Rocky Mountain Spotted Fever (RMSF): The Deadly Tick-borne Disease That Inspired a Hit Movie

History

Rocky Mountain Spotted Fever (RMSF) was first discovered in the 1890s in Idaho. The disease used to be called the ‘black measles’ because one of the characteristic symptoms was a dark, purplish skin rash. It wasn’t until 1906 that a pathologist, Dr. Howard T. Ricketts discovered that ticks spread the disease. A few years later, he had isolated the pathogen, Rickettsia rickettsii. Dr. Rickett’s pioneering work with RMSF fueled the discovery of other ricketts-related diseases in future years [3, 4]. 

RMSF infections can be severe and fatal. RMSF had a high mortality rate until the 1920s, when a high-profile tragedy changed the course of research related to the disease. In 1922, the Governor of Montana lost his daughter and son-in-law to RMSF. This loss funneled attention and research on RMSF at the Rocky Mountain laboratories in Montana. 

The next significant milestone in the history of Rocky Mountain spotted fever was the discovery of a vaccine. In 1924, Dr. Roscoe Spencer and his associate, Ralph Parker, are credited for discovering the Spencer-Parker vaccine against RMSF. As part of his research, Dr. Spencer injected himself with the disease-causing bacteria to study the immune response [3]. 

The vaccine was successful at the time in preventing RMSF-related deaths in humans. However, when effective antibiotics to treat RMSF were discovered in the 1940s, the Spencer-Parker vaccine against RMSF became obsolete [5]. 

The story of RMSF research is one of grit and good old-fashioned elbow grease in research, even under severe resource constraints. For example, Drs. Spencer and Parker discovered the vaccine in Canyon Creek Schoolhouse Laboratory, an old school. 

Eventually, as state and federal interest in RMSF grew, Montana became the epicenter of tick-borne research in America. In 1927, the Board of Etymology began building a larger lab in Hamilton, Montana. The news of this construction was met with much hostility from local residents who were fearful of the tick infestation spreading across their town. This lab was eventually built and called Rocky Mountain Laboratories (RML). Ten years after it was developed, RML became a part of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health [3, 4]. 

These twists and turns inspired the 1937 blockbuster hit movie starring Errol Flynn in a (surprisingly) non-swashbuckling role. The movie ‘Green Light’ was the second highest-grossing movie of the year.  

Epidemiology

Rocky Mountain spotted fever was first described as early as the 1800s. RMSF is primarily found in North, Central, and South America. According to the CDC, 4,000-6,000 tickborne spotted fevers are reported annually in the United States. Over 60% of these reported RMSF cases occur in five states: North Carolina, Tennessee, Oklahoma, Arkansas, and Missouri [6].

Notable Outbreaks

Notable outbreaks of RMSF in recent years include:

• 2004: 16 cases reported in Arizona, U.S. with 2 deaths
• 2008-2018: 4,000 reported cases in Mexicali, Baja California, Mexico (in Mexico, RMSF is known as fiebre machada) 
• 2009: 1,000 reported cases in an outbreak in Baja California, Mexico (4 fatal)
• 2013-2016: 4 deaths from RMSF in the U.S (cross-border events imported to the U.S. from Mexico) [2]

How is it Spread?

Rocky Mountain spotted fever is spread by ticks infected by Rickettsia rickettsii, the causative agent. Several species of hard-bodied (ixodidae) ticks can transmit the illness to humans including the American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), and brown dog tick (Rhipicephalus sanguineus) [7, 8]. 

It is important to note that humans are “accidental” hosts; Rocky Mountain spotted fever cannot be transmitted from person to person [8]. RMSF is transmitted to humans through: 

• Tick bites: When an infected tick bites and attaches itself to a person, it begins feeding on the host’s blood. Quite often, the bite is painless, and the person being bitten may never even feel it. This means the tick can continue feeding for hours and spread the infection. 
• Contact with the feces of an infected tick: Eating food contaminated with the feces of infected ticks can spread RMSF to a human or other mammal. Another way is when a mammal (including people) comes into contact with an open skin or wound that contains the feces of an infected tick. 
• Blood transfusions: Rarely can RMSF be transmitted through blood transfusions [1, 7]. 

Biology of the Disease

Rickettsia rickettsii is a gram-negative coccobacillus with a complicated life cycle. In the early stages of development, the bacteria grows in an invertebrate host, like a tick. Ticks can get an R. rickettsii infection when they feed on the blood of an infected host. Once infected, ticks can stay infected for life. Infected ticks can also infect other ticks: male ticks can infect females during mating, and females can transmit the bacteria to their eggs [9]. 

Ticks that are infected can bite a vertebrate animal like a mouse, other small mammals, or even larger ones like cats and dogs. When an infected tick latches on for about 6 to 10 hours, it can transmit the rickettsii bacteria to the host through its salivary glands [10]. 

Humans are accidental hosts of rickettsia rickettsii — we’re just collateral damage. However, once a person gets infected with R.rickettsii, the bacteria infect vascular endothelial cells, causing an inflammatory response [7, 8]. 

Diagnosis

Blood tests can help identify the source of infection, but if a doctor strongly suspects RMSF, antibiotic treatment can start before receiving test results. 

Diagnosing Rocky Mountain spotted fever early can be challenging. The ticks are very tiny, and their bites are often painless. They often attach to humans in locations like the scalp, armpits, or groin, making them hard to detect. A clinical diagnosis is also difficult in patients who do not develop the characteristic spotted rash [13].  

Additionally, patients who experience nausea and vomiting early on may be misdiagnosed as having gastrointestinal issues. In endemic regions, physicians may be trained to look for RMSF, particularly during the spring and summer. However, it’s important to note that diseases spread by ticks can be present all year round [1, 13]. 

Adding to the confusion is that RMSF symptoms may be confused with those of other diseases transmitted by ticks. These include Lyme disease, babesiosis, and ehrlichiosis infections [13, 14]. Getting a detailed record of a patient’s travel history, activity, and potential contact with animals can help detect early and save lives. 

Symptoms

Rocky Mountain spotted fever is hard to spot early. This is because symptoms are often similar to many other infections at this stage. However, the disease can cause severe illness and even death if not treated early. The incubation period (time for symptoms to appear) is 1 to 2 weeks. Most often, symptoms appear around 7 days after infection [11]. 

Clinicians who ask patients about recent travel and activities may learn about tick exposure from being outdoors or in contact with dogs. This is valuable information during differential diagnosis that can help catch tick-borne diseases early. 

Symptoms of Rocky Mountain spotted fever (RMSF) include: 

• High fever  
• Headache
• Characteristic red, spotted rash. The rash appears first on the wrists and ankles and can spread to the rest of the body. Note: Not everyone develops a rash, which makes it harder to detect RMSF 
• Chills 
• Muscle pain
• Nausea and vomiting [12]

Treatment

Rocky Mountain spotted fever is commonly treated with the antibiotic, Doxycycline. According to the CDC, using antibiotics other than doxycycline is associated with a higher risk of death from RSMF. Doxycycline is very effective at preventing the disease from progressing to a more severe stage if treatment starts in the first five days of infection [8, 14, 15]. The CDC recommends the following doxycycline protocol for at least 3 days after the fever subsides: 

• Adults: 100 mg, every 12 hours 
• Children under 100 lbs: 2.2 mg/kg body weight, 2 times daily.  

The minimum recommended course of treatment is 5-7 days.

Prevention

There is no vaccine for Rocky Mountain spotted fever in humans and dogs. The best way to help protect against tick-borne diseases are: 

• Keep your yard free of leaf litter, tall grass, and trash (old furniture and other unused appliances). Mow the lawn regularly.
• Avoid visiting places filled with thick grass and brushy or wooded areas since tick density is usually high in these places. 
• Cover your body entirely and wear closed shoes if you have to spend time outdoors or visit places where ticks are prevalent.
• You can use tick repellents that can be sprayed on clothes and tick repellents containing DEET on the exposed parts of your body for extra protection.
• Sometimes, ticks might cling to your clothes, and if you wear them again, they might come in contact with your body. So, it is better to tumble-dry your clothes at high heat each time you return from any outdoor activity.  
• Make it a practice to examine your body after spending time outdoors and remove any ticks attached to the body. Check your scalp, armpits, and groin regions for ticks and tick bites. Check for, and remove ticks early to lower your risk of getting bitten. 
• Shower once you are back from outdoor activity. 

When you’re outdoors during the spring and summer, there are other tick-borne viruses to watch out for, like the most common tick-borne infection in the United States, Lyme disease. Other diseases spread by ticks include ehrlichiosis, babesiosis, Powassan virus disease, anaplasmosis, Colorado tick fever, and more.