Pediatric Rocky Mountain Spotted Fever

Rocky Mountain spotted fever (RMSF) is the most common rickettsial infection and the second most commonly reported tick-borne disease (after Lyme disease) in the United States. RMSF is a member of the spotted fever group of rickettsial infections. RMSF gets its name from the initial epidemiological description in the Rocky Mountain region of the United States. It is a reportable disease in the United States to state or local health departments.

The causative agent is Rickettsia rickettsii (named after Howard T. Ricketts, the discoverer of the organism).

RMSF was first described in the late 1800s in the Bitterroot Valley of Idaho, and for several decades, the disease was thought to be limited to the Rocky Mountain area; however, it now has a high documented prevalence in the eastern United States. More than 60% of cases are reported in five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri).

The disease is spread mainly through the bites of infected ticks. The dog tick, wood tick, and Lone Star tick are all potential vectors and are responsible for RMSF in different parts of the United States. The distribution of RMSF disease parallels tick activity during peak season.

RMSF has the highest mortality of any tick-borne illness in the United States (up to 30%). Because of this, the Rocky Mountain Laboratory was established in Hamilton, Montana, to help investigate the disease. This laboratory is now part of the National Institute of Allergy and Infectious Diseases (NIAID).

Early treatment is critical to the outcome in RMSF and must be started on the basis of clinical diagnosis. Consider the possibility of RMSF in any child with potential tick exposure who develops fever, myalgia, or headache, even if they do not have a rash. If suspected, promptly begin antibiotic (doxycycline) treatment even before confirmation of the diagnosis, as delay in the initiation of treatment is associated with significantly higher mortality.

For additional discussion of the disease, see Rocky Mountain Spotted Fever. For patient education information, see the Bites and Stings Center, as well as Ticks.

Rocky Mountain spotted fever is a diffuse, small-vessel vasculitis. R rickettsii is a small (0.1-0.3 μ) nonmotile gram-negative, obligate intracellular coccobacillus, with a tropism for human endothelial cells.The plasma membrane of mammalian cells, expresses Ku70, which serves as a receptor for the outer surface proteins of OmpA, OmpB and sca 1 for R rickettsii attachment and subsequent phagocytoses by the host cell. It resides in the cytosol and less commonly in the nuclei of the host cells and divides via binary fission. This bacterium causes membrane disruption and increased permeability.

Possible mechanisms for cellular injury include injury to the cell membrane, depletion of adenosine 5-triphosphate (which leads to failure of the sodium pump), and damage to the cell caused by toxic products of rickettsial metabolism.

Vascular lesions are responsible for the clinical manifestations, including rash, headache, alteration in the level of consciousness, heart failure, and shock. Vascular lesions can be found throughout the body, with highest predilection for the skin, gonads, and adrenal glands.

Profound hyponatremia is common. Several mechanisms have been postulated, including a shift in water from the intracellular spaces to the extracellular spaces; increased loss of sodium in the urine; and an exchange of sodium for potassium at the cellular level. ^[4]

Edema of the medulla oblongata may contribute to fatality in some patients.

Concentrations of antidiuretic hormone and aldosterone are increased in some patients.

Ticks are the natural hosts, reservoirs, and vectors of R rickettsii. The species of tick acting as the vector varies by geographic location. R rickettsii is usually transmitted to humans by the bite of an infected tick. On occasion, transmission occurs by scratching or rubbing infectious tick feces into the skin.

Adult ticks transmit the disease to humans during feeding. At least 6 hours of tick attachment is needed for the transmission of R rickettsii.

Primary hosts of R rickettsii include the following {ref16-INVALID REFERENCE}

• Dermacentor variabilis (dog tick) in the eastern United States and eastern Canada

• Dermacentor andersoni (wood tick) in the western United States and western Canada

• Amblyomma americanum (Lone Star tick) in the southwestern United States

• Rhipicephalus sanguineus (brown dog tick) recently implicated as a vector in Arizona

• Tick identification. (i) American dog tick (Dermacentor variabilis), ii) Rocky Mountain wood tick (Dermacentor andersoni), and, iii) brown dog tick (Rhipicephalus sanguineus) iv) Lone star tick (Amblyomma americanum). Courtesy of the CDC.

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Laboratory personnel can be infected by inoculation or inhalation of aerosolized infectious specimens. For this reason, only specially equipped laboratories should attempt to culture and isolate Rickettsia species. Transmission has occurred on rare occasions by blood transfusion.

United States statistics

Rocky Mountain spotted fever has been a nationally notifiable condition since the 1920s under the category of Spotted Fever Rickettsiosis (SFR). It has been reported in almost every state in the continental United States, with an age-related annual incidence of 0.5-3 cases per million population. ^[5]  In 2000, 495 cases of SFR were reported, while in 2017, more than 6,248 cases were reported, a finding that has been attributed at least in part to increased awareness and testing for the disease, as the percentage of confirmed cases among the total reported, and the case-fatality rate, have both decreased.

Annual incidence (per million persons) for Spotted Fever Rickettsiosis (SFR) in the United States, 2017. Courtesy of the CDC.

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The term Rocky Mountain spotted fever is a misnomer because the disease is relatively rare in the Rocky Mountain states. States reporting the highest rate of disease include North Carolina, Missouri, Tennessee, Oklahoma, and Arkansas; these states have accounted for more than half the total cases.

About 90% of cases occur between April and September, the time of the year when ticks have maximal activity and when people participate in outdoor recreational activities.

International statistics

Rocky Mountain spotted fever is also found in Canada, Mexico, Central America, and South America. However, the arthropod vector differs by location. Other rickettsial illnesses similar to Rocky Mountain spotted fever are also found worldwide (see the table below).

Table 1. Human Disease Around the World Caused by Spotted Fever Group Rickettsiae. (Open Table in a new window)

Race-, sex-, and age-related differences in incidence

Prior to 2000, Native Americans had rates of Rocky Mountain spotted fever similar to those of other races in the United States. ^[6] From 2001-2005, rates increased disproportionately (16.8 cases per million vs 0.5-4.2 cases per million for other races). The highest rates were in Oklahoma (113.1 cases per million). ^[7]

Darker-skinned individuals tend to have a worse clinical course, probably due to delays in recognizing the rash. Native American have higher rates of incidence, as well as worse outcomes. The annual incidence of Rocky Mountain spotted fever was 277.2 cases per million in the Southern plains, 104.6 cases per million in the East, and 49.4 cases per million in the Southwest regions. ^[8] Rates described through the national surveillance network are approximately 5-fold lower than those described in the review by Folkema et al.

The incidence is higher in males than in females, with a male-to-female ratio of 1.7:1. Children are at greater risk of acquiring Rocky Mountain spotted fever than are adults. The highest incidence occurs in children aged 5-9 years. However, the highest mortality is in those aged 50 years or older.

Outcomes can vary from complete resolution to death. The mortality rate during the preantibiotic era was as high as 30%; however, the mortality rate now ranges from approximately 2% in children to 9% in elderly persons.

The outcome greatly depends on the early start of appropriate treatment. The case-fatality rate is higher (6.2%) for persons whose treatment begins more than 3 days after onset of symptoms than for those treated within the first 3 days of illness (1.3%).

The importance of early treatment may help explain the poorer prognosis in African Americans. Rocky Mountain spotted fever may be diagnosed later in Blacks than in people with lighter skin because of the difficulty in detecting the early macular rash. In addition, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency tend to have a severe course of Rocky Mountain spotted fever, and the prevalence of G6PD deficiency in Black males is 12%.

Severe disease may result in long-term sequelae, such as the following:

• Partial paralysis of the lower extremities

• Gangrene requiring amputation of fingers, toes, arms, or legs

• Hearing loss

• Blindness

• Loss of bowel or bladder control

• Movement disorders

• Speech disorders

Rocky Mountain spotted fever (RMSF) is a bacterial disease spread through the bite of an infected tick.

Prevention

There is no vaccine to prevent RMSF. Avoidance of illness is by preventing tick bites, preventing ticks on your pets, and preventing ticks in your yard.

Know where to expect ticks. Ticks live in grassy, brushy, or wooded areas, or even on animals, so spending time outside camping, gardening, or hunting will bring you in close contact with ticks.

Treat clothing and gear with products containing permethrin.

Use Environmental Protection Agency (EPA)-registered insect repellents containing DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), or 2-undecanone. Do not use products containing OLE or para-menthane-diol (PMD) on children under 3 years old.

After you come indoors, check your clothing for ticks and perform a full body check of yourself and your child's body, particularly at the following areas:

• Under the arms
• In and around the ears
• Inside the belly button
• At the back of the knees
• In and around the hair
• Between the legs
• Around the waist

Remove the attached tick as soon as you notice it by grasping with tweezers, as close to the skin as possible, and pulling it straight out.

Watch for signs of illness. Most people who get sick with RMSF will have a fever, headache, and rash. RMSF can be deadly if not treated early with the right antibiotic. Timely initiation of doxycycline in children in essential to reduce the risk of morbidity and mortality. A short course of doxycycline is safe even in children younger than 8 years of age.