Search

Background: Throughout the Americas, Lyssavirus rabies (RV) perpetuates as multiple variants among bat and mesocarnivore species. Interspecific RV spillover occurs on occasion, but clusters and viral host shifts are rare. The spillover and host shift of a big brown bat (Eptesicus fuscus) RV variant Ef-W1 into mesocarnivores was reported previously on several occasions during 2001-2009 in Flagstaff, Arizona, USA, and controlled through rabies vaccination of target wildlife. During autumn 2021, a new cluster of Ef-W1 RV cases infecting striped skunks (Mephitis mephitis) was detected from United States Department of Agriculture enhanced rabies surveillance in Flagstaff. The number of Ef-W1 RV spillover cases within a short timeframe suggested the potential for transmission between skunks and an emerging host shift. Materials and Methods: Whole and partial RV genomic sequencing was performed to evaluate the phylogenetic relationships of the 2021-2023 Ef-W1 cases infecting striped skunks with earlier outbreaks. Additionally, real-time reverse-transcriptase PCR (rtRT-PCR) was used to opportunistically compare viral RNA loads in brain and salivary gland tissues of naturally infected skunks. Results: Genomic RV sequencing revealed that the origin of the 2021-2023 epizootic of Ef-W1 RV was distinct from the multiple outbreaks detected from 2001-2009. Naturally infected skunks with the Ef-W1 RV showed greater viral RNA loads in the brain, but equivalent viral RNA loads in the mandibular salivary glands, compared to an opportunistic sample of skunks naturally infected with a South-Central skunk RV from northern Colorado, USA. Conclusion: Considering a high risk for onward transmission and spread of the Ef-W1 RV in Flagstaff, public outreach, enhanced rabies surveillance, and control efforts, focused on education, sample characterization, and vaccination, have been ongoing since 2021 to mitigate and prevent the spread and establishment of Ef-W1 RV in mesocarnivores.

Background: After months of few mpox cases, an increase in cases was reported in Chicago during May 2023, predominantly among fully vaccinated (FV) patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination., Methods: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics; mpox vaccine status; and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered the vaccine associated with breakthrough infections., Results: During 18 March-27 June 2023, we identified 49 mpox cases; 57% of these mpox patients were FV. FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3; interquartile range [IQR] = 1-4) versus not fully vaccinated patients (1; IQR = 1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period., Conclusions: Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Background: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies 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 patient contacts., Results: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that 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, 3 (0.9%) warranted PEP., Conclusions: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based 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., Competing Interests: Potential conflicts of interest. R. M. W. reports a role as a board member for the International Rabies Taskforce. R. L. reports roles on the ID Week Program Committee, the Council of State and Territorial Epidemiologists Executive Board, and the National Foundation for Infectious Diseases Executive Board and serving as an associate editor for AAP Red Book (Report of the Committee on Infectious Diseases) and declares support for attending meetings and/or travel from each; payment or honoraria received for their associate editor role was donated to the Minnesota Department of Health. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Competing Interests: Disclosure All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Alyse Kittner reports institutional travel and meeting attendance support from the Water Environment Federation. No other potential conflicts of interest were disclosed.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Alyse Kittner reports institutional travel and meeting attendance support from the Water Environment Federation. No other potential conflicts of interest were disclosed.

Objective: To provide epidemiological information on the occurrence of animal and human rabies in the US during 2021 and summaries of 2021 rabies surveillance for Canada and Mexico., Procedures: State and territorial public health departments and USDA Wildlife Services provided data on animals submitted for rabies testing in 2021. Data were analyzed temporally and geographically to assess trends in domestic animal and wildlife rabies cases., Results: During 2021, 54 US jurisdictions reported 3,663 rabid animals, representing an 18.2% decrease from the 4,479 cases reported in 2020. Texas (n = 456 [12.4%]), Virginia (297 [8.1%]), Pennsylvania (287 [7.8%]), North Carolina (248 [6.8%]), New York (237 [6.5%]), California (220 [6.0%]), and New Jersey (201 [5.5%]) together accounted for > 50% of all animal rabies cases reported in 2021. Of the total reported rabid animals, 3,352 (91.5%) involved wildlife, with bats (n = 1,241 [33.9%]), raccoons (1,030 [28.1%]), skunks (691 [18.9%]), and foxes (314 [8.6%]) representing the primary hosts confirmed with rabies. Rabid cats (216 [5.9%]), cattle (40 [1.1%]), and dogs (36 [1.0%]) accounted for 94% of rabies cases involving domestic animals in 2021. Five human rabies deaths were reported in 2021., Clinical Relevance: The number of animal rabies cases reported in the US decreased significantly during 2021; this is thought to be due to factors related to the COVID-19 pandemic.

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom onset. Fifty-seven persons who met criteria for suspected or known exposure to infectious secretions in this case were advised to consult with a medical provider about the need for rabies PEP in accordance with Advisory Committee on Immunization Practices (ACIP) guidelines (1). Rabies, an acute, progressive neuroencephalitis, is nearly always fatal. Although dogs are the most common source of human rabies deaths worldwide and account for an estimated 59,000 annual cases of human rabies globally (2), bats are the most common source of domestically acquired rabies in the United States and have been implicated in 31 (81.6%) of 38 human infections since 2000 (3). Attempts to prevent death or poor neurologic outcomes once rabies symptoms develop have been largely unsuccessful (4). Administration of rabies PEP, comprising rabies immunoglobulin and a series of doses of rabies vaccine, is critical to preventing rabies after an exposure; enhanced public education about the risk posed by bats, and the availability of PEP to prevent rabies, is needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

School violence is a global public health epidemic, with students with disabilities at a significantly greater risk than their non-disabled peers. Students with disabilities are more vulnerable to school violence from peers, teachers, and school staff due to stereotypes and prejudice. Teachers are pivotal in preventing violence and intervening, but literature on the role that teachers play in responding to disability-based violence is limited. Guided by the social-ecological framework of bullying, this qualitative study explored educators' responses to school violence against students with disabilities in Zambia. Data generation included document review, interviews, and focus groups with 33 teachers and 12 parents, and child-friendly methods with 90 students with disabilities. Findings illuminated that students with disabilities are less safe in schools. Teachers are not responding to violence seen or heard about due to stigmatizing beliefs and cultural norms surrounding disability and violence, with students with disabilities blamed for the violence and the response being their burden. Students with disabilities felt protected by special education teachers; however, disability-based stigma did not end with the student. By association, special education teachers were experiencing stigma from other teachers and were discouraged to respond. This stigma undermined the support special education teachers could provide to decrease school violence. Findings provide direction so teachers can respond to school violence in prosocial ways that create an environment where students with disabilities feel safe.

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.

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.

In the Western Hemisphere, bat-associated rabies viruses (RABVs) have established independent transmission cycles in multiple mammal hosts, forming genetically distinct lineages. In New Mexico, USA, skunks, bats, and gray foxes are rabies reservoir hosts and represent a public health risk because of encounters with humans. During 2015 and 2019, two previously undescribed RABVs were detected in 2 gray foxes (Urocyon cinereoargenteus) in Lincoln County, New Mexico. Phylogenetic analysis of the nucleoprotein gene indicated that the isolates are a novel RABV variant. These 2 cases probably represent repeated spillover events from an unknown bat reservoir to gray foxes. Molecular analysis of rabies cases across New Mexico identified that other cross-species transmission events were the result of viral variants previously known to be enzootic to New Mexico. Despite a robust rabies public health surveillance system in the United States, advances in testing and surveillance techniques continue to identify previously unrecognized zoonotic pathogens.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India., (© 2022. The Author(s).)

Objective: To provide epidemiological information on animal and human cases of rabies in the US during 2020 and summaries of 2020 rabies surveillance for Canada and Mexico., Animals: All animals submitted for laboratory diagnosis of rabies in the US during 2020., Procedures: State and territorial public health departments and USDA Wildlife Services provided 2020 rabies surveillance data. Data were analyzed temporally and geographically to assess trends in domestic and wildlife rabies cases., Results: During 2020, 54 jurisdictions submitted 87,895 animal samples for rabies testing, of which 85,483 (97.3%) had a conclusive (positive or negative) test result. Of these, 4,479 (5.2%) tested positive for rabies, representing a 4.5% decrease from the 4,690 cases reported in 2019. Texas (n = 580 [12.9%]), Pennsylvania (371 [8.3%]), Virginia (351 [7.8%]), New York (346 [7.7%]), North Carolina (301 [6.7%]), New Jersey (257 [5.7%]), Maryland (256 [5.7%]), and California (248 [5.5%]) together accounted for > 60% of all animal rabies cases reported in 2020. Of the total reported rabid animals, 4,090 (91.3%) involved wildlife, with raccoons (n = 1,403 [31.3%]), bats (1,400 [31.3%]), skunks (846 [18.9%]), and foxes (338 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (288 [6.4%]), cattle (43 [1.0%]), and dogs (37 [0.8%]) accounted for 95% of rabies cases involving domestic animals in 2020. No human rabies cases were reported in 2020., Conclusions and Clinical Relevance: For the first time since 2006, the number of samples submitted for rabies testing in the US was < 90,000; this is thought to be due to factors related to the COVID-19 pandemic, as similar decreases in sample submission were also reported by Canada and Mexico.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: To provide epidemiological information on animal and human cases of rabies occurring in the United States during 2019 and summaries of 2019 rabies surveillance for Canada and Mexico., Animals: All animals submitted for laboratory diagnosis of rabies in the United States during 2019., Procedures: State and territorial public health departments and USDA Wildlife Services provided data on animals submitted for rabies testing in the United States during 2019. Data were analyzed temporally and geographically to assess trends in domestic and wildlife rabies cases., Results: During 2019, 53 jurisdictions submitted 97,523 animal samples for rabies testing, of which 94,770 (97.2%) had a conclusive (positive or negative) test result. Of these, 4,690 tested positive for rabies, representing a 5.3% decrease from the 4,951 cases reported in 2018. Texas (n = 565 [12.0%]), New York (391 [8.3%]), Virginia (385 [8.2%]), North Carolina (315 [6.7%]), California (276 [5.9%]), and Maryland (269 [5.7%]) together accounted for almost half of all animal rabies cases reported in 2019. Of the total reported rabid animals, 4,305 (91.8%) were wildlife, with raccoons (n = 1,545 [32.9%]), bats (1,387 [29.6%]), skunks (915 [19.5%]), and foxes (361 [7.7%]) as the primary species confirmed with rabies. Rabid cats (n = 245 [5.2%]) and dogs (66 [1.4%]) accounted for > 80% of rabies cases involving domestic animals in 2019. No human rabies cases were reported in 2019., Conclusions and Clinical Relevance: The overall number of animal rabies cases decreased from 2018 to 2019. Laboratory diagnosis of rabies in animals is critical to ensure that human rabies postexposure prophylaxis is administered judiciously.

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

As a neglected zoonotic disease, rabies causes approximately 5.9 × 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., Competing Interests: The authors declare no conflict of interest.

Objective: To describe rabies and rabies-related events occurring during 2018 in the United States., Animals: All animals submitted for laboratory diagnosis of rabies in the United States during 2018., Procedures: State and territorial public health departments provided data on animals submitted for rabies testing in 2018. Data were analyzed temporally and geographically to assess trends in domestic animal and wildlife rabies cases., Results: During 2018, 54 jurisdictions reported 4,951 rabid animals to the CDC, representing an 11.2% increase from the 4,454 rabid animals reported in 2017. Texas (n = 695 [14.0%]), Virginia (382 [7.7%]), Pennsylvania (356 [7.2%]), North Carolina (332 [6.7%]), Colorado (328 [6.6%]), and New York (320 [6.5%]) together accounted for almost half of all rabid animals reported in 2018. Of the total reported rabies cases, 4,589 (92.7%) involved wildlife, with bats (n = 1,635 [33.0%]), raccoons (1,499 [30.3%]), skunks (1,004 [20.3%]), and foxes (357 [7.2%]) being the major species. Rabid cats (n = 241 [4.9%]) and dogs (63 [1.3%]) accounted for > 80% of rabid domestic animals reported in 2018. There was a 4.6% increase in the number of samples submitted for testing in 2018, compared with the number submitted in 2017. Three human rabies deaths were reported in 2018, compared with 2 in 2017., Conclusions and Clinical Relevance: The overall number of animal rabies cases increased from 2017 to 2018. Laboratory diagnosis of rabies in animals is critical to ensure that human rabies postexposure prophylaxis is administered judiciously.

Since the eradication of smallpox, there have been increases in poxvirus infections and the emergence of several novel poxviruses that can infect humans and domestic animals. In 2015, a novel poxvirus was isolated from a resident of Alaska. Diagnostic testing and limited sequence analysis suggested this isolate was a member of the Orthopoxvirus ( OPXV ) genus but was highly diverged from currently known species, including Akhmeta virus . Here, we present the complete 210,797 bp genome sequence of the Alaska poxvirus isolate, containing 206 predicted open reading frames. Phylogenetic analysis of the conserved central region of the genome suggested the Alaska isolate shares a common ancestor with Old World OPXVs and is diverged from New World OPXVs. We propose this isolate as a member of a new OPXV species, Alaskapox virus ( AKPV ). The AKPV genome contained host range and virulence genes typical of OPXVs but lacked homologs of C4L and B7R, and the hemagglutinin gene contained a unique 120 amino acid insertion. Seven predicted AKPV proteins were most similar to proteins in non-OPXV Murmansk or NY&#95;014 poxviruses. Genomic analysis revealed evidence suggestive of recombination with Ectromelia virus in two putative regions that contain seven predicted coding sequences, including the A-type inclusion protein., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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.

The genome sequence and annotation of two novel poxviruses, NY&#95;014 and Murmansk, are presented. Despite being isolated on different continents and from different hosts, the viruses are relatively similar, albeit distinct species. The closest known relative of the novel viruses is Yoka poxvirus. Five novel genes were found in these genomes, two of which were MHC class I homologs. Although the core of these genomes was well conserved, the terminal regions showed significant variability with large deletions and surprising evidence of recombination with orthopoxviruses.

B-type lamins are major constituents of the nuclear lamina in all metazoan cells, yet have specific roles in the development of certain cell types. Although they are speculated to regulate gene expression in developmental contexts, a direct link between B-type lamins and developmental gene expression in an in vivo system is currently lacking. Here, we identify lamin B1 as a key regulator of gene expression required for the formation of functional olfactory sensory neurons. By using targeted knockout in olfactory epithelial stem cells in adult mice, we show that lamin B1 deficient neurons exhibit attenuated response to odour stimulation. This deficit can be explained by decreased expression of genes involved in mature neuron function, along with increased expression of genes atypical of the olfactory lineage. These results support that the broadly expressed lamin B1 regulates expression of a subset of genes involved in the differentiation of a specific cell type.

Rabies, resulting from infection by Rabies virus (RABV) and related lyssaviruses, is one of the most deadly zoonotic diseases and is responsible for up to 70,000 estimated human deaths worldwide each year. Rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure prophylaxis in humans and control of the disease in animals. Currently, only the direct fluorescent antibody (DFA) test is recommended for routine rabies diagnosis. Reverse-transcription polymerase chain reaction (RT-PCR) based diagnostic methods have been widely adapted for the diagnosis of other viral pathogens, but there is currently no widely accepted rapid real-time RT-PCR assay for the detection of all lyssaviruses. In this study, we demonstrate the validation of a newly developed multiplex real-time RT-PCR assay named LN34, which uses a combination of degenerate primers and probes along with probe modifications to achieve superior coverage of the Lyssavirus genus while maintaining sensitivity and specificity. The primers and probes of the LN34 assay target the highly conserved non-coding leader region and part of the nucleoprotein (N) coding sequence of the Lyssavirus genome to maintain assay robustness. The probes were further modified by locked nucleotides to increase their melting temperature to meet the requirements for an optimal real-time RT-PCR assay. The LN34 assay was able to detect all RABV variants and other lyssaviruses in a validation panel that included representative RABV isolates from most regions of the world as well as representatives of 13 additional Lyssavirus species. The LN34 assay was successfully used for both ante-mortem and post-mortem diagnosis of over 200 clinical samples as well as field derived surveillance samples. This assay represents a major improvement over previously published rabies specific RT-PCR and real-time RT-PCR assays because of its ability to universally detect RABV and other lyssaviruses, its high throughput capability and its simplicity of use, which can be quickly adapted in a laboratory to enhance the capacity of rabies molecular diagnostics. The LN34 assay provides an alternative approach for rabies diagnostics, especially in rural areas and rabies endemic regions that lack the conditions and broad experience required to run the standard DFA assay., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Patents has been filed for assays described in this manuscript through CDC Technology Transfer Office/NIH Office.