Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (462 page)

Core laboratory
: Leukopenia (with left shift of PMNs), thrombocytopenia, and elevation of serum aminotransferases are commonly seen but are nonspecific findings in patients with HME and HGA.

CSF findings
: Pleocytosis and protein elevation are commonly seen in patients with neurologic complications of HME; CSF is usually normal in HGA patients with neurologic complications.

ANTHRAX (
BACILLUS ANTHRACIS
)

   Definition

Anthrax is caused by infection with
Bacillus anthracis
, a large, spore-forming grampositive rod (GPR). Naturally occurring anthrax is a zoonotic disease associated with grazing animals in regions without effective vaccination programs; humans may be infected as secondary hosts, usually through contact with spores. In the United States, sporadic infection has been associated with contact with animal products imported from regions with endemic infection.

Anthrax has been recognized as a potential agent of bioterrorism or biologic warfare because of the ability to “weaponize” the organism and the severity of disease caused by airborne spores.

Anthrax is a national notifiable infectious disease. Reporting to public health departments is mandated for all suspected or confirmed cases of
B. anthracis
infection.

   Who Should Be Suspected?

There are three major anthrax syndromes, cutaneous, alimentary tract, and inhalational, depending on the route of transmission. Other organ systems may be infected by spread from a primary site of infection. The diagnosis of anthrax requires a high index of suspicion. Early recognition and antibiotic treatment are critical for successful management of patients with GI, pulmonary, or other invasive infections.

   Laboratory Findings

Cultures
: Specimens may include vesicular fluid, swab, or tissue from below the leading edge of cutaneous lesions, lower respiratory secretions/sputum, feces, or CSF, or specimens from other infected sites. Blood cultures should be submitted for all patients with suspected anthrax.

Gram stain
: Shows large GPBs; may form short chains. Capsules may be apparent. Spores may be seen in subcultures.

BARTONELLOSIS

   Definition

Bartonellosis refers to a range of syndromes caused by infection with
Bartonella
species, fastidious GNBs. The bacteria may be isolated from a wide range of animals, which serve as the likely reservoir for human infection.

   Who Should Be Suspected?

Bartonella henselae
infection most commonly manifests as cat scratch disease (CSD). CSD is most commonly manifested by self-limited lymphadenopathy, but a number of organ systems may be involved.
Bartonella henselae
should be strongly suspected on the basis of typical clinical presentation after exposure to cats, especially if flea infested.

Almost all patients with CSD present with a cutaneous lesion at the site of inoculation and regional lymphadenopathy. Skin lesions appear within 3–10 days after inoculation and may show vesicular, erythematous, and papular phases. Lesions are minimally symptomatic and resolve after several weeks, healing without scarring. Primary lesions may occur on the mucous membranes or conjunctiva. Tender solitary lymphadenopathy, typically with overlying erythema, develops in the 2nd or 3rd week after infection but may be delayed up to several months. In uncomplicated cases, lymphadenopathy usually resolves within 1–4 months.

Bartonella quintana
was associated with trench fever during World War I. Trench fever is transmitted by the body louse; patients present with fever, malaise, sweats and chills, conjunctivitis, retro-orbital pain, back and neck pain, and anterior tibial pain. In recent years,
B. quintana
has emerged as a cause of “urban trench fever” in indigent populations with bacteremia and endocarditis, peliosis, and bacillary angiomatosis, primarily in patients with AIDS. Suspect infection in patients with culture-negative endocarditis, vascular proliferative lesions (bacillary angiomatosis [BA]), and cystic lesions of the liver or other internal organs (peliosis).

   Laboratory Findings

Direct examination and histopathology
: Histopathologic examination may provide strong support for diagnosis of bartonellosis. Demonstration of typical granulomas and typical organisms (Warthin-Starry stain) strongly supports the diagnosis of CSD. Histologic appearance of excised lymph node, skin lesions, and so on may be characteristic but are nonspecific. In BA, there is H&E staining of vascular proliferation. Lesions show eosinophilic debris; Warthin-Starry staining reveals masses of small bacteria.

Molecular diagnosis
: Sensitive and specific molecular diagnostic assays have been described. PCR and related methods are playing an increasing role in the diagnosis of infections caused by
Bartonella
species, when available. There are no FDA-approved methods, however.

Culture
: Isolation of
Bartonella
in culture provides a definitive diagnosis, but special culture techniques and prolonged incubation are required. Cultures are often negative in infected patients. In addition, most clinical laboratories cannot perform the testing required for specific identification, so isolates must be sent to a reference laboratory for further characterization. The lysis centrifugation method is recommended for blood cultures to detect
Bartonella
bloodstream infections.

Serology
: The sensitivity and specificity of serologic assays are not high, limiting their utility for the diagnosis of bartonellosis. There may be cross-reactions with other
Bartonella
species and other, unrelated organisms. The prevalence of seropositivity in general populations may be significant, suggesting that asymptomatic
Bartonella
infection is common. In CSD,
B. henselae
IFA IgG titer of ≥1:256 is consistent with recent infection, supporting a diagnosis of CSD. Titers ≥1:64 to 128 are suggestive but should be repeated after 2 weeks to confirm diagnosis; titers <1:64 indicate that recent infection is unlikely. A positive reaction for
B. henselae
IgM strongly supports recent infection, but IgM production is typically brief.

General laboratory
: ESR and CRP are usually increased in bartonellosis. WBC count is usually normal but may be slightly elevated ≤13,000/μL; eosinophils may be increased. Other laboratory findings are related to specific organ involvement.

BORDETELLA PERTUSSIS

See Chapter
13
, Respiratory, Metabolic, and Acid–Base Disorders.

BOTULISM (
CLOSTRIDIUM BOTULINUM
)

   Definition