Rocky Mountain Spotted Fever
- Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...
Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organism Rickettsia rickettsii. Although RMSF can be lethal, it is curable. RMSF is the most common rickettsial infection. The organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States. See Epidemiology and the map below.
Sophisticated microbiologic and serologic methods to distinguish infection by different members of the spotted-fever group reveal that RMSF may be more common in the tropics and subtropical regions of the Americas than previously thought. (See Epidemiology.)
RMSF has been described as a "wolf in sheep's clothing" and "the great imitator" of other disease processes. Because of its diverse clinical features, RMSF is often confused with other infections. The hallmark of RMSF is a petechial rash (see the image below) beginning on the palms of the hands and soles of the feet. (See Clinical and Differentials.)
See also 7 Bug Bites You Need to Know This Summer, a Critical Images slideshow, for helpful images and information on various bug bites.
The 2 principal tick vectors of RMSF in North America are Dermacentor variabilis (dog tick), in the eastern United States, and D andersoni, in the Rocky Mountain region and Canada. Other species also identified include Rhipicephalus sanguineus in Mexico and Central America and Amblyomma cajennense in Central and South America. A cooperi, A americanum, Ixodes pacificus, and Haemaphysalis leporispalustris are uncommon vectors for human infection. (See Etiology.)
Major Marshall H. Wood, a US Army physician in Boise, Idaho, first recognized R rickettsii infection and described RMSF in 1896. The first report in the medical literature of a case in the Snake River Valley of Idaho was published in 1899. In 1902, 7 people died of RMSF in Bitterroot Valley. Then, 111 cases of RMSF were studied on the west side of the Bitterroot River; 69% of these cases were fatal. Based on the history of tick exposure and the season, researchers concluded that the wood tick spreads RMSF.
Howard Ricketts, for whom the etiologic pathogen is named, identified R rickettsii, its vector, and the route of transmission of RMSF. In 1906, Ricketts demonstrated tick transmission of RMSF to guinea pigs, showed that the etiologic agent was present in blood from infected humans, and demonstrated that it could be removed via filtration. Ricketts reported "minute polar staining bacilli" in freshly laid eggs of infected ticks.
In 1916, Wolbach published 2 papers also describing the appearance of R rickettsii using the Giemsa stain. In 1919, he reported that R rickettsii is an intracellular pathogen, and he described the vasculitic lesion.
In the late 1940s, broad-spectrum antibiotics ̶ chloramphenicol and the tetracyclines ̶ were first shown to be effective in the treatment of RMSF.
Mortality rates as high as 30% were reported for RMSF in the preantibiotic era. Although its clinical manifestations and treatment of the disease are well known, RMSF still causes significant mortality and morbidity. The current mortality rate is 1.4%. A significant portion of this persistent mortality is likely due to delay in diagnosis and treatment.
For patient education information, see Ticks.
Etiology and Pathophysiology
R rickettsii is a small (0.3 µm X 1 µm), gram-negative, obligate, intracellular coccobacillus. It possesses outer-membrane protein A (OmpA) and OmpB, 2 major immunodominant, surface-exposed proteins with species-specific conformational epitopes. OmpB is the most abundant outer-membrane protein that shares genetic sequences and limited antigens with typhus group rickettsiae.
Ticks become infected by feeding on the blood of infected animals, through fertilization, or by transovarial passage. Rickettsiae are transmitted from tick to human during feeding. The tick needs to be attached to a host for 6-10 hours for rickettsiae to be released from the salivary glands, although transmission may not occur for 24 hours. In addition, this organism can infect people who remove ticks from other people or animals via contact with tick tissues and fluids.
The organism spreads through the body via blood and the lymphatic system. The incubation phase of infection ranges from 3-12 days, depending on the volume of the inoculum.
Notable characteristics of R rickettsii include its marked tropism for endothelial cells that line blood vessels and its enhanced ability to invade throughout the body compared with other rickettsiae. The organisms attach via OmpA to the endothelial membrane, where they induce their own engulfment. Once they invade the cell and effectively escape destruction by professional phagocytes, they replicate via binary fission in the cytosol and spread from cell to cell, propelled by polar polymerization of the host cell's actin, without producing cell lysis.
The rickettsial diseases, especially Rocky Mountain spotted fever (RMSF), are model examples of vasculitis with localization in endothelial cells. The major pathophysiologic effect of endothelial cell injury is increased vascular permeability, which results in edema, hypovolemia, hypotension, and hypoalbuminemia. The organisms also routinely infect vascular smooth-muscle cells.
The distribution of rickettsiae within the blood vessels causes vascular injury and the subsequent development of a host mononuclear-cell tissue response. Consequences of vascular injury include interstitial pneumonia, interstitial myocarditis, and perivascular glial nodules of the central nervous system (CNS), with similar vascular lesions in the skin, gastrointestinal (GI) tract, pancreas, liver, skeletal muscles, and kidneys. Large amounts of rickettsiae in damaged cells support the concept of direct injury.
The inflammation and damage to the blood vessels and capillaries activate platelets, generate thrombin, and activate the fibrinolytic system as part of the body's homeostatic physiologic response to endothelial injury.
As R rickettsii proliferates in the endothelial lining, it also causes thrombi to form. In severe cases, extensive vasculitis can lead to small-vessel occlusion. Vascular necrosis and thrombosis are more common in RMSF than in typhus and may mimic collagen-vascular disease.
Occurrence in the United States
Rocky Mountain spotted fever (RMSF) is the most common cause of fatal tick-borne disease in the United States. Anyone who is bitten by an infected dog tick and on whom the infected tick remains for several hours can develop RMSF. In spite of its name, RMSF is more common in the southeastern US tick belt than in the Rocky Mountain region (see the map below). The disease is more common in rural and suburban locations; however, it does occur in urban areas such as New York City.[2, 3, 4]
The regions with the highest incidences include the Southeast, the western South Central region (including Oklahoma and northern Texas), and selected areas of the Northeast (Cape Cod and Long Island). Most cases are reported from eastern and central states, such as North and South Carolina, Virginia, Georgia, Tennessee, Arkansas, Missouri, Kansas, and Oklahoma. The 2 states with the highest incidence are North Carolina and Oklahoma.
Cases have been reported in 48 states, with Vermont and Hawaii being the exceptions. In the northern United States, infections commonly occur in the spring; in the South, cases may occur at any time of the year, including winter.
From 1989-1996, more than 4700 cases were reported in 46 states. Of these reported cases, 90% occurred between April and September.
A prospective study of RMSF infection in residents of a known endemic area in North Carolina suggested an annual incidence of 42 cases per 100,000 children aged 5-9 years. Asymptomatic infection may be common; in one study, 12% of children living in high-risk zones had positive serology test results, indicating past exposure to RMSF.
In 2005, 1936 cases were reported—more than 4 times the 365 cases reported in 1998. The reasons for this increase are not known, but wide swings in the incidence of RMSF have occurred since 1920. Due to underdiagnosis, lack of testing, and lack of reporting, it is likely that the actual number of cases is much higher than surveillance data suggest.
Canada, Mexico, and Central and South America (particularly Panama, Columbia, Argentina, Costa Rica, Bolivia, and Brazil) have reported cases of RMSF. Serologic evidence of RMSF has been found in 6 Brazilian states, ranging from Rio Grande de Sol in the south to Bahia in the north. In Brazil, RMSF was unrecognized or unreported for decades in regions such as Espiritu Santo. In southern Brazil, the disease is more common from October to February, but, in the tropics, seasonal variation is less striking.
There have been no documented cases of RMSF infection outside of the Americas. However, a wide range of related spotted fever group (SFG) rickettsioses has been described across Europe, Africa, Asia, and Oceania. The true incidence of spotted fever infections internationally is not known.
Whites have twice the incidence of African Americans. However, African Americans have a higher case-fatality rate. This may be due to the greater difficulty of appreciating a rash in highly pigmented individuals.
American Indians are at greater risk for RMSF than the general population. From 2001-2005, the average annual incidence of RMSF reported among American Indians was 16.8 per 1,000,000 persons compared with 4.2 for whites, 2.6 for blacks, and 0.5 for Asian/Pacific Islanders. The incidence of RMSF in American Indians increased at a disproportionate rate during this period, although from 1990-2000, the rate was comparable to those for other races from 1990-2000.
Sex- and age-related demographics
The male-to-female ratio for RMSF is 1.7:1. The mortality risk is also higher in males than in females.
The incidence of Rocky Mountain spotted fever is highest among adults aged 60-69 years (3.1 cases/million persons) and children aged 5-9 years (an estimated 3.3 cases/million persons).
Mortality rates in Rocky Mountain spotted fever (RMSF) vary according to the following criteria:
Delay in diagnosis
Delay in effective antibiotic treatment - In a 1995 study, antirickettsial therapy within the first 5 days of illness reduced the risk of mortality 5-fold compared with treatment initiation after the 5-day mark 
Gender - Mortality risk is higher in males
Severity of the disease
Presence of chronic alcohol abuse
Presence of glucose-6-phosphate-dehydrogenase deficiency
The mortality rate in untreated cases of RMSF is 20-25%. Mortality rates can be as low as 5% with proper antibiotic therapy and as high as 70% in untreated elderly individuals. Death in 5 days can be expected in fulminant cases.
Complications may include the following[10, 11, 12] :
Disseminated intravascular coagulation
Noncardiogenic pulmonary edema
Acute tubular necrosis
Shock with myocarditis
Skin necrosis and gangrene - Particularly in fingers, toes, elbows, ears, and scrotum
Myocarditis - Usual cause of death
Bowel and bladder incontinence
Cerebellar and vestibular dysfunction
Blindness - The frequency of long-term ocular sequelae is low; in most cases, good binocular visual acuity is preserved
Hemophagocytic histiocytosis - Has been described in fatal cases of RMSF
Factors at presentation associated with development of acute renal failure (ARF) include increased bilirubin, advancing age, thrombocytopenia, and the presence of neurologic involvement. Age and decreased platelet count at presentation have been independently associated with the development of ARF by multivariate analysis. ARF development increases the odds ratio of dying by a factor of 17.
Sexton DJ, Corey GR. Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing. Clin Infect Dis. 1992 Sep. 15(3):439-48. [Medline].
Salgo MP, Telzak EE, Currie B, et al. A focus of Rocky Mountain spotted fever within New York City. N Engl J Med. 1988 May 26. 318(21):1345-8. [Medline].
Openshaw JJ, Swerdlow DL, Krebs JW, et al. Rocky mountain spotted fever in the United States, 2000-2007: interpreting contemporary increases in incidence. Am J Trop Med Hyg. 2010 Jul. 83(1):174-82. [Medline]. [Full Text].
Stromdahl EY, Jiang J, Vince M, Richards AL. Infrequency of Rickettsia rickettsii in Dermacentor variabilis removed from humans, with comments on the role of other human-biting ticks associated with spotted fever group Rickettsiae in the United States. Vector Borne Zoonotic Dis. 2011 Jul. 11(7):969-77. [Medline].
Marshall GS, Stout GG, Jacobs RF, et al. Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States. Arch Pediatr Adolesc Med. 2003 May. 157(5):443-8. [Medline].
Zavala-Castro JE, Dzul-Rosado KR, León JJ, Walker DH, Zavala-Velázquez JE. An increase in human cases of spotted fever rickettsiosis in Yucatan, Mexico, involving children. Am J Trop Med Hyg. 2008 Dec. 79(6):907-10. [Medline].
Demma LJ, Holman RC, Mikosz CA, et al. Rocky mountain spotted fever hospitalizations among American Indians. Am J Trop Med Hyg. 2006 Sep. 75(3):537-41. [Medline].
Holman RC, McQuiston JH, Haberling DL, Cheek JE. Increasing incidence of Rocky Mountain spotted fever among the American Indian population in the United States. Am J Trop Med Hyg. 2009 Apr. 80(4):601-5. [Medline].
Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis. 1995 May. 20(5):1118-21. [Medline].
Archibald LK, Sexton DJ. Long-term sequelae of Rocky Mountain spotted fever. Clin Infect Dis. 1995 May. 20(5):1122-5. [Medline].
Chen LF, Sexton DJ. What's new in Rocky Mountain spotted fever?. Infect Dis Clin North Am. 2008 Sep. 22(3):415-32, vii-viii. [Medline].
Sexton DJ, Gallis HA, McRae JR, Cate TR. Letter: Possible needle-associated Rocky Mountain spotted fever. N Engl J Med. 1975 Mar 20. 292(12):645. [Medline].
Buckingham SC, Marshall GS, Schutze GE, et al. Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children. J Pediatr. 2007 Feb. 150(2):180-4, 184.e1. [Medline].
Byrd RP Jr, Vasquez J, Roy TM. Respiratory manifestations of tick-borne diseases in the Southeastern United States. South Med J. 1997 Jan. 90(1):1-4. [Medline].
Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006 Mar 31. 55:1-27. [Medline].
Procop GW, Burchette JL Jr, Howell DN, Sexton DJ. Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin biopsies. A comparative study. Arch Pathol Lab Med. 1997 Aug. 121(8):894-9. [Medline].
Markley KC, Levine AB, Chan Y. Rocky Mountain spotted fever in pregnancy. Obstet Gynecol. 1998 May. 91(5 Pt 2):860. [Medline].
Holman RC, Paddock CD, Curns AT, Krebs JW, McQuiston JH, Childs JE. Analysis of risk factors for fatal Rocky Mountain Spotted Fever: evidence for superiority of tetracyclines for therapy. J Infect Dis. 2001 Dec 1. 184(11):1437-44. [Medline].
Minniear TD, Buckingham SC. Managing Rocky Mountain spotted fever. Expert Rev Anti Infect Ther. 2009 Nov. 7(9):1131-7. [Medline].
Lochary ME, Lockhart PB, Williams WT Jr. Doxycycline and staining of permanent teeth. Pediatr Infect Dis J. 1998 May. 17(5):429-31. [Medline].
Baggett MV, Turbett SE, Schwartzenberg SS, Stone JR. Case records of the Massachusetts General Hospital: Case 5-2014: 2014: A 59-year-old man with fever, confusion, thrombocytopenia, rash, and renal failure. N Engl J Med. 2014 Feb 13. 370(7):651-60. [Medline].
Lin L, Decker CF. Rocky Mountain spotted fever. Dis Mon. 2012 Jun. 58(6):361-9. [Medline].
Milagres BS, Padilha AF, Montandon CE, Freitas RN, Pacheco R, Walker DH, et al. Spotted fever group Rickettsia in small rodents from areas of low endemicity for Brazilian spotted fever in the eastern region of Minas Gerais State, Brazil. Am J Trop Med Hyg. 2013 May. 88(5):937-9. [Medline]. [Full Text].
Raoult D, Parola P. Rocky Mountain spotted fever in the USA: a benign disease or a common diagnostic error?. Lancet Infect Dis. 2008 Oct. 8(10):587-9. [Medline].
Woods CR. Rocky Mountain spotted fever in children. Pediatr Clin North Am. 2013 Apr. 60(2):455-70. [Medline].