Dog ecology and rabies control including canine vaccination coverage: Impacts from a survey in Madagascar.

BACKGROUND: Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans. Despite the existence of safe and effective vaccines to prevent the disease, an estimated 99% of human rabies deaths worldwide are caused by dog-mediated rabies with children at the highest risk of infection. Rabies has been endemic in Madagascar for over a century, yet there has been little research evaluating local knowledge and practices impacting on the rabies control and prevention. Thus, this study was undertaken to better understand the dog ecology including canine vaccine coverage and to assess knowledge and practices of dog owners and veterinarians. METHODOLOGY: A cross-sectional study was conducted among 123 dog-owning households in thirteen fokontanys in Mahajanga from July 4 to September 13, 2016. Single and multi-member dog-owning households in the study area on the day of the interview were eligible for inclusion and purposively selected with the support of a local guide. The survey included a household questionnaire capturing information on the dog's demographics, husbandry practices, knowledge and practices towards rabies and its control measures; the dog ecology questionnaire collected dog characteristics, vaccination status and husbandry practices. All households that reported a dog bite incident, were invited to participate in a dog bite questionnaire. In addition, direct observations of roaming dogs were conducted to assess dog population demographics and to document behavioural characteristics. Two veterinarians were purposively selected and took part in an interview during the survey period, providing information on rabies control activities, including dog-care practices in the area. Descriptive and inferential data analyses were performed using Epi Info version 7.1.5.0 (CDC Atlanta, USA). RESULTS: We recorded a total of 400 dogs, of which 338 (84.5%) were owned amongst 123 households. More than half (67.8%) of owned dogs were between 1 to 5 years old and 95.6% were kept for guarding purposes. 45% of the surveyed dogs had free access to roam outside the premises. The majority (85.4%) of dog owners were knowledgeable that a dog bite could potentially transmit RABV to humans. 19 dog bites were reported and of these 73.6% were caused by the owner's or a neighbour's dog. In 6 of the 19 cases, children between 7 and 15 years of age were the victims. Dog vaccination coverage against rabies was 34% among owned dogs. Of the participants aware of a veterinarian, the majority (55/82) indicated that they accessed veterinarian services at irregular intervals. The main obstacles to vaccinations cited by dog owners were limited financial resources and difficulty accessing veterinary care. CONCLUSION: This study contributes to enhanced understanding of the dog ecology including canine vaccine coverage as well as knowledge and practices of dog owners in Madagascar. Most dogs in the study area were accessible for preventive vaccination through their owners, however only one third of the investigated canine population was vaccinated against rabies. Concerted national efforts towards rabies prevention and control should aim to address financial challenges and access to veterinary services.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

The first confirmed human case of rabies, Timor-Leste, 2024.

In March 2024, the first ever human case of rabies, following a dog bite, was detected in Timor-Leste. This paper briefly discusses the circumstances of transmission, clinical presentation, palliative care of the case and public health measures taken. Timor-Leste was previously considered rabies-free. Any person who is bitten or scratched by an animal that could potentially transmit rabies virus (especially dogs, bats, monkeys or cats) in Timor-Leste should be assessed for consideration of provision of rabies post-exposure prophylaxis.

Protective Activity of Inactivated Rabies Vaccine Using Flagellin-Based Adjuvant.

Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method of preventing rabies disease in both animals and humans. In this study, the ability of an adjuvant based on recombinant Salmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats "Rabikan" (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the most widely used and internationally recommended method for testing effectiveness of the inactivated rabies vaccines. The value of specific activity of the tested rabies vaccine when co-administered with the adjuvant was significantly higher (48.69 IU/ml) than that of the vaccine without the adjuvant (3.75 IU/ml). Thus, recombinant flagellin could be considered as an effective adjuvant in the composition of future vaccine preparations against rabies virus.

Bayesian modeling of post-vaccination serological data suggests that yearly vaccination of dog aged <2 years old is efficient to stop rabies circulation in Cambodia.

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75-91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030.

What would be the impact on the rabies risk of reducing the waiting period before dogs are imported? A modelling study based on the European Union legislation.

AIMS: Lyssavirus rabies (RABV) is responsible for a major zoonotic infection that is almost always lethal once clinical signs appear. Rabies can be (re)introduced into rabies-free areas through transboundary dog movements, thus compromising animal and human health. A number of measures have been implemented to prevent this happening, one of which is the waiting period (WP) after anti-rabies vaccination and serological testing. This WP ensures that antibodies assessed through the serological test are due to the vaccine, not to infection. Indeed, if antibodies are due to RABV infection, the dog should display clinical signs within this WP and would not therefore be imported. METHODS AND RESULTS: Within a framework of quantitative risk assessment, we used modelling approaches to evaluate the impact of this WP and its duration on the risk of introducing rabies via the importation of dogs into the European Union. Two types of models were used, a classical stochastic scenario tree model and an individual-based model, both parameterised using scientific literature or data specifically applicable to the EU. Results showed that, assuming perfect compliance, the current 3-month waiting period was associated with a median annual number of 0.04 infected dogs imported into the EU. When the WP was reduced, the risk increased. For example, for a 1-month WP, the median annual number of infected dogs imported was 0.17 or 0.15 depending on the model, which corresponds to a four-fold increase. CONCLUSION: This in silico study, particularly suitable for evaluating rare events such as rabies infections in rabies-free areas, provided results that can directly inform policymakers in order to adapt regulations linked to rabies and animal movements.

Rabies post-exposure prophylaxis in the emergency department.

STUDY OBJECTIVES: Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. METHODS: This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. RESULTS: A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period.

Rabies vaccination adherence and associated factors among rabies-exposed patients in Shenzhen, China: a hospital-based cross-sectional study.

Adherence to post-exposure prophylaxis and post-exposure vaccination (PEV) is an important measure to prevent rabies. The purpose of this study was to explore the adherence to the vaccination protocol and its influencing factors among rabies-exposed patients in Shenzhen, China. A cross-sectional survey was conducted in a tertiary hospital in Shenzhen, China, to obtain epidemiological characteristics of patients; knowledge, attitude, and practice scores of rabies prevention; and medical records. A total of 326 patients requiring full rabies PEV were included in this study, and only 62% (202) completed the full course of vaccination according to the norms of the vaccination guidelines. After multifactor logistic regression, the factors influencing adherence to vaccination were as follows: age 31 to 40 years, time spent to reach the nearest rabies prevention clinic was >60 min, the time of injury was at night to early morning, the place of injury was a school/laboratory, the animal causing injury was a cat, the health status of the animal causing injury could not be determined, and patients with higher practice scores (all p<0.05). Understanding the factors influencing rabies vaccination adherence among rabies-exposed patients in urban areas of China and promote changes in patients' practice toward rabies prevention is essential for rabies elimination by 2030.

Avaliação epidemiológica dos casos de mordedura animal e factores associados a raiva em Moçambique, 2017-2021 / Epidemiological evaluation of animal bite cases, rabies and associated factors in Mozambique, 2017-2021

A mordedura por animal incluindo o cão é a principal forma de transmissão da raiva humana na África subsaariana, inclusive, Moçambique. Nos últimos anos tem-se registado um aumento de ocorrência de mordedura animal. Este estudo objetiva avaliar epidemiologia de mordedura animal e factores associados à raiva em Moçambique no período de 2017 a 2021.Realizou-se um estudo descritivo transversal de abordagem quantitativa. Foram usados dados secundários do sistema de vigilância da raiva em humano e animal. Calculou-se estatística descritiva, regressão logística multivariada, considerando um P ˂0,05 como significativo e um IC95%. O teste de Hosmer-Lemeshow foi usado para avaliar o ajuste do modelo final a um nível de significância de 0,05, através do programa estatístico IBM SPSS, versão 27. Durante o período de estudo, em média, foram registados 87,9 casos de mordedura animal por 100.000 habitantes (IC95%:86,8­89,0) com uma tendência. As províncias de Maputo Cidade 263,3 (IC95%:253,8­272,8), Sofála 222,3 (IC95%:216,3­228,3), Gaza 154,3 casos por 100.000 habitantes (IC95%:147,8­160,7) tiveram incidência acima da média nacional. Dos casos investigados, 42,4% (1831/4321) eram menores de 15 anos, 56,4% (2435/4321) foram masculinos, 77,6% (3454/4321) residiam em área urbana e 91,3% (3943/4321) foram mordidos por cão. Dos cães envolvidos, 85,4% (3368/3943) não estavam vacinados. Entre os casos investigados com critério, 50,0% (1874/3746) não tiveram profilaxia pós-exposição. As pessoas mordidas em Zambézia (ORa=91,3; IC95%:22,06­378,09; P˂0,001); Niassa (ORa=14,2; IC95%:10,13­19,96; P˂0,001) e Cabo Delgado (ORa =13,8; IC95%:8,34­22,69; P˂0,001) tiveram mais chances de não fazer profilaxia pós-exposição do que as pessoas mordidas em Maputo Província. Residir na área rural aumenta 70% vezes mais chance de não fazer profilaxia pós-exposição do que residir na área urbana (ORa=1,80; IC95%:1,50­2,18; P˂0,0001). No período de estudo, foram registados, em média, 187,7 casos de raiva humana por 100.000 pessoas mordidas (IC95%:134,9­240,6). A pessoa mordida em Niassa (ORa=12,1; IC95%:5,8-25,0; P˂0,001), ou Cabo Delgado (ORa=9,5; IC95%:4,0-22,6; P˂0,001), ou Zambézia (ORa=5,3; IC95%:2,6-10,8; P˂0,001) ou Inhambane (ORa=3,7; IC95%:1,5-8,8; P=0,004) tem mais chance para devolver raiva do que a pessoa mordida em Maputo Província. A raiva continua a ser um grave problema de saúde pública em Moçambique. Viver nas províncias de Niassa, Cabo Delgado, Zambézia e Inhambane diminui a chance para fazer a profilaxia pós-exposição em humano e aumenta o risco de desenvolver raiva após uma mordedura animal. Baixa cobertura vacinal dos animais. Recomenda-se melhorar a logística da distribuição das vacinas antirrábicas, priorizando as áreas de maior incidência de mordedura animal e raiva.

Introduction: Animal and dog bites are the main forms of human rabies transmission in sub Saharan Africa, including Mozambique. In recent years there has been an increase in the occurrence of animal bites. This study aims to evaluate the epidemiology of animal bites and factors associated with rabies in Mozambique from 2017 to 2021. Methodology: This was a cross-sectional descriptive study with a quantitative approach. Secondary data from the human and animal rabies surveillance system were used. Descriptive statistics, multivariate logistic regression, considering a P ˂0.05 as significant and a 95% CI were calculated. The Hosmer-Lemeshow test was used to assess the fit of the final model at a significance level of 0.05, using the IBM SPSS statistical program, version 27. Results: During the study period, on average 87.9 animal bite cases per 100,000 inhabitants (95%CI:86.8-89.0) were recorded with a trend. The provinces of Maputo City 263.3 (95%CI:253.8-272.8), Sofala 222.3 (95%CI:216.3-228.3), Gaza 154.3 cases per 100,000 inhabitants (95%CI:147.8-160.7) had incidence above the national average. Of the cases investigated, 42.4% (1831/4321) were under 15 years of age, 56.4% (2435/4321) were male, 77.6% (3454/4321) resided in an urban area and 91.3% (3943/4321) were bitten by a dog. Of the dogs involved, 85.4% (3368/3943) were not vaccinated. Among the cases investigated with criteria, 50.0% (1874/3746) did not have post-exposure prophylaxis. Persons bitten in Zambezia (ORa=91.3; 95%CI:22.06-378.09; P˂0.001); Niassa (ORa=14.2; 95%CI:10.13- 19.96; P˂0.001) and Cabo Delgado (ORa=13.8; 95%CI:8.34-22.69; P˂0.001) were more likely not to take post-exposure prophylaxis than persons bitten in Maputo Province. Living in a rural area increased the odds of not taking post-exposure prophylaxis 70% more than living in an urban area (ORa=1.80; 95%CI:1.50-2.18; P˂0.0001). During the study period, an average of 187.7 human rabies cases per 100,000 people bitten were recorded (95%CI:134.9-240.6). A person bitten in Niassa (ORa=12.1; 95%CI:5.8-25.0; P˂0.001), or Cabo Delgado (ORa=9.5; 95%CI:4.0-22.6; P˂0.001), or Zambezia (ORa=5.3; 95%CI: 2.6-10.8; P˂0.001) or Inhambane (ORa=3.7; 95%CI:1.5-8.8; P=0.004) are more likely to return rabies than the person bitten in Maputo Province. Conclusion: Rabies remains a serious public health problem in Mozambique. Living in the provinces of Niassa, Cabo Delgado, Zambézia and Inhambane decreases the chance to take post-exposure prophylaxis in humans and increases the risk of developing rabies after an animal bite. Low vaccination coverage of animals. It is recommended to improve the logistics of rabies vaccine distribution, prioritizing the areas with the highest incidence of animal bites and rabies.

Vacunacion antirrábica en caninos y felinos de la Ciudad de Buenos Aires: Año 2021 / Rabies vaccination in Buenos Aires City: Year 2021

El objetivo del presente informe es exponer la situación actual de la vacunación antirrábica de la Ciudad de Buenos Aires, con el fin de realizar una planificación estratégica de prevención y control de la enfermedad. Se utilizaron datos sobre vacunación realizada por veterinarias privadas estimados a partir de la venta de talonarios por parte del Consejo Profesional de Médicos Veterinarios (CPMV); así como la vacunación realizada por los efectores públicos de salud: Instituto de Zoonosis Luis Pasteur (IZLP) y Mascotas de la Ciudad (MC).

Scaling-up the delivery of dog vaccination campaigns against rabies in Tanzania.

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.

Review of Oral Rabies Vaccination of Dogs and Its Application in India.

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.

Profilaxia pós-exposição antirrábica: evidências sobre pré-medicação, administração de soro e esquema vacinal / Anti-rabies post-exposure prophylaxis: evidence on premedication, serum administration and vaccination scheme

A raiva é uma zoonose transmitida ao homem pela inoculação do vírus rábico contido na saliva do animal infectado. A infecção por este vírus causa encefalite aguda com índice de letalidade próximo a 100%.Embora não haja cura para a raiva clínica, a doença é facilmente evitável pelo fornecimento oportuno de profilaxia adequada. A profiaxia antirrábica humana pode ser realizada pré (PrEP) ou pós (PEP) exposição potencial ao virus da raiva. As tecnologias utilizadas para esta profilaxia são as vacinas e os soros. Há diversos esquemas de profilaxia PrEP e PEP utilizados no mundo. No Brasil, há ainda indicação de administração de medicações prévias à infiltração de soro heterólogo, a fim de mitigar potenciais reações anafiláticas. A administração concomitante de vacinas, imunoglobulinas e pré-medicação para hipersensibilidade (anti-histamínicos e corticoides) através da via intramuscular é uma prática instituída no contexto municipal de Campo Grande - MS, ocasionando problemas recorrentes de falta de sítios para administração completa da profilaxia, especialmente em crianças. Quais os cuidados necessários durante a realização de Profilaxia Pós Exposição Antirrábica em situações de limitação de vias de administração e risco de hipersensibilidade? Após análise do conteúdo, a fim de concluir a revisão em tempo oportuno para a tomada de decisão da gestão, a equipe de pesquisa deliberou pela extração de dados somente dos estudos secundários. Os principais achados estão sumarizados em infográfico no APÊNDICE A. É indicada a modernização do Procedimento Operacional Padrão vigente na prefeitura de Campo Grande. A substituição das práticas relacionadas à pré-medicação IM, vacinação IM e administração de soro IM é cientificamente embasada e elimina o problema que originou a questão de pesquisa desta revisão, apresentando benefícios para gestão, profissionais e usuários do SUS.

Current characteristics of animal rabies cases in Thailand and relevant risk factors identified by a spatial modeling approach.

The situation of human rabies in Thailand has gradually declined over the past four decades. However, the number of animal rabies cases has slightly increased in the last ten years. This study thus aimed to describe the characteristics of animal rabies between 2017 and 2018 in Thailand in which the prevalence was fairly high and to quantify the association between monthly rabies occurrences and explainable variables using the generalized additive models (GAMs) to predict the spatial risk areas for rabies spread. Our results indicate that the majority of animals affected by rabies in Thailand are dogs. Most of the affected dogs were owned, free or semi-free roaming, and unvaccinated. Clusters of rabies were highly distributed in the northeast, followed by the central and the south of the country. Temporally, the number of cases gradually increased after June and reached a peak in January. Based on our spatial models, human and cattle population density as well as the spatio-temporal history of rabies occurrences, and the distances from the cases to the secondary roads and country borders are identified as the risk factors. Our predictive maps are applicable for strengthening the surveillance system in high-risk areas. Nevertheless, the identified risk factors should be rigorously considered and integrated into the strategic plans for the prevention and control of animal rabies in Thailand.

Occurrence of mesocarnivores in montane sky islands: How spatial and temporal overlap informs rabies management in a regional hotspot.

Interspecific interactions among mesocarnivores can influence community dynamics and resource partitioning. Insights into these interactions can enhance understanding of local ecological processes that have impacts on pathogen transmission, such as the rabies lyssavirus. Host species ecology can provide an important baseline for disease management strategies especially in biologically diverse ecosystems and heterogeneous landscapes. We used a mesocarnivore guild native to the southwestern United States, a regional rabies hotspot, that are prone to rabies outbreaks as our study system. Gray foxes (Urocyon cinereoargenteus), striped skunks (Mephitis mephitis), bobcats (Lynx rufus), and coyotes (Canis latrans) share large portions of their geographic ranges and can compete for resources, occupy similar niches, and influence population dynamics of each other. We deployed 80 cameras across two mountain ranges in Arizona, stratified by vegetation type. We used two-stage modeling to gain insight into species occurrence and co-occurrence patterns. There was strong evidence for the effects of elevation, season, and temperature impacting detection probability of all four species, with understory height and canopy cover also influencing gray foxes and skunks. For all four mesocarnivores, a second stage multi-species co-occurrence model better explained patterns of detection than the single-species occurrence model. These four species are influencing the space use of each other and are likely competing for resources seasonally. We did not observe spatial partitioning between these competitors, likely due to an abundance of cover and food resources in the biologically diverse system we studied. From our results we can draw inferences on community dynamics to inform rabies management in a regional hotspot. Understanding environmental factors in disease hotspots can provide useful information to develop more reliable early-warning systems for viral outbreaks. We recommend that disease management focus on delivering oral vaccine baits onto the landscape when natural food resources are less abundant, specifically during the two drier seasons in Arizona (pre-monsoon spring and autumn) to maximize intake by all mesocarnivores.

Toll-Like Receptor 4 Regulates Rabies Virus-Induced Humoral Immunity through Recruitment of Conventional Type 2 Dendritic Cells to Lymph Organs.

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expressions of pattern recognition receptors (PRRs) also cause diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not yet been revealed. Based on TLR4-deficient (TLR4-/-) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type 2 dendritic cells (CD8α- CD11b+ cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of follicular helper T (Tfh) cells promotes the proliferation of germinal center (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4-deficient (TLR4-/-) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG compared to that occurred in wild-type (WT) mice. As a consequence, TLR4-/- mice exhibited higher mortality than that of WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α+ CD11b-), a subset of cDCs known to induce CD4+ T-cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

Evaluating Surveillance for and Estimating Administration of Rabies Postexposure Prophylaxis in the United States, 2012-2018.

BACKGROUND: An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. METHODOLOGY/PRINCIPLE FINDINGS: To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012-2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012-2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. CONCLUSIONS: Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment.

Loss of binding antibodies against rabies in a vaccinated dog population in Flores Island, Indonesia.

Effective parenteral vaccines are available to control rabies in dogs. While such vaccines are successfully used worldwide, the period between vaccine boosters required to guarantee protection of the population against rabies varies between vaccines and populations. In Flores Island, Indonesia, internationally and locally produced rabies vaccines are used during annual vaccination campaigns of predominantly free-roaming owned domestic dogs. The study objective was to identify the duration of the presence and factors associated with the loss of adequate level of binding antibodies (≥0.5 EU/ml) following rabies vaccination in a domestic dog population on Flores Island. A total of 171 dogs that developed an antibody titre higher or equal to 0.5 EU/ml 30 days after vaccination (D30), were repeatedly sampled at day 90, 180, 270, and 360 after vaccination. On the day of vaccination (D0), an interview was performed with dog owners to collect information on dog characteristics (age, sex, body condition score (BCS)), history of rabies vaccination, kind of daily food, frequency of feeding, and origin of the dog. Serum samples were collected and the level of antibodies was quantitatively assessed using ELISA tests. Dogs were categorized as having an adequate level of binding antibodies (≥0.5 EU/ml) or inadequate level of binding antibodies (<0.5 EU/ml) at each time points examined. A total of 115, 72, 23, and 31 dogs were sampled at D90, D180, D270, and D360, respectively, with the highest proportion of antibodies ≥ 0.5 EU/ml (58%, 95% CI, 49-67%) at D90, which reduced gradually until D360 (35%, 95% CI, 19-52%). Multivariable logistic regression models showed that loss of adequate level of binding antibodies is significantly associated with dogs having no history of vaccination or vaccination applied more than 12 months before D0, being less than 12 months of age, and having a poor BCS. These results highlight the importance of BCS regarding the immune response duration and provide insights into frequency of vaccination campaigns required for the internationally available vaccine used on Flores Island. For dogs without vaccination history or vaccination being applied more than 12 months before D0, a booster is recommended within 3 months (a largest drop of antibodies was detected within the first 90 days) after the first vaccination to guarantee measurable protection of the population that lasts at least for one year.

Data-Driven Management-A Dynamic Occupancy Approach to Enhanced Rabies Surveillance Prioritization.

Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, National Rabies Management Program (NRMP) collaborates with other agencies to implement broad-scale ORV and conducts extensive monitoring to measure the effectiveness of the management. Enhanced Rabies Surveillance (ERS) was initiated during 2005 and updated in 2016 to direct surveillance efforts toward higher-value specimens by assigning points to different methods of encountering specimens for collection (strange-acting, roadkill, surveillance-trapped, etc.; specimen point values ranged from 1 to 15). We used the 2016-2019 data to re-evaluate the point values using a dynamic occupancy model. Additionally, we used ERS data from 2012-2015 and 2016-2019 to examine the impact that the point system had on surveillance data. Implementation of a point system increased positivity rates among specimens by 64%, indicating a substantial increase in the efficiency of the ERS to detect wildlife rabies. Our re-evaluation found that most points accurately reflect the value of the surveillance specimens. The notable exception was that samples from animals found dead were considerably more valuable for rabies detection than originally considered (original points = 5, new points = 20). This work demonstrates how specimen prioritization strategies can be used to refine and improve ERS in support of wildlife rabies management.

Comparative Study of Optical Markers to Assess Bait System Efficiency Concerning Vaccine Release in the Oral Cavity of Dogs.

Oral vaccination of dogs against rabies has the potential to achieve mass coverage and thus deplete the virus of its most important reservoir host species. There is, however, no established non-invasive method to evaluate vaccine release in the oral cavity, following bait ingestion. In this study, two pre-selected marker methods in conjunction with their acceptance were assessed in local Thai dogs. Shelter dogs (n = 47) were offered one of four randomized bait formulations; bait type A-, containing Green S (E142) in a fructose solution; type B-, containing Patent Blue V (E131) in a fructose solution; type C-, containing the medium used for delivery of oral rabies vaccine in baits commercially produced; and type D-, containing denatonium benzoate, which was to serve as the negative control, due to its perceived bitterness. Patent Blue V was found to possess overall stronger dyeing capacities compared to Green S. Furthermore, there was no significant difference in the acceptance or bait handling of Patent Blue V baits compared to those containing the oral rabies vaccine medium alone, suggesting the potential use of this dye as a surrogate for rabies vaccine when testing newly developed bait formats.