Rapid Increase in Seroprevalence of Borrelia burgdorferi Antibodies among Dogs, Northwestern North Carolina, USA, 2017-20211.

We evaluated spatial-temporal risk for Lyme disease in northwestern North Carolina, USA, by using individual-level canine Borrelia burgdorferi seroprevalence data collected during 2017-2021 at routine veterinary screenings for tickborne diseases. Seroprevalence in dogs increased from 2.2% (47/2,130) in 2017 to 11.2% (339/3,033) in 2021. The percentage of incident seropositivity increased from 2.1% (45/2,130) in 2017 to 7.6% (231/3,033) in 2021. Exploratory geographic analyses found canine seroprevalence shifted from clustered (2017, Moran's I = 0.30) to dispersed (2021, Moran's I = -0.20). Elevation, slope, aspect, and forest land cover density were associated with canine seroprevalence within various household buffer regions in 2017. Slope was associated with seroprevalence at the household level in 2021. Results support the use of individual-level canine seroprevalence data for monitoring human risk for Lyme disease. Establishing sentinel veterinary clinics within Lyme disease-emergent communities might promote prevention and control efforts and provide opportunities for educational and behavioral interventions.

Point-of-care C-reactive protein measurement by community health workers safely reduces antimicrobial use among children with respiratory illness in rural Uganda: A stepped wedge cluster randomized trial.

BACKGROUND: Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. In many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHW). This study's objective was to determine the impact of CRP measurement on antibiotic use among children presenting with febrile ARI to CHW in Uganda. METHODS AND FINDINGS: We conducted a cross-sectional, stepped wedge cluster randomized trial in 15 villages in Bugoye subcounty comparing a clinical algorithm that included CRP measurement by CHW to guide antibiotic treatment (STAR Sick Child Job Aid [SCJA]; intervention condition) with the Integrated Community Care Management (iCCM) SCJA currently in use by CHW in the region (control condition). Villages were stratified into 3 strata by altitude, distance to the clinic, and size; in each stratum, the 5 villages were randomly assigned to one of 5 treatment sequences. Children aged 2 months to 5 years presenting to CHW with fever and cough were eligible. CHW conducted follow-up assessments 7 days after the initial visit. Our primary outcome was the proportion of children who were given or prescribed an antibiotic at the initial visit. Our secondary outcomes were (1) persistent fever on day 7; (2) development of prespecified danger signs; (3) unexpected visits to the CHW; (4) hospitalizations; (5) deaths; (6) lack of perceived improvement per the child's caregiver on day 7; and (7) clinical failure, a composite outcome of persistence of fever on day 7, development of danger signs, hospitalization, or death. The 65 participating CHW enrolled 1,280 children, 1,220 (95.3%) of whom had sufficient data. Approximately 48% (587/1,220) and 52% (633/1,220) were enrolled during control (iCCM SCJA) and intervention periods (STAR SCJA), respectively. The observed percentage of children who were given or prescribed antibiotics at the initial visit was 91.8% (539/587) in the control periods as compared to 70.8% (448/633) during the intervention periods (adjusted prevalence difference -24.6%, 95% CI: -36.1%, -13.1%). The odds of antibiotic prescription by the CHW were over 80% lower in the intervention as compared to the control periods (OR 0.18, 95% CI: 0.06, 0.49). The frequency of clinical failure (iCCM SCJA 3.9% (23/585) v. STAR SCJA 1.8% (11/630); OR 0.41, 95% CI: 0.09, 1.83) and lack of perceived improvement by the caregiver (iCCM SCJA 2.1% (12/584) v. STAR SCJA 3.5% (22/627); OR 1.49, 95% CI: 0.37, 6.52) was similar. There were no unexpected visits or deaths in either group within the follow-up period. CONCLUSIONS: Incorporating CRP measurement into iCCM algorithms for evaluation of children with febrile ARI by CHW in rural Uganda decreased antibiotic use. There is evidence that this decrease was not associated with worse clinical outcomes, although the number of adverse events was low. These findings support expanded access to simple, point-of-care diagnostics to improve antibiotic stewardship in rural, resource-constrained settings where individuals with limited medical training provide a substantial proportion of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294510. The study was reviewed and approved by the University of North Carolina Institutional Review Board (#18-2803), Mbarara University of Science and Technology Research Ethics Committee (14/03-19), and Uganda National Council on Science and Technology (HS 2631).

Neurological manifestations of ehrlichiosis among a cohort of patients: prevalence and clinical symptoms.

BACKGROUND: Ehrlichiosis is a potentially fatal tick-borne disease that can progress to involve the central nervous system (CNS) (i.e., neuro-ehrlichiosis), particularly in cases where diagnosis and treatment are delayed. Despite a six-fold national increase in the incidence of ehrlichiosis over the past 20 years, recent data on the prevalence and manifestations of neuro-ehrlichiosis are lacking. METHODS: We conducted a retrospective chart review of all patients tested for ehrlichiosis at University of North Carolina Health facilities between 2018 and 2021 and identified patients who met epidemiological criteria for ehrlichiosis as established by the Council of State and Territorial Epidemiologists and employed by the Centers for Disease Control and Prevention. We estimated the prevalence of neurological symptoms and described the spectrum of neurological manifestations in acute ehrlichiosis, documenting select patient cases in more detail in a case series. RESULTS: Out of 55 patients with confirmed or probable ehrlichiosis, five patients (9.1%) had neurologic symptoms, which is notably lower than previous estimates. Neurological presentations were highly variable and included confusion, amnesia, seizures, focal neurological deficits mimicking ischemic vascular events, and an isolated cranial nerve palsy, though all patients had unremarkable neuroimaging at time of presentation. All but one patient had risk factors for severe ehrlichiosis (i.e., older age, immunosuppression). CONCLUSIONS: Neuro-ehrlichiosis may lack unifying patterns in clinical presentation that would otherwise aid in diagnosis. Clinicians should maintain a high index of suspicion for neuro-ehrlichiosis in patients with acute febrile illness, diverse neurological symptoms, and negative neuroimaging in lone star tick endemic regions.

Evaluation of the Veterinary IDEXX SNAP 4Dx Plus Test for the Diagnosis of Lyme Disease in Humans.

Background: Lyme disease, caused by infection with Borrelia burgdorferi, is the most common vector-borne disease in the United States. The standard two-tier testing (STTT) algorithm suffers from low sensitivity, misinterpretation, and long turnaround time, preventing timely detection and treatment. To address these challenges, we hypothesized that the canine point-of-care (PoC) SNAP 4Dx Plus test used to detect Borrelia burgdorferi antibodies could be employed for human diagnosis. Materials and Methods: The SNAP 4Dx Plus testing was conducted in accordance with the manufacturer's instructions, with results read by manual inspection. All analyses were conducted using R version 4.3.1, and agreement between the PoC assay and the STTT was assessed using kappa statistics with GraphPad software. Results: We included 102 previously-tested human serum samples, of which 19 samples (18.6%) were STTT positive. Compared to the STTT, the SNAP 4Dx Plus test demonstrated a low sensitivity of 0.16 (95% CI 0.03 to 0.40). Conclusion: Overall, our results do not support the use of the SNAP 4Dx Plus LD assay for the diagnosis of human Lyme disease. Differences in antibody concentrations between human and canine samples may partly explain our findings.

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).

High frequency of artemisinin partial resistance mutations in the great lake region revealed through rapid pooled deep sequencing.

In Africa, the first Plasmodium falciparum Kelch13 (K13) artemisinin partial resistance mutation 561H was first detected and validated in Rwanda. Surveillance to better define the extent of the emergence in Rwanda and neighboring countries as other mutations arise in East Africa is critical. We employ a novel scheme of liquid blood drop preservation combined with pooled sequencing to provide a cost-effective rapid assessment of resistance mutation frequencies at multiple collection sites across Rwanda and neighboring countries. Malaria-positive samples (n=5,465) were collected from 39 health facilities in Rwanda, Uganda, Tanzania, and the Democratic Republic of the Congo (DRC) between May 2022 and March 2023 and sequenced in 199 pools. In Rwanda, K13 561H and 675V were detected in 90% and 65% of sites with an average frequency of 19.0% (0-54.5%) and 5.0% (0-35.5%), respectively. In Tanzania, 561H had high frequency in multiple sites while it was absent from the DRC although 675V was seen at low frequency. Conceringly candidate mutations were observed: 441L, 449A, and 469F co-occurred with validated mutations suggesting they are arising under the same pressures. Other resistance markers associated with artemether-lumefantrine are common: P. falciparum multidrug resistance protein 1 N86 at 98.0% and 184F at 47.0% (0-94.3%) and P. falciparum chloroquine resistance transporter 76T at 14.7% (0-58.6%). Additionally, sulfadoxine-pyrimethamine-associated mutations show high frequencies. Overall, K13 mutations are rapidly expanding in the region further endangering control efforts with the potential of engendering partner drug resistance.

Rickettsia africae infections in sub-Saharan Africa: A systematic literature review of epidemiological studies and summary of case reports.

Rickettsia africae is a tick-borne bacteria known to cause African tick bite fever (ATBF). While the disease was first described more than 100 years ago, knowledge of transmission risk factors and disease burden remain poorly described. To better understand the burden of R. africae, this article reviewed and summarized the published literature related to ATBF epidemiology and clinical management. Using a systematic approach, consistent with the PRISMA guidelines, we identified more than 100 eligible articles, including 65 epidemiological studies and 41 case reports. Most reports described R. africae in ticks and livestock, while human studies were less common. Human disease case reports were exclusively among returning travellers from non-endemic areas, which limits our disease knowledge among at-risk populations: people living in endemic regions. Substantial efforts to elucidate the ATBF risk factors and clinical manifestations among local populations are needed to develop effective preventative strategies and facilitate appropriate and timely diagnosis.

Microbiome of Invasive Tick Species Haemaphysalis Longicornis in North Carolina, USA.

Ticks are one of the most important vectors of human and animal disease worldwide. In addition to pathogens, ticks carry a diverse microbiota of symbiotic and commensal microorganisms. In this study, we used next-generation sequencing (NGS) to survey the microbiomes of Haemaphysalis longicornis (Acari: Ixodidae) at different life stages collected from field populations in North Carolina (NC), USA. Sequence analyses were performed using QIIME2 with the DADA2 plugin and taxonomic assignments using the Greengenes database. Following quality filtering and rarefaction, the bacterial DNA sequences were assigned to 4795 amplicon sequence variants (ASVs) in 105 ticks. A core microbiome of H. longicornis was conserved across all ticks analyzed, and included bacterial taxa: Coxiella, Sphingomonas, Staphylococcus, Acinetobacter, Pseudomonas, Sphingomonadaceae, Actinomycetales, and Sphingobium. Less abundant bacterial taxa, including Rickettsia and Aeromonas, were also identified in some ticks. We discovered some ASVs that are associated with human and animal infections among the identified bacteria. Alpha diversity metrics revealed significant differences in bacterial diversity between life stages. Beta diversity metrics also revealed that bacterial communities across the three life stages were significantly different, suggesting dramatic changes in the microbiome as ticks mature. Based on these results, additional investigation is necessary to determine the significance of the Haemaphysalis longicornis microbiome for animal and human health.

Changes in the Seroprevalence of Tick-Borne Rickettsia and Ehrlichia Among Soldiers-Fort Liberty, North Carolina, 1991-2019.

We obtained samples from the Department of Defense Serum Repository from soldiers who were stationed at Fort Liberty, North Carolina, between 1991 and 2019 to assess temporal trends in tick-borne rickettsiosis and ehrlichiosis. Serological evidence of infection was common, with nearly 1 in 5 (18.9%) demonstrating antibodies. We observed significant decreases in Rickettsia seroprevalence (adjusted odds ratio [aOR], 0.42 [95% CI, .27-.65], P = .0001) while over the same period Ehrlichia seroprevalence, albeit less common, nearly doubled (aOR, 3.61 [95% CI, 1.10-13.99], P = .048). The increase in Ehrlichia seroprevalence likely reflects increased transmission resulting from the expanding geographic range of the lone star tick.

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.

Does Paging Clinicians about Tick-Borne Disease Serological Results Impact Clinical Care? A Retrospective Analysis of 70 Cases in North Carolina.

Delayed treatment of Rocky Mountain spotted fever is associated with increased morbidity and mortality. Because the diagnosis cannot be established from a single serological test, guidelines recommend empirical antibiotic initiation in suspect patients. We evaluated a policy used by UNC Health of paging clinicians when acute testing for Rickettsia returned with a titer ≥1:256. Our objective was to assess the potential effect of paging on routine treatment practices. Notably, we found that a high proportion of cases (N = 28, 40%) were not prescribed antibiotics until the results were available. The vast majority of these cases did not have evidence of compatible symptoms or disease progression. These findings suggest that paging may have prompted unnecessary treatment. Overall, the policy, which has now been discontinued, appears to have had limited benefit. Efforts are urgently needed to improve adherence to testing and treatment guidelines.

Comparison of commercially available, rapid, point-of-care C-reactive protein assays among children with febrile illness in southwestern Uganda.

In Uganda, children with febrile illness are often treated with antibiotics even though most have self-limiting, likely viral, infections. C-reactive protein (CRP) measurement can help identify those who are more likely to have a bacterial infection and therefore need antibiotic treatment. Implementation of a CRP rapid diagnostic test (RDT) at the point-of-care in resource-constrained settings with minimal laboratory infrastructure could reduce unnecessary antibiotic use. In this study, we evaluated the performance of three semi-quantitative CRP RDTs (Actim, BTNX, Duo) against a reference CRP assay requiring an electrically powered analyzer (Afinion). While both tests demonstrated substantial agreement with Afinion, Actim had slightly higher agreement than BTNX. The sensitivity was higher for the BTNX test, whereas the Actim test had a higher specificity, at cut-offs of 40 mg/L and 80 mg/L. At a cut-off of 20 mg/L, Duo demonstrated substantial agreement with the Afinion test as well. Our results demonstrate the reliability of CRP RDTs when compared to a reference standard. CRP RDTs without the need for a laboratory-based analyzer are promising tools for optimizing antibiotic use in low-resource settings.

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain.

Importance: Tick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure. Objective: To evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis. Design, Setting, and Participants: This cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older. Main Outcome and Measures: The primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest. Results: Of the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions. Conclusions and Relevance: Results of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda.

BACKGROUND: Malaria epidemics result from extreme precipitation and flooding, which are increasing with global climate change. Local adaptation and mitigation strategies will be essential to prevent excess morbidity and mortality. METHODS: We investigated the spatial risk of malaria infection at multiple timepoints after severe flooding in rural western Uganda employing longitudinal household surveys measuring parasite prevalence and leveraging remotely sensed information to inform spatial models of malaria risk in the 3 months after flooding. RESULTS: We identified clusters of malaria risk emerging in areas (1) that showed the greatest changes in Normalized Difference Vegetation Index from pre- to postflood and (2) where residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage. CONCLUSIONS: The findings enhance our understanding not only of the spatial evolution of malaria risk after flooding, but also in the context of an effective intervention. The results provide a "proof of concept" for programs aiming to prevent malaria outbreaks after flooding using a combination of interventions. Further study of mitigation strategies-and particularly studies of implementation-is urgently needed.

Infection precaution adherence varies by potential exposure risks to SARS-CoV-2 and job role: Findings from a US medical center.

BACKGROUND: Infection precautions (IP) facilitate standardized and safe patient care. Research has demonstrated several barriers to IP adherence among health care personnel (HCP) but potential exposure risk to SARS-CoV-2 and job role has not been considered. METHODS: Researchers used self-reported baseline surveys with 191 HCPs at a university medical center to examine factors that may have affected IP adherence (eg, personal protective equipment [PPE] and hand hygiene errors) over the 2 weeks prior to the survey. Chi-square tests were used to determine if differences existed first, among job role and IP adherence, and second, the potential risk of exposure to SARS-CoV-2 and IP adherence. A binary logistic regression estimated if PPE nonadherence was associated with COVID-19 stress, job role, and potential exposure risk to SARS-CoV-2. RESULTS: PPE nonadherence varied by job role. Those in the Other group (ie, nonphysician/non-nursing HCP) reported significantly fewer errors (9.6%) compared to Physicians (26.5%) and Registered Nurses (33.3%). Hand/glove hygiene errors between COVID-19 patient rooms varied by job role. Respondents who had higher risks of exposure to SARS-CoV-2 were 5.74 times more likely to experience errors. CONCLUSIONS: The results provide implications for adopting systems-level approaches to support worker knowledge and engagement across job roles to improve IP adherence.

The clinical epidemiology, management, and outcomes of patients diagnosed with encephalitis in North Carolina, 2015-2020.

IMPORTANCE: Despite the relatively high mortality and the difficulty in diagnosis, nearly one-third of patients hospitalized with a documented diagnosis of encephalitis did not undergo a lumbar puncture (LP). When an LP was performed, pathogen-specific testing was greatly underutilized. Infectious etiologies were most common, but over 40% of cases were idiopathic at discharge. These findings suggest that there is a substantial opportunity to improve the quality of care through more accurate and timely diagnosis.

Implementation of Hepatitis B Screening Into Routine Antenatal Care to Prevent Mother-to-Child Transmission in Rural Western Uganda.

In rural Uganda where birth dose vaccination for hepatitis B is not routine, we implemented a pilot program for preventing mother-to-child transmission that effectively identified women with high-risk hepatitis B virus (HBV) infection and started antiviral treatment during pregnancy. Further work is required to enhance antiviral adherence through delivery to ensure effective prevention of vertical HBV transmission.

Impact of the COVID-19 pandemic on delays in diagnosis and treatment of tick-borne diseases endemic to southeastern USA.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic was marked by an increase in diagnosis and treatment delays for a range of medical conditions. Yet the impact of the pandemic on the management of tick-borne diseases, which frequently manifest as an acute febrile illness similar to COVID-19, has not been well described. METHODS: In this retrospective cohort study of patients with suspected tick-borne disease attending the University of North Carolina Health facilities, we compared the timeliness of diagnosis and treatment in a "pre-COVID" period (March 2019 to February 2020) and a "post-COVID" period (March 2020 to February 2021). Participants included patients with an ICD-10 diagnosis code of spotted fever group rickettsiosis or ehrlichiosis and a positive Rickettsia rickettsii or Ehrlichia indirect immunofluorescence assay immunoglobulin G antibody test result. Of the 897 patients who had an eligible diagnosis, 240 (26.8%) met the inclusion criteria. The main outcome was time from initial presentation to definitive diagnosis and treatment. RESULTS: During the 2-year study period, 126 (52.5%) patients were grouped in the pre-COVID period and 114 (47.5%) were grouped in the post-COVID period; 120 (50.0%) were female; and 139 (57.9%) were aged > 50 years. Comparing the post-COVID to the pre-COVID period, the adjusted odds ratio (aOR) for delay in treatment > 0 days was 1.81 (95% confidence interval [CI] 1.07-3.07, P = 0.03), and for a treatment delay > 7 days, 1.65 (95% CI 0.94-2.90, P = 0.08). The odds of a delay in diagnosis were similar for patients in the post- and pre-COVID periods, with an aOR of 1.61 (95% CI 0.96-2.72, P = 0.07) for delays > 0 days, and aOR of 1.72 (95% CI 0.99-3.00, P = 0.05) for delays > 7 days. CONCLUSIONS: The odds of a delay in treatment > 0 days were significantly higher in the post-COVID period than in the pre-COVID period. However, the odds of a delay in treatment > 7 days, or a delay in diagnosis, were similar between these two periods. Shifts in care-seeking, alternative care delivery models and prioritization of COVID-19 may contribute to diminished timeliness of treatment for patients with tick-borne diseases.

Estimation of SARS-CoV-2 Seroprevalence in Central North Carolina: Accounting for Outcome Misclassification in Complex Sample Designs.

BACKGROUND: Population-based seroprevalence studies are crucial to understand community transmission of COVID-19 and guide responses to the pandemic. Seroprevalence is typically measured from diagnostic tests with imperfect sensitivity and specificity. Failing to account for measurement error can lead to biased estimates of seroprevalence. Methods to adjust seroprevalence estimates for the sensitivity and specificity of the diagnostic test have largely focused on estimation in the context of convenience sampling. Many existing methods are inappropriate when data are collected using a complex sample design. METHODS: We present methods for seroprevalence point estimation and confidence interval construction that account for imperfect test performance for use with complex sample data. We apply these methods to data from the Chatham County COVID-19 Cohort (C4), a longitudinal seroprevalence study conducted in central North Carolina. Using simulations, we evaluate bias and confidence interval coverage for the proposed estimator compared with a standard estimator under a stratified, three-stage cluster sample design. RESULTS: We obtained estimates of seroprevalence and corresponding confidence intervals for the C4 study. SARS-CoV-2 seroprevalence increased rapidly from 10.4% in January to 95.6% in July 2021 in Chatham County, North Carolina. In simulation, the proposed estimator demonstrates desirable confidence interval coverage and minimal bias under a wide range of scenarios. CONCLUSION: We propose a straightforward method for producing valid estimates and confidence intervals when data are based on a complex sample design. The method can be applied to estimate the prevalence of other infections when estimates of test sensitivity and specificity are available.