A global analysis of One Health Networks and the proliferation of One Health collaborations.

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.

Towards rabies elimination in the Asia-Pacific region: From theory to practice.

Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25-26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic of human rabies mediated by dogs. The objective of the meeting was focused upon snowballing efforts towards achieving substantial progress in rabies prevention, control and elimination within Asia by 2030, and thereby to safeguard the Pacific region. Individual sessions focused upon domestic animal, wildlife and human vaccination; the production and evaluation of quality, safety and efficacy of existing rabies biologics; and the future development of new products. Participants reviewed the progress to date in eliminating canine rabies by mass vaccination, described supportive methods to parenteral administration by oral vaccine application, considered updated global and local approaches at human prophylaxis and discussed the considerable challenges ahead. Such opportunities provide continuous engagement on disease management among professionals at a trans-disciplinary level and promote new applied research collaborations in a modern One Health context.

Characteristics of owned dogs in rabies endemic KwaZulu-Natal province, South Africa.

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.

Pre-exposure rabies prophylaxis: a systematic review.

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.

New isolations of the rabies-related Mokola virus from South Africa.

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.

Scoping review of indicators and methods of measurement used to evaluate the impact of dog population management interventions.

BACKGROUND: Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change. METHODS: This scoping review collates 26 studies that have assessed the impacts of dog population management interventions. RESULTS: It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators. CONCLUSION: The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment.

Novel Paramyxoviruses in Bats from Sub-Saharan Africa, 2007-2012.

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.

A Bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data.

We describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. Previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. There are as yet no approaches appropriate for endemic situations in which a disease is already well established in a host population and in which there may be multiple origins of infection, or that can enumerate unobserved infections missing from the sample. Our proposed framework addresses these shortcomings, enabling reconstruction of partially observed transmission trees and estimating the number of cases missing from the sample. Analyses of simulated datasets show the method to be accurate in identifying direct transmissions, while introductions and transmissions via one or more unsampled intermediate cases could be identified at high to moderate levels of case detection. When applied to partial genome sequences of rabies virus sampled from an endemic region of South Africa, our method reveals several distinct transmission cycles with little contact between them, and direct transmission over long distances suggesting significant anthropogenic influence in the movement of infected dogs.

A Perspective of the Epidemiology of Rabies in South Africa, 1998-2019.

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.

Technical Note on the Role of Kambin's Triangle in the Evolution of Total Joint Replacement of the Lumbar Spine.

We provide a historical and technical perspective on the evolution of Kambin's triangle as a safe working corridor for percutaneous access to the intervertebral disc to an anatomically expanded space to accommodate and facilitate open lumbar total joint replacement. The nearly 6-decade progression from intradiscal access in the intact lumbar spine to an enlarged working space following facetectomy to accommodate a transforaminal lumbar interbody fusion, and eventual further expansion via pedicle vertebral body osteotomy to support motion preservation with total joint replacement, represents a unique evolutionary pathway in surgical technique development. For each of these steps in evolution, we detail and provide the historical context of the corresponding surgical modifications required to expand the original anatomical boundaries of Kambin's triangle. It is postulated that the introduction of machine learning technologies coupled with innovations in robotics, materials science, and advanced imaging will further accelerate and refine the adaptation of more complex, precise, and efficacious surgical procedures to treat spinal degeneration via this working corridor.

Investigating the Impact That Diagnostic Screening with Lateral Flow Devices Had on the Rabies Surveillance Program in Zanzibar, Tanzania.

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.

Discrepancies in data reporting for rabies, Africa.

Human rabies is an ancient disease but in modern times has primarily been associated with dog rabies-endemic countries of Asia and Africa. From an African perspective, the inevitable and tragic consequences of rabies require serious reflection of the factors that continue to drive its neglect. Established as a major disease only after multiple introductions during the colonial era, rabies continues to spread into new reservoirs and territories in Africa. However, analysis of reported data identified major discrepancies that are indicators of poor surveillance, reporting, and cooperation among national, international, and global authorities. Ultimately, the absence of reliable and sustained data compromises the priority given to the control of rabies. Appropriate actions and changes, in accordance to the One Health philosophy and including aspects such as synchronized, shared, and unified global rabies data reporting, will not only be necessary, but also should be feasible.

The Use of Dog Collars Offers Significant Benefits to Rabies Vaccination Campaigns: The Case of Zanzibar, Tanzania.

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.

Epidemiological Interface of Sylvatic and Dog Rabies in the North West Province of South Africa.

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.

Roles of traditional medicine and traditional healers for rabies prevention and potential impacts on post-exposure prophylaxis: A literature review.

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.

Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics.

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.

Lyssaviruses and the Fatal Encephalitic Disease Rabies.

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.

The Role of Waste Management in Control of Rabies: A Neglected Issue.

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.

Assessing the practicalities of joint snakebite and dog rabies control programs: Commonalities and potential pitfalls.

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.

Knowledge, attitudes and practices towards rabies: A survey of the general population residing in the Harare Metropolitan Province of Zimbabwe.

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.