Rocky Mountain Spotted Fever€¦ · The incubation period of Rocky Mountain spotted fever is Rickettsiae introduced through the skin spread via the lymphat- 2 to 14 days after the

1353

STATE-OF-THE-ART CLINICAL ARTICLE

Rocky Mountain Spotted Fever

Anna R. Thorner, David H. Walker, and The University of Virginia, Charlottesville, Virginia; and the Universityof Texas Medical Branch, Galveston, TexasWilliam A. Petri, Jr.

Rocky Mountain spotted fever (RMSF), a potentially fatal, blood obtained from infected humans, and that it could be re-moved by filtration. Ricketts reported the presence of ‘‘minutetick-borne disease caused by the gram-negative intracellular

bacterium Rickettsia rickettsii, is endemic in parts of North and polar staining bacilli’’ in freshly laid eggs of infected ticks [2].Four years after these classic investigations, Ricketts died ofSouth America, especially the southeastern and southcentral

United States. Although it was first recognized ú100 years epidemic typhus in Mexico City, but only after having describedthe distinctive microbe (Rickettsia prowazekii) found in the liceago, the disease remains difficult to diagnose because a rash

does not appear until an average of 3 days into the illness, and and blood from patients with that disease. In 1916, Wolbachpublished two papers in which he described the appearance ofdoes not manifest a petechial or purpuric character until later

in the course, if at all. Common presenting symptoms include R. rickettsii that he visualized in blood vessels by using theGiemsa stain [4]. In 1919, he reported that R. rickettsii is anfever, headache, myalgias, and gastrointestinal disturbances.

The mortality rate associated with RMSF is 20% to 25% if intracellular pathogen and he described the vasculitic lesion [5].The broad-spectrum antibiotics, chloramphenicol and the tetracy-untreated, and 5% with appropriate antibiotic therapy (if not

initiated early enough). Treatment with doxycycline may be clines, were first shown to be effective in the treatment of RMSFduring the late 1940s [6].preferable to chloramphenicol therapy, because the tetracy-

clines have been shown in a retrospective study to be associatedwith a higher survival rate. Physicians must maintain a high

Epidemiologyindex of suspicion for RMSF in patients with febrile illnessand a history of potential tick exposure who present in the

The tick is both the vector and the main reservoir ofspring through the fall.R. rickettsii. The most common species of tick implicatedin the transmission of RMSF are Dermacentor variabilis

History (dog tick), in the eastern two-thirds of the United States andparts of the West Coast; Dermacentor andersoni (wood tick),The first report of RMSF was published in 1896 by Majorin the Rocky Mountain states; Rhipicephalus sanguineus, inMarshall H. Wood, an army physician, in Boise, Idaho [1]. InMexico; and Amblyomma cajennense, in Central and South1899, in the first report of RMSF to be published in the medicalAmerica. Ticks become infected by feeding on the bloodliterature, Maxey described RMSF in the Snake River valley ofof infected animals, through fertilization, or by transovarialIdaho [2]. Wilson and Chowning [3] observed seven deaths duepassage. The tick transmits rickettsiae to humans duringto RMSF in the Bitterroot valley in the spring of 1902. Theyfeeding. After the tick has been attached to the host for asstudied 111 cases of RMSF, the majority of which were on theshort a period as 6 –10 hours, rickettsiae are released fromwest side of the Bitterroot River; 69% of the cases were fatal.the salivary glands, although transmission may not occur forOn the basis of the history of tick exposure and the seasonality24 hours or longer in some cases. In addition, humans mayof the disease, they concluded that RMSF was spread by thebecome infected by contact with tick tissues and fluids dur-wood tick [3]. While working in the Bitterroot valley in 1906,ing tick removal from people or animals [7]. Further, it isHoward Ricketts demonstrated tick transmission of RMSF topossible to acquire rickettsiosis in the laboratory by inhala-guinea pigs, and showed that the agent of RMSF was present intion of contaminated aerosol [8].

There are 600–1200 cases of RMSF reported each year inthe United States [9, 10]. Of these cases, 90% occur between

Publication of this State-of-the-Art Clinical Article has been made possible April and September. However, sporadic cases occur through-by an educational grant from Roche Laboratories. out the year, even in cold climates. RMSF was first reportedReceived 31 July 1998.

in the eastern United States in the 1930s, and has predominatedReprints or correspondence: Dr. William A. Petri, Jr., MR-4, Room 2115,Department of Medicine, University of Virginia School of Medicine, Char- there during the past few decades. During the 1940s, there waslottesville, Virginia 22908. a marked drop in the incidence of RMSF in the Rocky Moun-Clinical Infectious Diseases 1998;27:1353–60 tain states, a trend that has persisted and is of unknown cause.q 1998 by the Infectious Diseases Society of America. All rights reserved.1058–4838/98/2706–0001$03.00 Today, RMSF is most common in the South Atlantic states

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID

Downloaded from https://academic.oup.com/cid/article-abstract/27/6/1353/317826by gueston 01 September 2018

1354 Thorner, Walker, and Petri CID 1998;27 (December)

Figure 1. Average annual incidence of Rocky Mountain spotted fever according to county in the United States, 1981–1992. Reprinted withpermission from American Journal of Tropical Medicine and Hygiene [11].

(figure 1). Between 1981 and 1992, North Carolina and Okla- and reduced perfusion of tissue. A major manifestation of endo-thelial cell injury is increased vascular permeability, whichhoma accounted for 34% of all cases in the United States [11].

The incidence of RMSF is higher among males (63%) [11, leads to edema, hypovolemia, hypotension, and hypoalbumi-nemia [7]. The recent discoveries that mouse endothelial cells12], caucasians (1.5 per million vs. 0.8 per million in African

Americans) [11], and children (especially those between 5 and kill Rickettsia conorii by a nitric oxide-dependent mechanismwhen stimulated by the combination of IFN-g and TNF-a, and9 years of age) [10–12]. Exposure to dogs [13] and residence

in wooded areas or areas with high grass both increase the risk that immune CD8 T lymphocytes are necessary for clearanceof R. conorii from endothelial cells, help to elucidate the immu-of infection [12–15].nologic responses to the spotted fever rickettsioses [22, 23].

PathogenesisClinical Manifestations

Ticks live for up to 5 years, are resistant to desiccation,cold, and starvation and have high reproductive potential [16]. The incubation period of Rocky Mountain spotted fever is

2 to 14 days after the tick bite, with a mean of 7 days [24].Rickettsiae introduced through the skin spread via the lymphat-ics and blood vessels. The microorganisms attach to and enter Most patients present initially with fever, with or without head-

ache. The classic triad of fever, rash, and history of tickvascular endothelium and vascular smooth muscle cells bymeans of a surface-exposed protein and rickettsial phospholi- exposure is present in only 3% to 18% of cases at the initial

physician visit [15, 25]. A temperature ú1027F is observed inpase [17–19]. Rickettsiae invade and multiply within the endo-thelial and smooth muscle cells of blood vessels, and they are two-thirds of patients during the first 3 days of illness [15],

and a history of tick exposure is obtained in up to 85% ofdirectly cytopathic [20, 21]. Generalized vascular injury ensues,resulting in activation of clotting factors, extravasation of fluid, cases, but is often unavailable because of lack of awareness

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID


1355CID 1998;27 (December) Rocky Mountain Spotted Fever

Table 1. Cardinal findings of Rocky Mountain spotted fever.

Study

Dalton Hattwick Helmick KaplowitzFinding(s) et al. [11] CDC [26] et al. [14] et al. [15] et al. [27]

Fever 94 88 100* 99 100ú1027F 90 88

Headache 86 85 93* 91 79Myalgia 83 85 92* 83 72Rash

anywhere 80 74 85* 88 90palms &/or soles 56 49 74 82

Tick bite 66 54 58† 60Classic triad (fever, headache, and rash) 55 45 67 [3‡]Nausea or vomiting 60 56Other signs and symptoms present in ú10% of patients [13, 15]:Cough Hepatomegaly MeningismusPneumonitis Splenomegaly AtaxiaAbdominal pain Lymphadenopathy StuporDiarrhea Edema ConjunctivitisAnorexia

NOTE. Data are percentages of patients.* Fatal cases.† All cases, fatal and nonfatal.‡ In the first 3 days of illness.

or failure to remember, and in some cases because of CNS pathy, gastrointestinal bleeding, and skin necrosis. Long-termsequelae include paraparesis; hearing loss; peripheral neuropa-involvement (table 1) [12, 15]. The skin rash appears an average

of 2 to 3 days after the onset of illness as blanching, 1–4 mm thy; bladder and bowel incontinence; cerebellar, vestibular, andmotor dysfunction; language disorders; and disability resultingmacules that later become petechiae (figure 2). The rash starts

most often on the ankles and wrists and then appears on the from limb amputation [31].If the patient is untreated or if treatment is started too latetrunk, palms, and soles [28]. In some severe cases, the rash

progresses to become confluent, ecchymotic areas of skin that during the course of the illness, death usually occurs 8 to 15days after the onset of symptoms [32]. An exception to this ismay undergo necrosis, especially in regions supplied by termi-

nal arteries, such as the fingers, toes, nose, ears, and genitals. fulminant RMSF (which occurs in African American maleswith glucose-6-phosphate dehydrogenase deficiency) in whichYounger patients tend to develop the rash earlier [11, 29].

Nausea or vomiting is present in 56% to 60% of patients death occurs£5 days after the onset of illness [33]. Hemolysisis the most likely cause of this fulminant course [32].[15, 27].

Among adults with RMSF, there is a higher incidence ofunexpected symptoms and more severe illness, a later onset of

Diagnosisrash or less frequent occurrence of rash, a less frequent historyof tick bite, and longer delays before seeing a physician [15]. Because R. rickettsii is not routinely cultured, diagnosis mustRash is less likely to be recognized in African American pa- be based on only the history and physical examination findings.tients [30]. The difficulty of diagnosing RMSF is problematic, Direct immunofluorescence or immunoperoxidase staining ofgiven that there is a clear link between delay of treatment and skin biopsies for the detection of R. rickettsii in the vascularmortality. Among fatal cases of RMSF, late-appearing rash and endothelium is 70% to 90% sensitive, but the procedure islack of history of tick bite (or no history pursued) are more limited to patients who have a rash [34]. For patients withoutlikely, as are gastrointestinal, nonspecific, or atypical symptoms a rash, diagnosis is especially difficult, since neither the typical(table 2) [11, 25, 29]. rash nor results of these tests are available to aid clinicians.

Most of the major complications of RMSF result directly The utility of PCR amplification of R. rickettsii DNA fromfrom a vasculitic mechanism of injury. These complications blood is limited because of low sensitivity, particularly earlyinclude encephalitis, noncardiogenic pulmonary edema, adult in the course of illness when treatment is most effective

[35, 36].respiratory distress syndrome, cardiac arrhythmia, coagulo-

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID



Figure 2. Examples of the petechial rash of Rocky Mountain spotted fever (RMSF). Photographs courtesy of the Centers for Disease Controland Prevention (A and B) and from reference [28](C and D). (A) Early macular rash, (B) petechial rash in the same patient 24 hours later,and (C, D) other examples of petechial rash of RMSF.

Serological studies are used to confirm the clinical diagnosis, [32]. Early treatment may blunt the rise in antibody titer. Thebut are usually not useful when patients first present to a physi- indirect fluorescent antibody technique (IFA) is the most sensi-cian. Generally, antibodies are detectable 7 to 10 days after tive serological method available (sensitivity, 94%) and thethe onset of symptoms [37]. Serological diagnosis requires a most commonly used test [37]. The Weil-Felix test (Proteusfourfold rise in titer between the acute and convalescent sera OX-2 and OX-19) has very poor sensitivity and specificity and

should not be used. Although there are a number of laboratoryabnormalities that are common in RMSF (table 3), becausethese abnormalities are nonspecific, they cannot be used toTable 2. Risk factors for fatal outcome in Rocky Mountain spotted

fever. confirm the diagnosis.Diseases to consider in the differential diagnosis of a patient

• Age ú40 years with fever, headache, and/or a petechial rash include meningococ-• Nonwhite

cemia, thrombotic thrombocytopenic purpura, immune complex• Malevasculitis, typhus, ehrlichiosis and other rickettsial infections, en-• Absence of headache

• No history of tick attachment terovirus infection, typhoid fever, leptospirosis, infectious mono-• Delay in treatment nucleosis, and bacterial sepsis. Patients with prominent gastroin-• Gastrointestinal symptoms testinal symptoms may be misdiagnosed with gastroenteritis or• No treatment by the fifth day of illness

acute abdomen, and patients with pulmonary symptoms may beNOTE. Data are from [11], [25], and [29]. thought to have bronchitis or pneumonia [32].

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID



Table 3. Common laboratory findings in Rocky Mountain spotted choice for treatment of RMSF. Current recommendations in-fever. clude therapy with antibiotics for a minimum of 5–7 days and

until the patient has been afebrile for §2 days.• Peripheral WBC count usually normal

There are problems with the use of tetracyclines and chlor-• Thrombocytopeniaamphenicol. Repeated courses of treatment (five or more) with• Elevated aminotransferase levels

• Hyponatremia tetracyclines in children may cause permanent tooth discolor-• Anemia ation [40]. Doxycycline binds less strongly to calcium than• Increased bilirubin level other tetracyclines, and is therefore less likely to stain teeth• Increased creatine kinase level

[41]. The use of tetracyclines is contraindicated during preg-• Elevated CSF WBC count with monocyte predominancenancy because of the risk of temporary inhibition of bone• Serological tests negative until convalescence

growth and the risk of congenital malformations [42]. Chloram-NOTE. Data are from [13] and [15]. phenicol toxicities include a dose-related bone marrow suppres-

sion, idiosyncratic aplastic anemia unrelated to dose, and thegrey-baby syndrome, the latter two of which are fatal.

Antibiotic Treatment An additional consideration when deciding between thesetwo drug classes is the coverage of other possible organisms. IfThe only drugs proven to be effective in the treatment ofinfection due to Neisseria meningitidis is part of the differentialRMSF are the tetracyclines and chloramphenicol. In a largediagnosis of the patient’s illness, chloramphenicol might be theretrospective study, treatment with chloramphenicol was asso-treatment of choice, given that the agent is effective in theciated with a higher percentage of fatal outcomes than treatmenttreatment of both of these life-threatening infections. Doxycy-with tetracycline (8.2% vs. 1.6%) (figure 3). A confoundingcline is effective as therapy for ehrlichiosis, which may befactor of this analysis was the longer time between onset ofclinically indistinguishable from RMSF (at least one Ehrlichiasymptoms and initiation of treatment in the chloramphenicolchaffeensis isolate has been shown to be resistant to chloram-group (5 vs. 3 days). However, the median age of patientsphenicol in vitro [43]).receiving treatment with chloramphenicol was younger (7 vs.

The fluoroquinolones are a potential therapeutic option, al-28 years), and this difference should have resulted in an im-though their efficacy has not been demonstrated for treatmentproved outcome in the chloramphenicol group if the two antibi-of RMSF in humans. Ciprofloxacin therapy is adequate forotics were equivalent in efficacy [11]. Results of in vitro studiesmanagement of R. conorii, the rickettsia that causes Mediterra-have indicated that doxycycline has a lower MIC than eithernean spotted fever [44, 45]. The MIC of ciprofloxacin fortetracycline or chloramphenicol (MICs: 0.06–0.1, 0.25, andR. rickettsii is 1 mg/mL [46]. In dogs, chloramphenicol, en-0.3–0.5, respectively) [38, 39]. On the basis of these data, itrofloxacin, and tetracycline were found to be equally effectiveseems prudent to use doxycycline as the antibiotic of firstas therapy for RMSF [47]. Although there is reason to believethat the fluoroquinolones may be a good alternative to chloram-phenicol and the tetracyclines for the treatment of RMSF, itwould be difficult to study and implement the use of theseagents in humans since the risk of failure is increased mortality.

Prevention

There is no vaccine available against R. rickettsii, althoughRicketts demonstrated the existence of acquired immunity inguinea pigs almost 100 years ago. Promising leads for an effec-tive vaccine include major surface antigens of the bacteriumto which a protective immune response is directed [48–50].Prevention is possible through awareness: individuals who havebeen in tick-infested areas should habitually check themselvesand their children for the presence of ticks. Because ticks trans-

Figure 3. Case-fatality ratio for laboratory-confirmed cases of mit R. rickettsii after a minimum of 6 hours of attachment,Rocky Mountain spotted fever according to treatment group for all there is time for careful checking and removal before infectionpatients, hospitalized patients only, and patients 0–7 years of age. takes place. Patients should be instructed about proper tickNumbers above the bars represent the number of patients in each

removal, including removal of the entire tick without crushingsubset. Tet Å tetracycline; Chlor Å chloramphenicol. Reprinted withit. Further, the use of clothing that keeps individuals well-permission from American Journal of Tropical Medicine and Hygiene

[11]. covered and the use of tick repellents (permethrin on clothing

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID



20. Walker DH, Cain BG. The rickettsial plaque: evidence for direct cytopathicand DEET [N,N-diethyl-m-toluamide] on exposed skin) aid ineffect of Rickettsia rickettsii. Lab Invest 1980;43:388–96.the prevention of RMSF. Prophylactic treatment for patients

21. Walker DH, Firth WT, Edgell CS. Human endothelial cell culture plaqueswho have been bitten by ticks has not been shown to be useful, induced by Rickettsia rickettsii. Infect Immun 1982;37:301–6.and experimental studies have shown that prophylaxis merely 22. Walker DH, Popov Vl, Crocquet-Valdes PA, Welsh CJR, Feng H. Cyto-

kine-induced, nitric oxide-dependent, intracellular antirickettsial activityprolongs the incubation period.of mouse endothelial cells. Lab Invest 1997;76:129–38.

23. Feng H, Popov VL, Yuoh G, Walker DH. Role of T lymphocyte subsetsin immunity to spotted fever group rickettsiae. J Immunol 1997;158:References5314–20.

1. Harden VA. Rocky Mountain spotted fever. Baltimore: The Johns Hopkins 24. Walker DH, Lane TW. Rocky Mountain spotted fever: Clinical signs,University Press, 1990:18. symptoms, and pathophysiology. In: Walker DH, ed. Biology of Rickett-

2. Ricketts HT. Some aspects of Rocky Mountain spotted fever as shown by sial Diseases. Vol 1. Boca Raton: CRC Press, 1988:63–78.recent investigations. Rev Infect Dis 1991;13:1227–40. Reprinted from 25. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortalitythe Medical Record 1909;76:843–55. in Rocky Mountain spotted fever. Clin Infect Dis 1995;20:1118–21.

3. Wilson LB, Chowning WM. Studies in Pyroplasmosis hominis (‘‘spotted 26. Centers for Disease Control. Rocky Mountain spotted fever—Unitedfever’’ or ‘‘tick fever’’ of the Rocky Mountains). J Infect Dis 1904;1: States, 1990. MMWR Morb Mortal Wkly Rep 1991;40:451–9.31–57. 27. Kaplowitz LF, Fischer JJ, Sparling PF. Rocky Mountain spotted fever: a

4. Harden VA. Rocky Mountain spotted fever. Baltimore: The Johns Hopkins clinical dilemma. In: Remington JS, Swartz MN, eds. Current clinicalUniversity Press, 1990:104–5. topics in infectious diseases, Vol 2. New York: McGraw-Hill, 1981:

5. Woodward TE. Rickettsial diseases: certain unsettled problems in their 89–108.historical perspective. In: Burgdorfer W, Anacker RL, eds. Rickettsiae 28. Petri WA Jr. Tick-borne diseases: Am Fam Physician, 1988;37:95–104.and rickettsial diseases. New York: Academic Press, 1981;17–40. 29. Hattwick MAW, Retailliau H, O’Brien RJ, Slutzker M, Fontaine RE,

6. Harden VA. Rocky Mountain spotted fever. Baltimore: The Johns Hopkins Hanson B. Fatal Rocky Mountain spotted fever. JAMA 1978;240:1499–University Press, 1990:213–6. 1503.

7. Walker DH, Raoult D. Rickettsia rickettsii and other spotted fever group 30. Sexton DJ, Corey GR. Rocky Mountain ‘‘spotless’’ and ‘‘almost spotless’’rickettsiae (Rocky Mountain spotted fever and other spotted fevers). In: fever: a wolf in sheep’s clothing. Clin Infect Dis 1992;15:439–48.Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s 31. Archibald LK, Sexton DJ. Long-term sequelae of Rocky Mountain spottedprinciples and practice of infectious diseases. 4th ed. New York: fever. Clin Infect Dis 1995;20:1122–5.Churchill Livingstone, 1995:1721–7. 32. Walker DH. Rocky Mountain spotted fever: a seasonal alert. Clin Infect

8. Johnson JE, Kadull PJ. Rocky Mountain spotted fever acquired in a labora- Dis 1995;20:1111–7.tory. N Engl J Med 1967;277:842–7. 33. Walker DH, Hawkins HK, Hudson P. Fulminant Rocky Mountain spotted

9. Spach DH, Liles WC, Campbell GL, Quick RE, Anderson DE, Fritsche fever. Its pathologic characteristics associated with glucose-6-phosphateTR. Tick-borne diseases in the United States. N Engl J Med 1993;329: dehydrogenase deficiency. Arch Pathol Lab Med 1983;107:121–5.936–47. 34. Procop GW, Burchette JL, Howell DN, Sexton DJ. Immunoperoxidase

10. Centers for Disease Control and Prevention. Summary of notifiable dis- and immunofluorescent staining of Rickettsia rickettsii in skin biopsies:eases, United States, 1996. MMWR Morb Mortal Wkly Rep 1996; a comparative study. Arch Pathol Lab Med 1997;121:894–9.45:3. 35. Tzianabos T, Anderson BE, McDade JE. Detection of Rickettsia rickettsii

11. Dalton MJ, Clarke MJ, Holman RC, et al. National surveillance for Rocky DNA in clinical specimens by using polymerase chain reaction technol-Mountain spotted fever, 1981–1992: epidemiologic summary and eval- ogy. J Clin Microbiol 1989;27:2866–8.uation of risk factors for fatal outcome. Am J Trop Med Hyg 1995;52: 36. Sexton DJ, Kanj SS, Wilson K, et al. The use of a polymerase chain405–13. reaction as a diagnostic test for Rocky Mountain spotted fever. Am J

12. Wilfert CM, MacCormack JN, Kleeman K, et al. Epidemiology of Rocky Trop Med Hyg 1994;50:59–63.Mountain spotted fever as determined by active surveillance. J Infect 37. Kaplan JE, Schonberger LB. The sensitivity of various serological testsDis 1984;150:469–79. in the diagnosis of Rocky Mountain spotted fever. Am J Trop Med Hyg

13. Kirk JL, Fine DP, Sexton DJ, Muchmore HG. Rocky Mountain spotted 1986;35:840–4.fever: A clinical review based on 48 confirmed cases, 1943–1986. 38. Raoult D, Roussellier P, Vestris G, Tamalet J. In vitro antibiotic suscepti-Medicine (Baltimore) 1990;69:35–45. bility of Rickettsia rickettsii and Rickettsia conorii: plaque assay and

14. Hattwick MAW, O’Brien RJ, Hanson BF. Rocky Mountain spotted fever: microplaque colorimetric assay. J Infect Dis 1987;155:1059–62.epidemiology of an increasing problem. Ann Intern Med 1976;84: 39. Wisseman CL, Ordonez SV. Actions of antibiotics on Rickettsia rickettsii.732–9. J Infect Dis 1986;153:626–8.

15. Helmick CG, Bernard KW, D’Angelo LJ. Rocky Mountain spotted fever: 40. Grossman ER, Walchek A, Freedman H. Tetracyclines and permanentclinical, laboratory, and epidemiological features of 262 cases. J Infect teeth: the relation between dose and tooth color. Pediatrics 1971;47:Dis 1984;150:480–8. 567–70.

16. McDade JE, Newhouse VF. Natural history of Rickettsia rickettsii. Ann 41. von Wittenau MS. Some pharmacokinetic aspects of doxycycline metabo-Rev Microbiol 1986;40:287–309. lism in man. Chemotherapy 1968;13:41–50.

17. Walker DH, Lane TW. Pathology and pathogenesis of the vasculotropic 42. Cohlan SQ, Bevelander G, Tiamsic T. Growth inhibition of prematuresrickettsioses. In: Walker DH, ed. Biology of rickettsial diseases. Vol. receiving tetracycline. Am J Dis Child 1963;105:453–61.1. Boca Raton: CRC Press, 1988:115–38. 43. Brouqui P, Raoult D. In vitro susceptibility of the newly recognized agent

18. Li H, Walker DH. Characterization of rickettsial attachment to host cells of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob Agentsby flow cytometry. Infect Immun 1992;60:2030–3. Chemother 1992;36:2799–803.

19. Silverman DJ, Santucci LA, Meyers N, Sekeyova Z. Penetration of host 44. Beltran RR, Herrero JIH. Evaluation of ciprofloxacin and doxycycline incells by Rickettsia rickettsii appears to be mediated by a phospholipase the treatment of Mediterranean spotted fever. Eur J Clin Microbiol

Infect Dis 1992;11:427–31.of rickettsial origin. Infect Immun 1992;60:2733–40.

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID



45. Gudiol F, Pallares R, Carratala J, et al. Randomized double-blind evalua- 50. Sumner JW, Sims KG, Jones DC, Anderson BE. Protection of guinea-pigs from experimental Rocky Mountain spotted fever by immunizationtion of ciprofloxacin and doxycycline for Mediterranean spotted fever.

Antimicrob Agents Chemother 1989;33:987–8. with baculovirus-expressed Rickettsia rickettsii rOmpA protein. Vaccine1995;13:29–35.46. Jabarit-Aldighieri N, Torres H, Raoult D. Susceptibility of Rickettsia co-

norii, R. rickettsii, and Coxiella burnetti to PD 127,391, PD 131,628,pefloxacin, ofloxacin, and ciprofloxacin. Antimicrob Agents Chemother1992;36:2529–32.

The ‘‘Conflict-of-Interest Policy’’ of the Office of Con-47. Breitschwerdt EB, Davidson MG, Aucoin DP, et al. Efficacy of chloram-

tinuing Medical Education, UCLA School of Medicine,phenicol, enrofloxacin, and tetracycline for treatment of experimentalrequires that faculty participating in a CME activity dis-Rocky Mountain spotted fever in dogs. Antimicrob Agents Chemother

1991;35:2375–81. close to the audience any relationship with a pharmaceu-48. McDonald GA, Anacker RL, Garjian K. Cloned gene of Rickettsia rickett- tical or equipment company which might pose a poten-

sii surface antigen: candidate vaccine for Rocky Mountain spotted fever. tial, apparent, or real conflict of interest with regard toScience 1987;235:83–5.

their contribution to the program. The author reports no49. Anacker RL, List RH, Mann RE, Hayes SF, Thomas LA. Characterizationconflict of interest.of monoclonal antibodies protecting mice against Rickettsia rickettsii.

J Infect Dis 1985;151:1052–60.

/ 9c5c$$DE34 11-13-98 16:01:35 cidas UC: CID


1360

OFFICE OF CONTINUING MEDICAL EDUCATIONUCLA SCHOOL OF MEDICINE

This test affords you the opportunity to assess your knowl- C. 20–30 days.edge and understanding of the material presented in the preced- D. 2–4 months.ing clinical article, ‘‘Rocky Mountain Spotted Fever,’’ by Anna 4. Possible complications of Rocky Mountain spotted feverR. Thorner, David H. Walker, and William A. Petri, Jr., and include all of the following except:to earn continuing medical education (CME) credit. A. adult respiratory distress syndrome

B. renal failureCME Sponsor C. thyroiditis

D. coagulopathyThe Office of Continuing Medical Education, UCLA School5. The classic triad of Rocky Mountain spotted fever is:of Medicine, is accredited by the Accreditation Council for

Continuing Medical Education to sponsor continuing medical A. fever, rash, and history of a tick bite.education for physicians. B. fever, rash, and abdominal pain.

C. rash, myalgias, and history of a tick bite.Accreditation D. rash, age õ25 years, and history of a tick bite.

6. Serological testing for Rocky Mountain spotted fever:The Office of Continuing Medical Education, UCLAA. is essential for making the diagnosis.School of Medicine, designates this educational activity forB. is most sensitive within the first 3 days of infection.up to 1 hour in category I credit toward the AMA Physician’s

Recognition Award. Each physician should claim only those C. remains diagnostic for 2 years after the acute infection.hours of credit that he/she actually spent in the educational D. is usually useful during only the convalescent stage.activity. 7. The states with the highest incidence of Rocky Mountain

To earn credit, read the State-of-the-Art Clinical Article care- spotted fever are:fully and answer the following questions. Mark your answers, A. Virginia and Maryland.only one answer per question, by circling the correct responses

B. Connecticut and New Jersey.on the answer card (usually found toward the front of the issue),

C. Oklahoma and North Carolina.and mail this card after affixing first-class postage. To earnD. Montana and Colorado.credit, a minimum score of 80% must be obtained.

8. Among cases of Rocky Mountain spotted fever, patientsCertificates of CME credit will be awarded on a per-volumereport tick exposure up to percent of the time.(biannual) basis. Each answer card must be submitted within

3 months of the date of the issue. A. 20

B. 551. The most frequent initial presentation of Rocky Mountain C. 85

spotted fever is: D. 98A. fever and headache. 9. Factors associated with a fatal outcome in Rocky MountainB. fever and macular rash. spotted fever include all of the following except:

C. fever and petechial rash on the palms and soles. A. rash appearing late in the disease course

B. young ageD. fever and meningitis.C. atypical symptoms2. An effective treatment for Rocky Mountain spotted feverD. no history of tick biteis:

10. The fluoroquinolones:A. erythromycin.A. are an excellent alternative to the tetracyclines for theB. doxycycline.

treatment of Rocky Mountain spotted fever in children.C. penicillin.

B. have been proven to be ineffective in the eradicationD. ciprofloxacin. of Rocky Mountain spotted fever in humans.

3. The incubation period between the tick bite and the onset C. have been found to be effective against Rocky Moun-of Rocky Mountain spotted fever symptoms is: tain spotted fever in dogs and in vitro.A. 24–48 hours. D. have been proven to be effective in the treatment of

Rocky Mountain spotted fever in adult humans.B. 2–14 days.

/ 9c5c$$$cme 11-10-98 20:30:14 cida UC: CID


Documents

Rocky Mountain Spotted Fever€¦ · The incubation period of Rocky Mountain spotted fever is Rickettsiae introduced through the skin spread via the lymphat- 2 to 14 days after the