Search

Abstract Rabies causes 59,000 human deaths annually in over 150 countries. Mass dog vaccination (MDV) is key to controlling dog rabies, requiring 70% coverage in the susceptible dog population to eliminate rabies deaths. MDV campaigns must achieve geographical homogeneity of coverage. Although rabies elimination is feasible, operation challenges exist, especially in hard-to-reach areas. We conducted geospatial modelling to identify geographical factors affecting MDV success in terms of campaign completeness and vaccination coverage across 25 districts in south-eastern Tanzania. From October 2016 to January 2017, about 81,000 dogs were vaccinated in 1,379 (68%) villages within these districts. Multivariable regression analysis revealed that land cover, residence, poverty, and elevation were associated with campaign completeness. The odds of achieving completeness in croplands were 1.75 times higher compared to forests. Vaccination coverage was influenced by residence, area, poverty index, and elevation, with urban areas having lower odds of achieving coverage compared to rural areas. Coverage probabilities exceeding 70% were lower on islands, highlands, urban areas, and areas bordering protected areas. As the 2030 deadline for "zero dog-mediated human rabies deaths" approaches, operational and logistical challenges in MDV campaigns persist. Our data provide insights into MDV success and failure, guiding future control efforts to improve their effectiveness.

Abstract Rabies is a viral zoonosis that kills thousands of people annually in low- and middle-income countries across Africa and Asia where domestic dogs are the reservoir. ‘Zero by 30’, the global strategy to end dog-mediated human rabies, promotes a One Health approach underpinned by mass dog vaccination, post-exposure vaccination of bite victims, robust surveillance and community engagement. Using Integrated Bite Case Management (IBCM) and whole genome sequencing (WGS), we enhanced rabies surveillance to detect an outbreak in a formerly rabies-free island province in the Philippines. We inferred that the outbreak was seeded by at least three independent human-mediated introductions that were identified as coming from neighbouring rabies-endemic provinces. Considerable local transmission went undetected, and two human deaths occurred within 6 months of outbreak detection. Suspension of routine dog vaccination due to COVID-19 restrictions likely facilitated rabies spread from these introductions. Emergency response, consisting of awareness measures, and ring vaccination, were performed, but swifter and more widespread implementation is needed to contain and eliminate the outbreak and to secure rabies freedom. We conclude that strengthened surveillance making use of new tools such as IBCM, WGS, and rapid diagnostic tests can support One Health in action and progress towards the ‘Zero by 30’ goal.

Abstract A/goose/Guangdong/1/96-like (GsGd) highly pathogenic avian influenza (HPAI) H5 viruses cause severe outbreaks in poultry when introduced. Since emergence in 1996, control measures in most countries have suppressed local GsGd transmission following introductions, making persistent transmission in domestic birds rare. However, geographical expansion of clade 2.3.4.4 sublineages has raised concern about establishment of endemic circulation, while mechanistic drivers leading to endemicity remain unknown. We reconstructed the evolutionary history of GsGd sublineage, clade 2.3.4.4c, in Taiwan using a time-heterogeneous rate phylogeographic model. During Taiwan’s initial epidemic wave (January 2015 - August 2016), we inferred that localised outbreaks had multiple origins from rapid spread between counties/cities nationwide. Subsequently, outbreaks predominantly originated from a single county, Yunlin, where persistent transmission harbours the trunk viruses of the sublineage. Endemic hotspots determined by phylogeographic reconstruction largely predicted the locations of re-emerging outbreaks in Yunlin. The transition to endemicity involved a shift to chicken-dominant circulation, following the initial bidirectional spread between chicken and domestic waterfowl. Our results suggest that following their emergence in Taiwan, source-sink dynamics from a single county have maintained GsGd endemicity up until 2023, pointing to where control efforts should be targeted to eliminate the disease.

Abstract Background Rabies remains a major public health problem in low- and middle-income countries. However, human rabies deaths are rarely laboratory-confirmed or sequenced, especially in Africa. Five human rabies deaths from Tanzania and Kenya were investigated and the causative rabies viruses sequenced, with the aim of identifying implications for rabies control at individual, healthcare and societal levels. Case presentation The epidemiological context and care of these cases was contrasting. Four had a clear history of being bitten by dogs, while one had an unclear biting history. Two individuals sought medical attention within a day of being bitten, whereas three sought care only after developing rabies symptoms. Despite seeking medical care, none of the cases received complete post-exposure prophylaxis: one patient received only tetanus vaccination, one did not complete the post-exposure vaccination regimen, one followed an off-label vaccination schedule, and two did not receive any post-exposure vaccinations before the onset of symptoms. These cases highlight serious gaps in health-seeking behaviour, and in health systems providing appropriate care following risky exposures, including in the accessibility and effectiveness of post-exposure prophylaxis as it is administered in the region. Conclusions The viral genomic and epidemiological data confirms dog-mediated rabies as the cause of each of these deaths. The phylogenetic investigation highlights the transboundary circulation of rabies within domestic dog populations, revealing distinct rabies virus clades with evidence of regional spread. These findings underscore the importance of coordinated cross-border control efforts between the two countries. Urgent action is needed to improve awareness around the need for emergency post-exposure vaccines that should be accessible in local communities and administered appropriately, as well as investment in coordinated dog vaccination to control dog-mediated rabies, the underlying cause of these deaths. Graphical Abstract

The molecular clock hypothesis assumes that mutations accumulate on an organism's genome at a constant rate over time, but this assumption does not always hold true. While modelling approaches exist to accommodate deviations from a strict molecular clock, assumptions about rate variation may not fully represent the underlying evolutionary processes. There is considerable variability in rabies virus (RABV) incubation periods, ranging from days to over a year, during which viral replication may be reduced. This prompts the question of whether modelling RABV on a per infection generation basis might be more appropriate. We investigate how variable incubation periods affect root-to-tip divergence under per-unit time and per-generation models of mutation. Additionally, we assess how well these models represent root-to-tip divergence in time-stamped RABV sequences. We find that at low substitution rates (

Abstract A lack of methods to identify individual animals can be a barrier to zoonoses control. We developed and field-tested facial recognition technology for a mobile phone application to identify dogs, which we used to assess vaccination coverage against rabies in rural Tanzania. Dogs were vaccinated, registered using the application, and microchipped. During subsequent household visits to validate vaccination, dogs were registered using the application and their vaccination status determined by operators using the application to classify dogs as vaccinated (matched) or unvaccinated (unmatched), with microchips validating classifications. From 534 classified dogs (251 vaccinated, 283 unvaccinated), the application specificity was 98.9% and sensitivity 76.2%, with positive and negative predictive values of 98.4% and 82.8% respectively. The facial recognition algorithm correctly matched 249 (99.2%) vaccinated and microchipped dogs (true positives) and failed to match two (0.8%) vaccinated dogs (false negatives). Operators correctly identified 186 (74.1%) vaccinated dogs (true positives), and 280 (98.9%) unvaccinated dogs (true negatives), but incorrectly classified 58 (23.1%) vaccinated dogs as unmatched (false negatives). Reduced application sensitivity resulted from poor quality photos and light-associated color distortion. With development and operator training, this technology has potential to be a useful tool to identify dogs and support research and intervention programs.

Abstract: Sustained vaccination coverage of domestic dog populations can interrupt rabies transmission. However, challenges remain including low dog owner participation, high operational costs associated with current (centralized and annually delivered (pulse)) approaches and high dog population turnover. To address these challenges an alternative (community-based continuous mass dog vaccination (CBC-MDV)) approach was designed. We investigated the potential for successful normalization of CBC-MDV into routine practice within the context of local communities and the veterinary system of Tanzania Methods: In a process evaluation of a pilot implementation of CBC-MDV, we conducted in-depth interviews with implementers and community leaders (n = 24), focus group discussion with implementers and community members (n = 12), and non-participant observation (n = 157 h) of delivery of the intervention components. We analyzed these data thematically drawing on the normalization process theory, to assess factors affecting implementation and integration. Main findings: Implementers and community members clearly understood the values and benefits of the CBC-MDV, regarding it as an improvement over the pulse strategy. They had a clear understanding of what was required to enact CBC-MDV and considered their own involvement to be legitimate. The approach fitted well into routine schedules of implementers and the context (infrastructure, skill sets and policy). Implementers and community members positively appraised CBC-MDV in terms of its perceived impact on rabies and recommended its use across the country. Implementers and community members further believed that vaccinating dogs free of charge was critical and made community mobilization easier. However, providing feedback to communities and involving them in evaluating outcomes of vaccination campaigns were reported to have not been done. Local politics was cited as a barrier to collaboration between implementers and community leaders. Conclusion: This work suggests that CBC-MDV has the potential to be integrated and sustained in the context of Tanzania. Involving communities in design, delivery and monitoring of CBC-MDV activities could contribute to improving and sustaining its outcomes.

Abstract The “Zero by 30” strategic plan aims to eliminate human deaths from dog-mediated rabies by 2030 and domestic dog vaccination is a vital component of this strategic plan. In areas where domestic dog vaccination has been implemented, it is important to assess the impact of this intervention. Additionally, understanding temporal and seasonal trends in the incidence of animal rabies cases may assist in optimizing such interventions. Data on the incidence of probable rabies cases in domestic and wild animals were collected between January 2011 and December 2018 in thirteen districts of south-east Tanzania where jackals comprise over 40% of reported rabies cases. Vaccination coverage was estimated over this period, as five domestic dog vaccination campaigns took place in all thirteen districts between 2011 and 2016. Negative binomial generalized linear models were used to explore the impact of domestic dog vaccination on the annual incidence of animal rabies cases, whilst generalized additive models were used to investigate the presence of temporal and/or seasonal trends. Increases in domestic dog vaccination coverage were significantly associated with a decreased incidence of rabies cases in both domestic dogs and jackals. A 35% increase in vaccination coverage was associated with a reduction in the incidence of probable dog rabies cases of between 78.0 and 85.5% (95% confidence intervals ranged from 61.2 to 92.2%) and a reduction in the incidence of probable jackal rabies cases of between 75.3 and 91.2% (95% confidence intervals ranged from 53.0 to 96.1%). A statistically significant common seasonality was identified in the monthly incidence of probable rabies cases in both domestic dogs and jackals with the highest incidence from February to August and lowest incidence from September to January. These results align with evidence supporting the use of domestic dog vaccination as part of control strategies aimed at reducing animal rabies cases in both domestic dogs and jackals in this region. The presence of a common seasonal trend requires further investigation but may have implications for the timing of future vaccination campaigns.

Abstract Vaccine-based protection in populations that are vulnerable to infectious diseases represents a public good, whose successful attainment requires collective action. We investigated participation in mass domestic dog vaccination against dog-mediated human rabies endemic in Tanzania as a prototypical example of these issues. We employed advertising interventions, text messaging and/or engagement through community leaders, as well as operational adjustments to increase the saliency of rabies risks and reduce barriers to participation in vaccination campaigns. Neither advertising strategies were effective on their own, however, when taken together, the two advertising strategies substantially improved vaccination coverage. Operational interventions, such as increasing vaccination stations and extending time windows of delivery, greatly enhanced participation. Our experimental and theoretical findings highlight the importance of both salience and context: sparking successful collective action requires decision-making bodies to understand and respond to the challenges encountered by intended beneficiaries in their local contexts.

Rapid antigen tests and syndromic surveillance for identification of COVID-19 cases are limited by low sensitivity and specificity, respectively. Here, the authors use data from Bangladesh and show that combining the two methods improves diagnostic accuracy in a range of epidemiological scenarios.

Background: Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods: We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon. Results: We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island. Conclusions: A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding: Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa’s Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.

BackgroundCanine rabies causes about 59,000 human deaths each year globally but the disease can be eliminated by sustaining sufficient dog vaccination coverage over several consecutive years. A challenge to achieving high coverage is low participation of dog owners in vaccination campaigns. We explored whether and how previously identified contributory factors to low participation can be addressed through community engagement activities.MethodsWe engaged communities in two wards in Tanzania on dog behavior and handling, safe ways of interacting with dogs, and their perceptions of dog vaccination. We shared and elicited information from them through village meetings, video screenings, posters and leaflets and involved the leadership of one of the wards in planning and implementing a dog vaccination exercise to explore the feasibility of their participation. We assessed the impact of engagement activities with household surveys, meeting reports, observations and focus group discussions. We used a generalized linear mixed-effects model to identify predictors of knowledge and perceptions and compared knowledge amongst respondents before and after engagement activities. Qualitative data was analyzed inductively to explore perceptions of dog handling and vaccination and feasibility, opportunities and barriers to community leadership participation in organizing mass dog vaccination.Main findingsKnowledge of dog behavior, dog handling, and safe ways of interacting with dogs was positively associated with age (p < 0.0001), dog ownership (p = 0.0203), training (p = 0.0010) and previous experience of a dog bite (p = 0.0002); and was negatively associated with being afraid of dogs (p = 0.0061) and participation in a recent dog vaccination campaign (p = 0.0077). Knowledge was low before and significantly improved after engagement activities. The majority (92%) of respondents believed dog vaccination has no negative effects on dogs. Respondents perceived lack of bonding with their dog as a limitation to the ability to restrain a dog for vaccination. The community performed most roles assigned to them in the dog vaccination exercise, but barriers such as lack of motivation for volunteering exist.ConclusionEngaging communities regularly on dog vaccination can improve their knowledge of dog behavior and dog handling techniques, and may help improve owner participation in dog vaccination campaigns.

ObjectivesDog vaccination can eliminate rabies in dogs, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization.MethodsWe developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK Medical Research Council's guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively.ResultsThe final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDV's components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up.InterpretationCBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future.

Background: Non-pharmaceutical interventions (NPIs) used to limit SARS-CoV-2 transmission vary in their feasibility, appropriateness and effectiveness in different contexts. In Bangladesh a national lockdown implemented in March 2020 exacerbated poverty and was untenable long-term. A resurgence in 2021 warranted renewed NPIs. We sought to identify NPIs that were feasible in this context and explore potential synergies between interventions. Methods: We developed an SEIR model for Dhaka District, parameterised from literature values and calibrated to data from Bangladesh. We discussed scenarios and parameterisations with policymakers with the aid of an interactive app. These discussions guided modelling of lockdown and two post-lockdown measures considered feasible to deliver; symptoms-based household quarantining and compulsory mask-wearing. We compared NPI scenarios on deaths, hospitalisations relative to capacity, working days lost, and cost-effectiveness. Results: Lockdowns alone were predicted to delay the first epidemic peak but could not prevent overwhelming of the health service and were costly in lost working days. Impacts of post-lockdown interventions depended heavily on compliance. Assuming 80% compliance, symptoms-based household quarantining alone could not prevent hospitalisations exceeding capacity, whilst mask-wearing prevented overwhelming health services and was cost-effective given masks of high filtration efficiency. Combining masks with quarantine increased their impact. Recalibration to surging cases in 2021 suggested potential for a further wave in 2021, dependent on uncertainties in case reporting and immunity. Conclusions: Masks and symptoms-based household quarantining synergistically prevent transmission, and are cost-effective in Bangladesh. Our interactive app was valuable in supporting decision-making, with mask-wearing being mandated early, and community teams being deployed to support quarantining across Dhaka. These measures likely contributed to averting the worst public health impacts, but delivering an effective response with consistent compliance across the population has been challenging. In the event of a further resurgence, concurrent messaging to increase compliance with both mask-wearing and quarantine is recommended.

The prompt administration of post-exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. A delay in seeking the first dose of rabies PEP, or failure to complete the recommended dosage, may result in clinical rabies and death. We assessed the efficacy of short message system (SMS) phone texts in improving the adherence to scheduled PEP doses among bite patients in rural eastern Kenya. We conducted a single-arm, before-after field trial that compared adherence among bite patients presenting at Makueni Referral Hospital between October and December 2018 (control) and between January and March 2019 (intervention). Data on their demographics, socio-economic status, circumstances surrounding the bite, and expenditures related to the bite were collected. A total of 186 bite patients were enrolled, with 82 (44%) in the intervention group, and 104 (56%) in the control group. The odds of PEP completion were three times (OR 3.37, 95% CI 1.28, 10.20) more likely among patients who received the SMS reminder, compared to the control. The intervention group had better compliance on the scheduled doses 2 to 5, with a mean deviation of 0.18 days compared to 0.79 days for the control group (p = 0.004). The main reasons for non-compliance included lack of funds (30%), and forgetfulness (23%) on days for follow-up treatment, among others. Nearly all (96%, n = 179) the bite patients incurred indirect transport costs, at an average of USD 4 (USD 0–45) per visit. This study suggests that the integration of SMS reminders into healthcare service delivery increases compliance with PEP, and may strengthen rabies control and elimination strategies.

Objective To evaluate the diagnostic performance and feasibility of rapid antigen testing for SARS-CoV-2 detection in low-income communities.Design We conducted a cross-sectional community-based diagnostic accuracy study. Community health workers, who were trained and supervised by medical technicians, performed rapid antigen tests on symptomatic individuals, and up to two additional household members in their households and diagnostic results were calibrated against the gold standard RT-PCR.Setting Low-income communities in Dhaka, Bangladesh.Participants Between 19 May 2021 and 11 July 2021, 1240 nasal and saliva samples were collected from symptomatic individuals and 993 samples from additional household members (up to two from one household).Results The sensitivity of rapid antigen tests was 0.68 on nasal samples (95% CI 0.62 to 0.73) and 0.41 on saliva (95% CI 0.35 to 0.46), with specificity also higher on nasal samples (0.98, 95% CI 0.97 to 0.99) than saliva (0.87, 95% CI 0.85 to 0.90). Testing up to two additional household members increased sensitivity to 0.71 on nasal samples (95% CI 0.65 to 0.76), but reduced specificity (0.96, 95% CI 0.94 to 0.97). Sensitivity on saliva rose to 0.48 (95% CI 0.42 to 0.54) with two additional household members tested but remained lower than sensitivity on nasal samples. During the study period, testing in these low-income communities increased fourfold through the mobilisation of community health workers for sample collection.Conclusions Rapid antigen testing on nasal swabs can be effectively performed by community health workers yielding equivalent sensitivity and specificity to the literature. Household testing by community health workers in low-resource settings is an inexpensive approach that can increase testing capacity, accessibility and the effectiveness of control measures through immediately actionable results.

Deeply embedded in local social, cultural, and religious settings, traditional healing is part of dog bite and rabies management in many rabies endemic countries. Faith healing, which usually encompasses a more holistic approach to health including physical, mental and social dimensions, is rare in the context of rabies. In Gujarat, Western India, the Hindu goddess Hadkai Mata is worshiped by low-caste communities as the Mother of Rabies in the event of a dog bite to a person or their livestock. This belief might influence people's attitudes and behaviors toward rabies prevention but has never been investigated. Through 31 in-depth interviews with healers and staff of Hadkai Mata temples, this paper explores the system of knowledge around dog and human rabies that is built and shared in these places of worship and healing. Qualitative and quantitative data were analyzed looking for convergences and divergences with the recently launched National Action Plan for dog-mediated Rabies Elimination. Results suggest that while the etiology of human rabies as a social illness is usually explained as the goddess's wish to correct misbehaving people and restore positive interpersonal relations, there is some appreciation for the biological processes of infection that lead to rabies as a physical disease. Hadkai Mata is believed to cure rabies if her patients undergo the necessary process of moral growth. Although conventional post-exposure prophylaxis is not opposed per se, it is often delayed by patients who seek traditional treatment first. Some reluctance was expressed toward mass dog vaccination because it is seen as an interference in how the goddess controls dogs, by enraging them—hence infecting them with rabies—and sending them to bite wrongdoers. Addressing these cultural perceptions is likely to be critical in achieving effective control of dog rabies in this region. The study highlights the value of multidisciplinary approaches in the control and elimination of rabies, as well as other zoonoses. This includes the importance of understanding different culturally- and religiously- mediated ways in which humans relate to animals; and looking for points of convergence and mutual understanding, upon which context-tailored, linguistically-accurate, locally acceptable, feasible and effective strategies can be designed.

Abstract Background International organizations advocate for the elimination of dog-mediated rabies, but there is only limited guidance on interpreting surveillance data for managing elimination programmes. With the regional programme in Latin America approaching elimination of dog-mediated rabies, we aimed to develop a tool to evaluate the programme’s performance and generate locally-tailored rabies control programme management guidance to overcome remaining obstacles. Methods We developed and validated a robust algorithm to classify progress towards rabies elimination within sub-national administrative units, which we applied to surveillance data from Brazil and Mexico. The method combines criteria that are easy to understand, including logistic regression analysis of case detection time series, assessment of rabies virus variants, and of incursion risk. Subjecting the algorithm to robustness testing, we further employed simulated data sub-sampled at differing levels of case detection to assess the algorithm’s performance and sensitivity to surveillance quality. Results Our tool demonstrated clear epidemiological transitions in Mexico and Brazil: most states progressed rapidly towards elimination, but a few regressed due to incursions and control lapses. In 2015, dog-mediated rabies continued to circulate in the poorest states, with foci remaining in only 1 of 32 states in Mexico, and 2 of 27 in Brazil, posing incursion risks to the wider region. The classification tool was robust in determining epidemiological status irrespective of most levels of surveillance quality. In endemic settings, surveillance would need to detect less than 2.5% of all circulating cases to result in misclassification, whereas in settings where incursions become the main source of cases the threshold detection level for correct classification should not be less than 5%. Conclusion Our tool provides guidance on how to progress effectively towards elimination targets and tailor strategies to local epidemiological situations, while revealing insights into rabies dynamics. Post-campaign assessments of dog vaccination coverage in endemic states, and enhanced surveillance to verify and maintain freedom in states threatened by incursions were identified as priorities to catalyze progress towards elimination. Our finding suggests genomic surveillance should become increasingly valuable during the endgame for discriminating circulating variants and pinpointing sources of incursions.

Post-exposure prophylaxis (PEP) is necessary to prevent the fatal onset of rabies but requires optimization to avoid overuse in populations at risk of rabies. In Brazil, the incidence of dog bites remains high, with almost half of dog-bite patients not receiving the PEP recommended by the Ministry of Health guidelines between 2008 and 2017. In this study, we aimed to identify the factors that limit the appropriate prescribing of PEP by interviewing health professionals responsible for PEP administration and completion of the ‘Information System on Diseases of Compulsory Declaration’ (SINAN) form reporting human anti-rabies care for patients seeking health care after a dog bite. We conducted 147 questionnaires (45 questions each) in three Brazilian states (i.e., Rio Grande do Sul, Santa Catarina, Rio Grande do Norte) including questions related to the criteria used by professionals to classify a dog as “suspect” or “rabid”, knowledge on PEP prescription guidelines, SINAN and communication with veterinarians. Our analyses showed that most health professionals delivering PEP in these three states struggle to identify a rabies “suspect” dog according to the Ministry of Health guidelines, and to indicate the adequate PEP regimen, with only 11% of professionals prescribing the appropriate PEP under various dog-bite patient scenarios. PEP knowledge score was higher among professionals trained on PEP guidelines and working in facilities with the highest incidence of dog bites. In contrast, PEP knowledge scores did not vary significantly between states, and were not correlated to the professional's level of experience, the number of colleagues available at the health unit or the professional's confidence on prescribing appropriate PEP. Our results suggest that knowledge gaps in PEP administration among health professionals of Brazil can be reduced by implementing training programs to differentiate among rabies risk scenarios, prescribe the corresponding appropriate PEP and improve communication between health and veterinary authorities.

The availability of pathogen sequence data and use of genomic surveillance is rapidly increasing. Genomic tools and classification systems need updating to reflect this. Here, rabies virus is used as an example to showcase the potential value of updated genomic tools to enhance surveillance to better understand epidemiological dynamics and improve disease control. Previous studies have described the evolutionary history of rabies virus, however the resulting taxonomy lacks the definition necessary to identify incursions, lineage turnover and transmission routes at high resolution. Here we propose a lineage classification system based on the dynamic nomenclature used for SARS-CoV-2, defining a lineage by phylogenetic methods for tracking virus spread and comparing sequences across geographic areas. We demonstrate this system through application to the globally distributed Cosmopolitan clade of rabies virus, defining 96 total lineages within the clade, beyond the 22 previously reported. We further show how integration of this tool with a new rabies virus sequence data resource (RABV-GLUE) enables rapid application, for example, highlighting lineage dynamics relevant to control and elimination programmes, such as identifying importations and their sources, as well as areas of persistence and routes of virus movement, including transboundary incursions. This system and the tools developed should be useful for coordinating and targeting control programmes and monitoring progress as countries work towards eliminating dog-mediated rabies, as well as having potential for broader application to the surveillance of other viruses.

BackgroundIn Africa, rabies causes an estimated 24,000 human deaths annually. Mass dog vaccinations coupled with timely post-exposure prophylaxis (PEP) for dog-bite patients are the main interventions to eliminate human rabies deaths. A well-informed healthcare workforce and the availability and accessibility of rabies biologicals at health facilities are critical in reducing rabies deaths. We assessed awareness and knowledge regarding rabies and the management of rabies among healthcare workers, and PEP availability in rural eastern Kenya.MethodologyWe interviewed 73 healthcare workers from 42 healthcare units in 13 wards in Makueni and Kibwezi West sub-counties, Makueni County, Kenya in November 2018. Data on demographics, years of work experience, knowledge of rabies, management of bite and rabies patients, and availability of rabies biologicals were collected and analyzed.ResultsRabies PEP vaccines were available in only 5 (12%) of 42 health facilities. None of the health facilities had rabies immunoglobulins in stock at the time of the study. PEP was primarily administered intramuscularly, with only 11% (n = 8) of the healthcare workers and 17% (7/42) healthcare facilities aware of the dose-sparing intradermal route. Less than a quarter of the healthcare workers were aware of the World Health Organization categorization of bite wounds that guides the use of PEP. Eighteen percent (n = 13) of healthcare workers reported they would administer PEP for category I exposures even though PEP is not recommended for this category of exposure. Only one of six respondents with acute encephalitis consultation considered rabies as a differential diagnosis highlighting the low index of suspicion for rabies.ConclusionThe availability and use of PEP for rabies was sub-optimal. We identified two urgent needs to support rabies elimination programmes: improving availability and access to PEP; and targeted training of the healthcare workers to improve awareness on bite wound management, judicious use of PEP including appropriate risk assessment following bites and the use of the dose-sparing intradermal route in facilities seeing multiple bite patients. Global and domestic funding plan that address these gaps in the human health sector is needed for efficient rabies elimination in Africa.

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals, an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

An increasing number of countries are committing to meet the global target to eliminate human deaths from dog-mediated rabies by 2030. Mass dog vaccination is central to this strategy. To interrupt rabies transmission from dogs to humans, the World Health Organization recommends that vaccination campaigns should be carried out every year in all dog-owning communities vaccinating 70% of their susceptible dogs. Monitoring and evaluation of dog vaccination campaigns are needed to measure progress towards elimination. In this study, we measured the delivery performance of large-scale vaccination campaigns implemented in 25 districts in south-east Tanzania from 2010 until 2017. We used regression modelling to infer the factors associated with, and potentially influencing the successful delivery of vaccination campaigns. During 2010-2017, five rounds of vaccination campaigns were carried out, vaccinating in total 349,513 dogs in 2,066 administrative vaccination units (rural villages or urban wards). Progressively more dogs were vaccinated over the successive campaigns. The campaigns did not reach all vaccination units each year, with only 16-28% of districts achieving 100% campaign completeness (where all units were vaccinated). During 2013-2017 when vaccination coverage was monitored, approximately 20% of vaccination units achieved the recommended 70% coverage, with average coverage around 50%. Campaigns were also not completed at annual intervals, with the longest interval between campaigns being 27 months. Our analysis revealed that districts with higher budgets generally achieved higher completeness, with a twofold difference in district budget increasing the odds of a vaccination unit being reached by a campaign by slightly more than twofold (OR: 2.29; 95% CI: 1.69-3.09). However, higher budgets did not necessarily result in higher coverage within vaccination units that were reached. We recommend national programs regularly monitor and evaluate the performance of their vaccination campaigns, so as to identify factors hindering their effective delivery and to guide remedial action.

When a novel pathogen emerges there may be opportunities to eliminate transmission - locally or globally - whilst case numbers are low. However, the effort required to push a disease to elimination may come at a vast cost at a time when uncertainty is high. Models currently inform policy discussions on this question, but there are a number of open challenges, particularly given unknown aspects of the pathogen biology, the effectiveness and feasibility of interventions, and the intersecting political, economic, sociological and behavioural complexities for a novel pathogen. In this overview, we detail how models might identify directions for better leveraging or expanding the scope of data available on the pathogen trajectory, for bounding the theoretical context of emergence relative to prospects for elimination, and for framing the larger economic, behavioural and social context that will influence policy decisions and the pathogen’s outcome.

Music is a powerful approach to engage communities and disseminate information. Specifically, health campaigns employing music have been used to promote behaviors that can prevent emerging infectious diseases (EIDs). For example, hip hop artists supported campaigns to prevent acquired immunodeficiency syndrome in the 70s in the United States, while Brazilian funk promoted vaccination to mitigate the ongoing COVID-19 pandemic. Similarly, we broadcast musical messages in local languages to increase community awareness and support prevention measures in Guinea and Liberia in response to the recent Ebola outbreak in 2021. Given the potential of music to promote both individual and population-level behavioral changes to prevent transmission, there is a need to consolidate information on music-based health interventions, and on how we can measure their effectiveness. In this perspective, we provide examples of relevant initiatives, discussing challenges and solutions associated with implementing interventions based on our experience with the 2021 Ebola outbreak. We recommend four steps for a successful music-based health intervention including (1) establishing a task force, (2) compose a “catchy” song including critical preventive measures, (3) deliver the song to the target audience, and (4) evaluate the campaign effectiveness. We argue that close interactions between scientists and musicians can produce rapid musical content for disease prevention. We also identify and discuss several methodological frameworks for testing the effectiveness of such interventions. We conclude that support from public health authorities, government media departments, and international agencies, is necessary to deliver wide outreach and long-term sustainability of musical messaging toward effective EID prevention.

Background: Thermostable vaccines greatly improved the reach and impact of large-scale programmes to eliminate infectious diseases such as smallpox, polio, and rinderpest. A study from 2015 demonstrated that the potency of the Nobivac® Rabies vaccine was not impacted following experimental storage at 30°C for 3 months. Whether the vaccine would remain efficacious following storage under more natural, fluctuating temperature conditions remains unknown. We carried out a randomised controlled non-inferiority trial to compare serological responses in dogs following vaccination with doses stored under cold chain conditions with those stored within a locally made Passive Cooling Device (“Zeepot”) under fluctuating temperature conditions.Materials and Methods: Nobivac® Rabies vaccine was stored under either cold-chain conditions or within the Zeepot for 2 months. Daily ambient temperatures and temperatures within the Zeepot were recorded every 3 h. Following storage, 412 domestic dogs were randomly assigned to receive either cold-chain or Zeepot stored Nobivac® Rabies vaccine. Baseline and day 28-post vaccination blood samples were collected. Serological analysis using the Fluorescent Antibody Virus Neutralisation assay was carried out with a threshold of 0.5 IU/ml to determine seroconversion. In addition, the impact of dog Body Condition Score, sex, and age on seroconversion was examined.Results: The serological response of dogs vaccinated using Nobivac® Rabies vaccine stored within the Zeepot was not inferior to the response of dogs vaccinated using cold-chain stored vaccine (z = 1.1, df = 313, p-value = 0.25). Indeed, the 28-day post-vaccination group geometric mean titre was 1.8 and 2.0 IU/ml for cold-chain vs. non-cold-chain storage, respectively. Moreover, the percentage of dogs that seroconverted in each arm was almost identical (85%). There was a positive linear trend between Body Condition Score (O.R. 2.2, 95% CI: 1.1–5.1) and seroconversion, suggesting dogs of poor condition may not respond as expected to vaccination.Conclusions: Our study demonstrated the potency of Nobivac® Rabies vaccine is not impacted following storage under elevated fluctuating temperatures within a Zeepot. These results have potentially exciting applications for scaling up mass dog vaccination programmes in low-and-middle income countries, particularly for hard-to-reach populations with limited access to power and cold-chain vaccine storage.

BackgroundThe human resource gap in veterinary sectors, particularly in low-income countries, imposes limitations on the delivery of animal healthcare in hard-to-reach populations. Lay animal health workers have been deployed in these settings to fill the gap though there are mixed views about the benefits of doing this and whether they can deliver services safely. We mapped evidence on the nature and extent of roles assigned to lay animal vaccinators, and identified lessons useful for their future deployment.Methodology/principal findingsFollowing the PRISMA Extension for Scoping Reviews guidelines, we searched seven bibliographic databases for articles published between 1980 and 2021, with the search terms lay OR community-based OR volunteer AND "animal health worker" OR vaccinator*, and applied an a priori exclusion criteria to select studies. From 30 identified studies, lay vaccinators were used by non-government developmental (n = 12, 40%), research (n = 10, 33%) and government (n = 5, 17%) programmes to vaccinate domestic animals. The main reason for using lay vaccinators was to provide access to animal vaccination in the absence of professional veterinarians (n = 12, 40%). Reported positive outcomes of programmes included increased flock and herd sizes and farmer knowledge of best practice (n = 13, 43%); decreased disease transmission, outbreaks and mortality (n = 11, 37%); higher vaccination coverage (10, 33%); non-inferior seroconversion and birth rates among vaccinated herds (n = 3, 10%). The most frequently reported facilitating factor of lay vaccinator programmes was community participation (n = 14, 47%), whilst opposition from professional veterinarians (n = 8, 27%), stakeholders seeking financial gains to detriment of programmes goals (n = 8, 27%) and programming issues (n = 8, 27%) were the most frequently reported barriers. No study reported on cost-effectiveness and we found no record from a low and middle-income country of lay vaccinator programmes being integrated into national veterinary services.ConclusionAlthough the majority of included studies reported more benefits and positive perceptions of lay vaccinator programmes than problems and challenges, regularization will ensure the programmes can be designed and implemented to meet the needs of all stakeholders.

BackgroundPost-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning.Methodology & principal findingsWe use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI): 790-1120), with PEP averting an additional 800 deaths (95% PI: 640-970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust.Conclusions & significancePEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths.

Interventions tackling zoonoses require an understanding of healthcare patterns related to both human and animal hosts. The control of dog-mediated rabies is a good example. Despite the availability of effective control measures, 59,000 people die of rabies every year worldwide. In Tanzania, children are most at risk, contributing ~40% of deaths. Mass dog vaccination can break the transmission cycle, but reaching the recommended 70% coverage is challenging where vaccination depends on willingness to vaccinate dogs. Awareness campaigns in communities often target children, but do not consider other key individuals in the prevention chain. Understanding factors related to dog ownership and household-level responsibility for dog vaccination and child health is critical to the design of vaccination strategies. We investigated who makes household decisions about dogs and on health care for children in rural Tanzania. In the Kilosa district, in-depth interviews with 10 key informants were conducted to inform analysis of data from a household survey of 799 households and a survey on Knowledge Attitudes and Practices of 417 households. The in-depth interviews were analysed using framework analysis. Descriptive analysis showed responsibilities for household decisions on dogs' and children's health. Multivariate analysis determined factors associated with the probability of dogs being owned and the number of dogs owned, as well as factors associated with the responsibility for child health. Dog ownership varied considerably between villages and even households. The number of dogs per household was associated with the size of a household and the presence of livestock. Children are not directly involved in the decision to vaccinate a dog, which is largely made by the father, while responsibility for seeking health care if a child is bitten lies with the mother. These novel results are relevant for the design and implementation of rabies interventions. Specifically, awareness campaigns should focus on decision-makers in households to improve rabies prevention practices and on the understanding of processes critical to the control of zoonoses more broadly.

Direct contact with domestic animals and wildlife is linked to zoonotic spillover risk. Patients presenting with animal-bite injuries provide a potentially valuable source of surveillance data on rabies viruses that are transmitted primarily by animal bites. Here, we used passive surveillance data of bite patients to identify areas with high potential risk of rabies transmission to humans across Brazil, a highly diverse and populous country, where rabies circulates in a range of species. We analyzed one decade of bite patient data from the national health information system (SINAN) comprising over 500,000 patients attending public health facilities after being bitten by a domestic or wild animal. Our analyses show that, between 2008 and 2016, patients were mostly bitten by domestic dogs (average annual dog bite patients: 502,043 [436,391–544,564], annual incidence per state: 258 dog bites/100,000 persons) and cats (76,512 [56,588–97,580] cat bites, 41 cat bites/100,000/year), but bites from bats (4,172 [3,351–5,365] bat bites, 2.3/100,000/year), primates (3,320 [3,013–3,710] primate bites, 2.0/100,000/year), herbivores (1,908 [1,492–2,298] herbivore bites, 0.9/100,000/year) and foxes (883 [609–1,086] fox bites, 0.6/100,000/year) were also considerable. Incidence of bites due to dogs and herbivores remained relatively stable over the last decade. In contrast bites by cats and bats increased while bites by primates and foxes decreased. Bites by wild animals occurred in all states but were more frequent in the North and Northeast of Brazil, with over 3-fold differences in incidence between states across all animal groups. Most bites reported from domestic animals and wildlife occurred in urban settings (71%), except for bites from foxes, which were higher in rural settings (57%). Based upon the Ministry of Health guidelines, only half of patients received the correct Post-Exposure Prophylaxis following a bite by a suspect rabid animal. We identified areas and species of high-risk for potential zoonotic transmission of rabies in Brazil and reveal that, despite increasing human encroachment into natural ecosystems, only patients reporting bites by bats increased. Our study calls for future research to identity the socio-ecological factors underlying bites and the preventive measures needed to reduce their incidence and potential risk of rabies transmission.

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries.

Human rabies can be prevented through mass dog vaccination campaigns; however, in rabies endemic countries, pulsed central point campaigns do not always achieve the recommended coverage of 70%. This study describes the development of a novel approach to sustain high coverage based on decentralized and continuous vaccination delivery. A rabies vaccination campaign was conducted across 12 wards in the Mara region, Tanzania to test this approach. Household surveys were used to obtain data on vaccination coverage as well as factors influencing dog vaccination. A total 17,571 dogs were vaccinated, 2654 using routine central point delivery and 14,917 dogs using one of three strategies of decentralized continuous vaccination. One month after the first vaccination campaign, coverage in areas receiving decentralized vaccinations was higher (64.1, 95% Confidence Intervals (CIs) 62.1–66%) than in areas receiving pulsed vaccinations (35.9%, 95% CIs 32.6–39.5%). Follow-up surveys 10 months later showed that vaccination coverage in areas receiving decentralized vaccinations remained on average over 60% (60.7%, 95% CIs 58.5–62.8%) and much higher than in villages receiving pulsed vaccinations where coverage was on average 32.1% (95% CIs 28.8–35.6%). We conclude that decentralized continuous dog vaccination strategies have the potential to improve vaccination coverage and maintain herd immunity against rabies.

Abstract 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.

Rabies is a neglected zoonotic disease that causes an estimated 59,000 human deaths worldwide annually, mostly in Africa and Asia. A target of zero human deaths from dog-mediated rabies has been set for 2030, and large-scale control programs are now advocated. However, in most low-income endemic countries surveillance to guide rabies control is weak and few cases of rabies are recorded. There is an urgent need to enhance surveillance to improve timely case detection and inform rabies control and prevention, by operationalizing a “One Health” approach. Here we present data from a study piloting Integrated Bite Case Management (IBCM) to support intersectoral collaboration between health and veterinary workers in Tanzania. We trained government staff to implement IBCM, comprising risk assessments of bite patients by health workers, investigations by livestock field officers to diagnose rabid animals, and use of a mobile phone application to support integration. IBCM was introduced across 20 districts in four regions of Tanzania and results reported after 1 year of implementation. Numbers of bite patient presentations to health facilities varied across regions, but following the introduction of IBCM reporting of bite patients at high-risk for rabies more than doubled in all regions. Over 800 high-risk investigations were carried out, with 49% assessed as probable dog rabies cases on the basis of clinical signs, animal outcome, and rapid diagnostic testing. The status of a further 20% of biting animals could not be determined but rabies could not be ruled out. Livestock field officers reported that use of rapid diagnostic tests (RDTs) were useful for confirming rabies occurrence. Overall, our study provides further evidence that IBCM is a practical approach that can improve rabies detection in endemic countries, and be used to monitor the impact of mass dog vaccinations, including potential to verify rabies freedom. However, the main challenges to implementation are limited training of health workers in rabies, perceived burden of real-time recording and limited resources for livestock field officers to undertake investigations. Nonetheless, IBCM dramatically improved case detection and communication between sectors and we recommend further implementation research to establish best practice and applicability to other settings.

Infectious diseases are often transmitted through local interactions. Yet, both surveillance and control measures are implemented within administrative units. Capturing local transmission processes and spatial coupling between regions from aggregate level data is therefore a technical challenge that can shed light on both theoretical questions and practical decisions. Fox rabies has been eliminated from much of Europe through oral rabies vaccination (ORV) programmes. The European Union (EU) co-finances ORV to maintain rabies freedom in EU member and border states via a cordon sanitaire. Models to capture local transmission dynamics and spatial coupling have immediate application to the planning of these ORV campaigns and to other parts of the world considering oral vaccination. We fitted a hierarchical Bayesian state-space model to data on three decades of fox rabies cases and ORV campaigns from Eastern Germany. Specifically, we find that (i) combining regional spatial coupling and heterogeneous local transmission allows us to capture regional rabies dynamics; (ii) incursions from other regions account for less than 1% of cases, but allow for re-emergence of disease; (iii) herd immunity achieved through bi-annual vaccination campaigns is short-lived due to population turnover. Together, these findings highlight the need for regular and sustained vaccination efforts and our modelling approach can be used to provide strategic guidance for ORV delivery. Moreover, we show that biological understanding can be gained from inference from partially observed data on wildlife disease.

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries.

An effective surveillance system is critical for the elimination of canine rabies in Latin America. Brazil has made substantial progress towards canine rabies elimination, but outbreaks still occurred in the last decade in two states. Brazil uses a health information system (SINAN) to record patients seeking post-exposure prophylaxis (PEP) following contact with an animal suspected of having rabies. This study evaluated: (i) whether SINAN can be reliably used for rabies surveillance; (ii) if patients in Brazil are receiving appropriate PEP and (iii) the benefits of implementing the latest World Health Organization (WHO) recommendations on PEP. Analysing SINAN records from 2008 to 2017 reveals an average of 506,148 bite-injury patients/year [range: 437k-545k] in the country, equivalent to an incidence of 255 bite-injuries/100,000 people/year [range: 231-280]. The number of reports of bites from suspect rabid dogs generally increased over time. In most states, records from SINAN indicating a suspect rabid dog do not correlate with confirmed dog rabies cases reported to the Regional Information System for Epidemiological Surveillance of Rabies (SIRVERA) maintained by the Pan American Health Organization (PAHO). Analyses showed that in 2017, only 45% of patients received appropriate PEP as indicated by the Brazilian Ministry of Health guidance. Implementation of the latest WHO guidance using an abridged intradermal post-exposure vaccination regimen including one precautionary dose for dog bites prior to observation would reduce the volume of vaccine required by up to 64%, with potential for annual savings of over USD 6 million from reduced vaccine use. Our results highlight the need to improve the implementation of SINAN, including training of health workers responsible for delivering PEP using an Integrated Bite Case Management approach so that SINAN can serve as a reliable surveillance tool for canine rabies elimination.

Testing and isolation have been crucial for controlling the COVID-19 pandemic. Venezuela has one of the weakest testing infrastructures in Latin America and the low number of reported cases in the country has been attributed to substantial underreporting. However, the Venezuelan epidemic seems to have lagged behind other countries in the region, with most cases occurring within the capital region and four border states. Here, we describe the spatial epidemiology of COVID-19 in Venezuela and its relation to the population mobility, migration patterns, non-pharmaceutical interventions and fuel availability that impact population movement. Using a metapopulation model of SARS-CoV-2 transmission dynamics, we explore how movement patterns could have driven the observed distribution of cases. Low within-country connectivity most likely delayed the onset of the epidemic in most states, except for those bordering Colombia and Brazil, where high immigration seeded outbreaks. NPIs slowed early epidemic growth and subsequent fuel shortages appeared to be responsible for limiting the spread of COVID-19 across the country.

Canine rabies causes an estimated 60,000 human deaths per year, but these deaths are preventable through post-exposure prophylaxis of people and vaccination of domestic dogs. Dog vaccination campaigns targeting 70% of the population are effective at interrupting transmission. Here, we report on lessons learned during pilot dog vaccination campaigns in the Moramanga District of Madagascar. We compare two different vaccination strategies: a volunteer-driven effort to vaccinate dogs in two communes using static point vaccination and continuous vaccination as part of routine veterinary services. We used dog age data from the campaigns to estimate key demographic parameters and to simulate different vaccination strategies. Overall, we found that dog vaccination was feasible and that most dogs were accessible to vaccination. The static-point campaign achieved higher coverage but required more resources and had a limited geographic scope compared to the continuous delivery campaign. Our modeling results suggest that targeting puppies through community-based vaccination efforts could improve coverage. We found that mass dog vaccination is feasible and can achieve high coverage in Madagascar; however, context-specific strategies and an investment in dog vaccination as a public good will be required to move the country towards elimination.

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION’s potential for low-cost, high volume sequencing of pathogens in locations with limited resources.

Thermotolerant vaccines greatly improved the reach and impact of large-scale vaccination programs to eliminate diseases such as smallpox, polio and rinderpest. A recent study demonstrated that the potency of the Nobivac® Canine Rabies vaccine was not impacted following experimental storage at 30 °C for three months. We conducted a study to develop a passive cooling device (PCD) that could store thermotolerant vaccines under fluctuating subambient temperatures. Through a participatory process with local communities in Northern Tanzania, we developed innovative PCD designs for local manufacture. A series of field experiments were then carried out to evaluate the effectiveness of five PCDs for vaccine storage under varying climatic conditions. Following iterative improvement, a final prototype “Zeepot Clay” was developed at the cost of US$11 per unit. During a further field-testing phase over a 12-month period, the internal temperature of the device remained below 26 °C, despite ambient temperatures exceeding 42 °C. Our study thus demonstrated that locally designed PCDs have utility for storing thermotolerant rabies vaccines at subambient temperatures. These results have application for the scaling up of mass dog vaccination programs in low-and-middle income countries, particularly for hard-to-reach populations with limited access to power and cold-chain vaccine storage.

Background: Rabies causes an estimated 59,000 human deaths annually. In Kenya, rabies was first reported in a dog in 1912, with the first human case reported in 1928. Here we examine retrospective rabies data in Kenya for the period 1912 – 2017 and describe the spatial and temporal patterns of rabies occurrence in the country. Additionally, we detail Kenya’s strategy for the elimination of dog-mediated human rabies by 2030. Methods: Data on submitted samples and confirmed cases in humans, domestic animals and wildlife were obtained from Kenya’s Directorate of Veterinary Services. These data were associated with the geographical regions where the samples originated, and temporal and spatial trends examined. Results: Between 1912 and the mid 1970’s, rabies spread across Kenya gradually, with fewer than 50 cases reported per year and less than half of the 47 counties affected. Following an outbreak in the mid 1970’s, rabies spread rapidly to more than 85% of counties, with a 4 fold increase in the percent positivity of samples submitted and number of confirmed rabies cases. Since 1958, 7,584 samples from domestic animals (93%), wildlife (5%), and humans (2%) were tested. Over two-thirds of all rabies cases came from six counties, all in close proximity to veterinary diagnostic laboratories, highlighting a limitation of passive surveillance. Conclusions: Compulsory annual dog vaccinations between 1950’s and the early 1970’s slowed rabies spread. The rapid spread with peak rabies cases in the 1980’s coincided with implementation of structural adjustment programs privatizing the veterinary sector leading to breakdown of rabies control programs. To eliminate human deaths from rabies by 2030, Kenya is implementing a 15-year step-wise strategy based on three pillars: a) mass dog vaccination, b) provision of post-exposure prophylaxis and public awareness and c) improved surveillance for rabies in dogs and humans with prompt responses to rabies outbreaks.

Background: Rabies causes an estimated 59,000 human deaths annually. In Kenya, rabies was first reported in a dog in 1912, with the first human case reported in 1928. Here we examine retrospective rabies data in Kenya for the period 1912 – 2017 and describe the spatial and temporal patterns of rabies occurrence in the country. Additionally, we detail Kenya’s strategy for the elimination of dog-mediated human rabies by 2030. Methods: Data on submitted samples and confirmed cases in humans, domestic animals and wildlife were obtained from Kenya’s Directorate of Veterinary Services. These data were associated with the geographical regions where the samples originated, and temporal and spatial trends examined. Results: Between 1912 and the mid 1970’s, rabies spread across Kenya gradually, with fewer than 50 cases reported per year and less than half of the 47 counties affected. Following an outbreak in the mid 1970’s, rabies spread rapidly to more than 85% of counties, with a 4 fold increase in the percent positivity of samples submitted and number of confirmed rabies cases. Since 1958, 7,584 samples from domestic animals (93%), wildlife (5%), and humans (2%) were tested. Over two-thirds of all rabies cases came from six counties, all in close proximity to veterinary diagnostic laboratories, highlighting a limitation of passive surveillance. Conclusions: Compulsory annual dog vaccinations between 1950’s and the early 1970’s slowed rabies spread. The rapid spread with peak rabies cases in the 1980’s coincided with implementation of structural adjustment programs privatizing the veterinary sector leading to breakdown of rabies control programs. To eliminate human deaths from rabies by 2030, Kenya is implementing a 15-year step-wise strategy based on three pillars: a) mass dog vaccination, b) provision of post-exposure prophylaxis and public awareness and c) improved surveillance for rabies in dogs and humans with prompt responses to rabies outbreaks.

Eradication and elimination are increasingly a part of the global health agenda. Once control measures have driven infection to low levels, the ecology of disease may change posing challenges for eradication efforts. These challenges vary from identifying pockets of susceptibles, improving monitoring during and after the endgame, to quantifying the economics of disease eradication versus sustained control, all of which are shaped and influenced by processes of loss of immunity, susceptible build-up, emergence of resistance, population heterogeneities and non-compliance with control measures. Here we discuss how modelling can be used to address these challenges.

BackgroundKnowledge of infectious disease burden is necessary to appropriately allocate resources for prevention and control. In Latin America, rabies is among the most important zoonoses for human health and agriculture, but the burden of disease attributed to its main reservoir, the common vampire bat (Desmodus rotundus), remains uncertain.Methodology/principal findingsWe used questionnaires to quantify under-reporting of livestock deaths across 40 agricultural communities with differing access to health resources and epidemiological histories of vampire bat rabies (VBR) in the regions of Apurimac, Ayacucho and Cusco in southern Peru. Farmers who believed VBR was absent from their communities were one third as likely to report livestock deaths from disease as those who believed VBR was present, and under-reporting increased with distance from reporting offices. Using generalized mixed-effect models that captured spatial autocorrelation in reporting, we project 4.6 (95% CI: 4.4-8.2) rabies cases per reported case and identify geographic areas with potentially greater VBR burden than indicated by official reports. Spatially-corrected models estimate 505-724 cattle deaths from VBR in our study area during 2014 (421-444 deaths/100,000 cattle), costing US$121,797-171,992. Cost benefit analysis favoured vaccinating all cattle over the current practice of partial vaccination or halting vaccination all together.ConclusionsOur study represents the first estimate of the burden of VBR in Latin America to incorporate data on reporting rates. We confirm the long-suspected cost of VBR to small-scale farmers and show that vaccinating livestock is a cost-effective solution to mitigate the burden of VBR. More generally, results highlight that ignoring geographic variation in access to health resources can bias estimates of disease burden and risk.

Japan has been free from rabies since the 1950s. However, during the early 1900s several large-scale epidemics spread throughout the country. Here we investigate the dynamics of these epidemics between 1914 and 1933 in Osaka Prefecture, using archival data including newspapers. The association between dog rabies cases and human population density was investigated using Mixed-effects models and epidemiological parameters such as the basic reproduction number (R0), the incubation and infectious period and the serial interval were estimated. A total of 4,632 animal rabies cases were reported, mainly in dogs (99.0%, 4,584 cases) during two epidemics from 1914 to 1921, and 1922 to 1933 respectively. The second epidemic was larger (3,705 cases) than the first (879 cases), but had a lower R0 (1.50 versus 2.42). The first epidemic was controlled through capture of stray dogs and tethering of pet dogs. Dog mass vaccination began in 1923, with campaigns to capture stray dogs. Rabies in Osaka Prefecture was finally eliminated in 1933. A total of 3,805 rabid dog-bite injuries, and 75 human deaths were reported. The relatively low incidence of human rabies, high ratio of post-exposure vaccines (PEP) and bite injuries by rabid dogs (minimum 6.2 to maximum 73.6, between 1924 and 1928), and a decline in the proportion of bite victims that developed hydrophobia over time (slope = -0.29, se = 3, p < 0.001), indicated that increased awareness and use of PEP might have prevented disease. Although significantly more dog rabies cases were detected at higher human population densities (slope = 0.66, se = 0.03, p < 0.01), there were fewer dog rabies cases detected per capita (slope = -0.34, se = 0.03, p < 0.01). We suggest that the combination of mass vaccination and restriction of dog movement enabled by strong legislation was key to eliminate rabies. Moreover, the prominent role of the media in both reporting rabies cases and efforts to control the disease likely contributed to promoting the successful participation required to achieve rabies elimination.