LD is emerging in Nova Scotia, and public health surveillance data have been useful for characterizing risk and describing the clinical presentation of LD. Most cases are characterized by early localized disease. Compared with data from the United States, Nova Scotia case-patients were less likely to have EM reported as the presenting manifestation (69% vs. 53%) (11). Although published studies report that up to 80% of LD case-patients have EM, these findings were in the context of a vaccine trial or active laboratory-based surveillance study in a hyperendemic region where patients were followed closely and physicians were very experienced in diagnosing EM (12,13). The public health surveillance system in Nova Scotia captures both clinician-diagnosed EM and other skin rashes. Although almost 90% of case-patients reported a rash, only 53% had clinician-diagnosed EM. However, some of the other skin rash cases are also likely to represent EM. Central clearing in only 50% of EM lesions was consistent with other reports that EM might have diffuse erythema or enhanced central erythema rather than central clearing (14). An increase in the proportion of cases with clinician-diagnosed EM over time suggests physicians have become more aware of and/or better able to diagnose EM.

The most common manifestation of late LD in Nova Scotia was arthritis. Although up to 60% of untreated LD results in arthritis, earlier recognition and treatment is expected to greatly reduce its frequency (7,15–17). The increase in the proportion of Nova Scotia case-patients reporting recurrent brief episodes of large joint swelling to 32.5% in 2013 is similar to the proportion of US cases of Lyme arthritis (30%) (11). The higher proportion of cases with arthritis in 2013 does not necessarily reflect a large proportion of missed cases during earlier years but might be related to misreporting of arthralgia and reporting bias toward serologically confirmed cases, as well as a general increase in the number of cases and duration of LD in Nova Scotia. Further investigation is needed to understand how many case-patients reporting joint symptoms fit the clinical diagnosis of Lyme arthritis.

As in the United States, other manifestations, including atrioventricular block and neuroborreliosis, were uncommon (11). Only 26% of LD patients in Nova Scotia recalled a tick bite, consistent with US data where 84% and 86% of patients with EM and Lyme arthritis, respectively, failed to recall exposure to blacklegged ticks (18–21).

The incidence of LD in Canada has increased during the last decade (2,4), and Nova Scotia has the highest reported incidence (16 cases/100,000 population in 2013). Incidence varies greatly geographically; 1 health region (DHA 1) reported case rates of ≈200/100,000 population in 2013, which is higher than those in northeastern US states (11). The increased incidence most likely resulted from the increased number of established blacklegged tick populations; increases in the size, geographic range, and pathogen prevalence within these populations; increasing rates of human infection; and better identification and reporting of LD. Infected blacklegged ticks can be sporadically identified in other regions of the province, but only 1.5% of LD cases were not linked to known endemic regions, suggesting the risk remains localized. Our serosurvey did not identify any persons with B. burgdorferi antibodies based on CDC criteria, and even if the 2 borderline results were included, the estimated provincial seroprevalence was much less than 1%. Even in DHAs known to contain endemic foci of LD, we failed to detect any positive serum and found an estimated seroprevalence of <2% in the DHA with the highest reported LD incidence. B. burgdorferi seroprevalence in the northeastern United States, with similar environmental conditions to Nova Scotia, ranges from 0% to 18.8% (22,23). The fact that tick populations endemic to the northeastern United States have been established for much longer than in Nova Scotia might explain this difference. Widespread clinical testing, coupled with the serosurvey results, suggests LD cases most likely are not being missed in Nova Scotia.

Although all of the serum used for the serosurvey was negative by 2-tier testing, 8% of serum samples positive by whole-cell EIA (17/215) were positive on the C6 ELISA. Although some data suggest that classifying LD on the basis of C6 alone is more sensitive than the 2-tier algorithms (24), the potential exists for false-positive and false-negative results. The literature suggests that the C6 ELISA specificity is 98.4%–98.6% (24,25). However, when used as the supplemental test to positive whole-cell lysate EIA, as in our study, its specificity is estimated at 99.1%–99.8% (26). The 17 positive C6 results in our study could be in keeping with false-positive results, with this reported specificity. Alternatively, these reactive C6 serum samples could represent patients infected with B. burgdorferi and treated early with appropriate antimicrobial drugs. However, because the serum used could not be linked to patients, we have no clinical information to support this possibility. Data suggest that the C6 ELISA has a higher sensitivity for early infection and can be positive before the IgG WB completely matures to include the required 5/10 bands (27). In addition, evidence suggests that patients treated early in infection abort the seroconversion response, and a positive IgG WB might not develop (27,28). Another possibility is that the positive C6 ELISA results from cross-reactivity with another Borrelia species, such as B. miyamotoi, which has been identified in blacklegged ticks in the United States and Canada, including Nova Scotia (29,30). Using EIA and WB assays specific for B. miyamotoi, Krause et al. found serologic evidence of acute infection in patients living in endemic regions who had a viral-like illness (31). Although a recent study found 2 of 34 ticks from Nova Scotia submitted as part of passive surveillance had positive PCR for B. miyamotoi (30), no data are available that examined the potential cross-reactivity of whole-cell sonicate or C6 B. burgdorferi EIAs with patient serum containing antibodies to B miyamotoi. If these hypotheses are correct, we should have seen a disproportionate number of positive serum samples from regions with the highest risk for exposure to infected blacklegged ticks, such as DHA 1, where an infected population of blacklegged ticks has been established since 2003 and where most case-patients reside and were exposed. However, seroprevalence of C6 positive serum did not differ significantly among any of the DHAs.

Our study has several limitations. Our clinical data are limited to the case report forms used by Nova Scotia public health professionals; thus, the precision regarding the clinical presentation is limited. For example, the inclusion of categories of influenza-like illness is not specific and could represent a respiratory illness. Furthermore, the case reports do not always differentiate between single EM and multiple EM, so classification of early localized and early disseminated infection was not possible. Early LD, the most common presentation, is predominantly a clinical diagnosis for which sensitivity of serologic testing is poor (<50%) and not recommended. Thus, surveillance data might underestimate incidence if not all clinical cases are captured. We recognize that estimating the extent of underreporting is difficult and that underreporting could vary geographically. However, in the cohort reported here, 42 of 66 cases classified as “probable: EM + endemic exposure” followed the Infectious Diseases Society of America guidelines (7) and were not tested serologically. These reports have come from 5 different districts across the province suggesting that physicians are reporting at least some B. burgdorferi infections on the basis of clinical presentation alone.

Another limitation is that the serosurvey samples might not be representative of the population at risk. We used samples of residual serum from diagnostic testing that might be biased toward a population with more medical co-morbidities or different risk and health-seeking behaviors (32). Our study attempted to reduce this bias by selecting samples that were originally collected for routine diagnostic testing, with the aim of capturing persons undergoing routine well-person screening. However, this sample will exclude persons who generally do not access regular medical care. Despite this limitation, the sampling method has been used for other infections and is thought to provide an acceptable balance between representativeness and feasibility (both practical and financial). In fact, the only published study that has compared the residual serum approach with population-based sampling yielded comparable estimates of immunity against 5 vaccine-preventable diseases, with an ≈7-fold increased cost for the population-based approach (33). Still, risk for exposure to blacklegged ticks through outdoor activity in endemic regions was unavailable for serosurvey specimens and probably has greater heterogeneity than probability of vaccination. Also, our sample did not include the 0–9- or >65-year age groups.

Although LD incidence is increasing in Nova Scotia, infections appear to be restricted to regions within the province where populations of infected blacklegged ticks are known to be endemic. These findings support a targeted approach to public health risk messaging. Our seroprevalence study suggests that <1% of Nova Scotia residents have been exposed to B. burgdorferi. However, as tick populations continue to expand, we expect LD rates to continue to increase. Residents of, and travelers, to Nova Scotia need to be vigilant and take precautions to reduce their risk for LD when they venture into regions where ticks are present. Because only a minority of patients will report a tick bite, physicians should be aware of the manifestations of LD and consider it when patients have compatible symptoms and exposure to an endemic region, through residence or travel, in Nova Scotia.