Rocky Mountain Spotted Fever

Rocky Mountain Spotted Fever (RMSF) is a severe tick-borne illness caused by Rickettsia rickettsii, a Gram-negative, coccobacillary bacterium. This pathogen is an obligate intracellular parasite, requiring a host cell for replication. Transmission occurs through the bite of an infected tick. In the United States, the most important vectors are Dermacentor variabilis (American dog tick) and Dermacentor andersoni (Rocky Mountain wood tick), though other tick species may also serve as vectors. RMSF is primarily reported in the southeastern and south-central regions of the United States, particularly during the summer and spring months, when tick activity is at its peak. Ticks typically attach to exposed areas of the body, including the legs, arms, or scalp, where they feed on blood and may transmit Rickettsia rickettsii, the causative agent of RMSF. Following transmission, R. rickettsii rapidly enters the bloodstream and targets the vascular endothelial cells that line small blood vessels.

Pathogenesis and Cellular Invasion

After entering the host, the bacterium uses surface adhesion molecules to bind to endothelial cells and invades them through receptor-mediated endocytosis. Once internalized, R. rickettsii escapes from the phagosome into the cytoplasm, where it replicates. It hijacks host cell actin filaments to propel itself within and between adjacent cells, allowing it to bypass extracellular immune defenses. The infection compromises the integrity of endothelial membranes, increasing vascular permeability. This leads to leukocyte and plasma infiltration, resulting in localized edema, reduced tissue perfusion, and systemic hypotension due to widespread vascular leakage.

Clinical Manifestations and Disease Progression

RMSF typically has an incubation period of 2 to 14 days. Symptoms usually appear 2 to 4 days after onset and include high fever, severe headache, myalgia, and gastrointestinal symptoms such as nausea and vomiting. A hallmark feature is the appearance of a maculopapular rash, which typically begins at the wrists and ankles before spreading centripetally to the trunk. In severe cases, the rash progresses to petechiae—small red or purple spots caused by capillary hemorrhages. Without prompt treatment, RMSF can lead to life-threatening complications such as multiorgan failure, encephalitis, and coma.

Treatment and Prognosis

Early recognition and treatment are critical. Doxycycline is the antibiotic of choice for all age groups and should be administered immediately upon suspicion of RMSF, even before laboratory confirmation is obtained. Delayed treatment significantly increases the risk of severe outcomes. If left untreated, the case fatality rate can be as high as 20% to 30%, particularly among young children and individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.