1

Rocky Mountain Spotted

Fever

BREEANA BARDILL
MICROBIOLOGY 429 LAB
History of RMSF 2

 Rocky Mountain spotted fever was first  Howard T. Ricketts was the scientist that
discovered in the Snake River Valley in first discovered the bacterium while
1800s. During this time, the disease was conducting a study on local ticks in the
also known as "black measles" because of Bitterroot Valley. He took blood samples
the dark rash.  from a sick child and saw bacilli-like
bacteria in eukaryotic cells. (5)

 Fatality rates before treatments were

developed in the 1940s ranged from 20 –
80%. (7)
Geography 3

 Contrary to the name Rocky Mountain,

RMSF is more commonly found in the
south and southeast United States.
 The five states with the most cases per
year between 2008 – 2012 were:
Missouri, Arkansas, Tennessee, North
Carolina, and Oklahoma. (2)

This is the most recent charting from 2018.

(7)
 4

Background Information
 RMSF is the most severe and most common rickettsial
disease in North America.
 The disease is actually a bacterial infection transferred by tick
bites spreading the Rickettsia rickettsii pathogen.
 There are three main types of ticks that can act as a vector for
this disease: American dog tick (A), Rocky Mountain wood
tick (B), and brown dog tick (C). (2), (6)

https://www.nejm.org/doi/full/10.1056/NEJMoa050043
Transmission 5

 As previously stated, RMSF is generally

transferred through a tick vector making
it a zoonotic disease.
 The pathogen lives in the tick as it
matures and can be passed to humans or
dogs.
 Typical transference occurs through
contact with the saliva or other bodily
fluid from the infected tick.  (2), (10)
 6
Rickettsia rickettsii

 Gram-negative, coccobacilli
 Non-motile
 Obligate, intracellular parasite
 Infect and live within eukaryotic cells
 Non-pathogenic to arthropod host (tick), but will infect mammalian
hosts such as dogs and humans
 Fastidious organism
 Hard to culture
 Can take between 3 – 12 days for incubation in host.
Virulence Factors 7

 Lipopolysaccharide (LPS)
 Polysaccharide-rich slime layer or
capsule
 Protects bacteria from antimicrobial
agents and environment
 Avoid host immune system
 Phospholipase D
 Evade and escape phagosomes to avoid
phagocytosis. (10).
Virulence Factors 8

 Filopodia
 Long, thin cell projections
 Composed of actin from the eukaryotic
cells
 Used to leave host cells
without completely lysing it. (10)
 Tumor necrosis factor-α
 This disrupts endothelial cell junctions
of blood vessels.
 Increases vascular permeability (1).
 9
Effect on Human Hosts

 R. rickettsii spread through the bloodstream to infect

endothelial cells and damage blood vessels.
 T-lymphocyte mediated immune mechanisms and cytokines
fight against the infection. (10)
 Inflammatory response and coagulation activated
Signs and Symptoms 10

 Nausea
Petechial rash – red/purple
 Vomiting
spots indicative of
 Headache increasing severity of
 Fever disease.

 Rash
 Confusion
 Cardiovascular Instability
(8)
 11
Risk Factors

HIGHEST INCIDENCE HIGHEST CASE-FATALITY MEN ARE AT A HIGHER PEOPLE WHO OWN DOGS. THOSE WHO FREQUENT
OCCURS IN PEOPLE AGES RATE OCCURS IN RISK OF BECOMING THE OUTDOORS,
60 – 69. CHILDREN YOUNGER INFECTED THAN WOMEN.  ESPECIALLY SHADY,
THAN 10. WOODED AREAS .

(3)(10)
Diagnosis
 The most common way of diagnosing a
patient with RMSF is if they had the
"triad."
 Fever, rash, and tick bite
 However, such diagnoses are rare
because many signs and symptoms are
non-specific or mimic early stages of
other diseases.
12
 Another issue is that clinical presentation
of the disease can vary depending on
factors such as the patient's age and
location of residence. (4)
 The best way to diagnose RMSF is to go
ahead and run serological tests on blood
or tissue samples if RMSF is even
suspected. (2)
Lab work-up 13
Non-culture Based Techniques
 Immunohistology
 Immunofluorescence
 Polymerase Chain Reaction (PCR)
 Hemagglutination assay
 Serological tests for antibodies 
(9)
Culture Based
 Rarely done in clinical laboratory setting because of the
high risk of getting infected (Biosafety Level 3). (8)
 Rickettsiae can only be cultivated in viable eukaryotic
cells such as cell cultures, embryonated eggs, or
susceptible animals (Mice or Guinea pigs). (10)
Treatments 14

 It is imperative that RMSF is treated as soon as it is diagnosed or suspected

because antibiotics are most effective during early stages of the infection. Without
treatment or a delay, mortality rates of RMSF can be as high as 20 – 30%.
 Antibiotics
 Doxycycline
 Tetracyclines
 Chloramphenicol
 Rarely used because of hematological effects, so blood indices must be kept if in use to treat
RMSF. (2) (8)
Treatment Controversy
 Some doctors are hesitant to prescribe
Doxycycline as the antibiotic of choice
for children younger than 10 years old.
 This could be very dangerous
because delaying treatment within this
age group can increase the chance of
fatality. (3)
15
 The main reason they hesitate to use
Doxycycline with children is the tooth
staining it could cause when it binds to
calcium like other tetracycline antibiotics
 This controversy was disproved in a study
from 2007, that found Doxycycline did
not cause tooth staining. It was further
proven to not cause enamel hypoplasia in
2013. (2)
16
Current Research 17

 There are no vaccines available as a preventative measure, so more research has

gone into finding effective targets for therapeutic agents. 
 Researchers are currently studying the rapid entrance of R. rickettsii into cells and
downregulation of immune pathways allowing the disease to persist. (8)
 There is also research into the spread of Rickettsia species and spotted fever
groups around the world.
 Which species causes spotted fever in which countries? How similar are the
mechanisms to R. rickettsii and are they treated the same?
Global Rickettsia 18

(6)
 19
Summary

 Rocky Mountain spotted fever is a zoonotic disease caused by tick bites spreading R. rickettsii.
 R. rickettsii is a Gram-negative, coccobacilli that is obligately intracellular.
 The most common symptoms are fever, rash, headache, and muscle pain.
 Diagnoses can be hard to identify because symptoms are sometime non-specific or similar to
other diseases.
 Current treatment is Doxycycline.
 There is current research ongoing for new targets of therapeutic agents.
 RMSF is the most common and most severe rickettsial disease in North America
20
References 21

 1. Abdad, M. Y., Abou Abdallah, R., Fournier, P. E., Stenos, J., & Vasoo, S. (2018). A Concise Review of the
Epidemiology and Diagnostics of Rickettsioses: Rickettsia and Orientia spp. Journal of clinical
microbiology, 56(8), e01728-17. https://doi.org/10.1128/JCM.01728-17 
 2. Biggs, H., Behravesh, C., Bradley, K., Dahlgren, F., et al. (2016). Diagnosis and Management of Tickborne
Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses,
Ehrlichioses, and Anaplasmosis — United States: A Practical Guide for Health Care and Public Health
Professionals. Morbidity and Mortality Weekly Report: Recommendations and Reports, 65(2), 1-44.
doi:10.2307/24840634 
 3. Dahlgren, F. S., Holman, R. C., Paddock, C. D., et al. (2012). Fatal Rocky Mountain Spotted Fever in the
United States, 1999-2007. The American Journal of Tropical Medicine and Hygiene, 86(4):713—719.
https://doi.org/10.4269/ajtmh.2012.11-0453 
 4. Helmick, C. G., Bernard, K. W., D’Angelo, L. J. (1984). Rocky Mountain spotted fever: clinical, laboratory,
and epidemiological features of 262 cases. Journal of Infectious Diseases.150:480–8.
https://www.ncbi.nlm.nih.gov/pubmed/6491365 
 5. Margulis, L., Eldridge, B. P. (2005). Sensitive to the Environment in Which Diseases Occur, Howard T.
Ricketts Was One of the First Great Microbial Ecologists. American Society for Microbiology. 71(2):65-70.
Accessed online Mar. 24, 2020. http://www.antimicrobe.org/h04c.files/history/znw00205000065.pdf 
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 6. Parola, P., Paddock, C. D., Socolovschi, C., et al. (2013). Update on Tick-Borne Rickettsioses around the
World: a Geographic Approach. Clinical Microbiology Reviews. 26(4):657-702; doi: 10.1128/CMR.00032-
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 7. Rocky Mountain Spotted Fever. (2018). Retrieved Mar. 24, 2020, from Centers for Disease Control and
Prevention: https://www.cdc.gov/rmsf/transmission/index.html
 8. Snowden J, Simonsen KA. Rickettsia Rickettsiae (Rocky Mountain Spotted Fever) [Updated 2019 Jul 27].
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK430881/
 9. Walker D. H. (1980). Laboratory Diagnosis of Rocky Mountain Spotted Fever. South Medical Journal,
73(11):1443-6. https://www.ncbi.nlm.nih.gov/pubmed/6777873
 10. Walker DH. Rickettsiae. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX):
University of Texas Medical Branch at Galveston; 1996. Chapter 38. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK7624/