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.

Development and verification of qPCR method for detection of residual host DNA in human rabies vaccine(Vero cells) / 中国生物制品学杂志

@#Objective To develop and verify a qPCR method for the qualitative and quantitative analysis of residual host DNA in human rabies vaccine(Vero cells) stock solution.Methods The qPCR standard curve was established by using the Vero cell DNA quantitative national standard,and the residual host DNA was extracted using magnetic beads.The specificity,repeatability,intermediate precision,accuracy and durability of the method were verified,and the linear range and limit of quantification were determined.The residual DNA of three batches of human rabies vaccine(Vero cells) stock solution was quantitatively analyzed and the fragment size was qualitatively analyzed by using this method.Results The correlation coefficients(R~2) of Vero cell DNA quantitative national standard amplification standard curve were all more than 0.99 by qPCR,and the quantitative range was 0.3 pg/mL～30 ng/mL.The method showed good specificity and repeatability.In the verification of intermediate precision,accuracy and durability,the relative standard deviations(RSD)of detection results of the samples were all less than 10%.The residual DNA content of Vero cells in three batches of stock solution was 0.20～0.77 ng/dose,which met the relevant standard of Chinese Pharmacopoeia(Volume Ⅲ,2020edition).The residual DNA fragments greater than 154 bp accounted for 52%～63%.Conclusion The developed qPCR method for the detection of residual DNA in human rabies vaccine(Vero cells) stock solution had good specificity,repeatability,intermediate precision and durability,and qualitatively and quantitatively analyzed the residual DNA rapidly and accurately,which was of great significance for improving the detection and control of residual DNA content in the production process and final product of human rabies vaccine(Vero cells).

Characteristics of populations exposed to rabies in Anji County / 预防医学

Objective@#To investigate the epidemiological characteristics of rabies-exposed populations in Anji County, Zhejiang Province from 2017 to 2021, so as to provide insights into rabies control in the county.@*Methods@#All data pertaining to rabies were captured from Monthly Report of Rabies-exposed Populations in Huzhou City and Investigation Form of Multiple Dog Injuries reported by dog injury clinics in Anji County from 2017 to 2021, and the species of animals causing dog injuries, duration, degree and site of exposure, and post-exposure treatment of rabies-exposed populations were descriptively analyzed. @*Results@#Totally 46 186 cases with rabies exposure were reported in dog injury clinics in Anji County from 2017 to 2021, and the rate of exposure appeared a tendency towards a decline year by year (Z=-23.249, P<0.001), with an annual mean exposure rate of 1 739.59/105. The number of cases with exposure to rabies peaked in July and August (10 066 cases, 21.79%). Dogs were predominant animals causing injuries (31 732 cases, 68.70%), and the rate of exposure to dog bites appeared a tendency towards a decline year by year (Z=-35.541, P<0.001). There were 11 350 cases with cat-causing injuries (24.57%), and the rate of exposure to cat bites appeared a tendency towards a rise (Z=14.834, P<0.001). Lower extremity was the main site of exposure (22 364 cases, 48.42%), and the proportions of grade Ⅱ and Ⅲ exposure to rabies were 72.85% and 25.23%, the rates of exposure both appeared a tendency towards a decline (Z=-14.522, P<0.001; Z=-21.820, P<0.001). The proportion of using human rabies immune globulin was 25.72% among populations with grade Ⅲ exposure, which appeared a tendency towards a rise (Z=6.636, P<0.001). @*Conclusions@#The rate of exposure to rabies appeared a tendency towards a decline in Anji County from 2017 to 2021. Dogs were predominant animals causing injuries, and the rate of cat bites appeared a tendency towards a rise from 2017 to 2021; however, the proportion of using human rabies immune globulin remains to be improved among populations with grade Ⅲ exposure.

Total serum IgE in people immunized with human diploid cell rabies vaccines with different production processes / 中华微生物学和免疫学杂志

Objective:To investigate the effects of different production processes on sensitization responses to human diploid cell rabies vaccines.Methods:This study randomly collected 360 serum samples in clinical trials of four rabies vaccines with different production processes. Total IgE levels at different time points were detected by ELISA. SPSS19.0 software was used for statistical analysis.Results:Total IgE test results showed that the seropositive rate was 20% (6/30) for all four vaccines. The lowest mean value of total IgE was 9 IU/ml and the highest was 210 IU/ml. Repeated measures analysis of variance showed that there was no significant difference in total IgE levels at different sampling time points ( P=0.284), and the total IgE level in people injected with multistep concentrated human diploid cell rabies vaccine was significantly below that in people immunized with Vero cell rabies vaccine ( P=0.024). Conclusions:Increasing the immune dosage of human rabies vaccine could not result in a rise in total IgE. Human diploid cell rabies vaccines had good safety as the production process could remove most of allergenic impurities.

Consideration of clinical trial design for human rabies vaccines with different immunization schedules / 中华微生物学和免疫学杂志

This article referred to the relevant guidelines for vaccine clinical trials and the accumulated experience in the development and review of human rabies vaccines, as well as combined the technical recommendations for human rabies vaccines from major health facilities such as WHO, to discuss the key considerations in the design of clinical trials for human rabies vaccines, including control vaccines, evaluation of efficacy endpoints, clinical subjects, the sample size, immunity persistence, re-exposure immunization schedule and post-marketing study. This article aimed to provide reference for the design of human rabies vaccine clinical trials.

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.

A multicentric community survey on animal exposures among humans in India

Background: Rabies is a 100% fatal disease. There are inadequate data on animal exposures and rabies postexposure prophylaxis (PEP) from community-based field surveys in India. Objectives: The main objective of the study is to estimate the incidence of animal exposures (bite, scratch, or lick) in the study population and to describe the rabies PEP among the cases. Methods: A descriptive survey was conducted in seven states of India between July and November, 2017. In each state, multistage sampling methodology was followed for selection of district, taluka/tehsil, block, and clusters within the block. The primary sampling unit was a household (HH). A case was a patient with animal exposure (bite, scratch, or lick) in the last 1 year from the date of survey. The animal exposure was categorized based on the WHO guidelines (Category-I, Category-II, and Category-III). The patients with the history of multiple animal exposures any time during the survey period was considered as a single case. Results: A total of 1012 HHs were surveyed covering a population of 4294. 3016 (70.2%) participants were from rural settings and 1278 (29.8%) were living in urban settings. 2181 (50.8%) participants were male and 2113 (49.2%) were female. The annual incidence of animal exposure was 1.26% (confidence interval [CI]: 0.93%�59%). The annual incidence in urban setting was 1.33% (0.70 - 1.96) and rural settings were 1.23% (CI: 0.84 - 1.62). Majority (68.5%) of the cases were from rural settings, 61.2% of the cases were in the age group of 15� years. Among the 43 cases who had received PEP, 21 had Category-II exposures, of whom 66.7% had completed vaccination with either five doses intramuscular or four doses intradermal route. Similarly, 22 had Category-III exposures and only 4 (18.2%) cases had received rabies immunoglobulin and completed rabies vaccination. Six ( 11.1%) cases did not receive PEP. There was no report of human rabies case. Conclusion: The incidence of animal exposure was 1.26%. Rabies PEP in the cases was not satisfactory.

Appraisal of surveillance of human rabies and animal bites in seven states of India

Background: The key to understanding the burden of animal bites and rabies lies in accurate and timely data with the help of proper surveillance system across the country. Such a surveillance system needs to be evaluated also for a programmatic purpose. Objectives: The present study was conducted to appraise the surveillance system of human rabies and animal bites in seven states of India and also to describe the characteristics of human rabies cases in the states. Methods: The record-based study was conducted from July to December 2017. The survey team collected information about the surveillance status of human rabies from the infectious diseases hospitals and animal bites from integrated disease surveillance programme (IDSP) offices of the respective states for 2012�16. At the national level, also number of animal exposures and the human rabies cases were collected from the Central Bureau of Health Intelligence and IDSP and compared for concordance. Results: There was a gross underreporting of human rabies from the states to Government of India, and there was no concordance in the reports of animal bites between the IDSP offices of the states and NCDC, New Delhi, India. There was a gradual decline in the reported cases of human rabies from the states during the 5-year period of 2012�16, attributable to improvement in the overall rabies postexposure prophylaxis services. The documentation of information of the human rabies cases was poor in the infectious disease hospitals. Conclusion: The surveillance system on human rabies and animal bites in India has to be improved under the national rabies control program to eliminate rabies by the year 2030.

Rabia 99,9 % mortal, 100 % prevenible / Rabies 99,9 % deadly, 100 % preventable / Raiva 99,9 % mortal, 100 % evitável

La rabia es una zoonosis de causa viral que provoca una encefalitis aguda y progresiva invariablemente fatal, causante de unas 60.000 muertes anuales. La mayoría de los casos humanos se reportan en África y Asia, pero su distribución es mundial. Se bien se trata de una enfermedad en vías de eliminación en las Américas, ha habido un resurgimiento con nuevas áreas y países afectados en los últimos años. En áreas endémicas los casos humanos están relacionados con mordeduras por perros infectados, mientras que en el resto de los países se asocia a mordeduras de animales silvestres. Luego de las mordeduras, el uso apropiado de la profilaxis posexposición es universalmente efectiva. Por lo tanto, para disminuir la carga global de rabia humana, es fundamental el control de la rabia canina y la expansión de la disponibilidad de profilaxis. En Uruguay, si bien se eliminó la rabia humana en la década de 1960, desde el año 2007 asistimos a una situación epidemiológica compleja con la reintroducción de la rabia animal vinculada a murciélagos. Esto debe poner en alerta a la comunidad médica y veterinaria para evitar el resurgimiento de la rabia humana. Se necesita del esfuerzo conjunto de la medicina humana, veterinaria, de la población y del gobierno a través de políticas públicas con el fin de mantener la vigilancia epidemiológica, actuar sobre el control de la población de perros y aplicar medidas de profilaxis en humanos luego de la mordedura de animales. En la presente revisión se describe la situación en Uruguay, la presentación clínica de esta enfermedad y las indicaciones de profilaxis. (AU)

Rabies is a viral zoonosis that provokes severe and progressively fatal encephalitis, causing approximately 60,000 deaths per year. Most cases are reported in Africa and Asia, although it is globally distributed. Despite it being a disease that is about to be eradicated in the Americas, there has been an outbreak in new areas, affecting other countries in recent years. In endemic areas, human cases are caused by bites of an infected dog, whereas in the rest of the countries it is associated to bites by wild animals. After the bite, the appropriate use of the post-exposure prophylaxis is universally effective. Thus, in order to reduce the global burden of human rabies, it is essential to control dog rabies and to make prophylaxis even more available. In Uruguay, although human rabies was eradicated in the 60s, we have witnessed an epidemiologically complex situation since 2007, upon the new introduction of animal rabies associated to bats. The medical and veterinarian community needs to be alert to avoid this new outbreak of human rabies. We need the joint efforts of human medicine, veterinarians, the population and government by means of public policies with the purpose of conducting epidemiological surveillance, and work towards controlling the dog population and applying prophylactic measures in humans after dog bites. This review describes the situation in Uruguay, accounts for the clinical presentation of the disease and provides prophylactic guidelines. (AU)

La rabia es una zoonosis de causa viral que provoca una encefalitis aguda y progresiva invariablemente fatal, causante de unas 60.000 muertes anuales. La mayoría de los casos humanos se reportan en África y Asia, pero su distribución es mundial. Se bien se trata de una enfermedad en vías de eliminación en las Américas, ha habido un resurgimiento con nuevas áreas y países afectados en los últimos años. En áreas endémicas los casos humanos están relacionados con mordeduras por perros infectados, mientras que en el resto de los países se asocia a mordeduras de animales silvestres. Luego de las mordeduras, el uso apropiado de la profilaxis posexposición es universalmente efectiva. Por lo tanto, para disminuir la carga global de rabia humana, es fundamental el control de la rabia canina y la expansión de la disponibilidad de profilaxis. En Uruguay, si bien se eliminó la rabia humana en la década de 1960, desde el año 2007 asistimos a una situación epidemiológica compleja con la reintroducción de la rabia animal vinculada a murciélagos. Esto debe poner en alerta a la comunidad médica y veterinaria para evitar el resurgimiento de la rabia humana. Se necesita del esfuerzo conjunto de la medicina humana, veterinaria, de la población y del gobierno a través de políticas públicas con el fin de mantener la vigilancia epidemiológica, actuar sobre el control de la población de perros y aplicar medidas de profilaxis en humanos luego de la mordedura de animales. En la presente revisión se describe la situación en Uruguay, la presentación clínica de esta enfermedad y las indicaciones de profilaxis. (AU)

Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis / 药物分析学报

A simple method was established for the determination of β-propiolactone (BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry (GC-MS). The determination was performed on an Agilent HP-INNOWAX (30m × 0.32mm i.d., 0.25 μm) capillary column at the temperature of 80 °C. Electrospray ionization (ESI) was used by selective ion detection at m/z 42. The temperature for ESI source and inlet was set at 230 °C and 200 °C, respectively. Helium was used as the carrier gas at a flow rate of 25.1 mL/min. The total run time was 8 min. Acetonitrile and other components in the sample did not interfere with the determination of BPL. The results showed good linearity of BPL in the range of 0.50–10.01 μg/mL, with the limit of detection and the limit of quantification of 0.015 μg/mL and 0.050 μg/mL, respectively. Satisfactory precision was achieved for the current developed method. The method was applied to detect 6 batches of vaccine samples, and the results indicated that the target analyte BPL was present in three batches of unpurified samples, but was not detected in the purified samples, indicating the test samples were qualified. The established method was proved to be simple, versatile and sensitive, which can meet the requirements of quality control of BPL in human inactivated rabies vaccine.

The application of ARIMA in forecasting the cases of rabies in China different human groups / 中华劳动卫生职业病杂志

Objective@#To understand the situation of rabies in China different human groups. Seasonal ARIMA model is established to make forecasts and to provide suggestions for human rabies controlling in China.@*Methods@#Build a model with data during 2004-2013, and validate the model by data of 2014. Then predict the cases of rabies from 2015-2017.@*Results@#The long term trend is decreasing year by year, while seasonal effect is found that number of the third and fourth quarter are higher than others. The seasonal ARIMA model was built, whose residual are white noise. The RMAE in forecasting of peasants, students and scattered children are 19.10%、49.93% and 68.01%.@*Conclusion@#The decreasing of rabies cases in China with time shows that the measures for control are effective. October for peasants, September for students, August for scattered children are critical period in future for rabies' control. Seasonal ARIMA model is a feasible model in forecasting the cases of rabies in China different groups in some way, error will be reduced by modeling separately for different wave sequence and combining with other models like ARIMA-GARCH.

Analysis of 1019 cases with rabies exposure and prophylaxis / 中华实验和临床病毒学杂志

Objective@#To understand the prophylaxis of population exposed to rabies, and provide a basis for prevention and control of rabies.@*Methods@#The registration data of 1 019 cases with rabies exposure in Beijing Ditan Hospital Affiliated to Capital Medical University from Mar, 2017 to Feb, 2018 were analyzed using the descriptive epidemiologic method.@*Results@#Among the 1 019 cases of rabies exposure, the sex ratio of men to women was 0.90∶1, with the highest proportion of them were between 26 and 46 years of age old, accounting for 46.5%. Rabies exposure reached its peak (46.9%) between June and September. In addition, 63.3% of the injuries were caused by dogs and 36.7% by cats. Most of the wounds (55.1%) occurred in hands; and the second was lower limbs (26.6%). Most of the cases (60.7%) had grade II wounds; followed by grade III wounds (39.1%); 69.3% of the cases completed immunization with rabies vaccine. In grade III exposure, 73.7% of the patients were immunized with rabies immunoglobulin. Most of the persons of grade III exposure (73.7%) received inoculation with human rabies immunoglobulin (HRIG).@*Conclusions@#Measures to control rabies should be focused on the management of dogs and cats and the standardization of rabies post-exposure prophylaxis.

Analysis of the early immune effects of rabies vaccine combined with human rabies immunoglobulin / 中华实验和临床病毒学杂志

Objective@#To investigate the early immune effects of rabies vaccine combined with human rabies immunoglobulin (HRIG).@*Methods@#Rapid fluorescent focus inhibition test (RFFIT) was used to test the titers of rabies virus neutralizing antibodies (RVNA). The titers of RVNA of persons who had exposed to rabies at degree III on day 0, day 1, day 7, day 14 and day 45 were compared. The dynamic curves and seroconversion rates (SCR) of RVNA in persons of different genders, age and vaccine regimens (Essen and Zagreb) groups were analyzed.@*Results@#No significant differences of SCR among different genders, age and vaccine regimens groups were observed on the same day. SCR could be 100% on day14 in different groups. The dynamic curves of RVNA within the first 14 days showed the models of gradual rise, rapid rise and rapid decline.@*Conclusions@#The dynamic curves of RVNA within the first 14 days varied when rabies vaccines were used in combination with HRIG, and not all subjects were proved to be protected based on the RVNA detection within this period.

Encefalitis rábica: serie de casos clínicos / Rabiesencephalitis: case series

La rabia es una enfermedad aguda, infecciosa, zoonótica, producida por el virus del genero Lyssavirus de la Familia Rhabdoviridae, cuya principal fuente de transmisión es la inoculación del virus contenido en la saliva de un animal infectado al humano. Es una enfermedad mortal, se han descrito casos por ciclos urbanos y rurales4. Los casos reportados son del área rural del departamento de Cochabamba, con un cuadro clínico de cuatro días de evolución. Ambos presentaron hidrofobia, aerofobia, picos febriles y alteración del tracto respiratorio superior, con antecedentes de mordedura de perro de hace cuatro meses, el primer caso por un perro callejero y el segundo perro conocido sin vacunas, en ambos pacientes las mordeduras fueron en extremidades. Se realizó exámenes de gabinete y específicos para el diagnóstico. Confirmándose que la causa de la encefalitis fue por el virus de la rabia. Falleciendo ambos pacientes.

Rabies is an zoonotic and acute infectious, produced by the virus of the gender Lyssavirus of the Rhabdoviridae family, whose main source of transmission is the inoculation of the virus in the saliva of an infected animal to human. It is a deadly disease, have been reported cases by urban and rural cycles. The reported cases are in rural areas of Cochabamba, with a clinical of four days duration. Both had hydrophobia, aerophobia, fever peaks and upper respiratory disorder, a history of dog bite four months, the first case by a stray dog and the second known without vaccines, in both patients were bites in their extremities. Cabinet and specific tests were performed for diagnosis. Confirming that cause encephalitis was rabiesvirus.

Síndrome de Mendelson: reporte de un caso / Mendelson syndrome: a case report

El Síndrome de Mendelson es una presentación infrecuente pero catastrófica, consiste en la aspiración de contenido gástrico acido hacia los pulmones causando una neumonitis química por el paso de sustancias toxicas a las vías respiratoria inferiores. El cuadro clínico está caracterizado por hipoxemia, disnea, broncoespasmo, taquipnea, edema pulmonar, hipotensión, cianosis y atelectasias. La dificultad respiratoria se debe al edema agudo de pulmón y la necrosis. El diagnostico del Síndrome de Mendelson es de presunción en base a la sintomatología, la evolución de la enfermedad y los hallazgos en los exámenes de gabinete. Su tratamiento correcto es fundamental debido a la alta morbimortalidad que conlleva. Se presenta el caso de síndrome de Mendelson en un paciente de 89 años de edad debido a la enfermedad de Alzheimer, un trastorno neurodegenerativo. Se presentó a emergencias con un cuadro de vómitos postprandiales en abundante cantidad con contenido bilioso con secreciones flemosas, nauseas y dolor abdominal. La broncoscopia de urgencia fue clave para el diagnostico y el posterior tratamiento.

Mendelson's Syndrome is a rare but catastrophic presentation, is the aspiration of acidic gastric contents into the lungs causing chemical pneumonitis by the passage of toxic substances the lower respiratory tract. The clinical picture is characterized by hypoxemia, dyspnea, bronchospasm, tachypnea, pulmonary edema, hypotension, cyanosis, and atelectasis. Shortness of breath is due to acute pulmonary edema and necrosis. The diagnosis of Mendelson's Syndrome presumption is based on the symptoms, the disease evolution and the findings on tests of staff. Proper treatment is essential because of the high morbidity and mortality involved. For Mendelson's syndrome occurs in a patient of 89 years of age due to Alzheimer's disease, a neurodegenerative disorder. It was presented to emergency with symptoms of postprandial vomiting plenty flemosas content with bilious secretions, nausea and abdominal pain. Emergency bronchoscopy was key to the diagnosis and subsequent treatment.

Epidemiological characteristics of human rabies in Henan province in China from 2005 to 2013

Background Rabies is very common in People's Republic of China. Henan province, in the central portion of China, is one of the most densely populated provinces in the entire country. With the new rabies epidemic trend noted in northern and western China, it is necessary to investigate the characteristics of human rabies in this area and control the disease.Methods We chose patients in hospital isolation in 18 municipalities in Henan province as the investigation subjects. Data were collected through systematic reporting from these hospitals, whereas a questionnaire was applied to the relatives of patients.Results A total of 1022 rabies cases were reported. The incidence of human rabies in Henan has increased rapidly since 2005, having peaked in 2007, and maintained a high level in the remaining years. The cases were found mainly in rural areas in the south and east of the province. Rabies was often noted in summer and with the highest number in August. Most cases were noted in males and often in farmers. The patients aged between 40 and 60 years accounted for 36.8 % of all the cases. The wound treatment rate (12.2 %) and vaccination rate (2.6 %) of rabies cases after exposure were relatively low, while the rabies immunoglobulin utilization rate was only 2.8 %.Conclusions Rabies epidemic cases at the county level overall were increasing in Henan province during the period of 2005-2013; the epidemic has spread quickly. The data in this study imply that the disease could be better managed by more integrated surveillance across human health and veterinary sectors, improved education and better government policies.(AU)

Epidemiological characteristics of human rabies in Henan province in China from 2005 to 2013

Background Rabies is very common in Peoples Republic of China. Henan province, in the central portion of China, is one of the most densely populated provinces in the entire country. With the new rabies epidemic trend noted in northern and western China, it is necessary to investigate the characteristics of human rabies in this area and control the disease.Methods We chose patients in hospital isolation in 18 municipalities in Henan province as the investigation subjects. Data were collected through systematic reporting from these hospitals, whereas a questionnaire was applied to the relatives of patients.Results A total of 1022 rabies cases were reported. The incidence of human rabies in Henan has increased rapidly since 2005, having peaked in 2007, and maintained a high level in the remaining years. The cases were found mainly in rural areas in the south and east of the province. Rabies was often noted in summer and with the highest number in August. Most cases were noted in males and often in farmers. The patients aged between 40 and 60 years accounted for 36.8 % of all the cases. The wound treatment rate (12.2 %) and vaccination rate (2.6 %) of rabies cases after exposure were relatively low, while the rabies immunoglobulin utilization rate was only 2.8 %.Conclusions Rabies epidemic cases at the county level overall were increasing in Henan province during the period of 20052013; the epidemic has spread quickly. The data in this study imply that the disease could be better managed by more integrated surveillance across human health and veterinary sectors, improved education and better government policies.

Raiva humana / Human rabies

JUSTIFICATIVA E OBJETIVOS: A raiva humana é extremamente relevante do ponto de vista clínico e de saúde pública, por se tratar de moléstia fatal em aproximadamente 100,0% dos casos, embora haja relatos de cura após a instalação dos sinais e sintomas, um dos quais no Brasil, em 2008. O objetivo do presente estudo foi apresentar uma atualização sobre a raiva humana em seus aspectos epidemiológicos, clínicos e terapêuticos, destacando o Protocolo Recife, a fim de subsidiar médicos generalistas com informações úteis ao atendimento clínico de qualidade. CONTEÚDO: Após um período variável de incubação, iniciam-se os pródromos da doença (manifestações inespecíficas). A progressão da enfermidade é acompanhada de grave ansiedade, excitação e agitação psicomotora, evoluindo para manifestações relacionadas à disfunção do tronco cerebral. O tratamento é usualmente baseado nas medidas de apoio das complicações da infecção. CONCLUSÃO: A raiva humana permanece como significativo problema de saúde no Brasil, principalmente por ser uma doença - do ponto de vista clínico, diagnóstico e profilático - ainda pouco conhecida pelos médicos generalistas. Dessa forma, ações de educação continuada constituem um importante elemento para abordagem correta dos pacientes sob o risco de desenvolver a enfermidade.

BACKGROUND AND OBJECTIVES: The human rabies is extremely important for the internal medicine and public health, becauseis a fatal disease in nearly 100% of cases, although there are some reports of healing after the installation of signs and symptoms, one of which in Brazil in 2008, resulting Recife Protocol for treatmentof disease. The aim of this study is to present an update on the human rabies in their epidemiological, clinical and therapeutic aspects, highlighting the Recife Protocol, in order to subsidize generalpractitioners with useful information for clinical care quality. CONTENTS: After a variable period of incubation, begins the prodroms disease (nonspecific). The disease progression is accompanied by severe anxiety, arousal, and psychomotor agitation, progressing to complications due to dysfunction of the brainstem. The treatment is usually based on measures of support from complications of the infection. CONCLUSION: Human rabies remains a significant health problem in Brazil, mainly because it is a disease - the clinicalpoint of view, diagnosis and prophylaxis - that still not wellknown by general practitioners. Thus, actions of continuing education are an important element to appropriate approach for the individuals at risk of developing the disease.

Antemortem diagnosis of human rabies in a veterinarian infected when handling a herbivore in Minas Gerais, Brazil / Diagnóstico ante-mortem de raiva humana em médico veterinário infectado por manipulação de herbívoro, Minas Gerais, Brasil

The Ministry of Health's National Human Rabies Control Program advocates pre-exposure prophylaxis (PEP) for professionals involved with animals that are at risk of contracting rabies. We report an antemortem and postmortem diagnosis of rabies in a veterinarian who became infected when handling herbivores with rabies. The antemortem diagnosis was carried out with a saliva sample and a biopsy of hair follicles using molecular biology techniques, while the postmortem diagnosis used a brain sample and conventional techniques. The veterinarian had collected samples to diagnose rabies in suspect herbivores (bovines and caprines) that were subsequently confirmed to be positive in laboratory tests. After onset of classic rabies symptoms, saliva and hair follicles were collected and used for antemortem diagnostic tests and found to be positive by RT-PCR. Genetic sequencing showed that the infection was caused by variant 3 (Desmodus rotundus), a finding confirmed by tests on the brain sample. It is essential that professionals who are at risk of infection by the rabies virus undergo pre-exposure prophylaxis. This study also confirms that molecular biology techniques were used successfully for antemortem diagnosis and therefore not only allow therapeutic methods to be developed, but also enable the source of infection in human rabies cases to be identified accurately and quickly.

O Programa Nacional de Controle da Raiva Humana do Ministério da Saúde preconiza o esquema profilático pré-exposição (PEP) para profissionais envolvidos com animais expostos ao risco de contraírem raiva. O presente trabalho relata o diagnóstico de raiva (ante e post-mortem) em veterinário infectado por manipulação de herbívoros raivosos. O diagnóstico laboratorial ante-mortem foi efetuado a partir da saliva e biópsia de folículo piloso, utilizando técnicas de biologia molecular e o post-mortem a partir do tecido cerebral e de técnicas convencionais. O médico veterinário coletou amostras para diagnóstico de raiva em herbívoros (bovinos e caprinos) suspeitos que, posteriormente, foram confirmados positivos em laboratório. Após a apresentação dos sintomas clássicos de raiva e realizadas as provas de diagnóstico ante-mortem com saliva e folículo piloso, ambas as amostras apresentaram resultados positivos pelo nested-RT-PCR. O sequenciamento genético revelou que a infecção se deu pela variante 3 do Desmodus rotundus, resultados estes confirmados com a amostra do cérebro. É indispensável que profissionais expostos ao risco de infecção pelo vírus da raiva realizem a profilaxia pré-exposição. Ressalta-se, também, que as técnicas de biologia molecular apresentaram bons resultados para a realização de diagnóstico ante-mortem, propiciando o desenvolvimento de métodos terapêuticos, e determinando com precisão e rapidez a fonte de infecção dos casos de raiva humana.

The spatial distribution and dynamics of human rabies cases at the county level in Henan province / 中华流行病学杂志

Objective To study the spatial distribution and dynamics of human rabies cases at the county level, in Henan province to provide scientific evidence for the development of control program on rabies. Methods Data of human rabies cases at the county level from 2004 to 2010 in Henan province were analyzed by Poisson distribution and negative binomial distribution. Data calculation was conducted manually. Results According to the level of α =0.05 being set, there were three different results appeared: the first was fitted negative binomial distribution in 2004, 2005,2007 and 2009; the second was prioritized negative binomial distribution, but the poisson distribution could not be excluded in 2008 and 2010; the last one was fitted neither negative binomial distribution nor poisson distribution in 2006. By the clustering parameter k, the clustering degree at county level decreased from 2004 to 2008, then ascending in 2009 but descending again in 2010. The degree of clustering showed a positive correlation with the county mean cases in the prevalent counties (r=0.807,P=0.028). Conclusion As a whole,the distribution of human rabies at county level in Henan from 2004 to 2010 showed negative binomial distribution and presented the spatial clustering.However, the degree of clustering decreased in recent years and showed that the infection resource was possibly scattered more evenly at the county level.