Article: Rocky Mountain spotted fever

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Ixodidae

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Rickettsia

Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States, and has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include "tick typhus", "Tobia fever" (Colombia), "São Paulo fever" and "febre maculosa" (Brazil), and "fiebre manchada" (Mexico). The disease is caused by Rickettsia rickettsii, a species of bacteria that is spread to humans by hard ticks (Ixodidae). Initial signs and symptoms of the disease 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.

Rocky Mountain spotted fever was first recognized in 1896 in the Snake River Valley of Idaho and was originally called "black measles" because of the characteristic rash. It was a dreaded and frequently fatal disease that affected hundreds of people in this area. By the early 1900s, the recognized geographic distribution of this disease grew to encompass parts of the United States as far north as Washington and Montana and as far south as California, Arizona, and New Mexico.

Howard T. Ricketts was the first to establish the identity of the infectious organism that causes this disease. He and others characterized the basic epidemiological features of the disease, including the role of tick vectors. Their studies found that Rocky Mountain spotted fever is caused by Rickettsia rickettsii. This species is maintained in nature by a complex cycle involving ticks and mammals; humans are considered to be accidental hosts and are not involved in the natural transmission cycle of this pathogen. Tragically, Dr. Ricketts died of typhus (another rickettsial disease) in Mexico in 1910, shortly after completing his remarkable studies on Rocky Mountain spotted fever.

The name Rocky Mountain spotted fever is somewhat of a misnomer. Beginning in the 1930s, it became clear that this disease occurred in many areas of the United States other than the Rocky Mountain region. It is now recognized that this disease is broadly distributed throughout the continental United States, as well as southern Canada, Central America, Mexico, and parts of South America. Between 1981 and 1996, this disease was reported from every U.S. state except Hawaii, Vermont, Maine, and Alaska.

Rocky Mountain spotted fever remains a serious and potentially life-threatening infectious disease today. Despite the availability of effective treatment and advances in medical care, approximately 3% to 5% of individuals who become ill with Rocky Mountain spotted fever still die from the infection. However, effective antibiotic therapy has dramatically reduced the number of deaths caused by Rocky Mountain spotted fever; before the discovery of tetracycline and chloramphenicol in the late 1940s, as many as 30% of persons infected with R. rickettsii died.

Natural history

Rocky Mountain spotted fever, like all rickettsial infections, is classified as a zoonosis. Zoonoses are diseases of animals that can be transmitted to humans. Many zoonotic diseases require a vector (e.g., a mosquito, tick, or mite) in order to be transmitted from the animal host to the human host. In the case of Rocky Mountain spotted fever, ticks are the natural hosts, serving as both reservoirs and vectors of R. rickettsii. Ticks transmit the organism to vertebrates primarily by their bite. Less commonly, infections may occur following exposure to crushed tick tissues, fluids, or tick feces.

The life cycle of Dermacentor variabilis and Dermacentor andersoni ticks (Family Ixodidae)

Only members of the tick family Ixodidae (hard ticks) are naturally infected with Rickettsia rickettsii. These ticks have four stages in their life cycle: egg, larva, nymph, and adult. After the eggs hatch, each stage must feed once to develop into the next stage. Both male and female ticks will bite.

A female tick can transmit R. rickettsii to her eggs in a process called transovarial transmission. Ticks can also become infected with R. rickettsii while feeding on blood from the host in either the larval or nymphal stage. After the tick develops into the next stage, the R. rickettsii may be transmitted to the 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. These types of transmission represent how generations or life stages of infected ticks are maintained. Once infected, the tick can carry the pathogen for life.

Rickettsiae are transmitted to a vertebrate host through saliva while a tick is feeding. It usually takes several hours of attachment and feeding before the rickettsiae are transmitted to the host. The risk of exposure to a tick carrying R. rickettsii is low. In general, about 1%-3% of the tick population carries R. rickettsii, even in areas where the majority of human cases are reported.

There are two major vectors of R. rickettsii in the United States, the American dog tick and the Rocky Mountain wood tick. American dog ticks (Dermacentor variabilis) are 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. This tick is the most commonly identified species responsible for transmitting R. rickettsii to humans. Rocky Mountain wood ticks (Dermacentor andersoni) 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.

Other tick species have been shown to be naturally infected with R. rickettsii or serve as experimental vectors in the laboratory. However, these species are likely to play only a minor role in the ecology of R. rickettsii.

Epidemiology

Rocky Mountain spotted fever has been a reportable disease in the United States since 1918. In the last 50 years, approximately 250-1200 cases of Rocky Mountain spotted fever have been reported annually, although it is likely that many more cases go unreported (source: United States Centers for Disease Control).

Over 90% of patients with Rocky Mountain spotted fever are infected during April through August. This period is the season for increased numbers of adult and nymphal Dermacentor ticks. A history of tick bite or exposure to tick-infested habitats is reported in approximately 60% of all cases of Rocky Mountain spotted fever.

Over half of U.S. Rocky Mountain spotted fever infections are reported from 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 in other parts of the United States, namely the Pacific region (Washington, Oregon, and California) and west south-central (Arkansas, Louisiana, Oklahoma, and Texas) region.

The states with the highest incidences of Rocky Mountain spotted fever are North Carolina and Oklahoma; these two states combined accounted for 35% of the total number of U.S. cases reported to CDC during 1993 through 1996. Although Rocky Mountain spotted fever was first identified in the Rocky Mountain states, less than 3% of the U.S. cases were reported from that area during the same interval (1993-1996).

The frequency of reported cases of Rocky Mountain spotted fever is highest among males, Caucasians, and children. Two-thirds of the Rocky Mountain spotted fever cases occur in children under the age of 15 years, with the peak age being 5 to 9 years old. Individuals with frequent exposure to dogs and who reside near wooded areas or areas with high grass may also be at increased risk of infection.

Infection with Rickettsia rickettsii has also been documented in Argentina, Brazil, Colombia, Costa Rica, Mexico, and Panama. Closely related organisms cause other types of spotted fevers in other parts of the world.

Signs and symptoms

Petechial rash caused by rocky mountain spotted fever on the arm

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 1-14 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
• lack of appetite

Later signs and symptoms include:

• petechial rash
• abdominal pain
• joint pain
• 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. 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. 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.

Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include thrombocytopenia, hyponatremia, or elevated liver enzyme levels.

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.

Treatment

Appropriate antibiotic treatment is initiated immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiological 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 Rocky Mountain spotted fever. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive 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 (For adults, 100 mg every 12 hours. For children under 45 kg [100 lb], 4 mg/kg body weight per day in two divided doses) 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.

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 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.

"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." -Tom Brousseau