Rocky Mountain Spotted Fever

Overview

Rocky Mountain spotted fever (RMSF) is one of about a dozen spotted fever illnesses found in the Americas, Europe, Asia and Australia. All are caused by bacteria belonging to the genus Rickettsia, a group of pleomorphic (shape-changing), non-motile microbes that replicate only inside of eukaryotic host cells.

Although first described in the Snake River Valley region of Idaho in 1896 (hence its name), Rocky Mountain spotted fever is actually more common in the south Atlantic and south central parts of the United States. It is caused by Rickettsia rickettsii and is transmitted to humans in the United States by two primary tick vectors, the American dog tick (Dermacentor variabilis) and the Rocky Mountain wood tick (Dermacentor andersoni). The brown dog tick, Rhipicephalus sanguineus, has been implicated in some cases of RMSF as well.

Prior to the antibiotic era, Rocky Mountain spotted fever had a mortality rate of up to 30%. Even today, it remains the most common fatal tick-borne disease in the United States; about three to five percent of patients who acquire the infection will die from it. Most of these fatalities occur in the very young and very old and are due to delayed diagnosis and treatment.

The Centers for Disease Control typically receives somewhere between 300-1200 case reports of RMSF each year, although the number has been increasing in recent years. As with many tick-borne infections, there is a seasonal peak in the late spring and summer months, with May, June, and July accounting for the most cases. More than 90% of cases are reported from April through September. The disease strikes children disproportionately — peak incidence is in the five to nine age group, and more than half of all reported cases involve children under 15 years old.

An outbreak of Rocky Mountain Spotted Fever (RMSF) has reached epidemic proportions in one Northern Mexico town, and it’s starting to spread to the United States, according to a new study from the Centers for Disease Control and Prevention (CDC).

The outbreak, which began in 2008 in the Mexican border town of Mexicali, has affected 4,000 people and an unknown number of dogs as of 2018. Several hundred people have died of the disease in Mexico, and at least four have died in the US after crossing the border from Mexico.

RMSF, caused by the bacteria Rickettsia rickettsii, is responsible for more human deaths in North America than any other tickborne disease, killing as many as 10% of those infected. Between 1999 and 2007, 80 fatal cases were reported in Sonora, Mexico, alone. The genus Rickettsia is composed of bacteria that behave like viruses, reproducing only inside living cells. The bacteria live parasitically in ticks and are transmitted to vertebrate hosts by bite.

Of particular concern to scientists: The recent epidemic appears to be spreading through the bite of a new carrier.

Historically, most cases of RMSF reported in the US have been transmitted by the bite of an infected Dermacentor variabilis, also known as the American dog tick or wood tick. But recent epidemics in Sonora and Arizona have been associated with the brown dog tick (Rhipicephaluls sanguineus), a tick whose preferred host is a dog.

More than 80% of the dogs in one Mexicali neighborhood were found to be infected with brown dog ticks.

The risk to humans is heightened by the brown dog ticks’ habit of living in areas adjacent to towns and cities, and the fact they often spend their off-host time indoors.

Symptoms of RMSF in humans include fever, headache, and muscle aches, accompanied by a crusty skin rash at the bite site. Although not usually fatal, RMSF can kill as many as 10% of those infected.

Symptoms in dogs include depression, lethargy, arrhythmia, and discolored spots along the skin, often bruised or purplish in color. The fatality rate in dogs infected with RMSF is unknown—one study puts the survival rate at 100%, while another put the fatality rate at 60%. The discrepancy is thought to be a combination of delayed diagnosis and more severe manifestations of the disease.

Although both species can develop the disease, it can only be transmitted through a bite by an infected tick, so dogs can’t infect humans directly and vice versa.

As to why the outbreak happened, the CDC doesn’t know.

“More data are needed before we can understand why this epidemic emerged,” wrote the authors of the CDC study. “Studying this epidemic offers an opportunity to understand the origin and dynamics of this epidemic and can inform response to emerging tickborne diseases in general.”

Signs and Symptoms

The usual incubation time between tick bite and symptom onset is five to ten days. Only about half of patients recall a preceding tick bite. Initial symptoms of Rocky Mountain spotted fever are usually non-specific, consisting of fever, severe headache, myalgias, nausea, and loss of appetite. Many patients will present to physicians before the hallmark rash develops, which complicates diagnosis and increases the disease’s potential deadliness.

Rash onset is subtle and usually develops within two to five days after symptoms begin. The rickettsiae spread through the lymphatic system, eventually parasitizing and multiplying within endothelial cells. As the host cells die, blood leaks into adjacent tissues, causing both rash and damage to internal organs. Typically, pale spots first appear on the patient’s extremities (hands, feet, forearms, and ankles) and eventually spread inward, toward the trunk.

The “classic” RMSF rash, consisting of small, bright red petechial (spotted) lesions, does not usually appear until almost a week after symptom onset. Estimates vary as to its prevalence, with most sources stating that it presents eventually in about half of all RMSF patients. Close to 5% of patients will develop gangrene or skin necrosis, sometimes requiring amputation of the affected extremities.

Around 10-15% of RMSF patients will not develop rash at any stage.

Rocky Mountain spotted fever is multisystemic and potentially severe. Central nervous system manifestations include lethargy and confusion (about 25% of all cases), ataxia (18%), coma (9-10%), and seizures (8%). Other neurologic manifestations include meningitis, cranial neuropathies, deafness, paralysis, spasticity, vertigo, aphasia, and photophobia. Ophthalmologic complications can also occur.

In addition, RMSF affects the respiratory system, the gastrointestinal system, and the renal system. Pulmonary involvement includes edema, pneumonia, and respiratory distress syndrome. Microcirculatory vasculitis can lead to myocarditis. Close to 10% of patients develop jaundice during the course of their illness; a similar percentage will produce stools positive for occult blood. Hospitalization is frequently required in advanced cases of RMSF.

African-American males are at particular risk for serious complications of Rocky Mountain spotted fever, as they are genetically more likely to be deficient in glucose-6-phosphate dehydrogenase (G6PD), an enzyme associated with the maintenance of membrane integrity in red blood cells.

Agent

Rickettsia rickettsii

RMSF is most often transmitted by the American dog tick in the Eastern, Central and Western United States; by the Rocky Mountain wood tick in the Rocky Mountain states; and by the brown dog tick in the Southwestern United States, along the U.S.-Mexico border. RMSF can be rapidly fatal if not treated within the first 5 days of symptoms. Before tetracycline antibiotics were available, case fatality rates ranged from 20–80%.

Where Found

Although RMSF cases have been reported throughout most of the contiguous United States, five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri) account for over 60% of RMSF cases. RMSF has become increasingly common in certain areas of Arizona over the last several years; between 2003 and 2016, over 360 cases and 21 fatalities occurred.

Incubation Period

3–12 daysRash

• Typically appears 2–5 days after onset of symptoms; approximately 10% of RMSF patients never develop a rash.
• Decision to treat should not be based on presence of rash.

Early Rash

• Maculopapular: Small, flat, pink, non-itchy spots (macules) initially appear on the wrists, forearms, and ankles then spread to the trunk and sometimes palms and soles.

Late Rash

• Petechial: Red to purple spots (petechiae) are usually not seen until day 6 or later after onset of symptoms.
• Petechial rash is considered a sign of progression to severe disease. Every attempt should be made to begin treatment before petechiae develop.

Signs and Symptoms

Early (1–4 Days)

• High fever
• Severe headache
• Malaise
• Myalgia
• Edema around eyes and on the back of hands
• Gastrointestinal symptoms (nausea, vomiting, anorexia)

Late (5 Days and Beyond)

• Altered mental status, coma, cerebral edema
• Respiratory compromise (pulmonary edema, ARDS)
• Necrosis, requiring amputation
• Multiorgan system damage (CNS, renal failure)

Diagnosis

While a number of laboratory tests are available for Rocky Mountain spotted fever, none are both rapid and sensitive enough to provide useful diagnostic assistance to the examining physician. As prompt treatment of RMSF is critical to a positive outcome, diagnosis should be made on clinical grounds — i.e., history, epidemiology, and clinical exam. This can be challenging, as many patients will not recall the tick bite.

Conventional blood tests can produce results that hint at RMSF. Among the typical findings are hypoanotremia (low sodium), thrombocytopenia, white blood cell abnormalities, and/or elevated liver enzymes.

Serological assays are used mostly to confirm the diagnosis after treatment has been initiated. Indirect immunofluorescence assays (IFA) of both IgM and IgG antibodies are most commonly employed, but enzyme linked immunosorbent assays (ELISA) and dot immunoassays are also available.

Complement fixation is less sensitive, and less frequently used. Immunostaining of biopsied skin rashes can also be performed and is very rapid; results are available in a few hours. However, the test is only 70% sensitive, so a negative result does not exclude the diagnosis.

Polymerase chain reaction (PCR) assays for R. rickettsii DNA are considered perhaps the most timely and specific test for RMSF overall, but are still not widely available.