Rocky Mountain spotted fever overview

# Overview
Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States.  Some synonyms for Rocky Mountain spotted fever in other countries include tick typhus, Tobia fever (Colombia), Sao Paulo fever or febre maculosa (Brazil), and fiebre manchada (Mexico). The disease is caused by Rickettsia rickettsii, a species of bacteria that is spread to humans by Ixodid ticks (Dermacentor). Initial signs and symptoms of the disease include sudden onset of fever, headache, and muscle pain, followed by development of a rash. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment it can be fatal.  The name Rocky Mountain spotted fever is somewhat of a misnomer.  Beginning in the 1930s, it became clear that this disease occurred in many areas of the United States other than the Rocky Mountain region. It is now recognized that this disease is broadly distributed throughout the continental United States, and occurs as far north as Canada and as far south as Central America, Mexico, and parts of South America.  Between 1981 and 1996, this disease was reported from every U.S. state except Hawaii, Vermont, Maine, and Alaska. Rocky Mountain spotted fever remains a serious and potentially life-threatening infectious disease today. Despite the availability of effective treatment and advances in medical care, approximately 3% to 5% of individuals who become ill with Rocky Mountain spotted fever still die from the infection.  However, effective antibiotic therapy has dramatically reduced the number of deaths caused by Rocky Mountain spotted fever; before the discovery of tetracycline and chloramphenicol in the late 1940s, as many as 30% of persons infected with R. rickettsii died. 

# Historical Perspective
Rocky Mountain spotted fever was first recognized in 1896 in the Snake River Valley of Idaho and was originally called black measles. For a vast part of American history, the rash was dreaded as a frequently fatal disease in this endemic region. By the early 1900s, the recognized geographic distribution of this disease grew to encompass parts of the United States as far north as Washington and Montana and as far south as California, Arizona, and New Mexico.  After much anticipation and failure to cure the disease, there was finally a breakthrough in 1922. In Western Montana (1922) an Assistant Surgeon, R.R. Spencer, inoculated himself with a mixture of mush ticks and carboxylic acids to which later began the development of a vaccine for the disease. 

# Classification
There is currently no classification system established for Rocky Mountain spotted fever.

# Pathophysiology
Rocky Mountain spotted fever is caused by a bacterial organism of the Rickettsia genus known as Rickettsia rickettsii. The organism is a Gram-negative bacteria, ranging in sizes between 0.2 x 0.5 micrometers to 0.3 x 2.0 micrometers. Rickettsia rickettsii is non-spore forming, non- motile, and varies in shape. Early in it's life cycle, Rickettsia rickettsii survives within an invertebrate host. The invertebrate host may then transmit the organism through blood meals, open skin, and breakages in mucous barriers. 
The disease is most often transmitted through arthropod vectors, especially the hard tick- Ixodidae family. Rickettsia rickettsii requires an invertebrate vector and vertebrate host. Humans are considered an accidental host within the R. rickettsii life cycle. 
The organism has evolved a set of strategic mechanisms in order to evade the human immune system. Infection begin with an induced phagocytosis of the organism into an endothelial host cell. Usually endothelial cells are not phagocytic, however R. rickettsii is able to induce changes to the overall cytoskeleton of the cell. Invasion goes largely unnoticed, enabling the organism to avoid lysosomal fusion and an escape into the cytoplasm for future reproduction. 

# Epidemiology & Demographics
Since the 1920's the United States Center for Disease Control and Prevention has deemed Rocky Mountain spotted fever as a reportable disease. RMSF cases were most often reported within the Rocky Mountain region, although recent data reveals that the disease is widespread throughout the United States. Areas that currently harbor the majority of RMSF infections are Oklahoma, Tennessee, and Arkansas. The disease has also been reported throughout the Western Hemisphere.  Incidents are highest among children the between the ages of 5-9 years and adults between the ages of 40-64 years. Fatality rates are also higher among these groups, with the highest fatality rate in the elderly at 60 years or more. In terms of demographics, Rocky Mountain spotted fever has been reported at higher rates among males, especially of White and Native American descent. 

# Risk Factors
The primary risk factors associated with Rocky Mountain spotted fever are exposure to endemic environment and the time of that exposure. Wood Ticks have been identified as the primary vector of Rocky Mountain spotted fever infections, thus being bitten in an endemic area may result in the contraction of the disease.

# Causes
Rickettsia rickettsii (abbreviated as R. rickettsii) is a unicellular, Gram-negative coccobacillus (plural coccobacilli) that  is native to the New World. It belongs to the spotted fever group (SFG) of Rickettsia and is most commonly known as the causative agent of Rocky Mountain spotted fever (RMSF). By nature, R. rickettsii is an obligate intracellular parasite that survive by an endosymbiotic relationship with other cells.  R. rickettsii is a non-motile, non-spore forming aerobic organism. Cells are typically 0.30.5  0.82.0 m in size. They lack a distinct nucleus and membrane bound organelles. Their outer membrane is composed mostly of lipopolysaccharides. RMSF is transmitted by the bite of an infected tick while feeding on warm-blooded animals, including humans. Humans are considered to be accidental hosts in the Rickettsiatick life cycle and are not required to maintain the rickettsiae in nature.

# Differentiating Rocky Mountain spotted fever from other diseases
Rocky Mountain spotted fever (RMSF) must be differentiated from other diseases that cause fever, headaches, muscle pain, and rash. In virtually all cases, RMSF presents with a rash. When trying to differentiate RMSF from other infections, it should be noted that there has been a rare case in which RMSF has presented itself without the typical rash. Examples of misdiagnosed, rickettsiae caused, diseases include typhus-spotted fevers and Ehrlichiosis. Other misdiagnoses include pox diseases and acne.When diagnosing Rocky Mountain spotted fever it's important to account for patient history such as exposure to endemic regions and a history of tick bites. Although immunofluorescence assays, polymerase chain reactions, and immuno-staining remain the most effective ways of determining a RMSF infection.

# Natural History, Complications & Prognosis
If left untreated patients with Rocky Mountain spotted fever will undergo three developmental stages of infection. The early stages of infection begin within 2-14 days of inoculation by an infected tick and present themselves as a fever, nausea, vomiting, and a severe headache. Late stage progression of symptoms will result in a maculopapular rash, abdominal and joint pain. Further progression of the disease, if left untreated, will result in the following complications; gangrene, pulmonary complications, ARDS, cerebral edema as well as other long term complications. Ultimately, if Rocky Mountain spotted fever progresses entirely untreated, it will conclude in the patient's death. With a fatality rate as high as 87%, without antibiotic intervention.  

# History & Symptoms
The classic triad of findings for this disease are fever, rash, and history of tick bite.  However, this combination is often not identified when the patient initially presents for care. Early onset symptoms typically associated with Rocky Mountain spotted fever include fever, nausea, vomiting, and headache. 
Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include thrombocytopenia, hyponatremia, or elevated liver enzyme levels.

# Physical Examination
There are several aspects of Rocky Mountain spotted fever (RMSF) that make it challenging for healthcare providers to diagnose and treat. The symptoms of RMSF vary from patient to patient and can easily resemble other, more common diseases. Treatment for this disease is most effective at preventing death if started in the first five days of symptoms. Diagnostic tests for this disease, especially tests based on the detection of antibodies, will frequently appear negative in the first 7-10 days of illness. Due to the complexities of this disease and the limitations of currently available diagnostic tests, there is no test available at this time that can provide a conclusive result in time to make important decisions about treatment.For this reason healthcare providers must use their judgment to treat patients based on clinical suspicion alone. Healthcare providers may find important information in the patients history and physical examination that may aid clinical suspicion. Information such as recent tick bites, exposure to high grass and tick-infested areas, contact with dogs, similar illnesses in family members or pets, or history of recent travel to areas of high incidence can be helpful in making the diagnosis.

# Laboratory Findings
A diagnosis of Rocky Mountain spotted fever is based on a combination of clinical signs and symptoms and specialized confirmatory laboratory tests.  Other common laboratory findings suggestive of Rocky Mountain spotted fever include thrombocytopenia, hyponatremia, and elevated liver enzyme levels. There are three tests which are predominantly used for the diagnosis of RMSF, immunofluorescence assay (IFA), polymerase chain reaction (PCR), and immuno-staining. IFA is considered to be the "gold standard" in testing for the disease. It's important to consider that the most effective treatment for RMSF occurs when diagnosis and medical therapy begins within the first 5 days, early symptoms. Unfortunately however IFA can't usually detect IgG antibodies until 7-10 days of illness. Thus it is of utmost importance to successfully diagnose and begin medical therapy initially, even prior to confirmation by lab testing. 

# Chest X-ray
A chest x-ray may be helpful in the diagnosis of Rocky Mountain spotted fever. Findings on a chest x-ray indicating pulmonary edema may be suggestive of a Rocky Mountain spotted fever infection.

# Other Diagnostic Studies
There are no further diagnostic studies associated with Rocky Mountain spotted fever.

# Medical Therapy
The mainstay of therapy for Rocky Mountain spotted fever is doxycycline.  Pharmacologic therapy for Rocky Mountain spotted fever includes either Doxycycline or Chloramphenicol.

# Prevention
The most potent risk factor in the development of Rocky Mountain spotted fever is exposure to infected ticks. Therefore proper prevention is achieved by emphasizing personal protection from ticks when traveling through a tick-infested habitats. Other risk factors include race, age, and seasonal variation.