Vigilancia, prevención y control de la rabia: Ciudad de Buenos Aires: Junio 2018 / Surveillance, prevention and control of rabies: City of Buenos Aires: June 2018

La rabia es una enfermedad viral, de distribución mundial que afecta al hombre y a todos los mamíferos tanto domésticos como silvestres, con una letalidad del 100% afectando el sistema nervioso central. Se transmite por medio de la inoculación del virus contenido en la saliva del animal infectado, principalmente por mordeduras o el lamido de heridas, o por predación cuando un animal caza un murciélago infectado y toma contacto con el virus desde el encéfalo del quiróptero. Otras formas de transmisión, menos frecuentes son por trasplante de tejidos infectados o por aerosoles. En este apartado, se describe la situación epidemiológica de esta zoonosis en la Ciudad de Buenos Aires: observación de animales mordedores, detección de virus rábico en muestras mediante diagnóstico de laboratorio, vacunación de animales y control poblacional mediante esterilizaciones quirúrgicas, acciones de control de focos de rabia, y seguimiento de animales con exposición a murciélagos positivos a rabia o no analizables

Mordedura canina e atendimento antirrábico humano em Minas Gerais / Dog bite and human anti-rabies healthcare, Minas Gerais

O objetivo do presente trabalho foi descrever e avaliar a mordedura canina e o atendimento antirrábico humano em Minas Gerais, de 1999 a 2004, correlacionando fontes de informação e áreas de risco predeterminadas para raiva humana transmitida por cão. Realizou-se um estudo observacional descritivo retrospectivo, utilizando-se, de forma adaptada, a análise exploratória de prontuários dos atendimentos da Superintendência de Epidemiologia da Secretaria de Estado da Saúde de Minas Gerais (339.012 de atendimentos), do Sistema de Informação de Notificação de Agravos, do Sistema de Informações sobre Mortalidade, do Sistema de Informações Hospitalares e do Programa Nacional de Imunizações (132.452 fichas). Para a classificação dos agravos, usou-se o Código Internacional de Doenças (10ª revisão). Os dados foram armazenados e analisados com auxílio dos softwares Epi-Info, Tab-Win e Office®. Verificou-se que o tratamento antirrábico humano é excessivo nas áreas de baixo e médio risco para raiva e, ao contrário, reduzido nas áreas de alto risco. O perfil do paciente é estudante masculino, menor de 14 anos, residente em área urbana de baixo risco para raiva humana transmitida por cão, com mordedura única nos membros, provocada por cão sadio e observável. Os sistemas de informação não oferecem a confiabilidade necessária ao médico responsável para a prescrição do tratamento antirrábico adequado. A profilaxia da raiva deve ter um aspecto multicêntrico, com interfaces na atenção tanto à saúde humana quanto à animal, o que não tem ocorrido, propiciando falhas na vigilância e no atendimento do agravo.

The objective of the present paper is describe and evaluate dog bite and some aspects of anti-rabid human care in Minas Gerais during five years, correlating the sources of information and epidemiological risk areas defined for human rabies transmitted by dogs in the State. We performed an observational retrospective study by adapted exploration form analysis, from 1999 to 2004, using databases of Epidemiology of Minas Gerais and National Information Systems of reportable disease, Immunization, Mortality, Hospitalization, International Code of Diseases (10th revision). The areas of risk for human rabies transmitted by dogs were pre determined. The dog bite is still the main complaint that leads to care. The profile of the patient is a male student, under 14 years of age, with a single wound in members, resident in an urban low risk area for human rabies transmitted by dogs, and is healthy and observable. The treatment is excessive in areas of low and medium risk. In high-risk areas, there is a low indication of treatment. Information systems do not offer the reliability required by the doctor responsible for prescribing the appropriate anti-rabies treatment. Rabies prophylaxis should have a multi-centre aspect, with interfaces in attention to health and veterinary, which has not occurred, providing surveillance failures.

Frequency and causes for exclusion from randomization of healthy volunteers screened for a phase 1 study in India.

Background. Only a proportion of screened potential participants were actually randomized while conducting a phase 1 study of a humanized rabies monoclonal antibody. We aimed to assess the challenges in defining who is a normal volunteer and the issues that affect volunteer recruitment and thus accrual. Methods. One hundred and fifty-six volunteers were screened and 74 (47.4%) were randomized in a phase 1 study. Data on all participants screened for the study were analysed and reasons for their non-randomization were classified. Results. The reasons for volunteers not being randomized were: (i) deranged laboratory parameters (n=62); (ii) nonlaboratory causes (n=4); and (iii) withdrawal of consent (n=16). A large proportion of screen failures were due to low haemoglobin levels, which led to the protocol being amended midway during the study. An informal interview of those who declined consent showed that they had only wanted to get themselves investigated thoroughly or were interested in getting their HIV status evaluated. Conclusions. Our study shows that <50% participants screened for a phase 1 study in a developing country actually get randomized. The main reason for non-randomization is abnormal laboratory tests. This may help investigators and sponsors to plan protocols better, define normal ranges with acceptable variations based on their own populations a priori and have more pragmatic accrual targets.

Evaluación de la seroconversión como respuesta a la vacunación antirrábica en perros en el departamento del Valle del Cauca, Colombia, 2009 / Evaluation of the seroconversion as a response to rabies vaccination in dogs, Valle del Cauca, Colombia, 2009

Introducción. El departamento del Valle del Cauca ha estado libre de rabia canina por más de 20 años, aunque persisten focos de rabia silvestre que amenazan a humanos y sus mascotas; por ello, como medida preventiva. se realizan anualmente campañas de vacunación antirrábica canina. Objetivos. Medir el impacto de la vacunación en términos de seroconversión de anticuerpos neutralizadores y de porcentaje de perros con respuesta inmunitaria humoral adecuada, relacionando variables propias de estos animales y de las condiciones de vacunación. Discutir el significado epidemiológico de los resultados y sus implicaciones en salud pública. Materiales y métodos. Se obtuvo suero e información de 569 perros vacunados en los 42 municipios de Valle del Cauca. La inmunidad humoral se investigó por ELISA cuantitativa. La información se analizó con el programa Epi-Info 6.0. Resultados. El 9,1 % de los perros de la muestra fueron seronegativos y el 25,1 % no evidenciaron respuesta inmunitaria humoral adecuada a la vacunación. La concentración de anticuerpos disminuyó gradualmente desde la aplicación de la vacuna, y estuvo asociada a edad y calidad de las vacunas, aunque no estuvo asociada a sexo ni a raza. Conclusiones. Con el fin de aumentar los porcentajes de perros seropositivos y con respuesta inmunitaria humoral adecuada, se hacen las siguientes recomendaciones: 1) utilizar vacunas antirrábicas viables;2) aplicar dos dosis de vacuna durante los primeros seis meses de vida de los cachorros; 3) aplicar refuerzos de vacuna, por lo menos, una vez al año; 4) que las autoridades vigilen las actividades y los procesos programáticos relacionados con la vacunación antirrábica por particulares.

Introduction. The province of Valle del Cauca has been free of dog rabies for more than 20 years. However, sylvatic rabies foci remain which are threats to the health of the populace and its pets. Rabies vaccination campaigns are carried out annually in all 42 counties of the province. Objectives. The impact of dog vaccination was evaluated on the basis of humoral immunoresponse, population parameters and correlation with variables inherent to the vaccination process and logistics. Materials and methods. Sera and associated data were obtained from each of the 42 counties for a total sample of 569 rabies-vaccinated dogs. Rabies neutralizing antibodies were measured by quantitative ELISA. The data were analyzed with the statistical programs in Epi-Info 6.0. Results. Nearly 10% of dogs were seronegative (9.1%) and an additional 25.1% did not elicit an adequate humoral immune response to vaccination. Concentration of rabies neutralizing antibodies diminished gradually with the time after vaccination and was correlated with dog age and vaccine quality. No associations were noted between dog gender or breed. Conclusions. These data permit the following recommendations: (1) only viable, non expired rabies vaccines must be used to immunize animals, (2) two doses of rabies vaccine must be applied during the first six months of dog life, (3) booster immunizations must be administered every year, (4) practices and processes related to rabies vaccination in private institutions must inspected regularly by health authorities.

Is the skin sensitivity test required for administering equine rabies immunoglobulin.

Background. Rabies immunoglobulins are life-saving in patients with severe exposure to rabies. Despite the high degree of purification of equine rabies immunoglobulin (ERIG), the product inserts still recommend a skin sensitivity test before administration of this heterologous serum. A recent WHO recommendation states that there are no scientific grounds for performing a skin test before administering ERIG because testing does not predict reactions and it should be given irrespective of the result of the test. In this conflicting situation, we assessed the use of the skin sensitivity test in predicting adverse events to ERIG. Methods. The data analysed were from the Antirabies Clinic of the Kempegowda Institute of Medical Sciences Hospital, Bengaluru, India. The period of study was 26 months (June 2008–July 2010). The skin sensitivity test was validated by evaluating its sensitivity, specificity, predictability, falsepositive and false-negative results. Results. A total of 51 (2.6%) adverse events were reported in 31 (1.5%) subjects. Most of these were mild to moderate in nature and subsided without medication. There was no serious adverse event. The sensitivity and specificity of the skin sensitivity test to predict an adverse event was 41.9% and 73.9%, respectively. Conclusion. Our experience with the skin sensitivity test suggests that it may not be required before administering ERIGs, as recommended by WHO.

Pathogenicity of different rabies virus isolates and protection test in vaccinated mice / Patogenicidade de diferentes isolados do vírus da raiva e teste de proteção em camundongos vacinados

This study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. For evaluation of pathogenicity, mice were inoculated by the intramuscular route (IM) with 500MICLD50/0.03mL of the viruses. The cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (IC) route. Isolates were fully pathogenic when inoculated by the IC route. When inoculated intramuscularly, the pathogenicity observed showed different death rates: 60.0 percent for the Desmodus rotundus isolate; 50.0 percent for dog and Nyctinomops laticaudatus isolates; 40.0 percent for Artibeus lituratus isolate; 9.5 percent Molossus molossus isolate; and 5.2 percent for the Eptesicus furinalis isolate. Mice receiving two doses of the vaccine and challenged by the IC route with the isolates were fully protected. Mice receiving only one dose of vaccine were partially protected against the dog isolate. The isolates from bats were pathogenic by the IC route in mice. However, when inoculated through the intramuscular route, the same isolates were found with different degrees of pathogenicity. The results of this work suggest that a commercial vaccine protects mice from infection with bat rabies virus isolates, in addition to a canine rabies virus isolate.

O estudo avaliou e comparou as propriedades patogênicas de cinco isolados do vírus da raiva de morcegos e um isolado do vírus da raiva de cão e analisou a eficácia de vacina comercial contra estes isolados, em camundongos. Para o estudo de patogenicidade camundongos foram inoculados pela via IM com 0,1 mL contendo 500MICLD50/0,03mL das amostras de vírus. Quando inoculados pela via IC, os isolados do vírus da raiva provocaram a morte de 100 por cento dos camundongos. No entanto, 500MICLD50/0,03mL das mesmas amostras, inoculadas pela via IM, ocasionaram mortalidade de: 60,0 por cento quando a amostra era de Desmodus rotundus; 50,0 por cento de cão e de Nyctinomops laticaudatus; 40,0 por cento de Artibeus lituratus; 9,5 por cento de Molossus molossus; e 5,2 por cento de Eptesicus furinalis. Camundongos que receberam duas doses de vacina foram protegidos quando desafiados pela via IC, com todas as amostras testadas. Quando os camundongos receberam uma dose da mesma vacina, houve proteção parcial daqueles desafiados com a amostra de cão. Todos os isolados do vírus da raiva testados foram patogênicos para camundongos, inoculados pela IC. No entanto, pela via IM, os mesmos isolados mostraram diferentes graus de patogenicidade. Concluiu-se também que a vacina comercial contra raiva protegeu os camundongos desafiados com amostras de vírus isolados de morcegos e de cão.

Development in immunoprophylaxis against Rabies for animal and humans

Rabies is a fatal neurological disease and a persistent global problem. It is spread primarily by domestic dogs but other canid, viverrid [skink and raccoons] and chiropteran species are considered as the most efficient vectors of the disease. Since dogs are the main perpetuator of rabies, special attention has to be given to bring all the dogs including unauthorized stray dogs under immunization umbrella in order to control rabies. Vaccination is the only way to combat the disease before and after exposure or infection as there is no treatment available once the symptoms have appeared. After the first crude nerve tissue vaccine developed by Pasteur in 1885, a number of rabies vaccines for animal and human use have been developed with varying degree of safety and efficacy over the years. Recently, cell culture based inactivated rabies vaccines are largely used in most of the parts of the world. However, these vaccines are too expensive and unaffordable for vaccination of people and animals in developing countries. The comparatively cheaper inactivated nerves tissues vaccines can cause serious side-effects such as autoimmune encephalomyelitis in inoculated animals and production had been discontinued in several countries. Although attenuated live vaccines can efficiently elicit a protective immune response with a smaller amount of virus, they sometimes can cause rabies in the inoculated animals by its residual virulence or pathogenic mutation during viral propagation in the body. New-generation rabies vaccines generated by gene manipulation although in experimental stage may be a suitable alternative to overcome the disadvantages of the live attenuated vaccines. So, awareness must be created in general public about the disease and the cell culture based vaccines available in the market should be recommended for wide scale use to prevent and control this emerging and reemerging infectious disease in foreseeable future

Diagnóstico de un caso de rabia humana en Jujuy, 2008 / Diagnosis of a human rabies case in Jujuy, 2008

El 22 de Julio de 2008, un niño de 8 años de edad, residente en la provincia de Jujuy, Argentina, falleció por una encefalitis producida por el virus de la rabia. El diagnóstico se realizó mediante la detección de anticuerpos en suero y se confirmó por inmunofluorescencia en el cerebro. La tipificación antigénica correspondió a la variante 1 trasmitida por perros. El análisis molecular estableció que el virus detectado es de la misma variante genética que circula en Jujuy desde 2003. Este trabajo resume la evolución clínica del paciente y la posterior investigación epidemiológica que reveló el antecedente de mordedura por un perro 60 días antes de la iniciación de la enfermedad y la ausencia de un tratamiento antirrábico post-exposición.

On July 22, 2008, a previously healthy 8 years old boy from Jujuy, Argentina, died of encephalitis later confirmed as rabies. Diagnosis was made on the basis rabies-specific antibodies presence in a serum sample and it was confirmed by detection of the viral antigens in brain necropsy using the inmunofluorescent test. Antigenic characterization identified dog as source of infection. Molecular analysis recognized the same genetic variant circulating in Jujuy since 2003. This report presents the patient's clinical course and the epidemiologic investigation that revealed a dog bite 60 days before the illness onset and the lack of rabies treatment.

Rabies review: immunopathology, clinical aspects and treatment

Among the diseases of viral origin, rabies is unique in its distribution and range of victims since it can afflict all warm-blooded animals. The interaction between the virus and the host population has facilitated the survival of the disease. The rabies virus (RV) has not changed in any significant way and has been capable of taking advantage of conditions suited to the continuance of rabies. Infection by RV is invariably lethal in the absence of protective immune response which, however, can contribute to the pathogenesis of rabies. Proinflammatory cytokines might affect, directly or indirectly, the levels of neurotrophins, growth factors, neurotransmitters and neurotoxins in the brain by activating glia, neurons, and vascular and immune cells. Although understanding of the bases for neuronal dysfunction and neuronal death during RV infection has progressed, no fundamental abnormality has been identified so far.

Immunopathology of rabies infection in mice selected for high or low acute inflammatory reaction

Rabies is a severe and lethal disease that produces a slight inflammatory response during the infection process. We analyzed the immunopathological mechanisms that occur in the central nervous system (CNS) using mice genetically selected for maximal or minimal acute inflammatory reaction (AIRmax or AIRmin). As viral samples, we adopted the antigenic variant 3 (AgV3) of rabies virus from hematophagous bats and a fixed virus strain (PV1 43/3). Titration of specific antibodies was performed using enzyme-linked immunosorbent assay (ELISA). We observed a slight increase in IgG and IgG1 isotypes in infected AIRmax mice. Incubation period, determined by intracerebral inoculation with 100 LD50, was 6-7 days for PV1 43/4 strain and 9-10 days for AgV3. No difference in viral replication was noticed between AIRmax and AIRmin mice. Mortality was 100 percent with both viral strains. Histopathological analysis of brains and spinal cords showed inflammatory foci in all regions of the CNS. No differences were noticed in the number of neutrophils. Negri bodies were observed in practically all sites analyzed. Results suggested that inflammatory reaction is not a determining factor in the susceptibility to rabies infection.

Lack of correlation between rabies virus replication in the brain and antibody isotype profile in genetically modified mice

The relationship among the phenotypes resistance to infection, virus replication in the brain and isotype production was investigated in genetically modified High (H) or Low (L) antibody responder mouse lines. Although they express the same innate susceptibility to rabies infection, these lines differ as to different viral replication rates in the central nervous system and L mice showed a higher permissible state. After intramuscular infection with the Pasteur rabies strain (PV), the H-L interline differences on the earlier stage of virus replication were 1000 and 80 folds on days 5 and 6, respectively. The isotype profile in sera of the experimentally infected mice reflected an interline difference of 25 folds for IgG2a throughout the infection period, and for the IgE production the H-L difference was highly significant only at the beginning of the process. These results confirm the multi-specific effect of antibody immune responsiveness and the general isotype distribution of antibodies in these genetically selected mice. Contrary to the clear correlation between antibody responsiveness and the acquired resistance to rabies infection, the present study demonstrates that the constitutive genetic character of High and Low responder individuals does not intervene in the degree of resistance following infection. Altogether, this study contributes to the knowledge of the protective role of the general innate responsiveness on the pathological pattern to rabies virus infection

Antibody and cytokine seerum levels in patients subjected to anti-rabies prophylaxis with serum-vaccination

Rabies is considered a fatal disease once clinical symptoms have developed. The aim of this study was to evaluate epidemiological aspects and immune response in patients attacked by domestic and wild animals and subjected to post-exposure rabies treatment with equine serum and associated vaccine. Thirty-three patients were evaluated; they were between 13 and 65 years old, 75.8% were male and 24.2% female, and from the Botucatu neighborhood. Twenty healthy control individuals with the same age range were also studied. Specific antibodies to equine immunoglobulins and IFN-g, IL-2, IL-4, and IL-10 production were evaluated by ELISA. IgM, IgE, IgG and subclasses, and rabies virus antibodies serum levels were determined by nephelometry and seroneutralization methods, respectively. No anaphylactic or serum sickness allergic reactions were observed in patients after treatment. Anti-equine IgG levels were significantly higher than those of IgM after 14 and 28 days of treatment. Protective antibodies to rabies virus > 0.5 UI/ml were detected in 84.6% and 75% of patients at days 14 and 28, respectively. IFN-g, IL-2 and IL-10 levels in patients before and 48h after treatment were significantly higher than in controls suggesting that both Th1 and Th2 cells were activated in the patients. Serum IgM levels were higher at day 14, and IgG2 and IgE levels were higher at day 28 of treatment. These results suggest that post-exposure rabies treatment in humans induces significant alterations in patient immune response characterized by increased levels of cytokines, serum levels of specific rabies virus antibodies, and the equine serum components employed in the treatment

Effect of different adjuvants in equines for the production of equine rabies immunoglobulin.

BACKGROUND: Implementation of the recommended post-exposure prophylaxis by vaccination and specific immunoglobulin therapy for rabies is largely hampered by its high cost and inadequate production. Therefore, the development and availability of an economic preparation of rabies immunoglobulin is a high priority for India, where rabies is a major cause of death. We studied the efficacy of four different adjuvants in raising antibodies to rabies antigen in older, discarded equines. METHODS: Eleven equines, 23-26 years old, were divided into 4 groups to receive four different adjuvants in small amounts (1-2 ml)-Freund complete adjuvant with Mycobacterium tuberculosis, Freund complete adjuvant with M. butyricum, Freund incomplete adjuvant and bentonite--along with purified chick embryo cell vaccine. The immunization schedule was spread over 105 days and the antibody titres were measured on days 56, 91 and 119. RESULTS: On day 119 (third sampling), Freund complete adjuvant with M. tuberculosis provided a geometric mean titre of 654.03 IU/ml in comparison with a titre of 459.19 IU/ml with Freund complete adjuvant with M. butyricum, 630.95 IU/ ml with Freund incomplete adjuvant and 172.18 IU/ml with bentonite. CONCLUSION: Purified chick embryo cell vaccine in combination with Freund complete adjuvant containing M. tuberculosis and Freund incomplete adjuvant were better at eliciting an immune response. The low quantity of adjuvants used possibly helped by causing very few side-effects but without compromising the antibody titres.

Safety and immunogenicity of the intradermal Thai red cross (2-2-2-0-1-1) post exposure vaccination regimen in the Indian population using purified chick embryo cell rabies vaccine.

PURPOSE: To test the immunogenicity of the WHO recommended "2-2-2-0-1-1" post-exposure rabies vaccination regimen in Indian subjects to determine the feasibility of replacing crude sheep brain nerve tissue rabies vaccine with modern tissue culture rabies vaccine at major anti-rabies treatment centers throughout India. METHODS: Purified chick embryo cell vaccine (PCECV) was administered in the dosage of 0.1 mL per site to 53 Indian subjects. RESULTS: All subjects produced rabies antibodies above 0.5 IU/mL by day 14 post-vaccination. Only minor adverse reactions including swelling (6.6%), erythema (5.4%) and pain (1.4%) were observed for which no treatment was required. CONCLUSIONS: This study demonstrated that PCECV is safe and highly immunogenic in Indian subjects when administered intradermally as 0.1 mL/site using the "2-2-2-0-1-1" post-exposure regimen.

Comparative evaluation of immunogenicity, reactogenecity and safety of purified chick embryo cell rabies vaccine and neural tissue rabies vaccine.

OBJECTIVES: 1. To compare the protective antibody titres on day 14, 30 and 90 after giving intramuscular (IM) injections of PCECV and subcutaneous injections of Nervous Tissue Vaccine. 2. To compare the immunogenicity and safety of PCECV and NTV. METHODS AND MATERIALS: The study enrolled cases in three groups.Group 'C' or control group: (n = 38) : This group comprised of 38 normal healthy volunteers without dog-bite. Group 'A' (n = 102): This group included cases of dog-bite fulfilling inclusion/exclusion criteria. Each one of Group A and C were given PCECV as post exposure treatment (PET) on day 0-3-7-14-30 and 90. Group 'B' (n = 50): This group included 50 cases of dog-bite who received NTV. The rabies virus neutralizing antibody titres were estimated by RFFIT (Rapid Fluorescent Focus Inhibition Test) on day 0, 14, 30 and 90 days. 45 recipients of PCECV were re-tested for persistence of Protective Antibodies at the end of 1 year. RESULTS: Of these 37, 91 and 45 cases were evaluable in Groups C, A and B respectively. The antibody titres in Groups A, B, C were 13.4, 3.2, 22.8 IU/ml respectively; the protective titre being 0.5 IU/ml.5% PCECV recepients had delayed response on day 30.14% of NTV recepients did not seroconvert. CONCLUSIONS: The Immunogenicity, Reactogenicity and safety of PCECV is well established. 5% of PCECV receipients showed a delayed sero conversion. 14% of NTV receipients did not sero convert at all.Therefore it is desirable to estimate antibody titres on day 14 after vaccination. If difficult, then all the cases of animal bite must receive passive immunization with rabies immunoglobulins.

A passive haemagglutination test for rabies antibodies using rabies glycoprotein coupled erythrocytes.

The presently recommended tests for assaying rabies antibodies like mouse neutralization test (MINT) and rapid fluorescent focus inhibition test (RFFIT) are either time consuming or expensive and are generally performed in reference laboratories. There is a need to develop a specific and rapid method for detection of rabies antibodies that can be used to monitor sero-conversion after pre-or post-exposure vaccination. In this study, we have developed a passive haemagglutination (PHA) using purified rabies virus glycoprotein coupled to sheep erythrocytes using chromium chloride (0.04%) as a coupling agent. Two hundred and fifty five serum samples from people vaccinated with different rabies vaccines, 16 paired serum and CSF samples from autopsy confirmed cases of paralytic rabies, and serum samples from 65 normal healthy controls were tested and evaluated in comparison to standard MNT. Among the vaccinees, 250 samples were positive both by MNT and PHA but 5 samples were negative by PHA and positive by MNT. The titres obtained by PHA were lower compared to MNT, but there was significant correlation between the two (r=0.885). The specificity of the test was 99.7% and sensitivity was 100% as compared to MNT. Thus this PHA test promises to be a rapid and specific test for assaying rabies antibodies and may be useful in screening large number of serum samples for sero conversion after vaccination. It may also assist in rapid laboratory confirmation of paralytic rabies cases, based on detection of antibodies in CSF and serum.

Avaliação da imunogenicidade da vacina contra raiva em células Vero, desenvolvida no Instituto Butantan, segundo dois esquemas de imunização, em camundongos / Immunogenicity of Vero rabies vaccine developed at Butantan Institute: comparative study of two immunization protocols

A capacidade imunogênica de uma nova vacina contra raiva em células Vero, purificada, desenvolvida no Instituto Butantan, foi avaliada em camundongos. Grupos de animais da linhagem N:NIH foram imunizados com essa vacina, denominada VR/VERO, ou com vacinas comerciais de reconhecida eficácia: HDCV e VERORAB. Dois esquemas de imunização com três doses de vacina foram empregados, sendo que no primeiro estas foram aplicadas nos dias 0, 7 e 28 e no segundo nos dias 0, 28 e 63. Os títulos de anticorpos neutralizantes foram dosados 7 dias após cada dose de vacina e 30 dias após a última dose. Todos os camundongos imunizados com as vacinas VR/VERO ou HDCV e 83% dos vacinados com VERORAB apresentaram título satisfatório após a segunda dose, comprovando a imunogenicidade da vacina VR/VERO em relação às outras duas. As médias geométricas dos títulos de anticorpos neutralizantes obtidas com o esquema de doses mais espaçadas foram superiores às do esquema de doses mais próximas, sendo que essa diferença foi significativa na resposta secundária e 30 dias após a última dose de vacina. O esquema de imunização de intervalos longos propiciou uma resposta secundária similar à resposta terciária do esquema de intervalos curtos, sugerindo que há uma indução mais eficaz de memória à vacina. A cinética da produção de subclasses IgG1 e IgG2a foi avaliada no soro dos animais imunizados com as vacinasHDCV e VR/VERO, com os dois esquemas de imunização. A produção desses isótipos foi semelhante nos animais imunizados com as duas vacinas, sendo que tanto IgG1 quanto IgG2a apresentaram títulos muito superiores na resposta secundária do esquema de doses mais espaçadas,demonstrando a maior eficácia deste último

Guidelines for prophylaxis of rabies in Pakistan

Rabies is highly fatal and ends in an extremely painful and torturous death. All carnivorous animal [dog, cat, fox, jackal, skunk, mongoose, raccoon] and bats are considered potentially rabid. Rodents [rat, mouse, squirrel], rabbit or bird are not rabid. Transmission is usually through the bite of an infected animal. However, the percentage of rabid bites leading to clinical disease ranges from 10% [on the legs] to 80% [on the head]. Rabid animals can also transmit the disease by licking abraded skin or mucosa and by scratching. Patients with scratches from rabid animals are about 50 times less likely to develop rabies than those with bites. World Health Organization [WHO] Rabies Survey in 1992 estimated that 90% of human rabies occurred in the developing world. There are no known studies on the incidence of rabies in Pakistan; the problem of dog bite from possibly rabid dogs is rising alarmingly. Therefore the prevention of rabies infection after exposure is of utmost importance. It is preventable if WHO guidelines for post exposure treatment are followed. This guideline includes, immediate local treatment of the wound, passive immunization with rabies immunoglobulin and administration of an efficacious vaccine. Although there is a great urgency to improve post-exposure treatment, it will remain a costly and inefficient method of controlling rabies. It is the canine rabies epidemic which needs to be addressed

Immunogenicity of purified chick embryo cell anti-rabies vaccine in post-exposure treatment of animal bite cases.

The observations on immunogenicity of Purified Chick Embryo Cell (PCEC) anti rabies vaccination in post-exposure prophylaxis is reported. In total 207 serum samples collected from patients receiving 3 to 6 doses of PCEC were analysed for the presence of anti-rabies antibodies. The samples were collected from 10 days to 11 months after the last dose of vaccine. All the vaccinees (n=33) tested after 3 doses of PCEC showed protective titres (> or = 0.5 IU/ml) and those receiving 5-6 doses (n=161) showed 4-5 times higher than protective titres. The analysis pertains to specimens collected at one point of time only after the vaccination. However, in all 17 vaccinees where samples were collected 7-11 months after 3-6 doses of vaccine, the protective titres were sustained, these being 3-4 times higher than the protective titres in those receiving 5-6 vaccine doses. The results indicated that there was no need of routine anti-rabies antibody monitoring in healthy individuals receiving post-exposure prophylaxis in recommended doses of vaccine.