Reliable, validated diagnostic tests are critical for rabies control in animals and prevention in people. We present a performance assessment and updates to the LN34 real-time RT-PCR assay for rabies diagnosis in postmortem animal brain samples. In two U.S. laboratories during 2017 to 2022, routine used of the LN34 assay produced excellent diagnostic sensitivity (99.72% to 100%) and specificity (99.99% to 100%) compared to the direct fluorescence antibody test (DFA). Almost all (>90%) DFA indeterminate results caused by non-specific or atypical fluorescence were negative by LN34 testing, representing up to 111 cases where unnecessary post-exposure prophylaxis could be avoided. LN34 assay original primer sequences showed low sensitivity for some rare lyssaviruses. Increased primer concentration combined with new primer formulation showed improved performance for impacted lyssaviruses with no loss in performance across diverse rabies virus variants from clinical samples. The updated LN34 and internal control assays were combined into a single-well LN34 multiplexed (LN34M) format, run at half reagent volumes. The LN34M assay showed similar detection of rabies virus to the singleplexed assay with simplified assay set-up, lower cost, and improved quality controls.

The present report provides a detailed update on rabies epidemiology and events in the United States during 2014 as well as a brief summary of rabies events in 2015. Updates are also provided for Canada and Mexico. | | Rabies is caused by neurotrophic viruses of the genus Lyssavirus. It is almost always fatal once clinical signs develop, but is preventable if appropriate postexposure prophylaxis is administered in a timely manner. The primary route of transmission is through the bite of an infected mammal, but rabies may also be transmitted when fresh saliva from an infected animal comes into contact with a wound or mucous membranes. | | For human patients who have never been vaccinated against rabies, postexposure prophylaxis consists of immediate cleansing of any bite wounds with soap and water, infiltration of the wounds with human rabies immune globulin, and administration of 4 doses of rabies vaccine over the next 14 days.1,2

SUMMARY-During 2012, 49 states and Puerto Rico reported 6,162 rabid animals and 1 human rabies case to the CDC, representing a 2.1% increase from the 6,031 rabid animals and 6 human cases reported in 2011. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,953 raccoons (31.7%), 1,680 bats (27.3%), 1,539 skunks (25.0%), 340 foxes (5.5%), 257 cats (4.2%), 115 cattle (1.9%), and 84 dogs (1.4%). Compared with 2011, there was a substantial increase in the number of rabid cattle reported. One case of rabies involving a human was reported from California after the patient died abroad. The infection was determined to be a result of a rabies virus variant associated with Tadarida brasiliensis, with exposure occurring in California.

We thank the authors for their interest in our study comparing effectiveness of quadrivalent and trivalent inactivated influenza vaccines (IIV4 and IIV3, respectively) against the 2 influenza B lineages (Yamagata and Victoria) from 2013–2014 to 2016–2017 [1]. We found that increasing uptake of IIV4 was not associated with significantly increased protection against influenza B illness overall (VE of 53% [95% confidence interval {CI}, 45%–59%] for IIV4 vs 45% [95% CI, 34%–54%] for IIV3) despite higher effectiveness of IIV4 against the cross-lineage B viruses not included in IIV3 (VE of 56% for IIV4 vs 25% for IIV3) [1]. During the 2019–2020 season, all influenza vaccines distributed in the United States are quadrivalent except for 2 licensed only for use in adults aged ≥ 65 years [2]. Assuming low cross-lineage B virus protection, Reed et al [3] estimated additional public health benefit of quadrivalent vaccines from 1999–2000 to 2008–2009 to be modest reductions in influenza-associated outcomes. Because recent data from the US Flu VE Network [1] and Canada [4] over multiple seasons showed low to modest IIV3 cross-lineage protection against influenza B, an updated analysis of the public health impact and cost-benefit of quadrivalent vs trivalent influenza vaccines is possible.

BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017-2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

As ownership of NTP species is increasing, the number and size of outbreaks associated with NTPs in recent years has also increased. Non-traditional pet owners and members of the public who may come into contact with NTPs should be aware of the potential health risks and understand that even apparently healthy animals can transmit pathogens. The recommendations in this Compendium provide public health professionals, animal health professionals, industry, and healthcare providers (including veterinarians, physicians, and allied health professionals) resources to prevent disease transmission and spread. These recommendations aim to benefit all partners by preventing human infections,maintaining animal health and welfare, and providing economic benefits. © 2022 Mary Ann Liebert Inc.. All rights reserved.

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.

Condori Rene E, Aragon Adam, Breckenridge Mike, Pesko Kendra, Mower Kerry, Ettestad Paul, Melman Sandra, Velasco-Villa Andres, Orciari Lillian A, Yager Pamela, Streicker Daniel G, Gigante Crystal M, Morgan Clint, Wallace Ryan, Li Yu. Emerging infectious diseases 2022 28(6) 1137-1145

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

On November 3, 2018, the Utah Department of Health (UDOH) was notified of a suspected human rabies case in a man aged 55 years. The patient's symptoms had begun 18 days earlier, and he was hospitalized for 15 days before rabies was suspected. As his symptoms worsened, he received supportive care, but he died on November 4. On November 7, a diagnosis of rabies was confirmed by CDC. This was the first documented rabies death in a Utah resident since 1944. This report summarizes the patient's clinical course and the subsequent public health investigation, which determined that the patient had handled several bats in the weeks preceding symptom onset. Public health agencies, in partnership with affected health care facilities, identified and assessed the risk to potentially exposed persons, facilitated receipt of postexposure prophylaxis (PEP), and provided education to health care providers and the community about the risk for rabies associated with bats. Human rabies is rare and almost always fatal. The findings from this investigation highlight the importance of early recognition of rabies, improved public awareness of rabies in bats, and the use of innovative tools after mass rabies exposure events to ensure rapid and recommended risk assessment and provision of PEP.

As a neglected zoonotic disease, rabies causes approximately 5.9 x 10(4) human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.

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.

Human rabies is an encephalitic disease transmitted by animals infected with lyssaviruses. The most common lyssavirus that causes human infection is rabies virus (RABV), the prototypic member of the genus. The incubation period of RABV in humans varies from few weeks to several months in some instances. During this prodromal period, neither antibodies nor virus is detected. Antibodies, antigen and nucleic acids are detectable only after the onset of encephalitic symptoms, at which point the outcome of the disease is nearly 100% fatal. Hence, the primary intervention for human RABV exposure and subsequent post-exposure prophylaxis relies on testing animals suspected of having rabies. The most widely used diagnostic tests in animals focus on antigen detection, RABV-encoded nucleoprotein (N protein) in brain tissues. N protein accumulates in the cytoplasm of infected cells as large and granular inclusions, which are visualized in infected brain tissues by immuno-microscopy using anti-N protein antibodies. In this study, we explored a mass spectrometry (MS) based method for N protein detection without the need for any specific antibody reagents or microscopy. The MS-based method described here is unbiased, label-free, requires no amplification and determines any previously sequenced N protein available in the database. The results demonstrate the ability of MS/MS based method for N protein detection and amino acid sequence determination in animal diagnostic samples to obtain RABV variant information. This study demonstrates a potential for future developments of rabies diagnostic tests based on MS platforms.

Rabies is a fatal encephalitic disease in humans and animals caused by lyssaviruses, most commonly rabies virus (RABV). Human antemortem diagnosis of rabies is a complex process involving multiple sample types and tests for the detection of antibodies, antigen (protein), and nucleic acids (genomic RNA). Serological diagnosis of human rabies includes the detection of either neutralizing or binding antibodies in the cerebrospinal fluid (CSF) or serum samples from unimmunized individuals without prior rabies vaccination or passive immunization with purified immunoglobulins. While neutralizing antibodies are targeted against the surface-expressed glycoprotein (G protein), binding antibodies to viral antigens are predominantly against the nucleoprotein (N protein), although there can be antibodies against all RABV-expressed proteins. To determine N protein-specific antibody responses in the CSF and serum during RABV infection, we developed an enzyme-linked immunosorbent assay (ELISA) with purified recombinant N protein expressed in E. coli. N protein-specific immunoglobulin (Ig) subtypes IgG and IgM were detected in the CSF or serum of previously diagnosed human rabies cases. In addition, anti-N protein seroconversion was demonstrated over the course of illness in individual rabies cases. We compared the N protein ELISA results to those of an indirect fluorescent antibody (IFA) test, the current binding antibody assay used in diagnosis, and show that our ELISA is consistent with the IFA test. Sensitivity and specificity of the N protein ELISA ranged from 78.38-100% and 75.76-96.77% with respect to the IFA results. Our data provide evidence for the use of an N protein ELISA as an additional option for the detection of RABV-specific IgG or IgM antibodies in human CSF or serum specimens.

Rabies is a fatal zoonotic disease that requires fast, accurate diagnosis to prevent disease in an exposed individual. The current gold standard for post-mortem diagnosis of human and animal rabies is the direct fluorescent antibody (DFA) test. While the DFA test has proven sensitive and reliable, it requires high quality antibody conjugates, a skilled technician, a fluorescence microscope and diagnostic specimen of sufficient quality. The LN34 pan-lyssavirus real-time RT-PCR assay represents a strong candidate for rabies post-mortem diagnostics due to its ability to detect RNA across the diverse Lyssavirus genus, its high sensitivity, its potential for use with deteriorated tissues, and its simple, easy to implement design. Here, we present data from a multi-site evaluation of the LN34 assay in 14 laboratories. A total of 2,978 samples (1,049 DFA positive) from Africa, the Americas, Asia, Europe, and the Middle East were tested. The LN34 assay exhibited low variability in repeatability and reproducibility studies and was capable of detecting viral RNA in fresh, frozen, archived, deteriorated and formalin-fixed brain tissue. The LN34 assay displayed high diagnostic specificity (99.68%) and sensitivity (99.90%) when compared to the DFA test, and no DFA positive samples were negative by the LN34 assay. The LN34 assay produced definitive findings for 80 samples that were inconclusive or untestable by DFA; 29 were positive. Five samples were inconclusive by the LN34 assay, and only one sample was inconclusive by both tests. Furthermore, use of the LN34 assay led to the identification of one false negative and 11 false positive DFA results. Together, these results demonstrate the reliability and robustness of the LN34 assay and support a role for the LN34 assay in improving rabies diagnostics and surveillance.

OBJECTIVE To describe rabies and rabies-related events occurring during 2016 in the United States. DESIGN Observational study based on passive surveillance data. ANIMALS All animals submitted for rabies testing in the United States during 2016. PROCEDURES State and territorial public health programs provided data on animals submitted for rabies testing in 2016. Data were analyzed temporally and geographically to assess trends in domestic and sylvatic animal rabies cases. RESULTS During 2016, 50 states and Puerto Rico reported 4,910 rabid animals to the CDC, representing a 10.9% decrease from the 5,508 rabid animals reported in 2015. Of the 4,910 cases of animal rabies, 4,487 (91.4%) involved wildlife. Relative contributions by the major animal groups were as follows: 1,646 (33.5%) bats, 1,403 (28.6%) raccoons, 1,031 (21.0%) skunks, 313 (6.4%) foxes, 257 (5.2%) cats, 70 (1.4%) cattle, and 58 (1.2%) dogs. There was a 4.6% decrease in the number of samples submitted for testing in 2016, compared with the number submitted in 2015. No human rabies deaths were reported in 2016. CONCLUSIONS AND CLINICAL RELEVANCE Laboratory testing of animals suspected to be rabid remains a critical public health function and continues to be a cost-effective method to directly influence human rabies postexposure prophylaxis recommendations.

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody...test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

The introduction of rabies virus (RABV) to barrier islands, which are often popular tourist destinations with resource-rich habitats and connectivity and proximity to the mainland, is especially concerning because it can easily become endemic due to factors like dense rabies-vector populations (e.g., raccoons [ Procyon lotor]), high inter- and intraspecies contact rates, and anthropogenic activities such as supplemental feeding of feral cats ( Felis catus). In January 2013, a neurologic raccoon found on the Jekyll Island (JI), Georgia causeway tested positive for rabies. Mortality investigations of 29 raccoons have been conducted between December 2012-May 2017. The two most-common diagnoses were RABV ( n=11) and canine distemper virus (CDV; n=8). Parvoviral enteritis was diagnosed in four raccoons but no coinfections were diagnosed. There was no apparent seasonality for rabies cases, but all CDV cases occurred in spring-fall. Most (64%) rabies submissions came from residential or recreational use areas located near feral cat feeding stations. Jekyll Island is a popular destination where tourists engage in numerous outdoor activities which facilitate human-wildlife interactions. Concerns regarding public and animal health highlight the importance of rabies surveillance, prevention, and control on islands. This is the first report of rabies on JI and emphasizes the importance of disease investigations because the assumption that neurologic raccoons have CDV, an endemic pathogen, can miss the establishment of novel pathogens such as RABV.

On April 3, 2017, two Florida residents consumed part of the same prepackaged salad before reportedly discovering the partial remains of a bat carcass in the salad. Bats are known reservoirs for rabies virus, which causes rabies disease in both animals and humans (1). The persons who ate the salad contacted the Florida Department of Health (FLDOH), which notified CDC’s Poxvirus and Rabies Branch. CDC and FLDOH determined that the immediate concern was for potential rabies virus exposure, because approximately 6% of bats submitted to U.S. public health departments annually test positive for rabies virus (2,3). | Although percutaneous exposures are more likely to result in successful transmission of rabies virus to humans (1), transmission can occur when infectious material, such as saliva or nervous tissue from an infected animal, comes into direct contact with human mucosa (2). Infection with rabies virus causes an acute, progressive encephalitis that is nearly always fatal once clinical signs have begun. The disease is preventable if exposed persons receive timely postexposure prophylaxis (PEP), which includes human rabies immunoglobulin and 4 doses of inactivated rabies vaccine administered over 14 days (4).

OBJECTIVE To describe rabies and rabies-related events occurring during 2015 in the United States. DESIGN Observational study based on passive surveillance data. ANIMALS All animals submitted for rabies testing in the United States during 2015. PROCEDURES State and territorial public health programs provided data on animals submitted for rabies testing in 2015. Data were analyzed temporally and geographically to assess trends in domestic and sylvatic animal rabies cases. RESULTS During 2015, 50 states and Puerto Rico reported 5,508 rabid animals to the CDC, representing an 8.7% decrease from the 6,033 rabid animals reported in 2014. Of the 5,508 cases of animal rabies, 5,088 (92.4%) involved wildlife. Relative contributions by the major animal groups were as follows: 1,704 (30.9%) bats, 1,619 (29.4%) raccoons, 1,365 (24.8%) skunks, 325 (5.9%) foxes, 244 (4.4%) cats, 85 (1.5%) cattle, and 67 (1.2%) dogs. There was a 4.1% decrease in the number of samples submitted for testing in 2015, compared with the number submitted in 2014. Three human rabies deaths were reported in 2015, compared with only 1 in 2014. A 65-year-old man in Massachusetts was bitten by a rabid dog while abroad. A 77-year-old woman in Wyoming had contact with a bat. A 54-year-old man in Puerto Rico was bitten by a mongoose. The only connection among these 3 cases was that none received postexposure prophylaxis. CONCLUSIONS AND CLINICAL RELEVANCE Laboratory testing of animals suspected to be rabid remains a critical public health function and continues to be a cost-effective method to directly influence human rabies postexposure prophylaxis recommendations. (J Am Vet Med Assoc 2017;250:1117-1130).

The direct fluorescent antibody test (DFA), is performed in all rabies reference laboratories across Latin America and the Caribbean (LAC). Despite DFA being a critical capacity in the control of rabies, there is not a standardized protocol in the region. We describe the results of the first inter-laboratory proficiency exercise of national rabies laboratories in LAC countries as part of the regional efforts towards dog-maintained rabies elimination in the American region. Twenty three laboratories affiliated to the Ministries of Health and Ministries of Agriculture participated in this exercise. In addition, the laboratories completed an online questionnaire to assess laboratory practices. Answers to the online questionnaire indicated large variability in the laboratories throughput, equipment used, protocols availability, quality control standards and biosafety requirements. Our results will inform actions to improve and harmonize laboratory rabies capacities across LAC in support for the regional efforts towards elimination of dog-maintained rabies.

On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).

On September 18, 2014, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected rabies case in a Missouri resident. The patient, a man aged 52 years, lived in a rural, deeply wooded area, and bat sightings in and around his home were anecdotally reported. Exposure to bats poses a risk for rabies. After two emergency department visits for severe neck pain, paresthesia in the left arm, upper body tremors, and anxiety, he was hospitalized on September 13 for encephalitis of unknown etiology. On September 24, he received a diagnosis of rabies and on September 26, he died. Genetic sequencing tests confirmed infection with a rabies virus variant associated with tricolored bats. Health care providers need to maintain a high index of clinical suspicion for rabies in patients who have unexplained, rapidly progressive encephalitis, and adhere to recommended infection control practices when examining and treating patients with suspected infectious diseases.

BACKGROUND: The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant procedures). We describe their clinical management. METHODS: Because the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. RESULTS: All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. CONCLUSIONS: The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies.

BACKGROUND: Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies. METHODS: Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry. RESULTS: The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and CSF was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem. CONCLUSIONS:: Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the CNS by 76 days, but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain.

During 2013, 53 reporting jurisdictions reported 5,865 rabid animals and 3 human rabies cases to the CDC, representing a 4.8% decrease from the 6,162 rabid animals and 1 human case reported in 2012. Ninety-two percent of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,898 raccoons (32.4%), 1,598 bats (27.2%), 1,447 skunks (24.7%), 344 foxes (5.9%), 247 cats (4.2%), 86 cattle (1.5%), and 89 dogs (1.5%). One human case was reported from Maryland. The infection was determined to have been transmitted via organ transplantation. Infection in the organ donor, a North Carolina resident, was retrospectively diagnosed. Both the organ donor and the organ recipient were infected with the raccoon rabies virus variant. The third human case, reported by Texas, involved a Guatemalan resident who was detained while crossing the US border. The infection was determined to be caused by a canine rabies virus variant that circulates in Central America.

Eight years after emigrating from Brazil, an otherwise healthy man developed rabies. An exposure prior to immigration was reported. Genetic analysis revealed a canine rabies virus variant found only in the patient's home country, and the patient had not traveled internationally since immigrating to the United States. We describe how epidemiological, phylogenetic, and viral sequencing data provided confirmation that rabies encephalomyelitis may present after a long, multiyear incubation period, a consideration that previously has been hypothesized without the ability to exclude a more recent exposure. Accordingly, rabies should be considered in the diagnosis of any acute encephalitis, myelitis, or encephalomyelitis.

IMPORTANCE: 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. OBJECTIVES: 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. DESIGN: 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. MAIN OUTCOMES AND MEASURES: Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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.