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Lyme disease surveillance based on provider and laboratory reports underestimates incidence. We developed an algorithm for automating surveillance using electronic health record data. We identified potential Lyme disease markers in electronic health record data (laboratory tests, diagnosis codes, prescriptions) from January 2017-December 2018 in 2 large practice groups in Massachusetts, USA. We calculated their sensitivities and positive predictive values (PPV), alone and in combination, relative to medical record review. Sensitivities ranged from 57% (95% CI 47%-69%) for immunoassays to 87% (95% CI 70%-100%) for diagnosis codes. PPVs ranged from 53% (95% CI 43%-61%) for diagnosis codes to 58% (95% CI 50%-66%) for immunoassays. The combination of a diagnosis code and antibiotics within 14 days or a positive Western blot had a sensitivity of 100% (95% CI 86%-100%) and PPV of 82% (95% CI 75%-89%). This algorithm could make Lyme disease surveillance more efficient and consistent.

Background: The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease spirochete Borrelia burgdorferi in North America. Though the tick is found across the eastern United States, Lyme disease is endemic to the northeast and upper midwest and rare or absent in the southern portion of the vector's range. In an effort to better understand the tick microbiome from diverse geographic and climatic regions, we analysed the bacterial community of 115 I. scapularis adults collected from vegetation in Texas and Massachusetts, representing extreme ends of the vector's range, by massively parallel sequencing of the 16S V4 rRNA gene. In addition, 7 female I. scapularis collected from dogs in Texas were included in the study. Results: Male I. scapularis ticks had a more diverse bacterial microbiome in comparison to the female ticks. Rickettsia spp. dominated the microbiomes of field-collected female I. scapularis from both regions, as well as half of the males from Texas. In addition, the male and female ticks captured from Massachusetts contained high proportions of the pathogens Anaplasma and Borrelia, as well as the arthropod endosymbiont Wolbachia. None of these were found in libraries generated from ticks collected in Texas. Pseudomonas, Acinetobacter and Mycobacterium were significantly differently abundant (p < 0.05) between the male ticks from Massachusetts and Texas. Anaplasma and Borrelia were found in 15 and 63% of the 62 Massachusetts ticks, respectively, with a co-infection rate of 11%. Female ticks collected from Texas dogs were particularly diverse, and contained several genera including Rickettsia, Pseudomonas, Bradyrhizobium, Sediminibacterium, and Ralstonia. Conclusions: Our results indicate that the bacterial microbiomes of I. scapularis ticks vary by sex and geography, with significantly more diversity in male microbiomes compared to females. We found that sex plays a larger role than geography in shaping the composition/diversity of the I. scapularis microbiome, but that geography affects what additional taxa are represented (beyond Rickettsia) and whether pathogens are found. Furthermore, recent feeding may have a role in shaping the tick microbiome, as evident from a more complex bacterial community in female ticks from dogs compared to the wild-caught questing females. These findings may provide further insight into the differences in the ability of the ticks to acquire, maintain and transmit pathogens. Future studies on possible causes and consequences of these differences will shed additional light on tick microbiome biology and vector competence. [ABSTRACT FROM AUTHOR]

To evaluate a theory-based educational program to prevent Lyme disease and other tick-borne illnesses (TBI), a randomized controlled trial of an educational program was delivered to ferry passengers traveling to an endemic area in southeastern Massachusetts. Rates of TBI and precautionary and tick check behaviors were measured over three summers in 30,164 passengers. There were lower rates of TBI among participants receiving TBI education compared with control participants receiving bicycle safety education (relative risk [RR] = 0.79) and a 60% reduction in risk among those receiving TBI education who visited Nantucket Island for more than 2 weeks compared to control participants (RR = 0.41, 95% confidence intervals = 0.18 to 0.95, p < .038). TBI-educated participants were also significantly more likely to take precautions (use repellent, protective clothing, limit time in tick areas) and check themselves for ticks. The study demonstrates that a theory-based Lyme disease prevention program can increase precautionary behavior and result in a significant reduction in TBI.

The seasonal host-seeking pattern of nymphal Ixodes dammini infected with Babesia microti or Borrelia burgdorferi was determined on Nantucket Island, Massachusetts, during 1985. The peak period of host-seeking by infected nymphal I. dammini occurred in May and June. On a per person-hour basis, the number of infected ticks collected reached a maximum in May (Babesia = 17.3; Borrelia = 16.2). The number of infected ticks remained high in June, but decreased notably in July, August, and September. Transmission risk of the tick-borne etiologic agents of Lyme disease and human babesiosis in Massachusetts is greatest during the late spring-early summer months of May and June.

To determine whether short-tailed shrews (Blarina brevicauda) serve as reservoir hosts for the Lyme disease spirochete (Borrelia burgdorferi) and the agent of human babesiosis (Babesia microti), we examined nymphal ticks that had fed as larvae on shrews collected from 3 enzootic sites in coastal Massachusetts for evidence of infection by either or both of these agents. Xenodiagnosis indicated that 11 of 14 shrews were infected by B. burgdorferi. One of 3 piroplasm-infected shrews also infected ticks with B. microti. In a site where the piroplasm is endemic, 11 of 17 shrews showed patent parasitemias by thin blood smears. Of these, 4 had parasitemias exceeding 40%. Few immature ticks infested shrews, however, suggesting that B. brevicauda, although abundant in some endemic sites and serving as a competent reservoir, would contribute minimally to the population of infected nymphs.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

In evaluating the white-footed mouse as a reservoir host for the Lyme disease spirochete, we compared spirochete infection in vector ticks (Ixodes dammini) having different histories of attachment to these mice, estimated their relative importance as hosts for immature I. dammini and compared the seasonality of tick activity and spirochetemia in mice. Infection in trapped white-footed mice appears to be universal. Prevalence of spirochetal infection in I. dammini correlates with frequency of attachment to mice, and in mice, with the season of vector activity. The relative abundance of this mouse makes it numerically the most important host for I. dammini. Most immature I. dammini appear to attach to white-footed mice. Taken together, these considerations demonstrate that the white-footed mouse serves as reservoir for the Lyme disease spirochete in coastal Massachusetts.

To evaluate the role of deer in regulating the abundance of the deer tick (Ixodes dammini) we attempted to treat with acaricide, but eventually removed, about 70 percent of deer from Great Island, Cape Cod, Massachusetts. Deer were captured in box traps, a corral, an entanglement net, and with rifle-fired tranquilizer. Failure of these attempts, combined with ineffective acaricides, led us to deer destruction begun in fall 1982. Larval tick abundance on mice was monitored before and after deer removal. We concluded that deer removal, to the extent accomplished, did not markedly reduce the abundance of the tick. Reduced abundance of deer may not result in reduced abundance of immature ticks if deer removal follows the period of adult tick feeding, or if intensity of infestation per deer increases, or if other mammals substitute as suitable hosts. Reduced tick abundance may be delayed if unattached immature ticks survive more than one year.

To determine whether deer may serve as reservoir hosts for the Lyme disease spirochete, we sought evidence of infection in nymphal Ixodes dammini derived from larvae that had engorged on white-tailed deer. A total of 19 deer were shot in two Lyme disease foci in Massachusetts during September 1986, the season in which larvae were most abundant. An average of 342 larval ticks of this species were collected from each deer. Of those that developed to the nymphal stage, the gut contents of 185 were examined for Borrelia burgdorferi by a direct fluorescent antibody test. Spirochetes were detected in about 1% of these nymphs, a rate of infection attributable to transovarial transmission. In contrast, infection was detected in 23% of 39 field-swept nymphal ticks of the same cohort that were collected during the following season. Although deer may be infested by numerous larval I. dammini, such ticks appear not to become infected by Lyme disease spirochetes.

We describe a focal epidemic of Lyme disease, which spread from a nature preserve and affected an adjacent community of permanent residents in coastal Massachusetts. The attack rate from 1980 through 1987 was 35 percent among 190 residents living within 5 km of the nature preserve and was greatest (66 percent) among those living closest to the preserve. The risk of infection bore little relation to sex or age. Late Lyme disease, which clustered near the preserve, occurred mainly in residents infected early in the epidemic who did not have a history of erythema migrans and did not receive antibiotic therapy. All the residents with serologic evidence of infection had early or late clinical manifestations of Lyme disease, or both, during the period of study. The seasonal risk of infection was bimodal--greatest in June, with a secondary peak in October--and corresponded to periods of increased transmission. In the nature preserve, the density of the vector tick, Ixodes dammini, exceeded that in other New England sites. The zoonosis rapidly became endemic, and the severity of its impact correlated with the abundance of deer. This epidemic of Lyme disease demonstrated that outbreaks can be focal and can spread rapidly within a community of permanent residents.

Tick-borne zoonoses pose a serious burden to global public health. To understand the distribution and determinants of these diseases, the many entangled environment–vector–host interactions which influence risk must be considered. Previous studies have evaluated how passive tick testing surveillance measures connect with the incidence of human Lyme disease. The present study sought to extend this to babesiosis and anaplasmosis, two rare tick-borne diseases. Human cases reported to the Massachusetts Department of Health and submissions to TickReport tick testing services between 2015 and 2021 were retrospectively analyzed. Moderate-to-strong town-level correlations using Spearman's Rho (ρ) were established between Ixodes scapularis submissions (total, infected, adult, and nymphal) and human disease. Aggregated ρ values ranged from 0.708 to 0.830 for anaplasmosis and 0.552 to 0.684 for babesiosis. Point observations maintained similar patterns but were slightly weaker, with mild year-to-year variation. The seasonality of tick submissions and demographics of bite victims also correlated well with reported disease. Future studies should assess how this information may best complement human disease reporting and entomological surveys as proxies for Lyme disease incidence in intervention studies, and how it may be used to better understand the dynamics of human–tick encounters. [ABSTRACT FROM AUTHOR]

Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens' hosts. For example, CRISPR-based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha's Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits' proliferation, pending approvals from relevant constituents. Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats. [ABSTRACT FROM AUTHOR]

Background: The use of animal host-targeted pesticide application to control blacklegged ticks, which transmit the Lyme disease bacterium between wildlife hosts and humans, is receiving increased attention as an approach to Lyme disease risk management. Included among the attractive features of host-targeted approaches is the reduced need for broad-scale pesticide usage. In the eastern USA, one of the best-known of these approaches is the corn-baited "4-poster" deer feeding station, so named because of the four pesticide-treated rollers that surround the bait troughs. Wildlife visitors to these devices receive an automatic topical application of acaricide, which kills attached ticks before they can reproduce. We conducted a 5-year controlled experiment to estimate the effects of 4-poster stations on tick populations in southeastern Massachusetts, where the incidence of Lyme disease is among the highest in the USA., Methods: We deployed a total of forty-two 4-posters among seven treatment sites and sampled for nymph and adult ticks at these sites and at seven untreated control sites during each year of the study. Study sites were distributed among Cape Cod, Martha's Vineyard, and Nantucket. The density of 4-poster deployment was lower than in previous 4-poster studies and resembled or possibly exceeded the levels of effort considered by county experts to be feasible for Lyme disease risk managers., Results: Relative to controls, blacklegged tick abundance at treated sites was reduced by approximately 8.4%, which is considerably less than in previous 4-poster studies., Conclusions: In addition to the longer duration and greater replication in our study compared to others, possible but still incomplete explanations for the smaller impact we observed include the lower density of 4-poster deployment as well as landscape and mammalian community characteristics that may complicate the ecological relationship between white-tailed deer and blacklegged tick populations.

Background: To determine the age-specific prevalence of Lyme disease and whether preventive behaviors on Nantucket Island correlate with Lyme disease, we surveyed island residents., Methods: A survey with questions on Lyme disease symptoms, history, and preventive behaviors was mailed to all residents. Respondents were stratified by likelihood of having had Lyme disease. A subsample was selected for examination, and then classified according to the Lyme disease national surveillance case definition., Results: The overall lifetime prevalence of Lyme disease for Nantucket residents was 15% (CI, 10%-19.8%): 19% among females, and 11% among males. The prevalence was highest among age groups 0-16 and 30-49 years. Overall, 86% of the population practiced at least one behavior. The most frequently reported preventive behavior was checking oneself for ticks (80%), followed by wearing protective clothing (53%), avoiding tick areas (34%), and using tick repellent (11%). Younger individuals practiced fewer preventive behaviors than older individuals (p=0.001). Although males reported greater tick exposure than females, females uniformly practiced preventive behaviors more frequently (p=0.001). The practice of preventive behaviors was not associated with a history of Lyme disease, but finding more than 5 ticks per year on oneself was (p=0.001)., Conclusion: Lyme disease is highly prevalent on Nantucket Island. Young people are particularly at risk and health education should emphasize preventive behaviors less frequently practiced: using tick repellent, avoiding tick areas, and wearing protective clothing.

To determine whether the white-footed mouse reservoir host (Peromyscus leucopus) of the agent of Lyme disease (Borrelia burgdorferi) naturally mounts an immune response against the full range of antigens expressed by this zoonotic pathogen, we analyzed the pattern of immunoreactivity of these rodents at sites in which the intensity of transmission differs. Although the incidence of seroconversion within the reservoir population relates proportionally to the density of subadult deer ticks (Ixodes dammini), seroprevalence appears constant. About a fifth as many juvenile mice recognize spirachete antigens as do adult mice. Virtually all reservoir mice in nature recognize the p20, p35.5, p39, and p58 antigens, regardless of the intensity of transmission. Seropositive mice retain reactivity to a wide range of spirochetal antigens. Few mice recognize flagellin, OspB, and OspC. Although a third of serum samples include reactivity to a 31-kDa band, this reaction is irregular and may represent an uncharacterized antigen that comigrates with OspA. Mice captured where transmission is intense recognize the same spectrum of antigens as do mice captured where vector ticks are scarce.

The authors compared the contribution of white-footed mice (Peromyscus leucopus), chipmunks (Tamias striatus), and meadow voles (Microtus pennsylvanicus) to infection of vector ticks with the Lyme disease spirochete, Borrelia burgddorferi. At one Massachusetts location where Lyme disease is endemic, all three species of rodents were found to be infected. Prevalence of infection, however, varied from 90% for mice, and 75% for chipmunks to just 5.5% for meadow voles. Infectivity of these hosts for larval Ixodes dammini also varied, but mice were found to be the most infective, followed by chipmunks and meadow voles. Density estimates of these three hosts, collected between 1981 and 1986 in three coastal Massachusetts locations, revealed that mice were more abundant than the other two rodents in areas in which ticks were abundant. In addition, mice were infested more abundantly with larval I. dammini than the other two host species. Integrating these results, we determined each species' "reservoir potential," a novel term which describes the relative contribution made by a host species to the horizontal infection of a vector population. The authors' findings demonstrate that, at least in coastal Massachusetts, P. leucopus is the most important small mammal reservoir for B. burgdorferi.

Background. An investigation of the relationship between incident human cases of Lyme disease and seroprevalence of antibodies to B. burgdorferi in dogs was undertaken in order to determine whether dogs might serve as sentinels for Lyme disease. Methods. 3011 canine serum samples were analyzed by ELISA for antibody to B. burgdorferi. Records of incident human cases of Lyme disease were obtained from the Massachusetts Department of Public Health. Results. Regression analyses of the relationship between the log10 (mean incidence in people 1985-1989) and canine seroprevalence from July 1988-August 1989 revealed that canine seroprevalence was highly predictive of incidence (R² = 0.86, p < .0001). A logistic regression model that incorporates the altitude of the town where each dog was resident the date of sampling, and information on each dog's age, sex, and breed adequately explained the risk of canine seropositivity. Dogs resident at altitudes less than 200 feet, of sporting or large mixed breeds, and greater than two years of age were five times, four times, and almost three times more likely, respectively, to exhibit seropositivity than were other dogs. Conclusions. Estimates of the prevalence of antibody to B. burgdogferi in dog populations offers a sensitive, reliable and convenient measure of the potential risk to people of B. burgdogferi in the environment. Risk factors for canine seropositivity may directly of indirectly illuminate certain aspects of the epidemiology of human Lyme disease. [ABSTRACT FROM AUTHOR]

Objective Autoantigen presentation by HLA-DR molecules is thought to be a central component of many autoimmune diseases, but identifying disease-relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic-refractory Lyme arthritis, in which infection-induced autoimmunity is thought to play an important role. Methods Using tandem mass spectrometry, naturally presented HLA-DR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera. Results Of 120 HLA-DR-presented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in ∼10-30% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritis-associated HLA-DR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic-responsive arthritis, those with antibiotic-refractory arthritis had significantly higher concentrations of ECGF in synovial fluid ( P < 0.0001) and more often had ECGF antibody reactivity. Among non-antibiotic-treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis. Conclusion T and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic-refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness. [ABSTRACT FROM AUTHOR]

Objective Single-nucleotide polymorphisms (SNPs) that alter immune function, inflammatory responses, and disease susceptibility have been identified in several genes encoding Toll-like receptors (TLRs). The TLR SNPs with the best evidence of an effect on immune function are those in TLR1 (1805GG), TLR2 (2258GA), and TLR5 (1174CT). This study was undertaken to assess the frequency and functional outcomes of these polymorphisms in patients with Lyme disease. Methods SNP frequencies and functional outcomes were assessed in 248 patients with Lyme disease. Cytokine and chemokine levels were determined using multiplex assays in the serum of patients with erythema migrans (EM), joint fluid of patients with Lyme arthritis, and supernatants of Borrelia burgdorferi-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Lyme arthritis. Results The frequency of the TLR1-1805GG polymorphism was greater in patients with antibiotic-refractory arthritis compared with patients with EM or those with antibiotic-responsive arthritis. Early in the illness, patients with EM carrying 1805GG, primarily those infected with B burgdorferi 16S-23S ribosomal spacer RNA intergenic type 1 (RST1) strains, had higher serum levels of interferon-γ (IFNγ), CXCL9, and CXCL10 and had more severe infection than EM patients carrying the 1805TG/TT polymorphism. These inflammatory responses were amplified in patients with Lyme arthritis, and the highest responses were observed in patients with 1805GG in the antibiotic-refractory group who had been infected with RST1 strains. When PBMCs from patients with Lyme arthritis were stimulated with a B burgdorferi RST1 strain, the 1805GG group had a significantly larger fold increase in the levels of IFNγ, CCL2, CXCL9, and CXCL10 compared to the 1805TG/TT group. In contrast, the TLR2 and TLR5 polymorphisms did not vary in frequency or function among the groups. Conclusion The TLR1-1805GG polymorphism in B burgdorferi RST1-infected patients was associated with stronger Th1-like inflammatory responses, an environment that may set the stage for antibiotic-refractory arthritis. [ABSTRACT FROM AUTHOR]

Objective To determine the burden and viability of Borrelia burgdorferi in the skin and joints of patients with Lyme disease. Methods Standard and quantitative polymerase chain reaction (PCR) techniques were used to detect B burgdorferi DNA in skin samples from 90 patients with erythema migrans (EM) and in synovial fluid (SF) from 63 patients with Lyme arthritis (LA) and in synovial tissue from 9 patients. Quantitative PCR determinations of B burgdorferi DNA, messenger RNA (mRNA), and ribosomal RNA (rRNA) were made in 10 skin samples from EM patients and 11 SF samples from LA patients. Results Skin lesions in most patients with EM had positive PCR results for B burgdorferi DNA. In the majority of patients with LA, a late disease manifestation, PCR results in pretreatment SF samples were positive. In patients with antibiotic-refractory arthritis, positive PCR results persisted for as long as 11 months, but positive results in samples taken during the postantibiotic period did not correlate with relapse or with the subsequent duration of arthritis, and at synovectomy, all results of PCR of synovial tissue were negative. B burgdorferi mRNA, a marker of spirochetal viability, was detected in 8 of 10 skin samples from EM patients, but in none of 11 SF samples from LA patients, even when obtained prior to antibiotic administration. Moreover, the median ratio of spirochetal rRNA to DNA, a measure of ribosomal activity, was 160 in the 10 EM skin samples, but only 0.15 in the 3 LA SF samples with positive results. Conclusion B burgdorferi in the skin lesions of EM patients were active and viable, whereas those in the SF of LA patients were moribund or dead at any time point. Thus, detection of B burgdorferi DNA in SF is not a reliable test of active joint infection in Lyme disease. [ABSTRACT FROM AUTHOR]

Disease prevention models have shown individuals are more likely to engage in precautionary behavior if they have confidence in their ability to identify disease symptoms and understand health risks. In immigrant populations, communicating the risks poses greater challenges since linguistic and cultural barriers may impede acceptance of the new behavior. The Brazilian population on Martha’s Vineyard, Massachusetts, is at high risk for Lyme disease (LD), the most common vector-borne illness in the United States largely preventable by limiting tick exposure. We surveyed 103 Brazilians on MV about their health beliefs and perceptions of LD risk and assessed their level of precautionary behaviors and the cultural factors influencing them. The population had only a moderate perception of risk and little understanding of LD. Forty-one percent did not think LD posed a risk, while 79% were not sure they could recognize symptoms. Accordingly, the population as a whole reported taking few precautions. [ABSTRACT FROM AUTHOR]