Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time-to-death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding of the progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.

Resident Synovial Macrophages in Synovial Fluid: Implications for Immunoregulation in Infectious and Inflammatory Arthritis.

Objectives: Resident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces. Methods: We recruited human patients presenting with undifferentiated arthritis in multiple clinical settings. We used flow cytometry to identify mononuclear cells in peripheral blood and SF. We used a novel transwell migration assay with human ex-vivo synovium obtained intra-operatively to validate flow cytometry findings. We used single cell RNA-sequencing (scRNA-seq) to further identify macrophage/monocyte subsets. ELISA was used to evaluate the bone-resorption potential of SF. Results: We were able to identify a rare population of CD14dim, OPG+, ZO-1+ cells consistent with RSM in SF via flow cytometry. These cells were relatively enriched in the SF during infectious processes, but absolutely decreased compared to healthy controls. Similar putative RSM were identified using ex vivo migration assays when MCP-1 and LPS were used as migratory stimulus. scRNA-seq revealed a population consistent with RSM transcriptionally related to CD56+ cytotoxic dendritic cells and IDO+ M2 macrophages. Conclusion: We identified a rare cell population consistent with RSM, indicating these cells are likely migratory and able to initiate or coordinate both acute (septic) or chronic (autoimmune or inflammatory) arthritis. RSM analysis via scRNA-seq indicated these cells are M2 skewed, capable of antigen presentation, and have consistent functions in both septic and inflammatory arthritis.

Within-Host Bayesian Joint Modeling of Longitudinal and Time-to-Event Data of Leishmania Infection.

The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time of death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.

Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi.

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.

Unvaccinated Adolescents' COVID-19 Vaccine Intentions: Implications for Public Health Messaging.

PURPOSE: COVID-19 vaccine uptake remains low for US adolescents and contributes to excess morbidity and mortality. Most research has assessed parental intention to vaccinate their children. We explored differences between vaccine-acceptant and vaccine-hesitant unvaccinated US adolescents using national survey data. METHODS: A nonprobability, quota-based sample of adolescents, aged 13-17 years, was recruited through an online survey panel in April 2021. One thousand nine hundred twenty seven adolescents were screened for participation and the final sample included 985 responses. We assessed responses from unvaccinated adolescents (n = 831). Our primary measure was COVID-19 vaccination intent ("vaccine-acceptant" defined as "definitely will" get a COVID-19 vaccine and any other response classified as "vaccine-hesitant") and secondary measures included reasons for intending or not intending to get vaccinated and trusted sources of COVID-19 vaccine information. We calculated descriptive statistics and chi-square tests to explore differences between vaccine-acceptant and vaccine-hesitant adolescents. RESULTS: Most (n = 831; 70.9%) adolescents were hesitant, with more hesitancy observed among adolescents with low levels of concern about COVID-19 and high levels of concern about side effects of COVID-19 vaccination. Among vaccine-hesitant adolescents, reasons for not intending to get vaccinated included waiting for safety data and having parents who would make the vaccination decision. Vaccine-hesitant adolescents had a lower number of trusted information sources than vaccine-acceptant adolescents. DISCUSSION: Differences identified between vaccine-acceptant and vaccine-hesitant adolescents can inform message content and dissemination. Messages should include accurate, age-appropriate information about side effects and risks of COVID-19 infection. Prioritizing dissemination of these messages through family members, state and local government officials, and healthcare providers may be most effective.

Correction: Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

[This corrects the article DOI: 10.1371/journal.pntd.0010613.].

Bayesian multivariate longitudinal model for immune responses to Leishmania: A tick-borne co-infection study.

While many Bayesian state-space models for infectious disease processes focus on population infection dynamics (eg, compartmental models), in this work we examine the evolution of infection processes and the complexities of the immune responses within the host using these techniques. We present a joint Bayesian state-space model to better understand how the immune system contributes to the control of Leishmania infantum infections over the disease course. We use longitudinal molecular diagnostic and clinical data of a cohort of dogs to describe population progression rates and present evidence for important drivers of clinical disease. Among these results, we find evidence for the importance of co-infection in disease progression. We also show that as dogs progress through the infection, parasite load is influenced by their age, ectoparasiticide treatment status, and serology. Furthermore, we present evidence that pathogen load information from an earlier point in time influences its future value and that the size of this effect varies depending on the clinical stage of the dog. In addition to characterizing the processes driving disease progression, we predict individual and aggregate patterns of Canine Leishmaniasis progression. Both our findings and the application to individual-level predictions are of direct clinical relevance, presenting possible opportunities for application in veterinary practice and motivating lines of additional investigation to better understand and predict disease progression. Finally, as an important zoonotic human pathogen, these results may support future efforts to prevent and treat human Leishmaniosis.

Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

Visceral leishmaniasis (VL) is a vector-borne protozoan disease, which can be fatal if left untreated. Synthetic chemical insecticides are very effective tools for controlling of insect vectors, including the sand fly Phlebotomus argentipes, the vector of VL in the Indian subcontinent. However, repeated use of the same insecticide with increasing doses potentially can create high selection pressure and lead to tolerance and resistance development. The objective of this study was to determine the lethal concentrations and assess levels of susceptibility, diagnostic doses and times to death of laboratory-reared P. argentipes to five insecticides that are used worldwide to control vectors. Using the Center for Disease Control and Prevention (CDC) bottle bioassay, 20-30 sand flies were exposed in insecticide- coated 500-ml glass bottles. Flies were then observed for 24 hours and mortality was recorded. Dose-response survival curves were generated for each insecticide using QCal software and lethal concentrations causing 50%, 90% and 95% mortality were determined. A bioassay was also conducted to determine diagnostic doses and diagnostic times by exposing 20-30 flies in each bottle containing set concentrations of insecticide. Mortality was recorded at 10-minute intervals for 120 minutes to generate the survival curve. Phlebotomus argentipes are highly susceptible to alpha-cypermethrin, followed by deltamethrin, malathion, chlorpyrifos, and least susceptible to DDT. Also, the lowest diagnostic doses and diagnostic times were established for alpha-cypermethrin (3µg/ml for 40 minutes) to kill 100% of the flies. The susceptibility data, diagnostic doses and diagnostic times presented here will be useful as baseline reference points for future studies to assess insecticide susceptibility and resistance monitoring of field caught sand flies and to assist in surveillance as VL elimination is achieved in the region.

Hierarchical spatiotemporal modeling of human visceral leishmaniasis in Rio Grande do Norte, Brazil.

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions.

Health care provider knowledge around shared clinical decision-making regarding HPV vaccination of adults aged 27-45 years in the United States.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends shared clinical decision-making (SCDM) regarding HPV vaccination for adults aged 27-45 years who are not adequately vaccinated. The objective of this survey was to understand physician knowledge, attitudes, and practices regarding HPV vaccination in this age group. METHODS: An online survey was administered in June 2021 to physicians who reported practicing internal medicine, family medicine, or obstetrics and gynecology (targeted N = 250 in each practice specialty), selected randomly from potentially eligible physicians from a panel of 2 million U.S. health care providers. RESULTS: In total, 753 physicians participated in the survey: 33.3% practiced internal medicine, 33.1% practiced family medicine, and 33.6% practiced obstetrics/gynecology; 62.5% were male and mean physician age was 52.7 years. Despite the COVID-19 pandemic, at least a third of participating physicians in each practice specialty reported having more HPV vaccine SCDM discussions with patients aged 27-45 years in the past 12 months. While a majority of physicians (79.7%) reported being aware of the SCDM recommendation for adults in this age group, only half of physicians answered an objective knowledge question about SCDM recommendations correctly. CONCLUSIONS: Findings suggest that there are physician knowledge gaps related to SCDM for HPV vaccination. To improve access to HPV vaccination for people most likely to benefit, increasing availability and use of decision aids to support SCDM discussions might help healthcare providers and patients jointly make the most informed decisions about HPV vaccination.

Parental Perceptions Related to Co-Administration of Adolescent COVID-19 and Routine Vaccines.

PURPOSE: Vaccinating adolescents against COVID-19 while avoiding delays in other routine vaccination is paramount to protecting their health. Our objective was to assess parental preferences to have their adolescents aged 12-17 years receive COVID-19 and other routine vaccines at the same time. METHODS: An online survey with a national, quota-based cross-sectional sample of United States parents of youth aged 12-17 years was fielded in April 2021 ahead of FDA's Emergency Use Authorization of COVID-19 vaccine for age 12-15 years. Parents were asked about their willingness to have their adolescents aged 12-17 years receive both COVID-19 and routine vaccines at the same visit and/or to follow their provider's recommendation. Predictors included demographic characteristics, being behind on routine vaccines, and perceived risks and benefits. RESULTS: Few parents were willing to have their adolescent receive COVID-19 and routine vaccines at the same visit (10.6%) or follow the healthcare provider's recommendation (18.5%). In multivariate analyses, demographic characteristics had no effect on willingness, reporting that the adolescent was behind on routine vaccines correlated with decreased willingness (p = .004). Greater concern about the adolescent getting COVID-19 (p = .001), lower concern about the adolescent having side effects from the COVID-19 vaccine (p = .013), and more positive feelings about vaccines in general (p = .002) were associated with higher willingness. DISCUSSION: Few parents would prefer to have their adolescents receive COVID-19 and routine vaccines at the same visit. Understanding what drives willingness to receive all recommended vaccines in the context of the COVID-19 pandemic could inform policies to optimize adolescent vaccination.

Joint Bayesian longitudinal models for mixed outcome types and associated model selection techniques.

Motivated by data measuring progression of leishmaniosis in a cohort of US dogs, we develop a Bayesian longitudinal model with autoregressive errors to jointly analyze ordinal and continuous outcomes. Multivariate methods can borrow strength across responses and may produce improved longitudinal forecasts of disease progression over univariate methods. We explore the performance of our proposed model under simulation, and demonstrate that it has improved prediction accuracy over traditional Bayesian hierarchical models. We further identify an appropriate model selection criterion. We show that our method holds promise for use in the clinical setting, particularly when ordinal outcomes are measured alongside other variables types that may aid clinical decision making. This approach is particularly applicable when multiple, imperfect measures of disease progression are available.

Livestock and rodents within an endemic focus of Visceral Leishmaniasis are not reservoir hosts for Leishmania donovani.

Leishmaniasis on the Indian subcontinent is thought to have an anthroponotic transmission cycle. There is no direct evidence that a mammalian host other than humans can be infected with Leishmania donovani and transmit infection to the sand fly vector. The aim of the present study was to evaluate the impact of sand fly feeding on other domestic species and provide clinical evidence regarding possible non-human reservoirs through experimental sand fly feeding on cows, water buffalo goats and rodents. We performed xenodiagnosis using colonized Phlebotomus argentipes sand flies to feed on animals residing in villages with active Leishmania transmission based on current human cases. Xenodiagnoses on mammals within the endemic area were performed and blood-fed flies were analyzed for the presence of Leishmania via qPCR 48hrs after feeding. Blood samples were also collected from these mammals for qPCR and serology. Although we found evidence of Leishmania infection within some domestic mammals, they were not infectious to vector sand flies. Monitoring infection in sand flies and non-human blood meal sources in endemic villages leads to scientific proof of exposure and parasitemia in resident mammals. Lack of infectiousness of these domestic mammals to vector sand flies indicates that they likely play no role, or a very limited role in Leishmania donovani transmission to people in Bihar. Therefore, a surveillance system in the peri-/post-elimination phase of visceral leishmaniasis (VL) must monitor absence of transmission. Continued surveillance of domestic mammals in outbreak villages is necessary to ensure that a non-human reservoir is not established, including domestic mammals not present in this study, specifically dogs.

Possibility of Leishmania Transmission via Lutzomyia spp. Sand Flies Within the USA and Implications for Human and Canine Autochthonous Infection.

Purpose of Review: Leishmaniasis is a leading cause of parasitic death, with incidence rising from decreased resources to administer insecticide and anti-leishmanial treatments due to the COVID-19 pandemic. Leishmaniasis is nonendemic in the United States (U.S.), but enzootic canine populations and potentially competent vectors warrant monitoring of autochthonous disease as a fluctuating climate facilitates vector expansion. Recent studies concerning sand fly distribution and vector capacity were assessed for implications of autochthonous transmission within the U.S. Recent Findings: Climate change and insecticide resistance provide challenges in sand fly control. While most Leishmania-infected dogs in the U.S. were infected via vertical transmission or were imported, autochthonous vector-borne cases were reported. Autochthonous vector-borne human cases have been reported in four states. Further vaccine research could contribute to infection control. Summary: Both cutaneous and visceral leishmaniasis cases in the U.S. are increasingly reported. Prevention measures including vector control and responsible animal breeding are critical to halt this zoonotic disease.

COVID-19 Vaccination Intentions, Concerns, and Facilitators Among US Parents of Children Ages 6 Months Through 4 Years.

Importance: Children aged 6 months through 4 years have become eligible for COVID-19 vaccination, but little is known about parental intentions regarding, concerns about, or facilitators to COVID-19 vaccination for this age group. Objectives: To evaluate parental intentions, concerns, and facilitators for COVID-19 vaccination for children aged 6 months through 4 years and to help inform the US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices' deliberations and recommendations for COVID-19 vaccination for children aged 6 months through 4 years. Design, Setting, and Participants: This cross-sectional study fielded an online survey from February 2 to 10, 2022, among a nonprobability sample of US parents of children aged 6 months through 4 years who were recruited through Qualtrics using quota-based sampling for respondent gender, race and ethnicity, and child age group. Main Outcomes and Measures: COVID-19 vaccination intentions, time to COVID-19 vaccination, COVID-19 vaccination concerns and facilitators, and trusted COVID-19 vaccination locations for children aged 6 months through 4 years. Results: The final weighted sample of 2031 participants (73.5% participation rate) had more respondents who identified as male (985; weighted percentage, 54.8%) or White (696; weighted percentage, 66.2%), were aged 25 to 49 years (1628; weighted percentage, 85.6%), had at least a bachelor's degree (711; weighted percentage, 40.0%), lived in a metropolitan area (1743; weighted percentage, 82.9%) or the South (961; weighted percentage, 43.4%), or received at least 1 dose of a COVID-19 vaccine (1205; weighted percentage, 59.8%). Half of respondents (645; weighted percentage, 45.6%) indicated that they "definitely" or "probably" will vaccinate their child aged 6 months through 4 years once they became eligible. However, only one-fifth (396; weighted percentage, 19.0%) indicated they would get a COVID-19 vaccine for their child in this age group within 3 months of them becoming eligible for vaccination. Vaccine safety and efficacy were parents' top concerns, and receiving more information about safety and efficacy were the top facilitators to COVID-19 vaccination for this age group. A doctor's office or clinic and local pharmacy were the most trusted COVID-19 vaccination locations for this age group. Conclusions and Relevance: These results suggest that only a minority of parents of children in this age group are eager to vaccinate their children within the first few months of eligibility, with widespread concerns about COVID-19 vaccination for this age group. Thus, considerable efforts to increase parental COVID-19 vaccine confidence for children aged 6 months through 4 years may be needed to maximize COVID-19 vaccination for this age group in the United States.

Days of Flooding Associated with Increased Risk of Influenza.

Influenza typically causes mild infection but can lead to severe outcomes for those with compromised lung health. Flooding, a seasonal problem in Iowa, can expose many Iowans to molds and allergens shown to alter lung inflammation, leading to asthma attacks and decreased viral clearance. Based on this, the hypothesis for this research was that there would be geographically specific positive associations in locations with flooding with influenza diagnosis. An ecological study was performed using influenza diagnoses and positive influenza polymerase chain reaction tests from a de-identified large private insurance database and Iowa State Hygienic Lab. After adjustment for multiple confounding factors, Poisson regression analysis resulted in a consistent 1% associated increase in influenza diagnoses per day above flood stage (95% confidence interval: 1.00-1.04). This relationship remained after removal of the 2009-2010 influenza pandemic year. There was no associated risk between flooding and influenza-like illness as a nonspecific diagnosis. Associated risks between flooding and increased influenza diagnoses were geographically specific, with the greatest risk in the most densely populated areas. This study indicates that populations who live, work, or volunteer in flooded environments should consider preventative measures to avoid environmental exposures to mitigate illness from influenza in the following year.

Geographic Origin and Vertical Transmission of Leishmania infantum Parasites in Hunting Hounds, United States.

Vertical transmission of leishmaniasis is common but is difficult to study against the background of pervasive vector transmission. We present genomic data from dogs in the United States infected with Leishmania infantum parasites; these infections have persisted in the apparent absence of vector transmission. We demonstrate that these parasites were introduced from the Old World separately and more recently than L. infantum from South America. The parasite population shows unusual genetics consistent with a lack of meiosis: a high level of heterozygous sites shared across all isolates and no decrease in linkage with genomic distance between variants. Our data confirm that this parasite population has been evolving with little or no sexual reproduction. This demonstration of vertical transmission has profound implications for the population genetics of Leishmania parasites. When investigating transmission in complex natural settings, considering vertical transmission alongside vector transmission is vital.

Role of NK-Like CD8+ T Cells during Asymptomatic Borrelia burgdorferi Infection.

Lyme disease (LD) due to Borrelia burgdorferi is the most prevalent vector-borne disease in the United States. There is a poor understanding of how immunity contributes to bacterial control, pathology, or both during LD. Dogs in an area of endemicity were screened for B. burgdorferi and Anaplasma exposure and stratified according to seropositivity, presence of LD symptoms, and doxycycline treatment. Significantly elevated serum interleukin-21 (IL-21) and increased circulating CD3+ CD94+ lymphocytes with an NK-like CD8+ T cell phenotype were predominant in asymptomatic dogs exposed to B. burgdorferi. Both CD94+ T cells and CD3- CD94+ lymphocytes, corresponding to NK cells, from symptomatic dogs expressed gamma interferon (IFN-γ) at a 3-fold-higher frequency upon stimulation with B. burgdorferi than the same subset among endemic controls. Surface expression of activating receptor NKp46 was reduced on CD94+ T cells from LD, compared to cells after doxycycline treatment. A higher frequency of NKp46-expressing CD94+ T cells correlated with significantly increased peripheral blood mononuclear cell (PBMC) cytotoxic activity via calcein release assay. PBMCs from dogs with symptomatic LD showed significantly reduced killing ability compared with endemic control PBMCs. An elevated NK-like CD8+ T cell response was associated with protection against development of clinical LD, while excess IFN-γ was associated with clinical disease.

Inclusion of environmentally themed search terms improves Elastic net regression nowcasts of regional Lyme disease rates.

Lyme disease is the most widely reported vector-borne disease in the United States. 95% of confirmed human cases are reported in the Northeast and upper Midwest (25,778 total confirmed cases from Northeast and upper Midwest / 27,203 total US confirmed cases). Human cases typically occur in the spring and summer months when an infected nymph Ixodid tick takes a blood meal. Current federal surveillance strategies report data on an annual basis, leading to nearly a year lag in national data reporting. These lags in reporting make it difficult for public health agencies to assess and plan for the current burden of Lyme disease. Implementation of a nowcasting model, using historical data to predict current trends, provides a means for public health agencies to evaluate current Lyme disease burden and make timely priority-based budgeting decisions. The objective of the study was to develop and compare the performance of nowcasting models using free data from Google Trends and Centers of Disease Control and Prevention surveillance reports. We developed two sets of elastic net models for five regions of the United States: 1. Using only monthly proportional hit data from the 21 disease symptoms and tick related terms, and 2. Using monthly proportional hit data from terms identified via Google correlate and the disease symptom and vector terms. Elastic net models using the full-term list were highly accurate (Root Mean Square Error: 0.74, Mean Absolute Error: 0.52, R2: 0.97) for four of the five regions of the United States and improved accuracy 1.33-fold while reducing error 0.5-fold compared to predictions from models using disease symptom and vector terms alone. Many of the terms included and found to be important for model performance were environmentally related. These models can be implemented to help local and state public health agencies accurately monitor Lyme disease burden during times of reporting lag from federal public health reporting agencies.