Health and Wellness for all Arizonans azdhs.gov Rocky Mountain Spotted Fever (RMSF) in Arizona: 2003-2012 Erica Weis, MPH Laboratory Surveillance Epidemiologist

Health and Wellness for all Arizonansazdhs.gov

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








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








Rickettsia Taxonomy








National RMSF Incidence by County, 2000-2007








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








Why is the Epidemiology of RMSF different in Arizona?








The Primary U.S. Tick Vectors of RMSF

Dermacentor variabilisAmerican dog tick

Dermacentor andersoniRocky Mountain wood tick








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








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

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The Primary Arizona Tick Vector of RMSF

Rhipicephalus sanguineus Brown dog tick








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








Brown Dog Ticks in the Human Environment








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








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








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








Month of Onset for Fatalities








How is the clinical presentation of the disease different in

Arizona?








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)








ADULT TICK

NYMPH TICK

LARVAE TICK








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








Symptoms for Arizona

Symptom %Fever 81.2Rash 67.7

Fever and Rash 56.8Fever and Tick 44.3Rash and Tick 37.5








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








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






















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








Severe Sequelae








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








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








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








How do I diagnose RMSF?








You must use the clinical clues to decide to treat.

Never order an RMSF test without first starting the patient on

Doxycycline








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








How do I treat RMSF?








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








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








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








Antibiotics that do not prevent death

Azithromycin Ceftriaxone Ceftazidime Vancomycin Unasyn Clindamycin Amoxicillin Gentamicin








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.








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








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








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








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








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








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








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/

mailto:[email protected]

http://www.azdhs.gov/phs/oids/vector/rmsf/index.htm

mailto:[email protected]

http://www.cdc.gov/rmsf/








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Health and Wellness for all Arizonans azdhs.gov Rocky Mountain Spotted Fever (RMSF) in Arizona: 2003-2012 Erica Weis, MPH Laboratory Surveillance Epidemiologist