Human Rabies during the COVID-19 Pandemic: Insights into Rabies Worldwide and Brazil

ABSTRACT Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR transmitted by dogs has decreased in Latin America, there has been a corresponding rise in transmission via wild animals. Given the lack of effective treatments and specific therapies, the management of HR relies on the availability of post-exposure prophylaxis and animal control measures. This review examines the dynamics and spread of HR during the global pandemic.

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.

Establishment and preliminary application of dual fluorescent quantitative PCR for detection of RV and CAV2 / 公共卫生与预防医学

Objective To investigate the shedding of CAV2-ΔE3-CGS after immunization and the background of canine adenovirus (CAV) infection, and to establish a dual fluorescent quantitative PCR detection method for rabies virus (RV) and canine adenovirus type 2 (CAV2). Methods A dual fluorescent quantitative PCR detection method was established by designing specific primers and probes for E1 gene of CAV and G gene of RV for the detection of CAV2-ΔE3-CGS. Oral swabs, anal swabs and environmental samples of stray dogs from experimental animal farm and dog detention center were tested. Results The standard curves generated by this method were Y=-3.351 × logX + 44.895, R2 = .999 and Y=-3.413 × logX + 45.192, R2=0.996, respectively. The linear relationships were good, and the minimum detection limits were both 102 copies/μL. CAV2-ΔE3-CGS was not detected in experimental animal farm. CAV was detected in dog detention center, and the positive rates were 5.88% (5/85) in oral swabs, 8.24% (7/85) in anal swabs, and 4% (1/25) in environmental samples. Conclusion The dual fluorescent quantitative PCR method can be used for the detection of CAV2-ΔE3-CGS after immunization and the investigation of CAV infection. The present study has shown that no CAV2-ΔE3-CGS has been detected after immunization and CAV infection rate of stay dogs is low in Shanghai. CAV2-ΔE3-CGS oral immunization meets requirement and is applicable.

Construction and verification of recombinant chimeric vesicular stomatitis virus expressing rabies virus G protein / 中国生物制品学杂志

@#Objective To construct recombinant chimeric vesicular stomatitis virus(VSV)expressing G protein of rabies virus(RV)using VSV as vector.MethodsTo rescue the recombinant virus,G gene of VSV antigenome was replaced with G gene of RV vaccine CTN-1 strain,and co-transfected into 293T cells with helper plasmids coding T7 RNA polymerase and proteins N,P and L of VSV. The expression of RV G gene and G protein was detected by RT-PCR,immunofluorescence assay and Western blot. The recombinant virus was subcultured in Vero cells,the virus titer of different generations was detected and the virus growth curve was drawn.ResultsThe recombinant virus VSV-RVG was successfully rescued. RTPCR results demonstrated that the RV G gene was successfully inserted into the genome of the recombinant virus,and the expression of RVG protein was detected by immunofluorescence assay and Western blot. The recombinant virus was continuously passaged for 5 generations,and the virus titer was stable within 7. 5 ～ 8. 5 lgTCID50/mL.ConclusionThe recombinant chimeric VSV expressing RV G protein was successfully constructed with good genetic stability,which lays a foundation of the construction of reverse genetics technology platform based on VSV vector.

Rabies virus viability in vitro / 中华微生物学和免疫学杂志

Objective:To investigate the in vitro viability of rabies virus in tissues and body fluid samples. Methods:The viability of rabies virus in tissues and suspensions was analyzed by virus titer determination method, direct immunofluorescence, RT-PCR and laboratory techniques for virus isolation.Results:With the increase of temperature, the viability of rabies virus in brain tissues and suspensions decreased gradually. Rabies virus lost infectivity after 30 min at 56℃, but remained viable in tissues for 7 d at 37℃. The virus showed no viability after 1 h at pH9.6. The rabies virus in suspensions could be completely inactivated after the stimulation with ethanol at a final concentration above 30%, sodium hypochlorite above 500 mg/L or benzalkonium bromide above 100 mg/L for 3 min. It was found that 80% acetone had the strongest inactivation effect on rabies virus in tissues, and no virus could be isolated after soaking for 4 h.Conclusions:Rabies virus was not tolerant to high temperature and relatively stable in the environment with pH6.8-7.4. Common disinfectants could kill the virus. This study provided detailed data about the viability of rabies virus in vitro, which would be conducive to the prevention and control of rabies.

Comparison of immunization strategies for human rabies pre-exposure prophylaxis in laboratory animals / 中华微生物学和免疫学杂志

Objective:To compare the differences in the safety, efficacy and protective effects of rabies vaccine using the current pre-exposure prophylaxis schedule in China (0-7-21 or 28) and the newly recommended immunization program of WHO (0-7), aiming to provide data support for modifying the related content of Technical Guideline for Human Rabies Prevention and Control. Methods:The mice were randomly divided into five groups, namely 0-7-21 group (3-injection regimen), 0-7 group (2-injection regimen), 0-14 group, 0-21 group and control group, according to the current 3-injection regimen (0-7-21) in China and the 2-injection regimen (0-7) recommended by WHO. The survival status of the mice was observed. The mice were weighed every five days to compare the safety of different immunization procedures. Rabies virus neutralizing antibodies (RVNA) were detected 7, 14, 21, 28 and 35 d after the initial immunization. On day 35, the mice in each group were challenged with lethal dose of CVS-11 rabies virus to evaluate the protective effects of different pre-exposure immunization procedures.Results:There was no significant difference in weight gain of mice after vaccination. The positive rate of RVNA was 100% in all immunized groups from day 14, which could provide complete protection to mice. There was a significant difference in RVNA levels between 0-7-21 and 0-7 groups at 35 d( P<0.05), but there was no statistical difference at other time points ( P>0.05). RVNA level had a significant difference between 0-7 and 0-21 groups at 21 d and 35 d ( P<0.05). There was no statistical difference in RVNA level between other groups at each time point ( P>0.05). In the protective test, the survival rates of mice in all immune groups were 100%. Conclusions:The current 3-injection pre-exposure immunization procedure for rabies vaccine (0-7-21) and the newly recommended 2-injection immunization procedure (0-7) had similar efficacy and protective effects in animal tests. In view of the cost saving and better compliance of the 2-injection immunization procedure, it was recommended that relevant departments should conduct clinical trials as soon as possible to promote the implementation of this program.

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.

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.

Educação em saúde para prevenção da raiva humana / Health education for prevention of human rabies / Educación en salud para prevención de la rabia humana

A raiva é uma antropozoonose viral que se desenvolve de forma progressiva e aguda podendo apresentar até 100% de letalidade. O seu agente etiológico é o vírus rábico do gênero Lyssavirus pertencente à família Rhabdoviridae. O presente trabalho teve como objetivo divulgar informações acerca da ocorrência da raiva em humanos em virtude da sua expressiva importância para saúde pública e analisar a percepção da população sobre a raiva humana, de forma a obter dados relacionados a conhecimentos básicos sobre a doença. Para isso, foi criada uma página informativa denominada "@contraraiva_" na rede social Instagram para a realização de postagens interativas sobre o tema abordado, e uso de um questionário criado a partir da plataforma Google Forms em diferentes mídias sociais para a obtenção e coleta de dados. Foram obtidas 1.075 respostas, provenientes de diferentes localidades. O questionário alcançou todas as regiões brasileiras, todos 26 estados e o Distrito Federal. As informações publicadas pela página criada ajudaram a sanar dúvidas relacionadas aos principais aspectos da doença. Os dados obtidos a partir do questionário contribuem para o planejamento de ações voltadas para a educação em saúde de forma mais estratégica, visando contribuir para os pontos em que a população tem menos conhecimentos.(AU)

Rabies is a viral anthropozoonosis that is developed in a progressive and acute way and can present up to 100% lethality. Its etiologic agent is the rabies virus of the Lyssavirus gene belonging to the Rhabdoviridae family. This study aimed at disseminating information about the occurrence of rabies in humans due to its expressive importance for public health, and at analyzing the population perception on human rabies in order to obtain data related to basic knowledge about the disease. For that purpose, an information page called "@ contraraiva _" was created on the social network Instagram for providing interactive posts on the topic, and a questionnaire was created from the Google Forms platform on different social media to obtain and collect data. A total of 1,075 responses were obtained from different locations. The questionnaire included all Brazilian regions, all 26 states and the Federal District. The information published on the created page helped to clarify doubts related to the main aspects of the disease. The data obtained from the questionnaire contribute towards the planning of actions aimed at health education in a more strategic way, aiming at contributing to the points where the population is less knowledgeable.(AU)

La rabia es una antropozoonosis viral que se desarrolla de forma progresiva y aguda y puede presentar hasta un 100% de letalidad. Su agente etiológico es el virus de la rabia del género Lyssavirus perteneciente a la familia Rhabdoviridae. Este estudio tuvo como objetivo difundir informaciones sobre la ocurrencia de la rabia en humanos en virtud de su importancia expresiva para la salud pública, y analizar la percepción de la población sobre la rabia humana, con el fin de obtener datos relacionados a los conocimientos básicos sobre la enfermedad. Para ello, se creó una página de información denominada "@ contraraiva _" en la red social Instagram para realizar publicaciones interactivas sobre el tema abordado, y utilizar un cuestionario creado a partir de la plataforma Google Forms en diferentes redes sociales para la obtención y recolección de datos. Se obtuvieron 1.075 respuestas de diferentes lugares. El cuestionario llegó a todas las regiones brasileñas, a los 26 estados y al Distrito Federal. Las informaciones publicadas en el sitio web creado, ayudaron a sanar dudas relacionadas a los principales aspectos de la enfermedad. Los datos obtenidos del cuestionario contribuyen a la planificación de acciones orientadas a la educación para la salud de forma más estratégica, con el objetivo de contribuir a los puntos donde la población tiene menos conocimientos.(AU)

Phylogenetic analysis of nucleoprotein gene of Rabies virus in Malaysia from 2015 to 2018

@#Rabies is a fatal zoonotic disease caused by rabies virus (RABV) and remains a public health problem in Malaysia. Malaysia was declared rabies-free in 2012, however rabies outbreaks occurred at few states in Peninsular Malaysia three years later; and for the first time, in Sarawak (East Malaysia) in 2017 which has caused more than 20 human deaths. This study describes the phylogenetic analysis of the complete nucleoprotein (N) gene of RABV from animal samples in Malaysia from year 2015 to 2018. The N gene of 17 RABVs from Perlis, Kedah and Sarawak were amplified and sequenced. The nucleotide and deduced amino acid similarities of N gene analysis indicated that there is high similarity among the local RABVs. Phylogenetic analysis of the N gene revealed that all Malaysia RABVs belonged to the Asian clade. Among these, RABVs from Peninsular Malaysia were clustered together with RABVs from Thailand, Vietnam and other Southeast Asia countries except Indonesia. However, RABVs from Sarawak were grouped together with Indonesian strains from Kalimantan. Our study provides baseline genetic information of the potential origins of the circulating RABVs in Malaysia. This crucial information helped the authority in policies making and strategies to be taken in outbreak control. Continuous surveillance program to monitor the disease trend, strict border control, vaccination of dog and cat population and public awareness are important steps to control the spread of the RABV.

Algunos aspectos clínicos y epidemiológicos relacionados con mordeduras de perro en niños / Some clinical and epidemiological aspects related to dog bites in children

Introducción: Las mordeduras de perro afectan fundamentalmente a pacientes en la edad pediátrica, estas engendran peligros como secuelas estéticas y la posibilidad implícita de transmisibilidad del virus de la rabia a seres humanos. Objetivo: caracterizar el comportamiento clínico-epidemiológico de las mordeduras de perro en niños. Métodos: Se realizó un estudio observacional, longitudinal y prospectivo en pacientes con diagnóstico de mordedura de perro con necesidad de inmunización pasiva y activa, ingresados en el Servicio de Miscelánea del Hospital Infantil Sur Antonio María Béguez César de Santiago de Cuba, del 1ro de enero de 2017 al 31 de diciembre de 2018. Resultados: En los pacientes incluidos en el estudio predominaron los del sexo masculino (57,7 por ciento), los grupos de edades de 1 a 5 años 11 meses y 29 días, y de 6 a 10 años 11 meses y 29 días fueron los de mayor incidencia. Aunque no existió asociación estadística entre la localización anatómica de las lesiones y la edad, fueron las de miembros inferiores las más frecuentes en todas las edades con 63 pacientes (40,4 por ciento); destacándose como complicaciones la celulitis, las lesiones óseas y las secuelas estéticas; ningún niño presentó infección rábica. En el 50 por ciento de los casos la mordedura ocurrió en el horario nocturno y los perros de otro domicilio causaron la mayor parte de las agresiones. Conclusiones: El diagnóstico de mordeduras de perro se realizó con mayor frecuencia en niños del sexo masculino de uno y más años, en el horario nocturno y la principal complicación fue la celulitis(AU)

Introduction: Dog bites mainly affect patients in pediatric ages. They pose dangers such as esthetic sequels and the implicit possibility of transmission of the rabies virus to human beings. Objective: Characterize the clinical-epidemiological behavior of dog bites in children. Methods: An observational longitudinal prospective study was conducted of patients diagnosed with dog bite requiring passive and active immunization admitted to the Miscellany Service of Antonio María Béguez César South Children's Hospital in Santiago de Cuba from 1 January 2017 to 31 December 2018. Results: Among the patients included in the study there was a predominance of the male sex (57.7 percent). The age groups 1 to 5 years 11 months and 29 days and 6 to 10 years 11 months and 29 days showed the greatest incidence. Though no statistical association was found between anatomical location of the injuries and age, bites on the lower limbs were the most common at all ages with 63 patients (40.4 percent). Outstanding complications were cellulitis, bone lesions and esthetic sequels. No child had rabies infection. In 50 percent of the cases the bite occurred in the night hours. Most of the attacks were performed by dogs from other households. Conclusions: Dog bite diagnosis was more common among male children aged one year and over. Most bites occurred in the night hours. The main complication was cellulitis(AU)

In Vivo Two-photon Calcium Imaging in Dendrites of Rabies Virus-labeled V1 Corticothalamic Neurons / 神经科学通报·英文版

Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain. Two-photon Ca imaging in vivo using a cranial window and specific neuronal labeling enables real-time, in situ, and long-term imaging of the living brain. Here, we constructed a recombinant rabies virus containing the Ca indicator GCaMP6s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6s signal reliability. This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca imaging. Notably, we were able to record single-spine spontaneous Ca activity in specific circuits. Distinct spontaneous Ca dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits. Our method can be applied to monitor Ca dynamics in specific input circuits in vivo, and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice / 神经科学通报·英文版

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.

Vigilancia de las agresiones causadas por animales susceptibles a rabia, una lesión de causa externa evitable, Casanare-Colombia, 2012-2016 / Surveillance to Aggressions by Rabies-Susceptible Animals, a Preventable Injury Caused by External Causes in Casanare (Colombia) 2012-2016 / Vigilância de agressões causadas por animais susceptíveis à raiva, uma lesão de causa externa evitável, Casanare-Colômbia, 2012-2016

Resumen La vigilancia, prevención y control de la rabia es una prioridad para la salud pública, especialmente, la rabia transmitida por perros (variante 1) y la rabia silvestre. El objetivo de esta investigación fue describir el comportamiento epidemiológico del evento entre 2012-2016 en el departamento de Casanare-Colombia. El estudio fue descriptivo, retrospectivo a partir de la notificación de casos al Sistema Nacional de Vigilancia en Salud Pública-Sivigila-. Variables a estudio: a) características sociodemográficas, b) agresión/contacto, c) exposición, d) inmunización y e) tratamiento. Aplicación de estadística descriptiva y cálculo de indicadores de vigilancia. Datos analizados con el paquete estadístico Epi-Info 7.2.2.2™. El 98.5 % (6036/6131) de casos procedentes de Casanare, distribuidos en 2012 (1229; 20.4 %), 2013 (1180;19.5 %), 2014 (1227; 20.3 %); 2015 (1153;19.1 %), 2016 (1247; 20.7 %); del 72.5 % del área urbana; 55.4 % del sexo masculino; edad promedio 24.3(± 20.7) valor mínimo 0.01 y valor máximo 97 años; 40.7 % de 5-19 años; 37.5 % estudiantes, 13.3 % amas de casa, 5.4 % menores de edad, 19.4 % con registro de ocupación, de ellos, 29.8 % (349/1172) agricultores; 1.5 % hospitalizados; todos vivos. El 80.6 % (721/894) de exposición leve tuvieron tratamiento adecuado, 4.3 % (37/894) se aplicó suero antirrábico; 91.1 % (653/717) de exposición grave con tratamiento adecuado; 26.7 % (1611/6036) de los casos estuvieron expuestos al virus de la rabia. Incidencia por 100.000 habitantes de exposición rábica: 2012-2016 (344.8); tasa de hospitalización 11.5/100 000. Se evidencia el incumplimiento del indicador de tratamiento adecuado, es decir, en los casos clasificados como exposición leve, aplicar únicamente cinco dosis de vacuna antirrábica (esquema de vacunación completo); y, en exposición grave, aplicar el esquema de vacunación completo y suero antirrábico. Se recomienda continuar/mantener las actividades de vigilancia del evento y los esfuerzos para evitar la transmisión de la rabia humana.

Abstract Surveillance, prevention and control of the rabies are a priority in public health, especially when it is transmitted by dogs (variant 1) and by wild animals. This research intended to describe the epidemiological behavior of these events during 2012-2016 in the Casanare Province (Colombia). It is a retrospective descriptive study based on the cases reported to the National Surveillance System for Public Health -Sivigila-. The study variables are: a) socio-demographics; b) aggression/contact; c) exposure; d) immunization; and e) treatment. Application of descriptive statistics and calculation of surveillance indicators: Data were analyzed using the statistical software Epi-Info 7.2.2.2™. The 98.5% (6036/6131) of the cases in Casanare were distributed as follows: 2012 (1229; 20.4%), 2013 (1180;19.5%), 2014 (1227; 20.3%); 2015 (1153;19.1%), 2016 (1247; 20.7%). Out of them 72.5% were in the urban area; 55.4% were male subjects; average age was 24.3 (± 20.7) being the lowest age 0.01 and the highest 97 years and 40.7% were in the 5-19-year range; 37.5% were students, 13.3% housewives, 5.4% minors, and 19.4% had reported occupation (to wit, 29.8% (349/1172) farmers; 1.5% hospital patients; all of them alive). The 80.6% (721/894) with mild exposure were appropriately treated, 4.3% (37/894) were administered anti-rabies serum. The 91.1% (653/717) with serious exposure were appropriately treated. The 26.7% (1611/6036) of the cases were exposed to the rabies virus. Incidence per each 100,000 inhabitants exposed to the rabies was as follows: 2012-2016, 344.8 cases; hospitalization rate 11.5/100,000. It was found a non-compliance with the appropriate treatment indicator, i.e., the cases rated as mild exposure required administering only five doses of rabies vaccine (full vaccine scheme), and the cases rated as serious exposure required administering the full vaccine scheme plus the anti-rabies serum. It is recommended to keep/maintain the event surveillance activities as well as the efforts to prevent the human rabies transmission.

Resumo A vigilância, prevenção e controle da raiva são prioridade para a saúde pública, especialmente a raiva transmitida por cães (variante 1) e a raiva selvagem. O objetivo desta pesquisa foi descrever o comportamento epidemiológico do evento entre 2012-2016 no departamento de Casanare, Colômbia. O estudo foi descritivo, retrospectivo a partir da notificação de casos no Sistema Nacional de Vigilância em Saúde Pública-Sivigila-. Variáveis em estudo: a) características sociodemográficas, b) agressão/contato, c) exposição, d) imunização e e) tratamento. Aplicação de estatística descritiva e cálculo de indicadores de vigilância. Dados analisados com o pacote estatístico Epi-Info 7.2.2.2™. 98.5% (6036/6131) de casos procedentes de Casanare, distribuídos em 2012 (1229; 20.4%), 2013 (1180; 19.5%), 2014 (1227; 20.3%); 2015 (1153; 19.1%), 2016 (1247; 20.7%); de 72.5% da área urbana; 55.4% do sexo masculino; média de idade 24.3(±20.7) valor mínimo 0.01 e valor máximo 97 anos; 40.7% dos 5-19 anos; 37.5% estudantes, 13.3% donas de casa, 5.4% menores de idade, 19.4% com histórico de ocupação, sendo 29.8 % (349/1172) agricultores; 1.5% hospitalizados; todos vivos. 80.6% (721/894) de exposição leve tiveram tratamento adequado, 4.3% (37/894) foi aplicado soro antirrábico; 91.1% (653/717) de exposição grave com tratamento adequado; 26.7% (1611/6036) dos casos estiveram expostos ao vírus da raiva. Incidência por 100.000 habitantes em exposição à raiva: 2012-2016 (344.8); taxa de hospitalização 11.5/100 000. Evidencia-se desatenção do indicador de tratamento adequado, ou seja, nos casos classificados como exposição leve, aplicar unicamente cinco doses de vacina antirrábica (esquema de vacinação completo); e, em exposição grave, aplicar o esquema de vacinação completo e soro antirrábico. Recomenda-se continuar/manter as atividades de vigilância do evento e os esforços para evitar a transmissão da raiva humana.

La rabia como enfermedad re-emergente / Rabies as a re-emerging disease

RESUMEN En la actualidad, las enfermedades transmisibles afectan más de 14 millones de personas cada año, sobre todo en los países en desarrollo. Cerca del 50 % de las defunciones se producen por estas causas, de las cuales, el 90 % se atribuyen a las infecciones diarreicas y respiratorias agudas, el SIDA, la tuberculosis, el paludismo, el sarampión y la rabia. Esta última ha acompañado al hombre en toda su evolución, con una amplia distribución mundial y con la incorporación de un tratamiento exitoso desde el siglo XIX. Actualmente, sectores de la sanidad humana y animal establecen una alianza de colaboración en aras de eliminarla. En este artículo se realizó un recuento de la evolución epidemiológica de la rabia, su influencia en la humanidad y el desarrollo de la vacunación contra esta enfermedad; además de su re-emergencia como problema de salud.

ABSTRACT At present, communicable diseases affect more than 14 million people each year, especially in developing countries. Nearly 50% of deaths are caused by these causes; 90% of them are attributed to diarrheal and acute respiratory infections, AIDS, tuberculosis, malaria, measles and rabies. This latter disease has accompanied man throughout his evolution, with a wide global distribution and with the incorporation of a successful treatment since the 19th century. Currently, sectors of human and animal health establish a collaborative alliance in order to eliminate it. In this article, an account of the epidemiological evolution of rabies was made, its influence on humanity and the development of vaccination against this disease; in addition to its re-emergence as a health problem.

Transmisión vertical del virus de la rabia cría-madre, fenómeno que podría mantener al virus en especies reservorios de vida silvestre / Vertical transmission of the rabies virus from calf to mother, a phenomenon that could maintain the virus in reservoir species of wildlife

Resumen Introducción: La prueba biológica establecida por la Organización Mundial de la Salud para aislar y amplificar el virus de la rabia consiste en inocular vía intracraneal ratones lactantes para detectar signos de rabia en un periodo de 21 días. Objetivo: Constatar el contagio viral en las madres de ratones lactantes inoculados con virus de la rabia. Método: Veintisiete aislados mexicanos de virus de la rabia se inocularon vía intracraneal en ratones lactantes, los cuales fueron observados por 21 días y sus madres, por 60 días. El diagnóstico se llevó a cabo mediante inmunofluorescencia en cerebro. El virus se caracterizó por secuenciación y anticuerpos monoclonales. Resultados: Todas las camadas presentaron rabia entre siete y 15 días posinoculación (p. i.); tres de las 27 hembras (11 %), a los días 33, 37 y 39 p. i. de sus crías. La caracterización viral mostró que las madres se infectaron con la misma variante de sus crías, dos procedían de murciélago hematófago y una de perro. Las camadas que trasmitieron rabia a sus madres fueron nueve individuos. Conclusiones: En la naturaleza, el virus de la rabia podría preservarse mediante la transmisión de los neonatos (más susceptibles de contraer y amplificar el virus) a sus madres.

Abstract Introduction: The biological test established by the World Health Organization to isolate and amplify the rabies virus consists in inoculating lactating mice by intracranial route and detecting rabies signs for 21 days. Objective: To verify viral transmission in mothers of rabies virus-inoculated lactating mice. Method: Twenty-seven Mexican rabies virus isolates were inoculated by intracranial route in lactating mice, which were observed for 21 days. The mothers were observed for 60 days. The diagnosis was established by immunofluorescence in brain tissue. The virus was characterized by sequencing and with monoclonal antibodies. Results: All litters showed rabies at between 7 and 15 days post-inoculation (p. i.). Three of the 27 females (11 %) had developed rabies at days 33, 37 and 39 p. i. of their litters. Viral characterization showed that the mothers were infected with the same variant of their offspring, two of them stemming from hematophagous bat and one from dog. The liters that transmitted rabies to their mothers were nine individuals. Conclusions: In nature, the rabies virus could be preserved by transmission from neonates (more susceptible to contracting and amplifying the rabies virus) to their mothers.

Caracterización molecular de la nucleoproteína del virus de la rabia en canes procedentes de Arequipa, Perú / Molecular characterization of the rabies virus' nucleoprotein in dogs from Arequipa, Peru

RESUMEN Objetivos. Caracterizar la nucleoproteína (N) y establecer el origen del virus de la rabia en canes procedentes de Arequipa. Materiales y métodos. Se analizaron 30 muestras de tejido nervioso procedentes de los departamentos de Arequipa y Puno. Se extrajo el ARN total de las muestras y se sintetizó ADNc para amplificar el gen de la nucleoproteína, secuenciarlo y realizar el análisis bioinformático. Resultados. Se obtuvo la formación de un grupo definido con respecto al grupo externo (European bat lyssavirus). Este grupo fue clasificado en dos subgrupos, uno constituido por muestras procedentes de Puno y Arequipa (subgrupo A), y otro por muestras de Puno (subgrupo B), observándose una identidad nucleotídica de 99,9% en el subgrupo A. Conclusiones. Los agrupamientos de las secuencias virales muestran que los casos de rabia canina notificados en Arequipa son el resultado de la expansión de rabia canina procedente de la región endémica de Puno.

ABSTRACT Objective . To characterize the nucleoprotein (N) and establish the origin of the rabies virus in dogs coming from Arequipa. Materials and Methods. Thirty samples of nervous tissue from the departments of Arequipa and Puno were analyzed. Total RNA was extracted from the samples and cDNA was synthesized to amplify the nucleoprotein gene, sequence it, and perform bioinformatics analysis. Results . A defined group was formed with respect to the external group (European bat lyssavirus). This group was classified into two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), exhibiting a nucleotide identity of 99.9% in subgroup A. This group was classified in two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), observing a nucleotide identity of 99.9% in subgroup A. Conclusions. The groupings of viral sequences show that the cases of canine rabies reported in Arequipa are the result of the expansion of canine rabies from the endemic region of Puno.

Raiva humana no Brasil: estudo descritivo, 2000-2017 / La rabia humana en Brasil: estudio descriptivo, 2000-2017 / Human rabies in Brazil: a descriptive study, 2000-2017

Objetivo: descrever o perfil epidemiológico da raiva humana no Brasil. Métodos: estudo descritivo dos casos de raiva humana notificados em 2000-2017; estimou-se a incidência e distribuição espacial. Resultados: 188 casos humanos observados, na maioria homens (66,5%), residentes rurais (67,0%), menores de 15 anos de idade (49,6%), com exposição mais frequente por mordedura (81,9%); o período 2000-2008 apresentou maior frequência (85,6%), com 46,6% dos casos envolvendo cães e 45,9% morcegos; incubação mediana de 50 dias, seguida de sintomatologia predominante de febre (92,6%), agitação (85,2%), parestesia (66,7%) e disfagia/paralisia (51,9%); a maioria (70,2%) não fez profilaxia, os demais (29,8%) realizaram-na de forma inoportuna e/ou incompleta; 13 pacientes foram tratados pelo Protocolo de Recife e dois sobreviveram. Conclusão: houve redução na incidência de raiva humana e mudança no perfil epidemiológico, predominando casos transmitidos por morcegos; sugere-se investigar casos secundários e viabilizar a profilaxia pré-exposição em populações sob maior risco de acidentes com morcegos.

Objetivo: describir el perfil epidemiológico de la rabia humana en Brasil. Métodos: descripción de los casos en 2000-2017, con estimación de la incidencia y distribución espacial. Resultados: se observaron 188 casos humanos, la mayoría de hombres (66,5%), residentes rurales (67,0%), menores de 15 años de edad (49,6%), con exposición más frecuente por mordedura (81,9%); el período 2000-2008 presentó mayor frecuencia (85,6%), con un 46,6% de los casos involucrando a perros y 45,9% a murciélagos; la incubación promedio fue de 50 días, seguida de sintomatología predominante de fiebre (92,6%), agitación (85,2%), parestesia (66,7%) y disfagia/parálisis (51,9%); la mayoría (70,2%) no hizo profilaxis y los demás (29,8%) la realizaron de forma inoportuna y/o incompleta; se trataron 13 pacientes con el Protocolo de Recife y dos sobrevivieron. Conclusión: hubo reducción en la incidencia de rabia humana y cambio en el perfil epidemiológico, predominando casos transmitidos por murciélagos; se sugiere investigar casos secundarios y viabilizar la profilaxis preexposición en poblaciones de mayor riesgo a accidentes por murciélagos.

Objective: to describe the epidemiological profile of human rabies in Brazil. Methods: this is a descriptive study of human rabies cases reported in 2000-2017, with an estimate of incidence and spatial distribution. Results: 188 cases were studied, mostly males (66.5%), rural residents (67.0%), children under 15 years (49.6%), with biting being the most frequent form of exposure (81.9%); frequency was highest in the period 2000-2008 (85.6%), with 46.6% of cases involving dogs and 45.9% bats; median incubation was 50 days, followed by, predominantly, symptoms of fever (92.6%), agitation (85.2%), paresthesia (66.7%), and dysphagia/paralysis (51.9%); the majority (70.2%) did not have prophylaxis and for the rest (29.8%) who did have prophylaxis, it was untimely and/or incomplete; 13 patients were treated according to the Recife Protocol, and two survived. Conclusion: human rabies incidence reduced and its epidemiological profile changed, with predominance of cases transmitted by bats; we suggest that secondary cases be investigated, and that pre-exposure prophylaxis be made available to populations at greater risk of accidents involving bats.

Sequencing analysis of N and G gene of rabies viruses from Sichuan province of China in 2011- 2017 / 中华实验和临床病毒学杂志

Objective@#To analyze molecular feature of rabies virus (RABV) epidemic strains in Sichuan province during 2011 to 2017, and explore differences at nucleotide, amino acid and protein modification between these street strains and vaccine strains.@*Methods@#Nucleoprotein(N) and glycoprotein(G) genes were amplified by RT-PCR using specific primers for 23 antigen-positive canine brain specimens collected from 2011 to 2017. The evolutionary relationship and immune antigenicity of N and G genes was analyzed. Bioinformatics software was used to analyze and organize data.@*Results@#We obtained the N and G genes sequences of 23 RABV strains by sequencing. Genetic evolution relationship analysis showed that all the 23 RABV strains belonged to rabies virus species and could be divided into three branches, which had apparent geographically specific characteristics but some Sichuan strains co-circulated with the epidemic strains in the eastern and northern regions of China.The N genes of Sichuan strains had nucleotide and amino acid homology of 97.4% to 100% and 99.6%-100%. The nucleotide and amino acid homology between Sichuan strains and reference strains were 72.1%-99.8% and 81.6%-100%, respectively. There were some differences in antigenic sites, cell epitopes and signal peptide sequences between vaccine strain and Sichuan strains but no significant change was found in antigenicity, organizational preference and virulence.@*Conclusions@#The 23 strains of RABV of Sichuan belonged to rabies virus species and had no obvious differences. There were few differences between Sichuan strain and vaccine strain in amino acid sequences of G, but the virulence did not change.

Etiology analysis on a laboratory confirmed human rabies case with atypical symptoms / 中华实验和临床病毒学杂志

Objective@#To investigate and analyze the clinical features, epidemiologic information and pathogenic characteristics of a rabies patient.@*Methods@#Clinical data of the patient(boy) was collected and epidemiological survey was conducted, fluorescence quantitative reverse transcription-polymerase chain reaction (FQRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the samples of saliva, cerebrospinal fluid (CSF), skin tissue with hair follicle at the back of the neck for rabies laboratory diagnosis.@*Results@#Early symptoms of the boy were vomiting, diarrhea, fever and irritability, followed by coma and death. The boy had nasal trauma one month ago and the domestic dog died of illness during the same period. He did not accept the rabies post-exposure prophylaxis (PEP). The result of the saliva sample was positive by FQRT-PCR. The predicted segments of the glycoprotein(G), nucleoprotein (N) genes of rabies virus were amplified from the positive saliva sample of the patient by RT-PCR. Compared with rabies virus strains in Henan province, the nucleotide homology and amino acid homology in G gene segment were 96.5%-98.8% and 96.5%-99.2% respectively.@*Conclusions@#The case was diagnosed in laboratory as rabies case. The pathogenic rabies virus strain was endemic in Henan province. The nasal trauma, the dead domestic dog were probably related to the infection of the boy.