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Rocky Mountain Spotted Fever (RMSF) in Arizona: 2003-2012
Erica Weis, MPHLaboratory Surveillance Epidemiologist
Office of Infectious Disease ServicesArizona Department of Health Services
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Objectives• Give background information about
RMSF in Arizona• Discuss how and why the disease is
different in Arizona• Explain how to diagnose RMSF• Explain how to treat RMSF
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RMSF: Background• Caused by Rickettsia rickettsii
• Tickborne • Found in several species of ticks throughout North
and South America• Intracellular bacterial pathogen• Infects endothelial cells, causes widespread
vascular damage• Effectively treated with doxycycline
• Other antibiotics (even broad spectrum) ineffective
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Rickettsia Taxonomy
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National RMSF Incidence by County, 2000-2007
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RMSF in Arizona• From 2002-present, over 250 cases of RMSF have been reported
in Arizona
• Highest incidence in the U.S.• Incidence rate ~ 300 times higher than
expected
• There have been 19 deaths—Case fatality 7%, ~ 15 X higher than the U.S. rate
• Cases occur in clusters due to common household exposures
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Why is the Epidemiology of RMSF different in Arizona?
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The Primary U.S. Tick Vectors of RMSF
Dermacentor variabilisAmerican dog tick
Dermacentor andersoniRocky Mountain wood tick
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RMSF in Arizona: Background• Until 2003 RMSF was rarely seen in Arizona• In 2002 the first case in an AZ resident with no
travel was identified– From a tribal community in eastern AZ (Reservation
1)• In 2003 14 month old child died of suspected sepsis
following a febrile rash – From same tribal community in eastern AZ as 2002
case– PCR positive for R. rickettsii
• Environmental investigation found no Dermacentor variabilis or Dermacentor andersoni. 1000+ Rhipicephalus sanguineus found
• 5.6% of trapped ticks positive for R. sanguineus – 10.5% of dogs in the community positive for RMSF– First time R. sanguineus identified as a vector for
RMSF
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RMSF in Arizona: Background• Pediatric serosurvey identified antibodies to spotted
group– 10% seroprevalence in Reservation 1– 16% seroprevalence in a neighboring reservation
(Reservation 2)• Control efforts implemented in Reservation 1 and
Reservation 2, but limited by lack of funding and resources
• In 2009, three human cases (one death) identified in a third reservation (Reservation 3) – Limited spread. 5% of dogs were seropositive. No
new cases since 2009– Dog seroprevalance comparable to areas with no
human cases• In 2011, first human cases identified in a forth
reservation (Reservation 4) in southern Arizona– 29% of dogs seropositive, but >50% in some
communities• Two additional reservations with RMSF in dogs
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19891990
19911992
19931994
19951996
19971998
19992000
20012002
20032004
20052006
20072008
20092010
20112012*
0
10
20
30
40
50
60
70
80
90
Arizona RMSF Cases and Incidence
0
0.2
0.4
0.6
0.8
1
1.2
1.4
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The Primary Arizona Tick Vector of RMSF
Rhipicephalus sanguineus Brown dog tick
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Tick Biology
• Most ticks have moisture and temperature requirements — Vulnerable to desiccation, like high humidity, low tolerance for
temperature extremes
• The brown dog tick is different– Thrives in hot climates – Requires less water than other ticks– Vulnerable to colder temperature– Can live indoors as long as there are dogs – Can crawl up and hide in walls, stucco, cracks, carpet, and hide in
crevices
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Brown Dog Ticks in the Human Environment
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The Role of Dogs in RMSF• Dogs cannot transmit RMSF, but their are preferred host • The ticks require a dog to find a mate• Free-roaming dogs spread ticks into nearby homes and yards• New puppies (especially sick ones) may increase the number of
infected ticks• Seropositivity in dogs and human risk
– In general, no human cases have occurred in communities where canine seropositivity is ~5%
– Human cases observed in communities where canine seropositivity is >50%– Threshold for human cases somewhere in between– Canine seropositivity has been observed prior to first reported human
cases in some reservations
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RMSF in ArizonaSeveral factors put tribal lands at risk -Large population of free roaming dogs -Limited or no animal control -Lack of adequate waste disposal -Limited access to pest control
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Ticks and tickborne diseases are seasonally distributed
January
February
March
AprilMay
JuneJuly
August
Septem
ber
October
November
Decem
ber02468
101214161820
Peak of disease activity corresponds with peak of tick activ-ity (especially the life stages most important for transmis-
sion)
US SeasonalityAZ Seasonality
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Month of Onset for Fatalities
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How is the clinical presentation of the disease different in
Arizona?
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RMSF – Initial Presentation• Most patients present for medical care within
2 days (1.5 in AZ) of onset of fever• Patients may return several times as the disease
progresses (2.5 visits in AZ)• Many patients, especially adults, don’t have a
rash at the time of initial presentation• Not all patients recall a tick bite (30% in AZ)
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ADULT TICK
NYMPH TICK
LARVAE TICK
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RMSF: Clinical Manifestations• Early (first 4 days): fever, headache, myalgia, and
abdominal pain + N/V/D; light rash may be present• Thrombocytopenia, hyponatremia, elevated liver
enzymes (AST, ALT) may occur• Late (day 5 or later): definitive petechial rash, altered
mental status, seizures, cough, dyspnea, arrhythmias, hypotension, severe abdominal pain
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Symptoms for Arizona
Symptom %Fever 81.2Rash 67.7
Fever and Rash 56.8Fever and Tick 44.3Rash and Tick 37.5
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More symptoms for Reservations 1 and 2 RMSFSymptoms %Nausea 47.4Red, draining eyes 14.9Dizziness 19.1Neck pain 11.3Mental status change 17.2Peripheral edema 12.2Coughing 40.2Nasal congestion 27.7Ear pain 10.3Irritability 16.3
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RMSF: The Rash• Generally not apparent until day 2-5 of
symptoms (only seen in 68% of AZ patients)• Begins as 1 to 5 mm macules progressing to
maculopapular• May begin on ankles, wrists, and forearms,
spreads to trunk• Petechial rash is a late finding, occurs on or
after day 6• Rash may be asymmetric, localized, or absent
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Day of trxt (N) # Outpatient (%) # Hospitalized (%) # ICU (%) # fatal (%)
Day 1 (6) 5 (83%) 1 (17%) 0 (0%) 0 (0%)
Day 2 (11) 8 (73%) 3 (27%) 0 (0%) 0 (0%)
Day 3 (9) 4 (44%) 5 (56%) 1 (11%) 0 (0%)
Day 4 (7) 3 (43%) 4 (57%) 1 (14%) 0 (0%)
Day 5 (8) 2 (25%) 6 (75%) 4 (50%) 0 (0%)
Day 6 (9) 0 (0%) 9 (100%) 5 (55%) 3 (33%)
Day 7 (11) 0 (0%) 11 (100%) 4 (36%) 3 (27%)
Day 8 (5) 1 (20%) 4 (80%) 2 (40%) 2 (40%)
Day 9 (4) 0 (0%) 4 (100%) 4 (100%) 2 (50%)
Outcome by Day of Symptoms that Doxycycline was Started
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Severe Sequelae
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Deaths Attributable to RMSF• Historic case-fatality rate 20%-80% in untreated
patients • ARDS, DIC and organ failure may begin around day 5
in severe cases• Disease kills otherwise healthy adults and children• Median time from symptom onset to death is 8 days • Patients seek medical care early• Therefore, the cause of death is missed early
diagnosis and delay in doxycycline treatment
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Risk Factors for Death
• Lack of recognized tick bite• Late onset of rash• Symptoms consistent with more common
diseases• Presentation outside of tick season (June, July)• Wrong antibiotic, especially in children• Early presentation to doctor
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RMSF: Frequent Initial Diagnoses
1. Viral illness
2. Fever of undetermined etiology
3. Bacterial sepsis (meningococcemia)
4. Upper or lower respiratory tract infections, acute appendicitis, cholecystitis, pyelonephritis
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How do I diagnose RMSF?
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You must use the clinical clues to decide to treat.
Never order an RMSF test without first starting the patient on
Doxycycline
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RMSF Clinical AlgorithmPatient Presents with Fever (T > 100) or
History of Subjective Fever AND Resident of RMSF Endemic Area OR
History of Travel to Endemic Area Within 2 weeks of Onset of Symptoms OR
Contact with a dog from an endemic area 2 weeks of Onset of Symptoms
Yes
No or Unknown
Doxycycline & RMSF Labs
Any 1 of the following:
Rash?
Low Sodium?
Low Platelets?
Elevated AST?
Recent Exposure to Ticks or Untreated Dogs?
Educate Patient & Follow-up Next Day
Fever > 2 days?
No
Yes
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How do I treat RMSF?
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RMSF Treatment
• Doxycycline is the drug of choice: clinical response within 24-72 h• Chloramphenicol may be an alternative therapy
for some patients with RMSF but less likely to prevent death
• Other broad-spectrum antimicrobials are not effective, most fatal RMSF cases are on broad-spectrum antibiotics at the time of death
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Antimicrobial Therapy of RMSF Pregnant adult ortetracycline allergic
Non-pregnant adult or child >45 kg
Child <45 kg
Chloramphenicol500 mg qid i.v., lesslikely to prevent death
Doxycycline100 mg bidp.o. or i.v.
Doxycycline4.4 mg/kg/dayin 2 divideddoses p.o. or i.v.
Therapy should be continued at least 72 h after defervescence AND until evidence of clinical improvement
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Doxycycline and RMSF in Children• Doxycycline is drug of choice to treat RMSF in
children• Therapeutic dose has not been shown to
cause significant dental staining• Recommended by AAP and CDC for suspected
RMSF• Withholding doxycycline may result in the
death of the child
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Antibiotics that do not prevent death
Azithromycin Ceftriaxone Ceftazidime Vancomycin Unasyn Clindamycin Amoxicillin Gentamicin
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How do I confirm a case for
reporting purposes?
Diagnostic tests are used for case reporting purposes and not
clinical decision making. There is no RMSF test that can be
used for clinical decision making.
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Confirmation of R. rickettsii • Serology (RMSF titer)
• Indirect immunofluorescence assay (IFA) • Requires paired sera (acute and convalescent)• Look for a change (4-fold) in antibody titers for
confirmed infections• Positive single titers or titers that do not rise are
considered probable cases
• PCR• Available at CDC. Can give a rapid result (48 hours) • Skin biopsy (2-4mm) • Whole blood of severely ill/fatal cases• NOTE: negative PCR does not rule-out RMSF
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Surveillance and Reporting• RMSF is a nationally reportable disease• Cases should be reported to State Health
Department • Reports then submitted to CDC• Reports help us know the level of activity and
target prevention and control efforts• Notify your health department immediately
and they can investigate and treat the house
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RMSF Prevention• Disease awareness and recognition• Treat dogs with collars year round• Treat the yard and home • Careful inspection and removal of ticks • Where there is one case, there are likely to
be others - Prevent clusters by alerting the health department and family
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Summary• RMSF can be rapidly fatal, even in previously
healthy people• Early disease difficult to diagnose even for
experienced physicians• Do not delay treatment pending lab
confirmation• Use the algorithm to diagnose and treat• Use RMSF titers for surveillance purposes, not
for treatment decisions
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Summary Cont’d• Doxycycline the drug of choice for all patients
• Should be administered as soon as disease is suspected
• Should be administered urgently in patients with signs of sepsis
• Prevent cases by educating patients about treating dogs and yards
• Prevent clusters by notifying families and alerting the health department immediately
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Acknowledgements• Joanna Regan, MD, MPH, FAACP
— Center for Disease Control and Prevention, National Center for Environmental Health, Environmental Health Services Branch
• Jennifer McQuiston, DVM, MS, DACVPM— Center for Disease Control and Prevention, National Center for
Environmental Health, Environmental Health Services Branch
• Mark Miller, R.S. MPH– Center for Disease Control and Prevention, National Center for
Environmental Health, Environmental Health Services Branch
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Contact information• Erica Weis: [email protected]
• ADHS RMSF Website: http://www.azdhs.gov/phs/oids/vector/rmsf/index.htm
• For clinical consultation:• Joanna Regan, MD, MPH, FAACP: [email protected]
• CDC RMSF Website: http://www.cdc.gov/rmsf/
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Questions?