User:Nina717/Rickettsia rickettsii

Rickettsia rickettsii is a gram-negative intracellular alpha proteobacteria. This bacteria is one of the four groups that result from a rickettsial infection that include the spotted fever group, the typhus group, the ancestral group, and the transitional group. As a part of the spotted fever group, Rickettsia rickettsii is considered one of the most pathogenic of its family. R. rickettsii is the causative agent for Rocky Mountain Spotted Fever, which is transferred to its host via a tick bite. It is most common in the Americas, and was discovered by a professor at the University of Chicago in 1902.

History

Rocky Mountain Spotted Fever (RMSF) first emerged in the Idaho Valley in 1896 after being recognized by Major Marshal H Wood . This infection occurs mostly in North, Central, and South America . At the time of it's discovery, not much information was known about the disease; it was originally called "Black Measles" due to the manifestation of the thin skin of an infected person turning black in the late stages. The first clinical description of Rocky Mountain Spotted Fever was reported in Snake River Valley of Idaho in 1899. At this time, 69% of individuals diagnosed with RSMF had terminal effects. RMSF is the most commonly reported spotted fever in the United States.

Howard Ricketts (1871–1910), an associate professor of pathology at the University of Chicago in 1902, was the first to identify and study R. rickettsii . He was the individual to discover the virus's vector and route of transmission . His research entailed interviewing victims of the disease and collecting and studying infected animals. He was also known to inject himself with pathogens to measure their effects.

Simeon Burt Wolbach is credited for the first detailed description of the pathogenic agent that causes R. rickettsii in 1919. He described RMSF after using the process of Giemsa stain . He clearly recognized it as an intracellular bacterium which was seen most frequently in endothelial cells.

Overtime, the once lethal infection has become curable due to the research done in recent years. The cases of reported fatality has dropped to 5-10% since the 1940's.

On a Global Scale

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Pathogen Life Cycle and Transmission

• Gulf Coast Tick (Amblyomma maculatum)

There are currently three known tick species that commonly carry R. rickettsii. The American dog tick (Dermacentor variabilis), mostly found in the eastern United States, is the most common vector for R. rickettsii. The Rocky Mountain Wood Tick (Dermacentor andersoni), found in the Rocky Mountain States, and the Brown dog tick (Rhipicephalus sanguine), found in select areas of the southern United States, are also known vectors of the pathogen.

Genomic Structure

R. rickettsii is an obligate intracellular alpha proteobacteria that belongs to the Rickettsiacea family. This system has a genome that consists of about 1.27 Mbp with ~1,350 predicted genes , which is a smaller virus compared to other variations of bacteria. It is maintained in the host by transovarial transmission . The multiplication of R. rickettsii is done by binary fission inside of the cytosol .

Once the host, a tick, has bitten another organism, R. rickettsii is able to spread and replicate in the organisms endothelial cells through their actin. The genomic structure overall allows for R. rickettsii to be able to replicate efficiently in vivo in order to not only infect the host and survive.

There are many forms of R. rickettsii that have been discovered with key characteristics that differentiate them. The shape of R. rickettsii can be identified as a coccobacillus that is gram-negative. R. rickettsii Sheila Smith (and other similar virulent strains) are the virulent causes of spotted fever. Other forms of R. rickettsii , such as R. rickettsii Iowa, have a genomic structure consistent with an avirulent phenotype. A key feature allowing for differentiation is a rickettsial outer membrane protein, rOmpA and rOmpB , that contributes to the identification of R. rickettsii as virulent. Furthermore, the identification process can be conducted by looking through the genome and comparing their single- nucleotide polymorphisms (SNPs) to find differentiable results.

Ticks carrying R. rickettsia are found to be in the ixodoidea family. These are known as "hard body ticks" and are approximately 3 mm in length. They have tear-shaped bodies with brownish coloration.

Virulence

While humans are hosts for R. rickettsii they do not contribute to rickettsial transmission, rather the pathogen is maintained through its vector, ticks. R. rickettsii is highly virulent in the tick population, and infects less than 1% of their population. As it is a highly virulent organism, it relies on horizontal transmission to combat tick reproduction.

Recent studies have found an evolution in R. rickettsii that has allowed it to establish a replicative environment within phagocytes. Their survival in immune system cells increases the pathogen's virulence in mammalian hosts. Contributions to the virulence of R. rickettsii include a variety of different factors that allow for a more lethal version of the pathogen. Actin-Based Motility (ABM) is a virulence factor that allows for the pathogen to hide from the host's immune cells and to spread to neighboring cells. It is suggested that the Sca2 gene, which is an actin-polymerizing determinant, is a distinguishing factor for the Rickettsia family, as R. rickettsii mutants with a Sca2 transposon avoided autophagic processes. This leads to an increase in disease manifestation for the host.

Ultimately, the rate of infection is determined by the tick population and the species of Rickettsia. R. rickettsii invades the endothelial cells that line the blood vessels in the hosts body. Endothelial cells are not phagocytic in nature; however, after attachment to the cell surface, the pathogen causes changes in the host cell cytoskeleton that induces phagocytosis. Since the bacteria can now induce phagocytosis the R. rickettsii gene can be replicated and further invade other cells in the host's body. As it is a part of the Rickettsia family, it is likely that the pathogen is able to secrete novel virulence factors that allow it to survive, and will continue to evolve to adapt.

Clinical Manifestations

The majority of infections from R. rickettsii occur during the warmer months between April and September. Symptoms can take a 1-2 days to 2 weeks to present themselves within the host. The diagnosis of RMSF is easier when there is a known history of a tick bite or if the rash is already apparent on the affected individual. It is important to note that individuals of all demographics can be infected by R. rickettsii, with the most reported cases being males and individuals over the age of 40 years old.

Signs and Symptoms

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During the initial stages of the disease, the patient may experience headache, muscle ache, chills, and high fever. Other early symptoms may include nausea, vomiting, loss of appetite, and conjunctival injection (red eyes). Most people infected by R. rickettsii develop a spotted rash, that begins to appear 2-4 days after the individual develops fever. The determination factors for treatment and symptoms are largely determined by the age and medical history of the patient. If left untreated, more severe symptoms may develop; these symptoms may include insomnia, compromised mental ability, coma, and damage to the heart, nerves, kidneys, liver, lungs, or additional organs.

Rash

This image gives context to the symptoms displayed by individuals affected by Rickettsia rickettsii or better known as "Rocky Mountain Spotted Fever". The rashes described are displayed in this image. As detailed the red, flat, and itchy rash is present over the forearm of the infected individual.

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The rash can differ greatly in appearance along the progress of the R. rickettsii infection. It is not itchy and starts out as flat pink macules located on the affected individual's hands, feet, arms, and legs.

Severe Infections

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The later, more severe symptoms occur in response to of thrombosis (blood clotting) caused by R. rickettsii targeting endothelial cells in vascular tissue. The mortality rate for RMSF is 3-5 percent in all cases but 13-25 in untreated cases.

Diagnosis and Treatment

Laboratory Confirmation

Diagnosis of Rocky Mountain Spotted Fever (RMSF) often involves laboratory tests to confirm the presence of the causative bacterium, Rickettsia rickettsii. The Centers for Disease Control and Prevention (CDC) considers the indirect immunofluorescence assay (IFA) as the reference standard for RMSF diagnosis. The IFA detects an increase in immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies in the patient's bloodstream, indicating exposure to the bacterium.

A more specific and sensitive diagnostic tool is the polymerase chain reaction (PCR) test, which can detect the presence of R. rickettsii DNA in blood samples. PCR is particularly useful in early stages of the disease when antibody levels may be low or undetectable.

Immunohistochemical (IHC) staining is an additional diagnostic approach in RMSF diagnosis. A skin biopsy taken from the characteristic spotted rash is analyzed using IHC staining. However, its accuracy is approximately 70%.

Antibiotics

Doxycycline and Chloramphenicol are typically the primary drugs of choice for treating Rocky Mountain Spotted Fever (RMSF) and alleviating associated symptoms. Prompt administration of antibiotic therapy is crucial when RMSF is suspected, especially during the early stages of the disease. Delay in initiating antibiotic treatment can increase the risk of severe complications, including end-organ failure affecting the heart, kidneys, and lungs, as well as meningitis, brain damage, shock, and potentially fatal outcomes.

It's important to note that doxycycline is the preferred antibiotic for treating RMSF, even in children and pregnant women, due to its efficacy and the severity of the disease. The use of appropriate antibiotics is vital in preventing the progression of RMSF and aiding in a faster recovery.

Doxycycline is often the first-line treatment for RMSF due to its effectiveness against the causative bacterium, R. rickettsii, and its ability to quickly reduce symptoms and prevent complications when administered promptly.

Chloramphenicol may be an alternative for individuals who cannot tolerate or have contraindications for using doxycycline. However, it is not typically the first choice due to the potential for serious side effects and other factors, such as bacterial resistance and limited availability.

Preventative Measures

The primary prevention tactic used to prevent Rocky Mountain Spotted Fever (RMSF) is to prevent tick bites. Since tick bites transfer the causative agent, R. rickettsii, it is recommended to apply preventative measures year-round, despite the probability of infection increasing from April through September. Before going outside, it is important to remain aware of ticks in wooded or grassy areas, in particular leaf litter. They can also be found on animals. There are treatments used, such as permethrin or insect repellent, that are applied to clothing to deter ticks from latching onto a new host.

To prevent proximity to tick born locations, cut your grass regularly as longer grass (over 5 inches) serves as an area of interest to ticks. Once coming inside, examine clothing, pets, and body for ticks. Ticks can be carried into a home through clothing or pets, and attach later to a new host. When washing clothing, hot water and high heat will ensure that any ticks carried inside do not survive. When examining the body, look in key areas such as in hair, ears or belly buttons, as well as joints such as armpits, behind the knee, and around the waist. This can be done before showering, as showering two hours after being outdoors can reduce the risk of disease by washing away unattached ticks.

If a tick is found on the body, it is important to remove it immediately. Using a pair of tweezers, grab the tick as close to the skin as possible and pulling upward with even pressure. Once removed, wash the area with soap and water and dispose of the tick by flushing it down the toilet, putting it in rubbing alcohol, placing in a sealed bag, or wrapping it tightly in tape. If the tick is not removed in one piece, remove the remaining parts with the tweezers; however, if it cannot be or is difficult to remove, leave it.