https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140261/

Comment; While the prevalence of human pathogens has been quantified in ticks in Adair County, Missouri, the prevalence of residents acquiring tick-borne diseases and seeking medical treatment has not. A public survey (n=109) revealed that 96% of respondents reported finding attached ticks on their person; of these, 38% developed symptoms post tick bite; of these, 55% reported consultation with a health care provider. Overall, 89% of practitioners surveyed had treated at least one patient for tick-borne disease. This seems to be a tremendous under-estimate of the pervalence, making me wonder how many diagnosis’ are missed.

Deborah A. Hudman, MSAuthor informationCopyright and License informationDisclaimerGo to:

Abstract

While the prevalence of human pathogens has been quantified in ticks in Adair County, Missouri, the prevalence of residents acquiring tick-borne diseases and seeking medical treatment has not. A public survey (n=109) revealed that 96% of respondents reported finding attached ticks on their person; of these, 38% developed symptoms post tick bite; of these, 55% reported consultation with a health care provider. Overall, 89% of practitioners surveyed had treated at least one patient for tick-borne disease. Rocky Mountain spotted fever and Lyme disease were the most common illnesses diagnosed, however, the only confirmed cases reported by Missouri Department of Health and Senior Services from 2013–2017 were ehrlichiosis. Results from these surveys indicate that exposure to ticks is common and ehrlichiosis infections are likely underdiagnosed while Rocky Mountain spotted fever and Lyme disease are likely overdiagnosed.Go to:

Introduction

Land managers, farmers, and people who recreate outdoors have an increased risk of tick exposure and thus an increased risk of infection with tick-borne pathogens. Three tick species are present in Northeast Missouri: the lone star tick, Amblyomma americanum, (Linnaeus, 1758), American dog tick, Dermacentor variabilis (Say, 1821), and the blacklegged tick, Ixodes scapularis (Say, 1821). The lone star tick is the most prevalent species.12 Due to the abundance of this tick and its propensity to feed on humans, pathogens transmitted by lone star ticks pose an important threat to human health. Lone star ticks transmit the etiological agents which cause ehrlichiosis, Heartland virus, Southern tick-associated rash illness (STARI), tularemia, and their bites have been associated with Alpha-gal allergy or mammalian meat allergy.35 In addition, there is some evidence that lone star ticks may have a role in spotted fever group (SFG) rickettsiae like diseases.68 In Adair County, 436 adult lone star ticks demonstrated infection rates of 6% for Borrelia lonestari, 19% for Ehrlichia chaffeensis, 3% for Ehrlichia ewingii, 36% for Rickettsia amblyommatis, and 1% for Rickettsia montanensis.9 Briefly, B. lonestari and R. amblyommatis have been implicated, but not definitively proven, as putative agents of STARI which is a Lyme disease-like illness.1011 Ehrlichia chaffeensis and E. ewingii are the causative agents of ehrlichiosis which ranges from influenza-like symptoms in its mildest form to an occasionally fatal course. Both R. amblyommatisand R. montanensis have been implicated in the SFG rickettsiae like diseases.68

Mapping the public health threat of tick-borne diseases (TBDs) requires quantification of not only the density of infected host-seeking ticks but also the rate of human exposure to these ticks. The purpose of this study was to collect data on: a) the frequency of tick encounters in people who work outdoors in Adair County; b) the frequency of treatment of TBDs in clinics within Adair County; and c) the reported numbers of TBDs for Adair County by the Missouri Department of Health & Senior Services. It is known that many TBDs are widely underreported in the United States.1213 This study was designed to identify if people are actively seeking treatment for TBDs, if TBDs are being diagnosed in medical clinics, and provide a more accurate assessment and better understanding of the prevalence of these diseases in a highly endemic county.Go to:

Materials and Methods

Public Survey

Public exposure to ticks and the potential to acquire TBDs was assessed by a nine question survey. The survey was distributed to employees of the Missouri Department of Conservation and USDA National Resource Conservation Service who routinely work outside. In addition, surveys were distributed to people who attended the Agricultural fair that occurred in Adair County (February 3rd, 2018) to include the local farmers. A total of 109 responses were obtained. Areas covered by the survey included: experiences with ticks; concerns about contracting TBDs; visits made to health care professionals due to tick bites. It was calculated that for a population of 20,000, a confidence level of 95%, and with 109 responses that the margin of error is 9.40%. No personal data were collected and so the ATSU IRB committee found this study to be exempt under Section 45CFR46.101(b)(2).

Clinician Survey

Four separate primary care clinics with approximately 25 health care providers in Adair County were contacted to fill out a six-question survey to determine how often they see patients with suspected TBDs, types of TBDs treated, if any, and if a blood sample is routinely sent off to screen for TBDs. A total of 9 responses were collected for a 36% response rate. No personal or medical data was collected and so the ATSU institutional review board (IRB) found this study to be exempt under Section 45CFR46.101(b)(2).

Database Query

The past five years of tick-borne reported diseases for Adair County, Missouri 2013–2017 were obtained from the Missouri Department of Health and Senior Services (DHSS), Bureau of Reportable Disease Informatics, Missouri Health Surveillance Information System.Go to:

Results

Public Survey

Tick bites are common in Adair County; 97% of all respondents report seeing a tick on their person and 96% report finding a tick attached to their body (Table 1). On average, 60% report that they remove 1–5 attached ticks per year, 23% remove 6–10 attached ticks per year, 8% remove 11–25 attached ticks per year, and 9% remove 26–100 attached ticks per year (Table 1). Thirty-eight percent of people reported developing a rash, influenza-like symptoms, or both following a tick bite (Table 2). Of those 38% who developed symptoms after a tick bite only slightly more than half (55%) sought medical attention and of those 59% were treated for TBDs (Table 2). If an individual developed a rash from a tick bite they were not as likely to seek medical attention (36%) when compared to individuals that developed influenza-like symptoms (67%) or had both rash and influenza-like symptoms (83%) (Table 2).

Table 1

Residents of Northeast Missouri self-report annual exposure to and average number of ticks removed from persons

Have seen a tick on their personHave had an attached tick to their personAverage number of ticks removed per year from their person
Response(n=109)(n=109)Response(n=105)
1–563 (60%)
Yes106 (97%)105 (96%)6–1024 (23%)
No3 (3%)4 (4%)11–258 (8%)
Not Sure0026–10010 (9%)

Table 2

Residents in Northeast, Missouri who self-report symptoms post tick bite, visited healthcare, and were treated for those symptoms

Rash(n=22)(n=8)flu-like symptoms(n=6)(n=4)Both rash and flu(n=12)(n=10)
Response(n=104)visited healthcarereceived treatment(n=104)visited healthcarereceived treatment(n=104)visited healthcarereceived treatment
Yes22 (21%)8 (36%)4 (50%)6 (6%)4 (67%)2 (50%)12 (12%)10 (83%)7 (70%)
No77 (74%)14 (64%)3 (38%)86 (83%)2 (33%)2 (50%)92 (88%)2 (17%)2 (20%)
Not sure5 (5%)01 (12%)12 (11%)00001 (10%)

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Sixty-one percent of the respondents stated that they always perform tick checks after spending time outdoors, 28% stated that they performed tick checks most of the time, 10% stated they sometimes perform tick checks, and only 1% stated that they almost never perform a tick check (data not shown). When asked how concerned they were about tick bites, 48% stated they were very concerned, 47% stated not very concerned, 4% stated they were not concerned at all, and 1% did not answer the question (data not shown). The level of concern about tick bites seems directly proportional to the number of individuals who had symptoms associated with a tick bite. The individuals that were not concerned at all about tick bites never experienced any symptoms post tick bite while 27% of the not very concerned group and 44% of the very concerned group had experienced symptoms post tick bite.

Clinician Survey

Of the nine survey results, only one health care provider had not treated a patient in the past year for tick bites (Table 3). Four of the health care providers had treated eleven or more patients each for tick bites in the past year (Table 3). Five of the providers had treated for Lyme disease, six for Rocky Mountain spotted fever (RMSF), and one for ehrlichiosis in this past year (Table 3). Most providers (78%) send a blood sample to a diagnostic lab when they suspect their patient is presenting clinically with a TBD (Table 3).

Table 3

Estimates, by health care professionals, of number of patients treated for tick-borne diseases in the past year in Adair County, Missouri

# of patients# of diseases treated# of blood samples screened for tick- borne diseases
Response(n=9)ResponseResponse
None1 (11%)Lyme Disease5Never0
1–53 (34%)RMSF6Every time I suspect a tick-borne disease7
6–101 (11%)Ehrlichiosis1Only when the patient has insurance to cover the costs2
11–252 (22%)Tularemia0Only when the patient requests it0
26–1002 (22%)STARI0Only when I am confident it is a tick-borne disease3
None of these1

Database Query

For the past five years there were a total of 6 confirmed cases of E. chaffeensis and one confirmed case of E. ewingii. In addition, there was one probable case of E. chaffeensis, one probable ehrlichiosis/anaplasmosis undetermined, 16 probable RMSF, and one probable tularemia case in the past five years. A grand total of 26 probable and confirmed cases of TBDs in Adair County from 2013–2017 was reported (Table 4). Probable and confirmed cases are each characterized by clinically compatible illness. A probable case may have laboratory results that are consistent with the diagnosis but such results are not necessary. Confirmed cases have a fourfold or greater increase in antibody titer, polymerase chain reaction assay, or pathogen isolation in cellular culture.

Table 4

Tick-borne reported diseases and conditions, Adair County, Missouri 2013–2017, Missouri Department of Health and Senior Services. Numbers reflect reported cases that meet the Centers for Disease Control and Prevention’s definition of a probable or confirmed case.

Condition20132014201520162017
ConfirmedProbableConfirmedProbableConfirmedProbableConfirmedProbableConfirmedProbable
Ehrlichia chaffeensis2010002110
Ehrlichia ewingii0000100000
Ehrlichiosis/Anaplasmosis undetermined0001000000
Rocky Mountain Spotted Fever0204030205
Tularemia0000010000

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Discussion

It has been indicated that a low human population density, a high white-tailed deer density, and greater proportions of deciduous forest cover were all positively correlated with elevated incidence of ehrlichiosis in the state of Missouri.14 Adair County, which is located in Northeast Missouri, had a population of 25,607 (45 persons/mi2) as of the 2010 census.15 The white-tailed deer density is 18/mi2 and 28% of the county is forested.16 With an abundance of lone star ticks and white-tailed deer, a 22% infection rate in adult ticks with the pathogens that cause ehrlichiosis, and a rural population that includes 822 farms, it seems likely that ehrlichiosis would be a common diagnosis.17 However, from the past five years (2013–2017) there have only been seven confirmed cases of ehrlichiosis (DHSS). This data implies that ehrlichiosis may be asymptomatic, underreported, or being misdiagnosed.

Ehrlichiosis presents clinically most often as fever, chills, headache, malaise, myalgia, and nausea, and fewer than 30% of adult patients present with a rash.18 With 38% of all respondents developing symptoms post tick bite, whatever the TBDs may be, they are not asymptomatic. In addition, six percent of the respondents developed influenza-like symptoms with no concurrent rash and 12% developed a rash with influenza-like symptoms, which both would be symptomatically consistent with ehrlichiosis and thus make them probable cases.

Another possible explanation for the lower-than-expected number of reported ehrlichiosis cases is that 45% of those individuals that present symptoms post tick bite are not seeking medical attention, thus accounting for large numbers of unreported infections. As the infection tends to manifest as a generalized influenza-like illness, infected individuals may be less likely to visit a doctor unless more severe symptoms emerge. However, 78% of all respondents did seek medical attention if they presented with influenza-like symptoms, which they self-reported was associated with a tick bite. Data from this study implies that ehrlichiosis is not asymptomatic, but it is likely under-recognized.

Misdiagnosis is another factor that may explain the lower-than-expected probable or confirmed cases of ehrlichiosis. In Adair County, in the past year alone, 9 clinicians reported that they treated 12 patients for TBDs, but only one was treated for ehrlichiosis while RMSF was diagnosed six times. The majority of health care providers (78%) stated that when they suspect their patient is presenting with a TBD, they send a blood sample to be screened under a “tick panel”. In general, these tick panels test for RMSF IgG and IgM, ehrlichiosis, Lyme disease, and Tularemia antibodies. If a sample returns to the clinic as a positive for RMSF then RMSF will be the final diagnosis. Sixty-seven percent of the doctors surveyed stated that they never obtain a second blood sample from the patient to confirm the diagnosis unless the patient is still ill and 22% stated they never obtain a second blood sample. As a result, these RMSF cases are not confirmed because they cannot demonstrate a fourfold titer increase and may well represent false positive diagnoses because of the high background seropositivity for RMSF. It has been demonstrated that SFG rickettsiae like diseases with titers as high as 256 are not uncommon in children due to previous infections from tick bites which certainly meets the case definition for probable RMSF.19 DHSS did not report one confirmed case of RMSF in the past five years even though it is the most prevalent TBD reported by local health care professionals.

Rickettsia ricketsii, the etiological agent of RMSF, was not detected in any of the 309 D. variabilis(American dog) ticks sampled in Adair County over two consecutive years.2,9 The absence of R. rickettsiidetection in American dog ticks and lone star ticks which were screened with polymerase chain reaction is suggestive that RMSF is being misdiagnosed. It has been suggested that the cross-reactivity of antibodies of other SFG rickettsiae, such as R. amblyommatis, may explain these positive results from tick panels when R. ricketsii appears to not be prevalent in the tick population.20 In the 436 individual adult lone star ticks tested in 2015, R. amblyommatis demonstrated an infection rate of 36% and in the 189 individual American dog ticks screened four percent were infected.9 This data may support the notion that R. amblyommatis is associated with clinical illness or in the very least masking the results of an ehrlichiosis infection.21

In this study, 12 cases of TBDs were diagnosed by health care providers in Adair County during 2017. That is nearly half of what DHSS reports in the county for the past five years. It would be unreasonable to speculate as to why four clinics would be reporting higher numbers of TBDs than DHSS as these findings are subject to several limitations. For example, all data collected were self-reported, potentially subject to recall bias, and not independently validated. Further, some of the survey questions to which clinicians and the public responded are subject to variable interpretation, and there is no way to confirm that all the patients seen in the clinics or all individuals who completed a survey reside in Adair County. The reports from DHSS, however, have been confirmed to be Adair County residents and this may explain, to some degree, why DHSS reports lower numbers than the clinics who may be attending to patients from surrounding counties.

It is important to note that five of those 12 TBDs were diagnosed as Lyme disease. To date, there is still great uncertainty regarding the occurrence of Lyme disease in Missouri. Borrelia burgdorferi sensu lato(s.l.) was first reported to be isolated and cultivated from Missouri in 1995 from ticks that had been feeding on cottontail rabbits (Sylvilagus floridanus).22 However Borrelia burgdorferi sensu stricto (s.s.), the cause of Lyme disease, has not been reported in Missouri ticks. Nor has B. burgdorferi (s.l.) yet been isolated from any patient in Missouri showing symptoms consistent with Lyme disease.23 Data obtained here suggests that Lyme disease is continuing to be over-diagnosed in Missouri.

From 2008–2012 Missouri had the second highest reported incidence rate of E. chaffeensis, and was tied for the highest incidence rate of E. ewingii.24 Given the preponderance of lone star ticks, its aggressive predilection for biting humans, clinicians in this region should maintain ehrlichiosis high in the differential diagnosis for tick-borne disease. In nearly 30,000 ticks examined for human pathogens in Adair County, R. rickettsii was never once detected, while E. chaffeensis and E. ehrlichia are very prevalent in the tick populations. In addition, the only confirmed cases for the past five years in Adair County have been for ehrlichiosis. This data implies that infections with E. chaffeensis and E. ewingii are under-recognized, at least in Adair County, if not throughout a larger portion of Missouri.

This information serves to contribute to a more accurate picture of the overall burden of TBDs in Adair County and highlights the need for better understanding in our community about what diseases are present, in particular ehrlichiosis, how those diseases present clinically, and when people should seek treatment if at all possible.​Figure 1

Amblyomma americanum female tick (left) and male tick (right)

Photo credit: Kelly Rogers, ATSU photographerGo to:

Acknowledgments

I thank Missouri Department of Conservation, USDA National Resource Conservation Service, the participants at the Agricultural Fair, and the health care providers for filling out surveys. I thank Debby Hutton at the Bureau of Reportable Disease Informatics MO Department of Health and Senior Services for providing the data set on tick-borne diseases in Adair County. I thank Dr. Stephen P. Hudman for thoughtful review of the manuscript.Go to:

Biography

• 

Deborah A. Hudman, MS, is in the Department of Microbiology/Immunology, A.T. Still University Kirksville College of Osteopathic Medicine.

Contact: ude.usta@namduhd

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Object name is ms115_p0374f2.jpg

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Footnotes

Disclosure

None reported.Go to:

References

1. Petry WK, Fore SA, Fielden LJ, Kim HJ. A quantitative comparison of two sample methods for collecting Amblyomma americanum and Dermacentor variabilis (Acari: Ixodidae) in Missouri. Exp Appl Acarol Exp Appl Acarol. 2010;52:427–38. [PubMed] [Google Scholar]2. Hudman DA, Sargentini NJ. Detection of Borrelia, Ehrlichia, and Rickettsia spp. in ticks in northeast Missouri. Ticks Tick Borne Dis. 2016;7:915–21. [PubMed] [Google Scholar]3. CDC. Tickborne diseases of the United States. [Accessed January 30, 2018]. Available at:https://www.cdc.gov/ticks/tickbornediseases/index.html.4. Savage HM, Godsey MS, Jr, Lambert A, Panella NA, Burkhalter KL, Harmon JR, et al. First detection of Heartland Virus (Bunyaviridae: Phlebovirus) from field collected arthropods. Am J Trop Med Hyg. 2013;89:445–52. [PMC free article] [PubMed] [Google Scholar]5. Van Nunen S. Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance. Asia Pacific Allergy. 2015;5:3–16. [PMC free article] [PubMed] [Google Scholar]6. Apperson CS, Engber B, Nicholson WL, Mead DG, Engel J, Yabsley MJ, et al. Tick-borne diseases in North Carolina: is Rickettsia amblyommii a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonotic Dis. 2008;8:597–606. [PubMed] [Google Scholar]7. Billeter SA, Blanton HL, Little SE, Levy MG, Breitschwerdt EB. Detection of Rickettsia amblyommii in association with a tick bite rash. Vector Borne Zoonotic Dis. 2007;7:607–10. [PubMed] [Google Scholar]8. Smith MP, Ponnusamy L, Jiang J, Ayyash LA, Richards AL, Apperson CS. Bacterial pathogens in ixodid ticks from a Piedmont County in North Carolina: prevalence of rickettsial organisms. Vector Borne Zoonotic Dis. 2010;10:939–52. [PubMed] [Google Scholar]9. Hudman DA, Sargentini NJ. Prevalence of tick-borne pathogens in northeast Missouri. Missouri Medicine. 2018;115:155–61. [Google Scholar]10. James AM, Liveris D, Wormser GP, Schwartz I, Montecalvo MA, Johnson BJ. Borrelia lonestari infection after a bite by an Amblyomma americanum tick. J Infect Dis. 2001;183:1810–14. [PubMed] [Google Scholar]11. Parola P, Labruna MB, Raoult D. Tick-borne rickettsioses in America: unanswered questions and emerging diseases. Curr Infect Dis Rep. 2009;11:40–50. [PubMed] [Google Scholar]12. Schiffman EK, McLaughlin C, Ray JAE, Kemperman MM, Hinckley AF, Friedlander HG, et al. Underreporting of Lyme and other tick-borne diseases in residents of a high-incidence county, Minnesota, 2009. Zoonos Pub Hlth. 2018;65:230–37. [PubMed] [Google Scholar]13. Connally NP, Hinckley AF, Feldman KA, Kemperman M, Neitzel D, Wee S-B, et al. Testing practices and volume of non-lyme tickborne diseases in the United States. Ticks Tick Borne Dis. 2016;7:193–98.[PMC free article] [PubMed] [Google Scholar]14. Bayles BR, Allen BF. Social-ecological factors determine spatial variation in human incidence of tick-borne ehrlichiosis. Epidemiol Infect. 2014;42:1911–24. [PubMed] [Google Scholar]15. United States Census 2010. Interactive Population Search MO – Adair County. [Accessed February 19, 2018]. Available at: https://www.census.gov/2010census/popmap/ipmtext.php?fl=29:29001.16. MDC. 2015–16 Missouri Deer Season Summary& Population Status Report. [Accessed February 19, 2018]. Available at: https://huntfish.mdc.mo.gov/sites/default/files/downloads/Deer-Pop-status.pdf.17. USDA. 2012 Census of Agriculture. 2012. [Accessed February 19, 2018]. Available at:http://www.agcensus.usda.gov/Publications/2012/Online_Resources/County_Profiles/Missouri/cp29001.pdf.18. Centers for Disease Control and Prevention. Ehrlichiosis. 2016. [Accessed February 26, 2018]. Available at: https://www.cdc.gov/ehrlichiosis/symptoms/index.html.19. Marshall GS, Stout GG, Jacobs RF, Schutze GE, Paxton H, Buckingham SC, et al. Antibodies Reactive to Rickettsia rickettsii Among Children Living in the Southeast and South Central Regions of the United States. Arch Pediatr Adolesc Med. 2003;157:443–48. [PubMed] [Google Scholar]20. Delisle J, Mendell NL, Stull-Lane A, Bloch KC, Bouyer DH, Moncayo AC. human Infections by Multiple Spotted Fever Group Rickettsiae in Tennessee. Am J Trop Med Hyg. 2016;94:1212–17.[PMC free article] [PubMed] [Google Scholar]21. Gaines DN, Operario DJ, Stroup S, Stromdahl E, Wright C, Gaff H, et al. Ehrlichia and Spotted Fever Group Rickettsiae Surveillance in Amblyomma americanum in Virginia Through Use of a Novel Six-Plex Real-Time PCR Assay. Vector Borne and Zoonotic Dis. 2014;14:307–16. [PMC free article] [PubMed] [Google Scholar]22. Oliver JH, Jr, Kollars TM, Jr, Chandler FW, Jr, James AM, Masters EJ, Lane RS, et al. First isolation and cultivation of Borrelia burgdorferi sensu lato from Missouri. J Clin Microbiol. 1998;36:1–5.[PMC free article] [PubMed] [Google Scholar]23. DHSS. Lyme Disease Position Paper. 2009. [Accessed March 06, 2018].http://health.mo.gov/living/healthcondiseases/communicable/tickscarrydisease/ldpositionpaper.php.24. Heitman KN, Dahlgren FS, Drexler NA, Massung RF, Behravesh CB. Increasing incidence of ehrlichiosis in the United States: A summary of national surveillance of Ehrlichia chaffeensis and Ehrlichia ewingii infections in the United States, 2008–2012. Am J Trop Med Hyg. 2016;94:52–60.[PMC free article] [PubMed] [Google Scholar]

Dr. Raymond Oenbrink