| disease | Anthrax Disease |
| alias | Anthrax |
Anthrax is an acute infectious disease caused by Bacillus anthracis, which is zoonotic. Humans can become infected through contact with sick animals and their products, or by consuming the meat of infected animals. Clinically, it mainly manifests as skin necrosis, ulcers, eschars, extensive edema in surrounding tissues, and symptoms of toxemia. Occasionally, it can lead to acute infections of the lungs, intestines, and meninges, and may be accompanied by septicemia.
bubble_chart Epidemiology
Anthrax is distributed worldwide, particularly prevalent in pastoral areas such as South America, Asia, and Africa, exhibiting endemic characteristics as a natural focal disease. In recent years, due to the concentration of skin and hair processing industries in urban areas across various countries, anthrax outbreaks have also occurred in cities, becoming one of the significant occupational diseases. After liberation, with the active development of health and epidemic prevention efforts, the incidence of this disease has gradually declined in China.
(1) Source of Infection: Sick herbivorous animals such as cattle, horses, sheep, and camels are the primary sources of human anthrax infection. Pigs can contract the disease by ingesting contaminated green fodder, while carnivorous animals like dogs and wolves can become infected by consuming the meat of diseased livestock, serving as secondary sources of infection. The secretions and excretions of anthrax patients are also infectious.
(2) Transmission Routes: Human infection with anthrax bacilli primarily occurs through industrial and agricultural means. Contact infection is the main route of transmission. Direct skin contact with diseased animals and their skin and hair is the most common mode of infection. Inhaling dust or aerosols containing large amounts of anthrax spores or consuming contaminated meat can lead to pulmonary anthrax or intestinal anthrax, respectively. Using unsterilized brushes or being bitten by infected insects can occasionally cause the disease.
Bacillus anthracis is an aerobic or facultatively anaerobic, non-flagellated, large rod-shaped bacterium, measuring 4–8 μm in length and 1–1.5 μm in width. The bacterial cells have truncated ends and arrange in long chains resembling bamboo segments, staining Gram-positive. In the human body, it forms a capsule and exhibits strong pathogenicity, while non-virulent strains do not produce a capsule. Bacillus anthracis is highly viable and grows well on ordinary culture media. The vegetative forms of Bacillus anthracis can be killed at 56°C for 2 hours or 75°C for 1 minute. Common concentrations of disinfectants can also rapidly eliminate them. Under unfavorable external conditions, it forms oval-shaped spores. The spores are extremely resistant and can survive for long periods in natural environments or in cured meat. They can persist on skin and hair for several years. Direct sunlight exposure for 100 hours, boiling for 40 minutes, dry heat at 140°C for 3 hours, autoclaving at 110°C for 60 minutes, immersion in 10% formalin for 15 minutes, or treatment with freshly prepared 5% carbolic acid solution and 20% bleaching powder solution for several days are required to kill the spores.
The vegetative forms of Bacillus anthracis secrete anthrax toxin, which is a complex polymer composed of Factor I (edema factor, EF), Factor II (protective antigen, PA), and Factor III (lethal factor, LF). Individually, these components are non-toxic when injected into animals, but the combination of protective antigen with either edema factor or lethal factor can induce edema, necrosis, or animal death, respectively.
When a certain number of spores enter skin breaks, are ingested into the gastrointestinal tract, or inhaled into the respiratory tract, coupled with weakened human resistance, the pathogenic bacteria, protected by their capsule, first proliferate locally, producing large amounts of toxins. This leads to hemorrhagic infiltration, necrosis, and severe edema in tissues and organs, resulting in primary cutaneous anthrax, intestinal anthrax, and pulmonary anthrax. When the body's resistance declines, the pathogenic bacteria rapidly spread throughout the body via the lymphatic and circulatory systems, causing septicemia and secondary meningitis. Due to ischemia and the effects of toxins, the nerve fibers in the dermis degenerate in cutaneous anthrax, so the lesions often lack significant pain. If the person is healthy and the number of spores entering the body is small or their virulence is low, the disease may not manifest or may result in latent infection.
The pathogenicity of Bacillus anthracis is primarily related to the synergistic effects of its toxin components. Anthrax toxin can directly injure the endothelial cells of microvessels, increasing vascular permeability and leading to insufficient effective blood volume. Additionally, the release of certain bioactive substances during acute infection further dilates small blood vessels, exacerbating vascular permeability and reducing tissue perfusion. Furthermore, as the toxin injures the vascular endothelium, it activates the intrinsic coagulation system and releases tissue thromboplastin, causing a hypercoagulable state. Thus, DIC and septic shock are relatively common in anthrax. Moreover, Bacillus anthracis itself can obstruct capillaries, leading to tissue hypoxia, ischemia, and microthrombus formation in the microcirculation.
bubble_chart Pathological Changes
The main pathology of anthrax is hemorrhagic infiltration, necrosis, and edema in various organs and tissues. Cutaneous anthrax presents as a carbuncle-like lesion locally, surrounded by a zone of coagulative necrosis, with acute serous hemorrhagic inflammation in the skin tissue and significant interstitial edema. Due to the effect of toxins, the sensitivity of peripheral nerves is reduced, resulting in minimal local pain. Pulmonary anthrax manifests as hemorrhagic bronchitis, lobular pneumonia, and infarcted areas, with severe gelatinous edema in the mediastinum, marked swelling of the bronchial and mediastinal lymph nodes accompanied by hemorrhagic infiltration, and possible involvement of the pleura and pericardium. Intestinal anthrax primarily affects the small intestine, with localized carbuncle-like lesions and diffuse hemorrhagic infiltration in the intestinal wall, accompanied by severe edema and hemorrhage in the surrounding areas, as well as swelling of the mesenteric lymph nodes. The abdominal cavity contains serosanguinous exudate with a large number of pathogenic bacteria. When the meninges are affected, both the dura mater and pia mater become extremely congested and edematous, with extensive hemorrhage in the subarachnoid space, along with numerous bacterial cells and inflammatory cell infiltration. In cases of septicemia, widespread hemorrhagic infiltration, edema, and necrosis occur in other tissues and organs throughout the body, along with cloudy swelling of the liver and kidneys and splenomegaly.
bubble_chart Clinical Manifestations
The incubation period ranges from 1 to 5 days, with a minimum of only 12 hours and a maximum of 12 days. Clinically, it can be divided into the following five types.
(1) Cutaneous anthrax This is the most common type, accounting for about 95% of cases. It can be divided into anthrax carbuncle and malignant edema. Cutaneous anthrax mostly occurs on exposed skin areas such as the face, neck, shoulders, hands, and feet. Initially, it presents as a papule or maculopapular rash. On the second day, a blister filled with pale yellow fluid appears at the top, surrounded by hard and swollen tissue. On days 3–4, the central area shows hemorrhagic necrosis with slight depression, surrounded by clusters of small blisters, and the edema area continues to expand. By days 5–7, the blister necrotizes and ruptures, forming a shallow ulcer, with bloody secretions drying into a black, charcoal-like eschar. Beneath the eschar, granulation tissue forms an anthrax carbuncle. The surrounding tissue exhibits non-pitting edema. The diameter of the necrotic black eschar varies from 1–2 cm to 5–6 cm, while the edema area can reach 5–20 cm in diameter. Characteristics include firmness, minimal pain, and non-suppurative ulcers. Subsequently, the edema gradually subsides, the black eschar falls off within 1–2 weeks, and healing with scarring occurs after another 1–2 weeks. Fever, headache, local lymphadenopathy, and splenomegaly may appear 1–2 days after onset.
In a few cases, no black eschar forms locally, but instead, massive edema occurs, mostly affecting loose tissues such as the eyelids, neck, or thighs. The affected area becomes swollen, translucent, and tough, spreading rapidly and potentially leading to extensive necrosis. Systemic toxemia is severe, and the condition is critical. If treatment is delayed, death may occur due to circulatory failure. If the pathogen enters the bloodstream, it can cause septicemia, followed by pneumonia and meningitis.
(2) Pulmonary anthrax Most cases are primary, caused by inhaling Bacillus anthracis spores, but they can also be secondary to cutaneous anthrax. The onset is usually abrupt, but there is often a 2–4 day prodrome of common cold-like symptoms, followed by sudden worsening, presenting a biphasic pattern. Clinical manifestations include chills, high fever, dyspnea, wheezing, cyanosis, bloody sputum, and chest pain. Subcutaneous edema may sometimes appear on the neck or chest. The lungs may only exhibit scattered fine moist rales, or signs of meningitis may be present, often disproportionate to the severity of the condition. Most patients are critically ill, frequently complicated by septicemia and septic shock, and occasionally secondary meningitis. If diagnosis and treatment are delayed, death from respiratory or circulatory failure often occurs within 24–48 hours after acute symptoms appear.
(3) Intestinal anthrax Clinical symptoms vary, presenting as either acute gastroenteritis or acute abdomen. The former has an incubation period of 12–18 hours, with co-exposed individuals experiencing severe vomiting, abdominal pain, and watery diarrhea simultaneously or successively, usually recovering rapidly within days. The latter has a sudden onset, with severe toxemia, persistent vomiting, diarrhea, bloody watery stools, abdominal distension, and pain. Tenderness or signs of peritonitis may be present. Without timely treatment, septicemia and septic shock often develop, leading to death within 3–4 days of onset.
(4) Meningeal anthrax Most cases are secondary to other types of anthrax accompanied by septicemia, with primary cases being rare. Clinical symptoms include severe headache, vomiting, convulsions, and obvious meningeal irritation signs. The condition is extremely dangerous and progresses rapidly, with death possible within 2–4 days of onset. Cerebrospinal fluid is mostly bloody.
(5) Septicemic anthrax This type is usually secondary to pulmonary or intestinal anthrax, with cutaneous anthrax being a less common cause. It may be accompanied by high fever, headache, hemorrhage, vomiting, toxemia, septic shock, and DIC.
bubble_chart Auxiliary Examination
(1) Peripheral Blood Picture The total white blood cell count is mostly elevated, generally ranging from 10,000 to 20,000/mm3, with a few cases reaching as high as 60,000 to 80,000/mm3. The differential count shows a predominance of neutrophils.
(2) Smear Examination Smears are made from vesicle fluid, lesion exudates, secretions, sputum, vomitus, feces, blood, and cerebrospinal fluid. The smears are first fixed with 1:1000 mercuric chloride to destroy spores. After staining, typical large bacilli with a capsule and bamboo-joint appearance can be observed.
(3) Culture Specimens should be inoculated separately onto blood agar plates, ordinary agar plates, and sodium bicarbonate plates. Blood samples should undergo enrichment culture beforehand. For obviously contaminated specimens, heating at 65°C for 30 minutes can be applied to eliminate non-target bacteria, followed by enrichment in broth for 4 hours before inoculation onto plates. If suspicious colonies are observed, identification is performed based on biological characteristics and animal testing.
(4) Animal Inoculation Patient secretions, tissue fluids, or obtained pure cultures are inoculated into the subcutaneous tissue of animals such as mice or guinea pigs. A positive reaction is indicated by typical edema and hemorrhage at the injection site within 24 hours. Most animals die within 36 to 48 hours, with large quantities of encapsulated anthrax bacilli present in their viscera and blood. Isolated suspicious anthrax bacilli should undergo identification tests.
(5) Identification Tests These are used to distinguish anthrax bacilli from various Bacillus species (e.g., Bacillus subtilis, Bacillus cereus, Bacillus mycoides, Bacillus thermophilus). The main methods include the string-of-pearls wet mount, specific fluorescent antibody staining (targeting the bacterial body, capsule, spores, or bacteriophages), W bacteriophage lysis test, sodium bicarbonate agar plate CO2 culture method, penicillin G inhibition test, animal pathogenicity test, capsule swelling test, motility test, hemolysis test, and salicin fermentation test.
All the above tests should be conducted in a laboratory with specialized protective measures.
(6) Immunological Tests These include indirect hemagglutination, ELISA, enzyme-labeled SPA, and fluorescent immunoassays, used to detect various antibodies in serum, particularly capsule antibodies and serum antitoxin antibodies. These tests are generally employed for retrospective diagnosis and epidemiological investigations. The Ascoli precipitation test is primarily used to examine whether animal organs, skin, or fur are contaminated, but this method often yields false positives, so results should be interpreted cautiously.
The patient's occupation, work, and living conditions, such as frequent contact with cattle, horses, sheep, etc., among farmers and herders, or exposure to spore-laden dust in workplaces like skin and hair or leather processing factories, provide important reference value for diagnosing this disease. Cutaneous anthrax has certain characteristic features and is generally not difficult to diagnose. When factory workers develop respiratory infections, especially when symptoms and signs are disproportionate, vigilance should be heightened, and the possibility of pulmonary anthrax should be considered. Confirmation relies on smear examinations and cultures of various secretions, excretions, blood, and cerebrospinal fluid. Smear examination is the simplest method; if typical large bacilli with capsules are found, the diagnosis can be largely confirmed. Further confirmation can be achieved through fluorescent antibody staining, wet mount examination for bead-like chains, specific bacteriophage tests, and animal inoculation.
bubble_chart Treatment Measures
(1) General and symptomatic treatment Patients with this disease should be strictly isolated, and their secretions and excretions should be disinfected using spore disinfection methods. Provide high-calorie liquid or semi-liquid diets, and administer intravenous fluids if necessary. Patients with severe bleeding should receive appropriate blood transfusions. For patients with malignant skin edema, adrenal corticosteroids can be used to control the progression of local edema and alleviate toxemia. Typically, hydrocortisone 100–200 mg/day can be administered intravenously for a short period, but this must be done under the coverage of penicillin G. For patients with DIC, heparin and dipyridamole should be promptly administered.
(2) Local treatment For local skin lesions, aside from collecting samples for diagnosis, avoid squeezing or incising and draining them to prevent the spread of infection and the development of sepsis. The affected area can be washed with a 1:2000 potassium permanganate solution, covered with tetracycline ointment, and wrapped with sterile gauze.
(3) Pathogenic treatment Penicillin G is the first-line treatment. For cutaneous anthrax, adults should receive 1.6–3.2 million units per day, divided into multiple intramuscular injections, for a course of 7–10 days. For pulmonary anthrax, intestinal anthrax, meningitic anthrax, and septicemic anthrax, the daily dose should be increased to 10–20 million units, administered intravenously, combined with aminoglycosides (such as streptomycin, gentamicin, or kanamycin). The treatment course should be extended to 2–3 weeks or longer.
For patients allergic to penicillin G, tetracycline or chloramphenicol can be used, with a daily adult dose of 2 g, divided into four doses. Doxycycline is also effective, with a daily adult dose of 200–300 mg; ciprofloxacin 500 mg twice daily; or erythromycin 1.5 g per day for adults, with the same treatment duration as above.
Anti-anthrax serum therapy is rarely used today. If available, for patients with severe toxemia, in addition to antibiotic treatment, anti-anthrax serum can be administered intramuscularly or intravenously: 100 ml on the first day, followed by 30–50 ml on the second and third days. A skin test must be performed before administration.
The prognosis of this disease varies depending on the clinical type and the timeliness of diagnosis and treatment. The case fatality rate of cutaneous anthrax has decreased to about 1%, but cases located on the neck or face, complicated by sepsis, or of the malignant edema type have a poorer prognosis. For intestinal anthrax presenting as acute abdomen, pulmonary anthrax, meningoencephalitic anthrax, and septicemic anthrax, the rapid progression of the disease and the difficulty in early diagnosis result in a case fatality rate that can exceed 90%. Patients often die within days of onset.
(1) Management of pestilence sources: Patients should be isolated until wounds heal, scabs fall off, or symptoms disappear, and secretions or excretions test negative twice in cultures (with a 5-day interval).
Strictly isolate infected livestock and avoid using their milk. Dead animals must not be skinned or cooked; they should be incinerated or buried deep underground (below 2 meters) with a large amount of quicklime.
(2) Cutting off transmission routes: If necessary, quarantine the epidemic area. Disinfect and sterilize the patient's clothing, utensils, waste dressings, secretions, and excretions by boiling, using bleaching powder, ethylene oxide, peracetic acid, or high-pressure steam. Use the Ascoli precipitation test to inspect samples such as skin and hair or bone meal, and strictly disinfect contaminated or suspected contaminated items. Livestock product processing plants must improve working conditions, enhance protective measures, and require workers to wear protective clothing, masks, and gloves.
(3) Protecting susceptible individuals:
1. Strengthen health education: Cultivate good hygiene habits to prevent skin injuries. If the skin is broken, immediately apply 3–5% iodine tincture to avoid infection.
2. Healthy and infected livestock should be grazed separately. Administer live attenuated vaccines to livestock that have been in contact with infected animals.
3. For individuals engaged in animal husbandry, livestock product procurement, processing, slaughtering, or those in epidemic areas, administer an annual dose of live attenuated anthrax bacillus vaccine. Currently, the skin scarification method is used: 0.1 ml of the vaccine is applied to the outer arm skin, followed by a "#"-shaped scratch. A quadrivalent vaccine (containing anthrax bacillus, Francisella tularensis, plague bacillus, and Brucella) has also proven effective.
Internationally, protective antigen is used for vaccination: three intramuscular injections in the first year (each spaced 3 weeks apart), a fourth dose after 6 months, followed by an annual booster of 0.5 ml each.
Close contacts should be quarantined for 8 days. Early use of penicillin or tetracycline may be necessary, and the same measures apply to suspected cases.
Cutaneous anthrax must be differentiated from carbuncle, cellulitis, the eschar of scrub typhus, and the ulcer of Rebing (rabbit fever). Pulmonary anthrax should be distinguished from various types of pneumonia and pneumonic plague. Intestinal anthrax requires differentiation from acute bacillary dysentery and acute abdomen. The meningitic and septicemic forms of anthrax should be distinguished from various types of meningitis, subarachnoid hemorrhage, and sepsis.
