Rickettsial Diseases, including Typhus and Rocky Mountain Spotted Fever (page 5)
(This chapter has 6 pages)
© Kenneth Todar, PhD
Signs and Symptoms
Rocky Mountain spotted fever can be very difficult to diagnose in its
early stages, even among experienced physicians who are familiar with
disease. Patients infected with R. rickettsii generally visit a
physician in the first week of their illness, following an incubation
of about 5-10 days after a tick bite. The early clinical presentation
Rocky Mountain spotted fever is nonspecific and may resemble a variety
of other infectious and non-infectious diseases.
Initial symptoms may include fever, nausea, vomiting, severe
muscle pain, and lack of appetite. Later signs and symptoms include
abdominal pain, joint pain and diarrhea.
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. The rash first appears
days after the onset of fever and is often not present or may be very
when the patient is initially seen by a physician. Younger patients
develop the rash earlier than older patients. Most often it
as small, flat, pink, non-itchy spots (macules) on the wrists,
and ankles (Figure 13). These spots turn pale when pressure is
and eventually become raised on the skin. The characteristic red,
spotted (petechial) rash of Rocky Mountain spotted fever is usually not
seen until the sixth day or later after onset of symptoms, and this
of rash occurs in only 35% to 60% of patients with Rocky Mountain
fever (Figure 14). The rash involves the palms or soles in as
as 50% to 80% of patients; however, this distribution may not occur
later in the course of the disease. As many as 10% to 15% of
may never develop a rash.
Figure 13. Early
rash on sole of foot. (CDC)
Figure 14. Late
rash on palm and forearm. (CDC)
Rocky Mountain spotted fever can be a very severe illness and
often require hospitalization. Because R. rickettsii
the cells lining blood vessels throughout the body, severe
of this disease may involve the respiratory system, central nervous
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
dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a
genetic condition affecting approximately 12% of the U.S.
male population; deficiency of this enzyme is associated with a high
of severe cases of Rocky Mountain spotted fever. This is a rare
course that is often fatal within 5 days of onset of illness.
Long-term health problems following acute Rocky Mountain spotted
infection include partial paralysis of the lower extremities, gangrene
requiring amputation of fingers, toes, or arms or legs, hearing loss,
of bowel or bladder control, movement disorders, and language
These complications are most frequent in persons recovering from
life-threatening disease, often following lengthy hospitalizations.
There is no widely available laboratory assay that provides rapid
of early Rocky Mountain spotted fever. Treatment decisions must
based on epidemiologic and clinical clues, and should never be delayed
while waiting for confirmation by laboratory results.
Serologic assays are the most widely available and frequently used
for confirming cases of Rocky Mountain spotted fever. The indirect
assay (IFA) is generally considered the reference standard in Rocky
spotted fever serology and is the test currently used by CDC and most
public health laboratories (Figure 15).
Figure 15. IFA reaction of a
positive human serum on Rickettsia rickettsii grown in chicken
sacs, 400X. (CDC)
IFA can be used to detect either IgG or IgM antibodies. Blood
taken early (acute) and late (convalescent) in the disease are the
specimens for evaluation. Most patients demonstrate increased IgM
by the end of the first week of illness. Diagnostic levels of IgG
generally do not appear until 7-10 days after the onset of
It is important to consider the amount of time it takes for antibodies
to appear when ordering laboratory tests, especially because most
patients visit their physician relatively early in the course of the
diagnostic antibody levels may be present. The value of testing
sequential serum or plasma samples together to show a rising antibody
is considerably more important in confirming acute infection with
agents because antibody titers may persist in some patients for years
the original exposure.
Another approach to Rocky Mountain spotted fever diagnostics is
This method is used by taking a skin biopsy of the rash from an
patient prior to therapy or within the first 48 hours after antibiotic
therapy has been started. Because rickettsiae are focally
in lesions of Rocky Mountain spotted fever, this test may not always
the agent. Even in laboratories with expertise in performing this test,
the sensitivity is only about 70% on biopsied tissues. This assay
may also be used to test tissues obtained at autopsy and has been used
to confirm Rocky Mountain spotted fever in otherwise unexplained deaths
(Figure 16). Immunostaining for spotted fever group rickettsiae is
by the CDC, a few state health departments, and some university-based
and commercial laboratories in the United States.
Figure 16. Red
indicate immunohistological staining of Rickettsia rickettsii
endothelial cells of a blood vessel from a patient with fatal
Appropriate antibiotic treatment should be initiated immediately when
there is a suspicion of Rocky Mountain spotted fever on the basis of
and epidemiologic findings. Treatment should not be delayed until
confirmation is obtained.
If the patient is treated within the first 4-5 days of the disease,
fever generally subsides within 24-72 hours after treatment with an
antibiotic (usually a tetracycline). In fact, failure to respond
to a tetracycline antibiotic argues against a diagnosis of RMSF.
ill patients may require longer periods before their fever resolves,
if they have experienced damage to multiple organ systems. Prophylactic
therapy in non-ill patients who have had recent tick bites is not
and may, in fact, only delay the onset of disease.
Doxycycline (100 mg every 12 hours for adults or 4 mg/kg body weight
per day in two divided doses for children under 45 kg [100 lb.]) is the
drug of choice for patients with Rocky Mountain spotted fever. Therapy
is continued for at least 3 days after fever subsides and until there
unequivocal evidence of clinical improvement, generally for a minimum
total course of 5 to 10 days. Severe or complicated disease may require
longer treatment courses. Doxycycline is also the preferred drug for
with ehrlichiosis, another tick-transmitted infection with signs and
that may resemble Rocky Mountain spotted fever.
Tetracyclines are usually not the preferred drug for use in pregnant
women because of risks associated with malformation of teeth and bones
in unborn children. Chloramphenicol is an alternative drug that can be
used to treat Rocky Mountain spotted fever; however, this drug may be
with a wide range of side effects including aplastic anemia, and
may require careful monitoring of blood levels.
Prevention and Control
Limiting exposure to ticks is the most effective way to reduce the
likelihood of Rocky Mountain spotted fever infection. In persons
to tick-infested habitats, prompt careful inspection and removal of
or attached ticks is an important method of preventing disease. It may
take several hours of attachment before organisms are transmitted from
the tick to the host.
Currently, no licensed vaccine is available for Rocky Mountain
It is unreasonable to assume that a person can completely eliminate
activities that may result in tick exposure. Therefore, prevention
should be aimed at personal protection. CDC recommends the following
-Wear light-colored clothing to allow you to see ticks that are
on your clothing.
-Tuck your pants legs into your socks so that ticks cannot crawl up
the inside of your pants legs.
-Apply repellents to discourage tick attachment. Repellents
permethrin can be sprayed on boots and clothing, and will last for
days. Repellents containing DEET (diethyltoluamide) can be applied to
skin, but will last only a few hours before reapplication is necessary.
Use DEET with caution on children. Application of large amounts of DEET
on children has been associated with adverse reactions.
-Conduct a body check upon return from potentially tick-infested
by searching your entire body for ticks. Use a hand-held or full-length
mirror to view all parts of your body.
-Remove any tick you find on your body. Parents should check their
for ticks, especially in the hair, when returning from potentially
areas. Additionally, ticks may be carried into the household on
and pets. Both should be examined carefully.
Strategies to reduce populations of vector ticks through area-wide
application of acaricides (chemicals that will kill ticks and mites)
control of tick habitats (e.g., leaf litter and brush) have been
in small-scale trials. New methods being developed include applying
to rodents by using baited tubes, boxes, and feeding stations in areas
where these pathogens are endemic. Biological control with fungi,
nematodes, and parasitic wasps may play alternate roles in integrated
control efforts. Community-based, integrated, tick-management
may prove to be an effective public health response to reduce the
of tick-borne infections. However, limiting exposure to ticks is
the most effective method of prevention.