Tickborne Diseases in Massachusetts: a physician’s reference manual
second edition

Massachusetts Department of Public Health
Division of Epidemiology and Immunization
617.983.6800 www.mass.gov/dph

Table of Contents
Tick ID
Summer Fever Algorithm
Lyme Disease
Babesiosis
Human Granulocytic Anaplasmosis
Tularemia
Rocky Mountain Spotted Fever
Additional Resources

Tick ID

Ticks are generally found in brushy or wooded areas, near the ground; they cannot jump or fly.  Ticks are attracted to a variety of host factors including body heat and carbon dioxide.  They will transfer to a potential host when one brushes directly against them and then seek a site for attachment.

Photo of deer ticks, shows coloring and sizes of nymphs, adult male and adult female.

Latin name of deer tick: 
IXODES SCAPULARIS

Photo of dog ticks shows coloring and size of adult male and adult female.

Latin name of dog tick:
DERMACENTOR VARIBILIS

Deer ticks are capable of spreading the agents of Lyme disease, human granulocytic anaplasmosis/ehrlichiosis (HGA) and babesiosis.

The nymph and adult female stages of the deer tick most frequently bite humans.  The greatest risk of being bitten exists throughout the spring, summer and fall. However, deer tick adults may be out searching for a host any time winter temperatures are above freezing.

The adult female deer tick has a reddish-brown tear-drop shaped body with a dark brown dorsal scutum (plate) located behind the mouthparts.  

Unfed deer tick nymphs are the size of a poppy seed and unfed adults are the size of a sesame seed.

Dog ticks (also called wood ticks) are capable of spreading the agents of tularemia and Rocky Mountain spotted fever.  

The adult stage of the female dog tick most frequently bites humans. The highest risk of being bitten by a dog tick occurs during the spring and summer.

The adult female dog tick has a dark brown body with whitish markings on its dorsal scutum (plate) located behind the mouthparts.  

Unfed adult dog ticks are the size of a watermelon seed.

SUMMER FEVER ALGORITHM
Algorithm for Differentiating Tickborne Diseases in Massachusetts
This algorithm is intended for use as a general guide when pursuing a diagnosis. It does not replace the physician’s clinical judgment or the need for definitive laboratory testing.

The patient resides, works, or recreates in an area likely to have ticks and is exhibiting fever, headache, malaise and/or lymphadenopathy.

Does the patient have a rash?
 
If yes, see #1 below.

If no, go to #2 below.

#1.  The patient resides, works, or recreates in an area likely to have ticks and is exhibiting fever, headache, malaise and/or lymphadenopathy, and has a rash.

a)	Is the rash an erythema migrans?

If yes, consider Lyme disease.

b)	Is the rash maculopapular?

If yes, consider human granulocytic anaplasmosis/ehrlichiosis; further tests may be indicated. 

c)	Is the rash maculopapular to petechial*

If yes, consider RMSF; further tests may be indicated.

*If petechial rash of palms and soles (characteristic of RMSF) is present, treat immediately. 

d)	Is the rash a cutaneous ulcer?

If yes, consider tularemia (ulceroglandular); further tests may be indicated.

#2.  The patient resides, works, or recreates in an area likely to have ticks and is exhibiting fever, headache, malaise and/or lymphadenopathy, and does not have a rash.

a)  Do a blood smear review
If parasites found in RBC*, consider babesiosis. 

      *If patient has an international travel history, malaria should be ruled out.
If there are morulae in WBC, consider human granulocytic anaplasmosis/ehrlichiosis; further tests may be indicated.

b)  Do a Complete Blood Count (CBC).
If CBC is normal, consider RMSF*, tularemia** or Lyme disease; further tests may be indicated.

* RMSF -- thrombocytopenia may occur

** tularemia -- WBC normal or elevated, thrombocytopenia may occur

If WBC is low or normal with thrombocytopenia, low hematocrit and elevated reticulocytes, consider babesiosis; further tests may be indicated.

If hematocrit is normal with thrombocytopenia and leukopenia, consider human granulocytic anaplasmosis/ehrlichiosis; further tests may be indicated.

Other Considerations
•	Rash occurs in 70-80% of Lyme disease patients and in 10% or less of HGA patients.
•	Rash occurs in 70-80% of RMSF patients but only appears several days after onset of febrile illness.
•	Hyponatremia may occur with RMSF or tularemia.
•	Lyme disease can present as Bell’s palsy, further tests may be indicated.
•	Ulceroglandular tularemia usually presents as regional lymphadenopathy with a small ulceration distally, further tests may be indicated.
•	Coinfections involving Lyme disease, babesiosis, and/or HGA may occur because a single deer tick may carry multiple pathogens. 
•	Consider pneumonic tularemia in any patient presenting with community-acquired pneumonia who resides on, or has recently visited, Martha’s Vineyard.

LYME DISEASE

Photos show an assortment of the various shapes and sizes of Lyme disease rashes.

AGENT
BACTERIA: BORRELIA BURGDORFERI

SIGNS/SYMPTOMS
EARLY LOCALIZED STAGE (WITHIN 3-30 DAYS POST-EXPOSURE) 
•	Erythema migrans (EM) – red ring-like or homogenous expanding rash (this is a pathognomonic sign)
•	Flu-like symptoms including malaise, fatigue, headache, fever, chills, myalgia, regional lymphadenopathy

EARLY DISSEMINATED STAGE (WITHIN DAYS TO WEEKS OF EXPOSURE)
•	
•	Severe malaise and fatigue
•	Multiple secondary annular rashes
•	Regional or generalized lymphadenopathy
•	Migratory pain in joints, tendons, bursae, muscle and bone
•	Transient, migratory arthritis
•	Atrioventricular nodal block
•	Myopericarditis
•	Pancarditis
•	Meningitis, motor and sensory radiculoneuritis, subtle encephalitis, mononeuritis multiplex, pseudotumor cerebri
•	Bell’s palsy or other cranial nerve neuritis
•	Mild or recurrent hepatitis
•	Splenomegaly
•	Microsopic hematuria or proteinuria

LATE DISSEMINATED STAGE (WITHIN MONTHS POST-EXPOSURE)
•	
•	Prolonged episodes of arthritis 
•	Peripheral enthesopathy
•	Periostitis or joint subluxations below acrodermatitis
•	Chronic axonal polyradiculopathy
•	Spastic parapareses
•	Ataxic gait
•	Chronic encephalomyelitis
•	Subtle mental disorders
•	Keratitis
•	Fatigue

LABS
COMMON FINDINGS ON ROUTINE LABORATORY TESTS
•	Elevated sedimentation rate (generally with localized or early disseminated disease)
•	Mildly elevated hepatic transaminases (generally with early localized or early disseminated disease)
•	For cases of Lyme disease meningitis, CSF typically has a lymphocytic pleocytosis with slightly elevated protein levels and normal glucose levels

DIAGNOSTIC LABORATORY CRITERIA
•	Demonstration of diagnostic IgM or IgG antibodies in serum or cerebrospinal fluid.  Due to high false-positive rates in both enzyme immunoassay (EIA) and immunoflourescence assay (IFA) tests, a two-tier testing protocol is recommended; a positive or equivocal EIA or IFA should be followed by a Western blot; or
•	Isolation of organism from a clinical specimen.

LIMITATIONS TO SEROLOGICAL TESTS FOR LYME DISEASE:  
•	Serologic tests are insensitive during the first few weeks of infection.
•	In persons with illness > than 1 month, a positive IgM test alone is not recommended for determining current disease
•	Due to antibody persistence, single positive serologic test results can not distinguish between active and past infection and serologic tests can not be used to measure treatment response.
•	Due to their high sensitivity and low specificity, EIA and IFA tests may yield false-positive results due to cross-reactivity with antibodies to commensal or pathogenic spirochetes, certain viral infections (e.g., varicella, Epstein-Barr virus), or certain autoimmune diseases (e.g., systemic lupus erythematosus).

NOTE:  Coinfection with B. microti and/or A. phagocytophylum should be considered in patients who present with initial symptoms that are more severe than are commonly observed with Lyme disease alone, especially in those who have high-grade fever for more than 48 hours despite appropriate antibiotic therapy or who have unexplained leucopenia, thrombocytopenia, or anemia.  Coinfection might also be considered in patients whose erythema migrans skin lesion has resolved but have persistent viral infection-like symptoms.

TREATMENT
The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy status or allergies.  Consult an infectious disease specialist for the most current treatment guidelines or for individual patient treatment decisions.
EARLY LOCALIZED STAGE 
Age Category	Drug	Dosage	Maximum	Duration, days (range)	
Adults	Doxycycline	100 mg twice per day	N/A	14 (14-21)	
	Cefuroxime axetil	500 mg twice per day	N/A	14 (14-21)	
	Amoxicillin	500 mg 3 times per day	N/A	14 (14-21)	
	
Children	Amoxicillin	50 mg/kg per day in 3 divided doses	500 mg per dose	14 (14-21)	
	Doxycycline	4 mg/kg per day in 2 divided doses	100 mg per dose	14 (14-21)	
	Cefuroxime axetil	300 mg/kg per day in 2 divided doses	500 mg per dose	14 (14-21)	

NOTE:  For patients intolerant of amoxicillin, doxycycline, and cefuroxime axetil, the macrolides azithromycin, clarithromycin, or erythromycin may be used, although they have a lower efficacy.  Patients treated with macrolides should be closely observed to ensure resolution of clinical manifestations.

Treatment guidelines for patients with disseminated or late stage Lyme disease are outlined in the reference below†
REFERENCES
American Academy of Pediatrics. Lyme disease (Lyme borreliosis, Borrelia burgdorferi infection).  In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds.  Red Book:  2006 Report of the Committee on Infectious Diseases.  27th ed.  Elk Grove Village, IL: American Academy of Pediatrics; 2006: 430.

Bunikis J., Barbour A.  Laboratory Testing for Suspected Lyme Disease.  Medical Clinics of North America.  2002; 86(2): 311-340.

Nadelman RB.  The Clinical Spectrum of Early Lyme Borreliosis in Patients with Culture-Confirmed Erythema Migrans.  The American Journal of Medicine.  1996; 100: 502-508.

Steere AC., et al.  The Early Clinical Manifestations of Lyme disease.  Annals of Internal Medicine.  1983; 99: 76-82.

Steere AC.  Borrelia burgdoferi (Lyme Disease, Lyme Borreliosis).  In: Mandell GL, Bennett JE, Dolin R, editors.  Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.  6th ed.  Philadelphia, PA: Churchill Livingstone; 2005. p. 2798-2809.

† Wormser GP, Dattwyler RJ, Shapiro ED, 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: 1089-1134.

† REFERENCE FOR TREATMENT GUIDELINES

BABESIOSIS

Photo of  parasite: Babesia microti
AGENT
PARASITE: BABESIA MICROTI

SIGNS/SYMPTOMS 
[INCUBATION PERIOD 1-6 WEEKS]

•	Malaise, fatigue
•	Sustained or intermittent fever, chills
•	Gastrointestinal symptoms (anorexia, nausea, abdominal pain, vomiting)
•	Myalgia
•	Arthralgia
•	Depression, emotional lability
•	Photophobia
•	Conjunctival injection
•	Dark urine
•	Petechiae, splinter hemorrhages, ecchymoses
•	Mild splenomegaly and/or hepatomegaly
•	Cough
•	Sore throat

LABS
COMMON FINDINGS ON ROUTINE LABORATORY TESTS
•	Decreased hematocrit secondary to hemolytic anemia
•	Elevated reticulocyte counts
•	Elevated erythrocyte sedimentation rate
•	Thrombocytopenia
•	WBC count may be normal or mildly decreased

•	Decreased serum haptoglobin
•	Elevated serum BUN and creatinine
•	Mildly elevated hepatic transaminases
•	Proteinuria
•	Hemoglobinuria
•	Direct Coombs’ test may react positively

DIAGNOSTIC LABORATORY CRITERIA
•	Identification of intraerythrocytic Babesia parasites in a peripheral blood smear; or  
•	Isolation of the parasite from a whole blood specimen by animal inoculation; or
•	Positive Polymerase Chain Reaction (PCR) assay.

NOTE: Due to the sparse parasitemia typical of most Babesia microti infections, additional diagnostic tests should be performed in suspect patients if the initial blood smear is negative.

SUPPORTIVE LABORATORY CRITERIA
•	Demonstration of a Babesia-specific antibody titer by immunofluorescence assay (IFA) test for IgG.  In general, higher cutoff titers (> 1:256) are associated with greater diagnostic specificity.

TREATMENT 
The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy status or allergies.  Consult an infectious disease specialist for the most current treatment guidelines or for individual patient treatment decisions.

Age Category	Drug	Dosage	Maximum	Duration (days)	
Adults	Atovaquone	750 mg orally every 12 hours	N/A	7-10	
	Prescribe together with	
	Azithromycin	500-1000 mg on day 1 and 250 mg orally once per day thereafter	N/A	7-10	
	OR	
	Clindamycin	300-600 mg IV every 6 hours OR 600 mg orally every 8 hours	N/A	7-10	
	Prescribe together with	
	Quinine	650 mg orally every 6-8 hours	N/A	7-10	
	
Children	Atovaquone	20 mg/kg every 12 hours	750 mg per dose	7-10	
	Prescribe together with	
	Azithromycin	10 mg/kg once per day on day 1 and 5 mg/kg once per day thereafter orally	500 mg per dose on day 1 and 250 mg per dose thereafter	7-10	
	OR	
	Clindamycin	7-10 mg/kg IV or orally every 6-8 hours	600 mg per dose	7-10	
	Prescribe together with	
	Quinine	8 mg/kg orally every 8 hours	650 mg per dose	7-10	

NOTE: For adult patients who are immunocompromised, higher doses of azithromycin, 600-1000 mg per day, may be used.

NOTE:  The recommended treatment for patients with severe babesiosis, as indicated by high-grade parasitemia (=> 10%), significant hemolysis, or renal, hepatic or pulmonary compromise, is quinine and IV clindamycin, and the patient should be considered for partial or complete RBC exchange transfusion

NOTE:  Consider the possibility of coinfection with B. burgdorferi and/or A. phagocytophilum in patients with especially severe or persistent symptoms, despite appropriate antibabesial therapy. 

NOTE:  Asymptomatic patients with a positive babesial smear and/or PCR results should have these studies repeated. Treatment should be considered if parasitemia persists for more than three months.

REFERENCES

Gelfand JA., Vannier E.  Babesia Species.  In: Mandell GL, Bennett JE, Dolin R, editors.  Manell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.  6th ed.  Philadelphia, PA: Churchill Livingstone; 2005. p. 3209-3215.

Homer MJ, et al.  Babesiosis.  Clinical Microbiology Reviews.  2000; 13(3): 451-469.

Krause PJ.  Babesiosis Diagnosis and Treatment.  Vector-borne and Zoonotic Diseases.  2003; 3(1): 45-51.

Krause PJ, et al.  Comparison of PCR with Blood Smear and Inoculation of Small Animals for Diagnosis of Babesia microti Parasitemia.  Journal of Clinical Microbiology.  1996; 34(11): 2791-2794.

Persing DH, et al.  Detection of Babesia microti by Polymerase Chain Reaction.  Journal of Clinical Microbiology.  1992: 30(8): 2097-2103.

Ruebush TK, Juranek DD, Spielman A, Piesman J, Healy G.  Epidemiology of Human Babesiosis on Nantucket Island.  Am. J. Trop. Med. Hyg.  1981; 30 (5): 937-941.

Thompson C., Spielman A., Krause PJ.  Coinfecting Deer-Associated Zoonoses: Lyme Disease, Babesiosis, and Ehrlichiosis.  Clinical Infectious Diseases.  2001; 33: 676-685.

†Wormser GP, Dattwyler RJ, Shapiro ED, 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: 1089-1134.

† REFERENCE FOR TREATMENT GUIDELINES
Human Granulocytic Anaplasmosis (aka human granulocytic ehrlichiosis)
Photo of bacteria: Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum)
AGENT
BACTERIA: ANAPLASMA PHAGOCYTOPHILUM (FORMERLY EHRLICHIA PHAGOCYTOPHILUM)

SIGNS/SYMPTOMS

INCUBATION PERIOD [1-2 WEEKS]
•	
•	Fever, chills
•	Severe headache
•	Malaise
•	Myalgia
•	Gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia)
•	Cough
•	Arthralgia
•	Stiff neck
•	Confusion

LABS
COMMON FINDINGS ON ROUTINE LABORATORY TESTS 
Generally observed during the first week of clinical disease
•	Mild anemia
•	Thrombocytopenia
•	Leukopenia (characterized by relative and absolute lymphopenia and a left shift)
•	Modest elevations in hepatic transaminases

DIAGNOSTIC LABORATORY CRITERIA
•	Demonstration of a four-fold change in IgG-specific antibody titer by immunofluorescence assay (IFA) test in paired serum samples; or
•	Detection of DNA by polymerase chain reaction (PCR) assay; or
•	Immunohistochemical (IHC) staining of organism; or
•	Isolation of organism from a clinical specimen.

NOTE:  Visualization of morulae in the cytoplasm of neutrophils or eosinophils during examination of blood smears is highly suggestive of a diagnosis; however, blood smear examination is insensitive and should never be relied upon solely to rule HGA in or out. 

NOTE:  Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be delayed in a patient with a suggestive clinical presentation.

NOTE:  Consider the possibility of coinfection with B. microti and/or B. burgdorferi.

TREATMENT
The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy status or allergies.  Consult an infectious disease specialist for the most current treatment guidelines or for individual patient treatment decisions.

Age Category	Drug	Dosage	Maximum	Duration (days)	
Adults	Doxycycline	100 mg twice per day orally or IV	N/A	10	
	
Children
8 years of age or older
moderate illness	Doxycycline	4 mg/kg per day orally or IV in 2 divided doses	100 mg per dose	10	
	
Children
less than 8 years of age
severe illness
without Lyme disease	Doxycycline	4 mg/kg per day orally or IV in 2 divided doses	100 mg per dose	4-5 
OR approx. 3 days after resolution of fever	
	
Children 
less than 8 years of age
severe illness
with Lyme disease
	Doxycycline	4 mg/kg per day given orally or IV in 2 divided doses	100 mg per dose	4-5	
	FOLLOWED BY	
	Amoxicillin	50 mg/kg per day in 3 divided doses	500 mg per dose	to complete a 14 day total course of antibiotic therapy	
	OR	
	Cefuroxime axetil	30 mg/kg per day in 2 divided doses	500 mg per dose	to complete a 14 day total course of antibiotic therapy	

NOTE:  Patients with mild illness for whom doxycycline treatment is contraindicated may be treated with rifampin for 7-10 days using a dosage regimen of 300 mg twice per day by mouth for adults and 10 mg/kg twice per day for children (maximum, 300 mg per dose).

NOTE:  Because HGA can be life-threatening and limited courses of therapy do not pose a substantial risk for tooth staining, the American Academy of Pediatrics has identified doxycycline as the drug of choice for treating HGA in children of any age.

NOTE:  Treatment response is expected within 48 hours.

NOTE:  Treatment is not recommended for asymptomatic individuals who are seropositive for antibodies to A. phagocytophilum.

REFERENCES
Bakken JS., Aguero-Rosenfeld ME., Tilden RL., et al.  Serial Measurements of Hematologic Counts during the Active Phase of Human Granulocytic Ehrlichiosis.  Clinical Infectious Diseases.  2001; 32: 862-870.

Centers for Disease Control and Prevention.  Diagnosis and management of tickborne rickettsial diseases:  Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis—United States: a practical guide for physicians and other health-care and public health professionals.  MMWR 2006; 55 (No. RR-4).

Engel J, Bradley K., et al.  Revision of the National Surveillance Case Definition for Ehrlichiosis.  Council of State and Territorial Epidemiologists, Infectious Diseases Committee, 2007 Position Statement.  http://www.cste.org/PS/2007ps/2007psfinal/ID/07-ID-03.pdf

Gelfand JA., Vannier E.  Ehrlichia chaffeensis (human monocytotropic ehrlichiosis), Anaplasma phagocytophilum (human granulocytotropic anaplasmosis) and other ehrlichiae.  In: Mandell GL, Bennett JE, Dolin R, editors.  Manell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.  6th ed.  Philadelphia, PA: Churchill Livingstone; 2005. p. 2310-2318.

†Wormser GP, Dattwyler RJ, Shapiro ED, 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: 1089-1134.

† REFERENCE FOR TREATMENT GUIDELINES

TULAREMIA
Photo of a person’s thumb showing a tularemia infection
AGENT
BACTERIA: FRANCISELLA TULARENSIS 

SIGNS/SYMPTOMS
[AVERAGE INCUBATION PERIOD 3-5 DAYS, RANGE 1-21 DAYS]

NOTE: The clinical presentation of tularemia will depend on a number of factors, including the portal of entry.

GENERAL (MAY BE PRESENT IN ALL FORMS OF TULAREMIA)
•	Fever, chills
•	Headache
•	Malaise, fatigue
•	Anorexia
•	Myalgia
•	Chest discomfort, cough
•	Sore throat
•	Vomiting, diarrhea
•	Abdominal pain

ULCEROGLANDULAR
•	Localized lymphadenopathy
•	Cutaneous ulcer at infection site

GLANDULAR
Regional lymphadenopathy with no cutaneous lesion

TYPHOIDAL
•	Characterized by any combination of the general symptoms
OCULOGLANDULAR
•	Photophobia
•	Excessive lacrimation
•	Conjunctivitis
•	Preauricular, submandibular and cervical lymphadenopathy

PHARYNGEAL
•	Severe throat pain
•	Cervical, preparotid, and retropharyngeal lymphadenopathy

PNEUMONIC
•	Non-productive cough
•	Substernal tightness
•	Pleuritic chest pain

NOTE: Pneumonic tularemia should be considered in any patient presenting with community-acquired pneumonia who resides on, or has recently visited, Martha’s Vineyard.

LABS
COMMON FINDINGS ON ROUTINE LABORATORY TESTS 
•	Leukocyte count and sedimentation rate may be normal or elevated
•	Thrombocytopenia
•	Hyponatremia
•	Elevated hepatic transaminases
•	Elevated creatine phosphokinase
•	Myoglobinuria
•	Sterile pyuria

DIAGNOSTIC LABORATORY CRITERIA
•	Demonstration of a four-fold change in antibody titer in paired sera; or
•	Isolation of organism.
NOTE:  Detection of organism by immunofluorescence assay (IFA) test or a single elevated serum antibody titer is supportive of the diagnosis; however, these results should be confirmed by either one of the methods above.

TREATMENT
The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy status or allergies.  Consult an infectious disease specialist for the most current treatment guidelines or for individual patient treatment decisions.

Age Category	Drug	Dosage	Maximum	Duration, days	
Adults	Gentamicin	5 mg/kg IM or IV daily (with desired peak serum levels of at least 5mcg/mL)	N/A	10	
	OR	
	Streptomycin	1g IM twice daily 	N/A	10 	
	
Children	Gentamicin	2.5 mg/kg IM or IV 3 times daily	Consult a pediatric infectious disease specialist	10	
	OR	
	Streptomycin	15 mg/kg IM twice daily	2g/day	10	

NOTE: Doses of both streptomycin and gentamicin need to be adjusted for renal insufficiency.

NOTE: Chloramphenicol may be added to streptomycin to treat meningitis.

NOTE:  Alternative therapies to the preferred regimens of streptomycin and gentamicin are outlined in reference below.†

REFERENCES
Centers for Disease Control and Prevention.  Case definitions for infectious conditions under public health surveillance.  www.cdc.gov/epo/dphsi/casedef/case_definitions.htm.  Downloaded 1/11/08.

†Dennis D., Inglesby TV., Henderson DA., et al.  Tularemia as a Biological Weapon: Medical and Public Health Management.  Journal of the American Medical Association.  2001.  285(21): 2763-2773.

Feldman KA., Enscore RE, Lathrop SL., et al.  An Outbreak of Primary Pneumonic Tularemia on Martha’s Vineyard.  New England Journal of Medicine.  2001; 345: 1601-1606.

Penn RL.  Francisella tularensis (Tularemia).  In: Mandell GL, Bennett JE, Dolin R, editors.  Manell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.  6th ed.  Philadelphia, PA: Churchill Livingstone; 2005. p. 2674-2685.

† REFERENCE FOR TREATMENT GUIDELINES

ROCKY MOUNTAIN SPOTTED FEVER

Photo of a hand and arm covered with a Rocky Mountain Spotted Fever rash.

AGENT
BACTERIA: RICKETTSIA  RICKETTSII

SIGNS/SYMPTOMS
[INCUBATION PERIOD 2-14 DAYS]
•	Fever, chills
•	Severe headache
•	Malaise
•	Myalgia
•	Gastrointestinal symptoms (nausea, vomiting, anorexia, abdominal pain, diarrhea, abdominal tenderness)
•	Rash, 2-5 days after fever starts, begins as small, blanching, pink macules on the ankles, wrists, or forearms that evolve to maculopapules.  May expand to the entire body including the palms and soles.  The classic spotted, or generalized petechial, rash is not usually apparent until the 5th or 6th day of illness.
•	Cough
•	Conjunctival injection, +/-photophobia
•	Altered mental status
•	Focal neurologic deficits, including cranial or peripheral motor nerve paralysis or sudden transient deafness 

NOTE: Rash may be completely absent or atypical in up to 20% of RMSF cases.  Rocky Mountain “spotless” fever is more likely to occur in older patients.

LABS
COMMON FINDINGS ON ROUTINE LABORATORY TESTS
•	Anemia
•	Thrombocytopenia
•	Mildly elevated hepatic transaminase levels 
•	Hyponatremia
•	Azotemia

DIAGNOSTIC LABORATORY CRITERIA
•	Demonstration of a four-fold change in IgG-specific antibody titer by immunofluorescence assay (IFA) test in paired sera; or
•	Detection of DNA in a clinical specimen by polymerase chain reaction (PCR) assay (generally unreliable for acute blood samples); or
•	Immunohistochemical IHC staining of organism in a biopsy or autopsy specimen; or
•	Isolation of organism in cell culture.
NOTE:  Tests for IgM antibodies are generally not useful for serodiagnosis of acute disease, due to cross-reactivity and persistence of the antibody. 

NOTE:  Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be delayed in a patient with a suggestive clinical presentation.

TREATMENT 
The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, pregnancy status or allergies.  Consult an infectious disease specialist for the most current treatment guidelines or for individual patient treatment decisions.

Age Category	Drug	Dosage	Maximum	Duration (days)	
Adults

	Doxycycline	100 mg twice daily, orally or IV	N/A	At least 3 days after the fever subsides and until evidence of clinical improvement is noted which is typically for a minimum total course of 5-7 days.	
	
Children weighing > 100 lbs (45.4kg)	Doxycycline	100 mg twice daily, orally or IV	Consult a pediatric infectious disease specialist	At least 3 days after the fever subsides and until evidence of clinical improvement is noted which is typically for a minimum total course of 5-7 days.	

Children weighing < 100 lbs (45.4kg)	Doxycycline	2.2 mg/kg body weight per dose twice daily, orally or IV	Consult a pediatric infectious disease specialist	At least 3 days after the fever subsides and until evidence of clinical improvement is noted which is typically for a minimum total course of 5-7 days.	

NOTE:  Because RMSF can be life-threatening and limited courses of therapy do not pose a substantial risk for tooth staining, the American Academy of Pediatrics has identified doxycycline as the drug of choice for treating RMSF in children of any age.

REFERENCES
†Centers for Disease Control and Prevention.  Diagnosis and management of tickborne rickettsial diseases:  Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis—United States: a practical guide for physicians and other health-care and public health professionals.  MMWR 2006; 55 (No. RR-4).

Engel J, Bradley K., et al.  Revision of the National Surveillance Case Definition for Rocky Mountain spotted fever.  Council of State and Territorial Epidemiologists, Infectious Diseases Committee, 2007 Position Statement.  www.cste.org/PS/2007ps/2007psfinal/ID/07-ID-05.pdf

Walker DH, Raoult D.  Rickettsia rickettsii and Other Spotted Fever Group Rickettsiae (Rocky Mountain Spotted Fever and Other Spotted Fevers).  In: Mandell GL, Bennett JE, Dolin R, editors.  Manell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.  6th ed.  Philadelphia, PA: Churchill Livingstone; 2005. p. 2287-2295.

† REFERENCE FOR TREATMENT GUIDELINES

ADDITIONAL RESOURCES
FOR MORE INFORMATION ON TICKBORNE DISEASES:
Massachusetts Department of Public Health
Division of Epidemiology and Immunization
617-983-6800
www.mass.gov/dph

Centers for Disease Control and Prevention
www.cdc.gov

American College of Physicians/American Society of Internal Medicine
http://www.acponline.org/lyme/ 

TO REPORT A CASE OF TICKBORNE DISEASE OR OBTAIN INFORMATION ON THE NUMBER OF CASES OF TICKBORNE DISEASES IN YOUR AREA:

Massachusetts Department of Public Health
Office of Integrated Surveillance and Informatics Services
617-983-6801

June 2009

The second edition of this manual was supported by funding from the Centers for Disease Control and Prevention (CDC) and prepared by the Massachusetts Department of Public Health (MDPH).

The first edition was produced by collaboration between MDPH, Nancy Shadick, MD, MPH, and Nancy Maher, MPH of the RBB Arthritis and Musculoskeletal Diseases Clinical Research Center at Brigham and Women’s Hospital and Dennis Hoak, MD, of Martha’s Vineyard Hospital.