responsible for final content and interpretation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The Philippine government has an extensive network of 513 Animal Bite Treatment Centers (ABTCs) to supply rabies post exposure prophylaxis (PEP), reaching over 1 million bite victims in 2016. The network was evaluated using a review of existing national and provincial data, key informant interviews and surveys in sample ABTCs to determine the cost-effectiveness of this network in preventing human rabies deaths., Methodology and Principal Findings: One urban and one rural ABTC in each of three selected provinces were studied in more detail. PEP delivery generally followed national guidance based on best practices, but there was evidence of operational challenges in supplying all ABTCs with adequate biologics and recently trained staff. Funding was contributed by different levels of government and in some clinics, patients paid for a significant fraction of the total cost. From a health provider perspective including both fixed and variable costs, the average PEP course delivered cost USD 32.91 /patient across urban ABTCs (with higher patient throughput) and USD 57.21 /patient across rural ABTCs. These costs suggests that PEP provision in the Philippines cost USD 37.6 million in 2016, with a cost per life saved of USD 8,290. An analysis of the 2,239 suspected rabies deaths from 2008 to 2016 showed no significant decline, and from 2014-16 an average of 8,534 years of life were lost annually. The incidence of rabies deaths from 2014-16 was not clearly related to the provision of ABTCs (per 100,000 population) or human population density, but deaths were more common in higher income provinces., Conclusions/significance: In the context of comprehensive rabies control (including dog vaccination and public awareness) ways to reduce this high expenditure on PEP should be explored, to most cost-effectively reach the elimination of human rabies deaths. This paper is accompanied by another containing data on the operation of ABTCs network from a patient perspective., Competing Interests: Funding for this investigator-sponsored study was provided by GlaxoSmithKline Biologicals SA. ACBA, SIJ, LHT, MCR, and MCLQ were funded proportionate to their time spent on the study. GlaxoSmithKline Biologicals SA reviewed and approved the protocol, but did not influence the project implementation, data collection, analysis or interpretation. They were also provided with an opportunity to review a preliminary version of this report for factual accuracy but the authors are solely responsible for final content and interpretation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

An appreciation of the costs of implementing canine rabies control in different settings is important for those planning new or expanded interventions. Here we compare the costs of three canine rabies control projects in South Africa, the Philippines and Tanzania to identify factors that influence the overall costs of rabies control efforts. There was considerable variation in the cost of vaccinating each dog, but across the sites these were lower where population density was higher, and later in the projects when dog vaccination coverage was increased. Transportation costs comprised a much higher proportion of total costs in rural areas and where house-to-house vaccination campaigns were necessary. The association between the cost of providing PEP and human population density was less clear. The presence of a pre-existing national rabies management programme had a marked effect on keeping infrastructure and equipment costs for the project low. Finally, the proportion of the total costs of the project provided by the external donor was found to be low for the projects in the Philippines and South Africa, but likely covered close to the complete costs of the project in Tanzania. The detailed economic evaluation of three recent large-scale rabies control pilot projects provides the opportunity to examine economic costs across these different settings and to identify factors influencing rabies control costs that could be applied to future projects., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current rabies vaccines do not provide cross protection against phylogroup II lyssaviruses. To investigate the potential role of the LBV matrix protein (M) and glycoprotein (G) in pathogenesis, reverse genetics technology was used to construct recombinant viruses. The genes encoding the glycoprotein, or the matrix and glycoprotein of the attenuated RABV strain SPBN, were replaced with those of LBV resulting in SPBN-LBVG and SPBN-LBVM-LBVG, respectively. To evaluate the immunogenicity of the LBV G, the recombinant RABV SPBNGAS-LBVG-GAS was constructed with the LBV G inserted between two mutated RABV G genes (termed GAS). All the recombinant viruses were lethal to mice after intracranial (i.c.) inoculation although the pathogenicity of SPBNGAS-LBVG-GAS was lower compared to the other recombinant viruses. Following intramuscular (i.m.) inoculation, only SPBN-LBVM-LBVG was lethal to mice, indicating that both the M and G of LBV play a role in the pathogenesis. Most interestingly, serum collected from mice that were inoculated i.m. with SPBNGAS-LBVG-GAS neutralized phylogroup I and II lyssaviruses including RABV, Duvenhage virus (DUVV), LBV, and Mokola virus (MOKV), indicating that this recombinant virus has potential to be developed as a pan-lyssavirus vaccine., Competing Interests: The authors declare no conflict of interest.

Rabies is widespread throughout Africa and Asia, despite the fact that the control and elimination of this disease has been proven to be feasible. Lesotho, a small landlocked country surrounded by South Africa, has been known to be endemic for rabies since the 1980s but the epidemiology of the disease remains poorly understood due to limited sample submission, constrained diagnostic capabilities, and a lack of molecular epidemiological data. Considering the existing challenges experienced in Lesotho, we aimed to evaluate the direct, rapid immunohistochemical test (DRIT) as an alternative to the direct fluorescent antibody (DFA) test for rabies diagnosis in Lesotho. Towards this aim, extensive training on the implementation and interpretation of the DRIT was hosted in Lesotho in April 2016 before both tests were applied to all samples subjected to routine rabies diagnosis at the Central Veterinary Laboratory (CVL). We found agreement between the DFA and DRIT assays in 90/96 samples (93.75%). The samples that produced inconsistent results ( n = 6) were re-tested a further two times with both assays before being subjected to a real-time qPCR to confirm the diagnosis. Additionally, a statistically significant three-fold increase in the average number of samples submitted per month was observed after the DRIT implementation started, following continuous rabies awareness initiatives amongst the animal health professionals in the country over a 12-month period ( p = 0.0279). Partial G-L intergenic regions of selected rabies-positive samples ( n = 21) were amplified, sequenced, and subjected to phylogenetic analyses. Molecular epidemiological analyses, that included viruses from neighbouring provinces in South Africa, suggested that at least three independent rabies cycles within Lesotho were implicated in instances of cross-border transmission. This study has evaluated alternative methods for diagnosing and improving rabies surveillance in Lesotho, as well as providing new information that would be of importance in the planning of future disease intervention campaigns, not only in Lesotho, but also in neighbouring South Africa., Competing Interests: The authors declare no conflict of interest.

Free-roaming dogs and rabies transmission are integrally linked across many low-income countries, and large unmanaged dog populations can be daunting to rabies control program planners. Dog population management (DPM) is a multifaceted concept that aims to improve the health and well-being of free-roaming dogs, reduce problems they may cause, and may also aim to reduce dog population size. In theory, DPM can facilitate more effective rabies control. Community engagement focused on promoting responsible dog ownership and better veterinary care could improve the health of individual animals and dog vaccination coverage, thus reducing rabies transmission. Humane DPM tools, such as sterilization, could theoretically reduce dog population turnover and size, allowing rabies vaccination coverage to be maintained more easily. However, it is important to understand local dog populations and community attitudes toward them in order to determine whether and how DPM might contribute to rabies control and which DPM tools would be most successful. In practice, there is very limited evidence of DPM tools achieving reductions in the size or turnover of dog populations in canine rabies-endemic areas. Different DPM tools are frequently used together and combined with rabies vaccinations, but full impact assessments of DPM programs are not usually available, and therefore, evaluation of tools is difficult. Surgical sterilization is the most frequently documented tool and has successfully reduced dog population size and turnover in a few low-income settings. However, DPM programs are mostly conducted in urban settings and are usually not government funded, raising concerns about their applicability in rural settings and sustainability over time. Technical demands, costs, and the time necessary to achieve population-level impacts are major barriers. Given their potential value, we urgently need more evidence of the effectiveness of DPM tools in the context of canine rabies control. Cheaper, less labor-intensive tools for dog sterilization will be extremely valuable in realizing the potential benefits of reduced population turnover and size. No one DPM tool will fit all situations, but if DPM objectives are achieved dog populations may be stabilized or even reduced, facilitating higher dog vaccination coverages that will benefit rabies elimination efforts.

Rabies, a vaccine preventable neglected tropical disease, still claims an estimated 35,000-60,000 human lives annually. The international community, with more than 100 endemic countries, has set a global target of 0 human deaths from dog-transmitted rabies by 2030. While it has been proven in several countries and regions that elimination of rabies as a public health problem is feasible and tools are available, rabies deaths globally have not yet been prevented effectively. While there has been extensive rabies research, specific areas of implementation for control and elimination have not been sufficiently addressed. This article highlights some of the commonest perceived barriers for countries to implementing rabies control and elimination programs and discusses possible solutions for sociopolitical, organizational, technical, and resource-linked requirements, following the pillars of the global framework for the elimination of dog-mediated human rabies adopted at the global rabies meeting in December 2015.

As canine rabies control in Africa and Asia transitions from research-led proof-of-concept studies to government-led programs for elimination, experience and evidence of their impact and costs must be shared for the benefit of future programs. The Ilocos Norte Communities against Rabies Exposure project was implemented in April 2012 by the provincial veterinary and health offices and supported by many other partners. It delivered a comprehensive dog vaccination program and increased awareness of the need for postexposure prophylaxis (PEP), aiming to eliminate human and animal rabies cases from Ilocos Norte by 2015. Prior to the intervention, confirmed rabies cases in dogs were between 19 and 50 per year (2008-2011). The primary outcome of the project was a reduction in rabies cases in both dogs and humans to 0 in 2014 and 2015, which has subsequently been maintained. Animal bite consultations increased significantly during the project. Economic data for the dog vaccination and PEP components of the project were collated for two sites: Laoag City (an urban setting) and Dingras Municipality (a rural setting) between 2012 and 2014. The average programmatic cost of vaccinating each dog was $4.54 in Laoag City and $8.65 in Dingras, and costs fell as the project reached more dogs. The average costs of providing PEP were $69.72 per patient and $49.02 per patient for the two sites, respectively, again falling as the project reached more people. External donor contributions contributed less than 20% of dog vaccination costs and less than 1% of PEP costs. The project demonstrated that rabies elimination can be achieved in a short period of time, with concerted effort across multiple sectors. A lack of clear dog population estimates hampered interpretation of some aspects of the programme. From 2016, the provincial government has assumed complete responsibility for the programme and must now continue the vaccination and surveillance efforts. Although safeguards are in place, reintroduction from surrounding areas remains a threat, and vigilance must be maintained.

Rabies is a neglected zoonotic disease with veterinary and public health significance, particularly in Africa and Asia. The current knowledge of the epidemiology of rabies in Mozambique is limited because of inadequate sample submission, constrained diagnostic capabilities and a lack of molecular epidemiological research. We wanted to consider the direct, rapid immunohistochemical test (DRIT) as an alternative to the direct fluorescent antibody (DFA) for rabies diagnosis at the diagnostic laboratory of the Central Veterinary Laboratory (CVL), Directorate of Animal Science, Maputo, Mozambique. Towards this aim, as a training exercise at the World Organisation for Animal Health (OIE) Rabies Reference Laboratory in South Africa, we performed the DRIT on 29 rabies samples from across Mozambique. With the use of the DRIT, we found 15 of the 29 samples (52%) to be negative. The DRIT-negative samples were retested by DFA at the OIE Rabies Reference Laboratory, as well as with an established real-time Polymerase chain reaction, confirming the DRIT-negative results. The DRIT-positive results (14/29) were retested with the DFA and subsequently amplified, sequenced and subjected to phylogenetic analyses, confirming the presence of rabies RNA. Molecular epidemiological analyses that included viruses from neighbouring countries suggested that rabies cycles within Mozambique might be implicated in multiple instances of cross-border transmission. In this regard, our study has provided new insights that should be helpful in informing the next steps required to better diagnose, control and hopefully eliminate rabies in Mozambique.

Objective: To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings., Methods: We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines., Findings: Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability., Conclusion: Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

It is evident that rabies continues to be a neglected tropical disease; however, a recent global drive aims to eliminate canine-mediated human rabies by 2030. Global efforts have been vested into creating and developing resources for countries to take ownership of and overcome the challenges that rabies poses. The disconnect between the numbers of rabies cases reported and the numbers estimated by prediction models is clear: the key to understanding the epidemiology and true burden of rabies lies within accurate and timely data; poor and discrepant data undermine its true burden and negate the advocacy efforts needed to curb this lethal disease. In an effort to address these challenges, the Pan-African Rabies Control Network is developing a regional rabies-specific disease surveillance bulletin based on the District Health Information System 2 platform-a web-based, open access health information platform. This bulletin provides a data repository from which specific key indicators, essential to any rabies intervention program, form the basis of data collection. The data are automatically analyzed, providing useful outputs for targeted intervention. Furthermore, in an effort to reduce reporting fatigue, the data submitted, under authority from the respective governments, can automatically be shared with approved international authorities. The implementation of a rabies-specific bulletin will facilitate targeted control efforts and provide measurements of success, while also acting as a basis for advocacy to raise the priority of this neglected disease.

Background: Mokola virus (MOKV) is a rabies-related lyssavirus and appears to be exclusive to the African continent. Only 24 cases of MOKV, which includes two human cases, have been reported since its identification in 1968. MOKV has an unknown reservoir host and current commercial vaccines do not confer protection against MOKV., Results: We describe three new isolations of MOKV from domestic cats in South Africa. Two cases were retrospectively identified from 2012 and an additional one in 2014., Conclusions: These cases emphasize the generally poor surveillance for rabies-related lyssaviruses and our inadequate comprehension of the epidemiology and ecology of Mokola lyssavirus per se.

There is a need for innovation to improve control of all Neglected Zoonotic Diseases (NZDs). The Global Alliance for Rabies Control was formed to prevent human deaths from rabies and relieve the burden of rabies in other animal populations, especially dogs. It aims to identify reasons for the neglect of rabies in developing countries and to develop strategies to improve rabies control. Through initiatives such as World Rabies Day and the Partners for Rabies Prevention, progress has been made towards increased awareness of the burden of rabies transmitted by dogs at scales from local to international. An evidence base of the feasibility of canine rabies elimination has been built up and now easier access to information and tools enables countries to design and implement rabies elimination strategies in a logical way, utilizing the structures of regional networks for rabies control. The body of evidence has built consensus amongst international stakeholders in rabies control and is now being used to encourage international policy change, attract investment and increase delivery of effective rabies control programmes in canine rabies endemic countries., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Current passive surveillance data for canine rabies, particularly for the regions where the burden is highest, are inadequate for appropriate decision making on control efforts. Poor enforcement of existing legislation and poor implementation of international guidance reduce the effectiveness of surveillance systems, but another set of problems relates to the fact that canine rabies is an untreatable condition which affects very poor sectors of society. This results in an unknown, but potentially large proportion of rabies victims dying outside the health system, deaths that are unlikely to be recorded by surveillance systems based on health center records. This article critically evaluates the potential sources of information on the number of human deaths attributable to canine rabies, and how we might improve the estimates required to move towards the goal of global canine rabies elimination., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

International rabies networks have been formed in many of the canine-rabies endemic regions around the world to create unified and directed regional approaches towards elimination. The aim of the first sub-regional Eastern Africa rabies network meeting, which included Kenya, Ethiopia, Tanzania, Rwanda, and Uganda, was to discuss how individual country strategies could be coordinated to address the unique challenges that are faced within the network. The Stepwise Approach towards Rabies Elimination and the Global Dog Rabies Elimination Pathway tool were used to stimulate discussion and planning to achieve the elimination of canine-mediated human rabies by 2030. Our analysis estimated a total dog population of 18.3 million dogs in the Eastern Africa region. The current dog vaccination coverage was estimated to be approximately 5% (915,000 dogs), with an estimated 4910 vaccinators available. Assuming that every vaccinator performs rabies vaccination, this equated to each vaccinator currently vaccinating 186 dogs per year, whilst the target would be to vaccinate 2609 dogs every year for the community to reach 70% coverage. In order to achieve the World Health Organization-recommended 70% vaccination coverage, an additional 11 million dogs need to be vaccinated each year, pointing to an average annual shortfall of $ 23 million USD in current spending to achieve elimination by 2030 across the region. Improved vaccination efficiency within the region could be achieved by improving logistics and/or incorporating multiple vaccination methods to increase vaccinator efficiency, and could serve to reduce the financial burden associated with rabies elimination. Regional approaches to rabies control are of value, as neighboring countries can share their unique challenges while, at the same time, common approaches can be developed and resource-saving strategies can be implemented., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

The Stepwise Approach towards Rabies Elimination (SARE) tool was developed through a joint effort of the Food and Agriculture Organization (FAO) of the United Nations and the Global Alliance for Rabies Control (GARC), to provide a standard mechanism for countries to assess their rabies situation and measure progress in eliminating the disease. Because the African continent has the highest per capita death rate from rabies, and Ethiopia is estimated to have the second largest number of rabies deaths of all African countries, Ethiopia undertook a self-assessment by means of the Stepwise Approach towards Rabies Elimination (SARE) tool. In February 2016, the Ethiopian government hosted an intersectoral consultative meeting in an effort to assess the progress that has been made towards the control and elimination of canine rabies. The SARE assessment identified a number of critical gaps, including poor inter-sectoral collaboration and limited availability and access to dog vaccine, while the existence of a surveillance system for rabies and legislation for outbreak declaration and response were among the strengths identified. The SARE tool enabled key criteria to be prioritized, thereby accelerating the National Strategy and ensuring that Ethiopia will progress rapidly in line with the goals set by the global community for the elimination of human rabies deaths by 2030. Although the analysis showed that Ethiopia is still in the early stages of rabies control (Stage 0.5/5), the country shows great promise in terms of developing a SARE-guided National Rabies Prevention and Control Strategy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

World Rabies Day was set up in 2007 to raise global awareness about rabies, to provide information on how to prevent the disease in at-risk communities and support advocacy for increased efforts in rabies control. It is held annually on September 28th, with events, media outreach and other initiatives carried out by individuals, professionals, organisations and governments from the local to the international level. The Global Alliance for Rabies Control coordinates World Rabies Day, amplifying the campaign's reach through the provision of a central event platform and resources to support events across the world, the promotion of messages through key rabies stakeholders, and the implementation of specific activities to highlight particular issues. Over the last decade, more than 1,700 registered events have been held across the world and shared with others in the global rabies community. Events in canine rabies endemic countries, particularly in Africa and Asia, have increased over time. Beyond the individual events, World Rabies Day has gained the support of governments and international agencies that recognise its value in supporting existing rabies control initiatives and advocating for improvements. As the rabies landscape has changed, World Rabies Day remains a general day of awareness but has also become an integral part of national, regional and global rabies elimination strategies. The global adoption of 2030 as the goal for the elimination of rabies as a public health threat has led to even greater opportunities for World Rabies Day to make a sustainable impact on rabies, by bringing the attention of policy makers and donors to the ongoing situation and elimination efforts in rabies-endemic countries.

Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses-including age, sex, cerebral lateralization and temperature-are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host's response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.

Rabies remains a significant problem throughout much of the developing world. An estimated 69 000 people die annually from exposure to rabies. Most of these deaths are the result of being bitten by a rabid dog. Mass vaccination campaigns targeting dogs have been implemented around the world in an attempt to control or eliminate canine rabies. We analysed the vaccination and cost data for a campaign in the KwaZulu-Natal province of South Africa; we found that the cost per dog vaccinated to be $6.61 for mass campaigns and $5.41 for local campaigns. We also estimated the cost of human post-exposure prophylaxis (PEP). The cost of PEP is approximately $64.50 on average per patient, and $333 on average for the 9% of patients who receive RIG. We also found that the districts that vaccinated the most dogs per capita experienced the highest rates of human treatment and thus had the highest PEP costs., (© 2014 Blackwell Verlag GmbH.)

In addition to several emerging viruses, bats have been reported to host multiple bacteria but their zoonotic threats remain poorly understood, especially in Africa where the diversity of bats is important. Here, we investigated the presence and diversity of Bartonella and Rickettsia spp. in bats and their ectoparasites (Diptera and Siphonaptera) collected across South Africa and Swaziland. We collected 384 blood samples and 14 ectoparasites across 29 different bat species and found positive samples in four insectivorous and two frugivorous bat species, as well as their Nycteribiidae flies. Phylogenetic analyses revealed diverse Bartonella genotypes and one main group of Rickettsia, distinct from those previously reported in bats and their ectoparasites, and for some closely related to human pathogens. Our results suggest a differential pattern of host specificity depending on bat species. Bartonella spp. identified in bat flies and blood were identical supporting that bat flies may serve as vectors. Our results represent the first report of bat-borne Bartonella and Rickettsia spp. in these countries and highlight the potential role of bats as reservoirs of human bacterial pathogens.

Even though Africa has the highest per capita death rate from rabies of any continent, and the disease is almost entirely transmitted by the bites of rabid dogs, there has been no coordinated pan-African approach to controlling canine rabies. In order to attain an inclusive and unified network, the Pan-African Rabies Control Network (PARACON) was established in 2014. By following the 'One Health' concept, which involves close coordination between animal and human health sectors across national, regional and continental levels, PARACON will provide a platform to facilitate and promote coordinated and sustainable control strategies and programmes. Meetings will take place at regular intervals and will be centred on the involvement by key focal persons from the medical and veterinary sectors. The inaugural meeting was held in South Africa in June, 2015 and was focused around interactive discussions and workshops, whilst updating country representatives on the tools available to aid them in developing and implementing sustainable rabies intervention strategies. Experts from various global organizations, institutions and industry participated in the discussions and shared their experience and expertise. The workshops focused on the latest format of the Rabies Blueprint platform (www.rabiesblueprint.com), which in the broadest sense assists with control and elimination campaigns, including educational and advocacy drives, improvement of surveillance and diagnosis and the systematic monitoring of progress. Together with the Stepwise Approach towards Rabies Elimination, the Blueprint is a planning tool to help countries free themselves from canine-transmitted rabies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

As part of a larger survey for detection of pathogens among wildlife in sub-Saharan Africa conducted during 2007-2012, multiple diverse paramyxovirus sequences were detected in renal tissues of bats. Phylogenetic analysis supports the presence of at least 2 major viral lineages and suggests that paramyxoviruses are strongly associated with several bat genera.

This report describes four suspected rabies cases in domestic dogs that were involved inhuman exposures. In all these cases, the animals were buried for substantial times beforerabies testing was performed. Animal rabies is endemic in South Africa and domestic dogsare the main vector for transmission to humans. Diagnosis of rabies in humans is complicated,and diagnosis in the animal vector can provide circumstantial evidence to support clinicaldiagnosis of rabies in humans. The gold standard diagnostic method, fluorescent antibodytest (FAT), only delivers reliable results when performed on fresh brain material and thereforedecomposed samples are rarely submitted for diagnostic testing. Severely decomposed brainmaterial was tested for the presence of rabies virus genomic material using a quantitativereal-time reverse transcription polymerase chain reaction (q-real-time RT-PCR) assaywhen conventional molecular methods were unsuccessful. This may be a useful tool in theinvestigation of cases where the opportunity to sample the suspected animals post mortem wasforfeited and which would not be possible with conventional testing methodologies becauseof the decomposition of the material.