1 Epidemiology Research Center, Marshfield Medical Research and Education Foundation, Marshfield, WI.
2 Bureau of Communicable Diseases, Wisconsin Division of Public Health, Madison, WI.
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ABSTRACT |
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incidence; Lyme disease; population surveillance
Abbreviations: MESA, Marshfield Epidemiologic Study Area
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INTRODUCTION |
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In 1991, the Centers for Disease Control and Prevention established a Lyme disease case definition for use in state-based passive surveillance. A total of 88,967 cases of Lyme disease were reported to the Centers for Disease Control and Prevention between 1992 and 1998, including 3,237 from Wisconsin (1). The reported mean annual incidence rate in Wisconsin was highest among the north-central states and seventh highest nationally (1
). Few studies have assessed the accuracy and completeness of these state passive surveillance systems (2
4
). In Wisconsin, Lyme disease is often regarded by clinicians as a routine condition. It is frequently managed in urgent care centers or other high-volume outpatient settings, and thus substantial under-reporting of cases may occur.
Population-based studies of Lyme disease incidence in endemic areas have been limited (2, 5
, 6
). The Marshfield Epidemiologic Study Area (MESA) is a large population-based cohort covering 24 ZIP codes in north-central Wisconsin. Comprehensive inpatient and outpatient medical care data are available through the Marshfield Clinic for the nearly 80,000 residents of MESA. Retrospective review of medical records data for members of this cohort allows estimation of population-based incidence rates for disease and comparison with corresponding rates reported from other sources.
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MATERIALS AND METHODS |
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The Marshfield Epidemiologic Study Area was established in 1991 to facilitate population-based research using the integrated health care network of the Marshfield Clinic (7). The MESA region is a subset of the geographic area served by the clinic and includes 14 contiguous ZIP codes surrounding the city of Marshfield (MESA Central) and 10 ZIP codes surrounding three of the larger regional care centers (MESA North) (figure 1). These 24 ZIP codes were selected for inclusion in MESA on the basis of very high levels of population and health event coverage, as determined initially by market share data and later validated through random population surveys.
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Nearly all residents of MESA receive health care from the Marshfield Clinic (7). Previous validation efforts have indicated that the population coverage is 9496 percent or higher (7
) (Marshfield Medical Research Foundation, unpublished data). Across the 24 MESA ZIP codes, the median proportion of the population seeking care within the past 2 years was 86 percent.
In addition to high population coverage, the majority of health care services obtained by the residents of MESA are provided through the Marshfield Clinic or affiliated hospitals, and these events are captured by clinic data systems. In 2000, random sample surveys of the MESA population demonstrated that approximately 90 percent of outpatient visits are captured by the clinic data systems. Recent comparison of inpatient records with the state of Wisconsin hospital discharge database indicates that 93 percent of hospital discharges in MESA are captured. Comparison with state of Wisconsin mortality data indicates that the clinic captures 99 percent of deaths among residents of MESA. The high degree of population coverage and ascertainment of in-patient and outpatient health events makes MESA particularly well suited for studying the occurrence and clinical spectrum of disease in a general population.
Case definition and identification
Computerized International Classification of Diseases, Ninth Revision, codes from the Marshfield Clinic database were used to identify potential cases of Lyme disease that occurred in 19921998 in the MESA population. The specific codes identified were codes 088.81, 695.90, and 066.90. The Marshfield Clinic laboratory database was also searched for positive Lyme serologic tests (indirect fluorescent antibody or enzyme immunoassay, with or without Western immunoblot) to identify potential cases. Persons with a history of Lyme disease diagnosis prior to 1992 were excluded from study.
To validate these diagnostic codes and laboratory results, we abstracted data from patients' medical records. Potential cases were grouped into three categories (probable cases, possible cases, and noncases) based on the chart abstraction findings. Probable Lyme disease cases were defined as those patients who met the national case definition (1). The criteria for a probable case included physician-diagnosed erythema migrans of
5 cm in diameter or at least one late, noncutaneous manifestation with laboratory confirmation of infection. Late clinical manifestations included objective evidence of recurrent arthritis, cranial neuritis, radiculopathy, meningitis, encephalomyelitis, or cardiac manifestations.
Possible cases included patients with erythema migrans but no documented size information and patients with positive serology and recurrent joint pain or neurologic symptoms that did not meet the criteria for a probable case. A physician (E. A. B.) reviewed all final diagnoses, and patients with valid alternative diagnoses in their medical records were classified as noncases. Examples of valid alternative diagnoses included psoriatic arthritis, Osgood-Schlatter disease, cellulitis, tendonitis, figuratum erythema, palindromic rheumatism, allergic contact dermatitis, intradural schwannomas, carpal tunnel syndrome, and gout.
Probable and possible Lyme disease cases were further defined as either early or late Lyme disease. Patients with documented erythema migrans or a positive B. burgdorferi culture from skin biopsy were classified as early cases, while late Lyme disease cases had evidence of extracutaneous manifestations in addition to a positive diagnostic laboratory test in their medical records.
Estimation of reporting
Lyme disease has been a reportable disease in Wisconsin since 1980. Written case report forms, including information about patient demographics (name, race, gender, and date of birth), dates of onset and diagnosis, and clinical and laboratory information pertinent to the national Lyme disease case criteria, are completed by health care providers and mailed to local county health departments. These reports are then forwarded to the Wisconsin Division of Public Health where each form is reviewed, and those patients that have been determined to meet the national case criteria based on the information provided by the reporting form are included in the state database. Information about the patient's county of residence is included in this database, but no other geographic identifiers such as address or ZIP code were included in this database during the study period.
A list of the Lyme disease patients identified from Marshfield Clinic records was sent to the Wisconsin Division of Public Health, which linked this list of patients by name, birth date, and diagnosis date (within 4 weeks) to computerized records of reported Lyme disease cases that occurred during 19921998. This combined list of cases was used to calculate the percentage of Lyme disease cases reported to the state, and chi-squared tests were used to identify any differences in reporting across age, gender, and stage of disease at diagnosis. The Division of Public Health also provided statewide and county-specific reported Lyme disease incidence data for the years 19921998 to use in comparisons with the rates described below.
Incidence rate calculation
Annual incidence rates (19921998) were calculated for probable cases of Lyme disease in MESA. The denominators for these rates were based on linear interpolation of 1990 and 2000 Census population counts for the MESA ZIP code region. Average annual incidence rates stratified by gender, age (from birth to 20 years, 2144 years, 4564 years, and 65 years), and stage of Lyme disease at diagnosis (early vs. late) were also calculated. Used in the calculation of these stratified rates were 1990 Census estimates.
Incidence rates were then calculated for the state of Wisconsin on the basis of Division of Public Health surveillance data. However, the entire MESA ZIP code region covers only a small fraction of the state of Wisconsin and primarily lies within a geographic area that has moderate to high reported Lyme disease incidence (8) (figure 2). Therefore, to provide a more appropriate comparison with MESA rates, annual incidence rates based on Division of Public Health surveillance data were calculated for an eight-county region that surrounds and includes the MESA ZIP codes. The eight counties included in this group were Clark, Iron, Lincoln, Marathon, Price, Rusk, Taylor, and Wood. Annual intercensual estimates from the US Census Bureau were used in the calculation of annual incidence rates for the eight-county region and the state. Data from the 1990 US Census were used to calculate rates stratified by age, gender, and stage of disease at diagnosis for these regions.
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Human subjects
This study was approved by the Marshfield Clinic Institutional Review Board.
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RESULTS |
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Seven percent of the probable cases and 30 percent of the possible cases were identified for chart review on the basis of positive laboratory results alone and did not receive an International Classification of Diseases, Ninth Revision, code corresponding to Lyme disease. Six (86 percent) of these seven probable cases and 22 (85 percent) of these 26 possible cases were treated with antibiotics recommended for Lyme disease. Eighty-seven (85 percent) of the 102 probable cases had erythema migrans.
Cases reported to the state health department included 35 (34.3 percent) of the 102 probable Lyme disease cases and 17 (19.5 percent) of the 87 possible Lyme disease cases identified from patients' records. Twenty-three (6.7 percent) of the 342 noncases were also reported to the Wisconsin Division of Public Health as Lyme disease. As expected, the reporting rate for probable cases was significantly higher than the reporting rate for possible cases (p = 0.02). No significant differences in reporting were observed across time (data not shown), gender, age, or stage of disease at diagnosis (early vs. late) for probable cases (table 1). Among possible cases, late Lyme disease was three times more likely to be reported than early Lyme disease. Reporting of possible cases was most likely among the youngest patients and decreased substantially among patients older than age 20 years.
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No significant differences across gender or age were observed between the mean annual rates in MESA and the eight-county region (table 3). The rates in MESA and the eight-county region were higher than the statewide reported rates in every age and gender group. Overall, Lyme disease rates were highest in males and persons 4564 years of age. The lowest Lyme disease rates were observed in persons 2144 years of age. Within MESA, the incidence of late Lyme disease (2.8 per 100,000 per year) was substantially lower than the incidence of early Lyme disease (16.4 per 100,000 per year). No gender differences in the stage of Lyme disease at diagnosis were observed (data not shown).
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DISCUSSION |
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Lyme disease has been a reportable disease in all states since the early 1990s; however, underreporting of Lyme disease appears to be less common in Wisconsin compared with other states. In this study, approximately one third of probable Lyme disease cases were captured by the state surveillance system. Orloski et al. (4) note a 1036 percent reporting rate in their evaluation of Lyme disease reporting by physicians in New Jersey, and Meek et al. (11
) report an estimated Lyme disease reporting rate of 16 percent in their survey of Connecticut physicians. Only four of 17 confirmed cases were reported to the state health department in a study of Lyme disease in Olmsted County, Minnesota (2
), and Coyle et al. (3
) report estimated Lyme disease reporting rates of 10 percent in 1992 and 8 percent in 1993 in their survey of Maryland physicians. Studies of surveillance for other reportable diseases have shown that sensitivity varies from 6 percent to 90 percent (12
).
Direct comparison of probable cases from MESA with the cases that had actually been reported to the Division of Public Health suggests that, despite a degree of both underreporting and overreporting, the surveillance data provide a reasonable surrogate for characterizing the age, gender, and temporal distribution of Lyme disease cases detected in a general population. Reported patients, however, were less likely to have early stage Lyme disease. This is not surprising because early stage Lyme disease is often discovered and managed in high-volume care settings, which may reduce the likelihood of reporting.
The Lyme disease rates in MESA and the surrounding eight-county region were considerably closer in magnitude than anticipated given the observed underreporting of Lyme disease cases. Several factors might have contributed to this finding. First, a large number of patients initially identified by an International Classification of Diseases, Ninth Revision, code corresponding to Lyme disease were found not to meet the case criteria upon chart review. Forty (9 percent) of the persons classified as possible cases or noncases in MESA had been reported to the state and were included in state rate calculations. Inclusion of these possible cases and noncases in Division of Public Health incidence rates likely increased the similarity between the MESA and eight-county rates.
Second, it is expected that a relatively small number of cases of Lyme disease among residents of the MESA region were diagnosed by providers outside the Marshfield Clinic system. If these cases were reported to the Division of Public Health, they would have contributed to the eight-county rate but not to the MESA rate. The most recent MESA validation efforts indicate that a very high proportion of outpatient visits among residents of the MESA region (90 percent) are captured by the Marshfield Clinic data systems. Thus, the Division of Public Health might potentially have knowledge of approximately 10 or more additional Lyme disease cases from the MESA region. Lyme disease rates for MESA based on Division of Public Health data were not directly estimable because of a lack of ZIP code information in the Division of Public Health surveillance database.
Finally, the eight-county region encompasses a larger geographic area and population base than does MESA (322,297 residents vs. 77,280 residents, respectively; 2000 US Census), and the larger eight-county region includes health care providers who are not affiliated with the Marshfield Clinic. Although differences in the underlying risk of Lyme disease between residents of MESA and other residents of the eight-county region are expected to be small, it is plausible that the care-seeking behaviors of patients and the diagnostic and reporting practices of physicians do differ across providers and health care systems. It was not possible to determine the reporting rates of such physicians outside the Marshfield Clinic system.
In both MESA and the surrounding eight-county region, the Lyme disease incidence more than doubled from 1996 to 1998, but statewide rates increased by only 64 percent. This finding is not surprising because MESA is located in a region of Wisconsin with high endemic rates of Lyme disease, while the state rates include cases and denominators from nonendemic as well as endemic areas. This finding could also have been influenced by increased Lyme disease reporting by medical providers in north-central Wisconsin from 1996 to 1998. However, because this increase is reflected both in the passive surveillance data and by medical record abstraction of our population-based cohort, it is unlikely that reporting variability was a major contributing factor.
Findings from two earlier studies of tick populations in Wisconsin suggest that the regional increase in Lyme disease incidence may be related to an increase in the population density and geographic range of Ixodes scapularis (formerly Ixodes dammini), the tick vector of B. burgdorferi (13, 14
). This increase was especially noted in the north-central region of the state, while eastern Wisconsin remained relatively uninhabited by ticks during the entire 19811994 surveillance period. It may be that the overall state rates do not reflect the dramatic 19961998 increase in incidence, because the Lyme disease incidence rates calculated for the entire state were based on data from regions with relatively low and stable tick populations as well as high-risk areas. This finding emphasizes the need to examine incidence trends in smaller geographic areas representing high-risk populations.
In conclusion, these findings suggest that the Wisconsin Division of Public Health surveillance system is monitoring trends in Lyme disease incidence reasonably well across time, gender, and age categories and that underreporting of Lyme disease cases in Wisconsin is less common than reported in other published studies. This study highlights the need for continued assessment and validation of public health surveillance systems with data from population-based cohorts such as the Marshfield Epidemiologic Study Area.
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ACKNOWLEDGMENTS |
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The authors thank Juanita Herr, Sonia Weigel, Debbie Hilgemann, Katherine Nieman, and Carolee Schueller for their data collection efforts; Lorelle Ziegelbauer for programming assistance; and Carol Beyer for assistance in manuscript preparation.
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NOTES |
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REFERENCES |
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