Human Rabies Infection Research Articles

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I–VII), confirmed by analysing nucleotide sequences from both the G and N proteins.This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques.We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I–VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I–VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells.Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Rabies virus variants from bats closely related to variants found in marmosets (Callithrix jacchus), a neglected source of human rabies infection in Brazil.

Rabies is a fatal viral zoonosis caused by rabies virus (RABV). RABV infects the central nervous system and triggers acute encephalomyelitis in both humans and animals. Endemic in the Brazilian Northeast region, RABV emergence in distinct wildlife species has been identified as a source of human rabies infection and as such, constitutes a public health concern. Here, we performed post-mortem RABV analyses of 144 encephalic tissues from bats sampled from January to July 2022, belonging to 15 different species. We identified phylogenetically distinct RABV from Phyllostomidae and Molossidae bats circulating in Northeastern Brazil. Phylogenetic clustering revealed the close evolutionary relationship between RABV viruses circulating in bats and variants hosted in white-tufted marmosets, commonly captured to be kept as pets and linked to human rabies cases and deaths in Brazil. Our findings underline the urgent need to implement a phylogenetic-scale epidemiological surveillance platform to track multiple RABV variants which may pose a threat to both humans and animals.

Notifications of suspected rabies exposure increased in Finland: 26 years of one health surveillance, 1995–2020

Background Finland is a rabies virus-free country since 1991. Notification of suspected cases of rabies exposures, leading to post-exposure prophylaxis, is mandatory. We characterised suspected cases of rabies exposure, analysed animal surveillance data and calculated costs for vaccine and immunoglobulin and treatment to estimate the financial burden of rabies control in Finland. Methods The incidence rate ratios of suspected cases of rabies exposure were calculated from Finnish Infectious Disease Registry and Statistics Finland data. Animal surveillance data were obtained from the Finnish Food Authority’s registries. Calculation of costs were based on the medical and treatment costs of rabies control. Results In 2007, one human rabies infection linked to a dog bite in the Philippines and rabies infection in a dog imported from India were diagnosed in Finland. In 2009, 2016 and 2017, lyssaviruses were found in bats. Notifications of suspected rabies exposures increased during 2007–2019. Two-thirds of the exposures occurred abroad, mainly in Asian and African countries. Bats were the most frequent domestic exposing animal. The import of vaccine and immunoglobulin doses increased. The annual cost of Finnish rabies control is estimated to be over €1.65 million. Conclusions Increased awareness of rabies and bat lyssavirus infections probably increased post-exposure prophylaxis and reporting. Travellers need country-specific guidance on how to prevent exposures, and citizens need instructions on animal imports and how to handle bats.

Implementation of Clinical Decision Support on Emergency Department Delivery of Human Rabies Immune Globulin

Fatal human rabies infections can be prevented through appropriate rabies postexposure prophylaxis (PEP). Errors in patient selection and administration of human rabies immune globulin in the emergency department (ED) setting were identified in a previous study of rabies PEP administration. To test the a priori hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 human rabies immune globulin quality indicators compared with preimplementation controls. This quality improvement study was conducted in 15 EDs in a US multihospital health system. Patients who received human rabies immune globulin or rabies vaccine in the ED from January 2015 to June 2018 were included in the preimplementation control group and from December 2019 to November 2020 were included in the postimplementation intervention group. Data were analyzed in January 2021. The PEP bundle was implemented in December 2019 and consisted of electronic health record enhancements, including clinical decision support, ED staff education, and patient education. Full adherence to 6 human rabies immune globulin quality indicators: patient selection, dose, timing, infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock. The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women). Most patients presented to EDs embedded in a community hospital (231 patients [71%]). Full adherence increased from 37% in the preimplementation group to 61% postimplementation (absolute increase, 24%; 95% CI, 11% to 37%; P < .001). Adherence improved for quality indicators for infiltration into wounds (137 of 254 patients [54%] to 50 of 70 patients [71%]; P = .009), administration distant from rabies vaccine site (180 of 254 [71%] to 58 of 70 [83%]; P = .04), and administration that avoids the buttock (168 of 254 [66%] to 58 of 70 [83%]; P = .007). No instances of sciatic nerve injury or compartment syndrome were observed. In this quality improvement study, implementation of a rabies PEP bundle was associated with improved patient selection and delivery of human rabies immune globulin in EDs across a multihospital health system. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

Assessment of rabies immune globulin dose rounding at a university health system

PurposeDescribe a dose rounding strategy for rabies immune globulin (RIG) administration. MethodsMulticenter, retrospective, observational review of patients that received RIG following an exposure from an animal with potential to transmit rabies infection in one health-system from March 2011 through December 2021. The primary outcome was to describe the RIG dose rounding strategy and population of patients that received RIG rounded to the nearest vial size compared to those that did not. Secondary outcomes evaluated additional costs and RIG international units (IU) wasted that could have occurred (rounded group) or did occur (not rounded group), re-presentation to the ED or primary care provider (PCP) within 7 days due to RIG related complaint, and occurrence of rabies infection. Data collection included patient demographics, exposure information, and RIG dose administered. Descriptive data and univariate analyses are reported. Cost and RIG IU wasted were calculated for the dosing strategies. Results426 patients were included; 373 (88%) had RIG rounded to the nearest vial size and 53 (12%) did not (mean age 36.1 years ±20.5, 51.6% male, most common exposures were bats [50%], type was bite [58%], and category III exposures [92%]). Those that had RIG rounded were younger and had lower total RIG doses, but similar IU/kg doses to those not rounded. A cost savings of $144,815 and prevention of 40,572 RIG IU wasted was calculated from those patients that had RIG rounded. There was no difference in the rate of re-presentation within 7 days and no cases of human rabies infection in the region during the study period. ConclusionsRIG dose rounding to the nearest vial size is associated with cost savings and prevention of wasting RIG IU. There was no association with re-presentation to the ED or PCP with RIG related issues within 7 days from administration.

Case report on fatal human rabies infection in central India

Rabies is a zoonotic disease that affects the central nervous system of mammals and has a high mortality rate. It is a viral disease that can be prevented by vaccination. Dogs are the leading cause of human rabies deaths, accounting for up to 99% of all human rabies transmissions. On 15th December 2019 an 8 years old male child was bitten by a stray dog outside of his house. The patient visited with his parents to a nearby primary health care center on same day where his wound was washed with water. He received first dose of anti-rabies vaccine and was referred to a tertiary care center for immunoglobulin because of a history of wound bleeding. They did not visit tertiary care center for immunoglobulin as advised. 15 days after exposure on 1st January 2021 the patient presented with unusual behavior like fear of water and tremor. On examination his pupils were found dilated and he was referred to isolation ward of tertiary care center. Based on the history of animal bites and clinical signs, the patient was diagnosed as probable case of rabies. The patient eventually died within 24 hours of admission. Such kind of incident shows that there is lack of awareness regarding rabies in community. In this case, if the patient had completed the anti-rabies vaccination schedule and visited a higher centre on time for immunoglobulin, death could have been avoided. Mortality due to rabies can be prevented by raising public awareness about immunization.

CELL CULTURE AS THE MOST CERTAIN WAY OF DIAGNOSIS IN RABIES INFECTION

Rabies is a zoonotic disease that causes progressive and fatal inflammation of the brain and spinal cord. This disease is still widespread in the world and is a social and economic burden in many countries. Rabies is estimated to cause 60.000 human deaths annually in over 150 countries, with 95% of cases occurring in Africa and Asia. Several countries in Southeast Asia, including Indonesia, have become one of the endemic areas for rabies. The diagnosis of rabies infection in animals and humans can be made by histopathology, virus cultivation, serology, and virus antigen detection This paper discusses cell culture as a method in the diagnosis of rabies. This paper is a literature review through a literature search in scientific journals and research reports that explains the various studies on the isolation of Rabies virus in cell culture, cell types used, and the technique in diagnosing Rabies infection in cell culture. The diagnosis of rabies can be made by neuroblastoma cells, BHK-21 cell lines, HEK-293 cell lines, and others. It can be concluded that the diagnosis of Rabies virus can be done on several cell lines and needs to be followed by other tests. The nature of rabies disease dictates that laboratory tests be standardized, rapid, sensitive, specific, economical, and reliable.

The Spread of Rabies Among Dogs in Pranburi District, Thailand: A Metapopulation Modeling Approach

Rabies, a deadly zoonotic disease, is causing serious public health problems worldwide. Dogs are considered the main reservoir for rabies infection in humans. A better understanding of the dissemination of rabies in the dog population is crucial. The present study, therefore, aimed to explore the subpopulation of dogs roaming around rabies-outbreak areas and the model of its possible spread. We used a Cross-K function to investigate the spatial clustering between the locations of dog rabies cases and the feeding points of a stray dog feeder. We then observed the social interaction of dogs in a community using a metapopulation analysis and further simulated the possible spread of rabies within this population. We found that the reported rabies cases were spatially clustered with the routes of the dog feeder. Therefore, more sustainable stray dog management is required. Based on our community dog observations, we found 20 groups comprising 222 dogs with an average of 11 dogs per group. In our infectious model, we suggested that 47.7% of dogs are likely to be infected in a year if no interventions are implemented. Therefore, the veterinary authorities should rigorously strengthen their rabies prevention and control strategies to protect both animal and human health.

Reaching the zero by 30 dog-mediated human rabies goal

It is unacceptable that as we advance into the 21st century rabies is still a threat to humans and animals alike. Given public health interventions that focus solely on disease prevention in humans have no effect on the reduction of infection in the reservoir hosts, the most effective way to combat human rabies infection is to control the disease transmission by mass vaccination of the animal source, e.g. dogs and wildlife1. This short communication focuses on the global strategic target to end human deaths from dog-mediated rabies by 20302 in line with the Sustainable Development Goals by providing recent updates on World Health Organization (WHO) and OIE guidelines3–5 and recommendations as well as highlighting Australian rabies research activities to prevent an incursion of rabies into the country.

A community-based knowledge, attitude, and practice survey on rabies among cattle owners in selected areas of Bhutan.

Rabies remains a disease of significant zoonotic and economic concern in rabies endemic areas of Bhutan. Rabies outbreaks in livestock threaten the livelihoods of subsistence farming communities and pose a potential public health threat. As a part of identifying approaches to prevent rabies in cattle, a Knowledge, Attitude, and Practice (KAP) survey was conducted among cattle owners in selected rural areas of the southern rabies high-risk zone and low-risk zone in eastern Bhutan. Between March and April 2017, 562 cattle owners (281 in the east and 281 in the south) were interviewed using a questionnaire. Eighty-eight percent of the participants had heard of rabies but only 39% of the participants who had heard of rabies had adequate knowledge about rabies. Multivariable logistic regression analysis showed that residing in the south [OR = 9.25 (95% CI: 6.01–14.53)] and having seen a rabies case [OR = 2.46 (95% CI: 1.6–3.82)] were significantly associated with having adequate knowledge about rabies. Based on our scoring criteria, 65% of the total participants who had heard of rabies had a favorable attitude towards rabies control and prevention programs. The participants residing in the east were two times more likely to have a favourable attitude than their counterparts in the south [OR = 2.08 (95% CI: 1.43–3.05)]. More than 70% of the participants reported engaging in farm activities such as examining the oral cavity of sick cattle and assisting cattle during parturition. Only 25% of the participants reported using personal protective equipment while undertaking these activities. Despite a high level of rabies awareness, we observed that there is a lack of comprehensive knowledge about rabies regarding susceptible hosts, transmission routes, the health outcome of rabies infection in humans, and appropriate health-seeking behaviours. This study highlights the need to strengthen rabies education programs in rural communities to address the knowledge gaps that have been identified.

Determinants of health seeking behavior of animal bite victims in rabies endemic South Bhutan: a community-based contact-tracing survey

BackgroundDog bites are the main source of rabies infection and death in humans, contributing up to 99% of all cases. We conducted a contact-tracing study to evaluate the health seeking and treatment compliance behaviors of people following potential exposure to rabies in rabies endemic south Bhutan.MethodsUsing information from the rabies post exposure prophylaxis (PEP) register, animal-exposed victims who had visited five hospitals in south Bhutan between January and March 2017 were traced and further data were collected from them using a structured questionnaire. A snowballing technique was used to identify victims who did not seek PEP.The survey was conducted between April and June 2017. Logistic regression was performed to assess factors associated with PEP-seeking and compliance behavior by the victims.ResultsAmongst 630 who reported to hospitals, 70% (444) of people could be traced and additional 8% (39) who did not seek PEP was identified through contact tracing. Therefore, a total of 483 people were interviewed. Seventy one percent (344/483) of exposure were due to animal bites of which 80% (365/455) were considered to be provoked incidents. Common reasons for not seeking health care included assumptions that risks of infection were minor if bitten by an owned or vaccinated dog. The victims who are male (OR: 0.36; 95% CI: 0.16–0.77) and educated (OR: 0.41; 95% CI: 0.17–0.96) were less likely to seek PEP, while those that experienced unprovoked bite (OR: 5.10; 95% CI: 1.20–21.77) were more likely to seek PEP in the hospitals. Overall, 82% of the victims sought PEP from the hospitals within 24 h after exposure. Eighty three percent completed the PEP course prescribed by the physician. The respondents living in urban areas (OR: 2.67; 95% CI: 1.34–5.30) were more likely to complete the prescribed PEP course than rural dwellers.ConclusionsThere is high risk of rabies infection in southern Bhutan. It is critical to bridge knowledge gaps and dispel existing myths which will help to improve PEP seeking and compliance behavior of people exposed to rabies infection from animals. A risk-based advocacy program is necessary to prevent dog-mediated human rabies deaths.

Fatal case of human rabies infection: A case report

Rationale: Rabies, as an acute viral disease of the mammal’s central nervous system (CNS), with a high mortality rate, is transmitted to humans through the bite of a rabid animals, especially canine and feline. Patient concerns: An Afghan man, aged 50 years was bitten by a fox in a farm around the Qom-Tehran road, Central Iran in 2018. The patient visited the doctor after the bite, however the period between incidence and hospital visit was not established and no indication was given whether the bite site injury was thoroughly washed. The patient was neither referred to the health center for vaccination (post-exposure prophylaxis) nor an effective therapeutic measures was applied. Forty-five days post-exposure, the patient presented with symptoms such as headache, fever, tingling and burning sensation and was referred to the Centers for Disease Control and Prevention (CDC) unit of Qom Provincial Health Center. Diagnosis: Rabies infection. Interventions: Forty-five days after the animal bite, in CDC of Qom Health Center, he received rabies post-exposure prophylaxis treatment was referred to an infectious diseases physician. Based on the history of animal bites, the patient was classified as probable case of rabies. The clinical symptoms of rabies appeared in patient after hospitalization. Outcomes: Ultimately the patient died in hospital 4 days after hospitalization (50 days after the occurrence of animal bite). After referring the patient to the CDC, the patient’s saliva (0.5-1 mL) was sampled three times every 3-6 hours and tested by PCR. Human rabies was confirmed by Department of Virology in the Pasteur Institute of Iran. Lessons: Physicians and clinicians have responsibilities to be critical in observations and take prompt actions in case of animal bites, as rabies usually develops within 7 to 14 days, and delayed intervention after the onset of symptoms, vaccine and serum injections cannot lead to the survival of the patient.

Rabies in a Dog Imported from Egypt — Connecticut, 2017

In 2007, the United States successfully eliminated canine rabies virus variant. Globally, however, dogs remain the principal source of human rabies infections. Since 2007, three cases of canine rabies virus variant were reported in dogs imported into the United States, one each from India (2007), Iraq (2008), and Egypt (2015) (1–3). On December 20, 2017, a dog imported into the United States from Egypt was identified with rabies, representing the second case from Egypt in 3 years. An Egyptian-based animal rescue organization delivered four dogs from Cairo, Egypt, to a flight parent (a person solicited through social media, often not affiliated with the rescue organization, and usually compensated with an airline ticket), who transported the dogs to the United States. The flight parent arrived at John F. Kennedy International Airport (JFK) in New York City and, via transporters (persons who shuttle dogs from one state to another), transferred the dogs to foster families; the dogs ultimately were adopted in three states. The Connecticut Department of Public Health Laboratory (CDPHL) confirmed the presence of a canine rabies virus variant in one of the dogs, a male aged 6 months that was adopted by a Connecticut family. An investigation revealed the possibility of falsified rabies vaccination documentation presented on entry at JFK, allowing the unvaccinated dog entry to the United States. This report highlights the continuing risk posed by the importation of dogs inadequately vaccinated against rabies from high-risk countries and the difficulties in verifying any imported dog’s health status and rabies vaccination history.

Long term trends and spatial distribution of animal bite injuries and deaths due to human rabies infection in Uganda, 2001-2015.

BackgroundIn the absence of accurate data on trends and the burden of human rabies infection in developing countries, animal bite injuries provide useful information to bridge that gap. Rabies is one of the most deadly infectious diseases, with a case fatality rate approaching 100%. Despite availability of effective prevention and control strategies, rabies still kills 50,000 to 60,000 people worldwide annually, the majority of whom are in the developing world. We describe trends and geographical distribution of animal bite injuries (a proxy of potential exposure to rabies) and deaths due to suspected human rabies in Uganda from 2001 to 2015.MethodsWe used 2001–2015 surveillance data on suspected animal bite injuries, collected from health facilities in Uganda. To describe annual trends, line graphs were used and linear regression tested significance of observed trends at P<0.05. We used maps to describe geographical distribution of animal bites by district.ResultsA total of 208,720 cases of animal bite injuries were reported. Of these, 27% were in Central, 22% in Eastern, 27% in Northern and 23% in Western regions. Out of 48,720 animal bites between 2013 and 2015, 59% were suffered by males and 81% were persons aged above 5 years. Between 2001 and 2015, the overall incidence (per 100,000 population) of animal bites was 58 in Uganda, 76 in Northern, 58 in Central, 53 in Western and 50 in Eastern region. From 2001 to 2015, the annual incidence (per 100,000 population) increased from 21 to 47 (P = 0.02) in Central, 27 to 34 (P = 0.04) in Eastern, 23 to 70 (P = 0.01) in Northern and 16 to 46 (P = 0.001) in Western region. A total of 486 suspected human rabies deaths were reported, of which 29% were reported from Eastern, 28% from Central, 27% from Northern and 17% from Western region.ConclusionAnimal bite injuries, a potential exposure to rabies infection, and mortality attributed to rabies infection are public health challenges affecting all regions of Uganda. Eliminating rabies requires strengthening of rabies prevention and control strategies at all levels of the health sector. These strategies should utilize the “One Health” approach with strategic focus on strengthening rabies surveillance, controlling rabies in dogs and ensuring availability of post exposure prophylaxis at lower health facilities.

Strategies for controlling dog-mediated human rabies in Asia: using 'One Health' principles to assess control programmes for rabies.

Over 99% of human rabies cases in endemic areas are transmitted by dogs. Without the elimination of dog rabies, it is not easy to reduce human rabies infection. Controlling dog rabies, especially in ownerless or free-roaming dogs, is critical if we are to decrease the rate of human rabies infection. There are several components in a strategy to eliminate dog-mediated rabies in Asia. Each government must make sure that rabies is either a reportable disease or a notifiable disease and enforce the reporting requirements accordingly. They must also focus on organising and operating special rabies control committees that work with relevant agencies under the 'One Health' banner. They should also implement a national rabies control programme that includes mass dog vaccination, laboratory-based surveillance, stable budget allocation, a rapidreporting system, management of dog populations, international cooperation, prevention of animal introductions from other countries, and risk assessment to analyse the programme's weaknesses. As several developed countries have shown, an effective rabies control strategy leads to rabies-free status. In the Republic of Korea, human rabies has not occurred since 2004, and there have not been any confirmed cases of dog rabies or cases of rabies in wild animals, including raccoon dogs, since 2014. The successful implementation of the key strategies used to eliminate rabies in the Republic of Korea will enable other Asian countries to eliminate dog-mediated human rabies.

Epidemiological characteristics and post-exposure prophylaxis of human rabies in Chongqing, China, 2007\u20132016

BackgroundAccording to the global framework of eliminating human rabies, China is responding to achieve the target of zero human death from dog-mediated rabies by 2030. Chongqing is the largest municipality directly under central government in China. We described the epidemiological characteristics and post-exposure prophylaxis (PEP) of human rabies in this area, in order to provide a reliable epidemiology basis for further control and prevention of human rabies.MethodsThe most updated epidemiological data for human rabies cases from 2007 to 2016 in Chongqing were collected from the National Disease Reporting Information System. A standardized questionnaire was applied to the human rabies cases or family members of cases as proxy to investigate the PEP situation.ResultsA total of 809 fatal human rabies cases were reported in Chongqing from 2007 to 2016. There was a trend of gradual annual decline about number of cases from 2007 to 2013, followed by stable levels until 2016. Rabies was mostly reported in summer and autumn; a majority of cases were noted in farmers (71.8%), especially in males (65.3%). The cases aged 35–74 and 5–14 years old accounted for 83.8% of all the cases. We collected information of 548 human rabies cases’ rabies exposure and PEP situation. Of those, 95.8% of human rabies cases were victims of dog bites or scratch, and 53.3% of these dogs were identified as stray dogs. Only 4.0% of the domestic dogs were reported to have been vaccinated previously. After exposure, 87.8% of the 548 human rabies cases did not seek any medical services. Further investigation showed that none of the 548 cases received timely and properly standardized PEP.ConclusionHuman rabies remains a major public health problem in Chongqing, China. Dogs are the main reservoir and source of human rabies infection. Unsuccessful control of canine rabies and inadequate PEP of cases might be the main factors leading to the serious human rabies epidemic in this area. An integrated “One Health” approach should be encouraged and strengthened in this area; with combined effort it would be possible to achieve the elimination of human rabies in the expected date.

Re-evaluating the effect of Favipiravir treatment on rabies virus infection

There is no antiviral treatment available once clinical disease following rabies virus infection has initiated. Considered a neglected tropical disease, >60,000 human rabies deaths are estimated each year despite the availability of pre- and post-exposure prophylaxis for pre-immunisation or administration following a potential exposure before the onset of clinical disease. Such post-exposure treatments include administration of rabies immunoglobulin (RIG) and vaccination at a distant site to prime a humoral immune response. However, current therapeutic options are limited. Regardless there is a need for molecules that target virus infection following the onset of clinical disease where the outcome of infection is invariably fatal. Numerous molecules have been assessed as potential antivirals against rabies virus (RABV) but with little promise. Favipiravir (T-705) is a broad-spectrum RNA polymerase inhibitor, which has been shown to have antiviral activity against a range of RNA viruses including some against RABV. In the present study, the utility of T-705 has been reassessed in vitro as well as in vivo in a murine model using intraperitoneal administration to investigate any immune protective effect of the molecule. In vitro T-705 effectively reduces RABV replication. However, in vivo, following assessment of various applications of the molecule in both pre- and post-exposure scenarios, the effect was limited. T-705 treatment delayed the onset of clinical signs when virus was delivered intramuscularly at a higher dose (106.8 TCID50/ml) and reduced the number of mice that developed clinical signs when virus was delivered at a lower dose (105.8 TCID50/ml) during the observation period. The day at which treatment commenced did not appear to have a statistically significant effect on the results in either experiment. The use of T-705 as a single biological entity may be limited, however, further work is required to assess the synergistic effect of T-705 as a component of a multi-drug therapy for treating human rabies infections.

Retrospective diagnosis of two rabies cases in humans by high throughput sequencing

BackgroundRabies is prevalent in 150 countries and is definitely found in Russian Federation. The average registered incidence of rabies infection among animals in Russia is 3000 cases per year. At least 500,000 cases of animal bites and scratches are registered in the Russia every year, but only 2–4 cases of rabies infection in humans are reported per year. This relatively low incidence of rabies infection among humans is the result of a well-organized program of rabies surveillance and control as well as the readily available vaccination and immunoglobulin therapies. However, physician awareness of rabies infection in patients with acute encephalopathy is low, and some cases of rabies remain undiagnosed. ObjectivesA retrospective study of autopsy materials from patients who died of encephalitis of unknown etiology in the Astrakhan region of Russia in 2003. Study designA broad-range polymerase chain reaction (PCR) analysis followed by high throughput sequencing were used for the diagnosis. ResultsTwo cases of rabies were detected and subsequently confirmed using a fluorescent antibody test, an enzyme-linked immunosorbent assay (ELISA) and a mouse inoculation test. Two strains of rabies virus were isolated and characterized using virological methods. The entire genome of each strain was sequenced.

Human rabies: still a neglected preventable disease in Nigeria.

Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies infections among patients presenting to University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. This was a 10-year (January 1, 2004 to December 31, 2013) observational retrospective study. Case definition of rabies was based on ICD 10 criteria, while relevant clinical data were retrieved from individual folders of registered victims using a semi-structured questionnaire. Data were analyzed using SPSS version 17.0 while the level of statistical significance was set at P < 0.05. A total of 149 cases of dog bites were reported during the period under review, of which 6 (4.0%) had confirmed rabies. Ninety-six (64.4%) cases presented more than 24 h after the bites. Majority of the offending dogs were stray dogs 86 (57.7%), which attacked their victims unprovoked, in 54.6% of cases. Furthermore, most of the bites were from dogs with unknown history of rabies vaccination 72 (52.3%), while the case fatality rate was 100%. All the cases of rabies reported were as a result of bites from stray dogs with unknown history of rabies vaccinations, and the outcome was 100% fatality in all cases. Efforts should be made to create and strengthen awareness campaigns on control of rabies infections through responsible dog ownership including their regular vaccinations as well as provision and use of prompt postexposure prophylaxis in human cases of dog bites at all levels of health care.

Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report

BackgroundHuman rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management.Case presentationA 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen.ConclusionRapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are typical for the clinical course of rabies in humans. Management guided by the Milwaukee protocol is feasible within well-resourced intensive care units, but its role in improving outcome for canine-derived rabies remains theoretical.