BACKGROUND: Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy. METHODS: We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016-2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography. RESULTS: Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim. CONCLUSIONS: As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses.

CONTEXT: In the northeastern United States, recommendations to prevent diseases spread by black-legged ticks (Ixodes scapularis) and lone star ticks (Amblyomma americanum) often rely on individuals to use personal protection or yard-based strategies. The 4-Poster deer treatment stations (4-Posters) suppress tick populations by treating deer hosts with acaricide, potentially offering a community-wide approach for reducing tick-borne diseases in endemic areas. The 4-Poster deployment logistics in mainland community settings are not well documented but are needed for future public health tick control efforts. PROGRAM: As part of a public health research effort to design a population-based 4-Poster effectiveness study aimed at reducing tick-borne disease incidence, TickNET researchers partnered with the Town of Ridgefield (Connecticut) to understand the feasibility and operational logistics of deploying 4-Posters on public land within a residential community to inform future public health interventions by municipalities or vector control agencies. IMPLEMENTATION: We deployed three 4-Posters on a municipal property from July to December 2020 and used motion-activated cameras to record wildlife activity nearby. We documented per-device operational details, costs, materials consumed, and animal activity. EVALUATION: Operation of 4-Posters was feasible, and device challenges were easily remedied. Deer visitation and heavy nontarget animal use were documented at all devices. Unexpectedly, monthly corn consumption was not correlated with monthly deer-view days. The monthly cost per device was US $1279 or US $305 per hectare with an average 21 minutes of weekly service time. DISCUSSION: Use of 4-Posters by communities, public health agencies, or vector control programs may be a practicable addition to tick management programs in tick-borne disease endemic areas in the Northeast. Such programs should carefully consider local and state regulations, follow manufacturer and pesticide label guidelines, and include wildlife monitoring. High labor costs incurred in this project could be mitigated by training vector control agency or municipality staff to service 4-Posters.

The 4-Poster Tick Control Deer Feeder (4-poster) device applies acaricide to white-tailed deer (Odocoileus virginianus) and can reduce populations of the blacklegged tick (Ixodes scapularis), which transmits the agents of Lyme disease, anaplasmosis, babesiosis, and Powassan virus disease in the Northeastern United States. While 4-poster devices have the potential to provide community-wide management of blacklegged ticks in Lyme disease endemic areas, no recent study has assessed their acceptability among residents. We conducted a survey of residents from 16 counties with high annual average Lyme disease incidence (≥ 10 cases per 100,000 persons between 2013 and 2017) in Connecticut and New York to understand perceptions and experiences related to tickborne diseases, support or concerns for placement of 4-poster devices in their community, and opinions on which entities should be responsible for tick control on private properties. Overall, 37% of 1652 respondents (5.5% response rate) would support placement of a 4-poster device on their own property, 71% would support placement on other private land in their community, and 90% would support placement on public land. Respondents who were male, rented their property, resided on larger properties, or were very or extremely concerned about encountering ticks on their property were each more likely to support placement of 4-poster devices on their own property. The primary reason for not supporting placement of a 4-poster device on one's own property was the need for weekly service visits from pest control professionals, whereas the top reason for not supporting placement on other land (private or public) was safety concerns. Most respondents (61%) felt property owners should be responsible for tick control on private properties. Communities considering 4-poster devices as part of a tick management strategy should consider targeting owners of larger properties and placing devices on public lands.

Blacklegged ticks, Ixodes scapularis Say, transmit Lyme disease spirochetes and other human pathogens in the eastern United States. White-tailed deer (Odocoileus virginianus) are key reproductive hosts for I. scapularis adults, and therefore control methods targeting deer have the potential for landscape-wide tick suppression. A topical acaricide product, containing 10% permethrin, is self-applied by deer to kill parasitizing ticks when they visit 4-Poster Tick Control Deer Feeders (hereafter, 4-Posters) Previous 4-Poster intervention studies, including in residential settings, demonstrated suppression of I. scapularis populations but did not include human-based outcomes. To prepare for a proposed 4-Poster intervention trial in residential areas of Connecticut and New York that would include human-tick encounters and tick-borne diseases as outcomes, we sought to identify areas (study clusters) in the 80-100 ha size range and specific locations within these areas where 4-Poster devices could be deployed at adequate density (1 device per 20-25 ha) and in accordance with regulatory requirements. Geographic Information System-based data were used to identify prospective study clusters, based on minimum thresholds for Lyme disease incidence, population density, and forest cover. Ground truthing of potential 4-Poster placement locations was done to confirm the suitability of selected clusters. Based on these efforts, we failed to identify more than a few residential areas fulfilling all criteria for a treatment cluster. We, therefore, reconsidered pursuing the intervention trial, which required inclusion of >30 treatment clusters to achieve adequate statistical power. The 4-Poster methodology may be more readily evaluated in natural or public areas than in residential settings in NY or CT.

BACKGROUND: Nasopharyngeal specimens (NPS) are commonly used for SARS-CoV-2 testing but can be uncomfortable for patients. Self-collected saliva or anterior nasal specimens (ANS) for SARS-CoV-2 detection are less invasive but the sensitivity of these specimen types has not been thoroughly evaluated. METHODS: During September-November 2020, 730 adults undergoing SARS-CoV-2 testing at community testing events and homeless shelters in Denver provided self-collected saliva and ANS specimens before NPS collection and answered a short survey about symptoms and specimen preference. Specimens were tested for SARS-CoV-2 by rRT-PCR; viral culture was performed on a subset of specimens positive by rRT-PCR. Sensitivity of saliva and ANS for SARS-CoV-2 detection by rRT-PCR was measured against NPS. Subgroup analyses included test outcomes by symptom status and culture results. RESULTS: Sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for saliva than for ANS (85% vs. 80%) and among symptomatic participants than among those without symptoms (94% vs. 29% for saliva; 87% vs. 50% for ANS). Among participants with culture-positive SARS-CoV-2 by any specimen type, sensitivity of saliva and ANS by rRT-PCR was 94% and 100%, respectively. Saliva and ANS were equally preferred by participants; most would undergo NPS again despite being least preferred. CONCLUSIONS: Saliva was slightly more sensitive than ANS for SARS-CoV-2 detection by rRT-PCR. Both saliva and ANS reliably detected SARS-CoV-2 among participants with symptoms. Self-collected saliva and ANS offer practical advantages, are preferred by patients, and might be most useful for testing people with COVID-19 symptoms.

Entomological measures have long served as proxies for human risk of Lyme disease (LD) and other tickborne diseases (TBDs) in endemic areas of the United States, despite conflicting results regarding the correlation between these measures and human disease outcomes. Using data from a previous TBD intervention study in Connecticut, Maryland and New York, we evaluated whether human-tick encounters can serve as an accurate proxy for risk of TBDs in areas where LD and other Ixodes scapularis-transmitted infections are common. Among 2,590 households consisting of 4,210 individuals, experiencing a tick encounter was associated with an increased risk of both self-reported (RR = 3.17, 95% CI: 2.05, 4.91) and verified TBD (RR = 2.60, 95% CI: 1.39, 4.84) at the household level. Household characteristics associated with experiencing any tick encounter were residence in Connecticut (aOR = 1.86, 95% CI: 1.38, 2.51) or New York (aOR = 1.66, 95% CI: 1.25, 2.22), head of household having a graduate level education (aOR = 1.46, 95% CI: 1.04, 2.08), owning a pet (aOR = 1.80, 95% CI: 1.46, 2.23) and a property size of 2 acres or larger (aOR = 2.30, 95% CI: 1.42, 3.70). Results for individual characteristics were similar to those for households. Future prevention studies in LD endemic areas should consider using human-tick encounters as a robust proxy for TBD risk.

Consistent and effective use of personal prevention methods for tickborne diseases, including Lyme disease (LD), is dependent on risk awareness. To improve our understanding of the general U.S. population's experiences with tick exposure and use of personal prevention methods, we used data from ConsumerStyles, a web-based, nationally representative questionnaire on health-related topics. Questions addressed tick bites and LD diagnosis in the last year, use of personal prevention methods to prevent tick bites, and willingness to receive a theoretical LD vaccine. Of 10,551 participants surveyed over three years, 12.3 % reported a tick bite for themselves or a household member in the last year, including 15.4 % of participants in high LD incidence (LDI) states, 16.3 % in states neighboring high LDI states, and 9.4 % in low LDI states. Participants in high LDI states and neighboring states were most likely to use personal prevention methods, though 46.6 % of participants in high LDI states and 53.9 % in neighboring states reported not using any method. Participants in low LDI states, adults ≥ 75 years of age, those with higher incomes, and those living in urban housing tended to be less likely to practice personal prevention methods. Likeliness to receive a theoretical LD vaccine was high in high LDI (64.5 %), neighboring (52.5 %), and low LDI (49.7 %) states. Targeted educational efforts are needed to ensure those in high LDI and neighboring states, particularly older adults, are aware of their risk of LD and recommended personal prevention methods.

Atypical manifestations that can be severe and difficult to diagnosis develop in 5%-20% of patients with cat-scratch disease. To clarify the epidemiology of atypical cat-scratch disease in the United States, we analyzed data from the 2005-2014 MarketScan national health insurance claims databases by using the International Classification of Diseases, 9th Revision, Clinical Modification, codes for cat-scratch disease and selected atypical manifestations: retinitis/neuroretinitis, conjunctivitis, neuritis, encephalitis, hepatosplenic disease, osteomyelitis, erythema nodosum, and endocarditis. Atypical cat-scratch disease accounted for 1.5% of all cases, resulting in an average annual incidence of 0.7 cases/100,000 population. Atypical cat-scratch disease was associated with increased risk for hospitalization (risk ratios 8.77, 95% CI 6.56-11.72) and occurred most often in female patients 10-14 years of age. Ocular (48.7%), hepatosplenic (24.6%), and neurologic (13.8%) manifestations were most common among patients. A more comprehensive understanding of atypical cat-scratch disease can improve patient diagnosis and potentially elucidate pathophysiology of the disease.

Botulinum neurotoxins (BoNTs), produced by neurotoxigenic clostridial species, are the cause of the severe disease botulism in humans and animals. Early research on BoNTs has led to their classification into seven serotypes (serotypes A to G) based upon the selective neutralization of their toxicity in mice by homologous antibodies. Recently, a report of a potential eighth serotype of BoNT, designated "type H," has been controversial. This novel BoNT was produced together with BoNT/B2 in a dual-toxin-producing Clostridium botulinum strain. The data used to designate this novel toxin as a new serotype were derived from culture supernatant containing both BoNT/B2 and novel toxin and from sequence information, although data from two independent laboratories indicated neutralization by antibodies raised against BoNT/A1, and classification as BoNT/FA was proposed. The sequence data indicate a chimeric structure consisting of a BoNT/A1 receptor binding domain, a BoNT/F5 light-chain domain, and a novel translocation domain most closely related to BoNT/F1. Here, we describe characterization of this toxin purified from the native strain in which expression of the second BoNT (BoNT/B) has been eliminated. Mass spectrometry analysis indicated that the toxin preparation contained only BoNT/FA and confirmed catalytic activity analogous to that of BoNT/F5. The in vivo mouse bioassay indicated a specific activity of this toxin of 3.8 x 10(7) mouse 50% lethal dose (mLD50) units/mg, whereas activity in cultured human neurons was very high (50% effective concentration [EC50] = 0.02 mLD50/well). Neutralization assays in cells and mice both indicated full neutralization by various antibodies raised against BoNT/A1, although at 16- to 20-fold-lower efficiency than for BoNT/A1. IMPORTANCE Botulinum neurotoxins (BoNTs), produced by anaerobic bacteria, are the cause of the potentially deadly, neuroparalytic disease botulism. BoNTs have been classified into seven serotypes, serotypes A to G, based upon their selective neutralization by homologous antiserum, which is relevant for clinical and diagnostic purposes. Even though supportive care dramatically reduces the death rate of botulism, the only pharmaceutical intervention to reduce symptom severity and recovery time is early administration of antitoxin (antiserum raised against BoNTs). A recent report of a novel BoNT serotype, serotype H, raised concern of a "treatment-resistant" and highly potent toxin. However, the toxin's chimeric structure and characteristics indicate a chimeric BoNT/FA. Here we describe the first characterization of this novel toxin in purified form. BoNT/FA was neutralized by available antitoxins, supporting classification as BoNT/FA. BoNT/FA required proteolytic activation to achieve full toxicity and had relatively low potency in mice compared to BoNT/A1 but surprisingly high activity in cultured neurons.

BACKGROUND: Cowpox virus is an Orthopoxvirus that can cause infections in humans and a variety of animals. Infections occur in Eurasia; human nor animal infection has been reported in the United States. This report describes the occurrence of the first known human case of laboratory-acquired cowpox virus infection in the United States and ensuing investigation. METHODS: The patient and laboratory personnel were interviewed, and laboratory activities were reviewed. Real-time PCR and serologic assays were used to test the patient's specimens. PCR assays were used to test specimens obtained during the investigation. RESULTS: The patient's lesion tested positive for cowpox virus DNA. Genome sequencing revealed a recombinant region consistent with a strain of cowpox virus stored in the research laboratory's freezer. Cowpox virus contamination was detected in six additional laboratory stocks of viruses. Orthopoxvirus DNA was present in three of twenty environmental swabs taken from laboratory surfaces. CONCLUSIONS: The handling of contaminated reagents or contact with contaminated surfaces was likely the mode of transmission. Delays in recognition and diagnosis of this infection in a laboratory researcher underscore the importance of a thorough patient history--including occupational information--and laboratory testing to facilitate a prompt investigation and application of control and remediation measures.