TETANUS overactivity results in severe tachycardia, swings in blood pres-

sure, profuse sweating, and (rarely) ileus. An exaggerated startle-

Method of like response to stimuli with motor and autonomic components is
Dilip R. Karnad, MD also typical. Generalized spasms may mimic tonic seizures.␣

Tetanus is a potentially fatal illness caused by the neurotoxin
produced by the spore-bearing anaerobic bacterium Clostridium
tetani. As the causative organism and its spores are ubiquitous,
nonimmune individuals in any part of the world may get tetanus
unless they are protected by the highly effective vaccine.
Epidemiology
As a result of effective universal immunization, tetanus is rare in
the developed world. Twenty to 40 cases of tetanus occur annu-
ally in the United States and 12 to 15 cases per year have been
reported from the United Kingdom in the last 10 years. Although
progressively declining in the developing world due to improved
immunization coverage, according to WHO figures, more than
500 cases were reported in 2012 from each of these nations:
Angola, Bangladesh, Congo, India, and Uganda. While tetanus
may affect individuals of all ages, a significant number of cases in
developed countries are elderly people who did not receive a pri-
mary immunization or lacked the booster dosage needed to main-
tain protective immunity. In developing countries, most cases are
neonates (tetanus neonatorum), children who are born to nonim-
munized mothers and thus lack transplacentally acquired passive
immunity. Infection of the umbilical stump due to poor hygiene
results in severe tetanus that has mortality in excess of 60%.
The infection is caused by the gram-positive, spore-bearing bac-
VIII Infectious Diseases
Clinical Manifestations
An attempt should be made to locate the predisposing wound, such
as cuts, abrasions, burns, puncture wounds, and other skin lesions.
Uncommon causes include needle-sticks in intravenous drug abus-
ers, ulcerated malignant tumors, and chronic middle-ear infection
in children (otogenic tetanus). In up to 30% of patients, no site
of infection is discovered. The incubation period is the interval
between the injury and the onset of symptoms and can range from
a few days to a few months (usually 3–21 days). A short incubation
period (<7 days) suggests the likelihood of developing severe teta-
nus; however, a long incubation period does not necessarily indi-
cate a milder disease. The period of onset (the interval between the
first symptom and first paroxysmal muscle spasm) is a better pre-
dictor of severity: early elective tracheal intubation and mechanical
ventilation are usually required if the interval is <48 hours.
Generalized Tetanus
Initial symptoms include an inability to open the mouth (lockjaw
or trismus), difficulty in chewing and swallowing, and stiffness
of neck muscles. The contraction of facial muscles produces the
characteristic sneering smile (risus sardonicus) (Figure 1). In severe
cases, intermittent spasms are provoked by attempts to speak or
swallow. Pooled saliva from hypersalivation and dysphagia may
trigger cough and laryngeal spasms; if prolonged, these may prove
fatal. Rigidity of paraspinal muscles follows, and hyperextension

terium C. tetani, the spores of which exist in the soil, in animal of the spine results in opisthotonus (Figure 2). Finally, proximal
feces, and even in the human gastrointestinal tract. Spores remain muscles of the extremity are also affected. Deep tendon reflexes
dormant and viable for several months and are destroyed by auto- are always exaggerated and ankle clonus is common. Tonic muscle
claving at 1 atmosphere pressure at 120°C for 15 minutes. When
inoculated into human or animal tissues, they transform into
motile bacilli in an anerobic environment that produce a potent
exotoxin, tetanospasmin, which produces the manifestations of
tetanus. It must be emphasized that tetanus is not transmitted
from human to human, and patients do not require isolation.␣

Risk Factors
Elderly individuals are at increased risk, as they may not have
660 received adequate immunization or may have waning immunity.
Other predisposed groups include immigrants from countries
with an unreliable immunization program, immunosuppressed
individuals (with HIV infection or receiving immunosuppres-
sive drugs), and intravenous drug addicts. Local factors include
wounds with crushed, devitalized tissue or contaminated by
dirt or rust, such as open fractures, punctures, and abscesses.
However, even scratches, chronic ulcers, or tattooing may cause
tetanus. In developing countries, unsafe practices related to termi-
nation of pregnancy may cause maternal tetanus; newborn babies
born outside of medical facilities are at risk of neonatal tetanus.␣ Figure 1 Typical facial expression with the sneering smile (risus sardoni-
cus), wrinkled forehead, narrow palpebral fissures, and “crow’s feet” at
Pathophysiology the lateral palpebral margins from the tonic contraction of muscles of
Tetanospasmin is a highly toxic protein released by C. tetani. It facial expression in moderate tetanus.
is absorbed into the circulation and reaches the ends of motor
axons all over the body, from where it is transported proximally
along the axonal cytoplasm to motor nuclei in the brainstem and
spinal cord at a rate of 3 to 13 mm/hour. A fragment of the toxin
then binds inhibitory interneurons that produce gamma-amino
butyric acid (GABA) and glycine and inactivates synaptobrevin, a
protein that is essential for the release of these neurotransmitters
from presynaptic vesicles.
The loss of normal inhibition at motor and autonomic neu-
rons results in spontaneous discharge of nerve impulses as well
as exaggerated responses to stimuli manifesting as tonic muscle
contraction with superadded intermittent muscle spasms. As teta-
nospasmin reaches the motor nuclei of the shortest motor axons
first, muscles innervated by motor cranial nerves are affected first, Figure 2 Spasm of paraspinal muscles, producing the hyperextended
followed by trunk muscles, and finally the extremities. Autonomic opisthotonic posture in severe tetanus.

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spasms may affect head and neck muscles and laryngeal muscles,
or may be generalized. Paroxysmal spasms occur spontaneously
or in response to loud noise, bright lights, or attempts to speak or
swallow. Prolonged spasms may compromise breathing.
The Ablett classification is commonly used to grade the sever-
ity of tetanus. Grade I (mild) tetanus is characterized by mod-
erate trismus and general spasticity without spasms, dysphagia,
or respiratory distress. Grade II (moderate) tetanus has severe
trismus, intermittent short spasms, mild tachypnea, and dyspha-
gia. Grade III (severe) tetanus is associated with severe rigidity,
prolonged spasms, severe dysphagia, tachypnea, apneic spells,
and tachycardia. The presence of additional violent autonomic
disturbances with persistent or intermittent episodes of severe
hypertension and tachycardia alternating with hypotension and
bradycardia is classified as Grade IV (very severe) tetanus. Car- A
diac arrhythmias, peripheral vasoconstriction, and sudden asys-
tole may also occur in very severe tetanus.
Despite the use of antitetanus immune globulin (HyperTET) to
neutralize circulating tetanus toxin, the disease may progress for
up to 2 weeks as more intraaxonal toxin continues to reach the
central nervous system. Manifestations persist for another 2 to 3
weeks before gradually subsiding. During this period, an apparently
stable patient is at risk of developing sudden asphyxia due to severe
generalized or laryngeal spasms. Patients may develop fever, rha-
bodomyolysis, and hyperthermia due to excessive muscular activity.␣

Cephalic Tetanus
Following injuries to the head or face, in some patients, the toxin
reaches the local motor nuclei earlier and produces a combina-
tion of partial paralysis and overactivity—more severely affected
motor neurons stop functioning while the remaining fibers are
overactive and cause muscle spasm (Figure 3).␣
Localized Tetanus
In this rare form of tetanus, manifestations are restricted to
muscles in the region of the wound. These patients have a good
prognosis.␣
B
Figure 3 Cephalic tetanus: This 6-year-old child developed mild tetanus
3 weeks after a wound on his right cheek was sutured. He had cephalic
tetanus characterized by partial paralysis of the right facial nerve along
with overactivity of the unaffected nerve fibers. A, Note the overactivity
of the facial muscles with a narrow palpebral and prominent nasolabial
fold on the same side as the injury. On asking him to shut his eyes tight
(B), weakness of the orbicularis oculi and other facial muscles on the right

Diagnosis
C. tetani can be isolated from the wound in <30% of cases, and
microbiological and other laboratory tests do not help in confirm-
ing the diagnosis. The diagnosis is entirely clinical. In an individual
with a predisposing injury, the presence of trismus, rigidity of neck,
abdominal and paraspinal muscles, and severe hyperreflexia are sug-
gestive. The spatula test is a useful bedside test: A spatula (tongue
depressor) is inserted into the mouth to touch the posterior pharyn-
geal wall. Normally, a gag reflex is activated in an attempt to expel
the spatula. In tetanus, severe spasms of the masseters results in the
patient biting on the spatula, making it difficult to withdraw—a
positive test. In one study, the spatula test was positive in 94% of
patients with tetanus and in none without tetanus. The electromyo-
gram shows the continuous discharge of motor units in moderate
tetanus and the absence of the normal silent period.␣
Tetanus
side become manifest.
Neutralization of Toxin
Although unsupported by randomized studies, human tetanus
immune globulin (HyperTET) (3000–6000 units) is adminis- 661
tered intramuscularly to neutralize the circulating toxin. This
does not bind to the toxin that has already entered neurons.
There is insufficient evidence favoring intrathecal administra-
tion1 of tetanus immune globulin over the usual intramuscu-
lar route, although one randomized study showed a shortening
of the course of tetanus. Equine antiserum2 (10,000–20,000
units) may be administered after skin testing for hypersensitiv-
ity. Though rarely used today due to the risk of anaphylaxis
or serum sickness, it has the advantage of being administered
intravenously.␣

Differential Diagnosis Control of Clostridial Infection

While the diagnosis of tetanus is easy in severe tetanus, it may be
mistaken for other conditions in its initial stages (Table 1). The
spatula test is negative in other conditions causing trismus. Abdom-
inal muscles usually relax after adequate sedation. As in spasticity
due to cord compression, deep reflexes are exaggerated; however,
the plantar response, which is extensor in spinal cord disorders,
is always flexor with tetanus. Unlike seizures or other intracranial
diseases, the patient with tetanus is always fully alert and awake.␣
Treatment
In patients with life-threatening spasms, prompt, adequate seda-
tion is the first step in management. Patients must be observed in
an intensive care unit because the disease may rapidly worsen.
They should be nursed in a quiet, dimly lit room in order to keep
external stimuli to a minimum—this is difficult in modern inten-
sive care units.
Benzylpenicillin (Penicillin G) in a dose of 10 to 12 million units
per day is given intravenously for 10 days. In one study, metro-
nidazole (Flagyl) (500 mg every 6 hour for 10 days) was superior
to procaine penicillin (Wycillin),1 presumably because procaine
and penicillin are GABA antagonists and may worsen manifesta-
tions of tetanus. However, a more recent study showed that a
single intramuscular injection of 1.2 million units of benzathine
penicillin (Bicillin LA)1 was as effective as benzylpenicillin or
metronidazole. Fortunately, resistance to these antibiotics has not
been reported. Debridement of the infected wound and abscess
drainage should be performed after spasms have been adequately
controlled.␣
1 Not FDA approved for this indication.
2 Not available in the United States.

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TABLE 1 Conditions that Mimic Clinical Manifestations of
Tetanus
CLINICAL FEATURE DIFFERENTIAL DIAGNOSIS
Trismus Acute tonsillar abscess,
temporomandibular joint disease,
extraptramidal reaction to drugs,
dental pathology
Neck stiffness Cervical spine disease; extrapyramidal
reaction to drugs such as
antipsychotics, antiemetics, or
metoclopramide; meningitis;
subarachnoid hemorrhage
Abdominal rigidity Acute abdomen
Dysphagia Myasthenia gravis, acute bulbar
paralysis, rabies
Muscle spasms Seizures, spasticity due to spinal cord
disease, stiff man syndrome
Control of Muscle Spasms
Benzodiazepines (diazepam [Valium] or lorazepam [Ativan]1) are
the preferred drugs and act by enhancing the effect of GABA on its
receptor on the postsynaptic membrane, thus potentially antago-
nizing the effect of tetanospasmin. However, as very little GABA is
released in tetanus, large doses (up to 1000 mg/day3) of diazepam
may be required to achieve adequate sedation and muscle relax-
VIII Infectious Diseases
ation. Diazepam may be administered intravenously (10–30 mg
in 5 mg boluses every 5 minutes)3 or through a nasogastric tube
(10–40 mg every 1 to 2 hours).3 Barbiturates and chlorproma-
zine (Thorazine)1 are alternative agents. Other sedative hypnotic
agents such as midazolam (Versed)1 and propofol (Diprivan)1
have also been used with good effect. In mild to moderate tetanus,
drug doses can be titrated to achieve moderate sedation and con-
trol rigidity and spasms without causing respiratory depression. In
severe cases, however, spasms may not be controlled despite large
doses, increasing the risk of severe central nervous system (CNS)
depression. In these patients, heavy sedation combined with neu-
romuscular blockade and mechanical ventilation is required. In
662 about 10% of cases, benzodiazepines may produce paradoxical
excitation instead of sedation; increasing doses make the patient
more wakeful, agitated, and delirious, with increased spasms. Dis-
continuation of diazepam and the use of barbiturates and chlor-
promazine may prevent the need for paralysis and mechanical
ventilation. Pancuronium (Pavulon),1 vecuronium (Norcuron),1
and rocuronium (Zemuron)1 are often used for neuromuscular
blockade. Atracurium (Tracrium)1 could also be used but may
have unfavorable cardiovascular effects. Intravenous and intrathe-
cal baclofen (Lioresal Intrathecal)1 have been used in some case.␣
Airway Management
Tracheostomy or endotracheal intubation is required in moder-
ate and severe tetanus to prevent respiratory failure due to laryn-
geal spasm and aspiration of oropharyngeal secretions. In most
developing countries, elective tracheostomy is performed early in
severe tetanus. In countries with superior intensive care facilities,
heavy sedation, neuromuscular blockade, endotracheal intuba-
tion, and mechanical ventilation are preferred, with tracheostomy
being reserved for those who need prolonged ventilation.␣
Control of Autonomic Disturbances
With good intensive care, mortality due to respiratory failure
has been drastically reduced. Autonomic dysfunction is now the
major challenge in patients with severe tetanus; it is common even
in sedated and paralyzed patients. Various measures to control
autonomic fluctuations include intravenous fluid loading, oral
1Not FDA approved for this indication.
3Exceeds dosage recommended by the manufacturer.
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and parenteral beta-blockers, alpha-blockers, centrally acting
sympatholytics such as clonidine (Catapres)1 or dexmedetomi-
dine (Precedex),1 and epidural or spinal bupivacaine (Marcaine).1
More recently, infusion of dexmedetomidine has been used by
some authors. Many patients may develop sudden asystole, pos-
sibly due to sudden parasympathetic discharge, catecholamine-
induced myocardial damage, or sudden loss of sympathetic drive.
Consequently, the use of long-acting antiadrenergic drugs should
be avoided. Increasing the level of sedation itself is also effective,
to a significant extent.
The agent most frequently used for autonomic dysfunction is
intravenous magnesium sulfate.1 A randomized controlled trial
in Vietnamese patients showed that magnesium sulfate did not
decrease mortality, ICU stay, or the need for mechanical ventilation
but did reduce the dose of sedatives and neuromuscular blocking
drugs required. This study used a loading dose of 40 mg/kg over 30
minutes, followed by intravenous infusion of 2 g/hour in patients
>45 kg and 1 to 5 g/hour in patients ≤45 kg. Infusion was titrated to
maintain serum magnesium levels between 2 and 4 mmol/L.␣
Other Measures
Continuous muscle hyperactivity and spasms greatly increase
caloric requirements. Most patients require nasogastric tube
feeding because of trismus and dysphagia. A catabolic state simi-
lar to sepsis may develop in very severe tetanus. Consequently,
patients lose up to 15% of their body weight during the illness.
Good nursing care is essential to prevent pressure sores, deep vein
thrombosis, stress ulcers, and aspiration pneumonia. Urinary
catheterization is required in most patients as urinary retention
is common and distension of the urinary bladder may provoke
spasms and autonomic overactivity. All patients should be started
on a primary immunization schedule against tetanus.␣
Complications
Respiratory failure may occur due to laryngeal obstruction, pro-
longed spasm of respiratory muscles, aspiration pneumonia, or
sedative drugs. Severe spasms may result in tongue-bite, compres-
sion fractures of midthoracic vertebrae, rhabdomyolysis, myo-
globinuria, and renal failure. Rarely, patients may develop acute
respiratory distress syndrome (ARDS) either due to tetanus itself
or as a result of secondary bacterial sepsis. Cardiac arrhythmias
and sudden asystole are common in patients with autonomic
dysfunction. Acute myocardial infarction may occur in elderly
patients with underlying coronary artery disease due to sympa-
thetic overactivity. Deep vein thrombosis and pressure sores are
preventable complications. The overall mortality ranges from
40% to 60% in countries with inadequate health care facilities.
With good intensive care, mortality as low as 10% is reported
in some series. Mortality is higher in neonates, the elderly, and
patients with a short incubation period and period of onset.␣
Prevention
Adsorbed tetanus toxoid (Tt), derived from formaldehyde-treated
tetanus toxin, is extremely effective in inducing active immunity.
It is available as a single-antigen preparation or in combination
with diphtheria toxoid as pediatric diphtheria-tetanus toxoid
(DT) or adult tetanus-diphtheria (Td), and with both diphtheria
toxoid and acellular pertussis vaccine as DTaP (Infanrix, Tripe-
dia) or Tdap (Adacel, Boostrix) (lower-case alphabets indicate
lower doses of antigens). Pediatric vaccines (DT and DTaP) con-
tain identical amounts of tetanus toxoid as adult vaccines, but
three to four times as much diphtheria toxoid. The usual schedule
for primary immunization in children <7 years consists of four
doses of DTaP or DT at age 2, 4, 6, and 15 to 18 months. A
booster dose is recommended at 4 to 6 years of age. In individu-
als aged 7 years or older, three doses of the adult formulation are
administered; the second dose is given 4 to 8 weeks after the first,
and the third dose after another 4 to 6 months. Further booster
doses are needed every 10 years to maintain antibody titers above
the protective level of 0.1 IU/mL.
1Not FDA approved for this indication.
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 After administration of Tt to individuals with wounds, protective
titers of antibody are achieved after at least 2 weeks. Consequently,
passive immunization with 250 units of human tetanus immune
globulin (HyperTET) or 1500 units of equine antitetanus serum2
administered intramuscularly is needed to confer protection during
these initial few weeks. This is especially required in individuals
with tetanus-prone wounds who have not received at least three
doses of tetanus toxoid in the past. Previously unimmunized indi-
viduals with clean, minor, nontetanus prone wounds do not need
any passive immunization, but should receive active immunization.
Passive immunization is not necessary in those who have received
three or more doses of the toxoid. These individuals should receive
a dose of Tt (or Td) if more than 10 years have elapsed since the last
booster dose and they have nontetanus prone wounds or if >5 years
have elapsed after the booster dose and they have a tetanus-prone
wound. In countries where neonatal tetanus is common, primary
immunization of women during pregnancy has been advocated as
a public health program to prevent neonatal tetanus.
References
Apte NM, Karnad DR: The spatula test: A simple bedside test to diagnose tetanus,
Am J Trop Med Hyg 53:386–387, 1995.
Centers for Disease Control and Prevention: In Atkinson W, Wolfe S, Hamborsky J,
editors: Epidemiology and Prevention of Vaccine-Preventable Diseases, ed 12th,
Washington, DC, 2011, Department of Health and Human Services, Centers for
Disease Control and Prevention, pp 291–299.
Farrar JJ, Yen LM, Cook T, et al: Tetanus, J Neurol Neurosurg Psychiatry 69:292–
301, 2000.
Gibson K, Uwineza JB, Kiviri W, Parlow J: Tetanus in developing countries: A case
series and review, Can J Anaesth 56:307–315, 2009.
Lisboa T, Ho YL, Filho GTH, et al: Guidelines for the management of accidental
tetanus in adult patients, Rev Bras Ter Intensiva 23:394–409, 2011.
Rodrigo C, Samarakoon L, Fernando SD, Rajapakse S: A meta-analysis of magne-
sium for tetanus, Anaesthesia 67:1370–1374, 2012.
Roper MH, Vandelaer JH, Gasse FL: Maternal and neonatal tetanus, Lancet
370:1947–1959, 2007.
Thwaites CL, Yen LM, Loan HT, et al: Magnesium sulphate for treatment of severe
tetanus: A randomized controlled trial, Lancet 368:1436–1443, 2006.
Trujillo MH, Castillo A, Espana J, et al: Impact of intensive care management on the
prognosis of tetanus. Analysis of 641 cases, Chest 92:63–65, 1987.
TICKBORNE RICKETTSIAL DISEASES (ROCKY
MOUNTAIN SPOTTED FEVER AND OTHER
SPOTTED FEVER GROUP RICKETTSIOSES,
EHRLICHIOSES, AND ANAPLASMOSIS)
Method of
Robert Wittler, MD
CURRENT DIAGNOSIS
• Early diagnosis of Rocky Mountain spotted fever (RMSF) and
other tickborne rickettsial diseases is made clinically. RMSF
should be considered in the setting of fever, headache, rash,
and a history of possible tick exposure. The rash is not always
present and typically occurs 2 to 4 days after the onset of fever.
• Diagnostic laboratory tests for rickettsial diseases, particularly
RMSF, are usually not helpful in making a timely diagnosis
during the initial states of illness.
• Tickborne rickettsial diseases can be confirmed by polymerase
chain reaction (PCR) during the acute stage if readily avail-
able (whole blood for ehrlichiosis and anaplasmosis and skin
biopsy or whole blood for RMSF) or at later stages by subse-
quently demonstrating a fourfold increase between acute
and convalescent (ideally 2 to 4 weeks apart) serum immuno-
globulin G (IgG) indirect immunofluorescence antibody titers.
PCR of whole blood for RMSF has low sensitivity, although
sensitivity increases in patients with severe disease.
• Typical findings of ehrlichiosis and anaplasmosis include
fever, headache, malaise, leukopenia, thrombocytopenia, and
elevated serum transaminases. Rash is often not present.
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CURRENT THERAPY
• Treatment of choice for all tickborne rickettsial diseases in
patients of all ages (including children less than 8 years of
age) is doxycycline (Vibramycin).
• The dose for doxycycline is 100 mg twice daily (intravenously
[IV] or orally depending on severity of illness) for adults. For
children weighing <45 kg,1 the recommended dose is 2.2 mg/
kg/dose IV or orally twice daily.
• Delay in recognition and appropriate treatment is the most
important factor associated with death from RMSF. Empiric
treatment within 5 days of the onset of symptoms with doxycy-
cline is the best way to prevent morbidity and death. Treatment
decisions should never be delayed while awaiting laboratory
confirmation, nor should treatment be discontinued solely on
the basis of a negative test result with an acute-phase specimen.
• Although optimal duration of therapy has not been well stud-
ied, a common treatment course for RMSF and ehrlichiosis is
at least 3 days after the patient defervesces (typically the mini-
mum total course is 5–7 days) or longer for severe illness. Ana-
plasmosis should be treated for 10 days to provide appropriate
therapy for possible coinfection with Borrelia burgdorferi.
• Historically chloramphenicol has been recommended for the
treatment of RMSF during pregnancy based on adverse ef-
fects of older tetracycline drugs (but not specifically doxy-
cycline). Although there is limited evidence, doxycycline has
Tickborne Rickettsial Diseases
not been associated with teratogenicity or maternal hepatic
toxicity during pregnancy, and doxycycline has been used
successfully to treat tickborne rickettsial disease in several
pregnant women without adverse effects.
• Chloramphenicol is not an alternative treatment for hu-
man monocytic ehrlichiosis (HME) or HGA. Chloramphenicol
treatment of RMSF has been associated with a greater risk of
death compared with doxycycline treatment.
• Limited case report data suggest that rifampin1 can be used
as an alternative to doxycycline for the treatment of con-
firmed (RMSF ruled out) mild anaplasmosis during pregnancy
or with documented tetracycline allergy.
1Not FDA approved for this indication.
663
Tickborne rickettsial diseases in humans often share clinical features
but are epidemiologically and etiologically distinct. In the United
States included diseases are (1) Rocky Mountain spotted fever
(RMSF) caused by Rickettsia rickettsii; (2) other spotted fever group
(SFG) rickettsioses, caused by Rickettsia parkeri and Rickettsia spe-
cies 364D; (3) Ehrlichia chaffeensis ehrlichiosis, also called human
monocytic ehrlichiosis (HME); (4) other ehrlichioses, caused by
Ehrlichia ewingii and Ehrlichia muris-like agent; and (5) anaplas-
mosis, caused by Anaplasma phagocytophilum, also called human
granulocytic anaplasmosis (HGA). The reported incidence of tick-
borne rickettsial diseases has increased in the United States. Tick-
borne rickettsial diseases, especially RMSF, continue to cause severe
illness and death in otherwise healthy adults and children, despite the
availability of effective antibiotic therapy. SFG rickettsioses (includ-
ing RMSF), ehrlichioses, and anaplasmosis are nationally notifiable
diseases in the United States. Providers report potential cases to
state or local health departments. In 2010, the reporting category of
RMSF was changed to spotted fever rickettsiosis, as serology does
not readily distinguish RMSF from other SFG rickettsioses.
Epidemiology
Tickborne rickettsial pathogens are maintained in natural cycles
involving domestic or wild vertebrates and ticks. The epidemiol-
ogy of each disease reflects the geographic distribution and seasonal
activities of the tick vectors and the natural vertebrate hosts, as well
as the human activities resulting in tick exposure. Although cases
have been reported in every month, most cases occur during April to
September, coincident with peak levels of tick host-seeking activity.
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