Rosalie Sagraves, PharmD Associate Professor of Pharmacy Practice College of Pharmacy Adjunct Associate Professor of Pediatrics College of Medicine University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma

Treatment of .Rocky Mountain n Spotted Fever n Claudia

Kamper,

R

Mountain spotted fever (RMSF) is an acute, febrile, potentially fatal disease. The disease was first recognized on the North American continent by Native Americans who, even then, noted an association between RMSF and activities in wooded areas (Kelsey, 1979). Later,, through the discovery and description of the causative agent, vector, and method of transmission of the infection by Dr. Howard Taylor Ricketts in the early 19OOs, an understanding of the association of the disease to wooded areas became clear (Ricketts, 1906a; Ricketts, 1906b; Ricketts, 1909). Despite improved diagnostic methods and detailed descriptions of the typical clinical manifestations of the disease, RMSF may elude correct diagnosis by mimicking a host of conditions from influenza to ischemic heart disease. In keeping with this uncharacteristic behavior, Kubala and Losh (1989) have called Rocky Mountain spotted fever ‘the great mimicker.” Cases of RMSF in the United States have been reported to the Centers for Disease Control (CDC) since 1920, with two distinct periods of higher incidence occurring during the 1940s and 1950s and later during the late 1970s and early 1980s (Centers for Disease Control, 1985; Hattwick, Peters, Gregg, & Hanson, 1973). The overall incidence of RMSF peaked in 198 1 with 1192 reported cases (0.5 1 / 100,000 persons in the United Statesll. Over the past 6 years, the overall national incidence has remained between 0.25 and 0.35. Oklahoma consistently reports the highest incidence o&y

Claudia Kamper is as’sistant professor in the College of Pharmacy at The University of Oklahoma Health Sciences Center, The University of Oklahoma, and clinical pediatric specialist at Children’s Hospital of Oklahoma, Oklahoma City, Oklahoma.

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(1.9 to 3.2 cases/ 100,000 population), and North Carolina usually reports the highest number of cases (108 to 206 cases) (CDC, 1986; CDC, 1987; CDC, 1988; CDC, 1989; CDC, 1990). Figure 1 depicts the incidence of RMSF in Oklahoma and North Carolina compared with the overall United States totals for the years 1983 through 1989. n

EPIDEMIOLOGY

Rocky Mountain

spotted fever originally was reported states. Since that time, two areas have been identified as endemic: the south Atlantic states and the West South Central region. These regions are responsible for approximately 54% of reported cases, while the Rocky Mountain states now account for less than 5% of all casesin the United States (CDC, 1990; Hattwick, O’Brien, & Hanson, 1976). Although related organisms may cause vector-borne disease in humans, Rickettsia tikets#, which causes RMSF, has not been reported outside the western hemisphere (McDade & Newhouse, 1986; Walker, 1989). Originally associated with heavily wooded areas, unusual small endemic “islands” with distinct ecological habitats have been documented within larger uninfected areas (Linneman, Jansen, & Schiff, 1973). Spread from rural to urban areas also has been noted with the report of three casesof RMSF traced to a park in the Bronx (Salgo et al., 1988). The majority of cases occur in the spring and summer months between April and October, reflecting the life cycle and seasonal activity of the tick vector (CDC, 1984; Zaki, 1989). Approximately 50% of cases occur in persons less than 19 years old, with children aged 5 to 9 years being most frequently affected. The incidence is higher in males and Caucasians. in the Rocky Mountain

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Journal of Pediatric Health

The overall case-fatality rate has decreased from an average of about 4% to 1.2% in 1989. It continues to be higher with increasing age, the absence of a tick exposure history, und a delay in appropriate therapy (CDC, 1990). n

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MICROBIOLOGY

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United States Total Oklahoma North Carolina

R. rickatsii, the etiologic agent responsible for RMSF, is one of several spotted fever rickettsioses known throughout the world. R. vickettsii and related organisms are small, gram-negative, obligate intracellular bacteria that contain both RNA and DNA that are capable of invading the nucleus of host cells. n

PATHOCENESIS/TRANSMISSlON

Transmission of the rickettsial organism is geographically specific. The wood tick (Dermacentm adersom) is the transmitting tick in the West, the dog tick (DOmace&or variabih) in the East, and the Lone Star tick (Amblyomma amnkanum) in the Southwest. The reservoir, or continual source of infection, is maintained through transovarial passage of the rickettsiae from an adult female tick to her many offspring. Efficiency of transmission can reach 100%. Several factors contribute to the high incidence of infection in certain heavily tick infested areas: 1) survival of rickettsiae within hibernating ticks during freezing temperatures without loss of virulence, 2) life span of 2 to 5 years with repeated transmission to offspring, and 3) reactivation of w1 virulence with the first blood meal. Human disease occurs subsequent to transdermal transmission of the organism through infected tick saliva, feces, or tissue juices. Needle and aerosol transmission have been reported but rarely occur (Johnson & Kadull, 1967; Oster et al., 1977; Sexton, Gallis, McRae, & Cate, 1975). The prevalence of disease-laden ticks varies with the region. In general, wooded and uncultivated areas have a greater percentage of both infected and noninfected ticks. Some areas of Oklahoma, the state with the consistently highest incidence of RMSF cases, have been reported to have up to 14,000 ticks per acre (Sonenshine, Peters, & Levy, 1972). n

cLiNicAL

MA,NIFESTATIONS

Traditionally, a triad of symptoms has been associated with early disease. This triad consists of fever, headache, and rash (Haynes, Sanders, & Cramblett, 1970), and it is present in approximately 50% of cases (CDC, 1990). A history of tick bite or exposure is present in only 46% to 70% of confirmed cases (Haynes et al., 1970; R~z~010 & Addison, 1989). Two to 14 days generally is required for incubation; the average is 7 days. A short incubation period may be associated with severe disease (Wright &Trott, 1988). Onset of the nonspecific symp-

Ol 1982

1984

n FIGURE 1 Rocky Mountain States, 1983-l 989.

1986

1900

1990

spotted fever in the United

toms is usually quite acute. Significant fever (>39” C) usually unresponsive to antipyretics or antibiotics is present in the majority of patients in the first few days of infection, but may precede other signs and symptoms by a week or more (Haynes et al., 1970; Kelsey, 1979). A frontal headache unresponsive to analgesics, malaise, myalgias, nausea, and emesis often precede or accompany the fever. Abdominal pain, hepatomegaly, splenomegaly, anorexia, and diarrhea may be the initial symptoms in many cases. Diarrhea was specifically noted to be absent in one pediatric series, however (Haynes et al., 1970). Central nervous system involvement may also be present (57% of cases) with stupor, ataxia, and meningismus (Haynes et al., 1970). The rash associated with RMSF is said to be characteristic. When present (84% to 96% of laboratoryconfirmed cases) the rash usually occurs by day 5, but this may vary from day 1 to day 8 (Hattwick et al., 1976; CDC, 1984). The initial lesions are discrete, small (2 to 6 mm), irregular, pink macules or maculopapular areas usually found first on the ankles and soles of the feet, wrists, and hands (including the palms), and scrotum (correlating well with preferred temperature