Rabies Virus Exposure Research Articles

Evidences of non-lethal rabies virus exposure in free-ranging wild carnivores from Brazilian Pampa

Evidences of non-lethal rabies virus exposure in free-ranging wild carnivores from Brazilian Pampa

Modelling modifiable factors associated with the probability of human rabies deaths among self-reported victims of dog bites in Abuja, Nigeria.

Canine-mediated rabies kills tens of thousands of people annually in lesser-developed communities of Asia, Africa, and the Americas, primarily through bites from infected dogs. Multiple rabies outbreaks have been associated with human deaths in Nigeria. However, the lack of quality data on human rabies hinders advocacy and resource allocation for effective prevention and control. We obtained 20 years of dog bite surveillance data across 19 major hospitals in Abuja, incorporating modifiable and environmental covariates. To overcome the challenge of missing information, we used a Bayesian approach with expert-solicited prior information to jointly model missing covariate data and the additive effects of the covariates on the predicted probability of human death after rabies virus exposure. Only 1155 cases of dog bites were recorded throughout the study period, out of which 4.2% (N = 49) died of rabies. The odds for risk of human death were predicted to decrease among individuals who were bitten by owned dogs compared to those bitten by free-roaming dogs. Similarly, there was a predicted decrease in the probability of human death among victims bitten by vaccinated dogs compared to those bitten by unvaccinated dogs. The odds for the risk of human death after bitten individuals received rabies prophylaxis were predicted to decrease compared to no prophylaxis. We demonstrate the practical application of a regularised Bayesian approach to model sparse dog bite surveillance data to uncover risk factors for human rabies, with broader applications in other endemic rabies settings with similar profiles. The low reporting observed in this study underscores the need for community engagement and investment in surveillance to increase data availability. Better data on bite cases will help to estimate the burden of rabies in Nigeria and would be important to plan effective prevention and control of this disease.

Predictors of Delay in Seeking Post-Exposure Prophylaxis in Older Adults with Animal Bite Injuries: A Population-Based Study

Introduction: Animal bites are of the major health threats. Delayed post-exposure prophylaxis (PEP), especially in frail older people, may lead to mortal risks in this age group. The aim of this study was to investigate the pattern of delayed PEP in animal-bites injuries and to identify its contributing factors in older people of Tabriz city, Iran. Methods: In this cross-sectional study, the census method was used to obtain data from health records of older adults who were referred to Tabriz's Rabies Treatment Center between March 2013 and March 2018. The delay was defined as starting PEP longer than 24 hours after a suspected rabies virus exposure. The relations between delayed PEP and each of the predictors were investigated using the chi-square test in univariate analysis. The decision tree model was applied to predict the delay time of PEP. Results: A total of 322 older people with a mean age of 67.62 ± 7.18 were studied. In all, 31.7 % of the older persons victims who were bitten by an animal had a delayed PEP. Urban victims (34.1%) compared to rural (16.3 %), stray animal victims (42.0 %) compared to an owned animal-bite victim 24.6 %, all other animal bite-related victims (39.9 %) compared to dog-bite injuries (23.8%) experienced a higher frequency of delayed PEP. The decision tree revealed that animal ownership status, animal status, and animal species were the most important factors for predicting delayed PEP (p < 0.001). Conclusion: The possibility of delayed PEP in older adults bites victims, increased if the animal was ownerless and escaped. A reasonable approach to tackle this issue might be to conduct larger population studies in the future.

Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019-2020.

Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free.

Shared Odds of Borrelia and Rabies Virus Exposure in Serbia.

Lyme borreliosis (LB) is the most common tick-borne disease in Serbia and other European countries. Rabies is a fatal zoonosis distributed worldwide and is caused by the rabies virus. Professionals at risk of rabies—including veterinarians, hunters, communal service workers, and forestry workers—overlap with some professions at a higher risk of exposure to tick bites and tick-borne pathogen infections. We hypothesized that individuals identified by the public health system as at risk of rabies virus infection, and consequently vaccinated against rabies virus, also share a higher likelihood of Borrelia exposure. To test our hypothesis, a case-control study was carried out during 2019 in Serbia to determine the seroprevalence of anti-Borrelia antibodies in two case groups (individuals at risk and vaccinated against rabies virus) and a control group (individuals without risk of rabies). Individuals vaccinated against rabies following either “pre-exposure protocol” (PrEP, n = 58) or “post-exposure protocol” (PEP, n = 42) were considered as rabies risk groups and healthy blood donors (n = 30) as the control group. The results showed higher Borrelia seroprevalence in PrEP (17.2%; 10/58) and PEP (19.0%; 8/42) groups compared with the control group (6.67%; 2/30). Furthermore, odds ratio (OR) analysis showed that risk of rabies (in either the PrEP (OR = 2.91) or PEP (OR = 3.29) groups) is associated with increased odds of being seropositive to Borrelia. However, the difference in Borrelia seroprevalence between groups was not statistically significant (Chi-square (χ²) test p > 0.05). The shared odds of LB and rabies exposure found in this study suggest that, in countries where both diseases occur, the common citizen can be at risk of both diseases when in a risky habitat. These findings are important to guide physicians in targeting high-risk groups, and diagnose LB, and to guide decision-makers in targeting control and prevention measures for both infections in risk areas.

Rabies Virus Exposure in Wild Lowland Tapirs (Tapirus terrestris) from Three Brazilian Biomes.

We evaluated the presence of antibodies for rabies virus in 177 serum samples from 125 wild lowland tapirs (Tapirus terrestris) from three different Brazilian biomes. The rapid fluorescent focus inhibition test was performed. No antibody titers suggesting the circulation of the rabies virus in tapir habitat were detected.

Temporal patterns of vampire bat rabies and host connectivity in Belize

In the Neotropics, vampire bats (Desmodus rotundus) are the main reservoir host for rabies, a highly fatal encephalitis caused by viruses in the genus Lyssavirus. Although patterns of rabies virus exposure and infection have been well studied for vampire bats in South America and Mexico, exploring the ecology of vampire bat rabies in other regions is crucial for predicting risks to livestock and humans. In Belize, rabies outbreaks in livestock have increased in recent years, underscoring the need for systematic data on viral dynamics in vampire bats. In this study, we examine the first three years of a longitudinal study on the ecology of vampire bat rabies in northern Belize. Rabies seroprevalence in bats was high across years (29%–80%), suggesting active and endemic virus circulation. Across two locations, the seroprevalence time series per site were inversely related and out of phase by at least a year. Microsatellite data demonstrated historic panmixia of vampire bats, and mark–recapture detected rare but contemporary inter‐site dispersal. This degree of movement could facilitate spatial spread of rabies virus but is likely insufficient to synchronize infection dynamics, which offers one explanation for the observed phase lag in seroprevalence. More broadly, our analyses suggest frequent transmission of rabies virus within and among vampire bat roosts in northern Belize and highlight the need for future spatiotemporal, phylogenetic and ecological studies of vampire bat rabies in Central America.

A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C.

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000–159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs.

Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis

ABSTRACTRabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

Incidence of human rabies virus exposure in northwestern Amhara, Ethiopia

BackgroundClinical Rabies is a widely distributed almost 100% fatal viral zoonotic disease. Most human rabies cases occur in developing countries, especially in Asia and Africa. It can be prevented by immunization, post exposure prophylaxis. Ethiopia is assumed to be among African countries with high incidence of human rabies exposure cases. However, there is limited documented data on the incidence of human rabies exposure in the study area in particular and in Ethiopia in general. Thus, this study aimed to determine the Incidence of Human Rabies Virus exposure in Northwestern Amhara, Ethiopia.MethodsRetrospective cross-sectional study was conducted during August and September, 2017. The study was conducted at Addis Alem Hospital, a district level hospital in Bahir Dar. Data on human rabies exposure cases registered from September 1, 2015 to August 31, 2017 were collected from anti-rabies post exposure prophylaxis registration log book. Data was collected using a structured data collection questionnaire developed for this purpose. Descriptive statistics was used to describe relevant variables.The resultsA total of 924 human rabies exposure cases was recorded. The overall human rabies incidence per 100, 000 population was 6.5 in 2015 and 7.5 in 2016. Males (55.2%, 510/924) and children of age less than fifteen (46.3%, 428/924) were most affected groups. The majority of human rabies exposure cases (71.9%, 664/924) were from rural settings. Dogs were the principal sources of exposure (96.3%) followed by cat (1.5%) and donkey (1.3%). High incidence rate of rabies exposure was reported during spring (360, 39%) and summer (244, 26.4%) seasons. There was significant difference between rural and urban exposure cases (p = 0.001) in respect to the time of arrival to the hospital.ConclusionTaking these into account, a significant proportion of the population was exposed to rabies virus during the study years. There was high human rabies exposure rate in children and in the rural community.This shows the need for organizing preventive and control strategies and to build community awareness.

Epidemiology and surveillance of human animal-bite injuries and rabies post-exposure prophylaxis, in selected counties in Kenya, 2011\u20132016

BackgroundHuman animal-bite injuries are a serious public health problem due to associated risk for rabies virus exposure. Animal-bite injuries especially dog bites are useful indicators for assessing the risk of rabies virus transmission and need for rabies post exposure prophylaxis (PEP). Understanding the epidemiology and surveillance of animal bites and rabies post-exposure prophylaxis is critical in implementing Kenya’s national rabies elimination strategy. We aimed to describe the incidence of human animal-bite injuries, patient/biting animal characteristics, uptake of rabies PEP and factors associated with animal bite incidents.MethodsWe reviewed animal bite records from outpatient and anti-rabies vaccine (ARV) registers of 17 health facilities from five counties. An animal bite was defined as an entry of an animal bite of the class mammal including humans in registers in a person of any age from January 2011 to December 2016. We collected demographic and information on PEP uptake. We calculated descriptive statistics, odds ratios (OR) and 95% confidence interval (CI) to examine factors associated with being an animal bite case-patient. We also calculated incidence of animal bites using health facility catchment population for year 2016 as the denominator.ResultsWe analyzed 7307 records. The median age was 22 years (IQR = 31 years); there were 4019 (55%) male and age < 15 years were 2607 (37%). Dogs accounted for 6720 (93%) of bites of which 78% were owned free-roaming dogs. Of the 5674 (88%) cases that received rabies PEP, 2247 (40%) got at least three-doses. The median time from bite to seeking medical care was 2 days (IQR = 4 days). Being bitten on the head/face (OR = 5.8; CI: 3.3–10.2); being bitten by owned free-roaming dog (OR = 1.7; CI: 1.5–1.9) and being male (OR = 1.4; CI: 1.3–1.5) were significantly associated with being an animal-bite case-patient. Being male, being bitten on head/face and being bitten by owned free-roaming dog remained independently associated with being an animal bite case-patient at multivariable logistic regression. Bite-incidence was 289 bites /100,000 persons among all counties.ConclusionPreventing dog bites would most effectively reduce bite injuries by improving public health education among children below 15 years, encouraging early PEP initiation and completion, development and implementation of responsible dog ownership and animal behaviour educational programmes as well as improving human and veterinary health linkages.

In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants.

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally.

Rabies Virus Exposure of Brazilian Free-ranging Wildlife from Municipalities without Clinical Cases in Humans or in Terrestrial Wildlife.

Rabies is a zoonosis that causes thousands of animal and human deaths worldwide. Serological studies provide information concerning rabies virus circulation among animals and humans. We evaluated the circulation of the rabies virus in wildlife in nine municipalities of São Paulo State, Brazil. We took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. Sera were tested with the use of the rapid fluorescent focus inhibition test (RFFIT) for the detection of rabies virus-neutralizing antibodies (RVNA). The RFFIT was positive in 100% of the samples, with many (81.48%) showing protective titer levels (>0.5 IU/mL) with other samples (18.52%) showing titers representing exposure (<0.5 IU/mL). We report RVNA in novel species (e.g., Alouatta caraya and Tapyrus terrestris). Wild animals were exposed to rabies virus in municipalities without a history of human rabies cases, which demonstrated a need for research to understand the role of these animals in the circulation and transmission of the disease.

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

A Serological Study in Response to People at Occupational Risk of Rabies Virus Exposure in Nepal

A serological study to know the antibody titer against rabies virus in human beings, who are at occupational risk, was conducted in Nepal in 2014. A total 44 serum samples were collected out of which 21 samples were collected from medical professionals (working at Sukraraj Tropical Hospital) and 23 were collected from veterinary professionals (working at Central Veterinary Hospital, Central Veterinary Laboratory and Rabies Vaccine Production Laboratory) in Kathmandu. Among the 44 samples, 4 were collected from unvaccinated persons. The other 40 people sampled were vaccinated with inactivated rabies vaccine. All samples were subjected to the Rabies Fluorescent Focus Inhibition Test (RFFIT) test at Centre for Disease Control and Prevention, Atlanta, USA. The antibody level of 7 persons was found to be less than the WHO recommended titer of 0.5 IU/ml. Six medical professionals and one veterinary professional had a low rabies virus neutralizing antibody titer. The 4 samples collected from unvaccinated persons, and 3 collected from vaccinated persons had a titer below 0.5 IU/ml. This study shows that medical and veterinary professionals who are responsible to nurse or handle rabies patients, rabid animals or rabies virus are still at high risk. This underscores the importance of recommendations for regular serological testing of occupationally exposed individuals and vaccinating booster dose when necessary.

Rabies surveillance in bats in Northwestern State of São Paulo.

Introduction Rabies is an important zoonosis that occurs in mammals, with bats acting as Lyssavirus reservoirs in urban, rural and natural areas. Rabies cases in bats have been recorded primarily in urban areas in Northwestern State of São Paulo since 1998. This study investigated the circulation of rabies virus by seeking to identify the virus in the brain in several species of bats in this region and by measuring rabies-virus neutralizing antibody levels in the hematophagous bat Desmodus rotundus. Methods From 2008 to 2012, 1,490 bat brain samples were sent to the Universidade Estadual Paulista (UNESP) Rabies Laboratory in Araçatuba, and 125 serum samples from vampire bats that were captured in this geographical region were analyzed. Results Rabies virus was detected in the brains of 26 (2%) of 1,314 non-hematophagous bats using the fluorescent antibody test (FAT) and the mouse inoculation test (MIT). None of the 176 hematophagous bat samples were positive for rabies virus when a virus detection test was utilized. Out of 125 vampire bat serum samples, 9 (7%) had levels of rabies virus neutralization antibodies (RVNAs) that were higher than 0.5IU/mL; 65% (81/125) had titers between 0.10IU/mL and 0.5IU/mL; and 28% (35/125) were negative for RVNAs using the simplified fluorescent inhibition microtest (SFIMT) in BHK21 cells. The observed positivity rate (1.7%) was higher than the average positivity rate of 1.3% that was previously found in this region. Conclusions The high percentage of vampire bats with neutralizing antibodies suggests that recent rabies virus exposure has occurred, indicating the necessity of surveillance measures in nearby regions that are at risk to avoid diffusion of the rabies virus and possible rabies occurrences.

Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala

Vampire bat rabies is a public and animal health concern throughout Latin America. As part of an ecological study of vampire bat depredation on cattle in southern Guatemala, we conducted a vaccine seroconversion study among three dairy farms. The main objectives of this cross sectional and cohort study were to understand factors associated with bat bites among cattle, to determine whether unvaccinated cattle had evidence of rabies virus exposure and evaluate whether exposure was related to bat bite prevalence, and to assess whether cattle demonstrate adequate seroconversion to two commercial vaccines used in Guatemala. In 2012, baseline blood samples were collected immediately prior to intramuscular inoculation of cattle with one of two modified live rabies vaccines. Post vaccination blood samples were collected 13 and 393 days later. Sera were tested for rabies virus neutralizing antibodies (rVNA) by the rapid fluorescent focus inhibition test (RFFIT). Across two years of study, 36% (254/702) of inspected cattle presented gross evidence of vampire bat bites. Individual cattle with a bat bite in 2012 were more likely have a bat bite in 2013. Prior to vaccination, 12% (42/350) of cattle sera demonstrated rVNA, but bite status in 2012 was not associated with presence of rVNA. Vaccine brand was the only factor associated with adequate rVNA response of cattle by day 13. However, vaccine brand and rVNA status at day 13 were associated with an adequate rVNA titer on day 393, with animals demonstrating an adequate titer at day 13 more likely to have an adequate titer at day 393. Our findings support stable levels of vampire bat depredation and evidence of rVNA in unvaccinated cattle. Brand of vaccine may be an important consideration impacting adequate rVNA response and long-term maintenance of rVNA in cattle. Further, the results demonstrate that initial response to vaccination is associated with rVNA status over one year following vaccination.

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, Canada, 2001-2012.

In Ontario, Canada, the implementation of an annual rabies control programme in wildlife that began in 1989 resulted in a marked, steady decrease in the number of animal rabies cases. The number of animal rabies cases decreased from 1870 in 1989 to 183 in 2000 (Nunan et al., 2002 Emerg Infect Dis 8, 214). In our study period, the number of animal rabies cases continued to decrease from 210 in 2001 to 28 in 2012. The marked decrease in animal rabies cases since 1989 has resulted in a decrease in the risk of human infection. A concomitant decrease in the number of rabies post-exposure prophylaxis (RPEP) administered was anticipated but failed to occur. The mean rate of RPEP, 13.9 RPEP administered per 100,000 persons, from 2001-2012 was approximately the same as the rate in the 1990 s. Two possible reasons that the rate of RPEP administration has not decreased include strict adherence to RPEP recommendations and administration of RPEP when it is not recommended. A reduction in the number of RPEP administered, consistent with the decrease in the animal rabies cases, would provide some financial savings for the government. Ideally, an increased use of the risk assessment approach in keeping with recent guidelines, rather than adhering to previous prescriptive recommendations for RPEP administration, coupled with a continuing low incidence of animal rabies cases will result in decreased, and yet appropriate, use of RPEP. Consideration should be given to identify how guidelines could be revised to more effectively target high-risk exposures and reduce the administration of RPEP for instances in which the risk of rabies virus exposure is exceedingly low.

A Large‐scale, Rapid Public Health Response to Rabies in an Organ Recipient and the Previously Undiagnosed Organ Donor

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. In response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. An exposure investigation was conducted to determine the source of the organ donor's infection. Over 100 persons from more than 20 agencies spent over 2700 h conducting contact investigations in healthcare, military and community settings. The 564 persons assessed include 417 healthcare workers [5.8% recommended for post-exposure prophylaxis (PEP)], 96 community contacts (15.6% recommended for PEP), 30 autopsy personnel (50% recommended for PEP), and 21 other persons (4.8% recommended for PEP). Donor contacts represented 188 assessed with 20.2% recommended for PEP, compared with 5.6% of 306 recipient contacts recommended for PEP. Human rabies cases result in substantial use of public health and medical resources, especially when diagnosis is delayed. Although rare, clinicians should consider rabies in cases of encephalitis of unexplained aetiology, particularly for cases that may result in organ donation.

Raccoon Rabies Virus Variant Transmission Through Solid Organ Transplantation

The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.