Rocky Mountain spotted fever: From dog ticks to doxycycline

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Rocky Mountain spotted fever From dog ticks to
doxycycline

• David L. Swerdlow, MD
• Rickettsial Zoonoses Branch
• Division of Viral and Rickettsial Diseases
• National Center for Zoonotic, Vectorborne and
  Enteric Diseases

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Tick-borne infectious diseases in the United
States

• Lyme disease
• Ehrlichioses
• Rocky Mountain spotted fever
• Babesioses
• Colorado tick fever
• Tularemia
• Tick-borne relapsing fever

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RMSF background

• The most severe rickettsial illness of humans,
  caused by Rickettsia rickettsii
• First specific notation of the disease in 1896
• Endemic to the Americas
• Until recently, 300-800 U.S. cases/year

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Rocky Mountain spotted fever why is it important?

• Widely distributed with significant morbidity and
  mortality
• Difficult to diagnose
• Rapid diagnosis and treatment prevents deaths

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General properties

• Small, coccobacillary bacteria
• Slow growing
• Intracellular

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Gimenez staining for R. rickettsii
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BACKGROUNDThe Primary Tick Vectors of RMSF
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RMSF Incidence by County, 1997-2002
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RMSF epidemiology and patient demographics

• Over 90 of cases occur during April-September
• Peridomestic acquisition may account for majority
  of cases
• Age-specific incidence highest in children,
  disease more frequent in males
• Case clusters occur in hyperendemic foci

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RMSF clinical manifestations

• Early high fever, severe headache, myalgia, and
  gastrointestinal symptoms
• Late rash, photophobia, confusion, ataxia,
  seizures, cough, dyspnea, arrhythmias, jaundice,
  severe abdominal pain
• Thrombocytopenia, hyponatremia
• Long term sequelae CNS deficits, amputations

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RMSF the rash

• Generally not apparent until 2-5 days after onset
• of fever
• Begins as 1 to 5 mm macules, typically on ankles,
  wrists, and forearms, spreads centripetally to
  trunk
• Petechial rash occurs on or after day 6
• Rash may be asymmetric, localized, or absent

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Severe sequelae
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RMSF frequent initial diagnoses
1. Viral illness 2. Fever of undetermined
etiology 3. Bacterial sepsis 4. Upper or lower
respiratory tract infections, acute
appendicitis, cholecystitis
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Differential Diagnosis of Rocky Mountain Spotted
Fever
Disease Season History/ Onset Rash Other Features
Rocky Mountain Spotted fever Late spring/ summer Exposure to ticks, travel to endemic areas starts with fever and develops rash after 2 to 3 days Starts peripherally and spreads centrally most marked on extremities, usually involves the palms and soles. Often associated with thrombocytopenia and hyponatremia
Meningococcal infections Late winter/ early spring Often epidemics fever and rash usually appear within 24 hours Two patterns macular and petechial lesions, few in number and generalized in distribution. Gram-negative dipllococci in petechiae, buffy coat or in the CSF
Enteroviral Infections Summer-fall Febrile, illness in family or community, fever and rash often appear together Starts on face or trunk, may involve palms and soles. May be associated with aseptic meningitis
Measles Winter-spring Exposure to measles or killed measles vaccine, severe prodrome Starts on head and spreads to trunk and extremities Koplik spots during prodrome
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Confirmation of R. rickettsii
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Serologic diagnosis of RMSF

• 85 of patients lack diagnostic titers in the
  first week of illness
• As many as 50 of patients lack a diagnostic
  titer 7-9 days after onset of illness
• Need to test acute and convalescent samples (2-4
  weeks apart)
• Indirect immunofluorescence assay (IFA)- four
  fold rise in titers confirmatory
• ELISA not quantitative so cant quantify
  increases between acute and convalescent samples

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Deaths attributable to RMSF

• Case-fatality ratio as high as 20-30 in
  untreated patients
• CFR highest in older adults and males
• Disease kills otherwise healthy adults and
  children
• Clinical progression may be rapid (median time to
  death 8 days)

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RMSF deaths in the United States, 1940-1997
140
100
50
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1940
1950
1960
1970
1980
1990
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RMSF treatment

• Tetracyclines the drugs of choice clinical
  response within 24-72 h
• Chloramphenicol an alternative therapy for some
  patients with RMSF
• Other broad-spectrum antimicrobials
  characteristically ineffective

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Antimicrobial therapy of RMSF
Non-pregnant adult or child gt45 kg
Child lt45 kg
Pregnant adult or tetracycline allergic
Chloramphenicol 500 mg qid i.v.
Doxycycline 100 mg bid p.o. or i.v.
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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RMSF prevention

• Disease awareness and recognition
• Use of protective clothing and repellents
• Avoid tick areas
• Antimicrobial prophylaxis following tick bite
  not recommended
• Careful inspection for ticks and prompt removal
  (grace period)

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Prevention and Control

• Wear light-colored clothing
• Tuck your pants legs into
• your socks
• Use masking tape on your
• upper leg-sticky side up
• Apply repellant to
• discourage tick attachment

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Prevention and Control (cont.)

• Tick check and removal
• Transmission unlikely to occur in less than 6
  hours
• Use fine-tipped tweezers

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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

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RMSF Cases and Incidence
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Top Reporting States Cases
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Human Ehrlichiosis Cases
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Spread of Ehrlichiosis Cases, WI
2002
2005
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Spread of Ehrlichiosis Cases, MN
2005
2002
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Lyme Disease
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Explanations for Increases
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Summary

• RMSF is a potentially life-threatening disease,
  endemic throughout much of the United States
• Broad differential diagnoses, early disease
  difficult to diagnose even for experienced
  physicians
• Confirmatory assays
• Serology
• Polymerase chain reaction
• Immunopathology
• Isolation
• Consider RMSF as a cause of unexplained fever in
  spring and summer
• Doxycycline the drug of choice, regardless of age

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RMSF in eastern Arizona

• Since 2002, 24 cases RMSF mostly children with 2
  deaths in a small community
• Incidence rate 300 times higher than expected

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Summary of investigationRh. sanguineus vector of
RMSF

• Dermacentor ticks not found
• High density of Rh. sanguineus ticks surrounding
  patient homes and on dogs
• Rh. sanguineus ticks found attached to patient
• Confirmed the presence of R. rickettsii in ticks
  by PCR, sequencing/RFLP, culture
• First reported evidence of RMSF associated with
  Rhipicephalus sanguineus in the United States

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Rhipicephalus sanguineus (Brown dog tick)
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Environmental Assessment
Typical peridomestic environment surrounding
case-patient homes, found to be heavily populated
by Rh. sanguineus ticks
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Collaborative Intervention

• Community and physician education
• Treatment of homes
• Treatment of dogs
• Animal control

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Get Rid of Ticks on Dogs
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Keep Ticks Off Children
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Acknowledgments

• Christopher Paddock, MD
• John Openshaw
• Jennifer McQuiston, DVM