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Introduction Human non-live vaccines have been associated with detrimental non-specific effects (NSE), particularly in females. A large trial found 2-fold increased overall mortality in girls receiving a new malaria vaccine compared to the rabies vaccine used as a coontrol; a beneficial NSE of the rabies vaccine was proposed. Conversely, in dogs increased mortality was seen in females but not males following rabies vaccination of puppies born to immunized mothers. We investigated NSE of non-live rabies vaccine in piglets and the potential modifying effect of maternal priming with rabies vaccine. Methods In a Danish herd of commercial rabies virus-free pigs, 575 pregnant sows (2–3 weeks before scheduled farrowing) and 5747 of their offspring (median 6-day-old) were allocated (1:1) to non-live rabies vaccine (Versiguard rabies vet) or no rabies vaccine. Outcomes were overall mortality and antibiotic treatment until departure from the nursery (approximately age 12 weeks/30 kgs). Results Until weaning, overall offspring mortality was 2.2% (127 piglets died, rabies vaccine: n = 69; control: n = 58), the proportion ratio (PR) being 1.19 (95% confidence interval: 0.84–1.68). Until end of follow-up, mortality was 4.1% (233, rabies vaccine: n = 115; control = 118, PR: 0.97 (0.76–1.25)). Prior sow rabies vaccination did not affect piglet mortality. For mortality as well as risk of antibiotic treatment before weaning, there was indication of a beneficial effect of rabies vaccine in female piglets, but a negative effect in (castrated) male piglets from rabies-naive sows. Prior sow vaccination significantly modified the vaccine effect estimate in female piglets toward a detrimental effect of rabies vaccine on treatment risk. These effects had waned by 12 weeks of age. Conclusion The study did not support the hypothesized beneficial NSE of rabies vaccine. Although under-powered for subgroup analyses, the study indicated effect modification by sex and maternal vaccination. Results could be different in a herd with higher mortality and infectious burden.

Background: Robust dog vaccination coverage is the primary way to eliminate canine rabies. Haiti conducts annual canine mass vaccination campaigns, but still has the most human deaths in the Latin American and Caribbean region. We conducted an evaluation of dog vaccination methods in Haiti to determine if more intensive, data-driven vaccination methods, using smartphones for data reporting and geo-communication, could increase vaccination coverage to a level capable of disrupting rabies virus transmission.Methods: Two cities were designated into “Traditional” and “Technology-aided” vaccination areas. Traditional areas utilized historical methods of vaccination staff management, whereas Technology-aided areas used smartphone-supported spatial coordination and management of vaccination teams. Smartphones enabled real time two-way geo-communication between campaign managers and vaccinators. Campaign managers provided geographic instruction to vaccinators by assigning mapped daily vaccination boundaries displayed on phone handsets, whilst vaccinators uploaded spatial data of dogs vaccinated for review by the campaign manager to inform assignment of subsequent vaccination zones. The methods were evaluated for vaccination effort, coverage, and cost.Results: A total of 11,420 dogs were vaccinated during the 14-day campaign. The technology-aided approach achieved 80% estimated vaccination coverage as compared to 44% in traditional areas. Daily vaccination rate was higher in Traditional areas (41.7 vaccinations per team-day) compared to in technology-aided areas (26.8) but resulted in significantly lower vaccination coverages. The cost per dog vaccinated increased exponentially with the associated vaccination coverage, with a cost of $1.86 to achieve 25%, $2.51 for 50% coverage, and $3.19 for 70% coverage.Conclusions: Traditional vaccination methods failed to achieve sufficiently high vaccination coverages needed to interrupt sustained rabies virus transmission, whilst the technology-aided approach increased coverage above this critical threshold. Over successive campaigns, this difference is likely to represent the success or failure of the intervention in eliminating the rabies virus. Technology-aided vaccination should be considered in resource limited settings where rabies has not been controlled by Traditional vaccination methods. The use of technology to direct health care workers based on near-real-time spatial data from the field has myriad potential applications in other vaccination and public health initiatives.

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes.

Animal and human bites are a common cause of admission to the emergency room and the infections are common, although they are often trivialized. Complications can range from simple cellulitis to septic shock especially in asplenic patients with Capnoyctophaga canimorsus infection. Other less common infections are possible such as rat-bite fever, leptospirosis, tularemia, and evaluation of post-exposure prophylaxis (anti-tetanus, anti-rabies, HIV, HBV) is essential. Antibiotic prophylaxis remains controversial but is recommended for certain groups of patients and must cover common bite pathogens.

Rabies is one of the oldest and deadliest infectious diseases known by human beings and is commonly transmitted by animal bites. Dogs have a major role in the transmission of the virus. Rabies has no approved curative therapy, and its prevention, even though it is highly effective, it is complex, expensive and challenging in terms of accessibility, particularly regarding immunoglobulin. This review aims to provide a practical approach to cost-effective prevention as well as the future perspectives regarding the development of an effective and secure cure.This review article was based on a search in PubMed using the following MeSH terms: rabies, preexposure and postexposure prophylaxis, rabies immune globulin, treatment, Milwaukee Protocol.Concerning rabies infection, it's important to apply the prevention protocols effectively as early as possible due the unpredictable time window between infection and the appearance of symptoms. The literature shows that is possible to reduce the vaccination dosage and maintain the efficiency of the immunization, and booster vaccination is only required in specific risk groups/populations.The current philosophy of cost-effective prevention which consists of canine vaccination, restriction of vaccine overdosage used in humans and the appropriate use of rabies immunoglobulin - could make the prevention of the disease accessible for those countries that need it the most. There are several therapies in development but they're all in early stages of development.The development of new and more effective therapeutic and prophylactic approaches is a goal not yet achieved and relies on a better understanding of the disease pathophysiology.Introdução: A raiva é uma das doenças infecciosas mais antigas e fatais conhecidas pelo ser humano e é maioritariamente transmitida por mordeduras de animais. O cão é o principal vector. A raiva não possui uma terapia curativa aprovada e a sua prevenção ainda que possua altas taxas de eficácia, é complexa, dispendiosa e nem sempre conseguida, muito devido às dificuldades de acesso da imunoglobulina. Esta revisão pretende analisar uma abordagem prática de uma prevenção custo-efectiva e as perspectivas futuras em desenvolvimento de uma cura eficaz e segura.Material e Métodos: Foi utilizada a base de dados da PubMed para pesquisa bibliográfica. Usaram-se os termos MeSH: ‘rabies’, ‘preexposure prophylaxis’, ‘postexposure prophylaxis’, ‘rabies immune globulin’, ‘treatment’ e ‘Milwaukee Protocol’.Resultados: Relativamente à raiva, é importante executar os protocolos de prevenção atempadamente, devido à imprevisível janela de tempo entre a infecção e a sintomatologia. A literatura mostra que é possível reduzir a dose de vacina mantendo uma eficiente imunização, e que doses de reforço só são necessárias em grupos/populações de risco.Discussão: A actual filosofia de uma prevenção custo-efectiva, que assenta na vacinação canina, restrição de sobredose das vacinas usadas em seres humanos e o uso inteligente da imunoglobulina rábica – irá permitir maior acessibilidade da prevenção da doença aos países que mais carecem dela. Encontram-se em progresso terapias promissoras, ainda em estadios precoces de estudo.Conclusão: O desenvolvimento de novas abordagens terapêuticas e profilácticas mais eficazes é um objectivo ainda não alcançado e depende de uma melhor compreensão da patogénese subjacente à doença.

Background Estimates of current global rabies mortality range from 26,000 to 59,000 deaths per annum. Although pre-exposure prophylaxis using inactivated rabies virus vaccines (IRVs) is effective, it requires two to three doses and is regarded as being too expensive and impractical for inclusion in routine childhood immunization programmes. Methodology/ Principal findings Here we report the development of a simian-adenovirus-vectored rabies vaccine intended to enable cost-effective population-wide pre-exposure prophylaxis against rabies. ChAdOx2 RabG uses the chimpanzee adenovirus serotype 68 (AdC68) backbone previously shown to achieve pre-exposure protection against rabies in non-human primates. ChAdOx2 differs from AdC68 in that it contains the human adenovirus serotype 5 (AdHu5) E4 orf6/7 region in place of the AdC68 equivalents, enhancing ease of manufacturing in cell lines which provide AdHu5 E1 proteins in trans. We show that immunogenicity of ChAdOx2 RabG in mice is comparable to that of AdC68 RabG and other adenovirus serotypes expressing rabies virus glycoprotein. High titers of rabies virus neutralizing antibody (VNA) are elicited after a single dose. The relationship between levels of VNA activity and rabies virus glycoprotein monomer-binding antibody differs after immunization with adenovirus-vectored vaccines and IRV vaccines, suggesting routes to further enhancement of the efficacy of the adenovirus-vectored candidates. We also demonstrate that ChAdOx2 RabG can be thermostabilised using a low-cost method suitable for clinical bio-manufacture and ambient-temperature distribution in tropical climates. Finally, we show that a dose-sparing effect can be achieved by formulating ChAdOx2 RabG with a simple chemical adjuvant. This approach could lower the cost of ChAdOx2 RabG and other adenovirus-vectored vaccines. Conclusions/ Significance ChAdOx2 RabG may prove to be a useful tool to reduce the human rabies death toll. We have secured funding for Good Manufacturing Practice- compliant bio-manufacture and Phase I clinical trial of this candidate., Author summary Rabies was, after smallpox, the second human disease for which an efficacious vaccine was developed, by Pasteur in 1885. Although it is eminently preventable, with highly efficacious vaccines available for both humans and animals, it still causes considerable mortality in low and middle-income countries. It is a particular problem in areas with the weakest healthcare and veterinary infrastructure, where achieving prompt post-exposure prophylaxis or high-coverage dog vaccination are challenging. Here, we report the development of a new candidate rabies vaccine, designed to enable low-cost single-dose pre-exposure human rabies prophylaxis in such settings. ChAdOx2 RabG is based upon a simian adenovirus-vectored candidate previously shown to achieve protection after a single dose in non-human primates, now modified to allow clinical-grade bio-manufacture. We show that it induces a potent immune response in mice, that this response can be further enhanced by a clinically-relevant adjuvant, and that we can stabilise it such that it can withstand temperatures of up to 45 °C for a month. We will be performing a clinical trial of this candidate in the near future.

Resumo Objetivo: descrever as características das notificações de atendimento antirrábico humano nos municípios da Mesorregião do Agreste Pernambucano, Brasil, de 2010 a 2012. Métodos: estudo descritivo com dados das fichas de atendimento antirrábico humano do Sistema de Informação de Agravos de Notificação (Sinan). Resultados: foram incluídas 10.138 notificações de atendimento antirrábico humano; a espécie mais frequentemente envolvida foi a canina (68,1%), sob condição sadia (79,9%); a mordedura foi o tipo de contato mais comum (83,8%); predominaram ferimentos múltiplos (58,3%), em mãos/pés (39,4%), e ferimentos profundos (56,8%); observou-se baixa frequência de administração da combinação de soro+vacina (10.5%), mesmo com 47,9% das lesões consideradas graves e, consequentemente, necessitando dessa conduta profilática. Conclusão: foi identificada possível realização de condutas profiláticas inadequadas, evidenciando necessidade de capacitação dos profissionais de saúde para uma correta instituição da profilaxia antirrábica humana e preenchimento adequado das fichas de notificação. Resumen Objetivo: describir las características de las notificaciones de tratamiento anti-rabia humana en los municipios de la mesorregión del “agreste” de Pernambuco, Brasil, 2010-2012. Métodos: se realizó un estudio con datos de tratamiento anti-rabia humana del Sistema de Información de la Notificación de las Enfermedades (Sinan) Resultados: fueron incluidas 10.138 notificaciones de tratamiento anti-rabia humana; la especie involucrada en el mayor número de notificaciones fue canina (68,1%), bajo condiciones saludables (79,9%), y la mordedura fue el contacto más común (83,8%), causando lesiones múltiples (58, 3%) en manos/pies (39,4%), heridas profundas en el 56,8% de los casos; se observó un pequeño número da combinación suero+vacuna (10.5%), incluso a cuando 47,9% de las lesiones se consideró grave necesitando esa conducta profiláctica. Conclusión: se identificó la realización posible de medidas profilácticas inapropiadas, poniendo en evidencia la necesidad de una educación en salud a profesionales de salud para la correcta institución de la profilaxis para rabia humana y un mejor cumplimiento de los formularios de notificación. Abstract Objective: to describe the characteristics of reported human anti-rabies treatment in municipalities of the ‘agreste’ region of Pernambuco State, Brazil, 2010-2012. Methods: this was a descriptive study using data from human anti-rabies medical records filed on the Information System for Notifiable Diseases (Sinan). Results: 10,138 reported records of anti-rabies treatment were included; canines were the most involved species (68.1%), in good health condition (79.9%). Biting was the most common contact (83.8%), causing multiple injuries (58.3%), to hands/feet (39.4%), and deep wounds in 56.8% of cases; combined vaccine + serum administration frequency was found to be low (10.5%), even though 47.9% of injuries were considered severe and therefore required this prophylactic procedure. Conclusion: possible inadequate prophylaxis procedures were found, showing the need for health worker training aimed at ensuring correct human anti-rabies prophylaxis and the proper filling in of medical record files.