Magdalena E. Sobieszczyk, MD, MPH

Transcription

1 Learning Objectives Tick Borne Diseases 19 th Annual Update & Review of Internal Medicine June 7, 2013 Magdalena E. Sobieszczyk, MD, MPH Assistant Professor of Clinical Medicine Columbia University Review general principles of tick borne diseases Review tick borne pathogens Review clinical presentation, diagnosis and treatment of several tick borne diseases References and Further Reading General Principles Presentation is often very non specific flu like: fever, headaches, myalgias Review travel history, consider seasonal presentations and geography Diagnosis is clinical Treatment should be initiated before test results available May be associated with a specific rash Frequent abnormalities: LFT and CBC Convergence in tick vectors: Co infections are common DOXYCYCLINE is therapy for most common tick borne illnesses Hard Ticks Soft Ticks Tick-borne diseases (human tick vector) Rocky Mountain spotted fever Lyme disease Babesiosis Ehrlichiosis Anaplasmosis Tularemia Endemic typhus Southern-tick associated illness (STARI) Powassan and other tick-borne encephalitis Tick typhus: African tick typhus, Mediterranean tick typhus, Quennsland tick typhus Colorado tick fever Relapsing fever Tick-borne pathogens Case 1 Bacteria: Rickettsia species Borrelia species Parasites Protozoa Viruses 62 yo woman presents with 3 week history of fever, headaches and malaise She is otherwise healthy with a hx/o HTN treated with beta blockers Social Hx: Originally from Ecuador, last visit to Ecuador one month ago lives in Queens and has a dog Relatives on Cape Cod frequent visits

2 Blood smear Which of the following is the most likely diagnosis A. Lyme B. Colorado tick fever C. Anaplasmosis D. Babesiosis E. RMSF Question 1 Emerging infection Ixodes tick Intraerythrocytic protozoa Babesia Animals as natural reservoirs White tailed deer perpetuate tick White footed mouse perpetuate Babesia Babesiosis Epidemiology B. microti in North East (NE, CT, NY, P) hundreds of cases reported B. duncanii Washington State and Northern California (very few cases) B. divergens: Missouri, Kentucky, Washington State Europe: rare, B. divergens Other routes of transmission transfusion or vertical Geographic Areas Where Human Babesiosis and Ixodes Tick Vectors Are Endemic Transmission of Babesia microti by the Ixodes scapularis Tick Vannier & Krause NEJM 2012 Vannier & Krause NEJM 2012

3 Clinical presentation Incubation 1 6 weeks Spectrum of disease: Mild flu like illness in young and healthy Life threatening, malaria like in asplenic, immunocompromised elderly Most common symptoms: Fever (intermittent or sustained), shaking chills Fatigue, malaise, arthralgias, myalgias, SOB Mild hepato splenomegaly Slide courtesy A-C.Uhlemann Complications of B. microti Acute respiratory failure Disseminated intravascular coagulation Congestive heart failure Renal failure Severe anemia, high parasitemia (>10%) Fatal in 5 10% hospitalized B. divergens: hemoglobinuria, jaundice persistent high fevers, parasitemia up to 80% Slide courtesy A-C.Uhlemann Babesia (microti) Deer tick Ixodes scapularis Microscopy clues: Thin blood smear Maltese cross Varying shapes and sizes Vacuoles Lack of pigment production PCR Indirect immunofluorescent antibody test specificity 88 96% Symptoms precede rise in Ab by ~1week Algorithm for Diagnosis of Babesiosis Caused by Babesia microti. Treatment Not necessary in asymptomatic individuals but consider if parasites persist for >=3months Mild B. microtii: treatment 7 10 days Atovaquone + azithromycin (preferred) Quinine + clindamycin Severe disease B. microtii: longer course needed IV clindamycin + quinine Exchange transfusions in high grade parasitemia (>10%), severe anemia, pulmonary/renal complications B. divergens: immediate complete RBC exchange transfusion plus clindamycin and quinine Evaluate for Lyme s & Human granulocytotropic anaplasmosis (same vector) Babesiosis: Take home points Rare protozoal disease, non specific febrile illness Consider diagnosis if Flu like symptoms in residents of endemic areas of travelers to endemic areas Patients are presenting with Lyme or human granulocytic anaplasmosis (causative agents also transmitted by Ixodid Ticks) Acquired by humans if close to white footed mouse and white tailed deer Severe disease in immuno compromised Thin blood smear, PCR, serologies Long treatment courses for persistant and relapsing disease, RBC exchange

4 Case 2 A 65 y.o avid gardener and golfer who lives in Westchester, NY presents in June with fever, myalgias, arthralgias, headache, malaise, and nausea. Lab tests are notable for: Leukopenia thrombocytopenia and elevated liver enzymes What is the most likely diagnosis? A. Acute CMV B. Rocky Mountain spotted fever C. Tularemia D. Ehrlichiosis E. Lyme Question 2 Ehrlichioses Anaplasmataceae family Tickborne infections Ehrlichia chaffeensis causes Human Monocytic Ehrlichiosis (HME) Anaplasma phagocytophilium causes Human Granulocytic Anaplasmosis (HGA) Very small, obligate intracellular, Gram negative bacteria Target either monocytes OR granulocytes and are named accordingly Ehrlichia chaffeensis Morulae, Latin for mulberry CID 2007: 45 Dumler Anaplasma phagocytophilum Incidence by State Incidence by Age Group, Ehrlichiosis CDC.gov CDC.gov

5 HME--Epidemiology S. Central, SE, mid Atlantic states Vector: Ixodes ticks (hard ticks) Lone Star tick (Amblyomma americanum) Reservoir: white tailed deer HGA--Epidemiology NE, mid Atlantic, Upper Midwest, Pacific NW states + internationally Vector: Ixodes ticks (hard ticks) I. scapularis (aka blacklegged tick or deer tick) or Western Blacklegged tick Reservoir: small mammals (esp. whitefooted mice) CDC.gov CDC.gov Clinical Presentation Clinical Presentation: similar to rickettsial diseases, but less likely to get a rash Wide spectrum of disease Ranges from mild illness/asymptomatic to a severe, fatal infection (up to 3%) Risk factors for more severe disease: Immunocompromised status (HIV, asplenic, on steroids/chemotherapy) Diagnosis and Treatment Clinical suspicion (fever/flu symptoms) in endemic region during tick season PCR acutely, diagnostic tool of choice May not be available Serologic look for 4x rise in antibodies Most sensitive test Examination of peripheral blood for morulae Clumps of organisms in the cytoplasm of the Monocyte (HME) or granulocyte (HGA) very low yield Treatment: Doxycycline Case 3 52 y.o man reports spending a weekend hiking on Long Island. This morning he discovered a tick on his leg which he promptly removed (easily extracted) but is wondering whether or not he should do anything else.

6 Which of the following statements is most appropriate in this situation? A. Since the tick was removed promptly, no further action is needed B. You recommend 14 day course of Doxycycline C. You recommend a single dose of Doxycycline D. You recommend a single dose of Amoxicillin The I. scapularis nymphal ticks that spread B. burgdorferi are very small! I. scapularis Question 3 Removing the Tick per the CDC: Remove a tick from your skin as soon as you notice it. Use fine-tipped tweezers to firmly grasp the tick very close to your skin. With a steady motion, pull the tick s body away from your skin. Then clean your skin with soap and warm water. Throw the dead tick away with your household trash. Avoid crushing the tick s body. Do not be alarmed if the tick s mouthparts remain in the skin. Once the mouthparts are removed from the rest of the tick, it can no longer transmit the Lyme disease bacteria. If you accidentally crush the tick, clean your skin with soap and warm water or alcohol. Don t use petroleum jelly, a hot match, nail polish, or other products to remove a tick. Prophylactic antibiotics after tick bites? Epidemiology what to prevent? NE Lyme disease Transmission: < 24 hours 0/58 < 48 hours 4/50 (8%) < 72 hours 36/52 (69%) IDSA criteria (need all!): Ixodes scapularis, tick attached >36 hours Prophylaxis within 72 hours local infection rate of ticks with B. burgdorferi >20% No contraindication to doxycycline Case 3 continued The patient fails to fill the prescription and does not take Doxycycline. About 10 days later he s you this picture, reports a mild headache and a temperature of o F Case 3 continued Early Lyme disease is diagnosed and a 21 day course of oral doxycycline is initiated. Rash resolves after 2 days and the patient is asymptomatic One week after completing therapy, the patient presents with generalized malaise, diffuse aching, and a mild sore throat. The rash and the fever have not returned.

7 Case 3 continued Labs: Normal WBC and Hgb ESR 14 ALT 34 Serologic test for Borrelia burgdoferi: Positive What is the most appropriate next step in treatment? A. IV ceftriaxone for 4 weeks B. Oral amoxicillin for 4 weeks C. Oral atovaquone for 4 weeks D. Oral azithromycin for 4 weeks E. No additional antibiotics Question 4 Lyme Disease Etiology: Borrelia burgdorferi Gram negative spirochete Most common vector borne disease in the U.S. Predominant in the NE Vector:I. scapularis usually the nymph (must feed 24+ hrs) Reservoir: white footed mouse or other small mammals (i.e. chipmunk) fed upon by nymphs adult ticks feed on white tailed deer (deer not reservoir for the B. burgdorferi) Peak transmission: June, July, August Reported Cases of Lyme Disease by Year, United States, The graph displays the number of reported cases of Lyme disease from 2002 through The number of confirmed cases ranged from a low of 19,804 in 2004 to high of 29,959 in CDC Summary of Lyme Clinical Presentation Local: erythema migrans (> 5cm), 3 30d Early: may also have fever, flu symptoms Early neurologic disease: days to weeks Meningitis or radiculopathy Cranial nerve palsy Cardiac disease: Heart block, myopericarditis Late Disease: weeks to years Arthritis (can occur earlier), CNS or PNS disease Reported Clinical Findings Among Confirmed Lyme Disease Patients, CDC.gov

8 Diagnosis Two-Tiered Testing for Lyme Disease If there is erythema migrans, diagnosis can be clinical Acute/convalescent antibodies** Not useful acutely, sensitivity/specificity issues CSF examination may be indicated CSF profile: Lymphocytosis, elevated protein, normal glucose Test for antibodies Co infection with HGA and Babesia may occur (same vector!) Indication, route, and duration of therapy for Lyme disease INDICATION ROUTE REGIMEN DURATION Erythema migrans Oral Preferred: Doxycycline, Amoxicillin, Cefuroxime axetil 14 d (14-21d) Cranial nerve palsy Oral* Alternative: Azithromycin, 14 d (14- Clarithromycin, Erythromycin 21d) Meningitis IV Preferred: Ceftriaxone (2g daily) Alternative: Cefotaxime, Penicillin G 14 d (10-28d) Cardiac IV or Oral 28 d Arthritis no Oral 28 d neurologic disease Recurrent arthritis IV or Oral 28 d after oral regimen Antibioticrefractory Symptomatic (eg NSAIDS), no antibiotics arthritis Lyme-associated dementia IV 28 d Post Lyme disease syndrome Consider and evaluate other potential causes of symptoms; if none is found, then administer symptomatic therapy Treatment Essentials Doxycycline (or alternative) for erythema migrans Oral regimen may also be used for isolated Bell s palsy, mild cardiac disease, arthritis IV Ceftriaxone (3 rd gen cephalosporin) for heart block, symptomatic cardiac disease, other PNS/CNS disease Post Lyme Disease Syndrome No accepted definition Chronic symptoms after receiving standard treatment regimens May be an autoimmune issue without ongoing infection Additional antibiotics not recommended Re infection can occur Lyme: Take home points 80% of patients with Lyme disease develop EM, 5 14 days after inoculation; systemic presents may or may not be present Serologic testing is often negative in patients with early Lyme Lyme carditis most often consist of transient heart block Lyme arthritis typically presents as a mono or oligoarthritis most commonly involving the knees Seroreactivity often persists for at least months after antibiotic treatment of early infection and for years after treatment of late infection

9 Case 4 It s July and a 57 y.o. woman is evaluated for 1 day of fever, mylagia, frontal headache. Past medical hx/o negative Reports recent travel 2 week camping trip in Virginia and close to home. She returned 11 days ago and does not recall any insect/bug bites Has a dog and two cats On exam: mildly ill, temp o F BP 125/65, HR 90/min No lymphadenopathy or rash. Cardiopulmonary and abdominal exam normal Labs: Normal Hgb, platelets at 110,000/μL; Elevated AST/ALT Sodium 130 Which of the following is the most appropriate next step A. Doxycycline B. Oseltamivir C. Postpone treatment until we have results of diagnostic test D. Vancomycin and cefriaxone Question 5 Rocky Mountain Spotted Fever (RMSF) Caused by Rickettsia rickettsii, small gram negative coccobacilli (need special stain to see) Belongs to the spotted fever group of Rickettsiae Obligate intracellular bacteria (cell culture) RMSF The most severe rickettsial disease in U.S. Transmitted to humans via tick bite (60% recall a bite) Hard ticks (Ixodidae family) are both the reservoir and vector for RMSF Dermacentor species: American dog tick, brown dog tick or RM wood tick, depending on location in U.S. Hosts: various mammals depends on tick and stage of development Some thoughts about ticks By 1996: 869 species or subspecies! Two major families Ixodidae (hard ticks): most infections Argasidae (soft ticks): brief meals from host and drop off; rarely recalled, rodent infested cabins in Western US > Tick borne relapsing fever Basic life stages: larva, nymph, adult Second to mosquitos as vectors of human infections Slide courtesy of A-C. Uhlemann Rocky Mountain is now a Misnomer: most common in SE/S.Central states, 2010 Also has wide Geographic distribution in the Western hemisphere

10 RMSF in the US, cases/year RMSF: Clinical Presentation (if symptomatic) Decreasing fatality: 28% case fatality in 1944 to <1% case fatality beginning in Most cases between May and August After ~1 week incubation: acute onset of flu like symptoms (i.e. fever, severe headache, malaise, myalgias/arthralgias, nausea/vomiting/abd pain) Only 15% of patients with RMSF have a rash at time of presentation 2 5 days later a macular eruption on wrists/ankles (90 95%) Eruption can be blanching / papular Widespread and progresses centripetally (starts on extremities and spreads inwards). Palms and soles are classically involved. With progression, petechiae and palpable purpura can develop RMSF: Late/Severe Disease Rash Full body petechial rash with palm/sole involvement Edema, ischemia, hypovolemia, and multi organ system failure (from microvascular injury) Neurological, Renal, Hepatic, Pulmonary... Gangrene Amputation Immunohistochemistry on a skin biopsy reveals an infectious agent Labs: hyponatremia, thrombocytopenia, & elevated liver enzyme levels Slide courtesy of A-C. Uhlemann Risk factors for fatal disease Diagnosis Age > 60 and male gender Chronic alcohol abuse Non tetracycline use Delayed initiation of treatment (>5 days illness) Black race (rash can be missed) Clinical Suspicion Immunohistochemistry on a skin biopsy Serologic tests (IFA)* and PCR available results take time Shell vial cell culture (not usually done) Alternative stains (not usually done)

11 RMSF Treatment Doxycycline Treatment should not be delayed while awaiting laboratory confirmation Prompt treatment associated with better outcome: mortality rate increases from 6.5% to >20% when treatment is initiated more than 5 days after onset of symptoms RMSF: Take home points Rash: characterized by blanching erythema around wrists, ankles Lesions spread centripetally and become petechial Rash may occur in only 15% of patients on presentation but appears in majority by day 4 of illness Prompt treatment is key Additional References Wormser et al. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases 2006; 43: Chapman AS et al. Tickborne Rickettsial Disease Working Group. MMWR Recomm Rep. 2005; 55:1 27 Halperin JJ, Golightly M. Lyme borreliosis in Bell s palsy. Long Island. Neuroborreliosis Collaborative Study Group. Neurology 1992; 42: Krause PJ et al. Disease specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin Infect Dis. 2002;34(9):1184. Vannier E et al. Human babesiosis. N Engl J Med Jun;366(25):