Signs and Symptoms
Rocky Mountain spotted fever can be very difficult to diagnose in its early stages, even among experienced physicians who are familiar with the disease. Patients infected with R. rickettsii generally visit a physician in the first week of their illness, following an incubation period of about 5-10 days after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and non-infectious diseases.

Initial symptoms may include fever, nausea, vomiting, severe headache, muscle pain, and lack of appetite. Later signs and symptoms include rash, abdominal pain, joint pain and diarrhea.

The classic triad of findings for this disease are fever, rash, and history of tick bite. However, this combination is often not identified when the patient initially presents for care. The rash first appears 2-5 days after the onset of fever and is often not present or may be very subtle when the patient is initially seen by a physician. Younger patients usually develop the rash earlier than older patients. Most often it begins as small, flat, pink, non-itchy spots (macules) on the wrists, forearms, and ankles (Figure 13). These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted (petechial) rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after onset of symptoms, and this type of rash occurs in only 35% to 60% of patients with Rocky Mountain spotted fever (Figure 14). The rash involves the palms or soles in as many as 50% to 80% of patients; however, this distribution may not occur until later in the course of the disease. As many as 10% to 15% of patients may never develop a rash.

Figure 13. Early (macular) rash on sole of foot. (CDC)
 

Figure 14. Late (petechial) rash on palm and forearm. (CDC)

Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because R. rickettsii  infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or renal system. Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African-American race, chronic alcohol abuse, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a sex-linked genetic condition affecting approximately 12% of the U.S. African-American male population; deficiency of this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever. This is a rare clinical course that is often fatal within 5 days of onset of illness.

Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations.
 

Laboratory Diagnosis
There is no widely available laboratory assay that provides rapid confirmation of early Rocky Mountain spotted fever. Treatment decisions must be based on epidemiologic and clinical clues, and should never be delayed while waiting for confirmation by 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) is generally considered the reference standard in Rocky Mountain spotted fever serology and is the test currently used by CDC and most state public health laboratories (Figure 15).

Figure 15. IFA reaction of a positive human serum on Rickettsia rickettsii grown in chicken yolk sacs, 400X. (CDC)

IFA can be used to detect either IgG or IgM antibodies. Blood samples taken early (acute) and late (convalescent) in the disease are the preferred specimens for evaluation. Most patients demonstrate increased IgM titers by the end of the first week of illness. Diagnostic levels of IgG antibody generally do not appear until 7-10 days after the onset of illness. It is important to consider the amount of time it takes for antibodies to appear when ordering laboratory tests, especially because most patients visit their physician relatively early in the course of the illness, before diagnostic antibody levels may be present. The value of testing two sequential serum or plasma samples together to show a rising antibody level is considerably more important in confirming acute infection with rickettsial agents because antibody titers may persist in some patients for years after the original exposure.

Another approach to Rocky Mountain spotted fever diagnostics is immunostaining. This method is used by taking a skin biopsy of the rash from an infected patient prior to therapy or within the first 48 hours after antibiotic therapy has been started. Because rickettsiae are focally distributed in lesions of Rocky Mountain spotted fever, this test may not always detect the agent. Even in laboratories with expertise in performing this test, the sensitivity is only about 70% on biopsied tissues. This assay may also be used to test tissues obtained at autopsy and has been used to confirm Rocky Mountain spotted fever in otherwise unexplained deaths (Figure 16). Immunostaining for spotted fever group rickettsiae is offered by the CDC, a few state health departments, and some university-based hospitals and commercial laboratories in the United States.

Figure 16. Red structures indicate immunohistological staining of Rickettsia rickettsii in endothelial cells of a blood vessel from a patient with fatal RMSF. (CDC)
 

Treatment
Appropriate antibiotic treatment should be initiated immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiologic findings. Treatment should not be delayed until laboratory confirmation is obtained.

If the patient is treated within the first 4-5 days of the disease, fever generally subsides within 24-72 hours after treatment with an appropriate antibiotic (usually a tetracycline). In fact, failure to respond to a tetracycline antibiotic argues against a diagnosis of RMSF. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Prophylactic therapy in non-ill patients who have had recent tick bites is not recommended and may, in fact, only delay the onset of disease.

Doxycycline (100 mg every 12 hours for adults or 4 mg/kg body weight per day in two divided doses for children under 45 kg [100 lb.]) is the drug of choice for patients with Rocky Mountain spotted fever. Therapy is continued for at least 3 days after fever subsides and until there is unequivocal evidence of clinical improvement, generally for a minimum total course of 5 to 10 days. Severe or complicated disease may require longer treatment courses. Doxycycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble Rocky Mountain spotted fever.

Tetracyclines are usually not the preferred drug for use in pregnant women because of risks associated with malformation of teeth and bones in unborn children. Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever; however, this drug may be associated with a wide range of side effects including aplastic anemia, and may require careful monitoring of blood levels.

Prevention and Control
Limiting exposure to ticks is the most effective way to reduce the likelihood of Rocky Mountain spotted fever infection. In persons exposed to tick-infested habitats, prompt careful inspection and removal of crawling or attached ticks is an important method of preventing disease. It may take several hours of attachment before organisms are transmitted from the tick to the host.

Currently, no licensed vaccine is available for Rocky Mountain spotted fever.

It is unreasonable to assume that a person can completely eliminate activities that may result in tick exposure. Therefore, prevention measures should be aimed at personal protection. CDC recommends the following prevention measures:

-Wear light-colored clothing to allow you to see ticks that are crawling on your clothing.

-Tuck your pants legs into your socks so that ticks cannot crawl up the inside of your pants legs.

-Apply repellents to discourage tick attachment. Repellents containing permethrin can be sprayed on boots and clothing, and will last for several days. Repellents containing DEET (diethyltoluamide) can be applied to the skin, but will last only a few hours before reapplication is necessary. Use DEET with caution on children. Application of large amounts of DEET on children has been associated with adverse reactions.

-Conduct a body check upon return from potentially tick-infested areas by searching your entire body for ticks. Use a hand-held or full-length mirror to view all parts of your body.

-Remove any tick you find on your body. Parents should check their children for ticks, especially in the hair, when returning from potentially tick-infested areas. Additionally, ticks may be carried into the household on clothing and pets. Both should be examined carefully.

Tick Control
Strategies to reduce populations of vector ticks through area-wide application of acaricides (chemicals that will kill ticks and mites) and control of tick habitats (e.g., leaf litter and brush) have been effective in small-scale trials. New methods being developed include applying acaricides to rodents by using baited tubes, boxes, and feeding stations in areas where these pathogens are endemic. Biological control with fungi, parasitic nematodes, and parasitic wasps may play alternate roles in integrated tick control efforts. Community-based, integrated, tick-management strategies may prove to be an effective public health response to reduce the incidence of tick-borne infections. However, limiting exposure to ticks is currently the most effective method of prevention.