All rickettsial diseases are zoonoses; the animal host depends on which tick vector feeds on blood from the host in either the larval, nymphal, or adult stage. After an immature tick develops into the next stage, R. rickettsii may be transmitted to a second host during the feeding process. Furthermore, male ticks may transfer R. rickettsii to female ticks through body fluids or spermatozoa during the mating process. Once infected, a tick can carry the pathogen for life; it does not harm the tick. A female tick can also transmit R. rickettsii to her eggs in a process called transovarial transmission. 
Not all rickettsiae can transmit through generations of arthropods as does this organism. In the U.S., the major vectors are the American dog tick (Dermacentor variabilis) and the Rocky Mountain wood tick (Dermacentor andersoni). Other ticks appear to be involved in natural transmission in Central and South America.
American dog ticks, the most common vector, sare 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.
Rocky Mountain wood ticks are found in the Rocky Mountain states and in southwestern Canada. The life cycle of this tick may require up to 2 to 3 years for completion. Adult ticks feed primarily on large mammals. Larvae and nymphs feed on small rodents.
"Although it is technically feasible, specific rapid laboratory confirmation of early Rocky Mountain spotted fever is rarely done. Therefore, treatment decisions should be based on epidemiologic and clinical clues, and should never be delayed while waiting for confirmation by laboratory results. Fundamental understanding of the signs, symptoms, and epidemiology of the disease is crucial in guiding requests for tests for Rocky Mountain spotted fever, sample collection and submission, and interpretation of laboratory results."
"Serologic assays are the most widely available and frequently used methods for confirming cases of Rocky Mountain spotted fever. The indirect immunofluorescence assay (IFA)...The most rapid and specific diagnostic assays for Rocky Mountain spotted fever rely on molecular methods like PCR which can detect DNA present in 5-10 rickettsiae in a sample. While organisms can be detected in whole blood samples obtained at the acute onset of illness in a few hours, rickettsial DNA is most readily detected in fresh skin biopsies like those used in immunostaining procedures. PCR can also be done on the fixed tissues used in immunostaining, but it is less sensitive than with unfixed tissues. PCR methods can be R. rickettsii-specific but are usually confirmed by DNA sequencing of the amplified gene fragments. Consequently, this procedure is more specific than antibody-based methods which are often only genus or spotted fever group-specific.
- Centers for Disease Control (20 May 2005), Rocky Mountain Spotted Fever Home > Natural History
- Centers for Disease Control (20 May 2005), Rocky Mountain Spotted Fever Home > Laboratory Detection