Critical analysis of the cat's role in the epidemiology of rabies / Análise crítica do papel do gato na epidemiologia da raiva

Rabies is a fatal zoonosis of world importance that in many aspects is still neglected. Due to national vaccination campaigns for dogs and cats, there has been a drastic reduction in the number of cases of human rabies transmitted by dogs. However, due to species peculiarities, the cat can act as an important link in the epidemiological chain of rabies. Thus, this study aimed to evaluate Brazilian data on canine and feline rabies surveillance to determine the importance of the cat in the current context of rabies epidemiology. In Brazil, recent cases of ORCID ID 1. https://orcid.org/0000-0003-0764-5234 2. https://orcid.org/0000-0002-6569-749X 3. https://orcid.org/0000-0003-2999-323X human rabies transmitted by cats have been reported, showing the importance of this species in the epidemiological chain of the disease.(AU)

A raiva é uma zoonose fatal de importância mundial que em muitos aspectos ainda é negligenciada. Devido às campanhas nacionais de vacinação de cães e gatos, houve uma redução drástica no número de casos de raiva humana transmitida por cães. Contudo, por peculiaridades da espécie, o gato doméstico pode atuar como um elo importante na cadeia epidemiológica da raiva. Posto isto, objetivou-se avaliar os dados brasileiros da vigilância da raiva canina e felina para se determinar a importância do gato no contexto atual da epidemiologia da raiva. No Brasil, casos recentes de raiva humana transmitida por gatos foram relatados, evidenciando a importância dessa espécie na cadeia epidemiológica da doença.(AU)

Investigação de evento adverso associado à vacinação antirrábica / Investigation of adverse event following immunization associated with antirabies vaccine / Investigación del evento adverso asociado a la vacunación antirrábica

A raiva é uma antropozoonose endêmica no Brasil. O animal infectado transmite o vírus rábico principalmente através de mordeduras. Por muitos anos cães e gatos representaram a principal fonte de infecção para seres humanos em áreas urbanas. Desde o ano de 1973, o Programa Nacional de Profilaxia da Raiva estabelece que cães e gatos devem ser imunizados contra raiva. A vacinação animal é um meio seguro, confiável e eficaz para proteger animais contra doenças infecciosas e prevenir a transmissão de zoonoses, contudo a administração de vacinas não é isenta de riscos. Portanto as ocorrências de evento adverso associados à vacinação devem ser investigadas, pois a demonstração da segurança das vacinas contribuiu para o sucesso dos programas de imunização. Este estudo descreve o relato de caso de um animal suspeito de apresentar reação adversa à vacinação antirrábica.

Rabies is an endemic anthropozoonosis in Brazil. The infected animal transmits the rabies virus mainly by bites. For many years dogs and cats represented the main source of infection to humans in urban areas. Since 1973, the National Rabies Prophylaxis Program has established that dogs and cats must be immunized against rabies. The animal vaccination is safe, reliable and effective to protect animals against infectious diseases and prevent the transmission of zoonoses, however the administration of vaccines is not without risks. The occurrences of adverse events associated with vaccination should be investigated, because the demonstration of vaccine safety contributed to the success of immunization programs. This study describes a case report of one animal suspected of having an adverse reaction to rabies vaccination.

La rabia es una antropozoonosis endémica en Brasil. El animal infectado transmite el virus de la rabia principalmente a través de mordeduras. Durante muchos años, los perros y gatos representaron la principal fuente de infección para los humanos en las zonas urbanas. Desde 1973, el Programa Nacional de Profilaxis de la Rabia ha establecido que los perros y gatos deben ser inmunizados contra la rabia. La vacunación animal es una forma segura, fiable y eficaz de proteger a los animales contra enfermedades infecciosas y prevenir la transmisión de zoonosis, sin embargo, la administración de vacunas no está exenta de riesgos. Por lo tanto, se debe investigar la ocurrencia de eventos adversos asociados con la vacunación, ya que la demostración de la seguridad de la vacuna contribuyó al éxito de los programas de inmunización. Este estudio describe el reporte de un caso de un animal sospechoso de tener una reacción adversa a la vacunación antirrábica.

Human rabies post-exposure prophylaxis: a review of the treatment of accidents involving domestic cats / Profilaxia pós-exposição da raiva humana: uma revisão dos tratamentos envolvendo gatos domésticos

Rabies is an anthropozoonosis that presents approximately 100% lethality and expensive preventive assistance. Many human post-exposure anti-rabies treatments indicated for people at risk of exposure to rabies virus, usually due to some aggression by a mammalian animal, are instituted annually. This study aimed to evaluate the initial care of post-exposure prophylaxis of human rabies in Belo Horizonte between 2007 and 2016, involving accidents with domestic cats. It was found 71.1% agreement between the treatments instituted by health services and the protocol of the Ministry of Health. Treatments classified as insufficient totaled 18.3% and excessive, 10.6%. The animals were healthy in 68% and observable in 68.4% of the cases. Treatments involving the use of anti-rabies vaccine totaled 87.7%. The most frequent treatment adopted by the health services was observing the animals associated with the human anti-rabies vaccination in 56.7% of the cases. Imperfections in the filling of the notifications must be revised to enable improvements for future analyses. As for human prophylactic anti-rabies care, forming a multidisciplinary health team including veterinarians would be well on the way to improving the service offered.(AU)

A raiva é uma antropozoonose que apresenta aproximadamente 100% de letalidade e alto custo na assistência pre-ventiva. É instituído anualmente, um elevado número de tratamento antirrábico humano pós-exposição, o qual é indicado para pessoas que se encontram sob risco de exposição ao vírus rábico, geralmente devido a alguma agressão por animal mamí-fero. Este trabalho teve como objetivo avaliar o atendimento inicial da profilaxia pós-exposição da raiva humana, em Belo Horizonte, entre os anos de 2007 a 2016, envolvendo acidentes com gatos domésticos. Encontrou-se 71,1% de concordân-cia entre os tratamentos instituídos pelos serviços de saúde e o protocolo do Ministério da Saúde. Tratamentos classificados como insuficientes totalizaram 18,3% e excessivos 10,6%. Os animais eram sadios em 68% e observáveis em 68,4% dos casos. Tratamentos que envolviam o uso de vacina antirrábica totalizaram 87,7%. O tratamento adotado pelos serviços de saúde com maior frequência foi a observação do animal associada à vacinação antirrábica humana em 56,7% dos casos. É necessário que imperfeições no preenchimento das notificações sejam revistas de forma a possibilitar melhorias para análises futuras. Quanto ao atendimento antirrábico profilático humano, a formação de uma equipe multidisciplinar de saúde com inclusão de médi-cos veterinários seria uma forma de aprimorar o serviço oferecido.(AU)

Risk of rabies transmission and adverse effects of postexposure prophylaxis in health care workers exposed to a fatal case of human rabies.

On May 27, 2008, a patient died from rabies at the Cayenne Hospital in French Guiana. Postexposure prophylaxis vaccination was implemented for all health care workers exposed to this patient. Examining the management of such a rare risk reveals important factors in the education of personnel who may have contact with a patient with rabies, to permit appropriate risk assessment and reduce unnecessary postexposure prophylaxis, taking into account the risks and costs of adverse events.

Estudo imunológico e genético de 10 isolados do vírus da raiva de morcegos do Rio de Janeiro, Sudeste do Brasil / Immunological and genetic study of 10 bat rabies virus isolates from Rio de Janeiro State, Southeast

O presente trabalho visou estudar 10 isolados de vírus da raiva de morcegos hematófagos e não-hematófagos do Estado do Rio de Janeiro em suas características genéticas quanto aos genes N e G, além da resposta de camundongos vacinados com a vacina anti-rábica produzida pela replicação da amostra Pitman-Moore em cultivo celular, frente ao desafio com estes isolados virais, utilizando-se um ensaio imunológico baseado no teste de potência NIH. A vacina anti-rábica utilizada na imunização dos camundongos ofereceu proteção em mais de 80% dos camundongos vacinados com a diluição 1:5 da vacina, frente à maioria dos isolados. A análise filogenética do gene da proteína N apresentou um padrão de agregação dividido em variante de morcego hematófago e variante de morcego insetívoro, com todos os isolados de morcegos frugívoros Artibeus sp. tendo sido segregados com a variante característica de morcegos Desmodus rotundus. Foram observadas diferenças filogenéticas entre as variantes do vírus da raiva de morcego hematófago isoladas na Região Noroeste do Estado do Rio de Janeiro e aquelas isoladas nas Regiões Metropolitana e Sul do Estado. A substituição do resíduo ácido aspártico por ácido glutâmico na posição 118, encontradas na caracterização genética da proteína G dos isolados 704/97BR-DR e 151/98BR-DR, permite inferir que esta posição esteja relacionada à antigenicidade viral. Não foram observadas diferenças genéticas temporais entre os isolados estudados. A vacina anti-rabica utilizada ofereceu proteção satisfatória contra a maioria dos isolados estudados. (AU)

In the present study we analyzed 10 bats rabies viruses isolated from Rio de Janeiro State, focusing on its genetic characteristics from genes N and G, and also in the response of mice vaccinated with cell-culture rabies vaccine, produced with the Pitman-Moore strain, after viral challenge with bat rabies isolates, using an immunologic essay based on NIH vaccine potency test. The vaccine used conferred protection in more than 80% of the mice vaccinated with 1:15 vaccine dilution, after viral challenge. N gene genetic analysis divided the rabies virus isolates into haematophagous and insectivorous bat variants, with all isolates from Artibeus sp. frugivorous bats being clustered with the variant characteristic of the Desmodus rotundus vampire bat. Phylogenetic differences between isolates from Northeast Region and those from the Metropolitan and South Regions of Rio de Janeiro State were observed. The substitution of an aspartic acid to a glutamic acid found in the position 118 of G gene genetic characterization from samples 704/97BR-DR and 151/98BR-DR seems to be related to viral antigenicity. There were no time-related genetic differences between the studied samples. The vaccine employed was found with satisfactory protection against the majority of the isolates used.(AU)

Immunogenicity and safety of a new Vero cell rabies vaccine produced using serum-free medium.

The immunogenicity and safety of a new human rabies vaccine, produced in Vero cells by a process that does not require supplementation with human or animal derived components in production, were assessed. Thus, the objective is to produce a safer vaccine at a lower cost. A total of 296 volunteers was divided into two groups: Group 1, which received the study vaccine, and Group 2, which received the Vero cells vaccine produced by Sanofi Pasteur. Five doses were given on days 0, 3, 7, 14 and 28. Blood samples for determination of rabies virus neutralizing antibodies were collected on days 0, 14, 38 and 90. The geometric mean titers (GMT) were much higher than 0.5 IU/ml in both groups on days 14, 38 and 90, indicating seroconversion according to the World Health Organization. In Group 1, however, the GMTs were higher than in Group 2, the difference being statistically significant in the two last samples. There was no statistical difference between the groups in the ratio of individuals with titers > or =0.5 IU/ml in each sample. Pain at the injection site was the most common adverse reaction and occurred most often in Group 1 (p < 0.001). All cases had a favorable evolution. There were no severe adverse reactions. It was concluded that the new vaccine is safe and immunogenic.

Indirect oral immunization of captive vampires, Desmodus rotundus.

A vaccinia-rabies glycoprotein recombinant virus (V-RG) vaccine was tested in hematophagous bats (Desmodus rotundus) kept in captivity. The vaccine was applied in a neutral vehicle (Vaseline) spread on the back of one or two vector bats, which were then reintroduced into their groups. Our hypothesis was that, as in the case of vampire bat control by vampiricide paste, the administration of V-RG vaccine through paste to one bat could indirectly protect other bats from the same group. Eight groups were tested. The rabies virus strain used to challenge the bats was isolated from a naturally infected hematophagous bat (Desmodus rotundus). The survival proportion after the virus challenge ranged between 42.8 and 71.4%. The results are encouraging because a significant number of bats that did not receive the vaccine survived the challenge. The vaccine was shown to be safe and immunogenic to hematophagous bats. No adverse effects to vaccinia virus were observed.

Adverse reactions associated with a Fuenzalida-Palacios rabies vaccine: a quasi-experimental study.

The Fuenzalida-Palacios rabies vaccine has been used in South America for rabies post-exposure prophylaxis. To determine the frequency of adverse reactions associated with this vaccine compared to a control group a quasi-experimental study was carried out in Uberlândia, Brazil, from May 1997 to April 1998. Victims of bites or other injuries by dogs or other mammals and who received or not post-exposure prophylaxis with Fuenzalida-Palacios rabies vaccine were compared as to the occurrence of a list of signs and symptoms. Out of 2,440 victims of bites and other injuries from dogs and other mammals 2,114 participated in the study; 1,004 of them provided follow-up information within 10 to 15 days. Headache and pain at the injection sites were the most commonly found symptoms (125/1,000). No neuroparalytic event was detected. Patients who were given Fuenzalida-Palacios rabies vaccine and those who were not had similar incidences of symptoms (risk ratios close to 1). Regarding the occurrence of adverse reactions, Fuenzalida-Palacios rabies vaccine is a valid alternative for rabies post-exposure prophylaxis.

[Evaluation of the clinical manifestations in patients with reactions to the rabies vaccine or serum in the Ciego de Avila province (Cuba)]. / Evaluación de las manifestaciones clínicas en pacientes con reacciones a la vacuna o suero antirrábico en la provincia de Ciego de Avila (Cuba).

The present design is a descriptive study in which people bitten by animals, rabies treatment used and the reactions to it are described. The frequency of adverse effects to the vaccine and to the serum are pointed out. The forms of clinical presentation and the clinical symptoms of the reactions observed in the Ciego de Avila province, Cuba, in the period from 1981 to 2001, were evaluated. In this period prevailed the reactions to the heterologous serum and the reactions caused by the human rabies vaccine. Local reactions to the vaccine were more common than the systemic ones. Four neuroparalytic reactions produced by the vaccines were observed. The most frequent symptoms and signs of the patients with reaction to the vaccine were pruritus, rash, localized urticaria, papule in the point of injection and local pain. The clinical manifestations considered as reactions to the heterologous serum that prevailed in the patients were rash in gluteal regions, pruritus, local erythyema and fever. No patient was detected with neurological manifestations caused by the heterologous serum.

Reacciones al tratamiento antirrábico en Ciego de Avila, Cuba. Revisión de 17 años / Reactions to antirabic treatment in Ciego de Avila, Cuba Review of 17 years

Se evaluaron las reacciones al tratamiento antirrábico en la provincia Ciego de Ávila, Cuba, durante el periodo 1981-1997. Se consideraron reacciones vacunales a las manifestadas en pacientes que recibieron o no suero, presentaron pruebas de sensibilidad positiva e incrementaron el cuadro clínico durante la vacunación.Las pruebas de sensibilidad definidas al suero antirrábico en pacientes a los que se les aplicó este biológico resultaron positivas y no se aumentó el cuadro clínico durante la inmunización por vacuna. En la etapa analizada, el sistema de vigilancia detectó 114 reacciones, de ellas 39 (34 por ciento) tuvieron su origen en la aplicación de la vacuna y 75 (66 por ciento) se debieron al suero antirrábico heterólogo. Los inmunógenos utilizados fueron la vacuna antirrábica tipo Fuenzalida (CLR) producida por el Instituto Finlay, de la República de Cuba; el suero heterólogo equino del Instituto Mesnikov, de Rusia; y la gammaglobulina antirrábica homóloga de los laboratorios Berna, de Suiza. Predominaron las reacciones vacunales locales sobre las sistémicas. Se presentaron cuatro reacciones neuroparalíticas; uno de los pacientes falleció.De las reacciones al suero, 52 por ciento fueron locales y 48 por ciento sistémicas. No se presentaron reacciones a la gammaglobulina antirrábica humana.

Immunostimulatory effects of polar glycopeptidolipids of Mycobacterium chelonae for inactivated rabies vaccine.

Humoral and cellular immune responses were analyzed with Fuenzalida-Palacios rabies vaccine associated with pGPL-Mc, polar glycopeptidolipids extracted from Mycobacterium chelonae, aiming at its use as adjuvant. These results were compared to those obtained with BCG, a well-known immunostimulator, under the same conditions. Rabies vaccine plus pGPL-Mc (2.5 mg/kg) induced a significant increase in serum neutralizing activity, in vitro lymphocyte proliferation (spontaneous, specific and mitogen stimulation) and delayed type hypersensibility. In addition, pGPL-Mc, as well as BCG, enhanced the vaccine potency. Our results support further studies to encourage the use of pGPL-Mc as an immunostimulator of veterinary vaccines, before consideration for human vaccines.