THE GENUS RICKETTSIA

The genus Rickettsia includes some of the most highly virulent bacteria known. Historically, it has been divided into the typhus and the spotted fever groups. The former contains the human pathogens Rickettsia typhi and Rickettsia prowazekii, whereas the spotted fever group contains species africae, akari, australis, conorii, felis, honei, japonica, montana, rickettsii, and rhipicephali, most of which are human pathogens. Dogs may be naturally infected with rickettsiae (R. akari, R. conorii, R. montana, and R. rhipicephali), as well as cats (R. typhi, R. felis, and R. conorii), but no overt signs of disease are exhibited. Dogs and cats may serve as sentinel species for these rickettsiae.

The phylogeny of this genus has recently been delineated by sequence analysis of 16S rDNA, and of genes for citrate synthase, rickettsial outer-membrane proteins, and cytoplasmic antigenic protein genes. As a result, the genus Rickettsia currently contains 21 species with several agents described as species incertae sedis.

Rickettsia rickettsii

Rickettsia rickettsii is pathogenic for humans and other animals, and causes Rocky Mountain spotted fever (RMSF) in the former. RMSF was first recognized in 1896 in humans residing in the Snake River Valley of Idaho, where it was originally known as “black measles” because of its characteristic rash. It was a dreaded and frequently fatal disease that affected hundreds of people in the region. The geographic distribution of RMSF has grown to encompass most of the continental United States, as well as portions of southern Canada, Central America, Mexico, and South America. Thus RMSF has become a misnomer.

Rickettsia rickettsii is a very small gram-negative intracellular bacterium that ranges in size from 0.2 × 0.5 µm to 0.3 × 2 µm. These organisms are difficult to see in tissues stained by routine methods, and generally require the use of special staining methods (i.e., immunohistochemical or fluorescent antibody). The bacteria are present in the cytoplasm of infected cells (Figure 43-1).

FIGURE 43-1 Transmission electron photomicrograph of multiple Orientia tsutsugamushi free in the cytoplasm of a murine capillary endothelial cell.

(Courtesy Public Health Image Library, PHIL #928, Centers for Disease Control and Prevention, Atlanta, 1977, Edwin P. Ewing, Jr.)

DISEASE AND EPIDEMIOLOGY

Howard Ricketts established the identity of the etiologic agent of RMSF and described basic epidemiologic features of the disease, including the role of the tick. Humans and dogs are accidental hosts, and are the only species that display clinical illness. Natural transmission among dogs or humans, or between dogs and humans, does not occur in the absence of a vector.

RMSF, like all other rickettsial infections, is a zoonosis. Many of these diseases require a vector (e.g., a mosquito, tick, or mite) in order to be transmitted from the animal to human. Ticks are the natural hosts of RMSF, serving as both reservoirs and vectors of R. rickettsii. Transmission is primarily by bites, but may occur following exposure to crushed tick tissues, fluids, or feces. Only members of the tick family Ixodidae (hard ticks) are naturally infected with R. rickettsii. These ticks have four stages in their life cycle (egg, larva, nymph, and adult), across which transmission can occur. Transovarial transmission also occurs. Larval or nymphal ticks can become infected during feeding. Furthermore, male ticks may transfer R. rickettsii to female ticks through body fluids or spermatozoa during the mating process. The infected tick can maintain the pathogen for life.

The risk of exposure to a tick carrying R. rickettsii is relatively low because only 1% to 3% of the tick population carries R. rickettsii, even in areas where most human cases are reported. Transmission of rickettsiae by feeding ticks requires 6 to 20 hours of attachment and feeding.

The two major vectors of R. rickettsii in the United States are the American dog tick (Dermacentor variabilis) and the Rocky Mountain wood tick (Dermacentor andersoni) (Figure 43-2). The former is widely distributed east of the Rocky Mountains and also occurs in limited areas on the Pacific Coast. Dogs and medium-sized mammals are the preferred hosts of adult D. variabilis, although it feeds readily on other large mammals, including humans. It is the species most often responsible for transmitting R. rickettsii to humans and dogs. Dogs are sensitive indicators of the presence of disease, and they represent important transport hosts because they bring ticks into contact with humans.

FIGURE 43-2 Natural history of Rickettsia rickettsii infection.

Dermacentor andersoni is primarily found in the Rocky Mountain states and in southwestern Canada. The life cycle of this tick may require as long as 2 to 3 years for completion. Adult ticks feed primarily on large mammals, and larvae and nymphs feed on small rodents. Other tick species can be naturally infected with R. rickettsii or serve as experimental vectors in the laboratory (Rhipicephalus sanguineus and Amblyomma americanum), but these species are unlikely to play a major role in the ecology of R. rickettsii in the United States. In Mexico and South America, however, Amblyomma cajennense and R. sanguineus are commonly involved in transmission of RMSF to humans.

Human RMSF has been a reportable disease in the United States since the 1920s, and in the past 50 years there have been 250 to 1200 cases reported annually. It is likely that many more cases go unreported. More than 90% of patients with RMSF are infected from April through September, when the prevalence of adult and immature ticks is at its highest.

More than half of RMSF cases occur in the south Atlantic region of the United States (Delaware, Maryland, Washington, D.C., Virginia, West Virginia, North Carolina, South Carolina, Georgia, and Florida). Infection also occurs elsewhere in the country, including the Pacific Coast (Washington, Oregon, and California) and western south-central (Arkansas, Louisiana, Oklahoma, and Texas) regions. The highest incidence of RMSF is in North Carolina and Oklahoma, which, combined, accounted for 35% of all cases reported to the Centers for Disease Control and Prevention (CDC) from 1993 through 1996.

RMSF is the most severe and frequently reported rickettsial illness of humans in the United States. Initial symptoms include sudden onset of fever, headache, and muscle pain, followed by development of rash. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment it can be fatal; the case fatality rate is 3% to 5%.

Dogs are the only susceptible domestic species. Infection occurs more commonly in dogs younger than 2 years of age and in purebreds, especially German shepherds and English springer spaniels. The latter may have a genetic deficiency of phosphofructokinase production and are more likely to develop fulminant disease. Illness occurs most frequently between March and October.

Canine disease may be clinical or subclinical. Fever, occurring 4 to 5 days after contact with an infected tick, is the most consistent finding. The incubation period ranges from 2 days to 2 weeks. Cutaneous lesions include hyperemia and edema of the extremities, and pinna of the ears, lips, penile sheath, and scrotum. Petechial and ecchymotic hemorrhages may be found on the oral, genital, or ocular mucous membranes. Other clinical findings are vague and may include polyarthritis, myalgia, abdominal pain, vestibular deficits, anorexia, and altered mental status. In the latter stages of illness, necrosis of the extremities or nasal planum has been reported.