Rocky Mountain Spotted Fever (RMSF) in Arizona:
2003-2012
Erica Weis, MPH
Laboratory Surveillance Epidemiologist
Office of Infectious Disease Services
Arizona 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
expected
higher than
• 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 variabilis
American dog tick
Dermacentor andersoni
Rocky 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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Arizona RMSF Cases and Incidence
90
1.4
80
1.2
70
1
60
0.8
50
40
0.6
30
0.4
20
0.2
10
0
0
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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 Arizona
Several 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
Peak of disease activity corresponds with peak of tick activity
(especially the life stages most important for transmission)
20
18
16
14
12
10
8
6
4
2
0
US Seasonality
AZ 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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LARVAE TICK
ADULT TICK
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NYMPH
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
Rash
Fever and Rash
Fever and Tick
Rash and Tick
%
81.2
67.7
56.8
44.3
37.5
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More symptoms for Reservations 1 and 2 RMSF
Symptoms
Nausea
Red, draining eyes
Dizziness
Neck pain
Mental status change
Peripheral edema
Coughing
Nasal congestion
Ear pain
Irritability
%
47.4
14.9
19.1
11.3
17.2
12.2
40.2
27.7
10.3
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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Outcome by Day of Symptoms that Doxycycline was Started
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%)
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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 Algorithm
Patient 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
Fever > 2 days?
Yes
No
Any 1 of the following:
Doxycycline
&
RMSF Labs
Educate Patient &
Follow-up Next Day
Rash?
Yes
Low Sodium?
Low Platelets?
No or Unknown
Elevated AST?
Recent Exposure to
Untreated Dogs?
Ticks or
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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 broadspectrum antibiotics at the time of death
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Antimicrobial Therapy of RMSF
Pregnant adult or
tetracycline allergic
Chloramphenicol
500 mg qid i.v., less
likely to prevent death
Non-pregnant adult
or child >45 kg
Doxycycline
100 mg bid
p.o. or i.v.
Child <45 kg
Doxycycline
4.4 mg/kg/day
in 2 divided
doses 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: erica.weis@azdhs.gov
• ADHS RMSF Website:
http://www.azdhs.gov/phs/oids/vector/rmsf/index.htm
• For clinical consultation:
• Joanna Regan, MD, MPH, FAACP: dlo8@cdc.gov
• CDC RMSF Website: http://www.cdc.gov/rmsf/
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Questions?
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