Low Incidence Of Lyme Disease Research Articles

Tick Species Composition, Collection Rates, and Phenology Provide Insights into Tick-Borne Disease Ecology in Virginia.

To better understand tick ecology in Virginia and the increasing Lyme disease incidence in western Virginia, a comparative phenological study was conducted in which monthly collections were performed at twelve sampling locations in southwestern Virginia (high Lyme disease incidence) and 18 equivalent sampling locations in southeastern Virginia (low Lyme disease incidence) for one year. In western Virginia, we also explored the effect of elevation on collection rates of Ixodes scapularis Say (Acari: Ixodidae) and Amblyomma americanum (L.) (Acari: Ixodidae). In total, 35,438 ticks were collected (33,106 A. americanum; 2,052 I. scapularis; 134 Ixodes affinis Neumann [Acari: Ixodidae]; 84 Dermacentor variabilis [Say] [Acari: Ixodidae]; 49 Dermacentor albipictus [Packard] [Acari: Ixodidae]; 10 Haemaphysalis leporispalustris [Packard] [Acari: Ixodidae]; 2 Ixodes brunneus Koch [Acari: Ixodidae]; 1 Haemaphysalis longicornis Neumann [Acari: Ixodidae]). Within southwestern Virginia, Ixodes scapularis collection rates were not influenced by elevation, unlike A. americanum which were collected more frequently at lower elevations (e.g., below 500 m). Notably, I. scapularis larvae and nymphs were commonly collected in southwestern Virginia (indicating that they were questing on or above the leaf litter) but not in southeastern Virginia. Questing on or above the leaf litter is primarily associated with northern populations of I. scapularis. These findings may support the hypothesis that I. scapularis from the northeastern United States are migrating into western Virginia and contributing to the higher incidence of Lyme disease in this region. This comparative phenological study underscores the value of these types of studies and the need for additional research to further understand the rapidly changing tick-borne disease dynamics in Virginia.

Diagnosis, Treatment, and Prevention Practices for Lyme Disease by Clinicians, United States, 2013-2015.

Although tick-borne diseases account for a large number of health care visits in the United States, clinical practices for tick bite and Lyme disease treatment and prevention are not well understood. The objective of this study was to better understand factors associated with clinical practices related to tick bites and Lyme disease. In 2013-2015, questions about tick-bite evaluation, Lyme disease diagnosis and treatment, appropriate use of Lyme disease testing, and tick-bite prevention were included in Porter Novelli's DocStyles survey, a nationally representative annual web-based survey of health care providers. We performed analyses of responses by provider license type and state-level incidence (high or low) of Lyme disease in 2019. A total of 4517 providers were surveyed across the 3 study years. Overall, 80.9% of providers reported that they had evaluated at least 1 patient for a tick bite, 47.6% had diagnosed at least 1 patient with Lyme disease, and 61.9% had treated at least 1 patient for Lyme disease in the previous year. Providers from states with a high incidence of Lyme disease saw more patients for tick bites and Lyme disease than providers from states with a low incidence of Lyme disease. Few providers correctly chose Lyme disease testing as clinically useful in the hypothetical case of a patient from a state with a high incidence of Lyme disease with an arthritic knee (36.0%) or with new-onset atrioventricular block (39.5%), and respondents across all provider types incorrectly chose testing when not clinically indicated. Most providers (69.7%) reported routinely recommending tick-bite prevention methods to patients. Many providers evaluate patients for tick bites and treat patients for Lyme disease, but knowledge about appropriate testing is low. Providers may benefit from tailored education about appropriate Lyme disease diagnosis, testing, and effective tick-bite prevention.

Experiences with tick exposure, Lyme disease, and use of personal prevention methods for tick bites among members of the U.S. population, 2013–2015

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.

Geographic Variation in the Incidence of Marginal Zone Lymphoma Subtypes and Infectious Risk Factors in the United States

Background: Helicobacter pylori is a known etiologic factor for gastric marginal zone lymphoma (MZL) of the mucosa-associated lymphoid tissue (gMALT), but data for infectious etiology in other MZL subtypes are controversial. Proposed hypothetical factors include Borrelia burgdorferi for cutaneous MZL (cMALT), Campylobacter jejuni for intestinal MZL (iMALT), and hepatitis C (HCV) for splenic (SMZL) or nodal MZL (NMZL). These associations have been largely reported in studies from Europe, but they have not been confirmed in the United States (US) (Zucca E and Bertoni F, Blood, 2016;127:2082-92). We explored geographic variation in the incidence rate (IR) of MZL and of reportable infections in the US to examine these hypotheses. Methods: We used data from the US National Program of Cancer Registries, which has been collecting data on the incidence of all cancers from geographic areas representing 97% of the US population since 1992. We calculated age-adjusted IR (per 100 000 person-years) of MZL subtypes (gMALT, cMALT, iMALT, SMZL, and NMZL) for each US state in 2001-2016. We linked them to the 2010 US census data (to obtain demographic characteristics for each state), to state-level data on the incidence of Lyme disease (2001-2016) and of the Campylobacter infection (2016) published by the US Center for Disease Control, as well as to the published estimates of HCV prevalence (2013-2016; Rosenberg ES, et al., JAMA Netw Open, 2018;1:e186371). We examined specific etiologic hypotheses in multivariable Poisson models adjusting for median age, proportion of men, Black or Asian individuals in each state, reporting adjusted IR ratios (IRR) with 95% confidence intervals (CI). gMALT, known to not be associated with Borrelia, Campylobacter, or HCV infections, was used as a control subtype. Results: Between 2001 and 2016, there were 5,625 cases of cMALT, 4,247 of iMALT, 29,535 of NMZL, 13,472 of SMZL, and 17,072 of gMALT reported to the US cancer registries. We observed a large variation in the IR of MZL subtypes across the US. IR varied from 0.03 to 0.22 for cMALT, 0.04 to 0.12 for iMALT, 0.32 to 0.89 for NMZL, and 0.11 to 0.47 for SMZL. For all subtypes, IR was highest in the Northeast, and lowest in the South (Table), consistent with general epidemiology of non-Hodgkin lymphoma. However, the IRR for South relative to Northeast was significantly lower for cMALT (0.42) than iMALT (0.64), NMZL (0.67), SMZL (0.68), or aggregate MZL (0.66; CI, 0.65-0.68). In adjusted models, the IR of Lyme disease was significantly associated with increased IR of cMALT (IRR=2.51; CI, 1.63-3.87; Fig. A). Campylobacter infection was associated with iMALT (IRR=5.99; CI, 1.19-30.2; Fig. B). Additionally, a very high IR was observed in Nebraska and Utah for cMALT (states with very low incidence of Lyme disease), raising a hypothesis of other etiologic factors. In contrast, the HCV infection, most prevalent in the South, was inversely associated with the IR of NMZL and SMZL. We observed no significant association between the IR of gMALT (the control subtype with a well-established etiologic factor) and any of the studied infections, confirming the specificity of the findings. Conclusions: Our results support the putative association between cMALT and Borellia burgdorferi infection, and between iMALT and Campylobacter infection in the US, but also suggest potential other etiologies specific to certain regions in the US. Conversely, lack of a positive association between NMZL or SMZL and HCV suggests that HCV is not a major pathogenic factor in the US. This finding is consistent with the low prevalence of HCV among NHL patients in the US as compared with Japan or Italy (Gisbert et al., Gastroenterology 2003;125(6):1723-32.; Negri et al., Int J Cancer 2004;111(1):1-8). However, the ecological results do not rule out associations at the individual level, which will require further research. Elucidating reasons for geographical variation in the incidence of MZL subtypes may ultimately provide insight into novel pathogenic mechanisms and opportunities for therapeutic approaches. Disclosures Olszewski: Genentech: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding.

1614. Single-Dose Doxycycline as Lyme Disease Post-Exposure Prophylaxis in a National Commercial Insurance Claims Database―the United States, 2014–2017

BackgroundApproximately 300,000 cases of Lyme disease occur annually in the UNITED STATES, with children aged 5–9 years disproportionately affected. A single dose of doxycycline administered within 72 hours of a high-risk tick bite is recommended for post-exposure prophylaxis (PEP) to prevent Lyme disease in areas of high incidence. However, it is not known how often or for which patients PEP is used. We aimed to describe recent patterns of single-dose doxycycline medication claims in states with high and low Lyme disease incidence, and the associated patient and prescription characteristics in a large national commercial insurance claims database.MethodsOutpatient medication claims in the IBM Watson Health MarketScan Database®, a large nation-wide database of de-identified insurance claims filed between January 1, 2014–December 31, 2017 were reviewed. Claims of single-dose doxycycline were identified and associated patient demographics and medication characteristics were analyzed.ResultsDuring 2014–2017, 66,210 medication claims for single-dose doxycycline were filed by 63,112 enrollees; mean annual incidence of receiving at least one single-dose doxycycline prescription was 56 per 100,000 enrollees. Mean patient age was 43 years (IQR 33–56 years); only 8% were for children aged <18 years. About half (46%) were male patients. Most claims (71%) were made by patients residing in the 14 states with high Lyme disease incidence, defined as an average annual incidence of ≥ 10 confirmed Lyme disease cases per 100,000 population. The majority (80%) of medication claims were during the 6 months of peak tick activity (April–July for nymphal ticks and October–November for adult ticks).ConclusionSingle-dose doxycycline medication claims are common in states with high Lyme disease incidence and are highest during months of peak tick activity, consistent with the assumption that most single-dose doxycycline is used for Lyme disease PEP. Use of single-dose doxycycline to prevent Lyme disease is infrequent in children, despite being a group at high risk for Lyme disease. Efforts to educate pediatric healthcare providers and parents should be made to increase Lyme disease PEP access for children.Disclosures All authors: No reported disclosures.

Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.

A subset of patients reporting a diagnosis of Lyme disease can be described as having alternatively diagnosed chronic Lyme syndrome (ADCLS), in which diagnosis is based on laboratory results from a nonreference Lyme specialty laboratory using in-house criteria. Patients with ADCLS report symptoms similar to those reported by patients with chronic fatigue syndrome (CFS). We performed a case-control study comparing patients with ADCLS and CFS to each other and to both healthy controls and controls with systemic lupus erythematosus (SLE). Subjects completed a history, physical exam, screening laboratory tests, 7 functional scales, reference serology for Lyme disease using Centers for Disease Control and Prevention criteria, reference serology for other tick-associated pathogens, and cytokine expression studies. The study enrolled 13 patients with ADCLS (12 of whom were diagnosed by 1 alternative US laboratory), 25 patients with CFS, 25 matched healthy controls, and 11 SLE controls. Baseline clinical data and functional scales indicate significant disability among ADCLS and CFS patients and many important differences between these groups and controls, but no significant differences between each other. No ADCLS patient was confirmed as having positive Lyme serology by reference laboratory testing, and there was no difference in distribution of positive serology for other tick-transmitted pathogens or cytokine expression across the groups. In British Columbia, a setting with low Lyme disease incidence, ADCLS patients have a similar phenotype to that of CFS patients. Disagreement between alternative and reference laboratory Lyme testing results in this setting is most likely explained by false-positive results from the alternative laboratory.

Epidemiology of Lyme disease in low-incidence states

Lyme disease is the most common vector-borne disease in the U.S. Surveillance data from four states with a low-incidence of Lyme disease was evaluated. Most cases occurred after travel to high-incidence Lyme disease areas. Cases without travel-related exposure in low-incidence states differed epidemiologically; misdiagnosis may be common in these areas.

Different populations of blacklegged tick nymphs exhibit differences in questing behavior that have implications for human lyme disease risk.

Animal behavior can have profound effects on pathogen transmission and disease incidence. We studied the questing (= host-seeking) behavior of blacklegged tick (Ixodes scapularis) nymphs, which are the primary vectors of Lyme disease in the eastern United States. Lyme disease is common in northern but not in southern regions, and prior ecological studies have found that standard methods used to collect host-seeking nymphs in northern regions are unsuccessful in the south. This led us to hypothesize that there are behavior differences between northern and southern nymphs that alter how readily they are collected, and how likely they are to transmit the etiological agent of Lyme disease to humans. To examine this question, we compared the questing behavior of I. scapularis nymphs originating from one northern (Lyme disease endemic) and two southern (non-endemic) US regions at field sites in Wisconsin, Rhode Island, Tennessee, and Florida. Laboratory-raised uninfected nymphs were monitored in circular 0.2 m2 arenas containing wooden dowels (mimicking stems of understory vegetation) for 10 (2011) and 19 (2012) weeks. The probability of observing nymphs questing on these stems (2011), and on stems, on top of leaf litter, and on arena walls (2012) was much greater for northern than for southern origin ticks in both years and at all field sites (19.5 times greater in 2011; 3.6–11.6 times greater in 2012). Our findings suggest that southern origin I. scapularis nymphs rarely emerge from the leaf litter, and consequently are unlikely to contact passing humans. We propose that this difference in questing behavior accounts for observed geographic differences in the efficacy of the standard sampling techniques used to collect questing nymphs. These findings also support our hypothesis that very low Lyme disease incidence in southern states is, in part, a consequence of the type of host-seeking behavior exhibited by southern populations of the key Lyme disease vector.

Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector and agent, in Ohio.

Lyme disease, the most common vector-borne disease in the United States, is caused by a tick-borne infection with Borrelia burgdorferi. Currently, Ohio is considered by the Centers for Disease Control and Prevention (CDC) to be non-endemic for Lyme disease. The low incidence of Lyme disease in this state was largely attributed to the absence of the transmitting vector, Ixodes scapularis, commonly known as the blacklegged tick. However, a tick surveillance program established by Ohio Department of Health indicated that the number of I. scapularis in Ohio had increased sharply in recent years, from 0 - 5 ticks per year during 1983–2008 to 15 in 2009, 40 in 2010, and 184 in 2011. During the fall deer hunting season, examination of deer heads submitted to Ohio Department of Agriculture found 29 I. scapularis from 7 counties in 2010 and 1,830 from 25 counties in 2011. As of 2012, the tick had been found in 57 of the 88 counties of Ohio. In addition, all three active stages (larva, nymph, and adult) of I. scapularis were found in Tiverton Township of Coshocton County, demonstrating the presence of established tick populations at this central Ohio location. Of 530 nymphal or adult I. scapularis analyzed by quantitative polymerase chain reaction (qPCR), 32 (6.1%) tested positive for the B. burgdorferi flaB gene, ranging from 36 to 390,000 copies per tick. Antibodies to B. burgdorferi antigens were detected in 2 of 10 (20%) field-captured Peromyscus leucopus from Tiverton Township, and in 41 of 355 (11.5%) dogs residing in Ohio. Collectively, these data suggest that the enzootic life cycle of B. burgdorferi has become established in Ohio, which poses risk of Lyme disease to people and animals in the area.

&lt;I&gt;Borrelia burgdorferi&lt;/I&gt; Not Detected in Widespread &lt;I&gt;Ixodes scapularis&lt;/I&gt; (Acari: Ixodidae) Collected From White-Tailed Deer in Tennessee

Lyme disease (LD), caused by the bacterium Borrelia burgdorferi and transmitted in the eastern United States by blacklegged ticks, Ixodes scapularis Say, is classified as nonendemic in Tennessee and surrounding states in the Southeast. Low incidence of LD in these states has been attributed, in part, to vector ticks being scarce or absent; however, tick survey data for many counties are incomplete or out of date. To improve our knowledge of the distribution, abundance, and Borrelia spp. prevalence of I. scapularis, we collected ticks from 1,018 hunter-harvested white-tailed deer (Odocoileus virginianus (Zimmerman)) from 71 of 95 Tennessee counties in fall 2007 and 2008. In total, 160 deer (15.7%) from 35 counties were infested with adult I. scapularis; 30 of these counties were new distributional records for this tick. The mean number of I. scapularis collected per infested deer was 5.4 +/- 0.6 SE. Of the 883 I. scapularis we removed from deer, none were positive for B. burgdorferi and one tested positive for B. miyamotoi. Deer are not reservoir hosts for B. burgdorferi; nevertheless, past surveys in northern LD-endemic states have readily detected B. burgdoreferi in ticks collected from deer. We conclude that I. scapularis is far more widespread in Tennessee than previously reported. The absence of detectable B. burgdorferi infection among these ticks suggests that the LD risk posed by I. scapularis in the surveyed areas of Tennessee is much lower than in LD-endemic areas of the Northeast and upper Midwest.

Utilization and cost of serologic tests for Lyme disease in Maryland.

To ascertain use of serologic tests for Lyme disease (LD) in Maryland, all laboratories registered with the State Health Department were surveyed. Results show that from 1992 to 1995, 17 laboratories performed 100,000 serologic tests costing $7.1 million on Maryland residents; 90% of these tests were EIAs. The proportion of positive EIAs increased from 3.4% in 1992 to approximately 7.0% in 1994 and 1995, and the percentage of positive second tests (Western blot, WB) fell from 7.9% to 5.0%-5.5%. The large number of EIAs performed in comparison with the low incidence of LD in the state results in a low predictive value of a positive EIA test. Therefore, the WB is indicated to confirm equivocal and positive EIA tests when characteristic clinical findings of LD are not present. The 30,000 tests for LD performed annually on Maryland residents at a cost of over $2 million in direct medical costs must be added to the public health burden of LD in this state.

Diagnosis of Lyme borreliosis: non-specific serological reactions with Borrelia burgdorferi sonicate antigen caused by IgG2 antibodies

ELISA methods that measure IgG class antibodies to sonicated Borrelia burgdorferi may give false positive results. These errors could be traced to non-specific reactivity in subclass IgG2 in several instances. Sera were sampled randomly from two adult populations, which differed in having a high and low incidence of Lyme disease. If the binding of IgG2 subclass antibodies was left unrecorded in the test by the use of monoclonal reagent antibodies selective for IgG1 and IgG3, the frequency of positivity in the ELISA test decreased in samples from the low risk group. Twenty-one samples were found to be positive in an immunoblot confirmatory test. Correct prediction of positivity was obtained for 15 sera by ELISA restricted to IgG1 plus IgG3, for only four sera by ELISA restricted to IgG2 and for only six sera by IgG subclass non-restricted ELISA. A non-restricted ELISA with purified flagella of B. burgdorferi as the antigen predicted correctly 14 of the immunoblot-positive sera. The results of this ELISA correlated well with those of the IgG1 plus IgG3 subclass restricted ELISA in the high risk population (r = 0.95, prevalence of seropositivity 12%), but was significantly worse for the low risk group (r = 0.47, prevalence 2.9%). IgG subclass restriction also decreased cross-reactions of syphilitic sera in the ELISA with sonicated antigen.

Should we routinely screen for Lyme disease in patients with asymmetrical hearing loss?

Asymmetrical sensorineural hearing loss is usually investigated thoroughly but a diagnosis is often elusive. It is important to identify any treatable causes. Lyme disease is a tick-borne infection caused by the spirochaete Borrelia burgdorferi, which has been shown to cause asymmetrical sensorineural hearing loss, and has been successfully treated. Its incidence varies regionally; it occurs where there is a suitable environment for the tick and its animal hosts. We conducted a prospective study of 100 patients with asymmetrical sensorineural hearing loss. Serological testing for Lyme disease was performed. One patient had positive serology, but there was no improvement in her hearing following antibiotic treatment. We cannot conclude that our patient's hearing loss was caused by Lyme disease. We suggest that routine screening is not cost effective in regions with a low incidence of Lyme disease.