Clinical Laboratory Testing

Last updated May 25, 2011

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Specimen Collection and Transport
Laboratory Biosafety and Biosecurity Information
The Laboratory Response Network (LRN)
Standard Tests for Detection of B anthracis
Stepwise identification and confirmation
Antimicrobial Susceptibility Studies
Tests for Exposure
Bibliography

Specimen Collection and Transport

When the diagnosis of anthrax is being considered, the hospital clinical laboratory should be alerted because some laboratories will not further identify Bacillus species unless specifically requested. The following table outlines the collection of laboratory specimens for diagnosis of anthrax.

Collection and Transport of Laboratory Specimens for the Diagnosis of Anthrax^a-d
Type of Illness	Specimen Collection^e and Transport	Comments^f,g,h
Cutaneous anthrax^g	—All stages: Collect 2 swabs, one for Gram stain and culture, and 1 for PCR. —Vesicular stage: Perform Gram stain, culture, and PCR of fluids from unroofed vesicle (soak two dry sterile swabs in vesicular fluid). Note: Gram stain is most sensitive during vesicular stage. —Eschar stage: Perform Gram stain, culture, and PCR of ulcer base or edge of eschar without removing it. —Ulcer (no vesicle or eschar present): swab base of ulcer with pre-moistened sterile saline —A punch biopsy for IHC testing and a second biopsy for culture, Gram stain, PCR, and frozen-tissue IHC if patient has not received antibiotics should be obtained on all patients with suspected cutaneous anthrax. Include skin adjacent to papule or vesicle. If vesicles and eschars are both present, separate biopsies should be obtained. —Serum: collect acute serum within first 7 days of symptom onset, and convalescent serum 14-35 days after symptom onset. —Collect blood for culture and PCR with evidence of systemic involvement.	—Swabs: Moisten with sterile saline or water; transport in sterile tube at at 2^o-8^oC. Transport swabs for PCR only at –70^oC. Do not use transport medium. —Tissue, fresh, >5 mm³: Store and transport at 2^o-8^oC (<2 hr) or frozen at –70^oC (>2 hr). —Tissue, preserved in 10% buffered formalin, 1.0 cm³: Store and transport at room temperature. —Biopsy of lesions for histopathology, preserved in 10% buffered formalin, 0.3 mm diameter: Store and transport at room temperature. —Freeze serum after separation at –20^oC or colder, ship on dry ice. Ship part of sample (>1.0 mL) and retain part in case of shipping problems.^h —Obtain blood for culture per local protocol. Collect blood for PCR in EDTA (purple top) tube. Ship at room temperature (<2 hr transport time) or 2-8^oC (>2 hr transport time).
Inhalational anthrax^g	—If sputum is being produced, collect sputum specimen for Gram stain and culture (note: inhalational anthrax does not usually result in sputum production). —Obtain blood for smear, culture, and PCR. —If a pleural effusion is present, collect a specimen for culture, Gram stain, and PCR. —Collect CSF if meningeal signs are present or meningitis is suspected for culture, Gram stain, and PCR. —Serum: Collect acute serum within first 7 days of symptom onset, and convalescent serum 14-35 days after symptom onset. —Biopsy material: Bronchial or pleural biopsy material can be evaluated if available.	—Sputum: transport at room temperature in sterile, screw-capped container (<1 hr transport time) or at 2^o-8^oC (>1 hr transport time). —Blood cultures: Obtain appropriate blood volume, number, and timing of sets per laboratory protocol; transport at room temperature. —Blood for PCR: 10 mL in EDTA (purple top) tube (for pediatric patients, collect volumes allowable). Transport directly to laboratory at room temperature (2-8^oC if transport > 2 hr). —Pleural fluid: Collect >1.0 mL in sterile container; store and transport at 2-8^oC. —CSF: Transport directly to laboratory at room temperature, or 2-8^oC if transport >2 hr. —Transport serum or citrated plasma (separated and removed from clot) at 2-8^oC (transport <2 hr) or freeze at –20^oC or colder (transport >2 hr); ship on dry ice. Ship part of sample (>1.0 mL) and retain part in case of shipping problems.^h —Preserve biopsies in 10% buffered formalin, and transport at room temperature.
Gastrointestinal anthrax^g	—Obtain stool specimen for culture (>5.0 g). —Obtain rectal swab from patients unable to produce stool (insert swab 1 in. beyond anal sphincter). —Obtain blood for smear and culture (and possibly PCR testing). —Blood cultures most likely to yield B anthracis if taken 2-8 days postexposure and prior to administration of antibiotics. —If ascites is present, obtain a specimen for Gram stain and culture (and possibly PCR testing).	—Stool: Transport in sterile container unpreserved (<1 hr transport time) or at 2^o-8^oC in Cary-Blair medium or equivalent (>1 hr transport time); specimen >5.0 g. —Blood: Transport at room temperature.
Anthrax meningitis	—Obtain CSF specimen for Gram stain, culture, and PCR. —Obtain blood for Gram stain, culture, and PCR.	—See comments above for collection and transport of blood and CSF for Gram stain, culture, and PCR.
Abbreviations: CSF, cerebrospinal fluid; EDTA, ethylenediaminetetraacetic acid; IHC, immunohistochemistry; PCR, polymerase chain reaction. ^aCDC/ASM/APHL 2002. ^bCDC 2001: Investigation of bioterrorism-related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. ^cBell 2002. ^dCDC: Algorithm for laboratory diagnosis of anthrax. ^eSerologic testing may be useful in certain situations for retrospective diagnosis, since antibodies take several weeks to develop. Serum should be collected during the acute illness, and 14, 28, 42, and 60 days after onset (CDC 2001: Clinical diagnosis and management of anthrax—lessons learned). ^fConsult with testing laboratory for specific instructions. ^gCDC: Recommended specimens for microbiology and pathology for diagnosis: inhalation, cutaneous, and gastrointestinal anthrax. ^hCDC. Anthrax: collecting, preparing, and shipping serum samples to CDC for serology testing.

Guidelines have been published for packing and shipping of infectious substances, diagnostic specimens, and biological agents from suspected acts of bioterrorism (ASM 2008). Chain of custody should be documented for material that may constitute evidence of criminal activity.

B anthracis is classified under WHO risk group 4. Isolates that are reasonably suspected to contain B anthracis must be transported as "infectious substances." International Air Transport Association (IATA) rules require training of all individuals involved in the transport of dangerous goods, including infectious substances. Once B anthracis is identified, isolates and specimens are regulated as select agents and are subject to additional transport requirements (see below).

Laboratory Biosafety and Biosecurity Information

Most clinical and environmental screening can be conducted under biosafety level 2 (BSL-2) conditions. The B anthracis cells present in clinical samples are primarily vegetative, which are not easily transmitted to laboratory workers. However, most hospital laboratories are not sufficiently staffed, trained, or equipped for environmental testing. The most recent case of anthrax in a laboratory worker illustrates this potential risk (CDC 2002: Suspected cutaneous anthrax in a laboratory worker—Texas, 2002).
Anthrax spores may remain viable after standard DNA purification procedures (Rantakokko-Jalava 2003). Experimental heat treatment of anthrax spores at 121^oC for 45 minutes appears to eliminate viability without significantly affecting polymerase chain reaction (PCR) efficiency (Fasanella 2003). Spores also can be irradiated with gamma rays to inactivate them without affecting PCR results (Dauphin 2008).
Inadvertent exposure to B anthracis spores occurred in 2004 in a California laboratory when workers used a suspension from a contract laboratory that was supposed to contain nonviable vegetative cells but actually contained viable B anthracis spores (CDC 2005: Inadvertent laboratory exposure to Bacillus anthracis—California, 2004). Following this report, the CDC stated that "Research laboratory workers should assume that all inactivated B anthracis suspension materials are infectious until inactivation is adequately confirmed."
Biosafety level 3 (BSL-3) practices are required for "production quantities or concentrations of cultures, or activities with a high potential for aerosols," including suspect powders.
BSL-2 and BSL-3 criteria and practices are described elsewhere (CDC 2007).
B anthracis is classified as a select agent and therefore is regulated under 42 CFR part 73 (Possession, Use, and Transfer of Select Agents and Toxins), which was published in final form in the Federal Register in March 2005 (HHS 2005). As specified in the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, 42 CFR part 73 provides requirements for laboratories that handle select agents (including registration, security risk assessments, safety plans, security plans, emergency response plans, training, transfers, record keeping, inspections, and notifications). These new requirements went into effect on February 7, 2003, and override earlier government requirements regarding possession and transfer of select agents. Select agents are biological agents designated by the US government to be major threats to public health and safety. A current list of select agents is published on the CDC Web site under information about the Select Agent Program (CDC/APHIS 2008). In addition, the CDC has published additional guidelines for enhancing laboratory security for laboratories working with select agents (CDC 2002: Laboratory security and emergency response guidance for laboratories working with select agents).

The Laboratory Response Network (LRN)

The LRN is a national network of approximately 150 laboratories. The network includes the following types of labs: federal, state and local public health, military, food testing, environmental, veterinary, and international (located in Canada, the United Kingdom, and Australia) (CDC: Facts about the Laboratory Response Network, CDC: The Laboratory Response Network).

The LRN structure for bioterrorism designates laboratories as either national, reference, or sentinel. Designation depends on the types of tests a laboratory can perform and how it handles infectious agents to protect workers and the public.

National laboratories have unique resources to handle highly infectious agents and the ability to identify specific agent strains.
Reference laboratories, sometimes referred to as "confirmatory reference," can perform tests to detect and confirm the presence of a threat agent. These laboratories ensure a timely local response in the event of a terrorist incident. Rather than having to rely on confirmation from laboratories at the CDC, reference laboratories are capable of producing conclusive results; this allows local authorities to respond quickly to emergencies. These are mostly state or local public health laboratories with BSL-3 containment facilities that have been given access to nonpublic testing protocols and reagents.
Sentinel laboratories represent the thousands of hospital-based labs that are on the front lines. Sentinel laboratories have direct contact with patients. In an unannounced or covert terrorist attack, patients provide specimens during routine patient care. Sentinel laboratories could be the first facility to spot a suspicious specimen. A sentinel laboratory’s responsibility is to refer a suspicious sample to the right reference laboratory. These laboratories generally have at least BSL-2 containment.

Standard Tests for Detection of B anthracis

Direct examination of bacterial micromorphology may demonstrate broad encapsulated gram-positive rods (approved for LRN sentinel [formerly level A] laboratories). The laboratory must be notified that anthrax is being considered, because the laboratory may regard gram-positive rods as potential contaminants or not work them up beyond identifying them as Bacillus species.

Gram stain can be performed on appropriate clinical specimens (eg, vesicular fluid, swabs from cutaneous lesions, cerebrospinal fluid [CSF], pleural fluid) (Bell 2002, Inglesby 2002). Two positive Gram stain findings, one from CSF and one buffy-coat smear, have been reported in cases of inhalational anthrax (Jernigan 2001).
The sensitivity of the Gram stain and other biological stains (eg, H&E, silver stain) for direct detection of anthrax cells in infected tissues or blood has not been established. However, the organism appears to be present in large numbers in advanced cases, which suggests the probable utility of direct smears in those presenting with advanced disease (CDC 2001: Clinical diagnosis and management of anthrax—lessons learned, Inglesby 2002). In cutaneous anthrax, B anthracis cells are most likely to be seen by Gram stain during the vesicular stage of disease (CDC/ASM/APHL 2002).
Buffy-coat smears may be positive in patients with bacteremia. The specific usefulness of buffy coat for early diagnosis of bacteremia has been out of favor owing to early reports of low predictive value, but its use for anthrax has not been adequately studied (Coppen 1981). PCR of buffy-coats has been successfully used for diagnosis of other bloodstream infections both before and after antibiotic treatment (Michelow 2002, Newcombe 1996). The PCR detection limit in simulated blood specimens was 400 colony-forming units (CFU)/mL (Rantakokko-Jalava 2003).
Endospores and free spores can be seen in cultures and generally are not seen in direct microscopic examination of patient samples (CDC 2001: Clinical diagnosis and management of anthrax—lessons learned).
India ink staining (sentinel laboratories) or M'Fadyean stain (reference laboratories) can be performed for capsule visualization directly on clinical specimens (CDC: Approved tests for the detection of Bacillus anthracis in the Laboratory Response Network).

Culture of clinical specimens is the "gold standard" for diagnosis of anthrax (initial isolation approved for LRN sentinel laboratories) (CDC/ASM/APHL 2002, CDC: Approved tests for the detection of Bacillus anthracis in the Laboratory Response Network).

Culture should be performed using standard 5% SBA. After 15 to 24 hours of incubation at 35°C to 37°C, colonies are 2 to 5 mm in diameter, flat or slightly convex, irregularly round, and slightly irregular or have a wavy border and a ground-glass appearance. Colonies typically have a tenacious consistency (ie, teasing with an inoculating loop causes the colony to stand up like beaten egg white).
Motility is measured by wet mount (working in a BSL-2 cabinet) or by motility test medium.
Spores are visualized by Gram stain (sentinel laboratories), wet mount, or malachite green (reference laboratories) from cultures incubated for 18 to 24 hours at 35°C to 37°C without enhanced CO₂. Spores are oval, are central to subterminal, and do not appreciably swell the mother cell.
India ink for demonstration of capsule can be used on cultures grown on media supplemented with sodium bicarbonate.
Suspicious isolates should be forwarded to an LRN reference laboratory for confirmatory identification.
Blood culture sensitivity is compromised when samples are collected after administration of even one or two doses of antibiotics; therefore, cultures should be obtained before antibiotic therapy is initiated. If antibiotics have been administered, alternate diagnostic methods should be considered.

Stepwise Identification and Confirmation

Presumptive identification of anthrax in clinical specimens is based on Gram stain morphology and detection of a capsule (CDC/ASM/APHL 2002). Note: The absence of evidence for a capsule does not rule out B anthracis.

Large gram-positive rods in short chains of two to four cells: Possible Bacillus species
India ink test positive (evidence of encapsulation): Presumptive B anthracis
Other tests conducted at LRN laboratories may provide additional direct evidence of anthrax; definitive identification is by culture

Standard identification of isolates is based on classical biochemical and morphologic characteristics (CDC/ASM/APHL 2002, Sneath 1986). A stepwise protocol for identification of B anthracis is as follows:

Gram-positive broad spore-forming rods: Bacillus species
Spores are nonswelling and oval-shaped, and colonies have a ground-glass appearance: Bacillus morphology group 1 (includes B anthracis, B cereus, B thuringiensis, and B cereus var mycoides)
Nonmotile: B anthracis and B cereus var mycoides
Nonhemolytic: presumptive B anthracis (weak hemolysis may be observed under areas of confluent growth in aging colonies and should not be confused with beta-hemolysis)

Standard confirmatory testing (performed by LRN reference and national laboratories) includes the following tests (CDC: Algorithm for laboratory diagnosis of anthrax, CDC: Approved tests for the detection of Bacillus anthracis in the Laboratory Response Network):

Lysis by gamma phage (provides confirmatory testing when demonstrated concomitantly with the presence of a capsule). Performance characteristics have been described in detail (Abshire 2005).
Direct immunofluorescent assays (DFA) for cell-wall-associated polysaccharide and capsule produced by vegetative cells (demonstration of both antigens provides confirmatory identification) (De 2002).
Additional test procedures for visualizing spores by LRN reference laboratories include wet mount and malachite green stain.
PCR-based assays for rapid identification of B anthracis:

A real-time PCR assay for rapid identification of B anthracis was evaluated by the CDC during the 2001 anthrax outbreak (Hoffmaster 2002: Evaluation and validation of a real-time polymerase chain reaction assay for rapid identification of Bacillus anthracis, Hoffmaster 2002: Supplement to above). Sensitivity and specificity were reported as 100%. PCR testing for anthrax is available through the LRN.
Real-time PCR assays capable of detecing multiple agents have been developed and are able to detect B anthracis, Francisella tularensis, and Yersinia pestis in a single assay without any cross-reactivity. The assay may prove useful as a rapid tool for detection of category A bioterrorism agents (Skottman 2007). Commercial ready-to-use reagent systems have been developed for use in PCR assays (Sohni 2008).
PCR primers that distinguish B anthracis from related Bacillus species have been developed. The primers may be useful for developing an efficient diagnostic tool for rapid identification (Kim 2008). A restriction site insertion–PCR (RSI-PCR) method can distinguish B cereus group strains closely related to B anthracis from B anthracis strains (Gierczynski 2007).

IHC is a sensitive and specific method for detection of B anthracis in affected tissues that uses antibody directed against cell-wall and capsule components. This test is unaffected by prior administration of antibiotics or formalin fixation (Guarner 2003, Shieh 2003). IHC is not widely available, but requests for testing can be made through the LRN.
Molecular subtyping (multilocus variable-number tandem repeat analysis [MLVA]), is used by the CDC and others for strain identification and tracking (CDC: Approved tests for the detection of Bacillus anthracis in the Laboratory Response Network, Hoffmaster 2002: Molecular subtyping of Bacillus anthracis and the 2001 bioterrorism-associated anthrax outbreak, United States, Keim 1999, Keim 2000). Applications of single nucleotide polymorphism (SNP) and MLVA also have been used to discriminate closely related B anthracis isolates during outbreaks in animals. The combined SNP-MLVA analysis may hold promise for use in forensic investigations (Kenefic 2008).

Antimicrobial susceptibility testing (performed at LRN reference laboratories) should be performed on clinical isolates.

National Committee for Clinical Laboratory Standards (NCCLS) standard protocols for broth microdilution have been used with staphylococcal breakpoints.
Concerns about penicillin use hinge on potential inducible penicillinases and poor penetration into macrophages (Bell 2002).

Serologic testing can be used for retrospective diagnosis.

During the 2001 anthrax outbreak, the CDC developed, optimized, and qualified an enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to B anthracis PA (Quinn 2002). The diagnostic sensitivity of the assay was 97.8% and the diagnostic specificity was 97.6%; a competitive inhibition anti-PA IgG ELISA enhanced the diagnostic specificity to 100%.
Serum should be collected at 0 to 7 days for acute-phase testing and at 14 to 28 days for convalescent-phase testing.
Development of measurable antibodies in recent cases required 10 to 16 days after onset of overt disease, but peak IgG levels may not be seen until 40 days after symptom onset (Bell 2002).
Requests for serologic testing can be made through the LRN.
The Anthrax QuickELISA, a simplified lateral-flow immunochromatographic assay for anthrax antibody, has received approval from the Food and Drug Administration (FDA). The test, developed by Immunetics in collaboration with the CDC, has a diagnostic sensitivity and specificity of 100%, and is commercially available. Positive results on paired sera (-/+ or +/+) should be sent to the CDC for quantitative confirmation (Biagini 2006, CDC 2004: CDC collaboration yields new test for anthrax. Stephenson 2004).

Other tests for detection of B anthracis infection:

A skin test for delayed-type hypersensitivity to anthrax antigen has been widely used in the former Soviet Union since 1962 for retrospective diagnosis of human and animal anthrax infection and for vaccine evaluation. An 81.5% positivity rate has been reported during the first 3 days of disease; this increases to 97% to 99% within the next 2 to 3 weeks. Anthraxin, as the product is called, is not available in the United States and has not been evaluated in this country (Pfisterer 1991, Shlyakhov 1996, WHO 1998).

Antimicrobial Susceptibility Studies

Several studies have examined antimicrobial susceptibilities of B anthracis strains to various antibiotics. Data from four such studies are shown in the table below. Naturally occurring ciprofloxacin or doxycycline resistance has not been described, but isolates resistant to each of these antibiotics have been acquired in vitro (Brook 2001, Price 2003). Because resistance can be induced relatively rapidly in vitro, close monitoring of patients treated for anthrax is important (Athamna 2004).

MICs of Various Antibiotics for Bacillus anthracis Isolates as Identified in Four Studies
	Study^a
	Mohammed 2002		Coker 2002		Cavallo 2002		Turnbull 2004
*Antibiotic*	*MIC range^b*	*S-I-R (%)^c*	*MIC range^b*	*S-I-R (#)^c*	*MIC range^b*	*S-I-R (%)^c*	*MIC range^d*	*S-I-R (%)^c*
Amoxicillin					0.125-16	88.5-0-11.5
Amoxicillin–clavulanic acid							0.016-0.5	100-0-0
Azithromycin							1-12	26-64-10
Aztreonam					1->128	0-0-100
Cefaclor			0.125-0.75	25-0-0
Cefotaxime							3-32	1-0-99
Cefoxitin					1-64	74-15.3-10.7
Ceftriaxone	4-32	22-78-0			4-64	1-100-0
Cefuroxime			6-48	1-19-5
Cephalexin			0.38-2	25-0-0
Cephalothin					0.125-32	83.2-12.2-24.6
Chloramphenicol	2-8	100-0-0			1-4	100-0-0
Ciprofloxacin	0.03-0.12^e	100-0-0^e	0.032-0.38	25-0-0	0.03-0.5	100-0-0	0.032-0.094	100-0-0
Clindamycin	<0.5-1	94-6-0			0.125-1	100-0-0
Doxycycline			0.094-0.38	25-0-0	0.125-0.25	100-0-0
Erythromycin	0.5-1^f	3-97-0^f			0.5-4	95.4-4.6-0	0.5-4	15-85-0
Gatifloxacin					0.125-0.125	100-0-0
Gentamicin					0.125-0.5	100-0-0	0.064-0.5	100-0-0
Imipenem					0.125-2	100-0-0
Levofloxacin					0.03-1	100-0-0
Nalidixic acid					0.125-32	94.8-4.2-1
Ofloxacin					0.06-2	99-1-0
Penicillin	<0.06 -128	97-0-3	<0.016-0.5	22-0-3	0.125-16	88.5-0-11.5	<0.016->32	97-0-3
Pefloxacin					0.03-1	100-0-0
Piperacillin					0.25-32	99-1-0
Rifampin	<0.25-0.5	100-0-0			0.125-0.5	100-0-0
Streptomycin					0.5-2	100-0-0
Teicoplanin					0.125-0.5	100-0-0
Tetracycline	0.03-0.06	100-0-0					0.016-0.094	100-0-0
Tobramycin			0.25-1.5	25-0-0
Vancomycin	0.5-2	100-0-0			0.25-2	100-0-0	0.75-5	99-1-0
Abbreviation: MIC, minimum inhibitory concentration. ^aSee References: Cavallo 2002, Coker 2002, Mohammed 2002, Turnbull 2004. ^bMIC values in mcg/mL. ^cCategorical interpretation: susceptible (S), intermediate (I), and resistant (R); expressed as percent of isolates (%) or number of isolates (#), per author preference. (Note: Standard interpretive criteria for B anthracis have not been established.) ^dMIC determination by Etest. ^eA subset of 20 isolates were tested and found to be susceptible to clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin. ^fA subset of 20 isolates were also tested to clarithromycin (MIC range: 0.12-0.25 mcg/mL), azithromycin (MIC range: 1-2 mcg/mL), and doxycycline (MICs = <0.015 mcg/mL).

Multiple new antifolate compounds (multiple 2, 4-diaminopyrimidine derivatives, a class of compounds with dihydrophthalazine side chains) have demonstrated in vitro activity against trimethoprim (TMP)–resistant B anthracis and have the potential to become the basis of clinically important antibacterial therapies (Barrow 2007).

Tests for Exposure

Nasal swab cultures were used in the 2001 US outbreak as an epidemiologic tool to assess exposure to inhalational anthrax. In one study of 625 persons potentially exposed to anthrax spores in the Hart Senate Building, nasal swabs were positive in 28 (4.5%) (Hsu 2002).

All positive swabs were identified from persons who were in the immediate exposure area during the hour after the contaminated letter was opened. Seventy-one persons were in the exposure area during this time; therefore, the percentage of positive swabs among this group was 39% (28 of 71). Swabs from the 71 persons who were in the immediate area were obtained the day of exposure.
Swabs collected from persons other than those in the immediate area were collected 4 days after exposure; all were negative.
All exposed persons were placed on antimicrobial therapy, and repeat nasal swaps obtained 7 days later were negative. Results of serologic testing at 7, 21, and 42 days after exposure were negative for all exposed persons.

Another study at a worksite where a contaminated letter was opened demonstrated that two (<1%) of 1,076 nasal swabs taken from potentially exposed persons were positive; however, these swabs were obtained about 13 days after exposure (Traeger 2002). Similarly, all nasal swabs collected 9 to 10 days after exposure from 3,110 postal employees at a Washington, DC, postal facility that handled contaminated mail were negative (Dewan 2002). These findings, along with the findings from nasal swab testing of persons exposed in the Hart Senate Building, suggest that early collection of nasal swabs results in a higher yield of positive tests.

Because the sensitivity, specificity, and predictive value of nasal swab cultures are not known, nasal swabs are not recommended for use in the clinical setting. According to the CDC (CDC 2001: Interim guidelines for investigation of and response to Bacillus anthracis exposures), collection of nasal swabs is not indicated to:

Diagnose anthrax
Determine risk of exposure and the need for antimicrobial prophylaxis
Determine when antimicrobial prophylaxis should be stopped
Supplement random environmental sampling

Although nasal swabs should not be used to determine the need for antimicrobial prophylaxis, if a swab is performed for some reason and is positive, then the patient should receive a course of postexposure antibiotics, since a positive nasal swab indicates exposure to aerosolized B anthracis (Inglesby 2002). Methods for collection, labeling, transport, and processing of swabs have been published (CDC/ASM/APHL 2002).

Serologic testing does not appear to be a useful tool for assessing asymptomatic exposure to B anthracis (Dewan 2002, Hsu 2002, Traeger 2002).


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