Review
Rocky Mountain spotted fever

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Summary

Rocky Mountain spotted fever (RMSF) is a life-threatening disease caused by Rickettsia rickettsii, an obligately intracellular bacterium that is spread to human beings by ticks. More than a century after its first clinical description, this disease is still among the most virulent human infections identified, being potentially fatal even in previously healthy young people. The diagnosis of RMSF is based on the patient's history and a physical examination, and often presents a dilemma for clinicians because of the non-specific presentation of the disease in its early course. Early empirical treatment is essential to prevent severe complications or a fatal outcome, and treatment should be initiated even in unconfirmed cases. Because there is no vaccine available against RMSF, avoidance of tick-infested areas is still the best way to prevent the infection.

Introduction

Rocky Mountain spotted fever (RMSF) is a life-threatening disease caused by Rickettsia rickettsii, an obligately intracellular bacterium that is spread to human beings by infected ticks. The disease is the most common tickborne rickettsial disease in the USA and is potentially fatal even in previously healthy young people.1, 2, 3 RMSF is among the most virulent infections identified in human beings,4 and its diagnosis often presents a dilemma for clinicians.5, 6, 7, 8, 9

Section snippets

The so-called spotted fever of Idaho: early history

The history of RMSF began in the late 19th century, when Edward E Maxey provided the first clinical description of the so-called spotted fever of Idaho: “a febrile disease, characterized clinically by a continuous moderately high fever, and a profuse or purpuric eruption in the skin, appearing first on ankles, wrists, and forehead, but rapidly spreading to all parts of body”.10 This description became the first report of RMSF to be published in the medical literature.11

In 1904, Louis B Wilson

The pathogen

R rickettsii (panel 1) is a fastidious, small (0·2–0·5 μm by 0·3–2·0 μm), pleomorphic Gram-negative coccobacillus. The cell-wall composition and lipopolysaccharide of the pathogen resemble that seen in other Gram-negative bacteria.24, 25, 26 Most cell-surface antigens are recognised by antibodies present in sera of human beings and animals with active RMSF.26, 27, 28 R rickettsii possesses two major immunodominant surface proteins of 190 kDa and 135 kDa: outer membrane protein A (OmpA) and

Natural reservoir hosts and mode of transmission

Natural reservoirs of R rickettsii include hard ticks (family Ixodidae; figure 1) of various genera and species.39 The pathogen is maintained in nature, across several tick generations, through transovarial passage (from an infected female tick to her progeny) and transstadial passage (between developmental life stages). Although R rickettsii can also be found in domestic (eg, dogs) and wild mammals, the role of these animals as reservoirs of infection is not well understood.17, 39, 40, 41, 42,

Epidemiology

The geographical distribution of RMSF is restricted to countries of the western hemisphere (figure 4). The disease has been found in the USA, western Canada,66 western and central Mexico,67, 68 Panama,69 Costa Rica,70 northwestern Argentina,71 Brazil (states of São Paulo, Minas Gerais, Rio de Janeiro, Espírito Santo, Bahia, and Santa Catarina),51 and Colombia.72 In the USA, RMSF occurs in all contiguous 48 states, except for Vermont and Maine;73, 74 half of the cases are found in Oklahoma,

Clinical manifestations

Patients with RMSF display a diverse range of systemic, cutaneous, cardiac, pulmonary, gastrointestinal, renal, neurological, ocular, and skeletal muscle manifestations.30 Most patients have moderate or severe illness,30, 32 and a substantial proportion of them need to be admitted to hospital.83, 93 The mean incubation period of RMSF is 7 days (range 2–14 days).17, 30, 32, 34, 74 Initial clinical signs and symptoms are similar to those observed in other tickborne rickettsial diseases, making

Diagnosis: a dilemma for clinicians

The diagnosis of RMSF is based on physical examination of the patient and epidemiological data. However, clinical diagnosis is difficult because initial signs and symptoms are often non-specific and may lead clinicians to make the wrong diagnosis.5, 106, 116, 117, 118, 119, 120, 121, 122, 123

Antibodies to R rickettsii are not detectable until 7–10 days after disease onset;124 thus, serological tests are of limited diagnostic value.17, 30 A negative result does not exclude the possibility of

Treatment

Because fatal cases of RMSF are often associated with delayed diagnosis, the decision to treat should never be delayed by laboratory confirmation.9, 17, 30, 34 Any patient with a fever and rash should be considered for hospital admission and antimicrobial therapy.136

Tetracyclines and chloramphenicol are the only drugs proven to be effective for the treatment of RMSF.11 Because of its effectiveness, broad margin of safety, and convenient dosing schedule, doxycycline is currently considered the

Prevention

The development of vaccines against rickettsial diseases remains a low priority, as a result of the development of effective and safe antibiotics, and mainly because of the decreased perceived threat posed by these diseases. Although some rickettsial pathogens (R rickettsii and R prowazekii) are considered by the CDC to be select agents, there are no vaccines for any rickettsial disease currently approved by the US Food and Drug Administration.146 Thus, it is essential to emphasise that

Conclusions

Over a century has elapsed since the first clinical description of RMSF. Despite this, the disease remains among the most severe vector-borne diseases recognised to date, and many aspects of its natural history are still unknown. The diagnosis of RMSF remains a dilemma for clinicians because the diagnostic value of current tools is very limited, particularly during the early course of the illness. Better serological methods to detect specific antibodies to R rickettsii in the early phase of

Search strategy and selection criteria

Data for this Review were identified by searching PubMed. Search terms (alone or in combination) were “Rocky Mountain spotted fever”, “Rickettsia rickettsii”, “Dermacentor ticks”, and “tick-borne rickettsioses”. English, Portuguese, and Spanish languages papers were reviewed, without date restriction. Selected articles were also searched for relevant references. Papers already known to the author were also included, as well as several review articles, since they provided comprehensive

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