Chapter 26: Corynebacterium, Listeria, and Bacillus

This chapter includes a variety of highly pathogenic Gram-positive rods that are not currently common causes of human disease. Their medical importance lies in the lessons learned when they were more common, and the continued threat their existence poses. Corynebacterium diphtheriae, the cause of diphtheria, is a prototype for toxigenic disease. Listeria monocytogenes is a sporadic cause of meningitis and other infections in the fetus, newborn, and immunocompromised host. Occurrences in 2001 have served as a painful reminder that Bacillus anthracis, the cause of anthrax, is still the agent with the most potential for use in bioterrorism. The characteristics of these bacilli are presented in Table 26–1.

Corynebacteria (from the Greek koryne, club) are small and pleomorphic. The genus Corynebacterium includes many species of aerobic and facultative Gram-positive rods. The cells tend to have clubbed ends and often remain attached after division, forming “Chinese letter” or palisade arrangements. Spores are not formed. Growth is generally best under aerobic conditions on media enriched with blood or other animal products, but many strains grow anaerobically. Colonies on blood agar are typically small (1-2 mm), and most are nonhemolytic. Catalase is produced, and many strains form acid (usually lactic acid) through carbohydrate fermentation. Surface and cell wall structure is similar to other Gram-positive bacteria.

Corynebacterium diphtheriae

Corynebacterium diphtheriae produces a powerful exotoxin that is responsible for diphtheria. Other corynebacteria are nonpathogenic commensal inhabitants of the pharynx, nasopharynx, distal urethra, and skin; they are collectively referred to as “diphtheroids.” The species that have disease associations are included in Table 26–2.

BACTERIOLOGY

Corynebacterium diphtheriae are differentiated from other corynebacteria by the appearance of colonies on the selective media used for its isolation and a variety of biochemical reactions. Strains of C diphtheriae may or may not produce diphtheria toxin (DT). The gene for DT is contained in the genome of a bacteriophage, which is lysogenic in the C diphtheriae chromosome. For strains with the gene, DT production is controlled by a repressor protein (DtxR), which responds to iron concentrations and also regulates other toxin-related functions.

DT is an A-B toxin that acts in the cytoplasm to inhibit protein synthesis irreversibly in a wide variety of eukaryotic cells. After binding mediated by the B subunit, both the A and B subunits enter the cell in an endocytotic vacuole. In the low pH of the vacuole, the toxin unfolds, exposing sites that facilitate translocation of the A subunit from the phagosome to the cytosol. The target is elongation factor 2 (EF-2), which transfers polypeptidyl-transfer RNA from acceptor to donor sites on the ribosome of the host cell. The specific action of the A subunit is to inactivate EF-2, by ADP-ribosylation (ADPR), which shuts off protein synthesis. The details of DT action are illustrated in Chapter 1 (Figure 1–7) as a prototype toxin. Corynebacterium diphtheriae itself is unaffected because it uses a protein other than EF-2 for the same steps in protein synthesis.

DIPHTHERIA

EPIDEMIOLOGY

Corynebacterium diphtheriae is transmitted by droplet spread, by direct contact with cutaneous infections, and, to a lesser extent, by fomites (Figure 26–1). Some subjects become convalescent pharyngeal or nasal carriers and continue to harbor the organism for weeks, months, or longer. Diphtheria is rare where immunization is widely practiced. In the United States, for example, fewer than 10 cases are now reported each year. These usually occur as small outbreaks in populations that have not received adequate immunization, such as migrant workers, transients, and those who refuse immunization on religious grounds. It has been more than 25 years since any outbreak exceeded 50 cases.

Diphtheria still occurs in developing countries and in places where public health infrastructure has been disrupted. For example, in the former Soviet Union, where the annual number of diphtheria cases had been below 200, over 47 000 cases and 1700 deaths occurred between 1990 and 1995. This outbreak followed the reintroduction of C diphtheriae into a population where the public health systems had broken down as a result of the political situation. Reinstitution of effective immunization brought diphtheria rates back to base levels.

PATHOGENESIS

Corynebacterium diphtheriae has little invasive capacity, and diphtheria is due to the local and systemic effects of DT, a protein exotoxin with potent cytotoxic features (Figure 26–2). It inhibits protein synthesis in cell-free extracts of virtually all eukaryotic cells, from protozoa and yeasts to higher plants and humans. Its toxicity for intact cells varies among mammals and organs, primarily due to differences in toxin binding and uptake. In humans, the B subunit binds to one of a common family of eukaryotic receptors that regulate cell growth and differentiation, thus exploiting a normal cell function.

The production of DT has both local and systemic effects. Locally, its action on epithelial cells leads to necrosis and inflammation, forming a pseudomembrane composed of a coagulum of fibrin, leukocytes, and cellular debris. The extent of the pseudomembrane varies from a local plaque to an extensive covering of much of the tracheobronchial tree. Absorption and circulation of DT allow binding throughout the body. Myocardial cells are most affected; eventually, acute myocarditis develops.

IMMUNITY

Diphtheria toxin is antigenic, stimulating the production of protective antitoxin antibodies during natural infection. Formalin treatment of toxin produces toxoid, which retains the antigenicity but not the toxicity of native toxin and is used in immunization against the disease. It is clear that this process functionally inactivates fragment B. Whether it also inactivates fragment A or prevents its ability to dissociate from fragment B is not known. Molecular studies of the A subunit structure and action suggest that another approach to immunization may be by genetic engineering of the A subunit so that it fails to bind EF-2 but retains its antigenicity.

DIPHTHERIA: CLINICAL ASPECTS

MANIFESTATIONS

After an incubation period of 2 to 4 days, diphtheria usually manifests as pharyngitis or tonsillitis. Typically, malaise, sore throat, and fever occur, and a patch of exudate or membrane develops on the tonsils, uvula, soft palate, or pharyngeal wall. The gray-white pseudomembrane (Figure 26–3) adheres to the mucous membrane and may extend from the oropharyngeal area down to the larynx and into the trachea. Associated cervical adenitis is common, and in severe cases cervical adenitis and edema produce a “bull neck” appearance. In uncomplicated cases, the infection gradually resolves, and the membrane is coughed up after 5 to 10 days.

The complications and lethal effects of diphtheria are caused by respiratory obstruction or by the systemic effect of DT absorbed at the site of infection. Mechanical obstruction of the airway produced by the pseudomembrane, edema, and hemorrhage can be sudden and complete and can lead to suffocation, particularly if large sections of the membrane separate from the tracheal or laryngeal epithelial surface. The DT absorbed into the circulation causes injury to various organs, most seriously the heart. Diphtheritic myocarditis (Figure 26–4) can be detected by electrocardiography in two-thirds of patients and is serious enough to cause cardiac malfunction in up to 25%. It appears during the second or third week and is manifested by cardiac enlargement, arrhythmia, and congestive heart failure with dyspnea. Nervous system involvement appears later in the course of disease, most often involving paralysis of the soft palate, oculomotor (eye) muscles, or select muscle groups. The paralysis is reversible and is generally not serious unless the diaphragm is involved. The disease resolves with the formation of antitoxin antibody.

Corynebacterium diphtheriae may produce nonrespiratory infections, particularly of the skin. The characteristic lesion, ranges from a simple pustule to a chronic nonhealing ulcer, and is most common in tropical and hot, arid regions. Cardiac and neurologic complications from these infections are infrequent, suggesting that the efficiency of toxin production or absorption is low compared with that in respiratory infections.

DIAGNOSIS

The initial diagnosis of diphtheria is entirely clinical. There are presently no rapid laboratory tests of sufficient value to influence the decision regarding antitoxin administration. Direct smears of infected areas of the throat are not reliable diagnostic tools. Definitive diagnosis is accomplished by isolating and identifying C diphtheriae from the infected site and demonstrating its toxigenicity. Isolation is usually achieved with a selective medium containing potassium tellurite (eg, Tinsdale medium).

It should be recognized that although the diagnosis of diphtheria could once be made and confirmed with great confidence, it is now more difficult because experience with the disease is rare. Most physicians have never seen a case of diphtheria, and most laboratories have never isolated the organism and do not even stock the required medium. Because routine throat culture procedures do not detect C diphtheriae, the physician must advise the laboratory of the suspicion of diphtheria in advance. Generally, 2 days are required to exclude C diphtheriae (ie, no colonies isolated on Tinsdale agar); however, more time is needed to complete identification and toxigenicity testing of a positive culture.

TREATMENT

Treatment of diphtheria is directed at neutralization of the toxin with concurrent elimination of the organism. The former is most critical and is accomplished by promptly administering a diphtheria antitoxin, an antiserum produced in horses. It must be administered early because it only neutralizes circulating toxin and has no effect on toxin already fixed to or within cells. Corynebacterium diphtheriae is susceptible to a variety of antimicrobials, including penicillins, cephalosporins, erythromycin, and tetracycline. Of these, erythromycin has been the most effective. The complications of diphtheria are managed primarily by supportive measures.

PREVENTION

The mainstay of diphtheria prevention is immunization. The vaccine is highly effective. Three to four doses of diphtheria toxoid produce immunity by stimulating antitoxin production. The initial series is begun in the first year of life. Booster immunizations at 10-year intervals maintain immunity. Fully immunized individuals may become infected with C diphtheriae because the antibodies are directed only against the toxin, but the disease is mild. Serious infection and death occur only in unimmunized or incompletely immunized individuals. Immunization with DT toxoid prevents serious toxin-medicated disease.

BACTERIOLOGY

Listeria monocytogenes is a Gram-positive rod with some bacteriologic features that resemble those of both corynebacteria and streptococci. In stained smears of clinical and laboratory material, the organisms resemble diphtheroids. Listeria are not difficult to grow in culture, producing small, β-hemolytic colonies on blood agar. An unusual feature for human pathogens is the ability of L monocytogenes to grow slowly in the cold, even at temperatures below 0°C. This is due to the action of enzymes (RNA helicases) induced at low temperatures. Growth at refrigerator temperatures turns out to be important in the foodborne transmission of L monocytogenes (see epidemiology below). Listeria species are catalase-positive, which distinguishes them from streptococci, and they produce a characteristic tumbling motility in fluid media at temperatures below 30°C, which distinguishes them from corynebacteria.

Listeria monocytogenes is the only one of six Listeria species pathogenic for humans. There are 13 serotypes based on flagellar and surface antigens, but most human cases are limited to only three (1/2a, 1/2b, 4b). The major virulence factors are a group of invasion-associated surface proteins called internalins and a pore-forming cytotoxin, listeriolysin O (LLO).

LISTERIOSIS

EPIDEMIOLOGY

Listeria monocytogenes is widespread in nature, in soil, ground water, decaying vegetation, and the intestinal tract of animals including those associated with our food supply (eg, fowl, ungulates). The importance of foodborne transmission of listeriosis (Figure 26–5) was not recognized until the early 1980s. A widely publicized 1985 California outbreak involved consumption of Mexican-style soft cheese and included 86 cases and 29 deaths. Most of the cases were among mother–infant pairs. Dairy product outbreaks have been traced to postpasteurization contamination or deviation from recommended time and temperature guidelines. An important feature of some epidemics has been the ability of L monocytogenes to grow at refrigerator temperatures, allowing scant numbers to reach an infectious dose during storage. This persistence is enhanced by its ability to form biofilms, which make surfaces and packages more difficult to decontaminate. Heightened awareness has implicated many other foodstuffs, particularly those prepared from animal products in a ready-to-eat form such as sausages and delicatessen poultry items.

Listeria monocytogenes may also be transmitted transplacentally to the fetus, presumably following hematogenous dissemination in the mother. It may also be transmitted to newborns in the birth canal in a manner similar to group B streptococci. Listeriosis is still not a reportable disease in the United States, but active surveillance studies indicate that it may account for more than 1000 cases and 200 deaths each year. Most cases occur at the extremes of life (eg, in infants <1 month of age or adults >60 years of age).

PATHOGENESIS

Listeria monocytogenes animal models have long been used for the study of cell-mediated immunity because of the ability of the organism to grow in nonimmune macrophages and the requirement for activated macrophages to clear the infection. Listeria monocytogenes is able to induce its own uptake by nonprofessional and professional phagocytes including enterocytes, fibroblasts, dendritic cells, hepatocytes, endothelial cells, M cells, and macrophages. The first step in this process takes place when various surface proteins bind to fibronectin on the enterocyte surface followed by internalin attaching to its host cell receptor, E-cadherin. The internalin-E-cadherin binding triggers internalization of L monocytogenes in an endocytic vacuole. Inside the cell, the organism escapes from the phagosome to the cytosol in a matter of minutes. This escape is mediated by lysing of the vacuole's membrane by the pore-forming LLO and bacterial phospholipases. It takes place so quickly there is no time for lysosomes to fuse with the invading endosome.

Once in the cytosol, L monocytogenes continues to move through the cell by disrupting the metabolism of the cell's actin and microtubule infrastructure. This process is mediated by LLO and other proteins, particularly the ones that control actin polymerization (Figure 26–6). In this process actin monomers are sequentially concentrated directly behind the bacterium creating a bacterial “tail” that is connected to the long actin filaments. The addition of new actin units to the tail propels the organisms through the cytosol like a comet through the evening sky (Figure 26–7). The motile Listeria eventually reach the edge of the cell where, rather than stopping, they protrude into the adjacent cell taking the original cell membrane along with them. When these pinch off, the organisms are surrounded by a double set of host cell membranes that are again dissolved by LLO and phospholipases, releasing the organisms to restart the cycle in a new cell.

This complex strategy allows L monocytogenes to survive in macrophages by escaping the phagosome and then to spread from epithelial cell to epithelial cell without exposure to the immune system. How does Listeria keep its LLO from destroying the host cell membrane from the inside as the pore-forming toxins of other bacteria do from the outside? It appears that L monocytogenes may be able to not only regulate the timely production of LLO, but also to trigger its degradation by host cell proteolytic enzymes after it has left the endosome vacuole. LLO is also able to disrupt the response to infection by altering the host cell's posttranslational modification of its own proteins. One of these effects is suppression of antigen-induced T-cell activation. The genes for LLO, actin rearrangement, and several others are part of a virulence regulon contained in a pathogenicity island. The result is a surgically precise deployment of virulence factors.

IMMUNITY

Immunity to Listeria infection involves both innate and adaptive immune responses. In addition to neutrophil action, multiple toll-like receptors (TLRs) recognize Listeria peptidoglycan, lipoteichoic acid, lipoproteins, and flagellar protein. The adaptive response owes little to humoral and much to T_H1 cell-mediated mechanisms. The generation of antigen-specific CD4+ and CD8+ T-cell subsets is required for the resolution of infection and the establishment of long-lived protection. It is cytokine activation and gamma interferon that reverse the intracellular growth in macrophages. The importance of cellular immunity is emphasized by the increased frequency of listeriosis in situations where it is compromised due to disease (AIDS), immunosuppressive therapy, age, or pregnancy.

LISTERIOSIS: CLINICAL ASPECTS

MANIFESTATIONS

Listeriosis usually does not present clinically until there is disseminated infection. In foodborne outbreaks, sometimes gastrointestinal manifestations of primary infection such as nausea, abdominal pain, diarrhea, and fever occur. Disseminated infection in adults is usually occult, involving fever, malaise, and constitutional symptoms without an obvious focus. Listeria monocytogenes has a tropism for the central nervous system (CNS), including the brain parenchyma (encephalitis) and brainstem, but the meningitis it causes is not clinically distinct from that associated with other leading bacterial pathogens (Streptococcus pneumoniae, Neisseria meningitidis). Listeria meningitis does have a particularly high mortality rate.

Neonatal and puerperal infections appear in settings similar to those of infections with group B streptococci. Listeria monocytogenes appears to have a unique ability to infect the placenta (Figure 26–8), perhaps taking advantage of the mild impairment of cell-mediated immunity during pregnancy. Intrauterine infection leads to stillbirth or a disseminated infection at or near birth. If the pathogen is acquired in the birth canal, the onset of disease is later. The risk of disease is increased in the elderly and immunocompromised persons as well as in women in late pregnancy. The number of cases in AIDS patients has been estimated at 300 times that of the general population.

DIAGNOSIS

Diagnosis of listeriosis is by culture of blood, cerebrospinal fluid (CSF), or focal lesions. In meningitis, CSF Gram stains are usually positive. The first indication that Listeria is involved is often the discovery that the β-hemolytic colonies subcultured from a blood culture bottle are Gram-positive rods rather than streptococci.

TREATMENT AND PREVENTION

Listeria monocytogenes is susceptible to ampicillin and trimethoprim/sulfamethoxazole (TMP/SMX), both of which have been used effectively for treatment, including for meningitis. Ampicillin combined with gentamicin is considered the treatment of choice for fulminant cases and in patients with severe compromise of T-cell function. Intense surveillance to prevent the sale of Listeria-contaminated ready-to-eat meat products has led to a marked decrease in the incidence of new infections. Avoidance of unpasteurized dairy products and thorough cooking of animal products are wise measures and mandatory for immunocompromised persons. There is no vaccine available.

The genus Bacillus includes many species of aerobic or facultative, spore-forming, Gram- positive rods. With the exception of one species, B anthracis, they are low-virulence saprophytes widespread in air, soil, water, dust, and animal products. Bacillus anthracis causes the zoonosis anthrax, a disease of animals that is occasionally transmitted to humans. The genus is made up of rod-shaped organisms that can vary from coccobacillary to rather long-chained filaments. Motile strains have peritrichous flagella. Formation of round or oval spores, which may be central, subterminal, or terminal depending on the species, is characteristic of the genus.

With Bacillus, growth is obtained with ordinary media incubated in air and is reduced or absent under anaerobic conditions. The bacteria are catalase-positive and metabolically active. The spores survive boiling for varying periods and are sufficiently resistant to heat that those of one species are used as a biologic indicator of autoclave efficiency. Spores of B anthracis survive in soil for decades.

Bacillus Anthracis

BACTERIOLOGY

Bacillus anthracis has a tendency to form very long chains of rods and in culture is nonmotile and nonhemolytic; colonies are characterized by a rough, uneven surface with multiple curled extensions at the edge resembling a “Medusa head.” Bacillus anthracis has a polypeptide (poly-d-γ-glutamic acid) capsule of a single antigenic type that has antiphagocytic properties similar to those of bacterial polysaccharide capsules. Bacillus anthracis endospores are extremely hardy and have been shown to survive in the environment for decades. The organism also produces a potent exotoxin complex, which consists of two enzymes, edema factor (EF) and lethal factor (LF) together with a receptor-binding protein called protective antigen (PA). When PA binds to either EF or LF it then acts as a translocase forming a pore-like site on the host cell surface. This allows the complexes to enter the cell (Figure 26–9A). Once in the cytosol multiple toxin actions are expressed including adenylate cyclase activity and host protein inactivation. Bacillus anthracis also produces multiple other proteases that digest tissue components.

ANTHRAX

The isolation of B anthracis, the proof of its relationship to anthrax infection, and the demonstration of immunity to the disease are among the most important events in the history of science and medicine. Robert Koch rose to fame in 1877 by growing the organism in artificial culture using pure culture techniques. He defined the stringent criteria needed to prove that the organism caused anthrax (Koch's postulates), then met them experimentally. Louis Pasteur made a convincing field demonstration at Pouilly-le-Fort to show that vaccination of sheep, goats, and cows with an attenuated strain of B anthracis prevented anthrax. He was cheered and carried on the shoulders of the grateful farmers of the district, an experience now, unhappily, largely restricted to winning football coaches.

EPIDEMIOLOGY

Anthrax is primarily a disease of herbivores such as horses, sheep, and cattle, who acquire it from spores of B anthracis contaminating their pastures. Humans become infected through contact with these animals or their products in a way that allows the spores to be inoculated through the skin, ingested, or inhaled. In the 1920s, more than 100 cases occurred annually in the United States among farmers, veterinarians, and meat handlers, but the control of animal anthrax in developed countries has made human cases rare. A few endemic foci persist in North America and have been the source of naturally acquired disease. Another source is animal products such as wool, hides, or bone meal fertilizer that have been imported from a country where animal anthrax is endemic.

The real threat associated with anthrax comes from its continuing appeal to those bent on using it as an agent of biologic warfare or terrorism. The long life, stability, and low mass of the dried spores make the prospect of someone producing a “cloud of death” leading to massive pulmonary anthrax a chilling reality. A 1979 episode resulting in more than 60 anthrax deaths in the former Soviet Union is now attributed to an accidental explosion at a biologic warfare research facility that aerosolized more than 20 pounds of anthrax spores. United Nations inspection teams in Iraq uncovered facilities for the production of massive amounts of spores together with plans to create and spread infectious aerosols using missile warheads. The inhalation anthrax among postal workers after the September 11, 2001, terrorist attacks appears to have been due to the mailing of envelopes containing “weapons-grade” anthrax spores stolen from a biologic warfare research facility. Such spores had been treated to enhance their aerosolization and dissemination. The forms of anthrax are summarized in Figure 26–10.

PATHOGENESIS

When spores of B anthracis reach the rich environment of human tissues, they germinate and multiply in the vegetative state. The antiphagocytic properties of the capsule aid in survival, eventually allowing production of enough exotoxin to cause disease. The timing and relative importance of the EF, LF, and PA components is not known. The EF adenylate cyclase activity is believed to correlate with the striking edema seen at infected sites. In pulmonary anthrax the inhaled spores are taken up by alveolar macrophages but apparently do not germinate inside them at least until they drain to the mediastinum via the lymphatics. This most lethal of anthrax forms is manifest in the lung as a mediastinal process and systemically as a virulent bacteremia.

IMMUNITY

The specific mechanisms of immunity against B anthracis are not known. Experimental evidence favors antibody directed against the toxin complex, but the relative role of the components of the toxin is not clear. The capsular glutamic acid is immunogenic, but antibody against it is not protective.

ANTHRAX: CLINICAL ASPECTS

MANIFESTATIONS

Cutaneous anthrax usually begins 2 to 5 days after inoculation of spores into an exposed part of the body, typically the forearm or hand. The initial lesion is an erythematous papule, which may be mistaken for an insect bite. This papule usually progresses through vesicular and ulcerative stages in 7 to 10 days to form a black eschar (scab) surrounded by edema (Figure 26–9B and C). This lesion is known as the “malignant pustule,” although it is neither malignant nor a pustule. Associated systemic symptoms are usually mild, and the lesion typically heals very slowly after the eschar separates. Less commonly, the disease progresses with massive local edema, toxemia, and bacteremia.

Pulmonary anthrax is contracted by inhalation of spores. Historically, this has occurred when contaminated hides, hair, wool, and the like are handled in a confined space (wool-sorter disease) or after laboratory accidents. Today it is the form we would expect from the dissemination of a spore aerosol in biologic warfare. In the pulmonary syndrome, 1 to 5 days of nonspecific malaise, mild fever, and nonproductive cough lead to progressive respiratory distress and cyanosis. Spread to the bloodstream and CNS follow rapidly. Massive edema and hemorrhage are hallmark features of anthrax meningitis. Mediastinal edema was a prominent finding in the postal workers. If untreated, progression to a fatal outcome is usually very rapid once bacteremia has developed. An intestinal form of anthrax follows ingestion of contaminated food, usually meat. It is characterized by abdominal pain, ascites, and shock.

DIAGNOSIS

Culture of skin lesions, sputum, blood, and CSF are the primary means of anthrax diagnosis. Given some suspicion on epidemiologic grounds, Gram stains of sputum or other biologic fluids showing large numbers of long Gram-positive bacilli can suggest the diagnosis. In September 2001, diagnosis of the first case in Florida was speeded by an infectious disease specialist who knew such rods were extremely rare in the spinal fluid. Large Gram-positive bacilli are also unusual in sputum. Bacillus anthracis and other Bacillus species are not difficult to grow. In fact, clinical laboratories frequently isolate the nonanthrax species as environmental contaminants. The saprophytic species are usually β-hemolytic and motile, features not found in B anthracis, but most clinical laboratories are not skilled at separating Bacillus species. Blood cultures are positive in most cases of pulmonary anthrax.

TREATMENT

Antimicrobial treatment has little effect on the course of cutaneous anthrax but does protect against dissemination. Almost all strains of B anthracis are susceptible to penicillin, doxycycline, and ciprofloxacin. Although penicillin has long been the treatment of choice for all forms of anthrax, experience gained during the 2001 outbreak has caused the first-line recommendation to be changed to doxycycline or ciprofloxacin. These antibiotics are also recommended for chemoprophylaxis in the case of known or suspected exposure.

PREVENTION

The most important preventive measures are those that eradicate animal anthrax and limit imports from endemic areas. Vaccines are also useful. Pasteur's vaccine used a live strain attenuated by repeated subculture that resulted in the loss of a plasmid encoding toxin production. A similar live vaccine is still effective for animals. The human vaccine licensed in the United States is prepared by extraction from cultures of a nonencapsulated avirulent strain of B anthracis. The extract is made up of almost entirely the protective antigen component of the toxin complex. In 2002, the Institute of Medicine issued a detailed analysis of human and animal studies and declared the vaccine both safe and efficacious. Experts also feel that it is very unlikely that the architects of biologic warfare would be able to craft B anthracis strains for which this vaccine is not protective. In Russia and China, a live vaccine is used in which spores are inoculated by scarification.

Other Bacillus Species

Bacillus spores are widespread in the environment, and isolation of one of the more than 20 Bacillus species other than B anthracis from clinical material usually represents contamination of the specimen. Occasionally B cereus, B subtilis, and some other species produce genuine infections, including infections of the eye, soft tissues, and lung. Infection is usually associated with immunosuppression, trauma, an indwelling catheter, or contamination of complex equipment. The relative resistance of Bacillus spores to disinfectants aids their survival in medical devices that cannot be heat sterilized.

Bacillus cereus deserves special mention. This species is the one most likely to cause opportunistic infection, which suggests a virulence intermediate between that of B anthracis and the other species. Genes and plasmids similar to those found in B anthracis have been detected as has a destructive pyogenic toxin. Bacillus cereus can also cause food poisoning by means of enterotoxin production.