Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (463 page)

Botulism describes a toxin-mediated paralytic disease caused by heat-labile toxins of
Clostridium botulinum
. Botulism toxins bind to the synaptic vesicles of cholinergic nerves, preventing release of acetylcholine into the neurosynaptic cleft. Botulism intoxication results in acute, symmetrical, flaccid paralysis. Patients usually present with impairment of cranial nerves and muscles of the head and neck. Symptoms progress to symmetrical paralysis of the musculature of the trunk, progressing to the extremities. Respiratory paralysis is usually the most life-threatening manifestation of botulism.

Several distinct botulism syndromes have been described. Foodborne botulism usually presents in adults after ingestion of preformed toxin in
C. botulinum
– contaminated food. Infant botulism, the most commonly encountered form of botulism, results from the ingestion of
C. botulinum
organisms or spores that proliferate and produce toxin within the infant’s gut. Wound botulism is a rare form of botulism in which toxin is formed in vivo by
C. botulinum
organisms causing wound infection.

Clinicians must be alert to patients presenting with signs and symptoms compatible with botulism because they may represent an index case of a bioterror incident. Reporting to public health authorities is mandated for suspected or documented botulism.

   Laboratory Findings

Culture
: In the proper clinical setting, diagnosis may be established by isolation of
C. botulinum
or botulinum toxin from patient specimens or food. Isolation of
C. botulinum
by anaerobic culture may be attempted for infected patient specimens or feces. Isolation from food should only be attempted by specialized reference laboratories.

Toxin detection
: Typical specimens include any food suspected in an outbreak, serum (15–20 mL in adults; 2–3 mL in infants), gastric contents or vomitus, and feces (as much as possible, up to approximately 50 g). Toxin detection is performed by specialized reference or public health laboratories.

Core laboratory
: Routine laboratory tests are usually normal.

BRUCELLA

   Definition

Brucella
species are fastidious, slowly growing GNRs. Isolates are highly infectious and pose a serious risk of laboratory-acquired infections; clinicians should alert the laboratory when brucellosis is suspected. The CDC has classified
Brucella
species as potential bioterror agents, and reporting is mandated when
Brucella
infection is suspected or confirmed.

   Who Should Be Suspected?

Brucellosis causes a wide spectrum of clinical disease with acute and chronic forms. In affected patients, fever, chills, night sweats, malaise, headache, and other nonspecific symptoms are common and may mimic other acute or chronic illness or fever of unknown origin (FUO). Bacteremia often occurs and may result in secondary localized infections; suppurative lesions may affect any organ system, including bone and joints, liver, and spleen.

   Laboratory Findings

Cultures
:
Brucella
species primarily infect the RE system with secondary spread to other organ systems. Therefore, blood and bone marrow cultures are specimens of choice for diagnosis. Other infected patient samples may also be submitted for culture.

Serology
: Acute serum samples should be collected, followed by convalescent samples several weeks later. IgM titers are increased within the first 1–2 weeks of acute infection; there is a transition to IgG production after the 2nd week. Titers fall in response to effective therapy.

BURKHOLDERIA INFECTIONS

   Definition

Burkholderia
species are nonfastidious, glucose nonfermenting GNBs.
Burkholderia pseudomallei
and
Burkholderia cepacia
are the species most commonly associated with human disease.
Burkholderia pseudomallei
has a fairly restricted, geographically limited incidence; primary infection in the United States is uncommon.
Burkholderia cepacia
has been isolated from numerous environmental sources.

Burkholderia mallei
(a primary pathogen of horses) and
B. pseudomallei
have been classified by the CDC as potential bioterror agents. Reporting is mandated as soon as
B. mallei
or
B. pseudomallei
infection is suspected or confirmed.

   Who Should Be Suspected?

Burkholderia pseudomallei
causes melioidosis, an infection with a restricted geographic distribution; disease is largely confined to Southeast Asia and northern Australia. Direct contact with or inhalation of contaminated soil or water is the most common mode of transmission. Most infections are asymptomatic or minimally symptomatic with a flu-like syndrome but may present with acute or chronic illness, including pneumonia, skin and soft tissue infections, chronic suppurative infections, and bacteremia.

Burkholderia cepacia
has emerged as a significant pathogen, primarily causing disease in patients with CF and chronic granulomatous disease. In patients with CF, respiratory tract colonization may be associated with a rapid decline in pulmonary function and an increased mortality in the year following acquisition.

   Laboratory Findings

Culture
:
Burkholderia pseudomallei
or
mallei
may be isolated by routine bacterial culture but may require additional incubation time. Selective media should be used for isolation of
B. cepacia
from lower respiratory specimens collected from CF patients.

Susceptibility
:
Burkholderia cepacia
is intrinsically resistant to aminoglycosides but typically susceptible to TMP/SMX.

CAMPYLOBACTER GASTROENTERITIS

   Definition