Rabies Research Articles

Laboratory diagnostics in dog-mediated rabies: an overview of performance and a proposed strategy for various settings.

The diagnosis of dog-mediated rabies in humans and animals has greatly benefited from technical advances in the laboratory setting. Approaches to diagnosis now include the detection of rabies virus (RABV), RABV RNA, or RABV antigens. These assays are important tools in the current efforts aimed at the global elimination of dog-mediated rabies. The assays available for use in laboratories are reviewed herein, as well as their strengths and weaknesses, which vary with the types of sample analyzed. Depending on the setting, however, the public health objectives and use of RABV diagnosis in the field will also vary. In non-endemic settings, the detection of all introduced or emergent animal or human cases justifies exhaustive testing. In dog RABV-endemic settings, such as rural areas of developing countries where most cases occur, the availability of or access to testing may be severely constrained. Thus, these issues are also discussed along with a proposed strategy to prioritize testing while access to rabies testing in the resource-poor, highly endemic setting is improved. As the epidemiological situation of rabies in a country evolves, the strategy should shift from that of an endemic setting to one more suitable for a decreased rabies incidence following the implementation of efficient control measures and when nearing the target of dog-mediated rabies elimination.

Imported Dog Rabies

Rabies, the most lethal zoonosis, causes an estimated 59,000 deaths worldwide annually. Dogs are the most common vectors globally, but mandatory

Another Account of Interspecific Aggression Involving a Hoary Bat (Lasiurus cinereus)

Abstract We observed an incident of interspecific aggression between a male Hoary Bat (Lasiurus cinereus) and a male Silver-haired Bat (Lasionycteris noctivagans). The Silver-haired Bat suffered few external injuries, the most conspicuous of which were a missing lower right canine and small puncture wounds on the left wing membrane. The Hoary Bat experienced much more extensive external injuries, including sub-dermal bleeding on wing and tail membranes and bite marks and tears in both wings. Few published accounts describe physical altercations among bats, but Hoary Bats are frequently involved. Rabies is often implicated as a driving factor in the aggressive interactions. We decided not to euthanize the bat for rabies testing, but encourage others who encounter these types of interactions to have bats tested.

Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned.

The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.

First reported case of dog associated pig rabies in Ghana

First reported case of dog associated pig rabies in Ghana

Pattern of animal bites and post exposure prophylaxis in rabies: A five year study in a tertiary care unit in Sri Lanka.

BackgroundRabies is a global problem which occurs in more than 150 countries and territories including Sri Lanka, where human deaths from rabies are in decline whilst resources incurred for prevention of rabies are in sharp incline over the years. In this backdrop, we aim to audit the post-exposure treatment (PET) in rabies and the pattern of animal bites in a tertiary care hospital in Sri Lanka.MethodsThis study was carried out at Teaching Hospital Peradeniya (THP), in the Central Province of Sri Lanka from 2007-2012 where a registry of all PET has been maintained. The data from registries were extracted after obtaining permission from the hospital authority for analysis.ResultsThere were 19 661 cases of animal exposure presented to the THP over the study period of 5 years. Of them, the majority-17431(88.66 %) were definitive animal bites whilst scratches accounted for 2147(10.92 %) and 83(0.42 %) were miscellaneous exposures. According to the severity grading of injuries, 7 362(37 %) were major bites and 12 226(62 %) were minor bites. The domestic unvaccinated dogs and cats were responsible for 10,662 (54 %) and 3,982 (20 %) of exposures respectively. The total cost incurred for both anti-rabies vaccine and anti rabies serum during the study period is 24,795,888.00 Sri Lankan rupees (190,737.60US$).ConclusionsThe pattern of animal bite shows high dominance of domestic dogs and cats exposures. The age of victims ranged from infancy to old-age with higher incidence among children. Even though PET is costly, continued surveillance and rabies control is still necessary along with public education and vaccination of domestic pets.

Persistent mental symptoms and rabies.

We read the case report by Wang and colleagues[1] with great interest. The authors linked persistent mental symptoms of the patient with rabies encephalitis. However, we think that the points listed below should be explained more clearly before this diagnosis can be confirmed. 1) The incubation period of rabies is only three days. It was not mentioned which body part was bitten by the dog. If the bite was close to the central nervous system, it would be especially important for development of rabies. We think that the bite could be a coincidental event unrelated to the subsequent mental symptoms. 2) Is there any knowledge about the dog’s last status? It is important to know whether the dog was rabid or not. 3) Which method was used to investigate rabies immunoglobulin in the cerebrospinal fluid? What were the patient’s other cerebrospinal fluid findings? For instance, was herpes simplex virus encephalitis investigated? This would be important to know because this is another possible explanation of the condition. 4) It is well known that rabies is almost always fatal, but this patient survived. Which factors might have resulted in the patient’s survival in the presence of severe persistent mental symptoms due to rabies encephalitis? Information on these points will help to clarify the probable cause of the mental symptoms in this patient.

Kynanthropy: canine madness in Byzantine late antiquity.

Those afflicted bark like dogs, scramble on all fours and loiter around graveyards - canine madness, referred to as kynanthropy, was an illness concept in its own right in the medicine of late antiquity. At roughly the same time as the medical description produced by Aëtius of Amida, the Syrian chronicler John of Ephesus, also from Amida, reported an epidemic of dog-like madness sweeping his home town in ad 560. The symptoms are identical and both authors are from Amida - what is the connection between the two depictions? In addition to the history of the medical concept, the example of the canine madness of Amida and its cultural embedding allows us to contextualize and interpret the significance of dog-like behaviour for the people of the sixth century AD.

RABIES SURVEILLANCE AMONG BATS IN TENNESSEE, USA, 1996-2010.

Rabies virus (RABV) infects multiple bat species in the Americas, and enzootic foci perpetuate in bats principally via intraspecific transmission. In recent years, bats have been implicated in over 90% of human rabies cases in the US. In Tennessee, two human cases of rabies have occurred since 1960: one case in 1994 associated with a tricolored bat (Perimyotis subflavus) RABV variant and another in 2002 associated with the tricolored/silver-haired bat (P. subflavus/Lasionycteris noctivagans) RABV variant. From 1996 to 2010, 2,039 bats were submitted for rabies testing in Tennessee. Among 1,943 bats in satisfactory condition for testing and with a reported diagnostic result, 96% (1,870 of 1,943) were identified to species and 10% (196 of 1,943) were rabid. Big brown (Eptesicus fuscus), tricolored, and eastern red (Lasiurus borealis) bats comprised 77% of testable bat submissions and 84% of rabid bats. For species with five or more submissions during 1996-2010, the highest proportion of rabid bats occurred in hoary (Lasiurus cinereus; 46%), unspecified Myotis spp. (22%), and eastern red (17%) bats. The best model to predict rabid bats included month of submission, exposure history of submission, species, and sex of bat.

Rabi Oscillations in a Two-Level Atomic System with a Pseudo-Hermitian Hamiltonian: A Path Integral Approach

The time development of a two-level system with a pseudo-Hermitian Hamiltonian is studied using the spin coherent state path integral. The propagator is first written in the standard form by replacing the spin by a unit vector aligned along the polar and azimuthal directions (θ,φ). Then it is determined exactly using perturbation methods. The metric of the pseudo-Hermitian Hamiltonian and its bi-orthonormal basis of system states are deduced.

Analysis of epidemiological features of human rabies in China, 2012

To analyze epidemiological characteristics and trends of rabies and explore control and prevention measures based on the rabies surveillance data of 2012 in China. Data of 2012 from China's infectious disease surveillance reporting and management system and sentinel surveillance systems in 6 provinces were used, for a retrospective analysis in descriptive epidemiological methods. 1 425 cases were reported in 731 counties of 27 provinces in 2012 and 1 361 deaths were reported due to rabies, with the rabies incidence rate and mortality rate of 0.11/100 000 and 0.10/100 000 respectively, decreasing by 26.0% and 27.9% respectively from 2011. Rabies epidemic was mainly found in southern regions, followed by middle and eastern regions in China. 49.6% of total rabies cases were found in Guangxi, Guangdong, Hunan, Guizhou, and Henan province, which were the top five provinces. The rabies cases were mainly peasants, students and scattered children, accounting for 70.9%, 8.3% and 5.8% of total cases respectively. The male-female ratio in rabies cases was 2.6 : 1. In 2012, 294 epidemiological questionnaires were collected, revealing that 92.1% of the exposure was caused by dogs and 6.8% by cats. The median of latent period was 70 days. 62.4% of the cases were exposed in upper limb, and only 6.9% of such cases were vaccinated after exposure while the proportion of passive immunity biological vaccination was 2.9% for cases with exposure of category III. Surveillance data from PEP (post-exposure prophylaxis) clinics showed that 81.7% of the visitors were hurt by dogs and the exposure categories I, II and III accounted for 7.0%, 50.5% and 42.5% respectively. The proportion of of the exposure categories varied by PEP surveillance clinics. Despite continuing decrease of rabies cases in China in 2012, the number of counties (districts) affected fall relatively slow, with a tendency of rabies spreading to the western and northern regions in China. There were more rabies cases in rural areas than urban ones, and children and elderly people constitute the high-risk population. Animal reservoir of rabies was still dogs as before. Poor PEP and insufficient use of vaccination and passive immunity preparations were main causes for onset of human rabies.

Analysis of morbidity and mortality characteristics of the notifiable diseases reported in 2013 in China

To learn the characteristics of morbidity and mortality of notifiable diseases reported in China in 2013. Descriptive analysis method was used to analyze the morbidity and mortality of notifiable diseases in China in 2013, with Microsoft Excel 2010 and ArcGIS 10.0 used to develop statistical charts. In 2013, the morbidity of the nationwide notifiable diseases was 473.87/100 000, a decrease of 3% below the average of the recent 3 years, while the mortality was 1.23/100 000, an increase of 2% over the average of the recent 3 years. The rate of laboratory diagnosis of the reported cases was 38.4%. Top 5 diseases of the reported incidence were hand foot and mouth disease, other infectious diarrhea, hepatitis B, tuberculosis and syphilis. The death cases reported were mainly AIDS, tuberculosis and rabies. As classified by the transmission route analysis, intestinal infectious diseases accounted for 49% of the total incidence reported for the year, followed by the blood and sexually transmitted infectious diseases, respiratory infectious diseases, animal and vector borne infectious diseases. According to the pathogenic analysis, virus infectious diseases accounted for 68% of the total cases, higher than bacterial infectious diseases and animal-borne/vector-borne infectious diseases. In Shanghai, Zhejiang and Jiangsu, human infection with avian influenza A (H7N9) virus was emerging, as epidemic situation of measles, dengue fever and brucellosis were on the rise significantly nationwide, while the morbidity of infectious diseases decreased, namely pulmonary tuberculosis, hepatitis B among others. Morbidity of the top 5 provinces for notifiable infectious diseases were Hainan, Guangxi, Guangdong, Xinjiang and Zhejiang, respectively. The proportion of laboratory confirmed cases among totals was still low in 2013. The morbidity of the infectious diseases was higher in western provinces and parts of south-eastern province, the mortality was higher in western provinces. The emerging human infection with avian influenza A (H7N9) virus, and the high epidemic of measles, dengue fever and brucellosis in some areas had caught the society concerns.

Smartphone and GPS technology for free-roaming dog population surveillance - a methodological study.

Free-roaming dogs (FRD) represent a potential threat to the quality of life in cities from an ecological, social and public health point of view. One of the most urgent concerns is the role of uncontrolled dogs as reservoirs of infectious diseases transmittable to humans and, above all, rabies. An estimate of the FRD population size and characteristics in a given area is the first step for any relevant intervention programme. Direct count methods are still prominent because of their non-invasive approach, information technologies can support such methods facilitating data collection and allowing for a more efficient data handling. This paper presents a new framework for data collection using a topological algorithm implemented as ArcScript in ESRI® ArcGIS software, which allows for a random selection of the sampling areas. It also supplies a mobile phone application for Android® operating system devices which integrates Global Positioning System (GPS) and Google MapsTM. The potential of such a framework was tested in 2 Italian regions. Coupling technological and innovative solutions associated with common counting methods facilitate data collection and transcription. It also paves the way to future applications, which could support dog population management systems.

Rabies trends and surveillance capabilities in Zambia

The main objective of this study was to assess the trends, distribution and positivity rate of rabies cases in Zambia. A retrospective study for the period of 10 years between 2004 and 2014, was conducted by using rabies case reports. The data were analyzed with descriptive statistics and geo-coded in Quantum Geographical Information System (QGIS) with the help of shape files. The geo-referenced data were then used to map the trend and spatial distribution of the disease on maps in a Geographical Information System (GIS) platform. The findings showed that 61.5% (462/751, 95% CI=57.9- 65.0) of the samples were positive. Canines accounted for 81.6% (95%, CI=77.7- 85) of the total positive samples followed by Bovines 9.1% (95%, CI= 6.7- 12.2). A mean monthly occurrence of canine rabies was 2.9. The average provincial positivity rate was 0.7. Positivity rates equal to or closer to one indicate poor surveillance; with rates equal to or closer to zero indicate good surveillance. One on one in-depth interview was conducted with one officer from each of these institutions i.e. The University of Zambia (UNZA), National Livestock and Epidemiological Information Center (NALEIC) and Central Veterinary Research Institute (CVRI) in order to familiarize with the current rabies surveillance systems in Zambia. The findings were that; sample submission is done by veterinarians and livestock officers and only UNZA and CVRI have capability for rabies diagnosis with NALEIC as a data storage institution. Rabies is endemic in Zambia and the dog is maintenance host for the disease in human and livestock populations. Therefore, controlling rabies in dogs indirectly overcomes the problem in human and livestock. Keywords : Zambia, rabies, endemic, positivity rate, surveillance

Perceptions and treatment seeking behaviour of dog bite patients attending regional tertiary care hospital of central Gujarat, India

Background: Rabies is practically 100% fatal zoonotic disease but easily preventable with timely administration of vaccine to the dog bite victim, but very commonly myths and practices amongst people prevent them for adequate and appropriate treatment. Aim & Objective: To know perception of dog bite patients about Anti-rabies Vaccination (ARV) and to know health seeking behaviour of dog bite victims attending a tertiary care hospital. Material and Methods: A hospital based study was conducted among the animal bite victims who had attended Anti Rabies Clinic from February 2012 to May 2012 after taking their informed verbal consent. All enrolled patients were interviewed using a pretested semi-structured questionnaire. Results: Majority of the patients (45.6%) in the study were more than 50 years of age. Almost three-fourths of the study population was male (71.7%). One thirds of the population had primary education while 14.2% of the patients were illiterate. Most of the patients (64.1%) lived within 10 kilometres distance from ARV Clinic. There were 37.6% patients who had applied nothing on the wound site, while only 11% of them had washed the wound with soap and water. 93.9% (385) had approached other health facilities before coming to the ARV Clinic, of which no treatment/care was given in 18.8% of the cases. Conclusion: Animal bite was more common among adults, adolescents and males. The bite victims did not take proper wound care nor take prompt action to reach the health facility after the bite. Indigenous methods for wound care were quite prevalent. Key words: ARV, Health Seeking behaviour

Constrained spherical deconvolution provides evidence of extensive subcortical direct cerebellumbasal ganglia connections in human brain

Traditionally, the basal ganglia (BG) are thought to play a major role in the selection and inhibition of motor commands, while the cerebellum plays a role in tuning and reshaping on-going movement. In the past, the connections between the cerebellum and the cerebral cortex have been considered to be anatomically and functionally distinct from those linking the BG with the cerebral cortex. Evidences from recent anatomical experiments, using retrograde transneuronal transport of rabies virus in macaques, have challenged this old perspective demonstrating disynaptic subcortical pathways that directly link the cerebellum with the BG. Since the application of these techniques to the human brain remains elusive, due to the invasive nature of such methods, whether and to what extent these specific connections between the BG and cerebellum exist in the human brain remains unclear. However, recent developments in Diffusion Magnetic Resonance Imaging (dMRI) and diffusion tractography may allow for non-invasive and in vivo studies of the anatomical substrate of basal ganglia systems. Indeed, in our previous paper we studied the basal ganglia connectome providing strong evidences of a direct connection from cortex to Globus Pallidum (GPe and GPi) [1]. Thirteen normal subjects with no history of any overt neurological and/or psychiatric disorders were examined to test the hypotheses that substantial interactions, at least on the level shown in animal studies, also exist in the human brain. We demonstrated that it is feasible to disclose these cerebellar-subcortical connections by using constrained spherical deconvolution (CSD), an innovative approach which allows a reliable reconstruction of small- and long-fiber pathways, with subvoxel resolution in brain regions with multiple fiber orientations [2]. In particular we found evidences of subthalamic-cerebellar, dentate-thalamo-striatal, dentate-rubral-thalamic, dentate-rubral-pallidal and dentate-nigral connections. In addition to these connections, we found a direct cerebellar-dentate-pallidal connection never reported in literature to our knowledge; we identified and isolated two well-distinct tracts presenting an ipsilateral and contralateral component, converging mainly on the antero-medial part of the globus pallidus.

Antiviral therapy for human rabies.

Human rabies is virtually always fatal despite numerous attempts at aggressive therapy. Most survivors received one or more doses of rabies vaccine prior to the onset of the disease. The Milwaukee Protocol has proved to be ineffective for rabies and should no longer be used. New approaches are needed and an improved understanding of basic mechanisms responsible for the clinical disease in rabies may prove to be useful for the development of novel therapeutic approaches. Antiviral therapy is thought to be an important component of combination therapy for the management of human rabies, and immunotherapy and neuroprotective therapy should also be strongly considered. There are many important issues for consideration regarding drug delivery to the central nervous system in rabies, which are in part related to the presence of the blood-brain barrier and also the blood-spinal cord barrier. Ribavirin and interferon-α have proved to be disappointing agents for the therapy of rabies. There is insufficient evidence to support the continued use of ketamine or amantadine for the therapy of rabies. Minocycline or corticosteroids should not be used because of concerns about aggravating the disease. A variety of new antiviral agents are under development and evaluation, including favipiravir, RNA interference (for example, small interfering [si]RNAs) and novel targeted approaches, including interference with viral capsid assembly and viral egress.

Study on molecular characterization of rabies virus N gene segment from different animal species in the Sultanate of Oman

The present study was conducted to determine the molecular characterization of nucleoprotein (N) gene segment of the rabies virus (RV) in Sultanate of Oman. A portion of nucleotide sequence of N gene was amplified from the brains of 4 rabid animals (two goats, one sheep, and one camel) collected during 2011 to 2012, through reverse transcription polymerase chain reaction (RT-PCR). The nucleotide sequences of the gene were subjected to molecular and phylogenic analysis. The phylogenic analysis was performed in relation to Omani isolates and other sequences from the neighboring countries available in the GenBank. Results indicated that one genetic group of virus appeared to be circulating in the Sultanate of Oman with 99% of homology. The study also indicated that the Omani rabies virus is closely related (> 97% homology) to viruses isolated from Saudi Arabia, Jordan and Israel. It is clear from the results that since its first diagnosis in 1990 the rabies virus has not gone through significant variations from the one isolated from first outbreaks. Since, there is no evidence of any other rabies virus variant in Oman, it seem that rabies is maintained endemically in Oman through wild foxes. Key words: Rabies, Oman, molecular characterization, phylogenetic analysis, Oman.

Study on community knowledge, attitude and practice of rabies in and nearby Gondar town, North West Ethiopia

Rabies is one of the disastrous diseases for both animal and human beings. Questionaire based cross-sectional study was conducted in and nearby Gondar town from November 2013 to June 2014. A semi-structured questionnaire was administered to 139 respondents comprised of 96 from urban and 43 from peri-urban areas to assess knowledge, attitude and practice of community about rabies. The current study generally illustrated the presence of significant difference on knowledge and practice of the respondent from urban and peri-urban areas (P < 0.05). Although more than (96%) of the respondents were familiar with the disease, there is mis-perception about the cause and means of transmission of the disease. Starvation and thirst were mentioned by (49.6%) of the respondents as causes of the disease in dogs and 21.6% of them stated any type of contact (irrespective of the skin condition) with saliva of affected individual can transmit the diseases. The result also established that 124 (91.9%) of the respondents were aware that human and other different species of domestic animals can be affected by rabies. However, all respondents (100%) in peri-urban area perceived dog as the only source of infection for human being. Traditional medicine was stated as method of treatment in case of dog bite by 46% of the respondents whereas, 41.7% of respondent used post exposure vaccination. Only 35.8% of the respondent did vaccinate their dogs and level of low vaccination practice was higher in peri-urban area. Raising awareness about dog vaccination and improving access and affordability of the vaccine should be considered in control of the disease. Key words: Attitude, dog, Gondar, knowledge, practice, rabies.

Bat rabies in Oklahoma

Based on identification of bat species submitted to the Oklahoma State Department of Health for rabies testing, and from literature accounts, the incidence of rabies in bats in Oklahoma from 1987–2012 is discussed. Of the 1,079 bats submitted, 1,061 were tested for rabies over the last 26 y. Twelve species were identified. The most-frequently submitted species was the Eastern red bat, Lasiurus borealis. The percentage of bats that tested positive for rabies was 9.7%.