Increase in Tick-Borne Diseases in Minnesota: Lyme Disease and Human Granulocytic Ehrlichiosis
Despite the recent arrival of West Nile virus in the state, Lyme disease and human granulocytic ehrlichiosis (HGE) continue to be the most commonly reported vector-borne diseases in Minnesota. A striking increase in the number of reported cases of both of these tick-borne diseases has occurred over the last 3 years. The purpose of this article is to provide an update on the epidemiology of these diseases and to review important diagnostic criteria for each disease.
Epidemiology of Lyme Disease
From 1983, when the Minnesota Department of Health (MDH) began surveillance for Lyme disease, through 2002, 4,337 cases of Lyme disease were reported in Minnesota residents. The 867 cases reported in 2002 represent an 86% increase over the prior record of 465 cases in 2000 (Figure 1). As recently as 1999, the incidence of Lyme disease among Minnesota residents was 6.0 cases per 100,000 person-years; the incidence increased to 9.5 in 2000 and to 17.6 in 2002. The increase likely is not an artifact of surveillance and awareness efforts, which have not changed in recent years, but rather may be the product of factors such as increased numbers of infected ticks and/or changes in human behavior (e.g., people spending more time in tick habitat).
Most Minnesota residents with Lyme disease have had likely exposure to infected Ixodes scapularis (deer tick or black-legged tick) in certain east-central Minnesota counties or western Wisconsin (Figure 2). In 2002, Crow Wing and Cass Counties had the greatest numbers of likely exposures, with 187 and 56 cases, respectively. In the seven-county Twin Cities metropolitan area, I. scapularis and human Lyme disease exposures occur primarily in certain rural or semi-rural areas north and east of the Mississippi River (i.e., Anoka and Washington Counties and the northern edge of Ramsey County).
In areas where Lyme disease is endemic, the risk of infection is not uniform. I. scapularis are found in wooded and brushy habitats where humidity at ground level is sufficient to prevent their desiccation. The ticks generally are not found in open grassy fields or lawns, but can be found at the border between open habitat and thick brush or woods. People who engage in activities in wooded or brushy areas are at most risk.
The risk of Lyme disease also varies during the year. Eighty percent of the Lyme disease cases reported to MDH during 1995 to 2002 had onset from June to August (Figure 3), which corresponds to the May through July peak feeding period of I. scapularis nymphs. These immature ticks are so small that many people do not detect and remove them prior to the 24 to 48 hours of attachment necessary for disease transmission. Adult I. scapularis are active primarily during the early spring and again during the fall (i.e., September and October). Adult I. scapularis are large enough that many people can see and remove them prior to disease transmission. Rates of Borrelia burgdorferi (the Lyme disease agent) infection in Minnesota I. scapularis populations have not been studied well but are thought to be less than in endemic areas on the East Coast, where up to 50% of ticks may be infected.
Despite the record level of Lyme disease cases, demographic characteristics among cases have not changed. Similar to previous years, the median age of case-patients in 2002 was 38 years (range, <1 year to 91 years). In 2002, 546 (63%) case-patients were male, similar to the 1995-2001 figure of 60%. This predominance of males likely is due to behavioral factors (e.g., males participating more frequently in activities in woods and brush).
Epidemiology of HGE
HGE is a bacterial disease transmitted to humans by the same I. scapularis ticks that transmit Lyme disease. HGE was first recognized during 1993 in several patients from Minnesota and western Wisconsin. The HGE agent has been named Anaplasma phagocytophilum. (Note the genus change from Ehrlichia to Anaplasma.) A monocyctic form of ehrlichiosis caused by Ehrlichia chaffeensis is found throughout much of the southeastern and south central United States but rarely occurs in Minnesota.
Similar to Lyme disease, the number of HGE cases reported in Minnesota residents has increased recently. The 149 cases reported to MDH during 2002 represent a 60% increase over the prior high of 93 cases in 2001 and a 314% increase since 1999 (Figure 4). Some of this increase may be due to increasing recognition and testing by Minnesota physicians. However, the concurrent increase in Lyme disease cases suggests that at least part of the increase in HGE cases is “real.” Disease onsets peak in June (Figure 3), coinciding with the peak feeding period of I. scapularis nymphs. People are at greatest risk in the same counties where Lyme disease exposures are reported (Figure 2). In 2002, 55 HGE case-patients (50% of patients with known locations of exposure) likely had exposure to infected ticks in Crow Wing County.
Similar to Lyme disease, 61% of HGE case-patients during 1998-2002 were male. HGE case-patients ranged in age from <1 year to 95 years; the median age (59 years) has been older than that of Lyme disease case-patients (median age, 38 years in 2002).
In contrast to Lyme disease, a substantial majority (79%) of HGE case-patients in 1998-2002 were residents of greater Minnesota. This difference may be due in part to under-recognition of HGE among patients seeking health care in the Twin Cities metropolitan area after recreational exposures in other areas.
Clinical Aspects of Lyme Disease and HGE
The first sign of Lyme disease often is erythema migrans (EM); 87% of cases reported to MDH have EM. The rash occurs 3 to 30 days (median, 7 days) after exposure to an infected tick and typically is described as an erythematous annular border that gradually expands with partial central clearing. The EM usually expands to greater than 2 inches (5 cm) in diameter. This differs from smaller lesions (less than 1 inch in diameter) caused immediately by inflammation associated with the tick bite itself. Patients also may experience constitutional symptoms such as malaise, headache, fever, stiff neck, arthralgia, myalgia, and generalized lymphadenopathy. If untreated, the EM resolves within a median of 28 days (range, 1 day to 14 months); with treatment, EM diminishes within several days after initiating therapy.
Days or weeks following the onset of illness, B. burgdorferi disseminates through the bloodstream. Multiple skin lesions may occur but appear smaller than the primary EM. Constitutional symptoms and generalized lymphadenopathy are common. Within several weeks to months, some patients may experience signs of neurologic, cardiac, or rheumatologic involvement. Untreated or inadequately treated patients may experience late persistent Lyme disease months to years following the onset of acute illness.
Serology is the most useful laboratory test available as an adjunct to the clinical diagnosis of Lyme disease. Specimens should be screened first using a sensitive enzyme-linked immunosorbent assay (ELISA), and all samples judged to be positive or equivocal (borderline) should be confirmed by Western blot. Negative serological results in infected patients are rare but can occur when specimens are obtained before the patient has developed a significant antibody response (days to several weeks).
Onset of HGE occurs within 1 to 3 weeks of exposure to an infected tick. Common signs and symptoms include rapid onset of fever (often >102 F), chills, headache, and myalgia. Nausea, vomiting, anorexia, cough, and diarrhea are reported less frequently. Highly suggestive laboratory findings include leukopenia (WBC <4,500/mm3), thrombocytopenia (platelets <150,000/ mm3), and increased aminotransferase levels.
The diagnosis of HGE is based on clinical signs, a history of potential exposure to deer ticks, and supportive laboratory tests. The indirect immunofluorescence assay (IFA) for A. phagocytophilum antibodies has the highest sensitivity and specificity for HGE, when paired acute and convalescent serum samples are tested. Testing of a single serum sample less than 7 days after onset of illness is not a sensitive diagnostic method; in one recent study, only 24% of patients tested in this time frame had developed sufficient antibodies to be IFA positive.  Intracellular inclusions (morulae) also may be visualized in neutrophils of Wright-stained blood smears in approximately 60% of cases. Polymerase chain reaction (PCR) assays also may be used to detect A. phagocytophilum DNA, but PCR tests are not widely available at clinical laboratories.
Co-Infections With Tick-Borne Pathogens
Co-infections of Lyme disease and HGE from the same tick bite are possible. In 2002, 20 (13%) HGE cases also had objective evidence of Lyme disease.
Babesiosis, a third I. scapularis transmitted disease caused by Babesia microti, also can be found in combination with Lyme disease or HGE. An average of one or two cases of babesiosis are reported each year in Minnesota; a record seven cases were reported in 2002. Most cases are mild and self-limited, but severe infections may occur in patients with a history of splenectomy or immunosuppression.
Prevention of Tick-Borne Disease Co-Infections With Tick-Borne Pathogens
MDH continues to stress personal protective measures such as tick repellents, protective clothing, and frequent tick checks to prevent illness. There is no longer a Lyme disease vaccine on the market, and no large scale tick control methods currently are available. Persons should take appropriate precautions when they spend substantial time in woods or brushy areas in deer tick endemic areas, particularly during mid-May through mid-July.
For additional information about tickborne diseases contact the MDH Foodborne, Vectorborne and Zoonotic Diseases Unit at 651-201-5414 or 877-676-5414, or visit the MDH Lyme Disease website.