Board Review: Ticks and TB
Jordan Neviackas
September 10, 2013
Tick-borne diseases
Lyme disease
• Deer tick, Ixodes scapularis transmitting Borrelia burgdorferi
• Three distinct stages:
– Early localized – EM, Tx with empiric doxycycline
– Early disseminated – multiple EM lesions, cranial nerves, meningitis,
myocarditis (treat with IV)
– Late stage – 60% untreated patient: Arthritis, encephalomyelitis
• Serologic testing not recommended in early localized and restricted to
those with signs or symptoms in endemic areas
• Antibodies in people with nonspecific sxms of fatigue/myalgia are likely
false-positives
Babesiosis
• Babesia microti, same tick vector as Lyme
• Replicate inside erythrocytes, typically asymptomatic, but can
range from febrile illness to fulminant multiorgan failure
• Mild: fever, hemolysis, hepatomegaly, jaundice
• Severe: hemolytic anemia, AKI, DIC, heart failure
• Dx: PCR more sensitive than direct microscopy; serologic
testing not recommended
• Rx:
– Mild: atovaquone and azithromycin
– Severe: Quinine with clindamycin + exchange transfusion
Southern tick-associated rash illness
• Indistinguishable from early localized Lyme –
EM skin lesion a/w fever, HA, myalgias
• Southeast, mid-Atlantic, and south central US
• No causative agent known, but vector is the
Lone Star tick.
• Treat with doxycycline.
Ehrlichiosis & Anaplasmosis
• Monocytic ehrlichiosis and granulocytic
anaplasmosis, clinically similar rickettsial diseases 
nonfocal febrile illness with HA, myalgias and fatigue
+/- rash
• Antibodies appear 2-4 weeks after illness.
• Treat empirically with doxycycline
Rocky Mountain Spotted Fever
•
•
•
Rickettsial disease with 2-14 day incubation period
Fever, headache, myalgia, confusion, GI sxms
Petechial rash (90%), but only 15% at onset
–
•
•
Nonblanching macules on the wrist and ankles
progressing to petechial on trunk, extremitites palsm
and soles
Thrombocytopenia, elevated LFTs, normal WBC
Rx with doxycycline empirically and should not be
discontinued based on test results.
Tuberculosis
Background
• Rate of TB in foreign-born persons living in the
US is 11 times higher than that of persons
born in the US
• Progression to active TB can occur after initial
infection or by reactivation of LTBI
• Without Rx, 10% will develop active TB during
their lifetime.
Clinical manifestations
• LTBI is asymptomatic
• Active disease is insidious: fever, night sweats, cough (bloody
and/or purulent), chest pain, weight loss, anorexia
• Physical is nonspecific; immunocompromised patients do not
have typical signs or sxms and are more likely to develop
disseminated disease
• Any site may be involved; mimics other diseases
• If suspected active disease, obtain TST/IGRA; CXR;
microbiologic tests including AFBs and cultures
Diagnosis: TST
• Delayed-type hypersensitivity
• Based on patient’s risk factors for infection
• False negative: recent infection, age < 6 months,
overwhelming infection, recent live virus vaccine or
infection and anergy
• Remote exposure may result in an initially negative
result that can become positive several weeks later
>5mm
-HIV-infected persons
-A recent contact of a person with
active TB
-Persons with fibrotic changes on
chest radiograph consistent with
prior TB
-Patients with organ transplants
-Persons who are
immunosuppressed for other
reasons (e.g., taking the equivalent
of >15 mg/day of prednisone for 1
month or longer, taking TNF-a
antagonists)
>10mm
-Recent immigrants (< 5 years)
from high-prevalence countries
-Injection drug users
-Residents and employees of highrisk congregate settings
-Mycobacteriology laboratory
personnel
-Persons with clinical conditions
that place them at high risk
-Children < 4 years of age
- Infants, children, and adolescents
exposed to adults in high-risk
categories
>15mm
any person, including persons with
no known risk factors for TB.
However, targeted skin testing
programs should only be
conducted among high-risk groups.
Diagnosis: Interferon-y Release Assay
• Measure interferon-y by T cells as a response to MTB
associated antigens
• As sensitive but more specific than TST
• Preferred when person has received BCG either as Rx
or as vaccine (or poor follow up)
Cultures and micro tests
• If active disease suspected, cultures always need to
be performed for confirmation (solid slow, liquid
faster).
• AFB depends on the concentration of mycobacteria
• Nucleic acid amplification
• Consider bronch/BAL/biopsy; ADA fluid analysis
• CSF: lymphocytic pleocytosis, decreased glucose,
elevated protein; AFB/cultures usually negative; PCR
high specificity, but average sensitivity
Radiography
• Primary: localized infiltrates or paratracheal/hilar
LAD
• Reactivation: fibrocavitary disease in the superior
segments of the lower lobes or apical-posterior
segments of the upper lobes.
Treatment: LTBI
• 9 months of isoniazid with pyridoxine (or
rifampin for 4 months
• CDC included once-weekly rifapentine and
isonizid
Treatment: Active disease
• Multiple drugs for at least 6 months
– Treatment phase for 2 months (isoniazid, rifampin,
ethambutol, pyrazinamide) folllowed by
continuation phase (isoniazid and rifampin).
– If interrupted for >2 weeks, must restart
• TB meningitis for 12 months
• Steroids for pericarditis and meningitis
Medications
• Isoniazid – rash, LFTs, peipheral neuropathy, lupus like
syndrome
• Pyrazinamide – hepatitis, rash, hyperuricemia
• Rifampin – rash, GI upset; caution with protease inhibitors,
orange body fluids
• Ethambutol – optic neuritis, rash; get baseline visual acuity
and color vision
MDR and XDR TB
• 88 cases in the US in 2010
• Resistant to at least isoniazid and rifampin
• XDR also fluoroquinolones and to at least
kanamycin, capreomycin or amikacin
• Rx includes more medications and longer
duration
Questions
A 22-year-old man is evaluated for a skin eruption on his leg. The patient lives
in Virginia and is active outdoors. One week ago, he found a black tick on
his lower leg, which his roommate removed with a tweezers. Yesterday he
developed diffuse myalgia, neck stiffness, and fatigue. These symptoms
have persisted, and today he notes erythema at the site of the previously
attached tick.
On physical exam, temp is 38.1 C (100.6 F); other vitals are normal. There is
no nuchal rigidity.
Which of the following is the most appropriate initial management?
A. B. burgdorferi PCR on skin biopsy specimen
B. Empiric IV ceftriaxone
C. Empiric oral doxycycline
D. Serologic testing for Lyme disease
C. Empiric oral doxycycline
Empiric oral doxycycline is the recommended
treatment for erythema migrans regardless of
the cause.
A 72 year old man is evaluated for fatigue and weakness of 8 months’
duration. The patient is a retired businessman who is an avid gardener and
recalls many tick attachments over the past several years. He lives in Texas
but has traveled extensively throughout the US. He was seen in a walk-in
clinic 1 week ago and had lab testing for Lyme disease. An ELISA for
Borrelia burgdorferi was positive. A Western blot was negative for IgG and
positive for IgM antibodies.
Physical exam today revealed normal vital signs. An EKG is normal.
What is the most appropriate management?
A. Initiate additional evaluation for fatigue and weakness.
B. Repeat serologic testing for B. burgdorferi in 1 month
C. Treat with ceftriaxone
D. Treat with doxycycline
A. Initiate additional evaluation for fatigue and
weakness.
Nonspecific symptoms with low pretest
probability for Lyme disease. ELISA is sensitive
but nonspecific. When symptoms have been
present for more than 1 month, a positive IgM
in the absence of IgG most likely represents a
false-positive.
A 42 year old man is evaluated in the ED for a 3 day history of dyspnea and
dizziness. He is training for a marathon and initially attributed his
symptoms to overexertion and dehydration. Despite refraining from
training and increasing his fluid intake, his symptoms have persisted. He
has no chest pain, fever, or cough. The patient is a college professor in
Rhode Island. He has not noted any tick attachments or rash.
On physical, he has a normal temp, BP is 100/60 and pulse is 35. Lab results
show a normal CBC, metabolic panel and cardiac enzymes. EKG shows
complete heart block. Both ELISA and confirmatory Western blot are
positive.
What is the most appropriate initial treatment?
A. IV ceftriaxone
B. Oral cefuroxime
C. Oral doxycycline
D. Placement of a permanent pacemaker
E. Observation
A. IV ceftriaxone
IV ceftriaxone is the recommended therapy for
patients with Lyme myocarditis associated
with second or third degree heart block.
A 56 year old woman is seen in the ED in May for a 2 day history of fever, myalgia and
headache. She works as a horse trainer in Oklahoma and recalls removing at least
3 ticks from her skin in the past 2 weeks.
On physical, she appears ill with a temp of 102.7 F. Other vitals are normal. There is no
nuchal rigidity, lymphadenopathy or rash.
Labs:
Leukocyte count 14,600 with 87% neutrophils
Platelet count 136,000
ALT 177
AST 211
Serologic testing for Rickettsia rickettsii, Anaplasma and Ehrlichia is performed
What is the most appropriate next step in management?
A. Begin empiric amoxicillin
B. Begin empiric doxycycline
C. Withhold antibiotics unless a petechial skin rash develops
D. Withhold antibiotics while awaiting serologic results
B. Begin empiric doxycycline
Delay in therapy is associated with a significant
increase in morbidity (clinically difficult to
distinguish anaplasmosis, ehrlichiosis and
RMSF especially if there is no rash)
A 27 year old man is evaluated in the ED for a 2 day history of fever, weakness and
dark-colored urine. He returned yesterday from a 2 week camping trip to Cape
Cod. While there, he developed a target-shaped lesion on his thigh. He was
evaluated at a walk-in clinic, where early-stage Lyme disease was diagnosed. He is
currently on day 10 of a 14 day course of doxycycline.
On physical, temp is 101.3, BP 122/66 and pulse is 118. He is jaundiced and the liver is
palpable 5cm below the costophrenic margin.
Hemoglobin 8.4
Reticulocyte count 10%
Leukocyte count 12,600
Platelet count 110,000
LDH 675
Total bilirubin 8.3
Which of the following pathogens is most likely causing this patient’s findings?
A. Anaplasma phagocytophilum
B. Babesia microti
C. Borrelia burgdorferi
D. Rickettsia rickettsii
E. West Nile virus
B. Babesia microti
Because the same vector tick carries different
pathogens, coinfection may occur; only
babesiosis causes hemolysis.
A 33 year old man is evaluated after learning that a person living in his home
was recently found to have active TB. He has no acute symptoms. He was
recently diagnosed with HIV and his CD4 is 250. He is a US citizen and has
no history of incarceration, homelessness, or travel to areas with an
increased prevalence of TB. He takes no medications but had been
planning to begin antiretroviral therapy.
Physical exam is normal and a tuberculin skin test induces 0 mm of
induration. CXR is normal.
What is the most appropriate next step in management?
A. Begin isoniazid and pyridoxine
B. Begin isoniazid, rifampin, pyrazinamide, pyridoxine, and ethambutol
C. Begin rifampin and pyrazinamide
D. No additional evaluation or therapy is needed
A. Begin isoniazid and pyridoxine
Patients with HIV infection who have had a
known recent exposure to a close contact
with active TB should receive Rx for LTBI
after active disease has been excluded.
A 63 year old man undergoes annual screening for TB. He is a physician, and
this creening is required for maintaining his hospital appointment. His
medical history is significant for bladder cancer diagnosed 1 year ago that
was treated with bacillus Calmette-Guerin. There is no current evidence of
active bladder cancer on follow up cystoscopy, and he has no respiratory
or systemic symptoms.
Physical exam is otherwise normal.
What is the appropriate next step in management?
A. Chest radiograph
B. Interferon-y release assay
C. tuberculin skin test
D. two-step tuberculin skin testing
B. Interferon-y release assay
IGRA preferred for those who have received BCG
as a vaccine or as cancer therapy and those
who are unlikely to return for interpretation of
the TST.
A 30 year old man is admitted to the hospital with a 1 month history of fever,
night sweats, cough, weight loss and chest pain. A diagnosis of pericardial
tamponade is established.
Pericardiocentesis is performed, following which there is no recurrence of a
significnat pericardial effusion. Microbiologic examination of pericardial
fluid identifies Mycobacterium tuberculosis.
In addition to four-drug antituberculous therapy, which of the following is the
most appropriate next treatment?
A. Indomethacin and colchicine
B. Pericardial window
C. Prednisone
D. Surgical pericardiectomy
C. Prednisone
Patients with TB pericarditis should receive
prednisone for the first 11 weeks of therapy.
Associated with improved survival and
decreased need for pericardiectomy.
A 25 year old woman started treatment for active pulmonary TB 6 weeks ago.
The mycobacteria were susceptible to all first-line antituberculous agents,
and a 2-month course of isoniazid, rifampin, ethambutol, and
pyrazinamide was prescribed as initial therapy. However, the patient was
lost to follow up for 3 weeks, during which time she discontinued all
medications.
Physical exam reveals a temp of 99.9 F, BP 110/70, pulse 90. Otherwise
normal exam.
What is the most appropriate management option?
A. Continue the same Rx to complete the planned total number of doses,
provided all doses are complete within 3 months
B. Repeat sputum smear for AFB; if negative, Rx can be considered
complete
C. Restart different treatment with at least 2 new drugs to which the
mycobactera were originally suscptible
D. Restart the same treatment from the beginning
D. Restart the same treatment from the beginning
When a patient with active TB being treated with
initial-phase antituberculous agents discontinues
treatment for 2 weeks or longer, the same
antituberculous regimen should be restarted from
the beginning.
A 53 year old man is evaluated for a 2 day history of swelling and pain of the right
knee. Active TB was recently diagnosed, and he has been treated with isoniazid,
rifampin, and pyrazinamide for the past 7 weeks. Ethambutol, which was also
started 7 weeks ago, had to be discontinued 1 week ago after the patient
experienced decreased visual acuity ascribed to optic neuritis. Mycobacteria are
fully usceptible to all first-line anti-TB agents. His medicla history also includes
hypertension for which he takes amlodipine.
Vitals are normal. The right knee is warm, erythematous, and swollen, and he has
difficulty bearing weight on this leg because of intense pain. Range of motion of
the knee is restricted and elicits pain.
Serum uric acid level is 10.5. A CBC reveals WBC of 14,700 with 87% PMNs and 13%
lymphocytes. An arthrocentesis of the right knee reveals synovial fluid leukocyte
count of 30,000 (90% PMNs, 10% lymphs). Gram stain is negative, but polarized
light microscopy reveals intra and extracellular monosodium urate crystals.
What is most likley responsible for this patient’s clinical findings?
A. amlodipine
B. isoniazid
C. pyrazinamide
D. Rifampin
C. Pyrazinamide
Pyrazinamide can cause hyperuricemia by
inhibiting renal tubular excretion of uric acid.
Can also cause hepatitis, rash and GI upset.
Rifampin enhances kidney excretion of uric
acid and can cause rash, hepatitis, GI upset,
orange-colored body fluids.
A 23 year old man undergoes preliminary evaluation after being admitted to a
detox center because of injection drug use.
Temp is 98.2, BP 125/75, pulse 90. Findings on exam demonstrate evidence of
injection drug use on the bilateral upper extremities but are otherwise
normal.
TST testing induces 6mm of induration. The patient has no had previous TSTs.
Results of a serologic test for HIV infection are negative.
What is the most appropriate next step in management?
A. Chest radiograph
B. Isoniazid
C. Isoniazide, rifampin, pyrazinamide, and ethambutol
D. No additional therapy or evaluation
D. No additional therapy or evaluation
>5mm
-HIV-infected persons
-A recent contact of a person
with active TB
-Persons with fibrotic
changes on chest radiograph
consistent with prior TB
-Patients with organ
transplants
-Persons who are
immunosuppressed for other
reasons (e.g., taking the
equivalent of >15 mg/day of
prednisone for 1 month or
longer, taking TNF-a
antagonists)
>10mm
-Recent immigrants (< 5
years) from high-prevalence
countries
-Injection drug users
-Residents and employees of
high-risk congregate settings
-Mycobacteriology laboratory
personnel
-Persons with clinical
conditions that place them at
high risk
-Children < 4 years of age
- Infants, children, and
adolescents exposed to
adults in high-risk categories
>15mm
any person, including
persons with no known risk
factors for TB. However,
targeted skin testing
programs should only be
conducted among high-risk
groups.
A 30 year old man is evaluated for 3 months of fever, night sweats and
headache. He has a history of IVDU and is currently incarcerated.
On exam, temp is 101F, BP 110/65 and pulse 95. He is oriented but lethargic.
Leukocyte count is 15,000 with 70% neutrophils, 20% lymphs and 10%
monocytes and the serum albumin is 2.3. The remaining metabolic panel
and results of the UA are normal.
LP reveals an opening pressure of 250 mm H2O. CSF shows a cell count of 400
with 95% lymphs, protein level of 200 mg/dL and glucose of 20 mg/dL. CSF
PCR is positive for Mycobacterium TB and CSF culture grows M.
tuberculosis. Blood culture specimens show no growth. CT scan of the
head reveals basilar meningeal enhancement.
Treatment with isoniazid, rifampin, pyrazinamide, and ethambutol and
steroids is begun. Mycobacteria are fully susceptible to all four
antituberculous agents.
What is the most appropriate duration of treatment?
A. 4 to 6 months
B. 9 to 12 months
C. 15 to 18 months
D. 24 months
B. 9 to 12 months
Increased opening pressure, lyphocytic
pleocytosis and elevated protein and
decreased glucose in the CSF. CT with basilar
meningeal envolvement (may also see
hydrocephalus). Serial LPs should be
considered to assess the response of the CSF
cell count, protein and glucose levels to
therapy.