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Rickettsia Rickettsiae (Rocky Mountain Spotted Fever)

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Last Update: June 4, 2019.

Introduction

Rocky Mountain Spotted Fever (RMSF) is an acute febrile tick-borne illness caused by Rickettsia rickettsii. It is the most severe and most common of the rickettsial infections in North America.[1][2][3]

Etiology

Rickettsia rickettsii, the most well described and most lethal of the spotted group rickettsiae, causes Rocky Mountain Spotted Fever (RMSF). It is a coccobacillary, obligate, intracellular organism that accidentally infects human hosts after a bite with an infected tick vector. Transmission is believed to occur very quickly after a bite from an infected tick, with rapid entry of the bacteria into human endothelial cells.[4][5][6]

Epidemiology

R. rickettsia transmits into human hosts by the bite of an infected tick. Humans are not a natural reservoir of disease. The Rickettsia does not harm the tick. In the United States, transmission occurs most often after a bite of the American dog tick (Dermacentor variabilis), the Rocky Mountain wood tick (Dermacentor andersoni), or the brown dog tick (Rhipicephalus sanguineus). Because of its association with tick bites, it is typically diagnosed in the summer months in people with outdoor exposure. Despite its name, it is most commonly diagnosed in the southeastern and south-central United States. Importantly, because the tick bite may be brief, a lack of history of a tick bite should not exclude this diagnosis in a patient residing in or with a history of travel to an endemic area.[7][8]

Pathophysiology

Rickettsia preferentially infects the vascular endothelial cells lining small and medium vessels throughout the body, causing the systemic symptoms and high mortality seen with Rocky Mountain Spotted Fever. The infection of endothelial cells leads to disseminated inflammation, loss of barrier function, and altered vascular permeability throughout the body. This leads to fever, myalgias, central nervous system symptoms such as a headache and confusion, rash and cardiovascular instability that can be seen in patients with Rocky Mountain Spotted Fever. The mechanisms involved in the rapid entry of the organisms into the cell and the downregulation of immune pathways allowing for persistence of infection are being studied to identify new therapeutic targets in these illnesses.

History and Physical

Patients typically present with symptoms four to ten days after exposure to the Rickettsia via tick bite. Patients may or may not recall the tick bite, as the tick does not need to have prolonged contact with the host to cause infection. A detailed travel history is important to identify any outdoor activities in endemic areas and areas with other endemic Rickettsia, as symptoms overlap between the various Rickettsial infections. Symptoms classically include the triad of fever, headache, and a petechial or maculopapular rash but may also include lymphadenopathy, central nervous system changes such as confusion or nuchal rigidity, myalgias and arthralgias, hepatitis, vomiting, and cardiovascular instability. The rash often begins as a maculopapular rash around the wrists and ankles that progresses to petechia. It is important to have a high index of suspicion for rickettsial infection when patients present with these "influenza-like" symptoms during the summer months, regardless of known tick or insect exposure.

Evaluation

Currently, most cases of Rocky Mountain Spotted Fever are diagnosed based on Immunoglobulin M (IgM) and IgG serologic responses to R. rickettsiae, in conjunction with a high degree of clinical suspicion. It is important to consider repeat testing after resolution of symptoms, as serologic tests may be negative if testing occurs early in the course of illness. A rise in Rocky Mountain Spotted Fever IgG in the weeks after symptoms when comparing acute and convalescent testing is suggestive of infection. While Rickettsia can be cultured in the microbiology laboratory, this approach is not often used for clinical diagnosis as the technique is difficult and requires a high level of biosafety containment due to the risk of exposure. Other diagnostic options include molecular tests, such as polymerase chain reaction (PCR), in some centers and skin biopsy. Given its low sensitivity and specificity, the Weil-Felix agglutination assay is no longer recommended for the diagnosis of Rocky Mountain Spotted Fever. In addition to suggestive or positive serologic tests, patients with rickettsial infections may also have thrombocytopenia, hyponatremia, and cerebrospinal fluid pleocytosis. On a peripheral white blood cell count, it is important to note that this may be elevated, normal, or low and thus may not help to rule out Rickettsial infection. Given the possibility of negative serologic testing early in the illness and otherwise non-specific laboratory abnormalities, it is essential to have a high index of suspicion for Rocky Mountain Spotted Fever in patients with influenza-like symptoms in the warmer months if they reside in or have a history of travel to endemic areas.[9][10]

Treatment / Management

Doxycycline is the drug of choice for the treatment of Rocky Mountain Spotted Fever, including in children. Defervescence typically occurs within three days of starting appropriate antibiotic therapy, although other symptoms may be slower to resolve. The treatment course is usually seven to ten days, or for at least three days after defervescence. It is important to note than in severe rickettsial disease, such as Rocky Mountain Spotted Fever, mortality rates are as high as 20% to 30% without prompt antibiotic treatment. Thus, treatment should not be delayed while awaiting confirmatory laboratory testing in a patient with suspected rickettsial infection. This is particularly important in children, who are at high risk of morbidity and mortality but may experience delays in treatment due to concerns with doxycycline use in children younger than age 8. The risk of dental staining in the treatment of Rocky Mountain Spotted Fever is very low, as dental staining is a cumulative dose effect and treatment for Rocky Mountain Spotted Fever is typically seven to ten days. Thus, concerns regarding tooth staining should not delay treatment in suspected Rocky Mountain Spotted Fever.[11][12][13][14]

Pearls and Other Issues

There are currently no recommendations for or evidence to support prophylaxis against Rocky Mountain Spotted Fever in patients with a known tick bite. Additionally, as this is not transmissible from person to person, isolation is not required. There is no vaccine against Rocky Mountain Spotted Fever. Prevention of infection requires careful attention to tick avoidance, including insect repellant, long clothing and checking for ticks after any outdoor activities in endemic areas.

Enhancing Healthcare Team Outcomes

RMSF is best managed by a multidisciplinary team that includes a pharmacist and an infectious disease nurse. Once the diagnosis is made, treatment should be started ASAP. Because there is no vaccine, patients need to be educated on the prevention of tick bites.

Questions

To access free multiple choice questions on this topic, click here.

References

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Yaglom HD, Nicholson WL, Casal M, Nieto NC, Adams L. Serologic assessment for exposure to spotted fever group rickettsiae in dogs in the Arizona-Sonora border region. Zoonoses Public Health. 2018 Dec;65(8):984-992. [PMC free article: PMC6217800] [PubMed: 30133168]
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Trout Fryxell RT, Steelman CD, Szalanski AL, Billingsley PM, Williamson PC. Molecular Detection of Rickettsia Species Within Ticks (Acari: Ixodidae) Collected from Arkansas United States. J. Med. Entomol. 2015 May;52(3):500-8. [PubMed: 26334827]
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Denison AM, Amin BD, Nicholson WL, Paddock CD. Detection of Rickettsia rickettsii, Rickettsia parkeri, and Rickettsia akari in skin biopsy specimens using a multiplex real-time polymerase chain reaction assay. Clin. Infect. Dis. 2014 Sep 01;59(5):635-42. [PMC free article: PMC4568984] [PubMed: 24829214]
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Hardstone Yoshimizu M, Billeter SA. Suspected and Confirmed Vector-Borne Rickettsioses of North America Associated with Human Diseases. Trop Med Infect Dis. 2018 Jan 03;3(1) [PMC free article: PMC6136625] [PubMed: 30274401]
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Quiroz-Castañeda RE, Cobaxin-Cárdenas M, Cuervo-Soto LI. Exploring the diversity, infectivity and metabolomic landscape of Rickettsial infections for developing novel therapeutic intervention strategies. Cytokine. 2018 Dec;112:63-74. [PubMed: 30072088]
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Wood H, Artsob H. Spotted fever group rickettsiae: a brief review and a Canadian perspective. Zoonoses Public Health. 2012 Sep;59 Suppl 2:65-79. [PubMed: 22958251]
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Bookshelf ID: NBK430881PMID: 28613631

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