Presented by: Joseph Granato B.S. M.P.H. Capstone Project

Presented by: Joseph Granato B.S. M.P.H. Capstone Project

Relevant to the content of this presentation, I have nothing of importance to disclose.

Discuss tick biology & species in Tennessee Review risk factors and prevention methods Identify the signs &symptoms of tick-borne diseases in Tennessee Recognize current diagnostic and confirmatory tests for tick-borne diseases Examine current treatment guidelines for tick-borne diseases

Introduction to Acari Life Cycle Species of Public Health Importance Specific to Tennessee

Acari- taxonomic group including ticks & mites Blood sucking ectoparasites 2 nd only to mosquitoes in # diseases transmitted 2 types of ticks Hard ticks (Ixodidae) Soft ticks (Argasidae) 80 tick species in the US; 17 tick species documented in Tennessee <10 ever bite humans Currently >30 tick-borne diseases TN Human-biting ticks Lone Star tick American Dog tick Gulf Coast tick Blacklegged tick

Life cycles range from 1 to 3 yrs. Life cycle(*= feeds on host) Egg Larva (seed ticks)* Nymph* Adult* Each life stage requires a blood meal prior to molt Species/geography determine life cycle & preferred host Ixodes scapularis life cycle resulting in Borrelia burgdorfer infection Retrieved from: Little, S., Heise, S., Blagburn, B., Callister, S., & Mead, P. (2010). Lyme borreliosis in dogs and humans in the USA. Trends in Parasitology, 26(4), 213-218.

American dog tick questing Retrieved from: www.alexanderwild.com Host location/identification Questing- posture increasing chance of locating a host Detect CO₂/body heat/vibrations Attachment Chelicerae/Denticles/Hypostome Saliva- contains Analgesics Immunosuppressors Anticoagulants Neurotoxins (may be present) Generalized mouthparts of a hard tick, based on a species of Ixodes. Illustration by: Scott Charlesworth, Purdue University

Disease Transmission Tick ingests pathogens from infected host via feedings Pathogens secreted in saliva during blood meal Transmission times may vary depending on tick species and pathogen (24-48hrs) Pathogenic organisms can be transmitted if tick is removed using improper technique Tick bites infrequently cause disease Changes as a lone star tick engorges Retrieved from: http://www.tickinfo.com/lonestartick.htm

Spotted Fever Rickettsiosis (Rocky Mountain Spotted Fever) Ehrlichiosis Anaplasmosis Tularemia Babesiosis Lyme Disease Powassen encephalitis Masters Disease (Southern Tick Associated Rash Illness or STARI) Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

US Reported cases: 2011 Tularemia reported cases: 2011 Spotted Fever Rickettsiosis reported cases: 2011 Ehrlichiosis chaffeensis reported cases: 2011 Babesiosis reported cases: 2011 Lyme Disease reported cases: 2011 Anaplasmosis reported cases: 2011 Maps retrieved from: Centers for Disease Control and Prevention. (2013). Summary of notifiable diseases- United States, 2011. MMWR, Morbidity and Mortality Weekly Reports, 60(53). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6053a1.htm

Spotted Fever Rickettsiosis Confirmed & Probable Reported Cases Tennessee, 2012 Confirmed case: A clinically compatible case (meets clinical evidence criteria) that is laboratory confirmed. Probable case: A clinically compatible case (meets clinical evidence criteria) that has supportive laboratory results. Retrieved from/more info: http://health.state.tn.us/reportablediseases/reportabledisease.aspx

Ehrlichiosis Confirmed & Probable Reported Cases Tennessee, 2012 Confirmed case: A clinically compatible case (meets clinical evidence criteria) that is laboratory confirmed. Probable case: A clinically compatible case (meets clinical evidence criteria) that has supportive laboratory results. Retrieved from/more info: http://health.state.tn.us/reportablediseases/reportabledisease.aspx

Lyme Disease Confirmed & Probable Reported Cases Tennessee, 2012 Confirmed case: a) a case of EM with a known exposure, or b) a case of EM with laboratory evidence of infection and without a known exposure or c) a case with at least one late manifestation that has laboratory evidence of infection. Probable case: any other case of physician-diagnosed Lyme disease that has laboratory evidence of infection. Retrieved from/more info: http://health.state.tn.us/reportablediseases/reportabledisease.aspx

Spotted Fever Rickettsiosis 2011 US: 0.91 cases 2012 TN: 10.64 cases Ehrlichiosis/Anaplasmosis (combined) 2011 US: 1.22 cases 2012 TN: 1.25 cases Lyme Disease 2011 US: 10.78 cases 2012 TN: 0.43 cases Retrieved from: Centers for Disease Control and Prevention. (2013). Summary of notifiable diseases- United States, 2011. MMWR, Morbidity and Mortality Weekly Reports, 60(53). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6053a1.htm.; Tennessee Department of Health. (2013). Reportable diseases and events, by Tennessee health region, year-to-date and MMWR week 52. Retrieved from http://health.state.tn.us/ceds/weeklyreports/reports/wk52_2012.pdf; United States Census Bureau. Annual estimates of the resident population: April 1, 2010 to July 1,2012. Retrieved from http://factfinder2.census.gov/bkmk/table1.0/en/pep/2012/pepannres/0400000us47.05000#tab_table

Tick Species of Public Health Importance Vector: Amblyomma americanum Common name: Lone Star tick Pathogens: Ehrlichia chaffeensis; Ehrlichia ewingii; Francisella tularensis; Rickettsia rickettsii; Rickettsia parkeri Human diseases: Ehrlichia chaffeensis infection; Ehrlichia ewingii infection; Tularemia; Rocky Mountain Spotted Fever; Master s Disease or Southern Tick Associated Rash Illness Non-pathogens: Rickettsia amblyommi; R. andeanae; R. felis Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.; Dumler, J. S., Madigan, J., Pusterla, N., & Bakken, J. (2007). Ehrlichioses in humans: Epidemiology, clinical presentation, diagnosis, and treatment [Supplemental material]. Clinical Infectious Diseases, 45, S45-S51

Abundant in Tennessee Ehrlichiosis: most common disease transmitted Aggressive biter Characteristic white dot on back of adult females Irritating saliva Can cause allergic reaction Small red area of skin irritation (diameter <5 cm) Appears within 48 hours does not make disease transmission certain Lone star tick distribution Retrieved from: http://www.cdc.gov/ticks/maps/lone_star_tick.html Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf

Tick Species of Public Health Importance Vector: Dermacentor variabilis Common name: American dog tick Pathogens: Rickettsia rickettsii; Francisella tularensis Human diseases: Rocky Mountain Spotted Fever; Tularemia Non-pathogens: Rickettsia amblyommii; R. montanensis Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Abundant in Tennessee RMSF: most common disease transmitted by this species Dogs primary host Can survive 2yrs without host Dark brown with random silver streaks on back of adults RMSF transmission reduced: R. rickettsii has lethal effects D. variabilis produce rickettsiostatic proteins American dog tick distribution Retrieved from: http://www.cdc.gov/ticks/maps/american_dog_tick.html Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Tick Species of Public Health Importance Vector: Ixodes scapularis Common name: Blacklegged tick (deer tick) Pathogens: Borrelia burgdorferi; Anaplasma phagocytophilum; Babesia microti; Babesia duncani; Ehrlichia sp.; Powassen virus Human diseases: Lyme Disease; Anaplasmosis; Babesiosis; Ehrlichia muris-like infection; Powassen encephalitis Non-pathogens: Rickettsia massiliae (Italy) Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Scarce in Tennessee Lyme Disease: most common disease transmitted in North Dark brown/distinct black legs Hypothesized to be preferred host in TN: Lizard/small mammals Note: Reptile blood is bacteriostatic for B. burgdorferi Birds/White-tailed deer Less likely to carry pathogens due to lack of pathogen in preferred host Blacklegged tick distribution Retrieved from: http://www.cdc.gov/ticks/maps/blacklegged_tick.html Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Tick Species of Public Health Importance Vector: Rhipicephalus sanguineus Common name: Brown dog tick Pathogen: Rickettsia rickettsii Human disease: Rocky Mountain Spotted Fever (RMSF) Non-pathogen: Rickettsia massiliae (France) Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Scarce in Tennessee RMSF: most common disease transmitted by this species Dark reddish-brown with no ornamentation on the back Not considered to be an important vector in TN Can spend entire life cycle indoors Infestations can be difficult to resolve Preferred habitat: Animal pens/human homes Human bites uncommon Brown dog tick distribution Retrieved from: http://www.cdc.gov/ticks/maps/brown_dog_tick.html Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.

Rocky Mountain Spotted Fever Ehrlichiosis Lyme Disease Masters Disease

Rocky Mountain Spotted Fever: Case Presentation On April 27, a 65-year old woman from southeastern Tennessee was admitted to a community hospital with fever, nausea, vomiting and muscle aches. She rapidly developed septic shock and died on April 30. An acute-phase serum specimen was found to be reactive with Rickettsia rickettsii IgM antibody at a dilution of 1:256. On May 9, and May 28, two women presented to the same hospital with febrile illnesses and had R. rickettsii serologic tests yield positive results. On June 1, an internist in this same community saw a patient in his office who he suspected had RMSF. During the previous year, only one case of RMSF was diagnosed at this hospital.

Most fatal TBD in US 3-5% of reported cases are fatal Up to 80% fatal without treatment Causative agent Rickettsia rickettsii Gram-negative, obligate intracellular bacteria American/Brown dog ticks: most common vectors 2-14 day incubation period (mean 7) Included in Spotted Fever Rickettsiosis surveillance since 2010 Geography >60% of cases in TN, NC, MO, OK, AR Mostly rural/suburban areas Seasonality 90% of cases April- September 10% during winter month=danger: delayed or misdiagnosis Demographics Age > 40 years or <10 years Males 40% of cases don t recall tick bite Risk Factors Exposure to wooded/grassy areas Pets with exposure to tick habitat Professional/recreational activities Compromised immune system may increase risk of severe outcome Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Centers for Disease Control and Prevention. (2006). Diagnosis and management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis---United States. MMWR, Morbidity and Mortality Weekly Reports, 55(RR04), 1-27. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm#top; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 521-523.). Washington: American Public Health Association.; Childs, J. (2002). Passive surveillance as an instrument to identify risk factors for fatal Rocky Mountain Spotted Fever: Is there more to learn? The American Society of Tropical Medicine and Hygiene, 66(5), 450-457.

RMSF rash Retrieved from: http://phil.cdc.gov/phil/home.asp (Picture #: Top: 14489; Bottom: 1962) Clinical Presentation High fever/chills/headache/myalgias/gi symptoms Classic triad Fever/rash/tick bite Appears <20% of cases Rash Develops 2-5 days (post fever onset) 10% of cases rash is absent or atypical Macules (pink in coloration) Start on wrists/forearms/ankles-spreads centrally 1 to 4mm in size Palms & soles characteristic Petechiae Develops 6 or more days post symptom onset Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 521-523.). Washington: American Public Health Association.; Gayle, A., & Ringdahl, E. (2001). Tick-borne diseases. American Family Physician, 64(3), 461-466.; Centers for Disease Control and Prevention. (2006). Diagnosis and management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis---United States. MMWR, Morbidity and Mortality Weekly Reports, 55(RR04), 1-27. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm#top

RMSF: Diagnosis Laboratory Findings Normal WBC: increased bands Thrombocytopenia Hyponatremia Mildly elevated aminotransferases Hyperbilirubinemia Confirmatory Diagnosis Immunofluorescence assay (IFA) (Gold standard) R. rickettsii antibodies detectable 7-10 days after onset 94-100% sensitive after 14 days Cross reactivity possible Paired IgG antibody titers positive= 4-fold change Acute Convalescent (2-4 weeks post initial or acute sample draw) Note: Negative acute test does not rule out diagnosis of RMSF Note: Commercially available EIA tests are not quantitative=cannot be used to evaluate IgG titer changes Note: Must request reflexive titers (commercially available) Other available tests Immunohistochemical (IHC) staining of causative organism Polymerase Chain Reaction (PCR) Skin punch biopsy from rash site Antibiotic treatment decreases sensitivity of the assay Available at specialty labs Centers for Disease Control and Prevention. (2006). Diagnosis and management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis--- United States. MMWR, Morbidity and Mortality Weekly Reports, 55(RR04), 1-27. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm#top; Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf

Guidelines: CDC and American Academy of Pediatrics Doxycycline (4.4mg/kg per day)-recommended treatment Adults- 100mg BID (maximum: 100mg/dose) Pediatric (<100lbs.)- 2.2mg/kg BID (maximum: 100mg/dose) Note: No teeth staining observed at this dose and duration 7day minimum treatment Continue treatment until 3 days post fever Chloramphenicol-Alternative treatment Tetracycline hypersensitivity Pregnancy Less effective: Increased risk of death/anaplastic anemia Effectiveness Treatment most effective before day 5 Begin treatment as soon as RMSF is suspected Do not wait for lab results/development of rash Use permission granted from AAP; Retrieved from: http://aapredbook.aappublications.org/ Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Childs, J. (2002). Passive surveillance as an instrument to identify risk factors for fatal Rocky Mountain Spotted Fever: Is there more to learn? The American Society of Tropical Medicine and Hygiene, 66(5), 450-457.

Ehrlichiosis: Case Presentation In May, a 40 year old male construction worker sought medical attention with complaints of headache, fever, sore throat, and vomiting. He does not own pet and did not recall being bitten by a tick. The patient was diagnosed with pneumonia and prescribed 3 days of azithromycin and levofloxacin. Fevers >103º F persisted and he had an onset of confusion. Upon arrival to the ED skin examination revealed diffuse erythema with several scabs on the lower legs. CBC showed a slightly elevated white count 11,900 (normal 4,500 11,000), 3% lymphocytes (normal 16%-46%), and a decreased platelet count 50,000 (normal 150,000 350,000). Liver function tests were also abnormal; AST 439 (normal 10-40), ALT 471 (normal 10-55), and alkaline phosphatase 236 (normal 45-115). Antibodies tests for R. rickettsii and E. chaffeensis were negative. Antibiotic therapy was initiated with ceftriaxone and vancomycin. Approximately 6 hours later the patient developed seizures; acyclovir and doxycycline were added to the drug therapy. Serum obtained 31 days after the initial signs and symptoms contained no antibodies to R. rickettsii, but had an IgG titer of 1:256 to E. chaffeensis.

Ehrlichiosis: Epidemiology Ehrlichia species most prevalent pathogens in Tennessee ticks Up to 5% of ticks infected 2-3% of cases are fatal Up to 62% of cases are hospitalized Causative agent Ehrlichia chaffeensis Gram-negative, obligate intracellular bacteria found in monocytes Lone star tick: most common vector 7-10 day incubation period (mean 8d) Ehrlichia chaffeensis infection- a.k.a. Human Monocytic Ehrlichia (HME) Ehrlichia ewingii infection-canine pathogen until 1999 Anaplasma phagocytophilum infection-formerly Human granulocytic Ehrlichiosis/Anaplasmosis (HGE/HGA) Geography Most cases in MO, OK, & AR TN Cumberland Plateau:1993 outbreak Seasonality April through September Peak in May & June Demographics Median age ~44 years Slightly more males than females ~68% of cases don t recall tick bite Risk Factors Exposure to wooded/grassy areas Pets with exposure to tick habitat Professional/recreational activities Compromised immune system may increase risk of severe outcome Stromdahl, E.Y., & Hickling, G. J. (2012). Beyond Lyme: Aetiology of tick-borne human diseases with emphasis on the south-eastern United States [Supplemental material]. Zoonoses and Public Health, 59, 24-27.; The Center for Food Security & Public Health. (2013). Ehrlichiosis and Anaplasmosis: Zoonotic species (pp. 1-14). Ames, Iowa: Iowa State University. Retrieved from http://www.cfsph.iastate.edu/factsheets/pdfs/ehrlichiosis.pdf; Dumler, J. S., Madigan, J., Pusterla, N., & Bakken, J. (2007). Ehrlichiosis in humans: Epidemiology, clinical presentation, diagnosis, and treatment [Supplemental material]. Clinical Infectious Diseases, 45, S45-S51.; Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf

Ehrlichiosis: Signs & Symptoms Clinical Presentation Fever/headache i.e., an influenza-like illness after outdoor activity Malaise Less common symptoms Nausea/Vomiting/Diarrhea Altered mental state/confusion Rash Reported in 30% adults/60% children Appears on the trunk rarely on palms/soles Develops later in disease (average 5 days) Can resemble RMSF rash less prominent/more variable appearance Ehrlichiosis rash. Use permission granted from: Richard Jacobs, MD; Retrieved from: Ehrlichia and Anaplasma Infections (Human Ehrlichiosis and Anaplasmosis) Red Book 2012: 312-315. Centers for Disease Control and Prevention. (2006). Diagnosis and management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis--- United States. MMWR, Morbidity and Mortality Weekly Reports, 55(RR04), 1-27. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm#top; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 521-523.). Washington: American Public Health Association.; Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; The Center for Food Security & Public Health. (2013). Ehrlichiosis and Anaplasmosis: Zoonotic species (pp. 1-14). Ames, Iowa: Iowa State University. Retrieved from http://www.cfsph.iastate.edu/factsheets/pdfs/ehrlichiosis.pdf

Ehrlichiosis: Diagnosis Laboratory Findings Thrombocytopenia Leukopenia Anemia Elevated aminotransferases Confirmatory Diagnosis Immunofluorescence assay (IFA) (Gold standard) E. chaffeensis antibodies detectable 7-10 days after onset 94-100% sensitive after 14 days Cross reactivity possible Paired IgG antibody titers positive= 4-fold change Acute Convalescent (2-4 weeks post initial or acute sample draw) Note: Negative acute test does not rule out diagnosis of Ehrlichiosis Note: Commercially available EIA tests are not quantitative=cannot be used to evaluate IgG titer changes Note: Must request reflexive titers (commercially available) Other available tests Immunohistochemical (IHC) staining of organism Polymerase Chain Reaction (PCR) Skin punch biopsy from rash site Antibiotic treatment decreases sensitivity of the assay Available at specialty labs Ismail, N., Bloch, K., & McBride, J. (2010). Human Ehrlichiosis and Anaplasmosis. Clinics in Laboratory Medicine, 30(1), 261-292.; Centers for Disease Control and Prevention. (2006). Diagnosis and management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis---United States. MMWR, Morbidity and Mortality Weekly Reports, 55(RR04), 1-27. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm#top; Centers for Disease Control and Prevention. (2013). Symptoms, diagnosis, and treatment. Atlanta, GA. Retrieved from http://www.cdc.gov/ehrlichiosis/symptoms/index.html; Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf

Guidelines: CDC and American Academy of Pediatrics Committee Doxycycline-Recommended treatment (maximum: 100mg/dose) Adults- 100mg BID Pediatric (<100lbs.)- 2.2mg/kg BID Note: No teeth staining at this dose and duration 7day minimum treatment Continue treatment until 3 days post fever Rifampin-Alternative treatment Pregnancy/children/hypersensitivity Cautious use: resistance possible/may not cover differential diagnosis Effectiveness Treatment most effective within first 5 days Fever wanes 24-72hrs after treatment Note: If patient not responding consider alternative diagnosis Do not delay treatment for lab results/development of rash Persistent fever and malaise reported to occur in some cases Use permission granted from AAP; Retrieved from: http://aapredbook.aappublications.org/ The Center for Food Security & Public Health. (2013). Ehrlichiosis and Anaplasmosis: Zoonotic species (pp. 1-14). Ames, Iowa: Iowa State University. Retrieved from http://www.cfsph.iastate.edu/factsheets/pdfs/ehrlichiosis.pdf; Centers for Disease Control and Prevention. (2013). Symptoms, diagnosis, and treatment. Atlanta, GA. Retrieved from http://www.cdc.gov/ehrlichiosis/symptoms/index.html; Dumler, J. S., Madigan, J., Pusterla, N., & Bakken, J. (2007). Ehrlichioses in humans: Epidemiology, clinical presentation, diagnosis, and treatment [Supplemental material]. Clinical Infectious Diseases, 45, S45-S51.

Lyme Disease: Case Presentation In July, a 2 year old male Caucasian living in a rural area of southeastern Tennessee was seen by a pediatrician for lethargy, fever (102.2ºF), and a rash on his back. The child was placed on Doxycycline. The mother reported removing a tick from the child s back a few days before the rash appeared. The tick was attached approximately at the center of the circular rash. The family owned two outside dogs and both had a history of tick infestation. Laboratory analysis indicated an elevated erythrocyte sedimentation rate of 25mm/h (normal=25mm/h). The patients ELISA test results were equivocal with a value of 1.03 Lyme index units (range 0.91-1.09). A Lyme Disease diagnosis was ultimately confirmed when a Western blot assay was found to be positive for Borrelia burgdorferi, with 6 bands observed (18, 28, 30, 41, 45, and 66 kda). Retrieved from: http://ltd.aruplab.com/tests/pub/0050255; http://www.viracoribt.com/test-catalog/detail/c-6

Lyme Disease: Epidemiology Most common vector-borne illness in the United States Fatality with complications or secondary infections 1991:made nationally notifiable Causative agent Borrelia burgdorferi Spirochete bacteria 3-30 day incubation period Median 11 day incubation period Blacklegged tick: common vector Borreliosis taxonomy (*=not confirmed) Borrelia organisms that cause Lyme-like clinical manifestations Masters disease/southern Tick Associated Rash Illness (STARI)* Geography 95%:CT, VA, DE, ME, MD, MA, MN, NJ, NH, NY, PA, WI, VT Endemic in Upper Midwest and northeastern US Seasonality April to October Peak in June & July-50% of cases Demographics Young males 5-9 Adults 55-59 years Risk Factors Exposure to wooded/grassy areas Pets with exposure to tick habitat Immunocompromised=increase risk of severe outcome Travel to endemic areas Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 364-369.). Washington: American Public Health Association.

Early localized Summer flu 3-30 day incubation period Median 7-10 days Flu-like symptoms: Headache/ malaise/myalgia/ arthralgia Fever may or may not be present Erythema Migrans (EM) Bulls-eye lesion Up to 80% of cases Starts at bite site and expands to greater than 5cm in diameter Central clearing possible Early Disseminated (days-weeks) Multiple EM lesions possible anywhere (in 50% of cases) Transient, migratory arthritis Headache/neck stiffness/fatigue Cardiac: Myocarditis, pericarditis Neurologic: Meningitis/Bell s palsy Late Disseminated (untreated) Lyme arthritis (60% of cases) PTLDS (Post Treatment Lyme Disease Syndrome) Recurrent symptoms in up to 20% Antibiotic treatment shown to be unhelpful (possibly autoimmune) Longo, D. A., Fauci, D., Kasper, S., Hauser, J., Jameson, & Loscalzo, J.. (Eds.). (2013). Harrison s manual of medicine (18 th ed.). New York, NY: McGraw-Hill.; Gilbert, D.N., Moellering, R. C., Eliopolulos, G. M., Chambers, H.F., & Saag, M. S. (Eds.). (2013). The Sanford guide to antimicrobial therapy 2013 (43 rd ed.). Sperryville, VA: Antimicrobial Therapy.; Papadakis, M.A., & McPhee, S.J. (Eds.). (2014). Current medical diagnosis (53 rd ed.). New York, NY: McGraw-Hill.; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 364-369.). Washington: American Public Health Association.

Lyme Disease: Erythema Migrans (EM) Erythema Migrans examples Retrieved from: http://phil.cdc.gov/phil/home.asp (Picture #s: Left top:14475; Left bottom:14479; Middle:14480; Right:14482

Laboratory findings Elevated erythrocyte sedimentation rate>20mm/h (50% of cases) Mild elevation of hepatic transaminases (30% of cases) Hematuria or proteinuria (<10% of cases) Confirmatory Diagnosis: Two step approach Screen: ELISA Negative results warrant no further testing Increased number of false positives due to low specificity If screen is positive or equivocal perform confirmatory Western blot Confirmatory: Western blot Positive=2 IgM bands or 5 IgG bands present Cross reactivity with spirochetal/viral infections/autoimmune diseases Patients with non-specific symptoms and without objective signs of Lyme Disease should not have serologic testing done More false positives than true positives Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 364-369.). Washington: American Public Health Association.

Lyme Disease: Treatment Guidelines: CDC and American Academy of Pediatrics Treatment based on clinical manifestations and disease stage Doxycycline Adults-100mg BID Pediatric- 4mg/kg/day divided into 2 doses (100mg/dose maximum) Treatment duration: 14-21 days Cefuroxime axetil Adults- 500mg BID Pediatric- 30mg/kg/day divided into 2 doses (500mg/dose maximum) Treatment duration: 14-21 days Amoxicillin Adults- 500mg, TID Pediatric- 50mg/kg/day divided into 3 doses (100mg/ dose maximum) Treatment duration: 14-21 days Macrolides-Alternative treatment Azithromycin/Clarithromycin/Erythromycin Less effective/relapse possible Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf; Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed., pp. 364-369.). Washington: American Public Health Association. Use permission granted from AAP; Retrieved from: http://aapredbook.aappublications.org/

Causative agent- No etiological agent identified Most common vector: Lone Star tick Southern Tick Associated Rash Illness (STARI) or Lyme-like illness Incubation period 6-9 days Geography Across the southern US From TX north to OK and eastward Seasonality 90% of cases April- September Peak in June & July Demographics unknown Risk Factor No known fatal cases Masters, E., Grigery, C., & Masters, R. (2008). STARI, or Masters Disease: Lone star tick-vectored Lyme-like illness. Infectious Disease Clinics of North America, 22, 361-376.

Clinical Presentation Fatigue Likely to recall tick bite compared to Lyme Disease cases Occasional symptoms- less likely than Lyme Disease Fever/Headache/Stiff neck Myalgia/joint pain Unlikely symptoms Lymphadenopathy Tender/pruritic rash Rash Small Erythema Migrans (Bull s eye) ~6-10 cm diameter Appears quick ~6 days Multiple lesions unlikely Nearly impossible to differentiate from Lyme Disease EM Central clearing more common Masters, E., Grigery, C., & Masters, R. (2008). STARI, or Masters Disease: Lone star tick-vectored Lyme-like illness. Infectious Disease Clinics of North America, 22, 361-376.; Lone star tick a concern, but not for Lyme disease. In Southern Tick-Associated Rash Illness. Atlanta, GA. Retrieved from http://www.cdc.gov/stari/disease/index.html

Masters Disease: Erythema Migrans Masters Disease rash pictures Retrieved from: Masters, E., Grigery, C., & Masters, R. (2008). STARI, or Masters Disease: Lone star tick-vectored Lyme-like illness. Infectious Disease Clinics of North America, 22, 361-376.

Diagnosis Clinical presentation Lack of plasma cells in biopsy Identification of tick most important in differentiation Amblyomma americanum- Lone Star Tick Not Ixodes scapularis- Blacklegged tick Treatment Observation in the south and southeastern states Same as Lyme Disease-Mid-Atlantic states (Maryland/Virginia) Unknown if antibiotic treatment is effective Increased risk of serious reaction and increased cost with treatment in non-lyme Disease endemic areas Lantos, P. M., Brinkerhoff, R. J., Wormser, G. P., & Clemen, R. (2013). Empiric antibiotic treat of Erythema Migrans- Like skin lesions as a function of geography: A clinical and cost effectiveness modeling study. Vector-Borne and Zoonotic Diseases, 13(0).; Masters, E., Grigery, C., & Masters, R. (2008). STARI, or Masters Disease: Lone star tickvectored Lyme-like illness. Infectious Disease Clinics of North America, 22, 361-376; Feder, H., Jr., Hoss, D., Zemel, L., Telford, S., III, Dias, F., & Wormser, G. (2011). Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York. Clinical Infectious Diseases, 53(10), e142-e146.

TN Incidence Rate (per 100,000) Spotted Fever Rickettsiosis ~10 times higher than United States Lyme Disease ~10 times less than the United States Lone Star tick-most abundant species in Tennessee Ehrlichia species-most prevalent pathogen in TN 90% of cases April-September Symptoms-sudden onset Fever/headache Malaise/myalgia Rash in 30-90% of all Ehrlichiosis/RMSF cases 40-68% do not recall tick bite Laboratory (RMSF & Ehrlichiosis) Elevated aminotransferases Thrombocytopenia Diagnosis (RMSF & Ehrlichiosis) IFA (gold standard) testing sensitivity 94-100% after 14 days of illness Antibodies detected 7-10 days after onset of illness False negative/positive/crossreactivity possible Treatment-Doxycycline Adults-100mg/kg Children-2.2mg/kg; 4mg/kg (Borreliosis) Most effective within 5 days after symptom onset

Recent Developments-TBD Gulf Coast Tick-Amblyomma maculatum Western TN; Gulf of Mexico & Atlantic Ocean boarders Vectors Rickettsia parkeri-recently found to be pathogenic 2002 WV confirmed case Classic TBD febrile presentation Rash (trunk/palms/soles) Eschars-similar to African tickbite fever or rickettsialpox Culture-based or molecular based testing for diagnosis Responds to Doxycycline treatment Heartland Virus- Amblyomma americanum New Phlebovirus-2009 in MO Documented cases in MO & TN Fatal case with comorbidities 14 day incubation period Fever/headache/myalgia/nausea Leukopenia/Thrombocytopenia RT-PCR & PRNT: laboratory testing Borrelia miyamotoi-ixodes scapularis New relapsing-fever spirochete Disease endemic areas Progressive mental deterioration ± classic Lyme symptoms Diagnostic and treatment protocols unknown Gugliotta, J. L., Goethert, H. K., Berardi, V. P., & Telford, S. R. (2013). Meningoencephalitis from Borrelia miyamotoi in an immunocompromised patient. The New England Journal of Medicine, 368(3), 240-245.; Paddock, C. D., Sumner, J. W., Comer, J. A., Zaki, S. R., Goldsmith, C. S., Gooddard, J., & McLellan, S. L. F. (2004). Rickettsia parkeri: A newly recognized cause of Spotted Fever Rickettsiosis in the United States. Clinical Infectious Diseases, 38, 805-811.; Centers for Disease Control and Prevention. (2014). Notes from the field: Heartland Virus Disease-United States, 2012-2013. MMWR, Morbidity and Mortality Weekly Reports, 63(12). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6312a4.htm?s_cid=mm6312a4_e

Prophylaxis No vaccines in US No treatment recommended Observe asymptomatic tick bite patients Protect yourself/pets 20-50% DEET/Monthly preventatives Long sleeves/pants Tick checks Proper removal Protect your yard Limit tick habitat/wildlife Chemical treatment How to remove a tick permission granted from: Scott Leighton / medicusmedia.com; Retrieved from: http://www.health.harvard.edu/newsletters/harvard_womens_health_wa tch/2009/june/recognizing-and-avoiding-tick-borne-illness Centers for Disease Control and Prevention. (2013). Tickborne diseases of the United States: A reference manual for health care providers (1st ed.). U.S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/lyme/resources/tickbornediseases.pdf

Dr. Lorinda Sheeler-South College Vanessa Ross-Des Moines University Iowa Medical Society Additional resources American Academy of Pediatrics. Rocky mountain spotted fever. In: Pickering LK, editor. Red book: 2012 report of the committee on infectious diseases. 29 th edition. Elk Grove Village (IL): American Academy of Pediatrics; 2012. p. 623 5. Longo, D. A., Fauci, D., Kasper, S., Hauser, J., Jameson, & Loscalzo, J.. (Eds.). (2013). Harrison's manual of medicine (18th ed.). New York, NY: McGraw-Hill. Gilbert, D. N., Moellering, R. C., Eliopoulos, G. M., Chambers, H. F., & Saag, M. S. (Eds.). (2013). The Sanford guide to antimicrobial therapy 2013 (43rd ed.). Sperryville, VA: Antimicrobial Therapy. Papadakis, M. A., & McPhee, S. J. (Eds.). (2014). Current medical diagnosis (53rd ed.). New York, NY: McGraw-Hill. Heymann, D.L. (Ed.). Control of communicable diseases manual (19th ed.). Washington: American Public Health Association. Centers for Disease Control and Prevention http://www.cdc.gov Tennessee Department of Health http://health.tn.gov/reportablediseases University of Rhode Island Tick Encounter Resource Center http://www.tickencounter.org/