What Is Rocky Mountain Spotted Fever?

Introduction

Rocky mountain spotted fever (RMSF) is a bacterial disease that is spread through receiving a bite from an infected tick. RMSF was first called Black Measles due to the spotted rash that it causes across the body. The disease is caused by the coccobacillus bacterium Rickettsia rickettsii, and is the most common Rickettsia rickettsii infection. The organism is endemic within North, Central and South America, focusing on the South United States. RMSF is not found in the UK, however, travellers returning from endemic areas may carry the disease. RMSF is largely curable, but can be fatal if individuals are not treated early with the correct antibiotic.

Transmission of RMSF can occur through the bite of an infected tick, however, it can also be transmitted through the contamination of the skin with tick blood or faeces. The likelihood of acquiring a tick-borne infection is low, even if the tick has attached, fed and is a carrier of the disease. In the Eastern, Central and Western United States, RMSF is more often than not transmitted by the American dog tick. In the Southwestern United States it is mostly transmitted by the brown dog tick. RMSF has more recently begun transmission within the brown dog tick, this causes issues for humans as the preferred hosts of the brown dog tick are dogs. Family pets may carry the infected ticks in their coats, allowing the ticks to come into contact with humans and infect them with RMSF. Despite its name, RMSF is rare amongst the Rocky Mountain states of the US, and is spread by the Rocky Mountain wood tick in this region. The tick life cycle has three stages after the egg has hatched: larva, nymph and adult. The larva must have a blood meal before it is able to progress onto the next stage of its life.

RMSF has been a recognised condition since the 1920s, and as of 2010, RMSF cases have been reported under a new category ‘Spotted Fever Rickettsiosis’. The number of cases of RMSF has increased over time, however, the fatality rate has decreased, due to the introduction of tetracycline antibiotics, with the current fatality rate being 0.5% of cases. Most cases of RMSF occur between May and August, as this period coincides with when ticks are most active, due to the warmer weather. Cases of RMSF have been reported throughout the United States, however, Arkansas, Missouri, North Carolina, Tennessee and Virginia account for over 50% of cases, with a large number of these cases occurring within communities with a large number of free-roaming dogs, suggesting that dogs have been transferring these ticks to humans.

Symptoms

Symptoms of RMSF typically begin with a non-itchy rash that develops on the hands, arms, feet and legs. The rash initially looks small, flat and pink, but can then develop into purple or red spots, which is indicative of progression to severe disease. This may occur 5 - 10 days after the initial tick bite, and the original rash often isn’t found by the infected individual for a number of days. An infected individual may then display a fever, headache, nausea, decreased appetite, confusion or sensitivity to light. As these symptoms are indicative of many different diseases, it is important to seek medical attention quickly, as more than 20% of untreated cases of RMSF are fatal, with the average time from symptoms starting to death being only eight days. Adults and children are equally as likely to contract RMSF if they live in an endemic area, and immune-compromised individuals are particularly at risk.

Diagnosis

Diagnosis of RMSF can be difficult due to the non-specific symptoms in the early stages of the illness, which can resemble other more common diseases. Travel history, exposure to wooded areas and recent tick bites will all be taken into consideration when making a diagnosis of RMSF, as well as the type of rashes on the body. Laboratory testing will help to diagnose the diseases, as the standard serologic test for RMSF diagnosis is an indirect immunofluorescence antibody assay for immunoglobulin G, using antigens. PCR testing and immunohistochemistry assays can also be performed to confirm diagnosis. Doctors should not withhold or delay treatment whilst waiting for laboratory testing to be completed, as the health of individuals with RMSF can rapidly decrease.

Rickettsia rickettsii is a Gram-negative, obligate intracellular bacterium. The bacteria invade the cells that line the blood vessels, causing these cells to be killed as the bacteria replicates. As these cells are killed, blood leaks out of the blood vessels into the surrounding tissue. This leakage is what produces the characteristic spotted rash. As there are blood vessels around the entire body, RMSF is able to cause blood seepage into most tissues, making it a multi-organ disease.¹ Although endothelial cells are not immune cells, they produce mediators upon infection that contribute to the activation of immune cells. The production of bactericidal reactive oxygen species in neutrophils is pro-inflammatory in the attempt to fight the infection. Natural killer cells are innate cytotoxic cells that are implicated in the early defence against RMSF; these cells are able to kill infected cells. As well as this, B-cells, CD8+ T-cells, CD4+ T-cells and antibodies are vital in the protection against RMSF. B-cells produce specific antibodies that cause agglutination of the pathogen, aiding phagocytosis.²

Treatment

Tetracycline antibiotics are a broad-spectrum of antibiotics that have been in use since the 1940s. Doxycycline is the most effective antibiotic to treat suspected RMSF. Delay in the treatment of RMSF can be fatal, and children are five times more likely than adults to die from the disease, so it is vital to begin a course of antibiotics early. Doctors may be wary when prescribing doxycycline to children due to the risk of tooth staining in children under the age of eight; however, the CDC and HIS found that short causes of the antibiotic can be used in children without the risk of weakening tooth enamel. Doxycycline is most effective in treating RMSF within the first five days after infection, therefore clinicians must act on suspicion alone when prescribing the antibiotic, as this window of time is too short to conduct conclusive laboratory tests. Without the treatment from antibiotics, complications from RMSF can arise, including nerve damage,  hearing loss, incontinence, gangrene, partial paralysis and even death, therefore it is important to consult a medical professional if you have the symptoms of RMSF, especially if you live in or have visited an endemic area.

Prevention

Once you have contacted RMSF you can’t contract it again, however, to avoid initial contraction of the disease, individuals should wear long sleeved shirts tucked into trousers, long trousers tucked into socks and light coloured clothing so that ticks can be spotted more easily. These measures will make it much more difficult for a tick bite to occur, reducing the chance of contracting a tick-borne disease. Insect repellent can also be effective in reducing the likelihood of a tick bite, particularly products containing DEET, although this may not be 100% effective. After visiting an area in which ticks may have been present, it is important to check for ticks especially around the joints, in the belly button, behind the ears and in the hair, as ticks like to hide in these areas. When possible, individuals should walk on cleared paths or pavements, shower after outdoor activities and check pets for ticks. There are agencies throughout the United States that visit community centres, schools and clubs with the aim of educating adults and children about the dangers of RMSF, and how to check and protect yourself from ticks at home. These programmes are likely to be very beneficial in the reduction of RMSF cases across the United States.

Currently, there is no vaccine against RMSF, however, as CD4+ T-cells mediate protection against RMSF, current knowledge suggests that the induction of specific CD4+ T-cells is sufficient for protection. Therefore, CD4+ T-cell antigens could be used to develop a vaccine. This may even confer cross-protection between different rickettsial species. As well as this, a canine vaccine is being researched in order to prevent transmission from pets to humans. Live attenuated Rickettsia rickettsii and multiplex subunit vaccines are current possibilities. Antibiotic resistance could be a developing issue as Rickettsia rickettsii could develop resistance against doxycycline. As Rickettsia rickettsii is a Gram-negative bacterium, it has an outer membrane that protects it from antibiotic attack and selectively keeps antibiotics from entering, this could make it difficult to find new antibiotics to treat RMSF.³ 

Summary

Rocky mountain spotted fever (RMSF) is a disease that is transmitted to humans by ticks, and is caused by the bacteria Rickettsia rickettsii. The disease is endemic in areas of the United States and can be fatal if left untreated. Symptoms of the disease include a rash, high fever, nausea and severe headache. However, these symptoms can worsen into pulmonary oedema, necrosis and multi-organ system damage if left untreated. There is no current vaccine for RMSF, although, it can be prevented through the covering of skin when walking in endemic areas, and thoroughly checking the body for ticks after being outside.