Rocky Mountain spotted fever natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Overview

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.

Natural history

Rocky Mountain Spotted fever patients will progress from early symptoms to late symptoms and possible chronic conditions, as well as death, if left untreated. The infection begins with inoculation of the disease from an infected tick. Once inoculated, the organism Rickettsia rickettsii will incubate for 2- 14 days. As the incubation period concludes early onset symptoms will begin, these symptoms are listed below.

Early Onset Symptoms:

• Fever
• Vomiting
• Nausea
• Severe Headache
• Muscular Soreness and Pain
• Anorexia
• Rash (within may appear within 2-5 days of fever onset.)

Treatment is most effective if an antibiotic therapy is administered at this point. As the disease progresses, treatment loses effectiveness, thus it is of utmost importance to diagnose and begin treatment early on. Most individuals who begin treatment will usually clear the infection.

After the first three days of early onset symptoms, other symptoms will progress. These symptoms are described as late stage symptoms and will include the characteristic rash that is commonly associated with Rocky Mountain Spotted fever. Not all patients will have the same clinical presentation of the disease. Particularly, the rash is present within the majority of infected patients, yet 10-15% of patients may never develop the characteristic spotted rash. If the infection progresses in severity, patients will be hospitalized at this point. Late stage symptoms may be observed below.

Late Stage:

• Maculopapular Rash
• Diarrhea
• Abdominal Pain
• Joint Pain

With proper treatment and antibiotic therapy, most patients will have cleared the infection. However, if left untreated or improperly diagnosed, Rocky Mountain Spotted Fever will progress further and may involve chronic complications or severe tissue damage as well as death. Complications and chronic conditions associated with untreated development of Rocky Mountain Spotted fever are found below. Untreated or Improperly Diagnosed:

• Gangrene
• ARDS
• Myocarditis
• Acute Renal Failure
• Meningoencephalitis
• Pulmonary hemorrhaging
• Pulmonary Edema
• Cerebral Edema
• Death

Complications

Possible complications include:

• Meningitis
• Brain damage
• Clotting problems
• Heart failure
• Kidney failure
• Lung failure
• Adult Respiratory Distress Syndrome
• Pneumonitis (lung inflammation)
• Encephalitis
• Noncardiogenic pulmonary edema
• Cardiac arrythmia
• Impaired blood clotting
• Skin Necrosis
• Gastrointestinal Bleeding
• Shock

Long term complications:

• Paralysis of lower extremities
• Impaired bladder function
• Impaired bowel function
• Amputation
• Hearing impairment
• Speech Disorders

Prognosis

• The prognosis is usually good for patients suffering from a Rocky Mountain Spotted fever infection.
• Factors that might contribute to a poor prognosis are infections within children 0-9, especially 5-9, and adults over 60 years of age. With a higher rate of fatality within these groups.
• Other factors that contribute to a poor prognosis are race and gender. Infections rates are higher among populations of White and Native American males.
• It should be noted that although the prognosis is usually good, RMSF is a severe illness and many infected patients will be hospitalized.
• The mortality rate is approximately 20% if untreated and 5% if treated properly.
• Infection with R. rickettsii may provide long lasting immunity against re-infection.
• Previous infection with Rocky Mountain spotted fever should not deter persons from practicing good tick-preventive measures or visiting a physician if signs and symptoms consistent with Rocky Mountain spotted fever occur, especially following a tick bite, as other diseases may also be transmitted by ticks.

Epidemiology Graph 3 - Comparison between RMSF cases and their fatality.

Initial health problems

• Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because R. rickettsii infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or renal system.
• Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African-American race, chronic alcohol abuse, and

glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• Deficiency of G6PD is a sex-linked genetic condition affecting approximately 12% of the U.S.
• African-American male population; deficiency of this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever. This is a rare clinical course that is often fatal within 5 days of onset of illness.

• Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders.
• These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations.

Long term health problems

• Patients who had a particularly severe infection requiring prolonged hospitalization may have long-term health problems caused by this disease.
• Rickettsia rickettsii infects the endothelial cells that line the blood vessels.
• The damage that occurs in the blood vessels results in a disease process called a "vasculitis", and bleeding or clotting in the brain or other vital organs may occur. *Loss of fluid from damaged vessels can result in loss of circulation to the extremities and damaged fingers, toes or even limbs may ultimately need to be amputated. *Patients who suffer this kind of severe vasculitis in the first two weeks of illness may also be left with permanent long-term health problems such as profound neurological deficits, or damage to internal organs.
• Those who do not have this kind of vascular damage in the initial stages of the disease typically recover fully within several days to months.