Testing novel facial recognition technology to identify dogs during vaccination campaigns.

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.

Using Integrated Bite Case Management to estimate the burden of rabies and evaluate surveillance in Oriental Mindoro, Philippines.

Background: Despite national elimination efforts, dog-mediated rabies remains endemic in the Philippines. Free provision of post-exposure prophylaxis (PEP) through the widespread establishment of Animal Bite Treatment Centers (ABTCs) has improved accessibility; however, the resulting upsurge in PEP demand is not sustainable, and human rabies deaths continue. Dog vaccination coverage also remains inadequate, and it is unclear whether surveillance is effective. Methods: Here, we used Integrated Bite Case Management (IBCM) to collect enhanced rabies surveillance data in Oriental Mindoro Province over a 3-year period (2020-2022). Adapting a probabilistic decision tree model, we estimated the burden of rabies, evaluated surveillance performance, and analyzed the costs and benefits of current rabies prevention and control practices in the province. Results: The incidence of bite patients receiving PEP was high in Oriental Mindoro Province (1,246/100,000 persons/year), though < 3% of presenting patients were deemed high-risk for rabies exposure (24/100,000 persons/year). Using a decision tree model, we estimated that around 73.8% of probable rabies-exposed patients sought PEP (95% Prediction Interval, PrI: 59.4%-81.1%) and that routine surveillance confirmed < 2% of circulating animal rabies cases, whereas IBCM resulted in a nearly fourfold increase in case detection. Furthermore, we estimated that an average of 560 (95% PrI 217-1,090) dogs may develop rabies annually in the province, equating to 3-5 cases per 1,000 dogs per year. On average, 20 to 43 human deaths were averted by PEP each year in Oriental Mindoro at an annual cost of $582,110 USD (i.e., $51.44 USD per person) or $20,190 USD (95% PrI $11,565-79,400) per death averted. Conclusion: While current practices for PEP provisioning in the Philippines have improved access, a large proportion of people exposed to rabies (> 26%, 95% PrI 18.8%-40.1%) are still not seeking healthcare. Integrating an intersectoral surveillance system, such as IBCM, into national policy could greatly improve case detection if well implemented, with further benefits extending to guidance for PEP administration, potentially reducing unnecessary expenditure on PEP, and situational awareness to inform control of rabies through mass dog vaccination.

Evaluation of an iELISA for detection and quantification of rabies antibodies in domestic dog sera.

Many rabies endemic-countries have recognized rabies as a public health problem that can be eliminated. As a result, some countries have started implementing small-scale vaccination programs with the aim of scaling them up. Post-vaccination serological monitoring is crucial to assess the efficacy of these programs. The recommended serological tests, the rapid fluorescent focus inhibition test, and the fluorescent antibody virus neutralization (FAVN) are accurate; however, the procedures require considerable expertise and must be carried out in high containment facilities, which are often not available in rabies endemic countries. Given these constraints, enzyme linked immunosorbent assays (ELISAs) have been considered as alternative methods to neutralization tests. This is the first study to evaluate, under field conditions, the performance of the commercial rabies indirect-ELISA (iELISA), the PlateliaTM Rabies II kit ad usum Veterinarium kit, using sera from domestic dogs. Serum samples were collected from two groups of community dogs in northern Tanzania: i) dogs with no history of vaccination against rabies (n = 100) and ii) dogs vaccinated with the Nobivac Canine Rabies® vaccine (n = 101) four weeks previously. When compared to the gold standard FAVN test, the iELISA was found to be 99% specific and 98% sensitive and there was a significant correlation between the two tests (p < 0.001, r = 0.92). Given these findings, we conclude that the PlateliaTM Rabies II kit ad usum Veterinarium can be considered a valuable tool for the rapid assessment of vaccination status of animals in vaccination programs.

Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology.

Genomic data can be used to track the transmission and geographic spread of infectious diseases. However, the sequencing capacity required for genomic surveillance remains limited in many low- and middle-income countries (LMICs), where dog-mediated rabies and/or rabies transmitted by wildlife such as vampire bats pose major public health and economic concerns. We present here a rapid and affordable sample-to-sequence-to-interpretation workflow using nanopore technology. Protocols for sample collection and the diagnosis of rabies are briefly described, followed by details of the optimized whole genome sequencing workflow, including primer design and optimization for multiplex polymerase chain reaction (PCR), a modified, low-cost sequencing library preparation, sequencing with live and offline base calling, genetic lineage designation, and phylogenetic analysis. Implementation of the workflow is demonstrated, and critical steps are highlighted for local deployment, such as pipeline validation, primer optimization, inclusion of negative controls, and the use of publicly available data and genomic tools (GLUE, MADDOG) for classification and placement within regional and global phylogenies. The turnaround time for the workflow is 2-3 days, and the cost ranges from $25 per sample for a 96 sample run to $80 per sample for a 12 sample run. We conclude that setting up rabies virus genomic surveillance in LMICs is feasible and can support progress toward the global goal of zero dog-mediated human rabies deaths by 2030, as well as enhanced monitoring of wildlife rabies spread. Moreover, the platform can be adapted for other pathogens, helping to build a versatile genomic capacity that contributes to epidemic and pandemic preparedness.

Effect of Phone Text Message Reminders on Compliance with Rabies Post-Exposure Prophylaxis following Dog Bites in Rural Kenya.

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.

Integrating a community-based continuous mass dog vaccination delivery strategy into the veterinary system of Tanzania: A process evaluation using normalization process theory.

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.

Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study.

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.

The final stages of dog rabies elimination from Japan.

Rabies is a lethal zoonotic disease mainly transmitted to humans by dog bites. The purpose of this study was to assess the efficacy of rabies control policies in Japan, which resulted in the elimination of the disease from the country in 1957. Using historical records from the Kanto region (Chiba, Kanagawa, Saitama and Tokyo Prefectures) between 1947 and 1956 where the final canine cases were recorded, we undertook a descriptive epidemiological study, applying spatio-temporal scan statistics using SaTScan and estimating the effective reproduction number (Rt ) for the clusters and each prefecture using the growth rates. There were 1,567 dog rabies and 161 human rabies cases recorded during this period. Vaccination coverage in registered dogs was over 70% after 1951, with much lower coverage in free-roaming and unregistered dogs. Eight clusters of dog rabies cases were identified: the first appeared in 1947 in Tokyo and was linked to three further clusters in peripheral prefectures between 1947 and 1951. Three more clusters occurred in Tokyo again between 1952 and 1954, and the last cluster was in Tokyo and Kanagawa between 1955 and 1956. Rt in the first cluster was 1.68, and Rt values in the others ranged between 1.18 and 1.86, with an exception of 4.05 in the smallest cluster in Tokyo in 1952 (10 cases). The moving average of Rt coincided with the clusters. As dog vaccination and dog management progressed, and the number of dog rabies cases declined, the moving average of Rt declined to below 1. Delays in the implementation of dog management policies in Kanagawa may have prolonged this last outbreak. These results demonstrate the effectiveness of coordinated control policy involving dog vaccination and management of free-roaming dog populations for rabies elimination.

Understanding the incidence and timing of rabies cases in domestic animals and wildlife in south-east Tanzania in the presence of widespread domestic dog vaccination campaigns.

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.

Participation in mass dog vaccination campaigns in Tanzania: Benefits of community engagement.

Background: Canine 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. Methods: We 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 findings: Knowledge 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. Conclusion: Engaging 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.

Development, feasibility and potential effectiveness of community-based continuous mass dog vaccination delivery strategies: Lessons for optimization and replication.

OBJECTIVES: Dog 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. METHODS: We 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. RESULTS: The 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. INTERPRETATION: CBC-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.

Lineage BA.2 dominated the Omicron SARS-CoV-2 epidemic wave in the Philippines.

The Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant led to a dramatic global epidemic wave following detection in South Africa in November 2021. The BA.1 Omicron lineage was dominant and responsible for most SARS-CoV-2 outbreaks in countries around the world during December 2021-January 2022, while other Omicron lineages, including BA.2, accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only the BA.2 lineage underwent sustained transmission in the country, with an estimated emergence around 18 November 2021 (95 per cent highest posterior density: 6-28 November), while despite multiple introductions, BA.1 transmission remained limited. These results suggest that the Philippines was one of the earliest areas affected by BA.2 and reiterate the importance of whole genome sequencing for monitoring outbreaks.

Where Rabies Is Not a Disease. Bridging Healthworlds to Improve Mutual Understanding and Prevention of Rabies.

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.

Modelling how face masks and symptoms-based quarantine synergistically and cost-effectively reduce SARS-CoV-2 transmission in Bangladesh.

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.

Rapid antigen testing by community health workers for detection of SARS-CoV-2 in Dhaka, Bangladesh: a cross-sectional study.

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.

Making genomic surveillance deliver: A lineage classification and nomenclature system to inform rabies elimination.

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.

Combining rapid antigen testing and syndromic surveillance improves community-based COVID-19 detection in a low-income country.

Diagnostics for COVID-19 detection are limited in many settings. Syndromic surveillance is often the only means to identify cases but lacks specificity. Rapid antigen testing is inexpensive and easy-to-deploy but can lack sensitivity. We examine how combining these approaches can improve surveillance for guiding interventions in low-income communities in Dhaka, Bangladesh. Rapid-antigen-testing with PCR validation was performed on 1172 symptomatically-identified individuals in their homes. Statistical models were fitted to predict PCR-status using rapid-antigen-test results, syndromic data, and their combination. Under contrasting epidemiological scenarios, the models' predictive and classification performance was evaluated. Models combining rapid-antigen-testing and syndromic data yielded equal-to-better performance to rapid-antigen-test-only models across all scenarios with their best performance in the epidemic growth scenario. These results show that drawing on complementary strengths across rapid diagnostics, improves COVID-19 detection, and reduces false-positive and -negative diagnoses to match local requirements; improvements achievable without additional expense, or changes for patients or practitioners.

Factors Limiting the Appropriate Use of Rabies Post-exposure Prophylaxis by Health Professionals in Brazil.

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.

Rabies shows how scale of transmission can enable acute infections to persist at low prevalence.

How acute pathogens persist and what curtails their epidemic growth in the absence of acquired immunity remains unknown. Canine rabies is a fatal zoonosis that circulates endemically at low prevalence among domestic dogs in low- and middle-income countries. We traced rabies transmission in a population of 50,000 dogs in Tanzania from 2002 to 2016 and applied individual-based models to these spatially resolved data to investigate the mechanisms modulating transmission and the scale over which they operate. Although rabies prevalence never exceeded 0.15%, the best-fitting models demonstrated appreciable depletion of susceptible animals that occurred at local scales because of clusters of deaths and dogs already incubating infection. Individual variation in rabid dog behavior facilitated virus dispersal and cocirculation of virus lineages, enabling metapopulation persistence. These mechanisms have important implications for prediction and control of pathogens that circulate in spatially structured populations.