2/6/2017
Judy Streit, MD Assistant Clinical Professor Infectious Diseases
Be familiar with Lyme Disease in U.S.: epidemiology, chronology of clinical manifestations, diagnostic pitfalls and treatment Be familiar with less-common tick- borne infections Ehrlichiosis/Anaplasmosis RMSF Babesiosis Emerging diseases
A-C: Ixodes B. burgdorferi (B. miyamotoi, mayonii); Babesia; Anaplasma; Powassan enceph virus) D: Amblyomma Ehrlichiosis E: Dermacentor RMSF F: Ornithodoros Relapsing fever
NEJM Spach et al ’93 329(13):936-947
1 2/6/2017
2 2/6/2017
22 yr old farmer from Dubuque presents in July with 4 days of fever, myalgias, headache. On exam: T 37.5oC, VSS. Not acutely ill. Rash noted:
1. Skin bx or aspirate for Borrelia PCR 2. Lyme IgM Western Blot 3. Lyme screening antibody (ELISA) 4. Cefuroxime 500 mg bid x 28 days 5. Doxycycline 100 mg bid x 14 days
3 2/6/2017
1. Skin bx for Borrelia PCR 2. Lyme IgM Western Blot 3. Cephalexin and TMP-Sulfa 4. Cefuroxime 500 mg bid x 28 days 5. Doxycycline 100 mg bid
Early Localized Infection (Stage 1) Localized EM (only ~1/2 are target lesions) Occurs in 60-80% Incubation: ½-4 wks Duration: days to weeks (based on tx) Flu-like illness variably present Regional LAN Serology unreliable
(NEJM Steere 345:115-125)
4 2/6/2017
A 50 yo landscaper from Iowa City presented in July with 8 days of fever and malaise. Exam showed multiple, oval, erythematous patches scattered over the thorax and extremities, sparing palms/soles
1. Multiple sites of inoculation of B. burgdorferi due to multiple tick bites
2. Anaplasmosis
3. Early disseminated Lyme disease
4. Tularemia
Early disseminated LD
5 2/6/2017
Site Manifesta- Onset % Involved Systemic tion w/o Tx Sx’s Skin 2nd EM Days to 50 Yes Weeks Neurologic Lymphocytic Days- 15-20% Usually meningitis; Months cranial neuritis; radiculoneuriti s; myelitis Cardiac Carditis: Days- 5-10% Possibly AV Nodal Months block; Myopericard. MSK Migratory Days- Possibly pain, Months inflamm. Eye Conjunctivitis; other
6 2/6/2017
Site Onset Manifesta % if no Tx Systemic tion S/Sx’s Joint Months- Arthritis- > 50% No Years mono or oligo- articular (knee) Neuro Months- Peripheral No Years neuropathy or neuritis
Skin (EU) Months- Acroderm No Years atitis chronica atrophica
Recurrent, pauciarticular Usually large joints, cool effusion Baker’s cyst Minority: persistent synovitis x mon-years despite tx (Evidence does not support chronic infection) Enthesopathy Genetic risk Rare reports of autoimmune dz months after dx
Photo: Arvikar, Steere ID Clin NA ’15;29:269
Chronic axonal polyneuropathy Distal paresthesia; diffuse axonal change EMG/NCV
Chronic local peripheral neuritis Radicular pain
Encephalopathy: subtle cognitive disturbance, difficult to demonstrate objectively, some relation to underlying systemic illness
7 2/6/2017
Early Early Dissem Late Dissem
Signs and Symptoms c/w LD History of possible exposure to Ixodes Laboratory tests not recommended in absence of typical signs/symptoms Laboratory tests helpful if used correctly, performed with validated methods
8 2/6/2017
ELISA / EIA screening Ab negative (stop)
positive
Western Blot (IgM, IgG)
(+) IgM WB: > 2 of 3 bands (+); FPs seen (+) IgG WB: > 5 of 10 bands (+); > 4 wks illness ~3-4 wks: 65-75% Sens; >4-8 wks: Sens higher (caveat: 40% of healthy w/ (+) 41kDa band; Ab’s persist x years)
Manifestation % (+) Serology Erythema 29 migrans Early 100 Disseminated Late LD 100
Using serology at time of EM lesion ELISA / EIA without WB WB w/o screening ELISA Treating based on chronic (+) Ab Using IgM WB alone for dz > 4 wks
9 2/6/2017
2nd Gen Ab Assay: C6 peptide ELISA IgG (+) earlier; can forego IgM or detect FPs Part of 2-tier testing in some labs Micro Lab testing: limited utility Culture: special media (BSK), EM lesions PCR: synovial fluid: superior to cx CSF anti-B. burgdorferi Ab’s Acute meningitis: often positive Other CNS dz: not reliable
Endemicity Signs/Sx’s Pretest Prob Test?
Low/Absent (+) Mod low Yes (5-20%) Low/Absent Nonspecific sx’s Rel low Consider > 2 wks Moderate Present Mod Yes (20-80%) Mod-high Nonspecific sx’s Mod low Yes > 2 wks High Present High No (Clin dx)
87% decr in subsequent EM after doxy x 1 (Nadelman et al, NEJM ’01 345:79)
Doxycycline 200 mg x 1 if: Ixodes tick attached >/= 36 hrs < 72 hrs from tick removal Local rate of tick infection is >20% No contraindication to doxycycline, > 8 yo
10 2/6/2017
Preferred Oral Regimens Doxycycline Amoxicillin Cefuroxime (+/- Alternate oral: selected macrolide)
Preferred Parenteral Regimen Ceftriaxone (Alternate parenteral: Cefotaxime, PCN G)
Indication Treatment Duration (d) EM Oral regimen 14-21 Mening/radiculo Parenteral 14-21 (can consider oral) CN VII palsy Oral 14-21 Cardiac Parenteral->oral 14-21 Arthritis Oral 28 Recrnt arthritis Oral/Parenteral 28/14-28 Chronic Neuro Parenteral 14-28 Post-Lyme Dz Consider other Syndrome cause; tx sx’s
11 2/6/2017
1. Pain (HA/arthralgia) or fatigue for wks/months after stnd abx (10%)resolution
2. Diffuse joint/muscle pain, fatigue, neurocognitive problems, anxiety/depression begin months after treatment and last years/indefinitely . Theory: central sensitization syndrome . Prolonged abx tx: no sustained benefit or risk> benefit (Klempner et al, nejm 2001;345:85)(Berende et al, nejm 2016;374:13) . Antibody profile differs for PLDS patients (Chandra Clin and Vac Immun ‘11)
Organism: Borrelia lonestarii Vector: A. americanum Where: SE US Less systemically ill than w/ Lyme Chronic complications not known No serologic test (yet) Tx: doxycycline or amoxicillin
40 yo Amish farmer from Ft. Madison, IA 1 week of F/C, HA, malaise, myalgias, anorexia; 2 days abdominal pain & SOB. PE: Fever, ↑ WOB, conjunctivitis, fine blanching mac/pap rash on thorax, no eschar
Labs: WBC 4.9 K/mm3; Bands 1.6 K/mm3; Plt 44 K/mm3; AST/ALT 355/389 IU/L
12 2/6/2017
1. Ehrlichiosis 2. Rocky Mountain Spotted Fever 3. Lyme Disease 4. Tularemia (Francisella infection)
1. Ehrlichiosis 2. Rocky Mountain Spotted Fever 3. Lyme Disease 4. Tularemia (Francisella infection)
13 2/6/2017
Ehrlichia: HME Infects monocytes Amblyomma americanum tick
Anaplasma: formerly HGE Infects neutrophils Can have co-infx w/ B. burgdorferi & Babesia
RMSF (R. rickettsia) Infects endothelium Small-vessel vasculitis/MOSF
Fever, HA, myalgia, malaise Rash RMSF: eventually 90% of children Onset after 1st appt (> day 2-4) HME: occasionally HGE: rare Infrequent: abd pain, meningoencephalitis WBC, Plts AST/ALT (RMSF: WBC usually nml but w/ left shift)
14 2/6/2017
Dissem Neisseria infx TTP Enterovirus Drug Reaction Syphilis (2nd) Rheum Dz Parvovirus Leptospirosis EBV
15 2/6/2017
Recreational/Occupational exposure Travel to endemic areas (N & S Central, SE, NE) Illness in family members, coworkers, pets Absence of tick bite hx does not exclude dx
Use hx, symptoms, exam and labs If no strong clues, watch/wait x 24-48 hrs If presumptive TBRD: Doxycycline!! OK in children < 8 yrs old delays in tx can lead to fatalities rarely: alternate med b/c allergy/pregnancy Confirmatory labs: won’t guide empiric tx If diff dx includes N. meningitidis: tx both Prophylaxis of tick bites not recommended
Ehrlichia/Anaplasma Blood smear for morulae (+/-) Whole blood PCR Acute & convalescent serum (2-3 wks apart) (acute serology usually negative) RMSF Serology (acute/convalescent) Skin biopsy w/ immuno PCR: limited utility at present
16 2/6/2017
68 yr old woman returns from 2 wk camping/canoe trip in New England 1 week ago (July). 4 days of F/C, HA, malaise. No known tick bites. No eschars. PE: T = 100.3. +/- scleral icterus. No rash, LAN, neck stiffness. Labs: hgb 11.2, plt 130, WBC 7, total bili 1.6, direct bili 0.2. Alk Ph nml. AST/ALT ~100. Blood cultures pending.
Doxycycline 100 mg bid x 10 days 1 week later: -Anaplasma PCR (+) positive, -Lyme Ab negative -Continued F/C & malaise, albeit modest improvement Labs: hgb 10.5, plt 110, LDH 380, TB 2.0, Direct bili 0.2, AST/ALT 40/48
1. Begin ceftriaxone, d/c doxycycline 2. Change doxycycline to IV form 3. Blood smear for parasites 4. Complete doxycycline as planned
17 2/6/2017
1. Begin ceftriaxone, d/c doxycycline 2. Change doxycycline to IV form 3. Blood smear for parasites 4. Complete doxycycline as planned
Consider: any pt w/ febrile illness & residence in/travel to endemic area < 2 mos or blood transfusion < 6 mos Strong clinical suspicion required since no classic signs Automated blood counter will not detect Suspect co-infx w/ Anaplasma if more severe disease/poor response to tx for Lyme or Anaplasma (common vector)
18 2/6/2017
No sx’s & imm-competent: Tx if cont’d infx @ 3 months # weeks depends on imm state/relapse (1-2 wks vs 4+ wks) Severe disease: RBC exchange/add Clinda Poor tolerance of quinine regimen (cinchonism, N/V)
Agent Epidem Tick Illness Dx Tx B. Like LD Ixodes Flu-like, Ab/PCR Like LD miyamotoi relapsing not widely fever avail B. mayonii MN/WI Ixodes Flu-like + Same as Like LD N/V, LD tests diffuse rash Heartland MO Ambly- Flu-like, State None virus omma anorexia, Health ↓WBC/plt Dept, CDC Powassan Like LD Ixodes CNS dz State None virus possible Health Dept, CDC
19 2/6/2017
Disease Agent Classifi- Major Region cation Vector
Lyme B. burgdorf- Spirochete Ixodes NE, N Cen, eri NW
Ehrlichiosis E. chafeensis Rickettsia Amblyomma SE, S Cen, E. ewengii S Atlan
Anaplasmo- A.phagocy- Rickettsia Ixodes NE, N Cen, sis (HGA) tophilum NW
RMSF R. rickettsia Rickettsia Dermacent. SE, W, S Cen Babesiosis Babesia sp Protozoan Ixodes NE, N Cen
Disease Agent Classifi- Major Region cation Vector Tularemia Francisella Bacteria Dermacent. S Cen tularensis Amblyomma Relapsing Borrelia sp. Spirochete Ornitho- West Fever doros CO Tick Coltivirus Virus Dermacent. West Fever STARI ? ? Amblyomma S, SE
Tick Toxin Neurotoxin Dermacent. NW, S Paralysis Amblyomma
Risk: Spring/Summer/Fall (albeit not exclusively) Seek occupational/recreational/travel Hx Don’t rely on hx of tick bite EM: clinical diagnosis of Lyme Recognize diversity of Lyme s/sx’s vs time
Presumptive TBRD (hx, exam, labs)Tx Risk for co-infection w/ Ixodes vector Recognize emergence of new pathogens
20 2/6/2017
Steere, AC Lyme Disease NEJM 2001 345:115-125 Diagnosis and Management of Tickborne Rickettsial Diseases. MMWR 55(RR04) 1-27. Wormser et al. The Clinical Assessment, Treatment and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis and Babesiosis: Clinical Practice Guidelines. Clin Infect Dis 2006 43:1089- 1134. Krause et al. Disease-Specific Diagnosis of Coinfecting Tickborne Zoonoses: Babesiosis, Human Granulocytic Ehrlichiosis and Lyme Disease. Clin Infect Dis 2002;34:1184-1191. Halperin JJ et al. Common Misconceptions about Lyme Disease. Am Jour Med 2013;126:264e.1-e.7.
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