Delayed Diagnosis of Locally Acquired Lyme Disease, Central North Carolina, USA.

Healthcare providers in North Carolina, USA, have limited experience diagnosing and managing Lyme disease because few cases occur annually statewide. We outline the prolonged diagnostic course for a patient with locally acquired Lyme disease in North Carolina. This case highlights the need for greater awareness and professional education.

Rickettsia parkeri Rickettsiosis in Kidney Transplant Recipient, North Carolina, USA, 2023.

Spotted fever rickettsiosis is rarely observed in solid organ transplant recipients, and all previously reported cases have been associated with tick bite months to years after transplantation. We describe a kidney transplant recipient in North Carolina, USA, who had a moderately severe Rickettsia parkeri infection develop during the immediate posttransplant period.

Laboratory-Acquired Dengue Virus Infection, United States, 2018.

Investigation of a dengue case in a laboratory worker in North Carolina, USA, revealed that the case-patient prepared high-titer dengue virus stocks soon before illness onset. Improper doffing of gloves with an open finger wound likely resulted in cutaneous exposure. This case reinforces recommendations for enhanced precautions when working with high-titer dengue virus.

Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients.

BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

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.

Seroepidemiologic study of human infections with spotted fever group Rickettsiae in North Carolina.

Increasing entomologic and epidemiologic evidence suggests that spotted fever group rickettsiae (SFGR) other than Rickettsia rickettsii are responsible for spotted fever rickettsioses in the United States. A retrospective seroepidemiologic study was conducted on stored acute- and convalescent-phase sera that had been submitted for Rocky Mountain spotted fever testing to the North Carolina State Laboratory of Public Health. We evaluated the serologic reactivity of the paired sera to R. rickettsii, Rickettsia parkeri, and Rickettsia amblyommii antigens. Of the 106 eligible pairs tested, 21 patients seroconverted to one or more antigens. Cross-reactivity to multiple antigens was observed in 10 patients, and seroconversions to single antigens occurred in 11 patients, including 1 against R. rickettsii, 4 against R. parkeri, and 6 against R. amblyommii. Cross-absorption of cross-reactive sera and/or Western blots identified two presumptive cases of infection with R. parkeri, two presumptive cases of infection with R. rickettsii, and one presumptive case of infection with R. amblyommii. These findings suggest that species of SFGR other than R. rickettsii are associated with illness among North Carolina residents and that serologic testing using R. rickettsii antigen may miss cases of spotted fever rickettsioses caused by other species of SFGR.

Decompression and collagen wrapping of a fibrolipomatous hamartoma of the median nerve: a new approach for a rare and difficult problem.

Fibrolipomatous hamartoma is a rare benign slow growing fibrofatty tumor of peripheral nerves of unknown etiology. Clinical presentation may mimic carpal tunnel syndrome when involving the median nerve. We present a case of FLH of the median nerve in a 59-year-old female treated with decompression and collagen nerve wrapping.

Persistent spatial clustering and predictors of pediatric La Crosse virus neuroinvasive disease risk in eastern Tennessee and western North Carolina, 2003-2020.

The combined region of eastern Tennessee and western North Carolina has a persistently high risk of pediatric La Crosse virus neuroinvasive disease (LACV-ND). To guide public health intervention in this region, the objectives of this retrospective ecological study were to investigate the geographic clustering and predictors of pediatric LACV-ND risk at the ZIP code tabulation area (ZCTA) level. Data on pediatric cases of LACV-ND reported between 2003 and 2020 were obtained from Tennessee Department of Health and North Carolina Department of Health and Human Services. Purely spatial and space-time scan statistics were used to identify ZCTA-level clusters of confirmed and probable pediatric LACV-ND cases from 2003-2020, and a combination of global and local (i.e., geographically weighted) negative binomial regression models were used to investigate potential predictors of disease risk from 2015-2020. The cluster investigation revealed spatially persistent high-risk and low-risk clusters of LACV-ND, with most cases consistently reported from a few high-risk clusters throughout the entire study period. Temperature and precipitation had positive but antagonistic associations with disease risk from 2015-2020, but the strength of those relationships varied substantially across the study area. Because LACV-ND risk clustering in this region is focally persistent, retroactive case surveillance can be used to guide the implementation of targeted public health intervention to reduce the disease burden in high-risk areas. Additional research on the role of climate in LACV transmission is warranted to support the development of predictive transmission models to guide proactive public health interventions.

Spatiotemporal patterns of Lyme disease in North Carolina: 2010-2020.

Background: Lyme disease is the most common vector-borne disease in the United States with the majority of cases occurring in the Northeast, upper Midwest, and mid-Atlantic regions. While historically considered a low incidence state, North Carolina (NC) has reported an increasing number of cases over the past decade. Therefore, the aim of this study was to characterise the spatiotemporal evolution of Lyme disease in NC from 2010 to 2020. Methods: Confirmed and probable cases reported to the NC Division of Public Health without associated travel to high-transmission state were included in the analysis. The study period was divided into four sub-periods and data were aggregated by zip code of residence. The absolute change in incidence was mapped and spatial autocorrelation analyses were performed within each sub-period. Findings: We identified the largest absolute changes in incidence in zip codes located in northwestern NC along the Appalachian Mountains. The spatial distribution of cases became increasingly clustered over the study period (Moran's I of 0.012, p = 0.127 in 2010-2012 vs. 0.403, p < 0.0001 in 2019-2020). Identified clusters included 22 high-incidence zip codes in the 2019-2020 sub-period, largely overlapping with the same areas experiencing the greatest absolute changes in disease incidence. Interpretation: Lyme disease has rapidly emerged in northwestern NC with some zip codes reporting incidence rates similar to historically high incidence regions across the US Northeast, mid-Atlantic, and upper Midwest. Efforts are urgently needed to raise awareness among medical providers to prevent excess morbidity. Funding: Funding was provided by a "Creativity Hub" award from the UNC Office of the Vice Chancellor for Research. Additional support was provided by Southeastern Center of Excellence in Vector Borne Diseases (U01CK000662).

A Rare Presentation of Postaxial Polydactyly in a 2-Year-Old Female with Ellis-van Creveld Syndrome.

Postaxial or ulnar polydactyly is the most common form of polydactyly that may present with the duplication of soft-tissue structures only or with additional bony involvement. Surgical excision is the only viable treatment option for postaxial polydactyly with bony involvement, and psychological or cosmetic reasons are the main rationale for treatment. Ellis-van Creveld syndrome (EVC) is a rare congenital disorder characterized by chondral and ectodermal dysplasia, particularly postaxial polydactyly. The exact prevalence of EVC is unknown, and fewer than 300 cases have been reported. We present a case of a 2-year-old Hispanic female with EVC who presented with bilateral postaxial polydactyly and complete duplication of the metacarpal and phalanges. We describe the presentation and treatment of this patient, who ultimately underwent staged resection of the duplicated digits with reconstruction of the abductor muscle.

Patterns Testing for Tick-Borne Diseases and Implications for Surveillance in the Southeastern US.

Importance: Tick-borne diseases (TBD), including spotted fever group rickettsiosis (SFGR), ehrlichiosis, and, increasingly, Lyme disease, represent a substantial public health concern throughout much of the southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases because of pitfalls in existing diagnostic test methods. Objective: To examine patterns of diagnostic testing and incidence of TBD in a large, academic health care system. Design, Setting, and Participants: This cross-sectional study included diagnostic test results for TBD at UNC Health, a large academic health care system with inpatient and outpatient facilities, from January 1, 2017, to November 30, 2020. Participants included all individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis, or Lyme disease performed during the study period. Main Outcomes and Measures: Rates of test positivity, testing completeness, and incidence of TBD. Results: During the 4-year study period, 11 367 individuals (6633 [58.4%] female; 10 793 [95%] non-Hispanic individuals and 8850 [77.9%] White individuals; median [IQR] age, 53 [37-66] years) were tested for TBD. Among the 20 528 diagnostic tests performed, 47 laboratory-confirmed, incident cases of SFGR, 27 cases of ehrlichiosis, and 76 cases of Lyme were confirmed, representing incidence rates of 4.7%, 7.1%, and 0.7%, respectively. However, 3984 of SFGR tests (79.3%) and 3606 of Ehrlichia tests (74.3%) lacked a paired convalescent sample. Of 20 528 tests, there were 11 977 tests (58.3%) for Lyme disease from 10 208 individuals, 5448 tests (26.5%) for SFGR from 4520 individuals, and 3103 tests (15.1%) for ehrlichiosis from 2507 individuals. Most striking, testing for ehrlichiosis was performed in only 55% of patients in whom SFGR was ordered, suggesting that ehrlichiosis remains underrecognized. An estimated 187 incident cases of SFGR and 309 of ehrlichiosis were potentially unidentified because of incomplete testing. Conclusions and Relevance: In this cross-sectional study, most of the patients suspected of having TBD did not have testing performed in accordance with established guidelines, which substantially limits understanding of TBD epidemiology. Furthermore, the data revealed a large discrepancy between the local burden of disease and the testing performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBD and distribution of causative pathogens.

Association of doxycycline prescriptions and tick-related emergency department visits in North Carolina.

OBJECTIVES: To compare the seasonal frequency of doxycycline prescriptions with tick-related emergency department (ED) visits in North Carolina, and to determine if doxycycline prescriptions are associated in time with an increase in the number of ED visits for a tick-related patient complaint or a subsequent diagnosis of a tick-borne infection. METHODS: Aggregate monthly counts of total dispensed doxycycline prescriptions for each North Carolina Piedmont Metropolitan Statistical Area (MSA) were compared with the proportions of tick-related ED visits from August 2007 through July 2009. RESULTS: Epidemic curves of tick-related ED visits for each of the 6 MSAs were characterized by increased frequency in the spring and summer months followed by a decline in the fall. However, the pattern of doxycycline prescriptions varied by MSA. Doxycycline prescriptions in Durham-Chapel Hill and Raleigh-Cary MSAs increased in the spring and summer, while for the 4 other Piedmont MSAs there was no consistent or pronounced spring-summer increase. CONCLUSION: Doxycycline prescription use did not always correlate well with suspected tick activity in North Carolina. Therefore, doxycycline prescription use cannot necessarily be used as a surrogate measure of tick activity for infectious disease surveillance until the reasons for this variability are better understood.

Determining the role of natural SARS-CoV-2 infection in the death of domestic pets: 10 cases (2020-2021).

OBJECTIVE: To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS: 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES: A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals' course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS: SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE: This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.

Low SARS-CoV-2 Seroprevalence and No Active Infections among Dogs and Cats in Animal Shelters with Laboratory-Confirmed COVID-19 Human Cases among Employees.

Human-to-animal and animal-to-animal transmission of SARS-CoV-2 has been documented; however, investigations into SARS-CoV-2 transmission in congregate animal settings are lacking. We investigated four animal shelters in the United States that had identified animals with exposure to shelter employees with laboratory-confirmed COVID-19. Of the 96 cats and dogs with specimens collected, only one dog had detectable SARS-CoV-2 neutralizing antibodies; no animal specimens had detectable viral RNA. These data indicate a low probability of human-to-animal transmission events in cats and dogs in shelter settings with early implementation of infection prevention interventions.

A Statewide Survey of Container Aedes Mosquitoes (Diptera: Culicidae) in North Carolina, 2016: A Multiagency Surveillance Response to Zika Using Ovitraps.

Native and invasive container-inhabiting Aedes mosquitoes (Diptera: Culicidae) play important roles in the transmission of endemic and traveler-introduced arboviruses in the United States. In response to the emergence of Zika virus into the Americas, we surveyed the distribution of container Aedes spp. of public health importance within North Carolina during 2016 using ovitraps. A seasonal survey was conducted in 18 counties from the mountains to the coast to identify species incriminated in the transmission of chikungunya, dengue, La Crosse, yellow fever, and Zika viruses. Multiple local, state, and federal agencies participated in the study and submitted more than 3,600 ovistrips. Aedes albopictus (Skuse) (81.4%, n = 54,458) was the most common and widespread species found in this survey, followed by Aedes triseriatus (Say) (10.7%, n = 7,169) and Aedes japonicus (Theobald) (7.9%, n = 5,262). We did not find Aedes aegypti and rarely found Aedes hendersoni (Cockerell). We assessed broad-scale climatic and other factors and determined that longitude, elevation, rainfall, and temperature had significant effects on explaining the variation in presence, abundance, and phenology of container Aedes in North Carolina. However, much of the variation in these outcomes was not explained at this coarse scale and may benefit from finer-scale analyses. These efforts represent the largest ovitrap survey ever conducted in the state.

The Marijuana Check-up: promoting change in ambivalent marijuana users.

AIMS: To evaluate the efficacy of a two-session assessment and feedback intervention designed to reach and increase motivation for change in marijuana users who were experiencing negative consequences but were ambivalent about change. DESIGN: Random assignment to one of two types of feedback conditions or a delayed feedback control (DFC) with follow-up assessments at 7 weeks, 6 months and 12 months. Setting University of Washington research center in Seattle, Washington. PARTICIPANTS: A total of 188 adult male and female marijuana users who responded to advertisements. Interventions A personalized feedback (PF) condition utilizing motivational interviewing was compared to an educational control condition labeled multi-media feedback (MMF). MEASUREMENTS: Marijuana use, dependence symptoms, other associated negative consequences and motivational constructs were assessed at all time-points. FINDINGS: PF participants reported fewer days of use per week, fewer periods of use per day and fewer dependence symptoms at 7 weeks than those in the MMF and DFC conditions. PF participants also reported fewer days of use per week compared to MMF participants at the 12-month follow-up and fewer dependence symptoms at both the 6- and 12-month follow-ups compared to MMF participants. CONCLUSIONS: The PF intervention, delivered in the context of a check-up, shows potential as a way of reaching and motivating change in marijuana users with a diagnosable disorder who otherwise are not ready to approach treatment. Ways of augmenting the modest absolute levels of change are discussed.

Experimental study of high speed polarization-coding quantum key distribution with sifted-key rates over Mbit/s.

We present a quantitative study of various limitations on quantum cryptographic systems operating with sifted-key rates over Mbit/s. The dead time of silicon APDs not only limits the sifted-key rate but also causes correlation between the neighboring key bits. In addition to the well-known count-rate dependent timing jitter in avalanche photo-diode (APD), the faint laser sources, the vertical cavity surface emission lasers (VCSELs) in our system, also induce a significant amount of data-dependent timing jitter. Both the dead time and the data-dependent timing jitter are major limiting factors in designing QKD systems with sifted-key rates beyond Mbit/s.