Lack of documentation in animal bite cases and its impact on rabies biologicals utilization.

Introduction: Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post-exposure prophylaxis (PEP). There is a shortage of anti-rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re-administration of the anti-rabies vaccine, leading to a significant biological loss (anti-rabies vaccine). Material and Methods: A cross-sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years. Results: Majority of the patients reported within the first 24 hours after being bitten while approximately one-third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower-middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re-exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites. Conclusion: Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re-exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients.

Myocardial infarction with nonobstructive coronaries (MINOCA) following rabies postexposure prophylaxis: A case report.

Key Clinical Message: This case underscores the importance of considering myocardial infarction with nonobstructive coronary arteries (MINOCA) in patients experiencing acute chest pain following rabies vaccination, emphasizing the need for heightened awareness and further research into the association between MINOCA and Rabies vaccination. Abstract: Rabies is a vaccine-preventable deadly viral disease prevalent in Asia and Africa that causes thousands of deaths annually. Rabies pre (PrEP) and postexposure prophylaxis (PEP) is highly effective in annulling rabies-associated deaths. The adverse reactions following rabies vaccination are typically mild. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare condition, and its association with rabies vaccination is unprecedented. We present a case of a 43-year-old male with MINOCA following Rabies PEP. A 43-year-old male, nonsmoker and nonalcoholic, presented to the ER with complaints of acute onset left sided chest pain following the completion of the third dose of intradermal rabies vaccine, whose clinical features, ECG changes and lab reports were suggestive of acute presentation of inferior wall MI. Coronary angiography was performed, which however revealed normal coronaries with only slow flow being noted in the left anterior descending (LAD) artery. Echocardiography later showed a normal study with no other relevant diagnosis unveiled on further investigations. Hence a diagnosis of vaccine-induced MINOCA was made. Treatment included antiplatelet therapy, statins, and beta-blockers. MINOCA following rabies vaccination is an unprecedented finding. The clear etiology behind this couldn't be ascertained. The patient's treatment was conventional, emphasizing the need for further research and clinical trials in MINOCA diagnosis and management. This case highlights the need for clinicians to consider MINOCA in patients with acute chest pain post-rabies vaccination. Further research is essential to unravel the association between MINOCA and rabies vaccination, paving the way for optimal management strategies.

Immune response after rabies pre-exposure prophylaxis and a booster dose in Australian bat carers.

Periodic vaccination against rabies is essential for individuals at continuing risk of rabies exposure. There is limited evidence on long-term immunogenicity after a 3-dose intramuscular (3IM) pre-exposure prophylaxis (PrEP) and single IM booster dose, thus current guideline recommendations differ in the interval for serology tests following PrEP and boosters. This study investigated post-PrEP and post-booster persistence of antibodies in Australian bat carers. Bat carers who received 3IM PrEP/booster doses and had post-PrEP/booster serology test results were included. The proportion of antibody-negative (<0.5 EU/mL) individuals after PrEP/booster dose were examined. Three hundred and five participants (65.6% females, median age at PrEP 43.1 years) were included. The proportion who were antibody-negative varied depending on the time between 3IM PrEP and the serology test: 8.0% <1 year, 29.8% 1-2 years, 21.2% 2-3 years and 7.7% >3 years. Ninety-one participants receiving booster doses were further assessed. Only one participant was antibody-negative at >3 years after receiving one IM booster dose. Our findings support that a serology test should be performed 1 year after 3IM PrEP, followed by first booster if required. Rabies antibodies persist for many years after receiving the booster doses. The interval between subsequent serology tests and the first booster dose should be no longer than 3 years. Future studies are required to provide more insight into the most appropriate timing of subsequent boosters.

Virología molecular de la rabia: un enfoque clínico / Rabies molecular virology: a clinical approach

Introducción: La rabia es una enfermedad zoonótica asociada al virus RABV, el cual tiene características neurotrópicas. El virus se transmite por el contacto con saliva de animales infectados; la mordedura de un perro es la causa más común. Es un virus que causa la muerte de miles de personas cada año. Objetivo: Describir a profundidad los principios moleculares de la infección por rabia, así como su patogenia, diagnóstico y tratamiento. Métodos: Se realizó una búsqueda de bibliografía en PubMed, SciELO, Scopus, Researchgate; se consultaron 163 referencias y se seleccionaron 51 fuentes que contenían la información más relevante para cumplir con el objetivo del trabajo. Conclusión: Actualmente es posible entender de mejor manera los mecanismos de transmisión y propagación del virus en el organismo; existe nuevo conocimiento sobre los receptores involucrados, así como la función de estos en la replicación viral. Sin embargo, el objetivo de la erradicación de la rabia a corto plazo es complejo. La invasión de territorios selváticos vuelve a la rabia un posible patógeno reemergente; la vacunación de especies transmisoras es el medio ideal para conseguir el control de la enfermedad.

Introduction: Rabies is a zoonotic disease associated with the RABV virus, which has neurotropic characteristics. The virus is transmitted by contact with saliva from infected animals; a dog's bite is the most common cause. This virus causes the death of thousands of people every year. Objective: To describe in depth the molecular principles of rabies infection, as well as its pathogenesis, diagnosis and treatment. Methods: A literature search was conducted in PubMed, SciELO, Scopus, and Researchgate. A total of 163 references were consulted, and 51 sources containing the most relevant information were selected to fulfill the objective of the work. Conclusions: It is currently possible to better understand the mechanisms of transmission and spread of the virus in the organism; there is new knowledge about the receptors involved, as well as their function in viral replication. However, the goal of eradicating rabies in the short term is complex. The invasion of wild territories makes rabies a possible re-emerging pathogen; vaccination of transmitting species is the ideal means to achieve disease control.

Monitoring by Raman spectroscopy of rabies virus-like particles production since the initial development stages

BACKGROUND This study aimed to establish chemometric models using Raman spectroscopy data for biochemical monitoring of rabies Virus-Like Particles (VLP) production based on baculovirus/insect cell system. The models were developed using fresh and stored samples from the initial development stages (Schott culture flasks). The following modeling techniques were assessed: partial least squares (PLS) and artificial neural networks (ANN). The effects of spectral filtering approaches, spectral ranges (400–1850 cm−1; 100–3425 cm−1), and sample cryopreservation were also considered. The applicability of the models was evaluated using experimental data from assays carried out in a benchtop bioreactor. RESULTS The results showed that the prediction capacity of the chemometric models was negatively impacted when samples from rabies VLP production were cryopreserved. Further studies are needed to confirm the maximum storage time for samples (< 4 months) without a significant difference in model predictions compared to those from an in line database. The dilution of the sample should be kept constant throughout the rabies VLP development stages. A nonlinear correlation was observed between dilution and the predicted values of biochemical parameters from Raman spectral data. The choice of spectral filtering has a major impact on the prediction accuracy of chemometric models. CONCLUSION The optimal filtering approach should be individually optimized for each biochemical parameter. The ANN models were significantly more suitable for biochemical monitoring than the PLS approach. The 400–1850 cm−1 Raman shift range is recommended for biochemical monitoring of rabies VLP using a baculovirus/insect cell platform when samples are cell-free.

Associação entre fatores socioeconômicos e demográficos e vacinação antirrábica de cães e gatos domésticos / Association between socioeconomic and demographic factors and rabies vaccination of dogs and cats

Resumo Introdução A raiva é uma doença endêmica no Brasil, cuja forma de combate em humanos é a vacinação de animais. Objetivo Buscou-se analisar associação entre fatores sociodemográficos e econômicos de adultos com vacinação antirrábica de animais domésticos com amostra da Pesquisa Nacional de Saúde realizada em 2013. Método Estudo transversal tendo como desfecho vacinação antirrábica de cães e gatos e exposições: sexo, idade, escolaridade, renda per capita e cor da pele autodeclarada do chefe de domicílio. Foram realizadas análises bi e multivariadas por meio de regressão logística. Resultados No Brasil, 59,3% (IC95%59,1-59,5) dos domicílios tinham animal de estimação. Em relação à vacinação antirrábica, a região Sudeste possui a maior prevalência, em que 84,8% (IC95%83,3-86,2) dos domicílios vacinaram todos os cães e gatos, contra 63,7% (IC95%60,9-66,3) na região Sul. Indivíduos com ≥50 anos têm 64% mais chances de vacinar cães e gatos, comparados àqueles na faixa etária mais jovem (18-29 anos). Quanto à escolaridade, indivíduos com ≥12 anos de estudo têm 2,4 vezes mais chances de vacinar todos os animais do domicílio, em relação àqueles com 0-8 anos de estudo. Conclusão Os resultados deste estudo apontam para a necessidade de políticas públicas que orientem a população sobre guarda responsável e que ofertem serviços de imunização.

Abstract Background In Brazil, rabies is an endemic disease and the vaccination of animals is a form of combat for humans. Objective The study aimed to analyze the association between sociodemographic and economic factors of adults and rabies vaccination of domestic animals, using samples from the National Health Survey conducted in 2013. Method This is a cross-sectional study with the outcome of rabies vaccination of dogs and cats and exposures: sex, age, education, per capita income, and skin color of the head of household. Bi and multivariate analyses were performed by logistic regression. Results In Brazil, 59.3% (95% CI 59.1-59.5) of households have pets. Regarding rabies vaccination, the southeast region has the highest prevalence, with 84.8% (95% CI 83.3-86.2) of households vaccinating all dogs and cats against 63.7% (95% CI 60.9-66.3) in the south region. Individuals in the age group ≥50 years are 64% more likely to vaccinate dogs and cats compared to those in the younger age group (18-29 years old). Regarding education, individuals with ≥12 school years are 2.4 times more likely to vaccinate all animals in the household compared to those with 0-8 school years. Conclusion The results of this study point to the fact that there's a demand for public policies to guide the population on responsible custody and to provide immunization services.

Factors related to vaccines for both patients exposed with rabies and dogs

ABSTRACT Introduction: Rabies is a viral disease that can be transmitted from animals to humans. All warm-blooded animals, including humans, can host rabies's virus. Vaccination of dogs is an effective method of preventing rabies in humans. Objectives: To evaluate knowledge, attitudes and practices towards rabies prevention and factors related to vaccines for both patients exposed with rabies and dogs. Methods: A cross-sectional descriptive study, using the questionnaire on rabies prevention by interviewing 1 484 households. Multivariable logistic regression analysis was used to identify factors related to vaccines for both patients exposed to rabies and dogs. Results: Of all 67.32 % of the people surveyed with high knowledge, only 43.8 % and 31.47 % were assessed as having a good attitude and practice. Interviewees with poor knowledge and practice are independently related to low-rate vaccines provision for pets. Factors associated with low vaccination rates after pet bites were poor attitudes and practices. Conclusion: People with a high level of education, knowledge and practice, the rabies vaccination rate on pets is high. People with good attitudes and practices had a high rate of rabies vaccination after being bitten by an animal.

RESUMEN Introducción: La rabia es una enfermedad viral que puede transmitirse de animales a humanos. Todos los animales de sangre caliente, incluidos los humanos, pueden albergar el virus de la rabia. La vacunación de perros es un método eficaz para prevenir la rabia en humanos. Objetivos: Evaluar conocimientos, actitudes y prácticas de la comunidad hacia la prevención de la rabia y los factores relacionados con las vacunas, tanto para pacientes expuestos como para perros. Métodos: Estudio descriptivo transversal, se utilizó un cuestionario sobre prevención de la rabia, mediante entrevistas en 1 484 hogares. Se realizó un análisis de regresión logística multivariable para identificar los factores relacionados con las vacunas, tanto para pacientes expuestos como para los perros. Resultados: Del 67,32 % de encuestados, con alto conocimiento, solo el 43,8 % y el 31,47 % fueron evaluados como de buena actitud y práctica. Los entrevistados con insuficiente conocimiento y prácticas se relacionan de forma independiente con la baja provisión de vacunas para las mascotas. Las razones de bajas tasas de vacunación después de las mordeduras causadas por mascotas fueron las malas actitudes y prácticas. Conclusión: Las personas con nivel alto de práctica, educación y conocimientos, tienen elevados niveles de vacunación antirrábica de sus mascotas. Después de la mordedura de un animal, las personas con buenas prácticas y actitudes, tienen más altos niveles de vacunación antirrábica.

Description of human anti-rabies post-exposure prophylaxis care notifications in Brazil, 2014-2019 / Descripción de notificaciones de atención antirrábica humana para la profilaxis posexposición en Brasil, 2014-2019 / Descrição das notificações de atendimento antirrábico humano para profilaxia pós-exposição no Brasil, 2014-2019

Objective: To analyze human anti-rabies post-exposure prophylaxis notifications in Brazil. Methods: This was a descriptive study of human anti-rabies post-exposure prophylaxis care notified on the Notifiable Health Conditions Information System in Brazil between 2014 and 2019. Results: A total of 4,033,098 anti-rabies medical consultations were notified, averaging 672,183 a year. Percentage care was higher among males (n=2,111,369; 52.4%), those under 19 years old (n=1,423,433; 35.3%), living in urban areas (n=3,386,589; 88.1%), attacked by dogs (n=3,281,190; 81.5%) and bitten (n=3,575,717; 81.9%), mainly on the hands and feet (n=1,541,201; 35.3%). The most frequent prophylactic procedure was observation plus vaccination (n=1,736,036; 44.2%). Prophylactic procedure was appropriate in 57.8% (n=2,169,689) of cases and inappropriate in 42.2% (n=1,582,411) of cases. Conclusion: Although there were appropriate prophylactic procedures, we also found procedures that were inappropriate and which, when insufficient, can result in cases of human rabies and, when unnecessary, can result in waste, including shortage of immunobiological products

Objetivo: Analizar la atención antirrábica humana de profilaxis post exposición en Brasil, de 2014 a 2019. Métodos: Estudio descriptivo de la atención antirrábica humana de profilaxis post exposición, notificados en el Sistema de Información de Agravamientos de Notificación en Brasil, de 2014 a 2019. Resultados: Se notificaron 4.033.098 atendimientos antirrábicos, con un promedio de 672.183 al año. Hubo mayor porcentual de atención a personas del sexo masculino (n=2.111.369; 52,4%), menores de 19 años (n=1.423.433; 35,3%), residentes en área urbana (n=3.386.589; 88,1%), agredidas por perros (n=3.281.190; 81,5%) y con mordidas (n=3.575.717; 81,9%), principalmente en las manos y pies (n=1.541.201; 35,3%). La conducta profiláctica más frecuente fue la observación y vacuna (n=1.736.036; 44,2%). La conducta profiláctica fue adecuada en 57,8% (n=2.169.689) e inadecuada en 42,2% (n=1.582.411) de los casos. Conclusión: A pesar de las conductas profilácticas adecuadas, se observaron indicaciones inadecuadas que, cuando insuficientes, pueden resultar en casos de rabia humana y, cuando desnecesarias, desperdicios, incluso desabastecimiento de inmunobiológicos.

Objetivo: Analisar os atendimentos antirrábicos humanos de profilaxia pós-exposição no Brasil. Métodos: Estudo descritivo dos atendimentos antirrábicos humanos de profilaxia pós-exposição notificados no Sistema de Informação de Agravos de Notificação no Brasil, de 2014 a 2019. Resultados: Foram notificados 4.033.098 atendimentos antirrábicos, com média de 672.183 ao ano. Houve maior percentual de atendimentos em pessoas do sexo masculino (n=2.111.369; 52,4%), menores de 19 anos de idade (n=1.423.433; 35,3%), residentes em área urbana (n=3.386.589; 88,1%), agredidas por cães (n=3.281.190; 81,5%) e com mordeduras (n=3.575.717; 81,9%), principalmente em mãos e pés (n=1.541.201; 35,3%). A conduta profilática mais frequente foi observação e vacina (n=1.736.036; 44,2%). A conduta profilática foi adequada em 57,8% (n=2.169.689) e inadequada em 42,2% (n=1.582.411) dos casos. Conclusão: Apesar das condutas profiláticas adequadas, foram observadas indicações inadequadas que, quando insuficientes, podem acarretar casos de raiva humana e, quando desnecessárias, desperdícios, inclusive desabastecimento de imunobiológicos.

Immunogenicity and safety of human diploid cell vaccine (HDCV) vs. purified Vero cell vaccine (PVRV) vs. purified chick embryo cell vaccine (PCECV) used in post-exposure prophylaxis: a systematic review and meta-analysis.

This study comprehensively evaluated and compared three human rabies vaccines. Seven electronic databases were systematically searched. The Cochrane Handbook v5.1.0 was used to assess the risk of bias. A random-effects model was used to combine individual rates, and network meta-analysis was used for pairwise comparisons. Twenty-seven articles were included, with a total of 18,630 participants. The pooled incidence of the total adverse reaction to HDCV was significantly lower than that of PCECV. HDCV administration resulted in a lower incidence of local pain, fever, and weakness than purified Vero cell vaccine. HDCV caused a lower incidence of local pain and fever than PCECV. No significant difference was observed in terms of the seroconversion rate on day 7 or the rabies virus-neutralizing antibody titer on day 14. HDCV demonstrated superiority in terms of safety compared with the other two rabies vaccines, while the same was not observed in terms of immunogenicity.

Descrição das notificações de atendimento antirrábico humano para profilaxia pós-exposição no Brasil, 2014-2019 / Descripción de notificaciones de atención antirrábica humana para la profilaxis post-exposición en Brasil, 2014-2019 / Description of human anti-rabies post-exposure prophylaxis care notifications in Brazil, 2014-2019

Objetivo: Analisar os atendimentos antirrábicos humanos de profilaxia pós-exposição no Brasil. Métodos: Estudo descritivo utilizando dados do Sistema de Informação de Agravos de Notificação no Brasil, de 2014 a 2019. Resultados: Foram notificados 4.033.098 atendimentos antirrábicos, com média de 672.183 ao ano. Houve maior percentual de atendimentos em pessoas do sexo masculino (n = 2.111.369; 52,4%), menores de 19 anos de idade (n = 1.423.433; 35,3%), residentes em área urbana (n = 3.386.589; 88,1%), agredidas por cães (n = 3.281.190; 81,5%) e com mordeduras (n = 3.575.717; 81,9%), principalmente em mãos e pés (n = 1.541.201; 35,3%). A conduta profilática mais frequente foi observação e vacina (n = 1.736.036; 44,2%). A conduta profilática foi adequada em 57,8% (n = 2.169.689) e inadequada em 42,2% (n = 1.582.411) dos casos. Conclusão: Apesar das condutas profiláticas adequadas, foram observadas indicações inadequadas que, quando insuficientes, podem acarretar casos de raiva humana e, quando desnecessárias, desperdícios, inclusive desabastecimento de imunobiológicos.

Objetivo: Analizar la atención antirrábica humana de profilaxis post exposición en Brasil, de 2014 a 2019. Métodos: Estudio descriptivo utilizando datos del Sistema de Información de Agravamientos de Notificación en Brasil, de 2014 a 2019. Resultados: Se notificaron 4.033.098 atendimientos antirrábicos, con un promedio de 672.183 al año. Hubo mayor porcentual de atención a personas del sexo masculino (n = 2.111.369; 52,4%), menores de 19 años (n = 1.423.433; 35,3%), residentes en área urbana (n = 3.386.589; 88,1%), agredidas por perros (n = 3.281.190; 81,5%) y con mordidas (n = 3.575.717; 81,9%), principalmente en las manos y pies (n = 1.541.201; 35,3%). La conducta profiláctica más frecuente fue la observación y vacuna (n = 1.736.036; 44,2%). La conducta profiláctica fue adecuada en 57,8% (n = 2.169.689) e inadecuada en 42,2% (n = 1.582.411) de los casos. Conclusión: A pesar de las conductas profilácticas adecuadas, se observaron indicaciones inadecuadas que, cuando insuficientes, pueden resultar en casos de rabia humana y, cuando desnecesarias, desperdicios, incluso desabastecimiento de inmunobiológicos.

Objective: To analyze human anti-rabies post-exposure prophylaxis notifications in Brazil. Methods: This was a descriptive study using data from the Notifiable Diseases Information System in Brazil, from 2014 to 2019. Results: A total of 4,033,098 anti-rabies medical consultations were notified, averaging 672,183 a year. Percentage care was higher among males (n = 2,111,369; 52.4%), those under 19 years old (n = 1,423,433; 35.3%), living in urban areas (n = 3,386,589; 88.1%), attacked by dogs (n = 3,281,190; 81.5%) and bitten (n = 3,575,717; 81.9%), mainly on the hands and feet (n = 1,541,201; 35.3%). The most frequent prophylactic procedure was observation plus vaccination (n = 1,736,036; 44.2%). Prophylactic procedure was appropriate in 57.8% (n = 2,169,689) of cases and inappropriate in 42.2% (n = 1,582,411) of cases. Conclusion: Although there were appropriate prophylactic procedures, we also found procedures that were inappropriate and which, when insufficient, can result in cases of human rabies and, when unnecessary, can result in waste, including shortage of immunobiological products.

Staphylococcus aureus derived hyaluronic acid and bacillus Calmette-Guérin purified proteins as immune enhancers to rabies vaccine and related immuno-histopathological alterations.

PURPOSE: One of the essential goals regarding the successful control of rabies infection is the development of a safe, effective, and inexpensive vaccine. the current study aimed to evaluate the inactivation potential of ß-propiolactone (ßPL), binary ethyleneimine (BEI), and hydrogen peroxide (H2O2). MATERIALS AND METHODS: Estimating the inactivation kinetics of ßPL, BEI, and H2O2 revealed that the tested inactivants could completely and irreversibly inactivate rabies virus within 2, 12, and 4 hours, respectively while maintaining its viral immunogenicity. The potency of ßPL, BEI, and H2O2 inactivated vaccines was higher than the World Health Organization acceptance limit and were in the order of 3.75, 4.21, and 3.64 IU/mL, respectively. Monitoring the humoral and cellular immunity elicited post-immunization using Staphylococcus aureus derived hyaluronic acid (HA) and bacillus Calmette-Guérin purified protein derivative (PPD) adjuvanted rabies vaccine candidates were carried out using enzyme-linked immunosorbent assay. RESULTS: Results demonstrated that both adjuvants could progressively enhance the release of anti-rabies total immunoglobulin G as well as the pro-inflammatory mediators (interferon-gamma and interleukin-5) relative to time. However, a higher immune response was developed in the case of HA adjuvanted rabies vaccine compared to PPD adjuvanted one. The harmful consequences of the tested adjuvants were considered via investigating the histopathological changes in the tissues of the immunized rats using hematoxylin and eosin stain. Lower adverse effects were observed post-vaccination with HA and PPD adjuvanted vaccines compared to that detected following administration of the currently used alum as standard adjuvant. CONCLUSION: Our findings suggested that HA and PPD could serve as a promising platform for the development of newly adjuvanted rabies vaccines with elevated immune enhancing potentials and lower risk of health hazards.

Encefalitis por rabia o encefalitis post-vacunal en mujer gestante con neonato prematuro sobreviviente

La rabia humana es una infección grave que requiere aplicación de suero antirrábico y vacuna, la cual puede producir encefalomielitis desmielinizante aguda (EDMA) post-vacunal. Se reporta una gestante de 27 años mordida por un perro en mano derecha. No recibió suero antirrábico pero sí 5 vacunas. Con última vacuna presentó adormecimiento de mano, malestar, fiebre, hidrofobia, alteración de conciencia. Se realizó cesárea e indujo al coma terapéutico. La biopsia de piel de nuca e inoculación en ratón fueron negativos mientras que la seroneutralización en ratón y detección de anticuerpos antirrábicos fueron positivos. En cordón umbilical, la seroneutralización en ratón fue positiva. La resonancia magnética evidenció lesiones compatibles con EDMA. Según algunos criterios, podría tratarse de rabia; sin embargo, el cuadro sería más compatible con EDMA.

Human rabies is a serious infection that requires application of rabies serum and vaccine, which can cause post-vaccination acute demyelinating encephalomyelitis (ADEM). We report a 27-year-old pregnant woman who has been bitten by a dog on her right hand. She didn't receive rabies serum but she received 5 vaccinations. With last vaccination she presents hand numbness, malaise, fever, hydrophobia, altered consciousness. A cesarean section was performed and the patient was induced a therapeutic coma. Nape skin biopsy and inoculation in mice were negative, while seroneutralization in mice and detection of anti-rabies antibodies were positive. In umbilical cord, mouse seroneutralization was positive. Magnetic resonance imaging revealed lesions compatible with ADEM. By some criteria, it could be rabies; however, the chart would be more compatible with ADEM.

Delayed rabies post-exposure prophylaxis treatment among Dutch travellers during their stay abroad: a comprehensive analysis.

BACKGROUND: After an animal-associated injury (AAI) in rabies-endemic regions, post-exposure prophylaxis (PEP) is needed to prevent infection.1,2 PEP consists of rabies vaccinations (RV) and in some cases also additional rabies immune globulins (RIG). Not always PEP medication, and RIG in particular, is accessible. Along with an increased number of exposure notifications among Dutch travellers, this might lead to treatment delay and thus to increased health risks. Until now, research mainly focused on factors associated with exposition, but none on which factors are associated with PEP delay. This study aimed to identify which general sample characteristics are associated with PEP delay while being abroad. METHODS: A quantitative retrospective observational study was conducted. The study population consisted of insured Dutch international travellers who actively contacted their medical assistance company (2015-2019) because of an animal-associated injury (AAI) (N = 691). The association between general sample characteristics and delay of different PEP treatments was studied using survival analysis. RESULTS: Travellers without pre-exposure prophylaxis (PrEP) had an increased hazard, and therefore a shorter delay, for receiving their first RV as compared to travellers with PrEP (HR:1.11, 95%CI:1.01-1.22). The travellers needing both RV and RIG had a decreased hazard, and therefore a longer delay, as compared to travellers only needing RV (HR:0.81, 95%CI:0.67-0.96). General sample characteristic associated with RIG administration delay was travel destination. Travellers to Central and South America, East Mediterranean and Europe had a decreased hazard, and therefore a longer delay, for receiving RIG treatments relative to travellers to South East Asia (HR:0.31, 95%CI:0.13-0.70; HR:0.34, 95%CI:0.19-0.61; HR:0.46, 95%CI:0.24-0.89; HR:0.48, 95%CI:0.12-0.81, respectively). CONCLUSIONS: Our results suggest that the advice for PrEP should be given based on travel destination, as this was found to be the main factor for PEP delay, among travellers going to rabies-endemic countries.

The Colonial State, African Dog-Owners, and the Political Economy of Rabies Vaccination Campaigns in Southern Rhodesia in the 1950s and 1960s.

This paper examines histories of postvaccinal breaks in immunity to rabies in domestic dogs between 1950 and the 1960s. It utilizes Veterinary and Native Commissioner's reports and newspapers in arguing that there is a gap in current southern African rabies historiography as it is yet to grapple with narratives about vaccine technologies. Current southern African rabies histories overly focus on white South African urban case studies. Focusing on the histories of postvaccinal breaks in immunity to rabies in Southern Rhodesia helps to explain why rabies became an ineradicable canine disease in southern Africa during this period. The paper focuses on the political economy of the mass vaccination of dogs, the costs attached to the Veterinary Department's decision to ignore other canine diseases in African areas, and how this, combined with other policy measures such as dog taxation, in undermining rabies vaccination campaigns. Overall, it shows that African dog-owners resorted to a myriad of responses to coercive rabies regulations. This complexity ultimately resulted in canine rabies becoming a difficult disease to eradicate.

[Human Rabies: Optimization of Prevention and Paths Towards the Cure]. / Raiva Humana: Optimização da Prevenção e Caminhos Para a Cura.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.

Redefining Non-Inferiority in Anamnestic Antibody Responses Using the Mean Increase of Log-Transformed Antibody Titers after Revaccination: Secondary Analysis of a Randomized Controlled Rabies Vaccination Trial.

Non-inferiority in the anamnestic antibody response is conventionally determined by comparing seroconversion rates after revaccination. However, this approach is inadequate in the case of high pre-booster antibody titers. Therefore, we propose an alternative method to determine non-inferiority of booster responses. We used anonymized data from a randomized controlled trial (NCT01388985; EudraCT 2011-001612-62) in 500 adults, comparing a two-visit primary vaccination schedule (two intradermal 0.1 mL rabies vaccine doses on day 0 and 7) with a three-visit schedule (single intradermal 0.1 mL dose on day 0, 7, and 28). Participants were revaccinated intradermally (single dose) 1 to 3 years later. Rabies virus neutralizing antibody titers were measured on day 0 and 7 after revaccination. After log3-transformation of antibody titers, the mean increase in titers after revaccination was compared between schedules. Non-inferiority was defined as the lower bound of the two-sided 95% confidence interval not exceeding -0.369. Four hundred and ten participants fulfilled the inclusion criteria. The mean increase in log3 titer was 2.21 and 2.31 for the two-visit and three-visit schedule, respectively. The difference between these increases was -0.10 [-0.28, 0.08], meeting the non-inferiority criterion. In conclusion, comparing mean increases in log-transformed titers after revaccination appears to be a feasible and more informative method of studying non-inferiority regarding the anamnestic antibody response.

Laser-assisted skin delivery of immunocontraceptive rabies nanoparticulate vaccine in poloxamer gel.

A painless skin delivery of vaccine for disease prevention is of great advantage in improving compliance in patients. To test this idea as a proof of concept, we utilized a pDNA vaccine construct, pDNAg333-2GnRH that has a dual function of controlling rabies and inducing immunocontraception in animals. The pDNA was administered to mice in a nanoparticulate form delivered through the skin using the P.L.E.A.S.E.® (Precise Laser Epidermal System) microporation laser device. Laser application was well tolerated, and mild skin reaction was healed completely in 8 days. We demonstrated that adjuvanted nanoparticulate pDNA vaccine significantly upregulated the expression of co-stimulatory molecules in dendritic cells. After topical administration of the adjuvanted nano-vaccine in mice, the high avidity serum for GnRH antibodies were induced and maintained up to 9 weeks. The induced immune response was of a mixed Th1/Th2 profile as measured by IgG subclasses (IgG2a and IgG1) and cytokine levels (IFN-γ and IL-4). Using flow cytometry, we revealed an increase of CD8+ T-cells and CD45R B cells upon the administration of the adjuvanted vaccine. Our previous study used the same pDNA nanoparticulate vaccine through an IM route, and a comparable immune response was induced using P.L.E.A.S.E. However, the vaccine dose in the current study was four-fold less than what was applied through the IM route.We concluded that laser-assisted skin vaccination has a potential of becoming a safe and reliable vaccination tool for rabies vaccination in animals or even in humans for pre- or post-exposure prophylaxis.

Antibody Response Following Pre-Exposure Immunization Against Rabies in High-Risk Professionals.

Vaccination against rabies and routine antibody testing of subjects participating in programs for the surveillance and control of rabies in animals is strongly recommended. The scope of this study is to describe the antibody level as measured by a commercial enzyme-linked immunosorbent assay (ELISA) after primary and booster intramuscular vaccination with a purified vero-cell rabies vaccine (PVRV) in high-risk professionals and to determine the influence of an array of factors on antibody level, that is, time elapsed since primary immunization series and booster dose, sex, age, pathologic conditions, high-risk occupation, and peak antibody level after initial scheme and booster dose. A primary series of three doses of PVRV was administered and a commercial ELISA was recommended 14 days postimmunization with continuous repetition at 6 months and yearly intervals for the laboratory personnel and the rest of the professionals, respectively. The protective antibody titer was defined as a minimum of 0.5 equivalent units/mL (EU/mL) (seroconvertion) and a booster dose was applied if the titer was determined nonprotective. The seroconversion rate (SCR) after primary vaccination was 100%, with a geometric mean titer (GMT) of 2.90 EU/mL (interquartile range [IQR]: 1.85-3.45). After booster vaccination due to nonprotective titer, the SCR was 100% and the GMT increased by 678% (95% confidence interval [CI]: 514-887) reaching 4.25 EU/mL (IQR: 4.00-4.60), 2.5 times higher than the GMT elicited by the primary vaccine scheme in the respective recipients. The titer dropped by 1.20% per month (95% CI: 0.52-1.89) regardless of booster administration or any other factor. Women had 51% higher titer compared with men (95% CI: 6-116). High-risk professionals should be verified for adequate antibody titers, but routine administration of a single booster dose of PVRV 1 year after the primary series could be considered; more evidence is needed to support the benefit in terms of immunity and logistics.

Market mapping and landscape analysis of human rabies biologicals in India.

BACKGROUND: Rabies vaccines and immunoglobulins are lifesaving in humans following animal exposures. These biologicals should continuously be available throughout the year to prevent and eliminate human rabies by 2030. OBJECTIVES: The present study aimed at assessing availability of different kinds of human rabies biologicals in the country and undertaking market mapping and landscape analysis of human rabies biologicals in India. METHODS: The study comprising both quantitative and qualitative approach was conducted from May to November 2017 as a part of the Indian multicentric rabies survey by Association for Prevention and Control of Rabies in India. All stakeholders (agencies/personnel) associated with rabies biologicals were the study units/participants. Required data were generated through brainstorming sessions with key stakeholders; reviewing of databases/existing literature; conducting in-depth surveys; interviewing; focused group discussions, etc. RESULTS: Two types of cell culture rabies vaccines are available in the country manufactured by different pharmaceutical companies; most of the vaccines are indigenously produced and the market size of the rabies vaccines is about INR 125 crores with highest sales in the northern region followed by South. Likewise, there are 2 types of immunoglobulin available, i.e., equine rabies immunoglobulins (RIGs), which are indigenously produced and human RIGs, which are imported. The market value of RIGs is about INR 83 crores. A novel rabies monoclonal antibody is also been marketed in the country from November 2017. CONCLUSIONS: There are many lacunas in the market availability of rabies biologicals in different parts of the country; therefore, a significant expansion/shift in focus must be considered, through rigorous strategic planning process.