1. Vector-borne Infections Allison Liddell, M.D. Infectious Diseases September 22nd, 2003

3. Clinical Vignette • 28yo FBI agent on temporary assignment in the Nantahala forest in Western North Carolina presents with acute onset fever, chills, headache 3 days after Memorial Day. • Exam: confused, ill appearing, a few petechiae present on wrists and ankles • Labs: platelets=75K, mild leukocytosis, mildly elevated transaminase • LP with 75 WBC, mostly lymphocyes with protein=154

4. Tick-Borne Infections in the U.S. • Lyme disease • Rocky Mountain spotted fever • Ehrlichiosis • Tularemia • Babesiosis • Colorado tick fever • Tick-borne relapsing fever • Tick-borne encephalitis • Tick paralysis • Q Fever

5. Tick Classification

6. Questing tick

7. Rocky Mountain Spotted Fever • Described in late 1900’s in Bitter Root Valley • Caused by infection with Rickettsia rickettsii • Obligate intracellular, requires cell culture to cultivate

8. RMSFtransmission • Maintained transovarially in ticks • Tick vectors are hard ticks: • Dermacentor variabilis (eastern US) • D. andersoni (western US) • A. americanum (south-southwestern US)

9. Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928

10. RMSFepidemiology • Most cases occur May – September • Highest rate in children 5 - 9 years • Exposure to dogs, grassy areas risk factor • 8.5% mortality (Billings et al)

11. TDH Website

12. TDH Website

13. RMSFClinical Manifestations • Incubation period 2 - 14 days • Onset with fever, myalgias, headache • GI findings may mimic an acute abdomen • Rash appears 3 - 5 days after onset of fever • Meningismus and CSF pleocytosis may occur • WBC usually normal, platelets may be decreased • Hyponatremia occurs in 50%

16. RMSFDiagnosis • Serology • IF staining of tissue specimen • PCR under development

17. RMSFOutcome • N=6388 over 1981-1998 • Annual case-fatality rate 3.3% • Risk factors for mortality: • Old age • Chloramphenicol only • Tetracycline not primary therapy • Treatment delayed > 5 days Holman et al JID 2001

18. Clinical Vignette • 54 yo WM farmer in Missouri presents with 3 day h/o high fevers, chills, headache and marked malaise in June • Exam notes a confused, ill-appearing man but is otherwise unremarkable • Labs note transaminases 3 x normal, platelets 115K, WBC 2.1, CSF 32WBC, protein 127

19. History of Ehrlichiosis • 1935 - E. canis-hemorrhagic illness in Algerian dogs • 1950s – E. sennetsu-mononucleosis-like illness in Japan • 1986 – Ehrlichiosis-patient in Detroit after tick bites in Arkansas • 1991 - E. chaffeensis cultured from patient at Fort Chaffee in Arkansas

23. Genus Ehrlichia Small gram-negative bacteria closely related to Rickettsiae • Obligate intracellular parasites • Infect circulating blood elements • Reside and replicate within membrane-bound cytoplasmic vacuoles • Vertebrate reservoirs and arthropod vectors

27. Ehrlichia ewingii • First discovered in dogs with granulocytic ehrlichiosis, 1992 • Disease is milder than E. canis infection • Manifestations include fever, lethargy and polyarthritis • Found to date in dogs in Missouri, Arkansas, Oklahoma and N. Carolina • Member of E. canis genogroup (cross-reactivity) • Experimental transmission by A. americanum

29. Ehrlichiae Causing Human & Veterinary Disease

30. Human EhrlichiosisSymptoms Dumler et al, Annu. Rev. Med. 1998. 49:201-213

31. Human EhrlichiosisClinical Spectrum • DIC • Pancytopenia • Encephalitis/Meningitis • Pulmonary infiltrates/Respiratory failure • Gastrointestinal bleeding • Renal Failure

32. Human Ehrlichiosis LaboratoryFindings • Leukopenia • Thrombocytopenia • Elevated transaminases • Hyponatremia • >4-fold elevation in IFA • PCR

33. RMSF/EhrlichiosisTreatment • Adults: Doxycycline 100 mg bid • Children: Doxycycline 3 mg/kg/day in 2 divided doses Duration: 3 days after defervescence, minimum 5-7 days

34. Clinical Vignette • 34 yo WF owner of a campground presents with a nonhealing lesion on the right index finger for 2 weeks, adjacent to the nail bed. • Failed Augmentin and acyclovir by PCP for “infected paronychia” • Exam notes an ulcerated lesion and regional adenopathy

35. TularemiaHistory • McCoy & Chapin 1910 • “plague-like disease” of rodents in Tulare Co. CA • Bacterium Tularense • Edwards Francis • 1928 - 800 cases • isolated organism • proved vector • named the disease • developed culture and serology methods • noted risk to workers

36. Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928

37. 1368 cases 1990-2000 All states except Hawaii, but predominately MO, AK, OK & SD Reinstated on nationally notifiable list 2000 (n=142) Type A (biogroup tularensis) Multiple vectors (tick, deerfly) >250 animal species rabbits hares muskrats Other transmission carnivores direct contact inhalation/ingestion Peak incidence 1939 TularemiaEpidemiology

38. Outbreak 2001 Pneumonic Tularemia • 15 patients in Martha’s Vineyard • 11 primary pulmonary • 1 death Feldman et al, N Engl J Med 2001 Nov 29;345(22):1601-6

39. TularemiaClinical Manifestations • Ulceroglandular • black based ulcer • tender regional lymphadenopathy  bubo • Typhoidal • Oculoglandular • Primary pulmonary

42. TularemiaDiagnosis • Titers • 4-fold increase • single > 1:160 • Skin test • Culture – notify laboratory

43. TularemiaTreatment • Streptomycin 1 gm iv q12h for 10 days • Gentamicin 5 mg/kg/d for 10 days • Tetracycline/chloramphenicol • associated with 15-20% relapse • Quinolones • Excellent in vitro activity • Limited data, anecdotal experience suggests efficacy • Live attenuated vaccine for high risk groups

44. TularemiaComplications • Pneumonia  abscess, effusion • Rhabdomyolysis • Acute renal failure • Meningitis • Pericarditis

45. Lyme • Most commonly reported tick-borne infection in U.S. • 1993-1997, mean 12,451 annual cases (CDC)

46. LymeHistory • Cluster of cases near Lyme, CT 1975 • Johnson RC, Schmid GP, Hyde FW, Steigerwalt AG, Brenner DJ. Borrelia burgdorferi sp. nov.: etiological agent of Lyme disease. Int J Syst Bacteriol 1984; 34:496 7.

47. Lymeepidemiology • B. burgdorferi sensu lato • Tick vector • Black-footed mouse reservoir • White-tailed deer host • Birds and mammals implicated in Europe

48. Erythema migrans (90%) Occurs 8-14 days after bite Single lesion, average size 15cm Systemic symptoms may be present Secondary lesions may occur Carditis Aseptic meningitis Bell’s palsy Lyme DiseaseEarly Manifestations

49. Lyme DiseaseLate Manifestations • Arthritis • Knees involved in 90% • Usually resolves, 1-2 weeks • May recur • CNS disease (rare in children)

50. Serology ELISA Western blot Culture on BSK-II media 57-85% sensitive skin Blood, CSF, synovial fluid Warthin-Starry stain PCR Lyme DiseaseDiagnosis